102 research outputs found

    Therapeutic enhancement of a cytotoxic agent using Photochemical internalisation in 3D compressed collagen constructs of ovarian cancer

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    Photochemical internalisation (PCI) is a method for enhancing delivery of drugs to their intracellular target sites of action. In this study we investigated the efficacy of PCI using a porphyrin photosensitiser and a cytotoxic agent on spheroid and non-spheroid compressed collagen 3D constructs of ovarian cancer versus conventional 2D culture. The therapeutic responses of two human carcinoma cell lines (SKOV3 and HEY) were compared using a range of assays including optical imaging. The treatment was shown to be effective in non-spheroid constructs of both cell lines causing a significant and synergistic reduction in cell viability measured at 48 or 96 hours post-illumination. In the larger spheroid constructs, PCI was still effective but required higher saporin and photosensitiser doses. Moreover, in contrast to the 2D and non-spheroid experiments, where comparable efficacy was found for the two cell lines, HEY spheroid constructs were found to be more susceptible to PCI and a lower dose of saporin could be used. PCI treatment was observed to induce death principally by apoptosis in the 3D constructs compared to the mostly necrotic cell death caused by PDT. At low oxygen levels (1%) both PDT and PCI were significantly less effective in the constructs

    The n_TOF NEAR Station Commissioning and first physics case

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    The NEAR Station is a new experimental area developed at the n_TOF Facility at CERN. The activation station of NEAR underwent a characterization of the beam following the installation of the new n_TOF Spallation Target. The commissioning of the neutron beam comprises a set of simulations made with the FLUKA code and experimental verification. The experimental determination of the neutron spectrum was made using activation techniques with three separate set-ups. Two set-ups were based on the Multi-foil Activation technique (MAM-1 and MAM-2), and the third set-up relied on the process of neutron moderation and activation of a single material (ANTILoPE). The three set-ups are presented. Also the present plans and future perspectives of the activation station of NEAR are discussed

    Pushing the high count rate limits of scintillation detectors for challenging neutron-capture experiments

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    One of the critical aspects for the accurate determination of neutron capture cross sections when combining time-of-flight and total energy detector techniques is the characterization and control of systematic uncertainties associated to the measuring devices. In this work we explore the most conspicuous effects associated to harsh count rate conditions: dead-time and pile-up effects. Both effects, when not properly treated, can lead to large systematic uncertainties and bias in the determination of neutron cross sections. In the majority of neutron capture measurements carried out at the CERN n\_TOF facility, the detectors of choice are the C6_{6}D6_{6} liquid-based either in form of large-volume cells or recently commissioned sTED detector array, consisting of much smaller-volume modules. To account for the aforementioned effects, we introduce a Monte Carlo model for these detectors mimicking harsh count rate conditions similar to those happening at the CERN n\_TOF 20~m fligth path vertical measuring station. The model parameters are extracted by comparison with the experimental data taken at the same facility during 2022 experimental campaign. We propose a novel methodology to consider both, dead-time and pile-up effects simultaneously for these fast detectors and check the applicability to experimental data from 197^{197}Au(nn,γ\gamma), including the saturated 4.9~eV resonance which is an important component of normalization for neutron cross section measurements

    A Multicenter Retrospective Survey regarding Diabetic Ketoacidosis Management in Italian Children with Type 1 Diabetes

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    We conducted a retrospective survey in pediatric centers belonging to the Italian Society for Pediatric Diabetology and Endocrinology. The following data were collected for all new-onset diabetes patients aged 0-18 years: DKA (pH < 7.30), severe DKA (pH < 7.1), DKA in preschool children, DKA treatment according to ISPAD protocol, type of rehydrating solution used, bicarbonates use, and amount of insulin infused. Records (n = 2453) of children with newly diagnosed diabetes were collected from 68/77 centers (87%), 39 of which are tertiary referral centers, the majority of whom (n = 1536, 89.4%) were diagnosed in the tertiary referral centers. DKA was observed in 38.5% and severe DKA in 10.3%. Considering preschool children, DKA was observed in 72%, and severe DKA in 16.7%. Cerebral edema following DKA treatment was observed in 5 (0.5%). DKA treatment according to ISPAD guidelines was adopted in 68% of the centers. In the first 2 hours, rehydration was started with normal saline in all centers, but with different amount. Bicarbonate was quite never been used. Insulin was infused starting from third hour at the rate of 0.05-0.1 U/kg/h in 72% of centers. Despite prevention campaign, DKA is still observed in Italian children at onset, with significant variability in DKA treatment, underlying the need to share guidelines among centers

    Advances and new ideas for neutron-capture astrophysics experiments at CERN n_TOF

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    This article presents a few selected developments and future ideas related to the measurement of (n,γ) data of astrophysical interest at CERN n_TOF. The MC-aided analysis methodology for the use of low-efficiency radiation detectors in time-of-flight neutron-capture measurements is discussed, with particular emphasis on the systematic accuracy. Several recent instrumental advances are also presented, such as the development of total-energy detectors with γ-ray imaging capability for background suppression, and the development of an array of small-volume organic scintillators aimed at exploiting the high instantaneous neutron-flux of EAR2. Finally, astrophysics prospects related to the intermediate i neutron-capture process of nucleosynthesis are discussed in the context of the new NEAR activation area

    Advances and new ideas for neutron-capture astrophysics experiments at CERN n_TOF

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    This article presents a few selected developments and future ideas related to the measurement of (n,γ) data of astrophysical interest at CERN n_TOF. The MC-aided analysis methodology for the use of low-efficiency radiation detectors in time-of-flight neutron-capture measurements is discussed, with particular emphasis on the systematic accuracy. Several recent instrumental advances are also presented, such as the development of total-energy detectors with γ-ray imaging capability for background suppression, and the development of an array of small-volume organic scintillators aimed at exploiting the high instantaneous neutron-flux of EAR2. Finally, astrophysics prospects related to the intermediate i neutron-capture process of nucleosynthesis are discussed in the context of the new NEAR activation area

    Prognostic value of COX-2, P53, and EZH-2 evaluated by quantitative image analysis in premalignant and malignant breast lesions

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    Background Cytological differential diagnosis of atypical hyperplasia and well differentiated breast carcinoma may be challenging, because sometimes there is an overlap between the cytomorphological features of these lesions. The aim of the study was to investigate COX-2, EZH-2, p53 expression in carcinomas and the gray zone of breast cytology categories of atypical hyperplastic lesions with regard to biological behavior of the tumor. Methods FNA speciments from 100 patients with breast hyperplastic lesions and cancer were investigated by immunocytochemistry and a quantitative analysis for COX-2, p53, and EZH-2. Results Extent of staining for COX-2 correlated with percentage of positive for EZH-2 (P-&lt;-0.0001) and p53 nuclei (P-&lt;-0.001). The intensity of COX-2 was lower in the carcinoma group (118.57-±-12.43) than in the hyperplastic (127.16-±-11.71) group (P-=-0.006). On the contrary the mean value of staining extent was greater in the adenocarcinoma cases (15.96-±-13.03) than in hyperplastic (4.04-±-1.94) cases (P-&lt;-0.0001). The percentage of EZH-2 and p53 positive cells correlated with the histological type of the lesions (P-=-0.001 and P-=-0.011, respectively). There was also a statistically significant relation between tumor size and expression of COX-2 (P-=-0.007) and EZH-2 (P-=-0.010). Conclusion Our study showed that the expression of COX-2, EZH-2, and p53 as determined by immunocytochemistry at quantitative level may be a predictor for distinguishing cytologically atypical hyperplastic from malignant breast lesions and may be regarded as potential prognostic factor in breast cancer patients. © 2014 Wiley Periodicals, Inc

    Expression of substance P, vasoactive intestinal peptide and heat shock protein 70 in nasal mucosal smears of patients with allergic rhinitis: Investigation using a liquid-based method

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    Objective: The aim of this study was to investigate expression of the neuropeptides substance P, vasoactive intestinal peptide and heat shock protein 70 in the nasal mucosa cells of patients with seasonal allergic rhinitis, in order to obtain more information on the pathophysiological and immunological role of these markers in allergic rhinitis. Material and methods: Nasal epithelium specimens obtained from 42 patients with allergic rhinitis were studied, using Shandon&apos;s Papspin liquid-based cytology method. Smears were immunostained with antibodies against substance P, vasoactive intestinal peptide and heat shock protein 70, and the results were correlated with the clinical features of seasonal allergic rhinitis. Results: A positive reaction for substance P, vasoactive intestinal peptide and heat shock protein 70 was observed in 73.8, 66.7 and 69.0 per cent of the allergic rhinitis mucosal smears, respectively. The Pearson chi-square test showed that 40.5 per cent of the immunostained smears had a positive reaction for one or two of the markers studied (i.e. substance P, vasoactive intestinal peptide or heat shock protein 70), and that 47.6 per cent of the smears had a positive reaction for all the markers (p &lt; 0.0001). Conclusions: We found a high level of expression of substance P and vasoactive intestinal peptide in the nasal mucosa smears of patients suffering from allergic rhinitis. This indicates a role for these neuropeptides in the neuroregulation of immunity and hypersensivity in this disease. Furthermore, expression of heat shock protein 70 may contribute to the development of allergic rhinitis. © 2008 JLO (1984) Limited
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