Relationship between NOX4 level and angiotensin II signaling in Gitelman's syndrome. Implications with hypertension

Recent evidence showed that endogenous nicotinamide adenine dinucleotide phosphate-oxidase 4 (NOX4) may exert a protective role on the cardiovascular system inducing vasodilation, reduction of blood pressure, and anti-proliferative actions. However, the functional significance of NOX4 in the cardiovascular system in humans remains elusive. Mononuclear cell levels of NOX4 were assessed by immunoblotting in 14 Gitelman's patients (GS), a unique human model of endogenous Ang II signaling antagonism and activation of anti-atherosclerotic and anti-remodeling defenses, and compared to 11 untreated essential hypertensive patients as well as to 11 healthy normotensive subjects. The association between NOX4 and its effector heme oxygenase (HO-1) (sandwich immunoassay) was also evaluated. NOX4 protein levels were decreased in hypertensive patients as compared to both GS and healthy subjects (1.06±0.31 AU vs. 1.76±0.54, P=0.002 and vs. 1.61±0.54, P=0.018, respectively). NOX4 protein level did not differ between GS and healthy subjects. HO-1 levels were increased in GS patients as compared to both hypertensive patients and healthy subjects (8.65±3.08 ng/ml vs 3.70±1.19, P<0.0001, and vs 5.49±1.04, P=0.008, respectively. NOX4 levels correlate with HO-1 levels only in GS (r(2)=0.63; P=0.001), (r(2)=0.088; P=ns, in hypertensive patients and r(2)=0.082; P=ns, in healthy subjects). Our findings show that NOX4 and its effector HO-1 are reduced in hypertensive patients compared to GS patients, a human model opposite to hypertension. Although the functional significance of NOX4 needs further clarification, our preliminary data in a unique human model of anti-atherosclerotic and anti-remodeling defenses activation, highlight the potentially protective role of NOX4 in the human cardiovascular system

Differential neuropsychological profiles in Parkinsonian patients with or without vascular lesions.

The purpose of this study is to compare the neuropsychological profile of patients affected by parkinsonism and vascular lesions to that in patients with PD alone (PD) and to evaluate whether the brain vascular lesion load is associated with neuropsychological variables. Thirty-six nondemented patients with parkinsonism were divided into 3 groups of 12 patients each, according to both clinical history and the presence of brain vascular lesions and/or dopaminergic denervation as revealed by magnetic resonance and dopamine transporter imaging, respectively. The first group had vascular lesions without dopaminergic denervation (VP group); the second group had vascular lesions and dopaminergic denervation (DD) (VP+DD group); and the third group consisted of patients with dopaminergic denervation (PD group) without vascular lesions. All patients underwent neurological and neuropsychological assessments. The groups differed in disease duration, age at onset, and cerebrovascular risk factors. The VP and VP+DD groups performed worse than the PD group on frontal/executive tasks. Regardless of the presence of dopaminergic denervation, cerebrovascular lesions in hemispheric white matter, basal ganglia, and cerebellum have an important effect in determining early onset and severity of cognitive impairment in patients with parkinsonism

Multicriteria decision making for selecting an optimal survey approach for large building portfolios

Technological advances and innovations have led to various pre- and post-disaster data collection alternatives to traditional sidewalk surveys. Hence, selecting a suitable survey approach may be challenging for different decision-makers. This paper proposes a multicriteria decision-making (MCDM) method to choose the optimal survey approach to gather exposure information needed for reliable multi-hazard risk assessment of large building and infrastructure portfolios. Both deterministic and stochastic implementations of MCDM are investigated, considering primary sources of aleatory and epistemic uncertainties. The applicability of the proposed framework is demonstrated for a portfolio of 13,200 buildings in a hypothetical multi-hazard prone region. The results show that informed decisions on identifying an optimal survey technique could be efficiently derived using MCDM and a number of relevant criteria. The proposed methodology can support various decision-makers in pre- and post-disaster risk modeling and management/reduction

MicroRNAs from saliva of anopheline mosquitoes mimic human endogenous miRNAs and may contribute to vector-host-pathogen interactions

During blood feeding haematophagous arthropods inject into their hosts a cocktail of salivary proteins whose main role is to counteract host haemostasis, inflammation and immunity. However, animal body fluids are known to also carry miRNAs. To get insights into saliva and salivary gland miRNA repertoires of the African malaria vector Anopheles coluzzii we used small RNA-Seq and identified 214 miRNAs, including tissue-enriched, sex-biased and putative novel anopheline miRNAs. Noteworthy, miRNAs were asymmetrically distributed between saliva and salivary glands, suggesting that selected miRNAs may be preferentially directed toward mosquito saliva. The evolutionary conservation of a subset of saliva miRNAs in Anopheles and Aedes mosquitoes, and in the tick Ixodes ricinus, supports the idea of a non-random occurrence pointing to their possible physiological role in blood feeding by arthropods. Strikingly, eleven of the most abundant An. coluzzi saliva miRNAs mimicked human miRNAs. Prediction analysis and search for experimentally validated targets indicated that miRNAs from An. coluzzii saliva may act on host mRNAs involved in immune and inflammatory responses. Overall, this study raises the intriguing hypothesis that miRNAs injected into vertebrates with vector saliva may contribute to host manipulation with possible implication for vector-host interaction and pathogen transmission

Experimental investigation of a variable geometry vertical axis wind turbine

An experimental study is presented on the performance of a vertical axis wind turbine with variable blade geometry of the design developed by Austin Farrah. This is experimentally compared with the performance of a correspondingly sized Bach-type Savonius turbine using the same electrical generator and measurement instrumentation in a wind tunnel. Experiments were performed for Reynolds numbers, based on blade chord, in the range 5 × 103 to 1 × 105, and for blade settings between −40° and +40o. The study shows that for the tip speed ratios that have been investigated, the Farrah vertical axis wind turbine design can only marginally outperform a corresponding two-bladed Bach-type Savonius turbine and then only when its blades are set to 40° pitch angle. The presence of a small inner cylinder, which rotates with the turbine, does not enhance its performance due to the fact that it is immersed in an extensive column of relatively static air

Study of the shear strength evolution over time of two-component backfilling grout in shield tunnelling

The two-component backfilling system is the most commonly used method to fill the annular void created during the advancement of shield machines. This unavoidable void, strictly linked to the technology of shield machines, must be filled continuously in order to avoid mostly surface displacements and lining movements. Today, this technology is the most frequently used due to operative and technical advantages, which lead to economic savings. However, despite intensive use of this backfilling technology, very little information is currently available concerning the evolution of the material in function of the curing time. Historically, the uniaxial compressive strength has been used as the main parameter for testing the compliance of a certain grout with the site-specific technical requirements, but nowadays shear strength is also starting to be considered by designers even if this topic has never been investigated. In this work, a laboratory test campaign focused on shear strength and its evolution in function of curing was performed. These tests put alight the fast mechanical growing of the twocomponent grout from the shear strength point of view and it should be remarked that at the current state of research there are no investigations concerning the shear strength in the context of a drainage approach. Both short and long curing times were investigated according to the direct shear test, performed under drained conditions. The Mohr-Coulomb failure envelope model was selected for the study and its widening in time highlights the peculiarity of this technology. Starting from a liquid phase at t0, values of cohesion (c') and friction angle (phi') grow in function of curing, reaching 126 kPa and 22 degrees at 3 h and exceeding 270 kPa and 40 degrees at 28 days