Periodontal disease and inflammatory blood cytokines in patients with stable coronary artery disease

Periodontal disease has been associated with elevations of blood cytokines involved in atherosclerosis in systemically healthy individuals, but little is known about this association in stable cardiovascular patients. The aim of this study was to assess the association between periodontal disease (exposure) and blood cytokine levels (outcomes) in a target population of patients with stable coronary artery disease (CAD). Material and Methods This cross-sectional study included 91 patients with stable CAD who had been under optimized cardiovascular care. Blood levels of IL-1β, IL-6, IL-8, IL-10, IFN-γ, and TNF-α were measured by Luminex technology. A full-mouth periodontal examination was conducted to record probing depth (PD) and clinical attachment (CA) loss. Multiple linear regression models, adjusting for gender, body mass index, oral hypoglycemic drugs, smoking, and occurre:nce of acute myocardial infarction were applied. Results CAD patients that experienced major events had higher concentrations of IFN-γ (median: 5.05 pg/mL vs. 3.01 pg/mL; p=0.01), IL-10 (median: 2.33 pg/mL vs. 1.01 pg/mL; p=0.03), and TNF-α (median: 9.17 pg/mL vs. 7.47 pg/mL; p=0.02). Higher numbers of teeth with at least 6 mm of CA loss (R2=0.07) and PD (R2=0.06) were significantly associated with higher IFN-γ log concentrations. Mean CA loss (R2=0.05) and PD (R2=0.06) were significantly related to IL-10 concentrations. Elevated concentrations of TNF-α were associated with higher mean CA loss (R2=0.07). Conclusion Periodontal disease is associated with increased systemic inflammation in stable cardiovascular patients. These findings provide additional evidence supporting the idea that periodontal disease can be a prognostic factor in cardiovascular patients

Periodontal disease and inflammatory blood cytokines in patients with stable coronary artery disease

ABSTRACT www.scielo.br/jaos http://d

Genome wide association scan for chronic periodontitis implicates novel locus

Background: There is evidence for a genetic contribution to chronic periodontitis. In this study, we conducted a genome wide association study among 866 participants of the University of Pittsburgh Dental Registry and DNA Repository, whose periodontal diagnosis ranged from healthy (N = 767) to severe chronic periodontitis (N = 99).Methods: Genotypingi of over half-million single nucleotide polymorphisms was determined. Analyses were done twice, first in the complete dataset of all ethnicities, and second including only samples defined as self-reported Whites. From the top 100 results, twenty single nucleotide polymorphisms had consistent results in both analyses (borderline p-values ranging from 1E-05 to 1E-6) and were selected to be tested in two independent datasets derived from 1,460 individuals from Porto Alegre, and 359 from Rio de Janeiro, Brazil. Meta-analyses of the Single nucleotide polymorphisms showing a trend for association in the independent dataset were performed.Results: The rs1477403 marker located on 16q22.3 showed suggestive association in the discovery phase and in the Porto Alegre dataset (p = 0.05). The meta-analysis suggested the less common allele decreases the risk of chronic periodontitis.Conclusions: Our data offer a clear hypothesis to be independently tested regarding the contribution of the 16q22.3 locus to chronic periodontitis. © 2014 Feng et al.; licensee BioMed Central Ltd

Energetics of Propellant Options for High-Power Hall Thrusters

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/76265/1/AIAA-16376-173.pd

HIV Risks and Seroprevalence Among Mexican American Injection Drug Users in California

Latinos in the United States are an ethnically diverse group disproportionately affected by HIV/AIDS. We describe HIV seroprevalence, HIV risk behaviors and utilization of health services among Mexican American injection drug users (IDUs) in California (n = 286) and compare them to White (n = 830) and African American (n = 314) IDUs. Study participants were recruited from syringe exchange programs (n = 24) in California. HIV seroprevalence among Mexican Americans (0.5%) was dramatically lower than Whites (5%) and African Americans (8%). Mexican Americans reported fewer sex-related risks than Whites and African Americans though injection-related risks remained high. Compared to Whites, Mexican Americans were more likely to participate in drug treatment during a 6 month period (AOR 1.5, 95% CI 1.1, 2.0) but less likely to receive any health care (AOR 0.6, 95% CI 0.5, 0.8). Exploring cultural and structural factors among Mexican American IDUs may offer new insights into how to maintain low rates of HIV seroprevalence and reduce barriers to health care utilization

Development of Functional Genomic Tools in Trematodes: RNA Interference and Luciferase Reporter Gene Activity in Fasciola hepatica

The growing availability of sequence information from diverse parasites through genomic and transcriptomic projects offer new opportunities for the identification of key mediators in the parasite–host interaction. Functional genomics approaches and methods for the manipulation of genes are essential tools for deciphering the roles of genes and to identify new intervention targets in parasites. Exciting advances in functional genomics for parasitic helminths are starting to occur, with transgene expression and RNA interference (RNAi) reported in several species of nematodes, but the area is still in its infancy in flatworms, with reports in just three species. While advancing in model organisms, there is a need to rapidly extend these technologies to other parasites responsible for several chronic diseases of humans and cattle. In order to extend these approaches to less well studied parasitic worms, we developed a test method for the presence of a viable RNAi pathway by silencing the exogenous reporter gene, firefly luciferase (fLUC). We established the method in the human blood fluke Schistosoma mansoni and then confirmed its utility in the liver fluke Fasciola hepatica. We transformed newly excysted juveniles of F. hepatica by electroporation with mRNA of fLUC and three hours later were able to detect luciferase enzyme activity, concentrated mainly in the digestive ceca. Subsequently, we tested the presence of an active RNAi pathway in F. hepatica by knocking down the exogenous luciferase activity by introduction into the transformed parasites of double-stranded RNA (dsRNA) specific for fLUC. In addition, we tested the RNAi pathway targeting an endogenous F. hepatica gene encoding leucine aminopeptidase (FhLAP), and observed a significant reduction in specific mRNA levels. In summary, these studies demonstrated the utility of RNAi targeting reporter fLUC as a reporter gene assay to establish the presence of an intact RNAi pathway in helminth parasites. These could facilitate the study of gene function and the identification of relevant targets for intervention in organisms that are by other means intractable. More specifically, these results open new perspectives for functional genomics of F. hepatica, which hopefully can lead to the development of new interventions for fascioliasis

Rapid transcriptional plasticity of duplicated gene clusters enables a clonally reproducing aphid to colonise diverse plant species

Background: The prevailing paradigm of host-parasite evolution is that arms races lead to increasing specialisation via genetic adaptation. Insect herbivores are no exception and the majority have evolved to colonise a small number of closely related host species. Remarkably, the green peach aphid, Myzus persicae, colonises plant species across 40 families and single M. persicae clonal lineages can colonise distantly related plants. This remarkable ability makes M. persicae a highly destructive pest of many important crop species. Results: To investigate the exceptional phenotypic plasticity of M. persicae, we sequenced the M. persicae genome and assessed how one clonal lineage responds to host plant species of different families. We show that genetically identical individuals are able to colonise distantly related host species through the differential regulation of genes belonging to aphid-expanded gene families. Multigene clusters collectively upregulate in single aphids within two days upon host switch. Furthermore, we demonstrate the functional significance of this rapid transcriptional change using RNA interference (RNAi)-mediated knock-down of genes belonging to the cathepsin B gene family. Knock-down of cathepsin B genes reduced aphid fitness, but only on the host that induced upregulation of these genes. Conclusions: Previous research has focused on the role of genetic adaptation of parasites to their hosts. Here we show that the generalist aphid pest M. persicae is able to colonise diverse host plant species in the absence of genetic specialisation. This is achieved through rapid transcriptional plasticity of genes that have duplicated during aphid evolution

Comprehensive genomic profiles of small cell lung cancer

We have sequenced the genomes of 110 small cell lung cancers (SCLC), one of the deadliest human cancers. In nearly all the tumours analysed we found bi-allelic inactivation of TP53 and RB1, sometimes by complex genomic rearrangements. Two tumours with wild-type RB1 had evidence of chromothripsis leading to overexpression of cyclin D1 (encoded by the CCND1 gene), revealing an alternative mechanism of Rb1 deregulation. Thus, loss of the tumour suppressors TP53 and RB1 is obligatory in SCLC. We discovered somatic genomic rearrangements of TP73 that create an oncogenic version of this gene, TP73Dex2/3. In rare cases, SCLC tumours exhibited kinase gene mutations, providing a possible therapeutic opportunity for individual patients. Finally, we observed inactivating mutations in NOTCH family genes in 25% of human SCLC. Accordingly, activation of Notch signalling in a pre-clinical SCLC mouse model strikingly reduced the number of tumours and extended the survival of the mutant mice. Furthermore, neuroendocrine gene expression was abrogated by Notch activity in SCLC cells. This first comprehensive study of somatic genome alterations in SCLC uncovers several key biological processes and identifies candidate therapeutic targets in this highly lethal form of cancer

Coherent J/psi photoproduction in ultra-peripheral PbPb collisions at root s(NN)=2.76 TeV with the CMS experiment

Peer reviewe

Measurements of the associated production of a Z boson and b jets in pp collisions at root s=8 TeV

Peer reviewe