271 research outputs found
Confocal laser imaging in neurosurgery: A comprehensive review of sodium fluorescein-based CONVIVO preclinical and clinical applications.
No full textGiven the established direct correlation that exists among extent of resection and postoperative survival in brain tumors, obtaining complete resections is of primary importance. Apart from the various technological advancements that have been introduced in current clinical practice, histopathological study still remains the gold-standard for definitive diagnosis. Frozen section analysis still represents the most rapid and used intraoperative histopathological method that allows for an intraoperative differential diagnosis. Nevertheless, such technique owes some intrinsic limitations that limit its overall potential in obtaining real-time diagnosis during surgery. In this context, confocal laser technology has been suggested as a promising method to have near real-time intraoperative histological images in neurosurgery, thanks to the results of various studies performed in other non-neurosurgical fields. Still far to be routinely implemented in current neurosurgical practice, pertinent literature is growing quickly, and various reports have recently demonstrated the utility of this technology in both preclinical and clinical settings in identifying brain tumors, microvasculature, and tumor margins, when coupled to the intravenous administration of sodium fluorescein. Specifically in neurosurgery, among different available devices, the ZEISS CONVIVO system probably boasts the most recent and largest number of experimental studies assessing its usefulness, which has been confirmed for identifying brain tumors, offering a diagnosis and distinguishing between healthy and pathologic tissue, and studying brain vessels. The main objective of this systematic review is to present a state-of-the-art summary on sodium fluorescein-based preclinical and clinical applications of the ZEISS CONVIVO in neurosurgery
Umani e animali: questioni di etica
No full textGli animali sono presenti nella vita umana sin dalle origini. Sono utilizzati per l'alimentazione, il lavoro e la ricerca, vivono nelle nostre case, condividono con noi gli spazi urbani e abitano gli ambienti selvatici che ci circondano. Il loro trattamento suscita accese discussioni pubbliche e un vivace dibattito teorico, in particolare per quegli usi, come alcune sperimentazioni, ai quali allo stato attuale non sembra ragionevole rinunciare. Il libro presenta tali questioni etiche sullo sfondo di una ricostruzione della realtà biologica e culturale del rapporto con gli animali e di una rassegna delle concezioni filosofiche passate e contemporanee. L'autore individua nei sentimenti e nella capacità umana di simpatizzare con gli animali le risorse per includerli nella considerazione morale e per riformare il modo di interagire con essi.Animals are part of human life since its very beginning. They are used for food, work and research, the live in our houses, they share urban spaces with us and they live into the wild environment surrounding us. The way animals are treated triggers lively public discussions and a rich theoretical debate, with a particular regard to those uses, such as some experimentations, whose termination does not seem reasonable. The book presents such ethical issues starting from a review of past and contemporary philosophical approaches. The author identifies sentiments and human sympathy as the resources to include animals into moral respect and to reform the way we interact with them
The Internet of Things for the circular transition in the façade sector
No full textNel settore delle facciate, la transizione ecologica e circolare impone l’adozione di nuovi modelli di business che sfruttino al massimo il valore della materia. In questo contesto, l’Internet of Things (IoT) è identificato quale poten-ziale driver tecnologico per la diffusione di approcci circolari. Scopo dell’articolo è chiarire il ruolo dell’IoT nell’abilitare cinque modelli di business circolari nel settore delle facciate. Attraverso una matrice che evidenzia la relazione tra po-tenziali informazioni prodotte dall’IoT e azioni chiave per il raggiungimento dei modelli di business, si evidenziano i benefici di un sistema di facciata IoT-based. La discussione dei risultati apre il dibattito sulle prospettive di componenti edilizi digitalmente integrati
Internet of things for building façade traceability: A theoretical framework to enable circular economy through life-cycle information flows
No full textTraceability is considered a crucial requirement to enable Circular Economy (CE). Product and process life-cycledata can facilitate circular asset management preserving the asset’s value over time and reducing resource consumption. Many scholars point out how the loss of traceability data, lacking information reliability, and
unstructured data are still barriers to the widespread application of CE. In the building façade sector, an increased interest on traceability is dictated by a growing demand for environmental product certifications.
However, these aspects are often limited to collect data at supply chain stage, thus neglecting a huge amount of information produced during the asset service life. To foster an accessible and life-cycle oriented asset traceability, this research investigates the Internet of Things (IoT) as a potentially disruptive technology for sup-
porting information management. The objective of this work is twofold: (i) to identify what façade life-cycle information is needed to promote CE and (ii) to clarify the enabling role of IoT in tracking, storing, and sharing such information. Through a scoping review combined with interviews to professionals, a theoretical framework
structured on four key elements (stakeholders, information list, information management tools, and IoT) is proposed to fill the literature gap and support façade industry in the circular transition. Further research will have to be conducted to face the digital-physical integration issues and develop business models able to fully
exploit traceability information value
HGG-09. MicroRNAs expression profile in Meningioma 1 (MN1) gene altered astroblastoma
No full textAstroblastoma is a rare glial neoplasm arising more frequently in young, predominantly female, patients and with unclear clinical behavior and outcome. The diagnostic molecular alteration is the rearrangement of meningioma 1 (MN1) gene.However, little is known about the specific mechanism of tumor development driven by such genetic change. microRNAs (miRNAs) are important gene expression regulators with strong implications in several biological processes. In this study we investigated the microRNAs’ expression and regulation in MN1 altered neoplasms. We collected a cohort of 14 formalin-fixed, paraffin-embedded (FFPE) tumor samples histologically defined classified as astroblastoma. The DNA methylation analysis showed that only 8 cases harbored the MN1 rearrangement characteristic of astroblastoma. The 8 MN1 altered tumors were analyzed for their expression pattern of miRNAs by Nanostring technology. Thirty-nine deregulated miRNAs were found in the 8 astroblastomas compared to normal brain tissue. In order to understand the underlying mechanisms of the miRNAs aberrant expression, we first investigated the methylation status of themicroRNA promoters. Thirty-two out 39 deregulated miRNA resulted epigenetically regulated. with methylation status coherent with microRNA expression in 14/32 miRNAs.. Secondly, we investigated the hypothesis of a genomic alteration as a reason for the abnormal expression of the remaining 18/32 deregulated miRNAs by analyzing the Copy Number Variation (CNV) of tumor samples. but no alteration was found on miRNAs chromosome loci. Finally, we identified validated targets of the 32 deregulated miRNAs and uncovered biological processes putatively correlated to miRNA target genes, clinically and pathologically relevant in MN1-altered astroblastomas. Our findings shed light on the biology of this rare disease with potential implications on prognostic markers and therapy
Telomere elongation via alternative lengthening of telomeres (ALT) and telomerase activation in primary metastatic medulloblastoma of childhood
No full textPurpose: Elongation of telomeres is necessary for tumor cell immortalization and senescence escape; neoplastic cells use to
alternative pathways to elongate telomeres: telomerase reactivation or a telomerase-independent mechanism termed alternative
lengthening of telomeres (ALT). Telomerase and ALT pathway has been explored in adult and pediatric gliomas and
medulloblastomas (MDBs); however, these mechanisms were not previously investigated in MDBs metastatic at the onset.
Therefore, we analyzed the activation of telomerase and ALT pathway in a homogenous cohort of 43 pediatric metastatic
medulloblastomas, to investigate whether telomere elongation could play a role in the biology of metastatic MDB.
Methods: We evaluated telomeres length via telomere-specific fluorescence in situ hybridization (Telo-FISH); we assessed
nuclear expression of ATRX by immunohistochemistry (IHC). H3F3A and TERT promoter mutations were analyzed by
pyrosequencing, while UTSS methylation status was analyzed via methylation-specific-PCR (MS-PCR).
Results: H3F3A mutations were absent in all MDBs, 30% of samples showed ATRX nuclear loss, 18.2% of cases were
characterized by TERT promoter mutations, while 60.9% harboured TERT promoter hyper-methylation in the UTSS region.
Elongation of telomeres was found in 42.8% of cases. Metastatic MDBs control telomere elongation via telomerase activation
(10.7%), induced by TERT promoter mutations in association with UTSS hyper-methylation, and ALT mechanism
(32.1%), triggered by ATRX inactivation. Among non-metastatic MDBs, only 5.9% (1/17) showed ATRX nuclear loss with
activation of ALT.
Conclusions: Our metastatic cases frequently activate ALT pathway, suggesting that it is a common process for senescence
escape in primary metastatic medulloblastomas. Furthermore, the activation of mechanisms for telomere elongation is not
restricted to certain molecular subgroups in this high-risk group of MDBs
Aquaporin-4 contributes to the resolution of peritumoural brain oedema in human glioblastoma multiforme after combined chemotherapy and radiotherapy
No full textBrain tumour oedema is coupled with blood-brain barrier damage and alteration in water flow. Aquaporin-4 (AQP4) is involved in the development and resolution of brain oedema, and it is strongly upregulated in glioblastoma multiforme (GBM). Here, we evaluated AQP4 expression and content in GBM and correlated with VEGF-VEGFR-2 expression. In the relapse after chemotherapy and radiotherapy, AQP4 content reduced in parallel with VEGF-VEGFR-2, as compared with primary tumours, and in the peripheral areas of relapsed tumours AQP4 mimicked normal findings of perivascular rearrangement. After immunogold electron microscopy, gold particles were attached on the glial membrane facing the perivascular side, likewise AQP4 gold labelling of the vessels of the control areas. In primary tumours the peripheral vessels appeared faintly marked by AQP4, while the perivascular tumour cells showed a strong expression. The vasculature of the inner tumour areas was unlabelled by AQP4, while tumour cells were labelled, in both primary and relapsing tumours. Relapsed tumours after radiotherapy alone showed slight AQP4 reduction and perivascular restoring in the peripheral areas of the tumour. These data indicate that in GBM chemotherapy and radiotherapy induce a down-regulation in AQP4 expression restoring its perivascular rearrangement suggesting its potential role in the resolution of brain oedema. © 2009 Elsevier Ltd. All rights reserved
Tumor-initiating cell frequency is relevant for glioblastoma aggressiveness
No full textGlioblastoma (GBM) is maintained by a small subpopulation of tumor-initiating cells (TICs). The arduous assessment of TIC frequencies challenges the prognostic role of TICs in predicting the clinical outcome in GBM patients. We estimated the TIC frequency in human GBM injecting intracerebrally in mice dissociated cells without any passage in culture.All GBMs contained rare TICsand were tumorigenic in vivo but only 54% of them grew in vitro as neurospheres. We demonstrated that neurosphere formation in vitro did not foretell tumorigenic ability in vivo and frequencies calculated in vitro overestimated the TIC content.Our findings assert the pathological significance of GBM TICs. TIC number correlated positively with tumor incidence and inversely with survival of tumor-bearing mice. Stratification of GBM patients according to TIC content revealed that patients with low TIC frequency experienced a trend towards a longer progression free survival. The expression of either putative stem-cell markers or markers associated with different GBM molecular subtypes did not associate with either TIC content or neurosphere formation underlying the limitations of TIC identification based on the expression of some putative stem cell-markers
Hemangioblastomas and Other Vascular Origating Tumors of Brain or Spinal Cord
No full text: Hemangioblastomas (HBs) are highly vascularized, slow-growing, rare benign tumors (WHO grade I). They account for about 2% of intracranial neoplasms; however, they are the most common primary cerebellar tumors in adults. Another frequent seat is the spinal cord (2-10% of primary spinal cord tumors). HBs are constituted by stromal and capillary vascular cells; macroscopically, HBs appear as nodular tumors, with or without cystic components. Although most of the HBs are sporadic (57-75%), they represent a particular component of von Hippel-Lindau disease (VHL), an autosomal dominant syndrome with high penetrance, due to a germline pathogenic mutation in the VHL gene, which is a tumor suppressor with chromosomal location on the short arm of chromosome three. VHL disease determines a variety of malignant and benign tumors, most frequently HBs, renal cell carcinomas, pheochromocytomas/paragangliomas, pancreatic neuroendocrine tumors, and endolymphatic sac tumors. Up to 20% of cases are due to de novo pathogenic variants without a family history. Many epidemiologic details of these tumors, especially the sporadic forms, are not well known. The median age of patients with sporadic HBS is about 40 years. More than two-third of VHL patients develop one or more central nervous system HBs during their lifetime; in case of VHL, patients at first diagnosis are usually younger than the patients with sporadic tumors. The most common presenting signs and symptoms are related to increased intracranial pressure, cerebellar signs, or spinal cord alterations in case of spinal involvement. Magnetic resonance imaging is the gold standard for the diagnosis, assessment, and follow-up of HBs, both sporadic and syndrome-related; angiography is rarely performed because the diagnosis is easily obtained with magnetic resonance. However, the diagnosis of an asymptomatic lesion does not automatically result in therapeutic actions, as the risks of treatment and the onset of possible neurological deficit need to be balanced, considering that HBs may remain asymptomatic and have a static or slow-growing behavior. In such cases, regular follow-up can represent a valid therapeutic option until the patients remain asymptomatic. There are no actual pharmacological therapies that are demonstrated to be effective for HBs. Surgery represents the primary therapeutic approach for these tumors. Observation or radiotherapy also plays a role in the long-term management of patients harboring HBs, especially in VHL; in few selected cases, endovascular treatment has been suggested before surgical removal. This chapter presents a systematic overview of epidemiology, clinical appearance, histopathological and neuroradiological characteristics of central nervous system HBs. Moreover, the genetic and molecular biology of sporadic and VHL HBS deserves special attention. Furthermore, we will describe all the available therapeutic options, along with the follow-up management. Finally, we will briefly report other vascular originating tumors as hemangioendotheliomas, hemangiomas, or angiosarcomas
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