«Ibscenest nansence!» Oscurità, sogno e tempo in Finnegans Wake

Ilustración: "Grito", Gabriel Rodríguez de AlbaThis paper examines some aesthetic issues concerning James Joyce’s experimental novel Finnegans Wake (1939). First of all I will focus my attention I) on some principia, which are related to the novel’s obscurity (in both meanings of the word: darkness and lack of clarity), and second II) on the identity of the narrator who holds the «ordovico» together. I will finally III) try to show that by the convergence of memory and narration, the reader’s «act of oblivion» is to be considered as an essential gesture to let open the hermeneutic potential exhibited by the Wake.L’articolo esamina alcune questioni estetiche sul romanzo sperimentale Finnegans Wake (1939) di James Joyce. Innanzitutto si focalizzerà l’attenzione I) su alcuni principî costituitivi in relazione all’oscurità del romanzo (intesa in entrambi i sensi di tenebra e di mancanza di chiarezza) e, in secondo luogo, II) sull’identità del narratore garante dell’«ordovico». Si tenterà di mostrare infine III) come, nel convergere di narrazione e memoria, l’«atto di oblio» del lettore sia da considerarsi come gesto essenziale al fine di lasciare spazio all’apertura ermeneutica che il Wake esibisce

«Ibscenest nansence!» Oscurità, sogno e tempo in Finnegans Wake

This paper examines some aesthetic issues concerning James Joyce’s experimental novel Finnegans Wake (1939). First of all I will focus my attention I) on some principia, which are related to the novel’s obscurity (in both meanings of the word: darkness and lack of clarity), and second II) on the identity of the narrator who holds the «ordovico» together. I will finally III) try to show that by the convergence of memory and narration, the reader’s «act of oblivion» is to be considered as an essential gesture to let open the hermeneutic potential exhibited by the Wake.L’articolo esamina alcune questioni estetiche sul romanzo sperimentale Finnegans Wake (1939) di James Joyce. Innanzitutto si focalizzerà l’attenzione I) su alcuni principî costituitivi in relazione all’oscurità del romanzo (intesa in entrambi i sensi di tenebra e di mancanza di chiarezza) e, in secondo luogo, II) sull’identità del narratore garante dell’«ordovico». Si tenterà di mostrare infine III) come, nel convergere di narrazione e memoria, l’«atto di oblio» del lettore sia da considerarsi come gesto essenziale al fine di lasciare spazio all’apertura ermeneutica che il Wake esibisce

Brief communication "Calabria daily rainfall from 1970 to 2006"

Abstract. This brief communication introduces a new quality-controlled precipitation database for Calabria, shows the precipitation trend for the period considered, and correlates daily rainfall with some common teleconnection patterns. The database consists of daily accumulated precipitation collected by 61 rain gauges from 1 January 1970 to 31 December 2006. The 37-year trend in yearly rainfall shows a decrease of 4.7 mm/y, with a 17% reduction in the yearly mean value. The correlation of the daily rainfall with large-scale patterns shows that the Mediterranean Oscillation Index (MOI a/c) is a useful predictor of daily precipitation over Calabria

Ofatumumab and Early Immunological Cells Subset Characterization in Naïve Relapsing Multiple Sclerosis Patients: A Real-World Study

Background: Ofatumumab (OFA) is a fully human anti-CD20 monoclonal antibody administered with a 20 mg subcutaneous monthly dosing regimen. Methods: Inclusion criteria were patients: 1) aged 18-55; 2) with a confirmed diagnosis of relapsing Multiple Sclerosis (RMS), per the revised 2010 McDonald criteria; 2) who started OFA according to Italian Medicines Agency prescription rules and within 12 months from the RMS diagnosis; 3) naïve to any disease-modifying therapy. The primary outcome was to offer an overview of cellular subsets of RMS naïve patients (time 0) and then after 4 weeks (time 1) and 12 weeks (time 2) on therapy with OFA in a real-world setting. Results: Fifteen patients were enrolled. CD3+ T cell frequencies were higher at time 1 ( .4, SD 7.7) and time 2 ( .6, SD 5.8) when compared to time 0 (r.4, SD 9.8), p = .013. B naïve cells were barely detectable in the OFA group at time 1 (%0.4, SD 0.5) and 2 (%1.4, SD 2.9) when compared to time 0 ( .5, SD 3.8), p < .001. Conclusion: The progressive and increasing use of anti-CD20 drugs imposes the need for larger, prospective, real-world, long-term studies to characterize further immunophenotypes of patients with RMS treated with OFA

How the cognitive reserve interacts with β-amyloid deposition in mitigating FDG metabolism: An observational study

This observational study had the aim to assess the interaction between cognitive reserve (CR) and cerebrospinal fluid β-amyloid1-42 (Aβ1-42) in modulating brain [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) metabolism in patients with moderate Alzheimer disease (AD).Twenty-seven patients with probable AD and 25 neurological normal subjects (NNS) entered the study. All participants had an FDG-PET scan, and AD patients also received a lumbar puncture to measure Aβ1-42, 181p-tau, and Tau concentrations. Based on years of formal education, AD patients were classified as highly educated-AD (years of formal education >5) or less educated-AD (years of formal education <5). By using a voxel-wise approach, we first investigated differences in the cerebral glucose uptake between AD and NNS, then we assessed the interaction between level of education (a proxy of CR) and cerebrospinal fluid biomarkers on FDG-PET metabolism in the patient groups.Significantly lower glucose uptake was observed in the posterior cingulate gyrus, in the precuneus, in the inferior and medial temporal gyrus, and in the inferior parietal lobule of AD patients compared with NNS. A significant interaction was found between CR and Aβ1-42 values on brain metabolism in the inferior and medial temporal gyrus bilaterally.The AD patients with higher CR level and marked signs of neuropathology showed glucose hypometabolism in regions typically targeted by AD pathology. This finding supports the hypothesis that CR partially compensates for the effect of Aβ plaques on cognitive impairment, helps in patients' clinical staging, and opens new possibilities for the development of nonpharmacological interventions

Synergistic interaction of fatty acids and oxysterols impairs mitochondrial function and limits liver adaptation during nafld progression

The complete mechanism accounting for the progression from simple steatosis to steatohepatitis in nonalcoholic fatty liver disease (NAFLD) has not been elucidated. Lipotoxicity refers to cellular injury caused by hepatic free fatty acids (FFAs) and cholesterol accumulation. Excess cholesterol autoxidizes to oxysterols during oxidative stress conditions. We hypothesize that interaction of FAs and cholesterol derivatives may primarily impair mitochondrial function and affect biogenesis adaptation during NAFLD progression. We demonstrated that the accumulation of specific non-enzymatic oxysterols in the liver of animals fed high-fat+high-cholesterol diet induces mitochondrial damage and depletion of proteins of the respiratory chain complexes. When tested in vitro, 5α-cholestane-3β,5,6β-triol (triol) combined to FFAs was able to reduce respiration in isolated liver mitochondria, induced apoptosis in primary hepatocytes, and down-regulated transcription factors involved in mitochondrial biogenesis. Finally, a lower protein content in the mitochondrial respiratory chain complexes was observed in human non-alcoholic steatohepatitis. In conclusion, hepatic accumulation of FFAs and non-enzymatic oxysterols synergistically facilitates development and progression of NAFLD by impairing mitochondrial function, energy balance and biogenesis adaptation to chronic injury

New Insights Into Immune Cell-Derived Extracellular Vesicles in Multiple Sclerosis

Extracellular vesicles (EVs) are small vesicles including microvesicles and exosomes which differ in their distinct size, density, biogenesis, and content. Until recently, EVs were considered as simply scrap products. Nowadays, they are engendering huge interest and their shedding plays a well-recognized role in intercellular communication, not only participating in many physiological processes, but also suspected of being involved in the pathogenesis of many diseases. The present review aims to summarize the latest updates on immune cell-derived EVs, focusing on the current status of knowledge in Multiple Sclerosis. Significant progress has been made on their physical and biological characterization even though many aspects remain unclear and need to be addressed. However, it is worth further investigating in order to deepen the knowledge of this unexplored and fascinating field that could lead to intriguing findings in the evaluation of EVs as biomarkers in monitoring the course of diseases and the response to treatments

Treatment with metformin in twelve patients with Lafora disease

Background: Lafora disease (LD) is a rare, lethal, progressive myoclonus epilepsy for which no targeted therapy is currently available. Studies on a mouse model of LD showed a good response to metformin, a drug with a well known neuroprotective effect. For this reason, in 2016, the European Medicines Agency granted orphan designation to metformin for the treatment of LD. However, no clinical data is available thus far. Methods: We retrospectively collected data on LD patients treated with metformin referred to three Italian epilepsy centres. Results: Twelve patients with genetically confirmed LD (6 EPM2A, 6 NHLRC1) at middle/late stages of disease were treated with add-on metformin for a mean period of 18 months (range: 6-36). Metformin was titrated to a mean maintenance dose of 1167 mg/day (range: 500-2000 mg). In four patients dosing was limited by gastrointestinal side-effects. No serious adverse events occurred. Three patients had a clinical response, which was temporary in two, characterized by a reduction of seizure frequency and global clinical improvement. Conclusions: Metformin was overall safe in our small cohort of LD patients. Even though the clinical outcome was poor, this may be related to the advanced stage of disease in our cases and we cannot exclude a role of metformin in slowing down LD progression. Therefore, on the grounds of the preclinical data, we believe that treatment with metformin may be attempted as early as possible in the course of LD

The adipokine leptin modulates adventitial pericyte functions by autocrine and paracrine signalling

AbstractTransplantation of adventitial pericytes (APCs) improves recovery from tissue ischemia in preclinical animal models by still unknown mechanisms. This study investigates the role of the adipokine leptin (LEP) in the regulation of human APC biological functions. Transcriptomic analysis of APCs showed components of the LEP signalling pathway are modulated by hypoxia. Kinetic studies indicate cultured APCs release high amounts of immunoreactive LEP following exposure to hypoxia, continuing upon return to normoxia. Secreted LEP activates an autocrine/paracrine loop through binding to the LEP receptor (LEPR) and induction of STAT3 phosphorylation. Titration studies using recombinant LEP and siRNA knockdown of LEP or LEPR demonstrate the adipokine exerts important regulatory roles in APC growth, survival, migration and promotion of endothelial network formation. Heterogeneity in LEP expression and secretion may influence the reparative proficiency of APC therapy. Accordingly, the levels of LEP secretion predict the microvascular outcome of APCs transplantation in a mouse limb ischemia model. Moreover, we found that the expression of the Lepr gene is upregulated on resident vascular cells from murine ischemic muscles, thus providing a permissive milieu to transplanted LEP-expressing APCs. Results highlight a new mechanism responsible for APC adaptation to hypoxia and instrumental to vascular repair.</jats:p