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Stefania Gioia,1 Oliviero Riggio,1 Silvia Nardelli,1 Giulia d’Amati,2 Lorenzo Ridola1 1Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy; 2Department of Radiological, Oncological, and Pathological Sciences, Sapienza University of Rome, Rome, ItalyCorrespondence: Stefania GioiaDepartment of Translational and Precision Medicine, Sapienza University of Rome, Rome, ItalyTel +39 06 49970463Email stensgioia@hotmail.comAbstract: The term porto-sinusoidal vascular disease (PSVD) has been recently proposed to replace the term idiopathic non-cirrhotic portal hypertension (INCPH) to describe patients with or without signs of portal hypertension and typical histological lesions involving the portal venules or sinusoids in the absence of cirrhosis. According to the new definition, the presence of known causes of liver disease as well as of portal vein thrombosis does not rule out PSVD. Therefore, the patients in whom the diagnosis of PSVD is possible are much more than the patients strictly fulfilling the diagnostic criteria for INCPH. In this setting, the clinical challenge for the hepatologist is to identify patients at risk of developing PSVD and to indicate liver biopsy to confirm the diagnosis. We describe some possible scenarios in which PSVD should always be suspected, and we provide some tools useful to reach the diagnosis of PSVD.Keywords: porto-sinusoidal vascular liver disease, idiopathic non-cirrhotic portal hypertension, portal vein thrombosis, portal hypertension

Oliviero Riggio,1 Stefania Gioia,1 Ilaria Pentassuglio,1 Valeria Nicoletti,1 Michele Valente,2 Giulia d’Amati2 1Department of Clinical Medicine, Center for the Diagnosis and Treatment of Portal Hypertension, 2Department of Radiological, Oncological, and Pathological Sciences, Sapienza University of Rome, Rome, Italy Abstract: The term idiopathic noncirrhotic portal hypertension (INCPH) has been recently proposed to replace terms, such as hepatoportal sclerosis, idiopathic portal hypertension, incomplete septal cirrhosis, and nodular regenerative hyperplasia, used to describe patients with a hepatic presinusoidal cause of portal hypertension of unknown etiology, characterized by features of portal hypertension (esophageal varices, nonmalignant ascites, porto-venous collaterals), splenomegaly, patent portal, and hepatic veins and no clinical and histological signs of cirrhosis. Physicians should learn to look for this condition in a number of clinical settings, including cryptogenic cirrhosis, a disease known to be associated with INCPH, drug administration, and even chronic alterations in liver function tests. Once INCPH is clinically suspected, liver histology becomes mandatory for the correct diagnosis. However, pathologists should be familiar with the histological features of INCPH, especially in cases in which histology is not only requested to exclude liver cirrhosis. Keywords: idiopathic portal hypertension, obliterative portal venopathy, esophageal varices, splenomegaly

We apply a matched‐filter‐technique to augment the detected events in the time window between the two mainshocks of the 2012 Emilia seismic sequence (Italy), 20 (Mw 6.1) and 29 (Mw 6.0) May. Using well‐located templates, we increase the number of detections from 1,727 to 7,616. This greater detail allows evidencing migrations of seismic events from the nucleation point of the first shock to the second. Repeating earthquakes are also found between the two mainshocks. The seismicity pattern suggests a transient slip acting immediately after the shallow first event, weakening and loading the volume around the deep nucleation point of the 29 May Mw 6.0 earthquake. We interpret migrations and repeaters as the fingerprint of an early afterslip triggered by the first mainshock. By taking into account the earliest repeater we estimate a cumulative slip of approximately 27 cm (Mw 5.7). This value could represent the lower bound of the total released afterslip. Plain Language Summary: To improve our understanding of interactions between subsequent mainshocks, we investigated the spatiotemporal evolution of the seismicity for the 2012 Emilia seismic sequence (Italy) in the time window from 20 to 29 May 2012. We use a technique based on waveform matching to augment the detected earthquakes. From the new catalog, we observe along‐strike and at depth seismic migrations consistent with a phase of rapid postseismic slip concentrated near the base of the seismogenic zone immediately after the first main shock. We suggest that the afterslip contributed to loading the fault rupture area of the 29 May Mw 6.0 earthquake. Key Points: Newly detected early aftershocks suggest a fast migration at depth moving from the 20 May hypocenter to the 29 May nucleation pointRepeating earthquakes have been identified between the two mainshocksMigration and repeaters suggest an afterslip that could have contributed to loading the 29 May focal volume [ABSTRACT FROM AUTHOR]

Leber's hereditary optic neuropathy, the most frequent mitochondrial disease due to mitochondrial DNA point mutations in complex I, is characterized by the selective degeneration of retinal ganglion cells, leading to optic atrophy and loss of central vision prevalently in young males. The current study investigated the reasons for the higher prevalence of Leber's hereditary optic neuropathy in males, exploring the potential compensatory effects of oestrogens on mutant cell metabolism. Control and Leber's hereditary optic neuropathy osteosarcoma-derived cybrids (11778/ND4, 3460/ND1 and 14484/ND6) were grown in glucose or glucose-free, galactose-supplemented medium. After having shown the nuclear and mitochondrial localization of oestrogen receptors in cybrids, experiments were carried out by adding 100 nM of 17β-oestradiol. In a set of experiments, cells were pre-incubated with the oestrogen receptor antagonist ICI 182780. Leber's hereditary optic neuropathy cybrids in galactose medium presented overproduction of reactive oxygen species, which led to decrease in mitochondrial membrane potential, increased apoptotic rate, loss of cell viability and hyper-fragmented mitochondrial morphology compared with control cybrids. Treatment with 17β-oestradiol significantly rescued these pathological features and led to the activation of the antioxidant enzyme superoxide dismutase 2. In addition, 17β-oestradiol induced a general activation of mitochondrial biogenesis and a small although significant improvement in energetic competence. All these effects were oestrogen receptor mediated. Finally, we showed that the oestrogen receptor β localizes to the mitochondrial network of human retinal ganglion cells. Our results strongly support a metabolic basis for the unexplained male prevalence in Leber's hereditary optic neuropathy and hold promises for a therapeutic use for oestrogen-like molecules. [ABSTRACT FROM AUTHOR]

The aim of this work is an efficient methodology development for a real-time control of human assembling sequences of mechanical components. The method involves a CAD environment, an hardware system, referred to as a PAA (Personal Active Assistant), and a set of Mixed Reality features. The whole scheme is targeted to positively influence the connection between CAD and Mixed Reality in order to proficiently reduce the gap between engineers and manual operators. The system is based on a CAD assembly module and on an Mixed Reality wearable equipment. It can be used to improve several activities in the industrial field, such as operator professional training, optimal assembly sequence seeking or on-field teleconferencing (suitable for remote collaboration or for full exploitation of Concurrent Engineering suggestions during design and set up stages). The main characteristic of PAA is a real-time wireless linkage to a remote server or designer workstation, where project geometric database is stored. The Mixed Reality wearable equipment consists of an optical see-through display device and a PAA head-mounted camera. The user can freely operate in the mixed environment, while the camera can record the human driven assembly sequence and check the efficiency and correctness via object recognition: an incrementally sub-assembly detection algorithm has been developed in order to achieve complex dataset monitoring. Conversely, designer or assembly planner can exploit the peculiarities of Mixed Reality-based assembly: a straightforward interaction with the assembly operator can be obtained by sending vocal advices or by displaying superimposed visual information on the real scene. In the paper a new method for CAD models and Mixed Reality environment integration will be presented and discussed in order to improve and simplify personnel training or warehouse part seeking. [ABSTRACT FROM AUTHOR]

The results from direct numerical simulations of turbulent Boussinesq convection are briefly presented. The flow is computed for a cylindrical cell of aspect ratio 1/2 in order to compare with the results from recent experiments. The results span eight decades of Ra from 2×106 to 2×1014 and form the baseline data for a strictly Boussinesq fluid of constant Prandtl number (Pr=0.7). A conclusion is that the Nusselt number varies nearly as the 1/3 power of Ra for about four decades towards the upper end of the Ra range covered. [ABSTRACT FROM AUTHOR]

The kinetics of domain growth of fluid mixtures quenched from a disordered to a lamellar phase has been studied in three dimensions. We use a numerical approach based on the lattice Boltzmann method (LBM). A novel implementation for LBM which "fuses" the collision and streaming steps is used in order to reduce memory and bandwidth requirements. We find that extended defects between stacks of lamellae with different orientation dominate the late time dynamics. [ABSTRACT FROM AUTHOR]

In this article we discuss the dynamical features of intermittent fluctuations in homogeneous shear flow turbulence. In this flow the energy cascade is strongly modified by the production of turbulent kinetic energy related to the presence of vortical structures induced by the shear. As a consequence, the intermittency of velocity fluctuations increases with respect to homogeneous and isotropic turbulence. By using direct numerical simulations, we show that the refined Kolmogorov similarity is broken and a new form of similarity is observed, in agreement with previous results obtained in turbulent boundary layers. We find here that the statistical properties of the energy dissipation are practically unchanged with respect to homogeneous isotropic conditions, while the increased intermittency is entirely captured in terms of the new similarity law. © 2002 American Institute of Physics. [ABSTRACT FROM AUTHOR]

In this study, we reveal that leptin evokes an acute hypotensive effect in 6-hydroxydopamine sympathectomized rats (response to maximal leptin dose, mean blood pressure: from 92 +/- 4 to 78 +/- 2 mmHg, P < 0.01). This hemodynamic effect is related to a direct action of the hormone on vascular tone, since in aortic and mesenteric rings increasing doses of leptin evoke a dose-dependent vasorelaxation (aorta: from 3 +/- 1 to 36 +/- 3, n = 15; mesenteric: from 6 +/- 1 to 30 +/- 5, n = 10), which is impaired by endothelial denudation. In particular, leptin-evoked vasorelaxation is impaired by nitric oxide synthase inhibition in aorta (delta% of maximal response: from 36 +/- 3 to 3 +/- 1, P < 0.01) and by endothelium-derived hyperpolarizing factor (EDHF) inhibition in mesenteric arteries (delta% of maximal response: from 30 +/- 5 to 7 +/- 2, P < 0.01), suggesting that vasorelaxation evoked by leptin is heterogeneous and related to the vascular bed. Finally, the inhibition of nitric oxide synthase by NG-nitro-L-arginine-methyl ester does not modify blood pressure response to leptin, suggesting a predominant role of the EDHF mechanism in the hypotensive effect of leptin. [ABSTRACT FROM AUTHOR]

The goal of our study was to evaluate the incidence of heart involvement in AIDS patients during various stages of the disease. Between January 1988 to September 1991, we conducted a prospective study in 114 anti-HIV positive patients. The patients, whose mean age ( ± SD) was 34·6 ± 5·4 years (range 20 to 54), were divided into three groups: anti-HIV positive asymptomatic (n = 31; 27%), AIDS related complex (ARC) group IV-A (n=11; 10%), and AIDS subgroups IV-C1 (n = 62; 54%) and IV-D (n=10;9%). Overall, 84 patients (74%) were i.v. drug abusers, 24 (21%) were homosexuals, and six (5%) were partners at risk. Zidovudine (AZT) was administered to 94 patients (82%). Opportunistic infections and/or secondary malignancies were detected in 72 patients (63%). Electrocardiographic changes were of little clinical relevance. Of 72 AIDS patients, 47 (65·2%) presented a cardiac involvement: 12 subjects (16·6%) were affected by a dilated cardiomyopathy, 13 (18%) by pericardial effusion, three (4·1%) by mitral valve prolapse, four (5·5%) by myocarditis, five (6·9%) by valvular bacterial endocarditis, and 10 (13·8%) by alterations of left ventricle regional contractility. During a mean follow-up period of 44 months, 29 AIDS patients (40·2%) died. Death was attributed to a cardiac event in four patients; autopsy could be performed in 24 of the 29 patients who died. Our results demonstrate that heart involvement is present in 45·6% of HIV-infected patients, but only in the end-stage of the disease (AIDS) and it is presumably due to opportunistic infections and/or secondary malignancies. The direct role of HIV in the genesis of cardiomyopathy remains uncertain and will be evaluated by further studies. [ABSTRACT FROM PUBLISHER]

Proposes a new form of the refined Kolmogorov similarity hypothesis (RKSH) for wall bounded turbulence. Occurrence of a distinct violation of the RKSH together with the simultaneous persistence of scaling laws; Confirmation of the prevailing role of the momentum transfer towards the wall in the near wall dynamics.

We describe a rare case of Dirofilaria repens infection presenting as peripheral lung nodules and mimicking a metastatic focus from a previously diagnosed cutaneous melanoma. To avoid invasive investigations before arriving at the correct diagnosis, dirofilariasis should be included as a part of the diagnostic process in subjects with lung nodules who live in (or have traveled to) endemic regions. [ABSTRACT FROM AUTHOR]

Autophagy is usually a pro-survival mechanism in cancer cells, especially in the course of chemotherapy, thus autophagy inhibition may enhance the chemotherapy-mediated anti-cancer effect. However, since autophagy is strongly involved in the immunogenicity of cell death by promoting ATP release, its inhibition may reduce the immune response against tumors, negatively influencing the overall outcome of chemotherapy. In this study, we evaluated thein vitroandin vivoanti-cancer effect of curcumin (CUR) against Her2/neu overexpressing breast cancer cells (TUBO) in the presence or in the absence of the autophagy inhibitor chloroquine (CQ). We found that TUBO cell death induced by CUR was increasedin vitroby CQ and slightlyin vivoin nude mice. Conversely, CQ counteracted the Cur cytotoxic effect in immune competent mice, as demonstrated by the lack ofin vivotumor regression and the reduction of overall mice survival as compared with CUR-treated mice. Immunohistochemistry analysis revealed the presence of a remarkable FoxP3 T cell infiltrate within the tumors in CUR/CQ treated mice and a reduction of T cytotoxic cells, as compared with single CUR treatment. These findings suggest that autophagy is important to elicit anti-tumor immune response and that autophagy inhibition by CQ reduces such response also by recruiting T regulatory (Treg) cells in the tumor microenvironment that may be pro-tumorigenic and might counteract CUR-mediated anti-cancer effects. [ABSTRACT FROM PUBLISHER]

We perform a joint numerical and experimental study to systematically characterize the motion of 30 pi drops of pure water and of ethanol in water solutions, sliding over a periodic array of alternating hydrophobic and hydrophilic stripes with a large wettability contrast and a typical width of hundreds of microns. The fraction of the hydrophobic areas has been varied from about 20% to 80%. The effects of the heterogeneous patterning can be described by a renormalized value of the critical Bond number, i.e., the critical dimensionless force needed to depin the drop before it starts to move. Close to the critical Bond number we observe a jerky motion characterized by an evident stick-slip dynamics. As a result, dissipation is strongly localized in time, and the mean velocity of the drops can easily decrease by an order of magnitude compared to the sliding on the homogeneous surface. Lattice Boltzmann numerical simulations are crucial for disclosing to what extent the sliding dynamics can be deduced from the computed balance of capillary, viscous, and body forces by varying the Bond number, the surface composition, and the liquid viscosity. Beyond the critical Bond number, we characterize both experimentally and numerically the dissipation inside the droplet by studying the relation between the average velocity and the applied volume forces. [ABSTRACT FROM AUTHOR]

We present a comprehensive study of water drops sliding down chemically heterogeneous surfaces formed by a periodic pattern of alternating hydrophobic and hydrophilic stripes. Drops are found to undergo a stick-slip motion whose average speed is an order of magnitude smaller than that measured on a homogeneous surface having the same static contact angle. This motion is the result of the periodic deformations of the drop interface when crossing the stripes. Numerical simulations confirm this view and are used to elucidate the principles underlying the experimental observations. [ABSTRACT FROM AUTHOR]

An infant with normal facies and none of the extracardiac anomalies usually associated with Williams syndrome presented at birth with an echocardiographic pattern of supravalvular pulmonary stenosis and displastic pulmonary valve. A clinical reappraisal was planned at 3 months of age, but the girl died suddenly at home at 2 months of age. At autopsy, both ventricles were hypertrophic, and the valves showed mild dysplasia. The walls of the great arteries were thick, with a 'washed leather' consistency, but there was no gross evidence of discrete stenosis. The histologic mosaic appearance of the media of the great arteries, due to elastosis and extreme disarray of the elastic lamellae, prompted a postmortem diagnosis of supravalvar aortic stenosis and suggested a diagnosis of Williams syndrome, which was subsequently confirmed by fluorescence in situ hybridization. Pediatricians and pathologists should be alerted that Williams syndrome in the newborn may present as an isolated supravalvular pulmonary stenosis, whereas supravalvular aortic stenosis becomes clinically significant only a few months later. [ABSTRACT FROM AUTHOR]