Cara, vecchia metonimia: un ritorno inatteso

The countless changes in rhetorical studies have brought the classic “art of discourse” to a systematic breakdown: first, only in favor of elocutio, then, of poetic lexis and finally, of metaphor. The innumerable changes in rhetoric have led the classic “art of speaking” to a systematic breakdown, first in favor only of elocutio, then of poetic lexis, finally of metaphor. The metonymy was most affected by the new structure of “tropological reduction”. After a moment of success, starting from the last two decades of the twentieth century, the metonymy was mistreated and downgraded to a second-rate trope compared to the metaphor. In the last fifteen years, thanks to cognitive sciences and neurosciences, the scientific community has started to recognize metonymy as a primary role in the cognitive ecosystem. The metonymy has even been recognized as superior at a bio-evolutionary and neuro-physiological level, compared to the metaphor, considered a secondary phenomenon and more disconnected from the experiential spheres of the daily habitat. The functioning of the brain is programmed to use metonymies thanks to both the ability of inferential reasoning and the fact that emotions and physiological symptoms are linked in an incessant metonymic operation. In particular, this occurs when conditioned stimuli predict and subsume unconditioned emotions. In this way impulse self-control is encouraged.La retorica ha subito innumerevoli cambiamenti che hanno portato la classica “arte del parlare” a un sistematico sfaldamento, dapprima a favore della sola elocutio, poi della lexis poetica, infine della metafora. A risentire maggiormente del nuovo assetto di “riduzione tropologica” è la metonimia, bistrattata e declassata a tropo di second’ordine in confronto alla metafora, in particolare a partire dall’ultimo ventennio del XX secolo, dopo un momento di relativo successo. Negli ultimi quindici anni la comunità scientifica, grazie al cognitivismo e alle neuroscienze, ha iniziato a identificare nella metonimia un ruolo primario nell’ecosistema mentale e addirittura una supremazia a livello bio-evolutivo e neuro-fisiologico, a detrimento della metafora, fenomeno secondario e più slegato dalle sfere esperienziali dell’habitat quotidiano. Il funzionamento del cervello è programmato per utilizzare metonimie sia grazie alla capacità del ragionamento inferenziale, sia grazie al fatto che emozioni e sintomi fisiologici si linkano in una incessante operazione metonimica, in particolare dove gli stimoli condizionati predicono e sussumono le emozioni incondizionate, di fatto facilitando un autocontrollo pulsionale

Cara, vecchia metonimia: un ritorno inatteso

The countless changes in rhetorical studies have brought the classic “art of discourse” to a systematic breakdown: first, only in favor of elocutio, then, of poetic lexis and finally, of metaphor. The innumerable changes in rhetoric have led the classic “art of speaking” to a systematic breakdown, first in favor only of elocutio, then of poetic lexis, finally of metaphor. The metonymy was most affected by the new structure of “tropological reduction”. After a moment of success, starting from the last two decades of the twentieth century, the metonymy was mistreated and downgraded to a second-rate trope compared to the metaphor. In the last fifteen years, thanks to cognitive sciences and neurosciences, the scientific community has started to recognize metonymy as a primary role in the cognitive ecosystem. The metonymy has even been recognized as superior at a bio-evolutionary and neuro-physiological level, compared to the metaphor, considered a secondary phenomenon and more disconnected from the experiential spheres of the daily habitat. The functioning of the brain is programmed to use metonymies thanks to both the ability of inferential reasoning and the fact that emotions and physiological symptoms are linked in an incessant metonymic operation. In particular, this occurs when conditioned stimuli predict and subsume unconditioned emotions. In this way impulse self-control is encouraged.La retorica ha subito innumerevoli cambiamenti che hanno portato la classica “arte del parlare” a un sistematico sfaldamento, dapprima a favore della sola elocutio, poi della lexis poetica, infine della metafora. A risentire maggiormente del nuovo assetto di “riduzione tropologica” è la metonimia, bistrattata e declassata a tropo di second’ordine in confronto alla metafora, in particolare a partire dall’ultimo ventennio del XX secolo, dopo un momento di relativo successo. Negli ultimi quindici anni la comunità scientifica, grazie al cognitivismo e alle neuroscienze, ha iniziato a identificare nella metonimia un ruolo primario nell’ecosistema mentale e addirittura una supremazia a livello bio-evolutivo e neuro-fisiologico, a detrimento della metafora, fenomeno secondario e più slegato dalle sfere esperienziali dell’habitat quotidiano. Il funzionamento del cervello è programmato per utilizzare metonimie sia grazie alla capacità del ragionamento inferenziale, sia grazie al fatto che emozioni e sintomi fisiologici si linkano in una incessante operazione metonimica, in particolare dove gli stimoli condizionati predicono e sussumono le emozioni incondizionate, di fatto facilitando un autocontrollo pulsionale

Elogio della visual literacy

Le recenti acquisizioni neuroscientifiche e la loro applicazione in ambito estetico e narratologico offrono un’ulteriore spiegazione alla massiccia diffusione delle immagini avvenuta negli ultimi decenni anche a livello narrativo e ci permettono di comprendere ancora più a fondo il motivo e il modo in cui veniamo catturati dalle rappresentazioni iconiche: esse attivano meccanismi di simulazione incarnata (embodied simulation) delle azioni, delle emozioni e delle sensazioni corporee in esse raffigurate, garantendo un’esperienza immersiva più ‘diretta’, rispetto alla sola lettura di un testo verbale. Il visual storytelling è pertanto considerato una tipologia narrativa proto-adamitica rispetto a quella verbale, in quanto rappresenta una dotazione biologica e cognitiva disponibile all’uomo per trasmettere concetti in maniera semplificata o più emozionalmente attraente; di contro, è provato che quando leggiamo un testo trasformiamo in immagini i concetti, esattamente come accade nelle metafore. Esistono diversi studi sperimentali che mostrano le potenzialità del visual storytelling per lo sviluppo di alcune capacità, in particolare competenza inferenziale-predittiva-esplicativa; pensiero critico; empatia e transportation; pensiero sequenziale; etichettatura di frames e scripts; memoria e apprendimento.Recent neuroscientific advances and their application in the aesthetic and narratological fields offer a further explanation for the massive diffusion of images that has occurred in recent decades including at a narrative level. They allow us to understand even more deeply why and how we are captivated by iconic representations. The images activate mechanisms of embodied simulation of the actions, emotions and bodily sensations depicted in them. In this way the images guarantee a more 'direct' immersive experience, compared to just reading a written text. Therefore, visual storytelling is considered a proto-Adamic narrative typology compared to a written one, because visual language represents a biological and cognitive endowment available to man to convey concepts in a simplified or more emotionally attractive way. On the other hand, it is proven that when we read a text we transform concepts into images, exactly as happens in metaphors. There are several experimental studies that show the potential of visual storytelling for the development of certain skills, in particular inferential-predictive-explanatory competence; critical thinking; empathy and transportation; sequential thinking; labeling of frames and scripts;memory and learning

Solubility and Transdermal Permeation Properties of a Dehydroepiandrosterone Cyclodextrin Complex from Hydrophilic and Lipophilic Vehicles

The permeation ability of a compound is due principally to its concentration in the vehicle and to its aptitude to cross the stratum corneum of the skin. In this work ex-vivo permeation studies on newly developed formulations containing dehydroepiandrosterone (DHEA) were carried out to investigate vehicles that increase drug permeation through the skin. To enhance the solubility of DHEA, its complex form with alpha-cyclodextrin was used. In addition, the two forms (pure drug and complex form) were introduced in hydrophilic (water), lipophilic (paraffin oil), and microemulsion vehicles to evaluate the synergic effect of cyclodextrins and microemulsion vehicles on solubility and permeation. From the results, DHEA solubility is notably conditioned by the type of the vehicle used: the highest solubilities (both for pure and complex drug forms) were obtained with microemulsion, followed by paraffin oil and water. Moreover, in all the studied vehicles, the c-DHEA was more soluble than DHEA. Permeation profile fluxes showed very interesting differences. That reflect the varying drug forms (pure drug and complex form), vehicles used, and drug concentrations in the vehicles. The major flux was obtained in complex of DHEA with alpha-cyclodextrins in the microemulsion vehicle. Therefore, this type of vehicle and drug form would be very useful in the development of a topical formulation containing DHEA

Hydrogen Sulfide and Carnosine: Modulation of Oxidative Stress and Inflammation in Kidney and Brain Axis

Emerging evidence indicates that the dysregulation of cellular redox homeostasis and chronic inflammatory processes are implicated in the pathogenesis of kidney and brain disorders. In this light, endogenous dipeptide carnosine (β-alanyl-L-histidine) and hydrogen sulfide (H2S) exert cytoprotective actions through the modulation of redox-dependent resilience pathways during oxidative stress and inflammation. Several recent studies have elucidated a functional crosstalk occurring between kidney and the brain. The pathophysiological link of this crosstalk is represented by oxidative stress and inflammatory processes which contribute to the high prevalence of neuropsychiatric disorders, cognitive impairment, and dementia during the natural history of chronic kidney disease. Herein, we provide an overview of the main pathophysiological mechanisms related to high levels of pro-inflammatory cytokines, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and neurotoxins, which play a critical role in the kidney–brain crosstalk. The present paper also explores the respective role of H2S and carnosine in the modulation of oxidative stress and inflammation in the kidney–brain axis. It suggests that these activities are likely mediated, at least in part, via hormetic processes, involving Nrf2 (Nuclear factor-like 2), Hsp 70 (heat shock protein 70), SIRT-1 (Sirtuin-1), Trx (Thioredoxin), and the glutathione system. Metabolic interactions at the kidney and brain axis level operate in controlling and reducing oxidant-induced inflammatory damage and therefore, can be a promising potential therapeutic target to reduce the severity of renal and brain injuries in humans

Choroid plexus volume in multiple sclerosis can be estimated on structural MRI avoiding contrast injection

We compared choroid plexus (ChP) manual segmentation on non-contrast-enhanced (non-CE) sequences and reference standard CE T1- weighted (T1w) sequences in 61 multiple sclerosis patients prospectively included. ChP was separately segmented on T1w, T2-weighted (T2w) fluid-attenuated inversion-recovery (FLAIR), and CE-T1w sequences. Inter-rater variability assessed on 10 subjects showed high reproducibility between sequences measured by intraclass correlation coefficient (T1w 0.93, FLAIR 0.93, CE-T1w 0.99). CE-T1w showed higher signal-to-noise ratio and contrast-to-noise ratio (CE-T1w 23.77 and 18.49, T1w 13.73 and 7.44, FLAIR 13.09 and 10.77, respectively). Manual segmentation of ChP resulted 3.073 ± 0.563 mL (mean ± standard deviation) on T1w, 3.787 ± 0.679 mL on FLAIR, and 2.984 ± 0.506 mL on CE-T1w images, with an error of 28.02 ± 19.02% for FLAIR and 3.52 ± 12.61% for T1w. FLAIR overestimated ChP volume compared to CE-T1w (p < 0.001). The Dice similarity coefficient of CE-T1w versus T1w and FLAIR was 0.67 ± 0.05 and 0.68 ± 0.05, respectively. Spatial error distribution per slice was calculated after nonlinear coregistration to the standard MNI152 space and showed a heterogeneous profile along the ChP especially near the fornix and the hippocampus. Quantitative analyses suggest T1w as a surrogate of CE-T1w to estimate ChP volume.Relevance statement To estimate the ChP volume, CE-T1w can be replaced by non-CE T1w sequences because the error is acceptable, while FLAIR overestimates the ChP volume. This encourages the development of automatic tools for ChP segmentation, also improving the understanding of the role of the ChP volume in multiple sclerosis, promoting longitudinal studies.Key points • CE-T1w sequences are considered the reference standard for ChP manual segmentation.• FLAIR sequences showed a higher CNR than T1w sequences but overestimated the ChP volume.• Non-CE T1w sequences can be a surrogate of CE-T1w sequences for manual segmentation of ChP

Immune Response after COVID-19 mRNA Vaccination in Multiple Sclerosis Patients Treated with DMTs

The impact of disease-modifying therapies (DMTs) on the immune response to coronavirus disease-2019 (COVID-19) vaccines in persons with multiple sclerosis (pwMS) needs further elucidation. We investigated BNT162b2 mRNA COVID-19 vaccine effects concerning antibody seroconversion, inflammatory mediators' level and immunophenotype assessment in pwMS treated with cladribine (c-pwMS, n = 29), fingolimod (f-pwMS, n = 15) and ocrelizumab (o-pwMS, n = 54). Anti-spike immunoglobulin (Ig)-G detection was performed by an enzyme immunoassay; molecular mediators (GrB, IFN-gamma and TNF-alpha) were quantified using the ELLA platform, and immunophenotype was assessed by flow cytometry. ANCOVA, Student's t-test and Pearson correlation analyses were applied. Only one o-pwMS showed a mild COVID-19 infection despite most o-pwMS lacking seroconversion and showing lower anti-spike IgG titers than c-pwMS and f-pwMS. No significant difference in cytokine production and lymphocyte count was observed in c-pwMS and f-pwMS. In contrast, in o-pwMS, a significant increase in GrB levels was detected after vaccination. Considering non-seroconverted o-pwMS, a significant increase in GrB serum levels and CD4+ T lymphocyte count was found after vaccination, and a negative correlation was observed between anti-spike IgG production and CD4+ T cells count. Differences in inflammatory mediators' production after BNT162b2 vaccination in o-pwMS, specifically in those lacking anti-spike IgG, suggest a protective cellular immune response

The Wilms' tumor (WT1) gene expression correlates with the International Prognostic Scoring System (IPSS) score in patients with myelofibrosis and it is a marker of response to therapy

The Wilms tumor gene WT1 is a useful marker of clonal hematopoiesis and it has been shown to be a good marker of residual disease and it reflects the response to therapy. Although myelofibrosis is characterized by mutations of JAK2 and calreticulin (CALR), these mutations are not useful to monitor response to therapy. In this study we demonstrated that in patients affected by myelofibrosis WT1 correlates with the International Prognostic Scoring System (IPSS) score at diagnosis. Furthermore WT1 is a good marker of response to JAK2 inhibitors especially for patients without blasts and for patients who develop anemia or thrombocytopenia not for progression but as therapy related toxicity. Finally, WT1 transcript reduction can mirror a benefit of therapy on the disease burden. This study demonstrated that WT1 is a good marker for monitoring the response to therapy in patients affected by myelofibrosis

Cerebrospinal fluid IgM levels in association with inflammatory pathways in multiple sclerosis patients

Background Intrathecal immunoglobulin M (IgM) synthesis has been demonstrated in the early disease stages of multiple sclerosis (MS) as a predictor factor of a worsening disease course. Similarly, increased cerebrospinal fluid (CSF) molecules related to B-cell intrathecal activity have been associated with a more severe MS progression. However, whether CSF levels of IgM are linked to specific inflammatory and clinical profile in MS patients at the time of diagnosis remains to be elucidated. Methods Using customized Bio-Plex assay, the protein levels of IgG, IgA, IgM, and of 34 other inflammatory molecules, related to B-cell, T-cell, and monocyte/macrophage activity, were analyzed in the CSF of 103 newly diagnosed relapsing-remitting MS patients and 36 patients with other neurological disorders. CSF IgM levels were also correlated with clinical and neuroradiological measures [advanced 3-T magnetic resonance imaging (MRI) parameters], at diagnosis and after 2 years of follow-up. Results A 45.6% increase in CSF IgM levels was found in MS patients compared to controls (p = 0.013). CSF IgM levels correlated with higher CSF levels of CXCL13 (p = 0.039), CCL21 (p = 0.023), interleukin 10 (IL-10) (p = 0.025), IL-12p70 (p = 0.020), CX3CL1 (p = 0.036), and CHI3L1 (p = 0.048) and were associated with earlier age of patients at diagnosis (p = 0.008), white matter lesion (WML) number (p = 0.039) and disease activity (p = 0.033) after 2 years of follow-up. Conclusion IgMs are the immunoglobulins mostly expressed in the CSF of naive MS patients compared to other neurological conditions at the time of diagnosis. The association between increased CSF IgM levels and molecules related to both B-cell immunity (IL-10) and recruitment (CXCL13 and CCL21) and to macrophage/microglia activity (IL-12p70, CX3CL1, and CHI3L1) suggests possible correlation between humoral and innate intrathecal immunity in early disease stage. Furthermore, the association of IgM levels with WMLs and MS clinical and MRI activity after 2 years supports the idea of key role of IgM in the disease course