Pensare l'infondato. Una lettura di Schelling a partire dal corsodel 1936 di Martin Heidegger

In his 1936 lecture-course on the Philosophical Inquiries into the Essence of Human Freedom Heidegger notices a tension towards a non-metaphysical ontology in Schelling's philosophy, and in particular in the introduction of the thought of the not-being into the one of being, of the non-ground (Un-grund) into the one of ground (Grund). What I aim to show, in the wake of Heidegger's interpretation, is how the attempt of thinking of a deity as a guarantee of the rationality of finite existence clashes, not only in the Inquiries but also in the Philosophy of Revelation, with the need to acknowledge irrational, unchosen and therefore unfounded conditions at the basis of God's manifestation: contrast, opposition, the existence of evil

La durée dans la dureté: Espaces de la mémoire et mémoires de l’espace chez Paul Ricœur

In Memory, History, Forgetting, Ricœur does not provide us with a clear definition of collective memory. In this article, we will try to show how it could nevertheless be described, based on the same text, as the capacity for recognition, by way of reciprocal attribution, memories that are engraved in temporal spaces and are shared with our neighbors and, through them, with strangers. To verify this hypothesis, we will analyse Ricœur’s reflection on architecture as public memory’s engraving into space, presented for the first time in the text “Architecture et narrativité.” Lastly, we will consider imagination and bodily memory, i.e. habit emanating from the act of inhabiting, as the conditions of possibility for the crystallization of memories in shared places.Dans La mémoire, l’histoire, l’oubli, Ricœur ne parvient pas à donner une définition claire de la mémoire collective. Dans cet article, nous cherchons à montrer comment elle se laisse néanmoins décrire, à partir de ce même texte, comme la capacité à reconnaître, à travers l’attribution réciproque, des souvenirs qui s’inscrivent dans les espaces temporels partagés avec nos proches et, à travers ces derniers, avec les étrangers. Afin d’appuyer cette hypothèse, nous analysons les réflexions de Ricœur sur l’architecture en tant qu’inscription de la mémoire publique dans l’espace, présentées pour la première fois dans le texte “Architecture et narrativité.” Deuxièmement, nous considérons l’imagination et la mémoire corporelle, à savoir l’habitude qui découle de l’acte d’habiter, comme les conditions de possibilité de la cristallisation des souvenirs dans les lieux partagés

La pensée des lieux de Paul Ricœur à l’épreuve du paysage. Un dialogue possible entre herméneutique, esthétique performative et phénoménologie

In this article, we argue that Paul Ricœur’s hermeneutics of spaces and the aesthetics vision of the landscape as a performance, based on the contemporary theories of Erika Fischer-Lichte, can integrate each other through the mediation of Mikel Dufrenne’s phenomenology of the a priori. In particular, we will show how the representations and the hermeneutics of a landscape as a peculiar “text” are essentially connected with its the pre-reflective experience, which, being made possible by the activation of precise material – and therefore historical and cultural – a priori, can be thus translated into images and words. By intertwining hermeneutics, phenomenology, and performative esthetics we will provide with a non-reductive philosophical description of a landscape, i.e., a definition that does not neglect the aspects of it suggested by its linguistic pre-comprehension and artistic representations.Dans cet article, nous soutenons que l’herméneutique des espaces de Paul Ricœur et la vision esthétique du paysage comme performance, basée sur les théories contemporaines de Erika Fischer-Lichte, peuvent être réconciliées par la médiation de la phénoménologie de l’a priori de Mikel Dufrenne. Nous montrons en particulier comment la représentation du paysage et son interprétation en tant que « texte » sont essentiellement liées à l’expérience pré-réflexive que nous en faisons. Cette expérience, rendue possible par l’activation d’a priori matériels précis – et donc historiques et culturels –  peut être ainsi traduite en images et en textes. En entrelaçant l’herméneutique, la phénoménologie et l’esthétique performative, nous proposerons une description philosophique aussi exhaustive que possible du paysage ; c’est-à-dire une définition du paysage qui ne néglige pas les aspects de ce phénomène suggérés par sa précompréhension linguistique et par ses représentations artistiques

Atypical cellular neurothekeoma (ACN) of the elderly: case report and brief review of the literature

Atypical cellular neurothekeoma (ACN) is an aggressive and rare variant of cellular neurothekeoma. Only few cases have been reported in the literature and the biological behavior seems to be uncertain. We describe the case of an ACN presenting on the scalp of an elderly man, emphasizing the cytologic features of malignancy. In addition, we provide a brief overview of the literature and discuss the differential diagnosis with other entities, and the possible diagnostic pitfalls

Rapid and Efficient Invasion Assay of Glioblastoma in Human Brain Organoids

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Ultra-Early Treatment of Neurosurgical Emergencies with Endoscopic Endonasal Approach: Experience from Three Italian Referral Centers

Purpose: the aim of this multicenter study is to preliminarily assess the role of the Endoscopic Endonasal Approach (EEA) in ultra-early (i.e., within 12 h) management of selected neurosurgical emergencies in terms of clinical and radiological outcomes. Methods: 26 patients affected by sellar/parasellar pathologies with rapid progression of symptoms were managed with EEA within 12 h from diagnosis in three Italian tertiary referral Centers from January 2016 to December 2019. Both clinical and radiological data have been collected preoperatively as well as post-operatively in order to perform retrospective analysis. Results: The average time from admission to the operating room was 5.5 h (±2.3). The extent of resection was gross-total in 20 (76.9%), subtotal in 6 (23.1%) patients. One patient experienced re-bleeding after a subtotal removal of a hemorrhagic lesion. Patients with a longer time from admission (>4 h) to the operatory room (OR) experienced stable impairment of the visual acuity (p = 0.033) and visual field (p = 0.029) in the post-operative setting. Conclusions: The Endoscopic Endonasal Approach represents a safe, effective technique that can be efficiently used with good results in the management of selected neurosurgical emergencies in centers with adequate experience

Olfactory groove meningioma: report of 99 cases surgically treated at the Catholic University School of Medicine, Rome

OBJECTIVE: We reviewed our series of olfactory groove meningiomas (OGMs) with the aim to relate the surgical approach with outcome and to define clinical and pathologic predictors of prognosis. METHODS: Ninety-nine patients who underwent 113 craniotomies at our Institution between 1984 and 2010 were entered this study. The relationship between surgical approach (bifrontal, fronto-orbito-basal, and pterional) and either tumor diameter, extent of tumor resection, complication rate, need of reoperation, and Karnofsky Performance Status (KPS) was analyzed. The impact of age ( 64 70 vs. > 70 years), sex, tumor diameter (< 6 vs. 65 6 cm), pre- and postoperative KPS (< 80 vs. 65 80), Simpson grade (I-II vs. III-IV), and World Health Organization (WHO) histologic grade (I vs. II-III) on survival was assessed. Kaplan-Meier survival curves were plotted and differences in survival between groups of patients were compared. A multivariate analysis adjusted for age, pre- and postoperative KPS, Simpson grade, tumor diameter, and WHO histologic grade also was performed. RESULTS: The fronto-orbito-basal approach (n = 22) allowed a significantly greater percentage of Simpson I-II removals than the bifrontal (n = 70) and pterional approach (n = 21) (P = 0.0354 and P = 0.0485, respectively). The risk of life-threatening complications trended to be lower in patients operated upon either via the fronto-orbito-basal and via the pterional approach than in those treated via the bifrontal approach. Retraction-related brain swelling did not occur in any case after the fronto-orbito-basal approach (P = 0.0384); however, this approach was associated with a greater rate of cerebrospinal fluid leak (P = 0.0011). Among prognostic factors, age 64 70 years (P = 0.0044), tumor diameter <6 cm (P = 0.0455), pre- and postoperative KPS 65 80 (both P < 0.0001), Simpson grade I-II (P = 0.0096), and WHO histologic grade I (P = 0.0112) were significantly associated with longer overall survival. Age (P = 0.0393) and WHO histologic grade (P = 0.0418) emerged as independent prognostic factors for overall survival on multivariate analysis. CONCLUSION: In the largest series of OGMs published to date, the bifrontal approach was associated with a greater risk of life-threatening complications compared with the lateral pterional and fronto-orbito-basal approaches. The fronto-orbito-basal approach provided greater chances of total tumor removal than the bifrontal and pterional approaches. Two independent factors for overall survival of patients with OGM were identified, namely age and WHO grade

AVNP2 protects against cognitive impairments induced by C6 glioma by suppressing tumour associated inflammation in rats

© 2020 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/).Glioblastoma is a kind of malignant tumour and originates from the central nervous system. In the last century, some researchers and clinician have noticed that the psychosocial and neurocognitive functioning of patients with malignant gliomas can be impaired. Many clinical studies have demonstrated that part of patients, adults or children, diagnosed with glioblastoma will suffer from cognitive deficiency during their clinical course, especially in long-term survivors. Many nanoparticles (NPs) can inhibit the biological functions of tumours by modulating tumour-associated inflammation, which provokes angiogenesis and tumour growth. As one of the best antiviral nanoparticles (AVNPs), AVNP2 is the 2nd generation of AVNP2 that have been conjugated to graphite-graphene for improving physiochemical performance and reducing toxicity. AVNP2 inactivates viruses, such as the H1N1 and H5N1influenza viruses and even the SARS coronavirus, while it inhibits bacteria, such as MRSA and E. coli. As antimicrobials, nanoparticles are considered to be one of the vectors for the administration of therapeutic compounds. Yet, little is known about their potential functionalities and toxicities to the neurotoxic effects of cancer. Herein, we explored the functionality of AVNP2 on inhibiting C6 in glioma-bearing rats. The novel object-recognition test and open-field test showed that AVNP2 significantly improved the neuro-behaviour affected by C6 glioma. AVNP2 also alleviated the decline of long-term potentiation (LTP) and the decreased density of dendritic spines in the CA1 region induced by C6. Western blot assay and immunofluorescence staining showed that the expressions of synaptic-related proteins (PSD-95 and SYP) were increased, and these findings were in accordance with the results mentioned above. It revealed that the sizes of tumours in C6 glioma-bearing rats were smaller after treatment with AVNP2. The decreased expression of inflammatory factors (IL-1β, IL-6 and TNF-α) by Western blotting assay and ELISA, angiogenesis protein (VEGF) by Western blotting assay and other related proteins (BDNF, NF-ĸB, iNOS and COX-2) by Western blotting assay in peri-tumour tissue indicated that AVNP2 could control tumour-associated inflammation, thus efficiently ameliorating the local inflammatory condition and, to some extent, inhibiting angiogenesis in C6-bearing rats. In conclusion, our results suggested that AVNP2 could have an effect on the peri-tumor environment, obviously restraining the growth progress of gliomas, and eventually improving cognitive levels in C6-bearing rats.Peer reviewedProo

A BMP7 variant inhibits tumor angiogenesis in vitro and in vivo through direct modulation of endothelial cell biology

Bone morphogenetic proteins (BMPs), members of the TGF-\u3b2 superfamily, have numerous biological activities including control of growth, differentiation, and vascular development. Using an in vitro co-culture endothelial cord formation assay, we investigated the role of a BMP7 variant (BMP7v) in VEGF, bFGF, and tumor-driven angiogenesis. BMP7v treatment led to disruption of neo-endothelial cord formation and regression of existing VEGF and bFGF cords in vitro. Using a series of tumor cell models capable of driving angiogenesis in vitro, BMP7v treatment completely blocked cord formation. Pre-treatment of endothelial cells with BMP7v significantly reduced their cord forming ability, indicating a direct effect on endothelial cell function. BMP7v activated the canonical SMAD signaling pathway in endothelial cells but targeted gene knockdown using shRNA directed against SMAD4 suggests this pathway is not required to mediate the anti-angiogenic effect. In contrast to SMAD activation, BMP7v selectively decreased ERK and AKT activation, significantly decreased endothelial cell migration and down-regulated expression of critical RTKs involved in VEGF and FGF angiogenic signaling, VEGFR2 and FGFR1 respectively. Importantly, in an in vivo angiogenic plug assay that serves as a measurement of angiogenesis, BMP7v significantly decreased hemoglobin content indicating inhibition of neoangiogenesis. In addition, BMP7v significantly decreased angiogenesis in glioblastoma stem-like cell (GSLC) Matrigel plugs and significantly impaired in vivo growth of a GSLC xenograft with a concomitant reduction in microvessel density. These data support BMP7v as a potent anti-angiogenic molecule that is effective in the context of tumor angiogenesis

Human mesenchymal stromal cells inhibit tumor growth in orthotopic glioblastoma xenografts

Background: Mesenchymal stem/stromal cells (MSCs) represent an attractive tool for cell-based cancer therapy mainly because of their ability to migrate to tumors and to release bioactive molecules. However, the impact of MSCs on tumor growth has not been fully established. We previously demonstrated that murine MSCs show a strong tropism towards glioblastoma (GBM) brain xenografts and that these cells are able to uptake and release the chemotherapeutic drug paclitaxel (PTX), maintaining their tropism towards the tumor. Here, we address the therapy-relevant issue of using MSCs from human donors (hMSCs) for local or systemic administration in orthotopic GBM models, including xenografts of patient-derived glioma stem cells (GSCs). Methods: U87MG or GSC1 cells expressing the green fluorescent protein (GFP) were grafted onto the striatum of immunosuppressed rats. Adipose hMSCs (Ad-hMSCs), fluorescently labeled with the mCherry protein, were inoculated adjacent to or into the tumor. In rats bearing U87MG xenografts, systemic injections of Ad-hMSCs or bone marrow (BM)-hMSCs were done via the femoral vein or carotid artery. In each experiment, either PTX-loaded or unloaded hMSCs were used. To characterize the effects of hMSCs on tumor growth, we analyzed survival, tumor volume, tumor cell proliferation, and microvascular density. Results: Overall, the AD-hMSCs showed remarkable tropism towards the tumor. Intracerebral injection of Ad-hMSCs significantly improved the survival of rats with U87MG xenografts. This effect was associated with a reduction in tumor growth, tumor cell proliferation, and microvascular density. In GSC1 xenografts, intratumoral injection of Ad-hMSCs depleted the tumor cell population and induced migration of resident microglial cells. Overall, PTX loading did not significantly enhance the antitumor potential of hMSCs. Systemically injected Ad- and BM-hMSCs homed to tumor xenografts. The efficiency of hMSC homing ranged between 0.02 and 0.5% of the injected cells, depending both on the route of cell injection and on the source from which the hMSCs were derived. Importantly, systemically injected PTX-loaded hMSCs that homed to the xenograft induced cytotoxic damage to the surrounding tumor cells. Conclusions: hMSCs have a therapeutic potential in GBM brain xenografts which is also expressed against the GSC population. In this context, PTX loading of hMSCs seems to play a minor role