Nearly free silanols drive the interaction of crystalline silica polymorphs with membranes: Implications for mineral toxicity

Crystalline silica (CS) is a well-known hazardous material that causes severe diseases including silicosis, lung cancer, and autoimmune diseases. However, the hazard associated to crystalline silica is extremely variable and depends on some specific characteristics, including crystal structure and surface chemistry. The crystalline silica polymorphs share the SiO(2) stoichiometry and differentiate for crystal structure. The different crystal lattices in turn expose differently ordered hydroxyl groups at the crystal surface, i.e., the silanols. The nearly free silanols (NFS), a specific population of weakly interacting silanols, have been recently advanced as the key surface feature that governs recognition mechanisms between quartz and cell membrane, initiating toxicity. We showed here that the nearly free silanols occur on the other crystalline silica polymorphs and take part in the molecular interactions with biomembranes. A set of crystalline silica polymorphs, including quartz, cristobalite, tridymite, coesite, and stishovite, was physico-chemically characterized and the membranolytic activity was assessed using red blood cells as model membranes. Infrared spectroscopy in highly controlled conditions was used to profile the surface silanol topochemistry and the occurrence of surface nearly free silanols on crystalline silica polymorphs. All crystalline silica polymorphs, but stishovite were membranolytic. Notably, pristine stishovite did not exhibited surface nearly free silanols. The topochemistry of surface silanols was modulated by thermal treatments, and we showed that the occurrence of nearly free silanols paralleled the membranolytic activity for the crystalline silica polymorphs. These results provide a comprehensive understanding of the structure-activity relationship between nearly free silanols and membranolytic activity of crystalline silica polymorphs, offering a possible clue for interpreting the molecular mechanisms associated with silica hazard and bio-minero-chemical interfacial phenomena, including prebiotic chemistry

Nearly free silanols drive the interaction of crystalline silica polymorphs with membranes: Implications for mineral toxicity

Crystalline silica (CS) is a well-known hazardous material that causes severe diseases including silicosis, lung cancer, and autoimmune diseases. However, the hazard associated to crystalline silica is extremely variable and depends on some specific characteristics, including crystal structure and surface chemistry. The crystalline silica polymorphs share the SiO2 stoichiometry and differentiate for crystal structure. The different crystal lattices in turn expose differently ordered hydroxyl groups at the crystal surface, i.e., the silanols. The nearly free silanols (NFS), a specific population of weakly interacting silanols, have been recently advanced as the key surface feature that governs recognition mechanisms between quartz and cell membrane, initiating toxicity. We showed here that the nearly free silanols occur on the other crystalline silica polymorphs and take part in the molecular interactions with biomembranes. A set of crystalline silica polymorphs, including quartz, cristobalite, tridymite, coesite, and stishovite, was physico-chemically characterized and the membranolytic activity was assessed using red blood cells as model membranes. Infrared spectroscopy in highly controlled conditions was used to profile the surface silanol topochemistry and the occurrence of surface nearly free silanols on crystalline silica polymorphs. All crystalline silica polymorphs, but stishovite were membranolytic. Notably, pristine stishovite did not exhibited surface nearly free silanols. The topochemistry of surface silanols was modulated by thermal treatments, and we showed that the occurrence of nearly free silanols paralleled the membranolytic activity for the crystalline silica polymorphs. These results provide a comprehensive understanding of the structure-activity relationship between nearly free silanols and membranolytic activity of crystalline silica polymorphs, offering a possible clue for interpreting the molecular mechanisms associated with silica hazard and bio-minero-chemical interfacial phenomena, including prebiotic chemistry

Multimodality therapy approaches, local and systemic treatment, compared with chemotherapy alone in recurrent glioblastoma

BACKGROUND: Long-term local control in Glioblastoma is rarely achieved and nearly all patients relapse. In this study we evaluated the clinical effect of different treatment approaches in recurrent patients. METHODS: Forty-three patients, with median age of 51 years were evaluated for salvage treatment: re-resection and/or re-irradiation plus chemotherapy or chemotherapy alone. Response was recorded using the Response Assessment in Neuro-Oncology criteria. Hematologic and non-hematologic toxicities were graded according to Common Terminology Criteria for Adverse Events 4.0. Twenty-one patients underwent chemotherapy combined with local treatment, surgery and/or radiation therapy, and 22 underwent chemotherapy only. RESULTS: The median follow up was 7 months (range 3–28 months). The 1 and 2-years Progression Free Survival was 65 and 10 % for combined treatment and 22 and 0 % for chemotherapy alone (p < 0.01). The 1 and 2-years overall survival was 69 and 29 % for combined and 26 and 0 % for chemotherapy alone (p < 0.01). No toxicity greater than grade 2 was recorded. CONCLUSION: These data showed that in glioblastoma recurrence the combination of several approaches in a limited group of patients is more effective than a single treatment alone. This stress the importance of multimodality treatment whenever clinically feasible

Comparison between intrasylvian and intracerebral hematoma associated with ruptured middle cerebral artery aneurysms: clinical implications, technical considerations, and outcome evaluation

Background: Subarachnoid hemorrhage (SAH) due to a middle cerebral artery (MCA) aneurysms rupture is often associated with intracerebral (ICH) or intrasylvian hematomas (ISH). Materials and methods: We reviewed 163 patients with ruptured MCA aneurysms associated with pure SAH or SAH+ICH/ISH. Patients were first dichotomized according to the presence of a hematoma (ICH/ISH). Then, we performed a subgroup analysis comparing ICH versus ISH in order to explore their relationship with the most relevant demographic, clinical, and angioarchitectural features. Results: Overall, 85 patients (52%) had a pure SAH, whereas 78 (48%) presented an associated ICH/ISH. No significant differences were observed in demographics and angioarchitectural features between the two groups, but Fisher grading and Hunt-Hess score were higher in patients with hematomas. A good outcome was observed in a higher percentage of patients with pure SAH compared with the others (76% Vs 44%), although mortality rates were comparable. Age, Hunt-Hess and treatment-related complications were the main outcome predictors at multivariate analysis. Patients with ICH appeared clinically worse than those with ISH. We also found that older age, higher Hunt-Hess, larger aneurysms, decompressive craniectomy and treatment-related complications were associated with poor outcome among patients with ISH, but not with ICH, which appeared per se as a more severe clinical condition. Conclusions: Our study confirm that age, Hunt-Hess and treatment-related complications influence the outcome of patients with ruptured MCA aneurysms. However, in the subgroup analysis of patients with SAH associated with ICH or ISH, only the Hunt-Hess at onset appeared as an independent predictor of outcome

ExoClock project: an open platform for monitoring the ephemerides of Ariel targets with contributions from the public

The Ariel mission will observe spectroscopically around 1000 exoplanets to further characterise their atmospheres. For the mission to be as efficient as possible, a good knowledge of the planets’ ephemerides is needed before its launch in 2028. While ephemerides for some planets are being refined on a per-case basis, an organised effort to collectively verify or update them when necessary does not exist. In this study, we introduce the ExoClock project, an open, integrated and interactive platform with the purpose of producing a confirmed list of ephemerides for the planets that will be observed by Ariel. The project has been developed in a manner to make the best use of all available resources: observations reported in the literature, observations from space instruments and, mainly, observations from ground-based telescopes, including both professional and amateur observatories. To facilitate inexperienced observers and at the same time achieve homogeneity in the results, we created data collection and validation protocols, educational material and easy to use interfaces, open to everyone. ExoClock was launched in September 2019 and now counts over 140 participants from more than 15 countries around the world. In this release, we report the results of observations obtained until the 15h of April 2020 for 120 Ariel candidate targets. In total, 632 observations were used to either verify or update the ephemerides of 84 planets. Additionally, we developed the Exoplanet Characterisation Catalogue (ECC), a catalogue built in a consistent way to assist the ephemeris refinement process. So far, the collaborative open framework of the ExoClock project has proven to be highly efficient in coordinating scientific efforts involving diverse audiences. Therefore, we believe that it is a paradigm that can be applied in the future for other research purposes, too