91 research outputs found
1-Phenyl-6,7-dihydroxy-isochroman inhibits inflammatory activation of microglia
No full textInflammation plays a central role in the pathogenesis of several brain disorders and neuronal injury, and it develops as a consequence of glial cell activation. Activated microglial cells generate potentially damaging nitric oxide, oxygen free radicals, prostanoids, and pro-inflammatory cytokines. Naturally occurring polyphenols have recently received attention for their potential protective effect on neurodegenerative disorders characterized by microglial activation, due to their anti-inflammatory and antioxidant properties. In the present study, we investigated, using an in vitro model of primary microglia, the ability of 1-phenyl-6,7-dihydroxy-isochroman (encoded L 137), a natural polyphenolic compound, to inhibit microglia activation induced by an inflammatory insult. So, L137 effects (1-100 mu M) on production of pro-inflammatory mediators in lipopolysaccharide (LPS)-activated microglial cells were evaluated. The expression of inducible isoforms of nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) as well as of the nuclear transcription Factor-kappa B (NF-kappa B) was also performed in cellular lysates by Immunoblot. L137 significantly reduced tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, IL-6 secretion, as well as nitric oxide (NO) and prostanoids [Thromboxane (TX)B-2, prostaglandin (PG)E-2] production in activated microglial cells. Western blot analyses showed an inhibitory effect of L137 on the iNOS and COX-2 expression, mediated by a modulation of redox-sensitive nuclear transcriptional factor (NF)-kappa B, known to control a wide array of genes involved in inflammation. In conclusion, this study demonstrate that L137 is able to inhibit the production of pro-inflammatory and neurotoxic mediators by LPS-activated microglial cells thus suggesting L137 as a potential lead compound for drug development for neurodegenerative disorders where microglia-mediated inflammatory responses play an important pathogenic role. (C) 2013 Elsevier Inc. All rights reserved
Product differentiation and the relative importance of wine attributes: U.S. retail prices
No full textThis paper investigates the relative importance of various attributes, including varietal, brands, and geographic origin, in explaining retail wine prices for the United States market. We use a metric based on the Shapely value, from cooperative game theory, in the context of an empirical hedonic price equation estimated using a large sample of retail wine sales for home consumption over the period 2007–2019. We find that brands alone explain more than 70% of the variation in wine prices, but geographic origin and varietals retain additional explanatory power. Furthermore, information about the geographic origin appears to be a considerably more important attribute than varietals.This article is published as Chandra, R., & Moschini, G. (2022). Product differentiation and the relative importance of wine attributes: U.S. retail prices. Journal of Wine Economics, 17(3), 177-208. doi:10.1017/jwe.2022.23.© The Author(s), 2022. This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited
CAG Repeats Within the Non-pathological Range in the HTT Gene Influence Personality Traits in Patients With Subjective Cognitive Decline: A 13-Year Follow-Up Study
No full textHTT is a gene containing a key region of CAG repeats. When expanded beyond 39 repeats, Huntington disease (HD) develops. HTT genes with <35 repeats are not associated with HD. The biological function of CAG repeat expansion below the non-pathological threshold is not well understood. In fact higher number of repeats in HTT confer advantageous changes in brain structure and general intelligence, but several studies focused on establishing the association between CAG expansions and susceptibility to psychiatric disturbances and to other neurodegenerative disease than HD. We hypothesized that HTT CAG repeat length below the pathological threshold might influence mood and personality traits in a longitudinal sample of individuals with Subjective Cognitive Decline
Plasma neurofilament light chain predicts Alzheimer's disease in patients with subjective cognitive decline and mild cognitive impairment: A cross‐sectional and longitudinal study
No full textBackground and purpose: We aimed to evaluate the accuracy of plasma neurofilament light chain (NfL) in predicting Alzheimer's disease (AD) and the progression of cognitive decline in patients with subjective cognitive decline (SCD) and mild cognitive impairment (MCI). Methods: This longitudinal cohort study involved 140 patients (45 with SCD, 73 with MCI, and 22 with AD dementia [AD-D]) who underwent plasma NfL and AD biomarker assessments (cerebrospinal fluid, amyloid positron emission tomography [PET], and 18F-fluorodeoxyglucose-PET) at baseline. The patients were rated according to the amyloid/tau/neurodegeneration (A/T/N) system and followed up for a mean time of 2.72 ± 0.95 years to detect progression from SCD to MCI and from MCI to AD. Forty-eight patients (19 SCD, 29 MCI) also underwent plasma NfL measurements 2 years after baseline. Results: At baseline, plasma NfL detected patients with biomarker profiles consistent with AD (A+/T+/N+ or A+/T+/N−) with high accuracy (area under the curve [AUC] 0.82). We identified cut-off values of 19.45 pg/mL for SCD and 20.45 pg/mL for MCI. During follow-up, nine SCD patients progressed to MCI (progressive SCD [p-SCD]), and 14 MCI patients developed AD dementia (progressive MCI [p-MCI]). The previously identified cut-off values provided good accuracy in identifying p-SCD (80% [95% confidence interval 65.69: 94.31]). The rate of NfL change was higher in p-MCI (3.52 ± 4.06 pg/mL) compared to non-progressive SCD (0.81 ± 1.25 pg/mL) and non-progressive MCI (−0.13 ± 3.24 pg/mL) patients. A rate of change lower than 1.64 pg/mL per year accurately excluded progression from MCI to AD (AUC 0.954). Conclusion: Plasma NfL concentration and change over time may be a reliable, non-invasive tool to detect AD and the progression of cognitive decline at the earliest stages of the disease
The role of plasma neurofilament light chain and glial fibrillary acidic protein in subjective cognitive decline and mild cognitive impairment
No full textNfL and GFAP are promising blood-based biomarkers for Alzheimer's disease. However, few studies have explored plasma GFAP in the prodromal and preclinical stages of AD. In our cross-sectional study, our aim is to investigate the role of these biomarkers in the earliest stages of AD. Materials and methods We enrolled 40 patients (11 SCD, 21 MCI, 8 AD dementia). All patients underwent neurological and neuropsychological examinations, analysis of CSF biomarkers (Aβ42, Aβ42/Aβ40, p-tau, t-tau), Apolipoprotein E (APOE) genotype analysis and measurement of plasma GFAP and NfL concentrations. Patients were categorized according to the ATN system as follows: normal AD biomarkers (NB), carriers of non-Alzheimer's pathology (non-AD), prodromal AD, or AD with dementia (AD-D). Results GFAP was lower in NB compared to prodromal AD (p = 0.003, d = 1.463) and AD-D (p = 0.002, d = 1.695). NfL was lower in NB patients than in AD-D (p = 0.011, d = 1.474). NfL demonstrated fair accuracy (AUC = 0.718) in differentiating between NB and prodromal AD, with a cut-off value of 11.65 pg/mL. GFAP showed excellent accuracy in differentiating NB from prodromal AD (AUC = 0.901) with a cut-off level of 198.13 pg/mL. Conclusions GFAP exhibited excellent accuracy in distinguishing patients with normal CSF biomarkers from those with prodromal AD. Our results support the use of this peripheral biomarker for detecting AD in patients with subjective and objective cognitive decline
Il pensare dialogico nel percorso intellettuale di Hilary Putnam
No full textIl confronto di Putnam con Rosenzwig, Buber e Levinas è maturato in una monografia pubblicata nel 2008. Allo scopo di valorizzarla, propongo di leggerla alla luce di un triplice contesto. Innanzitutto, inserendola nell’itinerario speculativo di Putnam e nelle tappe che hanno seguito la sua adesione alla fede ebraica; in secondo luogo, interpretandola alla luce della proposta di Putnam in ambito di filosofia della religione; infine, mettendola in parallelo con le questioni chiave della sua (meta)filosofia. I limiti dell’interpretazione offerta da Putnam sono evidenti sotto il profilo filologico e per via di una profondità ermeneutica non esente da lacune. Anche la conoscenza dell’ambito giudaico da cui questo pensiero emerge risulta solo in parte sfruttata e, di conseguenza, le questioni su che cosa significhi realmente occuparsi di filosofia vengono affrontate senza essere sistematicamente definite. Ciò nonostante la presenza di “pensatori dialogici” nella riflessione di un autore classificato come “analitico”, rappresenta un fatto decisivo e non trascurabile nell’ambito della storia della filosofia contemporanea.Putnam's comparison with Rosenzwig, Buber and Levinas matured in a monograph published in 2008. In order to enhance it, I propose to read it in the light of a threefold context. First, by placing it in Putnam's speculative itinerary and in the stages that followed his adherence to the Jewish faith; secondly, by interpreting it in the light of Putnam's proposal in the field of philosophy of religion; finally, by placing it in parallel with the key questions of his (meta)philosophy. The limits of the interpretation offered by Putnam are evident from a philological point of view and because of a hermeneutic depth that is not free from gaps. Even the knowledge of the Jewish context from which this thought emerges is only partially exploited and, consequently, the questions on what it really means to deal with philosophy are addressed without being systematically defined. Nonetheless, the presence of "dialogical thinkers" in the reflection of an author classified as "analytic" represents a decisive and non-negligible fact in the history of contemporary philosophy
Data-driven subtypes of mixed semantic-logopenic primary progressive aphasia: Linguistic features, biomarker profiles and brain metabolic patterns
No full textMixed primary progressive aphasia (mPPA) accounts for a substantial proportion of primary progressive aphasia (PPA) cases. However, the lack of a standardised definition of this condition has resulted in misclassification of PPA cases. In this study, we enrolled 55 patients diagnosed with PPA, comprising 12 semantic variant (svPPA), 23 logopenic variant (lvPPA), and 20 mPPA cases with linguistic characteristics consistent with both svPPA and lvPPA (s/lvPPA). All patients underwent language assessments, evaluation of Alzheimer's disease biomarkers (via cerebrospinal fluid analysis or Amyloid-PET), and 18F-FDG-PET brain scans. An agglomerative hierarchical clustering (AHC) analysis based on linguistic characteristics revealed two distinct clusters within the s/lvPPA group: cluster k1 (n = 10) displayed an AD-like biomarker profile, with lower levels of Aβ42 and Aβ42/Aβ40 ratio, along with higher levels of t-tau and p-tau compared to cluster k2 (n = 10). Interestingly, k1 exhibited linguistic features that were similar to those of svPPA. Both clusters exhibited extensive temporoparietal hypometabolism. These findings support the hypothesis that a subgroup of s/lvPPA may represent a clinical manifestation of AD-related PPA
Romanzi di guerra nel Novecento italiano. Comisso, Malaparte, Viganò
No full textQuesto lavoro ha preso in esame le opere di tre autori della letteratura italiana novecentesca che si sono dedicati alla trattazione del tema bellico. Giovanni Comisso in "Giorni di guerra" ci dà un’immagine di un sé giovane e spensierato il quale, arruolatosi volontario durante la Prima guerra mondiale, vive e affronta con ingenuo entusiasmo questo periodo. Di tutt’altro sapore è "La pelle" di Curzio Malaparte, tanto per periodo storico, poiché ci troviamo all’altezza della Seconda guerra mondiale, quanto per carattere narrativo. Lo sguardo dello scrittore osserva con lucidità il degrado al quale il popolo di Napoli è giunto a seguito dei molti anni di guerra e dello sbarco degli alleati. A questo fine si impegna in descrizioni che a volte appaiono esagerate e ai limiti della credibilità, ma che hanno lo scopo di dar prova del suo sdegno di fronte a certe realtà. "L’Agnese va a morire" di Renata Viganò si incentra sul periodo della Resistenza e della lotta partigiana durante la Seconda guerra mondiale nelle valli di Comacchio e della Romagna. La narrazione è affrontata dal punto di vista di un’anziana contadina, Agnese, ponendo così in risalto l’importante ruolo che le donne svolsero nella lotta contro i nazi-fascisti. Leggendo e studiando queste opere mi sono persuasa del grande valore che potrebbero avere anche in sede didattica, dal momento che propongono diverse angolazioni dalle quali poter affrontare la tematica bellica nella sua trasformazione, da un’ottica di soli combattenti a quella del coinvolgimento dei civili e al ruolo assunto gradualmente dalle donne, in parallelo al modificarsi della società nella prima metà del secolo
Plasma p-tau181 as a promising non-invasive biomarker of Alzheimer's Disease pathology in Subjective Cognitive Decline and Mild Cognitive Impairment
No full textThe aim of this study is to investigate the role of plasma phosphorylated tau (p-tau) 181 as a potential biomarker for Alzheimer's Disease (AD) pathology in the early stages of the disease, as a valuable marker for tauopathy. Materials and methods: Thirty-three Subjective Cognitive Decline (SCD), 32 Mild Cognitive Impairment (MCI) and 14 AD demented (AD-d) patients underwent plasma p-tau181 analysis with SiMoA assay. Twenty-six SCD, 32 MCI and 14 AD-d patients also underwent CSF biomarkers analysis (Aβ1–42, Aβ1–42/1–40, p-tau, t-tau) and were classified as carriers of AD pathology (AP+) when A+ was associated with T+ (regardless of N), or non-carriers (AP-) when they were A- (regardless of T and N), or A+/T-/N-, or A+/T-/N+ according to the A/T(N) system. Results: Plasma p-tau181 levels were higher in SCD AP+ than in SCD AP- (2.85 ± 0.53 vs 1.73 ± 0.64, p < 0.001), and in MCI AP+ than in MCI AP- (4.03 ± 1.07 vs 2.04 ± 0.87, p < 0.001). In a multivariate linear regression analysis, AP status was the only variable that influenced plasma p-tau181 (B = 1.670 [95% CI 1.097:2.244], p < 0.001). Plasma p-tau181 was highly accurate for discriminating between AP+ and AP- patients (AUC = 0.910). We identified a cut-off level of 2.69 pg/mL to distinguish between AP+ and AP- (sensibility 0.86, specificity 0.82, PPV 75.00% NPV 90.32%). Conclusions: Plasma p-tau181 levels were influenced by the presence of underlying AD pathology, independently from the cognitive status and were highly accurate in differentiating SCD-MCI patients who were carriers of AD pathology from non-carriers. Plasma p-tau181 might be a promising non-invasive biomarker of AD pathology at a very early stage.Introduction: The aim of this study is to investigate the role of plasma phosphorylated tau (p-tau) 181 as a potential biomarker for Alzheimer's Disease (AD) pathology in the early stages of the disease, as a valuable marker for tauopathy.Materials and methods: Thirty-three Subjective Cognitive Decline (SCD), 32 Mild Cognitive Impairment (MCI) and 14 AD demented (AD-d) patients underwent plasma p-tau181 analysis with SiMoA assay. Twenty-six SCD, 32 MCI and 14 AD-d patients also underwent CSF biomarkers analysis (A beta 1-42, A beta 1-42/1-40, p-tau, t-tau) and were classified as carriers of AD pathology (AP+) when A+ was associated with T+ (regardless of N), or non-carriers (AP-) when they were A- (regardless of T and N), or A+/T-/N-, or A+/T-/N+ according to the A/T(N) system.Results: Plasma p-tau181 levels were higher in SCD AP+ than in SCD AP- (2.85 +/- 0.53 vs 1.73 +/- 0.64, p < 0.001), and in MCI AP+ than in MCI AP- (4.03 +/- 1.07 vs 2.04 +/- 0.87, p < 0.001). In a multivariate linear regression analysis, AP status was the only variable that influenced plasma p-tau181 (B = 1.670 [95% CI 1.097:2.244], p < 0.001). Plasma p-tau181 was highly accurate for discriminating between AP+ and AP- patients (AUC = 0.910). We identified a cut-off level of 2.69 pg/mL to distinguish between AP+ and AP- (sensibility 0.86, specificity 0.82, PPV 75.00% NPV 90.32%).Conclusions: Plasma p-tau181 levels were influenced by the presence of underlying AD pathology, independently from the cognitive status and were highly accurate in differentiating SCD-MCI patients who were carriers of AD pathology from non-carriers. Plasma p-tau181 might be a promising non-invasive biomarker of AD pathology at a very early stage
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