Use of wild bird surveillance, human case data and GIS spatial analysis for predicting spatial distributions of West Nile Virus in Greece

West Nile Virus (WNV) is the causative agent of a vector-borne, zoonotic disease with a worldwide distribution. Recent expansion and introduction of WNV into new areas, including southern Europe, has been associated with severe disease in humans and equids, and has increased concerns regarding the need to prevent and control future WNV outbreaks. Since 2010, 524 confirmed human cases of the disease have been reported in Greece with greater than 10% mortality. Infected mosquitoes, wild birds, equids, and chickens have been detected and associated with human disease. The aim of our study was to establish a monitoring system with wild birds and reported human cases data using Geographical Information System (GIS). Potential distribution of WNV was modelled by combining wild bird serological surveillance data with environmental factors (e.g. elevation, slope, land use, vegetation density, temperature, precipitation indices, and population density). Local factors including areas of low altitude and proximity to water were important predictors of appearance of both human and wild bird cases (Odds Ratio = 1,001 95%CI = 0,723–1,386). Using GIS analysis, the identified risk factors were applied across Greece identifying the northern part of Greece (Macedonia, Thrace) western Greece and a number of Greek islands as being at highest risk of future outbreaks. The results of the analysis were evaluated and confirmed using the 161 reported human cases of the 2012 outbreak predicting correctly (Odds = 130/31 = 4,194 95%CI = 2,841–6,189) and more areas were identified for potential dispersion in the following years. Our approach verified that WNV risk can be modelled in a fast cost-effective way indicating high risk areas where prevention measures should be implemented in order to reduce the disease incidence

Treatment of bipolar disorder: a complex treatment for a multi-faceted disorder

Background: Manic-depression or bipolar disorder (BD) is a multi-faceted illness with an inevitably complex treatment. Methods: This article summarizes the current status of our knowledge and practice of its treatment. Results: It is widely accepted that lithium is moderately useful during all phases of bipolar illness and it might possess a specific effectiveness on suicidal prevention. Both first and second generation antipsychotics are widely used and the FDA has approved olanzapine, risperidone, quetiapine, ziprasidone and aripiprazole for the treatment of acute mania. These could also be useful in the treatment of bipolar depression, but only limited data exists so far to support the use of quetiapine monotherapy or the olanzapine-fluoxetine combination. Some, but not all, anticonvulsants possess a broad spectrum of effectiveness, including mixed dysphoric and rapid-cycling forms. Lamotrigine may be effective in the treatment of depression but not mania. Antidepressant use is controversial. Guidelines suggest their cautious use in combination with an antimanic agent, because they are supposed to induce switching to mania or hypomania, mixed episodes and rapid cycling. Conclusion: The first-line psychosocial intervention in BD is psychoeducation, followed by cognitive-behavioral therapy. Other treatment options include Electroconvulsive therapy and transcranial magnetic stimulation. There is a gap between the evidence base, which comes mostly from monotherapy trials, and clinical practice, where complex treatment regimens are the rule

A 2-D DNS study of the effects of nozzle geometry, ignition kernel placement and initial turbulence on prechamber ignition

A parametric direct numerical simulation study was conducted to investigate the effects of the initial flow field (quiescent or turbulent), nozzle inlet sharpness and width, main chamber composition (lean and stoichiometric), and ignition kernel placement in a two-dimensional prechamber (PC) ignition system. The strongly coupled operating and geometric parameters determine the time at which the flame exits the prechamber, the transient structure and penetration of the initially cold and subsequently hot reactive jet and their impingement on the lower main chamber (MC) wall, affecting the combustion mode and the fuel consumption rate. The temperature of the flame reaching and crossing the nozzle is affected by the flame exit time and is significantly lower than the adiabatic flame temperature of the planar flame, although no quenching is observed. Interaction with the flow field (strong small scale vortices for narrow and sharp entry nozzles, large vortices for wide nozzles) generated close to the exit increases the surface area of the flame and its interaction with the MC mixture. Jet penetration and impingement on the lower MC wall is determined by combustion in the PC and the flow field it generates in the main chamber. Impingement results in large scale vortical structures, which further contribute to the flame area increase and accelerate the consumption of the MC charge at later times. For the conditions studied, budget analysis shows that the main combustion mode is premixed deflagration with locally enhanced or reduced reactivity. Local flame–flame interactions which are more pronounced close to the nozzle exit and the lower MC wall can increase the propagation speed up to six times compared to the planar flame. The evolution of the probability density functions of different quantities is used to characterize the strongly transient process. © 2020 The Combustion Institute

Characterizing the Evolution of Boundary Layers in IC Engines by Combined Direct Numerical and Large-Eddy Simulations

The structure of boundary layers (BLs) and wall heat flux is investigated as they evolve during the compression stroke in an optically accessible, single-cylinder research engine of passenger-car dimensions with a typical four-valve pent-roof design operated at motored and throttled conditions. Three-dimensional direct numerical simulations (DNS) of the compression stroke were carried out, which enable full resolution in space and time of all flow and temperature field structures in the entire domain, including the BLs. Since the high computational cost precludes calculation of the scavenging cycle, scale-resolving simulations were employed to provide initial fields for the DNS at intake valve closure. The analysis revealed that BLs deviate from ideal scaling laws commonly adopted in algebraic wall models, and that the non-zero streamwise pressure gradient correlates with changes in the near-wall profiles. Phenomenologically, such deviations are similar to those for developing BLs, and in particular for impinging flows. The momentum BL structure was found to be affected by the large-scale bulk flow motion, in contrast to the thermal BLs which exhibit a more structured behavior following the density increase due to compression. Inspection of the heat flux distribution confirmed the similarity between the flow and heat flux patterns and identified regions of intense heat flux, mainly in locations of strong directed flow towards the wall. The improved characterization of the boundary layer structure and its evolution during the compression stroke not only constitutes an important step towards improved understanding of near-wall phenomena in internal combustion engines, but the vast dataset also serves as a database for development of improved wall models.ISSN:1386-6184ISSN:1573-198

Mismatch repair hMSH2, hMLH1, hMSH6 and hPMS2 mRNA expression profiles in precancerous and cancerous urothelium

Changes in the expression of the mismatch repair (MMR) genes hMSH2, hMLH1, hMSH6 and hPMS2 reflect dysfunction of the DNA repair system that may allow the malignant transformation of tissue cells. The aim of the present study was to address the mRNA expression profiles of the mismatch DNA repair system in cancerous and precancerous urothelium. This is the first study to quantify MMR mRNA expression by applying quantitative real-time PCR (qPCR) and translate the results to mRNA phenotypic profiles (r, reduced; R, regular or elevated) in bladder tumors [24 urothelial cell carcinomas (UCCs) and I papillary urothelial neoplasm of low malignant potential (PUNLMP)] paired with their adjacent normal tissues (ANTs). Genetic instability analysis was applied at polymorphic sites distal or close to the hMSH2 and hMLH1 locus. Presenting our data, reduced hMSH2, hMSH6 and hPMS2 mRNA expression profiles were observed in cancerous and precancerous urothelia. Significantly, the ANTs of UCCs revealed the highest percentages of reduced hMSH2 (r(2)), hMSH6 (r(6)) and hPMS2 (p(2)) m RNA phenotypes relative to their tumors (P<0.03). In particular, combined r(2)r(6) (P<0.02) presented a greater difference between ANTS of low-grade UCCs vs. their tumors compared with ANTS of high-grade UCCs (P=0.000). Reduced hMLH1 (r(1)) phenotype was not expressed in precancerous or cancerous urothelia. The hMSH6 mRNA was the most changed in UCCs (47.8%). while hMSH2, hMLH1 and hPMS2 showed overexpression (47.8, 35 and 30%, respectively) that was associated with gender and histological tumor grading or staging. Genetic instability was rare in polymorphic regions distal to hMLH1. Our data reveal a previously unrecognized hMSH2 and hMSH6 mRNA combined phenotype (r(2)r(6)) correlated with a precancerous urothelium and show that hMLH1 is transcriptionally activated in precancerous or cancerous urothelium. In the present study, it is demonstrated that reduction of hMSH6 mRNA is a frequent event in bladder tumorigenesis and reflects a common mechanism of suppression with hMSH2, while alterations of hMSH2 or hMLH1 mRNA expression in UCCs does not correlate with the allelic imbalance of polymorphic regions harboring the genes

Endothelial cell activation by antiphospholipid antibodies is modulated by Krüppel-like transcription factors

Antiphospholipid syndrome is characterized by thrombosis and/or recurrent pregnancy loss in the presence of antiphospholipid antibodies (APLAs). The majority of APLAs are directed against phospholipid-binding proteins, particularly β2-glycoprotein I (β2GPI). Anti-β2GPI antibodies activate endothelial cells in a β2GPI-dependent manner through a pathway that involves NF-κB. Krüppel-like factors (KLFs) play a critical role in regulating the endothelial response to inflammatory stimuli. We hypothesized that activation of endothelial cells by APLA/anti-β2GPI antibodies might be associated with decreased expression of KLFs, which in turn might facilitate cellular activation mediated through NF-κB. Our experimental results confirmed this hypothesis, demonstrating markedly decreased expression of KLF2 and KLF4 after incubation of cells with APLA/anti-β2GPI antibodies. Restoration of KLF2 or KLF4 levels inhibited NF-κB transcriptional activity and blocked APLA/anti-β2GPI–mediated endothelial activation despite NF-κB p65 phosphorylation. Chromatin immunoprecipitation analysis demonstrated that inhibition of NF-κB transcriptional activity by KLFs reflects sequestration of the cotranscriptional activator CBP/p300, making this cofactor unavailable to NF-κB. These findings suggest that the endothelial response to APLA/anti-β2GPI antibodies reflects competition between KLFs and NF-κB for their common cofactor, CBP/p300. Taken together, these observations are the first to implicate the KLFs as novel participants in the endothelial proinflammatory response to APLA/anti-β2GPI antibodies