16 research outputs found

    Short-Term Memory and Sign Languages. Sign Span and its Linguistic Implications

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    In this paper we discuss two distinct, although related questions. The first question is what explains the well-known fact that short-term memory (span) is lower for signs than for words. We review some explanations that have been proposed for this fact at the light of the results of a novel experiment involving gating of signs. The second question is how signers can process fully-fledged grammatical systems like sign languages even if they rely on a limited short-term memory. In order to deal with this issue, we discuss the distribution in sign languages of the configuration that is most challenging for short-term memory, namely center embedding. The conclusion is that center embedding is possible only if special strategies based on the use of space are used that are likely to reduce the short-term memory burden

    Bowel parasitosis and neuroendocrine tumours of the appendix. A report from the Italian TREP project

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    Five children with a neuroendocrine tumour (NET) of the appendix associated with a parasitic bowel infection are described, and the possibility of inflammation-triggered carcinogenesis is discussed. Schistosoma haematobium is linked primarily to bladder cancer but it has been reported in association with several other histotypes, including NETs of the gastrointestinal tract. Conversely, Enterobius vermicularis has not yet been claimed to participate in the onset of pre-cancerous conditions or tumours. The rare occurrence of contemporary appendiceal NETs and parasitic infection, raises the intriguing hypothesis of an inflammation-related carcinogenesis, although a cause-effect relationship cannot be established. Larger international series of childhood appendiceal NETs, which also include countries with higher prevalence of parasitic bowel infections, are needed to further clarify this possible cause-effect relationshi

    Synthetic Lethal Screen Identifies NF-ÎșB as a Target for Combination Therapy with Topotecan for patients with Neuroblastoma

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    <p>Abstract</p> <p>Background</p> <p>Despite aggressive multimodal treatments the overall survival of patients with high-risk neuroblastoma remains poor. The aim of this study was to identify novel combination chemotherapy to improve survival rate in patients with high-risk neuroblastoma.</p> <p>Methods</p> <p>We took a synthetic lethal approach using a siRNA library targeting 418 apoptosis-related genes and identified genes and pathways whose inhibition synergized with topotecan. Microarray analyses of cells treated with topotecan were performed to identify if the same genes or pathways were altered by the drug. An inhibitor of this pathway was used in combination with topotecan to confirm synergism by <it>in vitro </it>and <it>in vivo </it>studies.</p> <p>Results</p> <p>We found that there were nine genes whose suppression synergized with topotecan to enhance cell death, and the NF-ÎșB signaling pathway was significantly enriched. Microarray analysis of cells treated with topotecan revealed a significant enrichment of NF-ÎșB target genes among the differentially altered genes, suggesting that NF-ÎșB pathway was activated in the treated cells. Combination of topotecan and known NF-ÎșB inhibitors (NSC 676914 or bortezomib) significantly reduced cell growth and induced caspase 3 activity <it>in vitro</it>. Furthermore, in a neuroblastoma xenograft mouse model, combined treatment of topotecan and bortezomib significantly delayed tumor formation compared to single-drug treatments.</p> <p>Conclusions</p> <p>Synthetic lethal screening provides a rational approach for selecting drugs for use in combination therapy and warrants clinical evaluation of the efficacy of the combination of topotecan and bortezomib or other NF-ÎșB inhibitors in patients with high risk neuroblastoma.</p

    Serum Albumin Is Inversely Associated With Portal Vein Thrombosis in Cirrhosis

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    We analyzed whether serum albumin is independently associated with portal vein thrombosis (PVT) in liver cirrhosis (LC) and if a biologic plausibility exists. This study was divided into three parts. In part 1 (retrospective analysis), 753 consecutive patients with LC with ultrasound-detected PVT were retrospectively analyzed. In part 2, 112 patients with LC and 56 matched controls were entered in the cross-sectional study. In part 3, 5 patients with cirrhosis were entered in the in vivo study and 4 healthy subjects (HSs) were entered in the in vitro study to explore if albumin may affect platelet activation by modulating oxidative stress. In the 753 patients with LC, the prevalence of PVT was 16.7%; logistic analysis showed that only age (odds ratio [OR], 1.024; P = 0.012) and serum albumin (OR, -0.422; P = 0.0001) significantly predicted patients with PVT. Analyzing the 112 patients with LC and controls, soluble clusters of differentiation (CD)40-ligand (P = 0.0238), soluble Nox2-derived peptide (sNox2-dp; P &lt; 0.0001), and urinary excretion of isoprostanes (P = 0.0078) were higher in patients with LC. In LC, albumin was correlated with sCD4OL (Spearman's rank correlation coefficient [r(s)], -0.33; P &lt; 0.001), sNox2-dp (r(s), -0.57; P &lt; 0.0001), and urinary excretion of isoprostanes (r(s), -0.48; P &lt; 0.0001) levels. The in vivo study showed a progressive decrease in platelet aggregation, sNox2-dp, and urinary 8-iso prostaglandin F2 alpha-III formation 2 hours and 3 days after albumin infusion. Finally, platelet aggregation, sNox2-dp, and isoprostane formation significantly decreased in platelets from HSs incubated with scalar concentrations of albumin. Conclusion: Low serum albumin in LC is associated with PVT, suggesting that albumin could be a modulator of the hemostatic system through interference with mechanisms regulating platelet activation

    Sintassi: 2 La struttura frasale

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    La Grammatica della lingua dei segni italiana (LIS) (A Grammar of Italian Sign Language (LIS)) ù un’ampia presentazione delle proprietà grammaticali della LIS. È stata pensata come uno strumento per studenti, insegnanti, interpreti, la Comunità Sorda, ricercatori, linguisti e chiunque sia interessato allo studio della LIS. È uno dei risultati del progetto Horizon 2020 SIGN-HUB. È composta da sei Parti: la Parte 1 ù dedicata al panorama sociale e storico in cui si ù sviluppata la lingua, mentre le altre cinque Parti descrivono i domini linguistici di Fonologia, Lessico, Morfologia, Sintassi e Pragmatica. Grazie al formato digitale della grammatica, i testi e i video sono saldamente interconnessi, progettati per adattarsi ad hoc alla descrizione di una lingua visiva

    Syntax: 2 Clause structure

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    A Grammar of Italian Sign Language (LIS) is a comprehensive presentation of the grammatical properties of LIS. It has been conceived as a tool for students, teachers, interpreters, the Deaf community, researchers, linguists and whoever is interested in the study of LIS. It is one output of the Horizon 2020 SIGN-HUB project. It is composed of six Parts: Part 1 devoted to the social and historical background in which the language has developed, and five Parts covering the main properties of Phonology, Lexicon, Morphology, Syntax and Pragmatics. Thanks to the electronic format of the grammar, text and videos are highly interconnected and are designed to fit the description of a visual language

    Arachidonic acid metabolites and endothelial dysfunction of portal hypertension

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    Increased resistance to portal flow and increased portal inflow due to mesenteric vasodilatation represent the main factors causing portal hypertension in cirrhosis. Endothelial cell dysfunction, defined as an imbalance between the synthesis, release, and effect of endothelial mediators of vascular tone, inflammation, thrombosis, and angiogenesis, plays a major role in the increase of resistance in portal circulation, in the decrease in the mesenteric one, in the development of collateral circulation. Reduced response to vasodilators in liver sinusoids and increased response in the mesenteric arterioles, and, viceversa, increased response to vasoconstrictors in the portal-sinusoidal circulation and decreased response in the mesenteric arterioles are also relevant to the pathophysiology of portal hypertension. Arachidonic acid (AA) metabolites through the three pathways, cyclooxygenase (COX), lipoxygenase, and cytochrome P450 monooxygenase and epoxygenase, are involved in endothelial dysfunction of portal hypertension. Increased thromboxane-A2 production by liver sinusoidal endothelial cells (LSECs) via increased COX-1 activity/expression, increased leukotriens, increased epoxyeicosatrienoic acids (EETs) (dilators of the peripheral arterial circulation, but vasoconstrictors of the portal-sinusoidal circulation), represent a major component in the increased portal resistance, in the decreased portal response to vasodilators and in the hyper-response to vasoconstrictors. Increased prostacyclin (PGI2) via COX-1 and COX-2 overexpression, and increased EETs/heme-oxygenase-1/K channels/gap junctions (endothelial derived hyperpolarizing factor system) play a major role in mesenteric vasodilatation, hyporeactivity to vasoconstrictors, and hyper-response to vasodilators. EETs, mediators of liver regeneration after hepatectomy and of angiogenesis, may play a role in the development of regenerative nodules and collateral circulation, through stimulation of vascular endothelial growth factor (VEGF) inside the liver and in the portal circulation. Pharmacological manipulation of AA metabolites may be beneficial for cirrhotic portal hypertension

    Characterization of a murine model of cardiorenal syndrome type 1 by high-resolution Doppler sonography

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    ABSTRACT: Cardiorenal syndrome type 1 (CRS-1) is the acute kidney disfunction caused by an acute worsening of cardiac function. CRS-1 is the consequence of renal vasoconstriction secondary to renin-angiotensin system (RAS) activation. No animal models of CRS-1 are described in literature. PURPOSE: To characterize a murine model of CRS-1 by using a high-resolution ultrasound echo-color Doppler system (VEVO2100). MATERIALS: Post-ischemic heart failure was induced by coronary artery ligation (LAD) in seven CD1 mice. Fifteen and thirty days after surgery, mice underwent cardiac and renal echo-color Doppler. Serum creatinine and plasma renin activity were measured after killing. Animals were compared to seven CD1 control mice. RESULTS: Heart failure with left ventricle dilatation (end diastolic area, p < 0.05 vs. controls) and significantly reduced ejection fraction (EF; p < 0.01 vs. controls) was evident 15 days after LAD. We measured a significant renal vasoconstriction in infarcted mice characterized by increased renal pulsatility index (PI; p < 0.05 vs. controls) associated to increased creatinine and renin levels (p < 0.05 vs. controls). CONCLUSIONS: The mice model of LAD is a good model of CRS-1 evaluable by Doppler sonography and characterized by renal vasoconstriction due to the activation of the renin-angiotensin system secondary to heart failure

    Tactile short-term memory in sensory deprived individuals

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    To verify whether loosing a sense or two has consequences on a spared sensory modality, namely touch, and whether these consequences depend on practice or are biologically determined, we investigated 13 deafblind participants, 16 deaf participants, 15 blind participants, and 13 matched normally sighted and hearing controls on a tactile short-term memory task, using checkerboard matrices of increasing length in which half of the squares were made up of a rough texture and half of a smooth one. Time of execution of a fixed matrix, number of correctly reproduced matrices, largest matrix correctly reproduced and tactile span were recorded. The three groups of sensory- deprived individuals did not differ in any measure, while blind and deaf participants outscored controls in all parameters except time of execution; the difference approached significance for deafblind people compared to controls only in one measure, namely correctly reproduced matrices. In blind and deafblind participants, performance negatively correlated with age of Braille acquisition, the older being the subject when acquiring Braille, the lower the performance, suggesting that practice plays a role. However, the fact that deaf participants, who did not share tactile experience, performed similarly to blind participants and significantly better than controls highlights that practice cannot be the only contribution to better tactile memory
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