High-speed optical coherence tomography as a reliable adjuvant tool to grade ocular anterior chamber inflammation.

PURPOSE: To evaluate the high-speed anterior segment optical coherence tomography (AS-OCT) grading of the AS inflammation in patients with ocular inflammation. METHODS: A retrospective consecutive case series study. Patients with clinically visible AS inflammation in at least one eye underwent AS-OCT (Visante; Zeiss Meditec) with three to eight line scans per eye, performed by a trained masked examiner. The images were reviewed for hyperreflective spots, noise, and artifact, and these were correlated to clinical examination. RESULTS: Seventy-eight eyes of 41 patients were imaged. Forty-seven eyes had anterior chamber cells on clinical examination, and 68 had hyperreflective spots visible on AS-OCT. There was a significant correlation (Spearman r = 0.7274) between clinical examination and Visante OCT images. Several patterns of inflammation and artifacts were apparent. CONCLUSION: The AS-OCT is a promising technique for grading anterior chamber cells. There was a significant correlation between clinical examination and Visante grading

Prasugrel Metabolites Inhibit Neutrophil Functions s

ABSTRACT Clopidogrel and prasugrel belong to a thienopyridine class of oral antiplatelet drugs that, after having been metabolized in the liver, can inhibit platelet function by irreversibly antagonizing the P2Y 12 receptor. Furthermore, thienopyridines influence numerous inflammatory conditions, but their effects on neutrophils have not been evaluated, despite the important role of these cells in inflammation. Therefore, we investigated the effect of prasugrel metabolites on neutrophils to further clarify the role of thienopyridines in inflammation. Interestingly, a prasugrel metabolite mixture, produced in vitro using rat liver microsomes, significantly inhibited N-formyl-methionyl-leucylphenylalanine (fMLP)-and platelet-activating factor (PAF)-induced neutrophil activation. More specifically, prasugrel metabolites inhibited neutrophil transmigration, CD16 surface expression, and neutrophil-platelet aggregation. Moreover, prasugrel metabolite pretreatment also significantly decreased fMLP-or PAF-induced extracellular-signal-regulated kinase phosphorylation as well as calcium mobilization. To determine the target of prasugrel in neutrophils, the role of both P2Y 12 and P2Y 13 receptors was studied using specific reversible antagonists, AR-C69931MX and MRS2211, respectively. Neither antagonist had any direct effect on the agonist-induced neutrophil functional responses. Our findings indicate that prasugrel metabolites may directly target neutrophils and inhibit their activation, suggesting a possible explanation for their antiinflammatory effects previously observed. However, these metabolites do not act through either the P2Y 12 or P2Y 13 receptor in neutrophils

Viral and Epidemiological Determinants of the Invasion Dynamics of Novel Dengue Genotypes

Dengue fever and the more severe dengue haemorrhagic fever and dengue shock syndrome are mosquito borne viral infections that have seen a major increase in terms of global distribution and total case numbers over the last few decades. There are currently four antigenically distinct and potentially co-circulating dengue serotypes and each serotype shows substantial genetic diversity, organised into phylogenetically distinct genotypes or lineages. While there is some evidence for positive selection, the evolutionary dynamics of dengue virus (DENV) is supposed to be mostly dominated by purifying selection due to the constraints imposed by its two-host life-cycle. Motivated by a recent genotype replacement event whereby the resident American/Asian lineage of dengue virus serotype 2 (DENV2) had been displaced by the fitter Asian-1 lineage we investigated some of the epidemiological factors that might determine the success and invasion dynamics of a novel, advantageous dengue genotype. Our results show that although small differences in viral fitness can explain the rapid expansion and fixation of novel genotypes, their fate is ultimately determined by the epidemiological landscape in which they arise

Lipoproteomics: Methodologies and Analysis of Lipoprotein-Associated Proteins along with the Drug Intervention

Lipoproteins are specialized particles involved in the transport and distribution of hydrophobic lipids, as cholesterol and triglycerides, throughout the body. The lipoproteins exhibit a basic spherical shape as complexes of lipids and proteins, and these latter are known as apolipoproteins. Initially, the proteins associated with lipoproteins were recognized as integral or peripheral proteins that only maintain the dynamics and metabolism of lipoproteins. However, there exist many studies on different lipoproteins evidencing that the quantity and type of apolipoproteins and lipoprotein-associated proteins are diverse and could be associated with different lipoprotein function outcomes. Here, we summarized recent processes in the determination of apolipoproteins and lipoprotein-associated proteins profiles through a proteomic approach, analyzing the major methods available and are used to achieve this. We also discuss the relevance of these lipoproteomic analyses on the human disease outcomes

Characterising the KMP-11 and HSP-70 recombinant antigens' humoral immune response profile in chagasic patients

11 pages, 6 figures.-- The pre-publication history for this paper can be accessed here: http://www.biomedcentral.com/1471-2334/9/186/pre pubBackground: Antigen specificity and IgG subclass could be significant in the natural history of Chagas' disease. The relationship between the different stages of human Chagas' disease and the profiles of total IgG and its subclasses were thus analysed here; they were directed against a crude T. cruzi extract and three recombinant antigens: the T. cruzi kinetoplastid membrane protein-11 (rKMP-11), an internal fragment of the T. cruzi HSP-70 protein192-433, and the entire Trypanosoma rangeli HSP-70 protein. Methods: Seventeen Brazilian acute chagasic patients, 50 Colombian chronic chagasic patients (21 indeterminate and 29 cardiopathic patients) and 30 healthy individuals were included. Total IgG and its subtypes directed against the above-mentioned recombinant antigens were determined by ELISA tests. Results: The T. cruzi KMP-11 and T. rangeli HSP-70 recombinant proteins were able to distinguish both acute from chronic chagasic patients and infected people from healthy individuals. Specific antibodies to T. cruzi crude antigen in acute patients came from IgG3 and IgG4 subclasses whereas IgG1 and IgG3 were the prevalent isotypes in indeterminate and chronic chagasic patients. By contrast, the specific prominent antibodies in all disease stages against T. cruzi KMP-11 and T. rangeli HSP-70 recombinant antigens were the IgG1 subclass.This work was supported by Colciencias Research project No. 1203-333- 18692. IDF was supported by Colciencias and the Universidad Javeriana's Young Researcher 2008 Programme (Bogotá, Colombia). MCT and MCL were supported by P06-CTS-02242 Grant from PAI (Junta de Andalucia) and RICET-RD06/0021-0014, Spain. MS received financial support from the Brazilian agency - CNPq.Peer reviewe

The ICARUS Experiment, A Second-Generation Proton Decay Experiment and Neutrino Observatory at the Gran Sasso Laboratory

The final phase of the ICARUS physics program requires a sensitive mass of liquid Argon of 5000 tons or more. The T600 detector stands today as the first living proof that such large detector can be built and that liquid Argon imaging technology can be implemented on such large scales. After the successful completion of a series of technical tests to be performed at the assembly hall in Pavia, the T600 detector will be ready to be transported into the LNGS tunnel. The operation of the T600 at the LNGS will allow us (1) to develop the local infrastructure needed to operate our large detector (2) to start the handling of the underground liquid argon technology (3) to study the local background (4) to start the data taking with an initial liquid argon mass that will reach in a 5-6 year program the multi-kton goal. The T600 is to be considered as the first milestone on the road towards a total sensitive mass of 5000 tons: it is the first piece of the detector to be complemented by further modules of appropriate size and dimensions, in order to reach in a most efficient and rapid way the final design mass. In this document, we describe the physics program that will be accomplished within the first phase of the program

Immunodominant Antigens of Leishmania chagasi Associated with Protection against Human Visceral Leishmaniasis

One of the most striking features of infection by Leishmania chagasi is that infection leads to a spectrum of clinical outcomes ranging from asymptomatic infection to active disease. The existence of asymptomatic infected people has served as an incentive to believe that an effective vaccine is possible, but unfortunately no successful immunological characterization of such cases was obtained. Patients recovered from visceral leishmaniasis show a similar immunological profile to asymptomatic infected individuals and both exhibit a strong cell-mediated immune response against Leishmania antigens and are resistant to disease. Since the past decade several approaches were undertaken to try to shed light on the immunological profile associated with such “resistance” to infections, notwithstanding antigenic recognition profile associated to resistance to infection was not successfully explored. In the present manuscript we describe a specific IgG recognizing pattern associated with resistant individuals (asymptomatic infected people and recovery patients to visceral leishmaniasis). These data highlight the possibility of using specific proteins in serological tests for the identification of asymptomatic infected individuals

Perinatal outcomes among immigrant mothers over two periods in a region of central Italy

<p>Abstract</p> <p>Background</p> <p>The number of immigrants has increased in Italy in the last twenty years (7.2% of the Italian population), as have infants of foreign-born parents, but scanty evidence on perinatal outcomes is available. The aim of this study was to investigate whether infants of foreign-born mothers living in Italy have different odds of adverse perinatal outcomes compared to those of native-born mothers, and if such measures changed over two periods.</p> <p>Methods</p> <p>The source of this area-based study was the regional hospital discharge database that records perinatal information on all births in the Lazio region. We analysed 296,739 singleton births born between 1996-1998 and 2006-2008. The exposure variable was the mother's region of birth. We considered five outcomes of perinatal health. We estimated crude and adjusted odds ratios and 95% confidence intervals (CIs) to evaluate the association between mother's region of birth and perinatal outcomes.</p> <p>Results</p> <p>Perinatal outcomes were worse among infants of immigrant compared to Italian mothers, especially for sub-Saharan and west Africans, with the following crude ORs (in 1996-1998 and 2006-2008 respectively): 1.80 (95%CI:1.44-2.28) and 1.95 (95%CI:1.72-2.21) for very preterm births, and 1.32 (95%CI:1.16-1.50) and 1.32 (95%CI:1.25-1.39) for preterm births; 1.18 (95%CI:0.99-1.40) and 1.17 (95%CI:1.03-1.34) for a low Apgar score; 1.22 (95%CI:1.15-1.31) and 1.24 (95%CI:1.17-1.32) for the presence of respiratory diseases; 1.47 (95%CI:1.30-1.66) and 1.45 (95%CI:1.34-1.57) for the need for special or intensive neonatal care/in-hospital deaths; and 1.03 (95%CI:0.93-1.15) and 1.07 (95%CI:1.00-1.15) for congenital malformations. Overall, time did not affect the odds of outcomes differently between immigrant and Italian mothers and most outcomes improved over time among all infants. None of the risk factors considered confounded the associations.</p> <p>Conclusion</p> <p>Our findings suggest that migrant status is a risk factor for adverse perinatal health. Moreover, they suggest that perinatal outcomes improved over time in some immigrant women. This could be due to a general improvement in immigrants' health in the past decade, or it may indicate successful application of policies that increase accessibility to mother-child health services during the periconception and prenatal periods for legal and illegal immigrant women in Italy.</p

Chromatin regulation by Histone H4 acetylation at Lysine 16 during cell death and differentiation in the myeloid compartment

Histone H4 acetylation at Lysine 16 (H4K16ac) is a key epigenetic mark involved in gene regulation, DNA repair and chromatin remodeling, and though it is known to be essential for embryonic development, its role during adult life is still poorly understood. Here we show that this lysine is massively hyperacetylated in peripheral neutrophils. Genome-wide mapping of H4K16ac in terminally differentiated blood cells, along with functional experiments, supported a role for this histone post-translational modification in the regulation of cell differentiation and apoptosis in the hematopoietic system. Furthermore, in neutrophils, H4K16ac was enriched at specific DNA repeats. These DNA regions presented an accessible chromatin conformation and were associated with the cleavage sites that generate the 50 kb DNA fragments during the first stages of programmed cell death. Our results thus suggest that H4K16ac plays a dual role in myeloid cells as it not only regulates differentiation and apoptosis, but it also exhibits a non-canonical structural role in poising chromatin for cleavage at an early stage of neutrophil cell death

Genome-wide analysis identifies 12 loci influencing human reproductive behavior.

The genetic architecture of human reproductive behavior-age at first birth (AFB) and number of children ever born (NEB)-has a strong relationship with fitness, human development, infertility and risk of neuropsychiatric disorders. However, very few genetic loci have been identified, and the underlying mechanisms of AFB and NEB are poorly understood. We report a large genome-wide association study of both sexes including 251,151 individuals for AFB and 343,072 individuals for NEB. We identified 12 independent loci that are significantly associated with AFB and/or NEB in a SNP-based genome-wide association study and 4 additional loci associated in a gene-based effort. These loci harbor genes that are likely to have a role, either directly or by affecting non-local gene expression, in human reproduction and infertility, thereby increasing understanding of these complex traits