Search

Introduction: The present study was designed to describe tumour features and treatments for patients with breast cancer. It also aimed at assessing the risk of distant metastases in relation to biological profiles, disease stages and treatment., Methods: Data were analysed from 81,882 patients in the EUSOMA database (disease stages at diagnosis 0-IV; median age 61 years; range 20-100 years). All patients were treated between January 2016 and December 2021 in 53 Breast Centres within the EUSOMA certification process in 13 European countries. Cases were classified as HR+ /HER2-, HR+ /HER2 + , HR-/HER2 + or HR-/HER2- and data were analysed accordingly., Results: Univariable and multivariable analyses for distant metastases were conducted on a subset of 38,119 cases with information on whether or not they had developed them. Potential determinants included sub-group type, Ki67 value, disease stage, adjuvant systemic therapies and post-operative radiation therapy. In multivariable analysis, the HR-/HER2 + and HR-/HER2- sub-groups were associated with a higher risk of distant metastases than HR+ /HER2-. Ki67 > 20 % and advanced stage disease also carried a high risk. Radiation therapy emerged as a protective factor against distant metastases., Conclusions: Present results show a large patient database offers an information stream that can be applied to reduce uncertainties in clinical practice. Database parameters need to be updated dynamically for outcome monitoring. Molecular prognostic factors, gene-expression signatures, tumour-infiltrating lymphocytes and circulating tumoral DNA should be added., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: LG: Advisory Board: Astra Zeneca/Daiichi Sankyo, Seagen. Support for attending meetings and/or travel: Ipsen, Novartis, Pfizer. Other non-financial interests: Member of Olympia Steering committee. FPD: Grants or contracts from any entity: Fondation belge contre le cancer (post-doctoral research grant). Consulting fees: Roche, Pfizer, AstraZeneca, Lilly, Novartis, Amgen, Daiichi Sankyo, Pierre Fabre, Gilead Sciences, Seagen, MSD (payment made to my institution). Support for attending meetings and/or travel: Amgen, Roche, Teva, Pfizer, Daiichi Sankyo/AstraZeneca, Gilead Sciences., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Practice indicators (PI) measure provided care making use of real-world data. This study describes trends and variations in adjuvant treatment of early breast cancer (EBC) using the European Society of Breast Cancer Specialists (EUSOMA) database., Methods: The analysis was conducted on anonymous cumulative data registered by 56 certified breast centres, which all entered at least 500 new diagnoses in the database in the 10-year period 2010-2019. Practice trends of radiotherapy, endocrine treatment, chemotherapy, and anti-HER2 therapy were evaluated. The association with age group (<50, 50-69, ≥70) and geographical area of the centre (Northern, Central, Southern Europe; NE, CE, SE) was assessed with the Pearson Chi 2 test for independence in contingency tables., Results: In total, 150,150 patients with EBC were selected. Overall, radiotherapy was administered more frequently in NE centres, and conversely, endocrine, chemo-, and anti-HER2 therapy were used more frequently in SE centres (p<0.001). 46.9% of the pN1 patients received postmastectomy radiotherapy, with significant differences by age and geographical region (p < 0.001). Adjuvant endocrine treatment for endocrine-sensitive carcinoma in situ was administered in 46.1%, with a decreasing trend during the study period (58.5-34.5%; p < 0.001). Anti-HER2 therapy was delivered in 75.6% of all patients with HER2BC T1a/bN0, patients older than 70 received anti-HER2 in 67.6% in SE compared to 31.3% in NE centres., Conclusion: Important variations in EBC management between European certified breast centres have been demonstrated. PI using real-world data can help to monitor, evaluate, and eventually guide and align good clinical practice in the management of breast cancer., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

The environmental impact of natural occurrences of asbestos (NOA) and asbestos-like minerals is a growing concern for environmental protection agencies. The lack of shared sampling and analytical procedures hinders effectively addressing this issue. To investigate the hazard posed by NOA, a multidisciplinary approach that encompasses geology, mineralogy, chemistry, and toxicology is proposed and demonstrated here, on a natural occurrence of antigorite from a site in Varenna Valley, Italy. Antigorite is, together with chrysotile asbestos, one of the serpentine polymorphs and its toxicological profile is still under debate. We described field and petrographic analyses required to sample a vein and to evaluate the NOA-hazard. A combination of standardized mechanical stress and automated morphometrical analyses on milled samples allowed to quantify the asbestos-like morphology. The low congruent solubility in acidic simulated body fluid, together with the toxicity-relevant surface reactivity due to iron speciation, signalled a bio-activity similar or even greater to that of chrysotile. Structural information on the genetic mechanism of antigorite asbestos-like fibres in nature were provided. Overall, the NOA site was reported to contain veins of asbestos-like antigorite and should be regarded as source of potentially toxic fibres during hazard assessment procedure., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Waste PVC is scarcely recycled due to its high chlorine content and its use in composite materials, which reduces the applicability of conventional waste treatment methods, including thermal, mechanical and chemical recycling. For this reason, alternative treatment options are being developed to increase the recyclability of waste PVC. This paper focuses on one such option which utilises ionic liquids (ILs) for material separation and dehydrochlorination of PVC contained in composite materials. Taking blisterpacks used as a packaging for medicines as an example of a composite material, the paper presents for the first time the life cycle environmental impacts of this novel PVC recycling method, in comparison with thermal treatment (low-temperature pyrolytic degradation of PVC). Three ILs were considered for the PVC recycling process: trihexyl(tetradecyl)phosphonium chloride, bromide and hexanoate. The results suggested that the impacts of the process using the first two ILs were comparable, while the system with hexanoate-based IL had 7-229 % higher impacts. Compared to the thermal treatment of waste blisterpacks, the IL assisted process had significantly higher impacts (22-819 %) in all 18 categories considered due to the greater heat requirements and the IL losses. Reducing the latter would lower most impacts by 8-41 %, while optimising the energy requirements would reduce the impacts by 10-58 %. Moreover, recovering HCl would increase significantly the environmental sustainability of the process, resulting in net-negative impacts (savings) in most categories. Overall, these improvements would lead to lower or comparable impacts to those of the thermal treatment. The findings of this study will be of interest to the polymer, recycling and related industries, as well as to process developers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Exposure to asbestos and asbestos-like minerals has been related to the development of severe lung diseases, including cancer and malignant mesothelioma (MM). A high incidence of non-occupational MM was observed in New Caledonia (France) in people living in proximity of serpentinite outcrops, containing chrysotile and fibrous antigorite. Antigorite is a magnesium silicate, which shares with chrysotile asbestos the chemical formula. To achieve information on antigorite toxicity, we investigated the physico-minero-chemical features relevant for toxicity and cellular effects elicited on murine macrophages (MH-S) and alveolar epithelial cells (A549) of three fibrous antigorites (f-Atg) collected in a Caledonian nickel lateritic ore and subjected to supergene alteration. Field Atg were milled to obtain samples suitable for toxicological studies with a similar particle size distribution. UICC chrysotile (Ctl) and a non-fibrous antigorite (nf-Atg) were used as reference minerals. A high variability in toxicity was observed depending on shape, chemical alteration, and surface reactivity. The antigorites shared with Ctl a similar surface area (16.3, 12.1, 20.3, 13.4, and 15.6 m 2 /g for f-Atg1, 2, 3, nf-Atg, and Ctl). f-Atg showed different level of pedogenetic weathering (Ni depletion f-Atg1 ≪ f-Atg2 and 3) and contained about 50% of elongated mineral particles, some of which exhibited high aspect ratios (AR > 10 μm, 20%, 26%, 31% for f-Atg1, 2, and 3, respectively). The minerals differed in bio-accessible iron at pH 4.5 (f-Atg1 ≪ f-Atg3, < f-Atg2, nf-Atg < Ctl), and surface reactivity (ROS release in solution, f-Atg1 ≪ f-Atg2, 3, nf-Atg, and Ctl). f-Atg2 and f-Atg3 induced oxidative stress and pro-inflammatory responses, while the less altered, poorly reactive sample (f-Atg1) induced negligible effects, as well nf-Atg. The slow dissolution kinetics observed in simulated body fluids may signal a high biopersistence. Overall, our work revealed a significative cellular toxicity of f-Atg that correlates with fibrous habit and surface reactivity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Water scarcity and the consequent increase of freshwater prices are a cause for concern in regions where shale gas is being extracted via hydraulic fracturing. Wastewater treatment methods aimed at reuse/recycle of fracking wastewater can help reduce water stress of the fracking process. Accordingly, this study assessed the catalytic performance and life cycle environmental impacts of cerium-based mixed oxide catalysts for catalytic wet oxidation (CWO) of organic contaminants, in order to investigate their potential as catalysts for fracking wastewater treatment. For these purposes, MnCeO x and CuCeO x were tested for phenol removal in the presence of concentrated NaCl (200 g L -1 ), which represented a synthetic fracking wastewater. Removal of phenol in pure ("phenolic") water without NaCl was also considered for comparison. Complete (100 %) phenol and a 94 % total organic carbon (TOC) removal were achieved in both the phenolic and fracking wastewaters by utilising MnCeO x (5 g L -1 ) and insignificant metal leaching was observed. However, a much lower activity was observed when the same amount of CuCeO x was utilised: 23.3 % and 20.5 % for phenol and TOC removals, respectively, in the phenolic, and 69.1 % and 63 % in the fracking wastewater. Furthermore, severe copper leaching from CuCeO x was observed during stability tests conducted in the fracking wastewater. A life cycle assessment (LCA) study carried out as part of this work showed that the production of MnCeO x had 12-98 % lower impacts than CuCeO x due to the higher impacts of copper than manganese precursors. Furthermore, the environmental impacts of CWO were found to be 94-99 % lower than those of ozonation due to lower energy and material requirements. Overall, the results of this study suggest that the adoption of catalytic treatment would improve both the efficiency and the environmental sustainability of both the fracking wastewater treatment and the fracking process as a whole., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Evidence on the efficacy of minimally invasive (MI) segmental resection of splenic flexure cancer (SFC) is not available, mostly due to the rarity of this tumor. This study aimed to determine the survival outcomes of MI and open treatment, and to investigate whether MI is noninferior to open procedure regarding short-term outcomes., Methods: This nationwide retrospective cohort study included all consecutive SFC segmental resections performed in 30 referral centers between 2006 and 2016. The primary endpoint assessing efficacy was the overall survival (OS). The secondary endpoints included cancer-specific mortality (CSM), recurrence rate (RR), short-term clinical outcomes (a composite of Clavien-Dindo > 2 complications and 30-day mortality), and pathological outcomes (a composite of lymph nodes removed ≧12, and proximal and distal free resection margins length ≧ 5 cm). For these composites, a 6% noninferiority margin was chosen based on clinical relevance estimate., Results: A total of 606 patients underwent either an open (208, 34.3%) or a MI (398, 65.7%) SFC segmental resection. At univariable analysis, OS and CSM were improved in the MI group (log-rank test p = 0.004 and Gray's tests p = 0.004, respectively), while recurrences were comparable (Gray's tests p = 0.434). Cox multivariable analysis did not support that OS and CSM were better in the MI group (p = 0.109 and p = 0.163, respectively). Successful pathological outcome, observed in 53.2% of open and 58.3% of MI resections, supported noninferiority (difference 5.1%; 1-sided 95%CI - 4.7% to ∞). Successful short-term clinical outcome was documented in 93.3% of Open and 93.0% of MI procedures, and supported noninferiority as well (difference - 0.3%; 1-sided 95%CI - 5.0% to ∞)., Conclusions: Among patients with SFC, the minimally invasive approach met the criterion for noninferiority for postoperative complications and pathological outcomes, and was found to provide results of OS, CSM, and RR comparable to those of open resection., (© 2022. The Author(s).)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Pavan, Escolano-Casado, Bellomo, Cananà, Tomatis, Leinardi, Mino and Turci.)

Chrysotile asbestos is a carcinogenic mineral that has abundantly been used in industrial and consumer applications. The carcinogenicity of the fibers is partly governed by reactive Fe surface sites that catalyze the generation of highly toxic hydroxyl radicals (HO • ) from extracellular hydrogen peroxide (H 2 O 2 ). Chrysotile also contains Cr, typically in the low mass permille range. In this study, we examined the leaching of Cr from fibers at the physiological lung pH of 7.4 in the presence and absence of H 2 O 2 . Furthermore, we investigated the potential of cells from typical asbestos-burdened tissues and cancers to take up Cr leached from chrysotile in PCR expression, immunoblot, and cellular Cr uptake experiments. Finally, the contribution of Cr to fiber-mediated H 2 O 2 decomposition and HO • generation was studied. Chromium readily dissolved from chrysotile fibers in its genotoxic and carcinogenic hexavalent redox state upon oxidation by H 2 O 2 . Lung epithelial, mesothelial, lung carcinoma, and mesothelioma cells expressed membrane-bound Cr(VI) transporters and accumulated Cr up to 10-fold relative to the Cr(VI) concentration in the spiked medium. Conversely, anion transporter inhibitors decreased cellular Cr(VI) uptake up to 45-fold. Finally, chromium associated with chrysotile neither decomposed H 2 O 2 nor contributed to fiber-mediated HO • generation. Altogether, our results support the hypothesis that Cr may leach from inhaled chrysotile in its hexavalent state and subsequently accumulate in cells of typically asbestos-burdened tissues, which could contribute to the carcinogenicity of chrysotile fibers. However, unlike Fe, Cr did not significantly contribute to the adverse radical production of chrysotile.

Aims: We analysed the impact of the SARS-CoV-2 pandemic (COVID-19) on the quality of breast cancer care in certified EUSOMA (European Society of Breast Cancer Specialists) breast centres., Materials and Methods: The results of the EUSOMA quality indicators were compared, based on pseudonymised individual records, for the periods 1 March 2020 till 30 June 2020 (first COVID-19 peak in most countries in Europe) and 1 March 2019 till 30 June 2019. In addition, a questionnaire was sent to the participating Centres for investigating the impact of the COVID-19 pandemic on the organisation and the quality of breast cancer care., Results: Forty-five centres provided data and 31 (67%) responded to the questionnaire. The total number of new cases dropped by 19% and there was a small significant higher tumour (p = 0.003) and lymph node (p = 0.011) stage at presentation. Comparing quality indicators (12,736 patients) by multivariable analysis showed mostly non-significant differences. Surgery could be performed in a COVID-free zone in 94% of the centres, COVID testing was performed before surgery in 96% of the centres, and surgical case load was reduced in 55% of the centres. Modifications of the indications for neoadjuvant endocrine therapy, chemotherapy, and targeted therapy were necessary in 23%, 23%, and 10% of the centres; changes in indications for adjuvant endocrine, chemo-, targeted, immune, and radiotherapy in 3%, 19%, 3%, 6%, and 10%, respectively., Conclusion: Quality of breast cancer care was well maintained in EUSOMA breast centres during the first wave of the COVID-19 pandemic. A small but significantly higher tumour and lymph node stage at presentation was observed., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Aim of the Study: The study aims to evaluate the performance of selected, high-volume, highly specialized, Italian Breast Centers at the time of COVID-19 pandemic (year 2020), compared to pre-pandemic time (year 2019), highlighting differences in terms of clinical presentation of breast cancer (BC) and therapeutic strategies., Methods: Patients' data were provided by the Senonetwork data warehouse Senonet. In order to examine changes in the surgical and oncological management of BC patients during different phases of COVID-19 pandemic, we took advantage of a selection quality indicators (QIs). We performed the analyses in two time-frames, from July to September (Jul-Sep) (2019 versus 2020) and from October to December (Oct-Dec) (2019 versus 2020)., Results: Our analysis did not show any statistically significant difference in terms of diagnosis, surgical, oncological and radiation therapy procedures between the two trimesters 2019 and 2020. Nevertheless, we observed statistically significant differences, favoring 2020, when analyzing time-to surgery and time-to radiotherapy. On the other hand, we observed a significant reduction of neoadjuvant chemotherapy and we did not recollect any data on a major use of neoadjuvant endocrine therapy., Conclusions: In Italian Breast Centers, partners of Senonetwork, we could not observe any treatment delay or change in standard clinical practice for BC care during the 2020 pandemic year, compared to 2019 pre-pandemic year. This finding is in contrast with the globally reported decrease in the performance of the Italian Breast Centers due to the COVID-19 pandemic, and has to be linked to the sharp selection of Senonetwork Breast Centers., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aim: Anastomotic leakage after restorative surgery for rectal cancer shows high morbidity and related mortality. Identification of risk factors could change operative planning, with indications for stoma construction. This retrospective multicentre study aims to assess the anastomotic leak rate, identify the independent risk factors and develop a clinical prediction model to calculate the probability of leakage., Methods: The study used data from 24 Italian referral centres of the Colorectal Cancer Network of the Italian Society of Surgical Oncology. Patients were classified into two groups, AL (anastomotic leak) or NoAL (no anastomotic leak). The effect of patient-, disease-, treatment- and postoperative outcome-related factors on anastomotic leak after univariable and multivariable analysis was measured., Results: A total of 5398 patients were included, 552 in group AL and 4846 in group NoAL. The overall incidence of leaks was 10.2%, with a mean time interval of 6.8 days. The 30-day leak-related mortality was 2.6%. Sex, body mass index, tumour location, type of approach, number of cartridges employed, weight loss, clinical T stage and combined multiorgan resection were identified as independent risk factors. The stoma did not reduce the leak rate but significantly decreased leak severity and reoperation rate. A nomogram with a risk score (RALAR score) was developed to predict anastomotic leak risk at the end of resection., Conclusions: While a defunctioning stoma did not affect the leak risk, it significantly reduced its severity. Surgeons should recognize independent risk factors for leaks at the end of rectal resection and could calculate a risk score to select high-risk patients eligible for protective stoma construction., (© 2021 The Authors. Colorectal Disease published by John Wiley & Sons Ltd on behalf of Association of Coloproctology of Great Britain and Ireland.)

Many phase III trials failed to demonstrate a survival benefit from the addition of molecular therapy to conventional chemotherapy for advanced and metastatic gastric cancer, and only three agents were approved by the FDA. We examined the efficacy and safety of novel drugs recently investigated. PubMed, Embase and Cochrane Library were searched for phase III randomized controlled trials published from January 2016 to December 2020. Patients in the experimental arm received molecular therapy with or without conventional chemotherapy, while those in the control arm had conventional chemotherapy alone. The primary outcomes were overall and progression-free survival. The secondary outcomes were the rate of tumor response, severe adverse effects, and quality of life. Eight studies with a total of 4223 enrolled patients were included. The overall and progression-free survival of molecular and conventional therapy were comparable. Most of these trials did not find a significant difference in tumor response rate and in the number of severe adverse effects and related deaths between the experimental and control arms. The survival benefits of molecular therapies available to date for advanced and metastatic gastric cancer are rather unclear, mostly due to inaccurate patient selection, particularly concerning oncogene amplification and copy&nbsp;number.

Background: Ageing is associated with an increased prevalence of comorbidities and sarcopenia as well as a decline of functional reserve of multiple organ systems, which may lead, in the context of the disease-related and/or treatment-related stress, to functional deconditioning. The multicomponent 'Prehabilitation & Rehabilitation in Oncogeriatrics: Adaptation to Deconditioning risk and Accompaniment of Patients' Trajectories (PROADAPT)' intervention was developed multiprofessionally to implement prehabilitation in older patients with cancer., Methods: The PROADAPT pilot study is an interventional, non-comparative, prospective, multicentre study. It will include 122 patients oriented to complex medical-surgical curative procedures (major surgery or radiation therapy with or without chemotherapy). After informed consent, patients will undergo a comprehensive geriatric assessment and will be offered a prehabilitation kit that includes an advice booklet with personalised objectives and respiratory rehabilitation devices. Patients will then be called weekly and monitored for physical and respiratory rehabilitation, preoperative renutrition, motivational counselling and iatrogenic prevention. Six outpatient visits will be planned: at inclusion, a few days before the procedure and at 1, 3, 6 and 12 months after the end of the procedure. The main outcome of the study is the feasibility of the intervention, defined as the ability to perform at least one of the components of the programme. Clinical data collected will include patient-specific and cancer-specific characteristics., Ethics and Dissemination: The study protocol was approved by the Ile de France 8 ethics committee on 5 June 2018. The results of the primary and secondary objectives will be published in peer-reviewed journals., Trial Registration Number: NCT03659123. Pre-results of the trial., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Anatase titanium dioxide nanoparticles (TiO 2 NPs) are used in a large range of industrial applications mainly due to their photocatalytic properties. Before entering the lung, virtually all TiO 2 NPs are exposed to some UV light, and lung toxicity of TiO 2 NPs might be influenced by photoexcitation that is known to alter TiO 2 surface properties. Although the TiO 2 NPs toxicity has been extensively investigated, limited data are available regarding the toxicity of TiO 2 NPs that have been pre-exposed to UV light, and their impact on humans remains unknown. In this study, five types of TiO 2 NPs with tailored physicochemical features were characterized and irradiated by UV for 30 min. Following irradiation, cytotoxicity, pro-inflammatory response, and oxidative stress on a human lung coculture system (A549 epithelial cells and macrophages differentiated from THP-1 cells) were assessed. The surface charge of all samples was less negative after UV irradiation of TiO 2 NPs, and the average aggregate size was slightly increased. A higher cytotoxic effect was observed for preirradiated TiO 2 NPs compared to nonirradiated samples. Preirradiation of TiO 2 NPs had no significant impact on the pro-inflammatory response and oxidative stress as shown by a similar production of IL-8, TNF-α, and reactive oxygen species.

Inhalation of silica particles can induce inflammatory lung reactions that lead to silicosis and/or lung cancer when the particles are biopersistent. This toxic activity of silica dusts is extremely variable depending on their source and preparation methods. The exact molecular moiety that explains and predicts this variable toxicity of silica remains elusive. Here, we have identified a unique subfamily of silanols as the major determinant of silica particle toxicity. This population of "nearly free silanols" (NFS) appears on the surface of quartz particles upon fracture and can be modulated by thermal treatments. Density functional theory calculations indicates that NFS locate at an intersilanol distance of 4.00 to 6.00 Å and form weak mutual interactions. Thus, NFS could act as an energetically favorable moiety at the surface of silica for establishing interactions with cell membrane components to initiate toxicity. With ad hoc prepared model quartz particles enriched or depleted in NFS, we demonstrate that NFS drive toxicity, including membranolysis, in vitro proinflammatory activity, and lung inflammation. The toxic activity of NFS is confirmed with pyrogenic and vitreous amorphous silica particles, and industrial quartz samples with noncontrolled surfaces. Our results identify the missing key molecular moieties of the silica surface that initiate interactions with cell membranes, leading to pathological outcomes. NFS may explain other important interfacial processes involving silica particles., Competing Interests: Competing interest statement: The study was supported financially by the European Association of Industrial Silica Producers., (Copyright © 2020 the Author(s). Published by PNAS.)

Cement production is a highly energy-intensive process, contributing 7% to global CO 2 emissions. Over 80% of the energy used in cement production is consumed by the calcination process. This paper considers a novel solar thermal technology for calcination, to investigate if it could help mitigate the climate change and other environmental impacts from cement production on a life cycle basis. The following three solar options are compared to conventional fossil-fuel calcination via life cycle assessment: a full solar system, which provides all the required thermal energy, and two hybrid systems, where the solar system provides 14% and 33% of the thermal energy, respectively. The results show that all three solar options have lower impacts than conventional calcination in 14 out of 17 categories. The full solar system is the best alternative, with major reductions in climate change (48%), fossil depletion (75%), photochemical ozone formation (92%) and terrestrial ecotoxicity (79%). Based on insolation levels in different parts of the world, the solar systems could be applied to 26% of current global cement production. This would reduce the climate change impact by 15-40%, as well as most other impacts by 14-87%, depending on the fuel mix. However, a limiting factor might be two times greater land occupation than by the conventional process. Furthermore, the solar system has higher human toxicity-cancer (102%) and metals and minerals depletion (6%) due to the construction of solar facilities. Coupling conventional calcination with carbon capture and storage (CCS) is more efficient in reducing the climate change impact (63%) than the solar system (48%) relative to conventional calcination without CCS. However, adding CCS to the solar calciner would still be a better option, decreasing the impact by 81% relative to conventional calcination without CCS. These findings will be of interest to the solar and cement industries as well as other industrial sectors using high-temperature processes., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2018 Elsevier B.V. All rights reserved.)

This study discloses the morphological and chemical-structural modifications that occur during thermal degradation of amphibole asbestos. Low-iron tremolite and iron-rich crocidolite were heated at temperatures ranging from r.t. to 1200 °C. Heating promoted a complex sequence of iron oxidation, migration and/or clustering and, finally, the formation of brittle fibrous pseudomorphs consisting of newly formed minerals and amorphous nanophases. The effects of the thermal modifications on toxicologically relevant asbestos reactivity were evaluated by quantifying carbon- and oxygen-centred, namely hydroxyl (OH), radicals. Heating did not alter carbon radicals, but largely affected oxygen-centred radical yields. At low temperature, reactivity of both amphiboles decreased. At 1200 °C, tremolite structural breakdown was achieved and the reactivity was further reduced by migration of reactive iron ions into the more stable TO 4 tetrahedra of the newly formed pyroxene(s). Differently, crocidolite breakdown at 1000 °C induced the formation of hematite, Fe-rich pyroxene, cristobalite, and abundant amorphous material and restored radical reactivity. Our finding suggests that thermally treated asbestos and its breakdown products still share some toxicologically relevant properties with pristine fibre. Asbestos inertization studies should consider morphology and surface reactivity, beyond crystallinity, when proving that a thermally inactivated asbestos-containing material is safe., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Comparable performance indicators for breast cancer screening in the European Union (EU) have not been previously reported. We estimated adjusted breast cancer screening positivity rate (PR) and detection rates (DR) to investigate variation across EU countries. For the age 50-69 years, the adjusted EU-pooled PR for initial screening was 8.9% (cross-programme variation range 3.2-19.5%) while DR of invasive cancers was 5.3/1,000 (range 3.8-7.4/1,000) and DR of ductal carcinoma in situ (DCIS) was 1.3/1,000 (range 0.7-2.7/1,000). For subsequent screening, the adjusted EU-pooled PR was 3.6% (range 1.4-8.4%), the DR was 4.0/1,000 (range 2.2-5.8/1,000) and 0.8/1,000 (range 0.5-1.3/1,000) for invasive and DCIS, respectively. Adjusted performance indicators showed remarkable heterogeneity, likely due to different background breast cancer risk and awareness between target populations, and also different screening protocols and organisation. Periodic reporting of the screening indicators permits comparison and evaluation of the screening activities between and within countries aiming to improve the quality and the outcomes of screening programmes. Cancer Screening Registries would be a milestone in this direction and EU Screening Reports provide a fundamental contribution to building them., (© 2020 UICC.)

The concern about titanium dioxide nanoparticles (TiO 2 -NPs) toxicity and their possible harmful effects on human health has increased. Their biological impact is related to some key physicochemical properties, that is, particle size, charge, crystallinity, shape, and agglomeration state. However, the understanding of the influence of such features on TiO 2 -NP toxicity remains quite limited. In this study, cytotoxicity, proinflammatory response, and oxidative stress caused by five types of TiO 2 -NPs with different physicochemical properties were investigated on A549 cells used either as monoculture or in co-culture with macrophages differentiated from the human monocytic THP-1 cells. We tailored bulk and surface TiO 2 physicochemical properties and differentiated NPs for size/specific surface area, shape, agglomeration state, and surface functionalization/charge (aminopropyltriethoxysilane). An impact on the cytotoxicity and to a lesser extent on the proinflammatory responses depending on cell type was observed, namely, smaller, large-agglomerated TiO 2 -NPs were shown to be less toxic than P25, whereas rod-shaped TiO 2 -NPs were found to be more toxic. Besides, the positively charged particle was slightly more toxic than the negatively charged one. Contrarily, TiO 2 -NPs, whatever their physicochemical properties, did not induce significant ROS production in both cell systems compared to nontreated control groups. These results may contribute to a better understanding of TiO 2 -NPs toxicity in relation with their physicochemical features.

The pathogenicity of quartz involves lysosomal alteration in alveolar macrophages. This event triggers the inflammatory cascade that may lead to quartz-induced silicosis and eventually lung cancer. Experiments with synthetic quartz crystals recently showed that quartz dust is cytotoxic only when the atomic order of the crystal surfaces is upset by fracturing. Cytotoxicity was not observed when quartz had as-grown, unfractured surfaces. These findings raised questions on the potential impact of quartz surfaces on the phagolysosomal membrane upon internalization of the particles by macrophages. To gain insights on the surface-induced cytotoxicity of quartz, as-grown and fractured quartz particles in respirable size differing only in surface properties related to fracturing were prepared and physico-chemically characterized. Synthetic quartz particles were compared to a well-known toxic commercial quartz dust. Membranolysis was assessed on red blood cells, and quartz uptake, cell viability and effects on lysosomes were assessed on human PMA-differentiated THP-1 macrophages, upon exposing cells to increasing concentrations of quartz particles (10-250 µg/ml). All quartz samples were internalized, but only fractured quartz elicited cytotoxicity and phagolysosomal alterations. These effects were blunted when uptake was suppressed by incubating macrophages with particles at 4 °C. Membranolysis, but not cytotoxicity, was quenched when fractured quartz was incubated with cells in protein-supplemented medium. We propose that, upon internalization, the phagolysosome environment rapidly removes serum proteins from the quartz surface, restoring quartz membranolytic activity in the phagolysosomes. Our findings indicate that the cytotoxic activity of fractured quartz is elicited by promoting phagolysosomal membrane alteration.

The 2003 European Council recommendation urging the Member States to introduce or scale up breast, cervical and colorectal cancer screening through an organized population-based approach has had a remarkable impact. We argue that the recommendation needs to be updated for at least two sets of reasons. First, some of the current clinical guidelines include new tests or protocols that were not available at the time of the Council document. Some have already been adopted by organized screening programs, such as newly defined age ranges for mammography screening, Human Papillomavirus (HPV)-based cervical cancer screening, fecal immunochemical test (FIT) and sigmoidoscopy for colorectal cancer screening. Second, the outcomes of randomized trials evaluating screening for lung and prostate cancer have been published recently and the balance between harms and benefits needs to be pragmatically assessed. In the European Union, research collaboration and networking to exchange and develop best practices should be regularly supported by the European Commission. Integration between primary and secondary preventive strategies through comprehensive approaches is necessary not only to maximize the reduction in cancer burden but also to control the rising trend of other noncommunicable diseases sharing the same risk factors., (© 2020 International Agency for Research on Cancer (IARC/WHO); licensed by UICC.)

Conventional nanotoxicological assays are subjected to various interferences with nanoparticles and especially carbon nanotubes. A multiparametric flow cytometry (FCM) methodology was developed here as an alternative to quantify oxidative stress, mitochondrial impairment, and later cytotoxic and genotoxic events. The experiments were conducted on RAW264.7 macrophages, exposed for 90 min or 24 h-exposure with three types of multiwalled carbon nanotubes (MWCNTs): pristine (Nanocyl™ CNT), acid functionalized (CNTf), or annealed treatment (CNTa). An original combination of reactive oxygen species (ROS) probes allowed the simultaneous quantifications of broad-spectrum ROS, superoxide anion (O 2 •- ), and hydroxyl radical (•OH). All MWCNTs types induced a slight increase of broad ROS levels regardless of earlier antioxidant catalase activity. CNTf strongly stimulated the O 2 •- production. The •OH production was downregulated for all MWCNTs due to their scavenging capacity. The latter was quantified in a cell-free system by electron paramagnetic resonance spectroscopy (EPR). Further FCM-based assessment revealed early biological damages with a mitochondrial membrane potential collapse, followed by late cytotoxicity with chromatin decondensation. The combined evaluation by FCM analysis and cell-free techniques led to a better understanding of the impacts of MWCNTs surface treatments on the oxidative stress and related biological response.

Background: Li-ion batteries (LIB) are used in most portable electronics. Among a wide variety of materials, LiCoO 2 (LCO) is one of the most used for the cathode of LIB. LCO particles induce oxidative stress in mouse lungs due to their Co content, and have a strong inflammatory potential. In this study, we assessed the mutagenic potential of LCO particles in lung cells in comparison to another particulate material used in LIB, LTO (Li 4 Ti 5 O 12 ), which has a low inflammatory potential compared to LCO particles., Results: We assessed the mutagenic potential of LCO and LTO particles in vitro by performing a cytokinesis-block micronucleus (MN) assay with rat lung epithelial cells (RLE), as well as in vivo in alveolar type II epithelial (AT-II) cells. LCO particles induced MN in vitro at non-cytotoxic concentrations and in vivo at non-inflammatory doses, indicating a primary genotoxic mechanism. LTO particles did not induce MN. Electron paramagnetic resonance and terephthalate assays showed that LCO particles produce hydroxyl radicals (•OH). Catalase inhibits this •OH production. In an alkaline comet assay with the oxidative DNA damage repair enzyme human 8-oxoguanine DNA glycosylase 1, LCO particles induced DNA strand breaks and oxidative lesions. The addition of catalase reduced the frequency of MN induced by LCO particles in vitro., Conclusions: We report the mutagenic activity of LCO particles used in LIB in vitro and in vivo. Our data support the role of Co(II) ions released from these particles in their primary genotoxic activity which includes the formation of •OH by a Fenton-like reaction, oxidative DNA lesions and strand breaks, thus leading to chromosomal breaks and the formation of MN. Documenting the genotoxic potential of the other LIB particles, especially those containing Co and/or Ni, is therefore needed to guarantee a safe and sustainable development of LIB.

Purpose: Nuclear grade is an important indicator of the biological behaviour of ductal carcinoma in situ (DCIS). De-escalation of treatment has been suggested for low-grade DCIS. Our aim is to estimate the relative rate of progression of DCIS by nuclear grade by analysing the distribution of nuclear grade by detection at initial or subsequent screening., Methods: We asked International Cancer Screening Network sites to complete, based on their screening and clinical databases, an aggregated data file on DCIS detection, diagnosis and treatment., Results: Eleven screening programs reported 5068 screen-detected pure DCIS in nearly 7 million screening tests in women 50-69 years of age. For all programs combined, low-grade DCIS were 20.1% (range 11.4-31.8%) of graded DCIS, intermediate grade 31.0% and high grade 48.9%. Detection rates decreased more steeply from initial to subsequent screening in low compared to high-grade DCIS: the ratios of subsequent to initial detection rates were 0.39 for low grade, 0.51 for intermediate grade, and 0.75 for high grade (p < 0.001)., Conclusions: These results suggest that the duration of the preclinical detectable phase is longer for low than for high-grade DCIS. The findings from this large multi-centre, international study emphasize that the management of low-grade DCIS should be carefully scrutinized in order to minimize overtreatment of screen-detected slow-growing or indolent lesions. The high variation by site in the proportion of low grade suggests that further pathology standardization and training would be beneficial.

Objective: To present comparative data about the performance of colorectal cancer (CRC) screening programmes in the European Union Member States (EU MSs)., Design: Cross-sectional study. We analysed key performance indicators-participation rate, positivity rate (PR), detection rate (DR) and positive predictive value for adenomas and CRC-based on the aggregated quantitative data collected for the second EU screening report. We derived crude and pooled (through a random effects model) estimates to describe and compare trends across different MSs/regions and screening protocols., Results: Participation rate was higher in countries adopting faecal immunochemical test (FIT) (range: 22.8%-71.3%) than in those using guaiac faecal occult blood test (gFOBT) (range 4.5%-66.6%), and it showed a positive correlation (ρ=0.842, p<0.001) with participation in breast cancer screening in the same areas. Screening performance showed a large variability. Compliance with referral for colonoscopy (total colonoscopy (TC)) assessment ranged between 64% and 92%; TC completion rate ranged between 92% and 99%. PR and DR of advanced adenomas and CRC were higher in FIT, as compared with gFOBT programmes, and independent of the protocol among men, older subjects and those performing their first screening., Conclusions: The variability in the results of quality indicators across population-based screening programmes highlights the importance of continuous monitoring, as well as the need to promote quality improvement efforts, as recommended in the EU guidelines. The implementation of monitoring systems, ensuring availability of data for the entire process, together with initiatives aimed to enhance reproducibility of histology and quality of endoscopy, represent a priority in screening programmes management., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

The aim of this study was to describe the compliance of the population-based cancer screening programmes in the European Union Member States to the invitation strategies enumerated in the European Guidelines and the impact of such strategies on the invitational coverage. Experts in screening programme monitoring from the respective countries provided data. Coverage by invitation was calculated as the proportion of individuals in the target age range receiving a screening invitation over the total number of annualized eligible population. The invitation strategies of 30 breasts, 25 cervical and 27 colorectal national or regional population-based screening programmes are described. Individual mail invitations are sent by 28 breasts, 20 cervical and 25 colorectal screening programmes. Faecal occult blood test kits are sent by post in 17 of the colorectal cancer screening programmes. The majority of programmes claimed to have a population registry, although some use health insurance data as the database for sending invitations. At least 95% invitation coverage was reached by 16 breast, six cervical and five colorectal screening programmes. Majority of the programmes comply with the invitation strategies enumerated in the European guidelines, although there is still scope for improvements. Coverage by invitation is below the desirable level in many population-based cancer screening programmes in European Union.

Iron and its role as soul of life on Earth is addressed in this review as iron is one of the most abundant elements of our universe, forms the core of our planet and that of telluric (i.e., Earth-like) planets, is a major element of the Earth's crust and is hosted in an endless number of mineral phases, both crystalline and amorphous. To study iron at an atomic level inside the bulk of mineral phases or at its surface, where it is more reactive, both spectroscopy and diffraction experimental methods can be used, taking advantage of nearly the whole spectrum of electromagnetic waves. These methods can be successfully combined to microscopy to simultaneously provide chemical (e.g. iron mapping) and morphological information on mineral particles, and shed light on the interaction of mineral surfaces with organic matter. This review describes the crystal chemistry of iron-bearing minerals of importance for the environment and human health, with special attention to iron in toxic minerals, and the experimental methods used for their study. Special attention is devoted to the Fenton-like chain reaction involving Fe 2+ in the formation of highly reactive hydroxyl radicals. The final part of this review deals with release and adsorption of iron in biological fluids, coordinative and oxidative state of iron and in vitro reactivity. To disclose the very mechanisms of carcinogenesis induced by iron-bearing toxic mineral particles, crystal chemistry and surface chemistry are fundamental for a multidisciplinary approach which should involve geo-bio-scientists, toxicologists and medical doctors., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background and Objectives: We studied a large series of ductal carcinoma in situ with microinvasion (MIDC) an infrequent disease whose diagnosis and management are not well defined., Methods: 17,431 cases of breast carcinoma were treated between 2011 and 2016 by ten Italian Breast Units. Our analysis included diagnostic and clinic-pathological characteristics, surgical management, and the use of adjuvant therapies., Results: 15,091 cases (86.6%) were infiltrating carcinomas (IC), 2107 (12.1%) ductal carcinoma in situ (DCIS), and 233 (1.3%) MIDC. Age at diagnosis did not differ between DCIS and MIDC. MIDC were usually larger and expressed more frequently biologically aggressive features (higher Ki67 values, hormone receptor negativity and HER2/neu over-expression) (p < 0.01). Axillary lymph nodes were involved in 25 MIDC cases (12%), but >3 lymph nodes were involved in two cases only (1%). At multivariable analysis, only lymphovascular invasion (LVI) was associated with lymph node status (p < 0.01). Hormone therapy was prescribed in 388/1462 DCIS cases (26.5%), in 84/200 MIDC cases (42%), and in 11,086/14,188 IC cases (84.7%) (p < 0.01). Chemotherapy was administered in 28/190 MIDC cases (14.7%), and in 4080/11,548 IC cases (35.3%) (p < 0.001)., Conclusions: This is one of the largest studies of MIDC reported in the literature. Approximately 10% of DCIS harbor one or more foci of MIDC, and the latter often expresses aggressive biological features. LVI is a predictor of axillary node involvement, but this is infrequent and usually limited. Conservative surgery is performed less often than in DCIS, and adjuvant chemotherapy is less frequently utilized compared to IC., (Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Objectives: Available evidence on axillary surgery has accumulated dramatically in the last two decades in favor of less invasive care. The aim of this paper is to study 16-years trends in the surgical management of the axilla in a large population-based data set of screen-detected breast cancers in Italy and to document at what extent recommendations have been adopted in actual clinical care., Material and Methods: This is a retrospective cohort study documenting the surgical management of the axilla in primary breast cancer patients over time. We retrieved from the Italian database of screen-detected cancers 41213 cases diagnosed in women aged 50-69 between years 2000 and 2015 in twelve Italian Regions., Results: In pN0 cases, an increasing trend (p < 0.001) in the number of patients who received sentinel lymph node biopsy (SLNB) as the only axillary staging procedure was observed. In pN + cases SLNB was the only staging procedure in an increasing number of patients (p < 0.001) especially since the publication of the ACOSOG-Z0011 paper. In ductal carcinoma in situ (DCIS) SLNB was more frequent in mastectomies and in high grade and large lesions. However, 45% of low grade, small DCIS over the whole time period had some form of axillary surgery., Conclusion: This large series of screen-detected cases documents a strong time trend in the direction of reducing axillary surgery and hence potential harms from treatment. The continuing practice of SLNB in low risk DCIS is of concern in an era of increasing awareness towards overdiagnosis and overtreatment., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Amine functionalized layered double hydroxide (LDHs) adsorbents prepared using three different routes: co-precipitation, sono-chemical and ultrasonic-assisted high pressure hydrothermal. The prepared adsorbent samples were characterized using X-ray diffraction (XRD), X-ray Photoelectron Spectroscopy (XPS), Scanning electron microscope-Energy dispersive X-ray spectroscopy (SEM-EDX), Temperature Programmed Desorption (TPD), Brunauer-Emmett-Teller (BET), and Thermogravimetric analysis (TGA), respectively. The performance of the prepared adsorbents was tested in a controlled thermal-swing adsorption process to measure its adsorption capacity, regeneration and cyclic efficiencies subsequently. The characterisation results were compared with those obtained using the conventional preparation routes but taking into account of the impact of sonochemical and hydrothermal pre-treatment on textural properties, adsorption capacity, regeneration and cyclic efficiencies. Textural results depicts a surge in surface area of the adsorbent synthesised by hydrothermal route (311m 2 /g) from 25 to 171m 2 /g for conventional and ultrasonic routes respectively. Additionally, it has been revealed from the present study that adsorbents prepared using ultrasonic-assisted hydrothermal route exhibit a better CO 2 uptake capacity than that prepared using sonochemical and conventional routes. Thus, the ultrasonic-assisted hydrothermal treatment can effectively promote the adsorption capacity of the adsorbent. This is probably due to the decrease of moderate (M-O) and weak (OH - groups) basic sites with subsequent surge in the number of strong basic sites (O 2- ) resulting from the hydrothermal process. Moreover, the cyclic adsorption efficiency of the ultrasonic mediated process was found to be 76% compared with 60% for conventional and 53% for hydrothermal routes, respectively. According to the kinetic model analysis, adsorption mechanism is mostly dominated by physisorption before amine modification and by chemisorption after the modification process., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The second report on the implementation status of cancer screening in European Union (EU) was published in 2017. The report described the implementation status, protocols and organization (updated till 2016) and invitation coverage (for index year 2013) of breast, cervical and colorectal cancer screening in the EU. Experts in screening programme monitoring (N = 80) from the EU Member States having access to requisite information in their respective countries provided data on breast, cervical and colorectal cancer screening through online questionnaires. Data was collected for screening performed in the framework of publicly mandated programmes only. Filled in questionnaires were received from 26 Member States for all three sites and from one Member State for breast cancer only. Substantial improvement in screening implementation using population-based approach was documented. Among the age-eligible women, 94.7% were residents of Member States implementing or planning population-based breast cancer screening in 2016, compared to 91.6% in 2007. The corresponding figures for cervical cancer screening were 72.3 and 51.3% in 2016 and 2007, respectively. Most significant improvement was documented for colorectal cancer screening with roll-out ongoing or completed in 17 Member States in 2016, compared to only five in 2007. So the access to population-based screening increased to 72.4% of the age-eligible populations in 2016 as opposed to only 42.6% in 2007. The invitation coverage was highly variable, ranging from 0.2-111% for breast cancer, 7.6-105% for cervical cancer and 1.8-127% for colorectal cancer in the target populations. In spite of the considerable progress, much work remains to be done to achieve optimal effectiveness. Continued monitoring, regular feedbacks and periodic reporting are needed to ensure the desired impacts of the programmes., (© 2017 UICC.)

Background: The eruptions of Eyjafjallajökull (2010) and Grímsvötn (2011), Iceland, triggered immediate, international consideration of the respiratory health hazard of inhaling volcanic ash, and prompted the need to estimate the potential hazard posed by future eruptions of Iceland's volcanoes to Icelandic and Northern European populations., Methods: A physicochemical characterization and toxicological assessment was conducted on a suite of archived ash samples spanning the spectrum of past eruptions (basaltic to rhyolitic magmatic composition) of Icelandic volcanoes following a protocol specifically designed by the International Volcanic Health Hazard Network., Results: Icelandic ash can be of a respirable size (up to 11.3 vol.% < 4 μm), but the samples did not display physicochemical characteristics of pathogenic particulate in terms of composition or morphology. Ash particles were generally angular, being composed of fragmented glass and crystals. Few fiber-like particles were observed, but those present comprised glass or sodium oxides, and are not related to pathogenic natural fibers, like asbestos or fibrous zeolites, thereby limiting concern of associated respiratory diseases. None of the samples contained cristobalite or tridymite, and only one sample contained quartz, minerals of interest due to the potential to cause silicosis. Sample surface areas are low, ranging from 0.4 to 1.6 m 2  g -1 , which aligns with analyses on ash from other eruptions worldwide. All samples generated a low level of hydroxyl radicals (HO • ), a measure of surface reactivity, through the iron-catalyzed Fenton reaction compared to concurrently analyzed comparative samples. However, radical generation increased after 'refreshing' sample surfaces, indicating that newly erupted samples may display higher reactivity. A composition-dependent range of available surface iron was measured after a 7-day incubation, from 22.5 to 315.7 μmol m -2 , with mafic samples releasing more iron than silicic samples. All samples were non-reactive in a test of red blood cell-membrane damage., Conclusions: The primary particle-specific concern is the potential for future eruptions of Iceland's volcanoes to generate fine, respirable material and, thus, to increase ambient PM concentrations. This particularly applies to highly explosive silicic eruptions, but can also hold true for explosive basaltic eruptions or discrete events associated with basaltic fissure eruptions.

Among the physico-chemical features responsible for the so-called "variability of quartz hazard", a key role has been assigned to the silica surface charge, evaluated by means of ζ potential measurement. The ζ potential of silica describes the protonation state of silanols which, in turn, determine interactions with cell membranes. To gain a molecular understanding of the role of silanols in silica pathogenicity, we conducted a systematic investigation of the variation of the ζ potential as a function of pH (ζ plot titration curve) on a large set of respirable quartz particles with different levels of metal contaminants. The membranolytic activity of the particles on red blood cells, used as a readout of pathogenic activity, was assessed in parallel. Pure quartz surfaces showed sigmoid-shaped ζ plots suggesting the presence of silanol families with similar acidity, whereas contaminated dusts exhibited convex-shaped ζ plots, indicating a higher silanol heterogeneity on contaminated surfaces with respect to the pure ones. The quartz particles with a higher surface heterogeneity related to metal contamination showed a higher membranolytic activity. By removing structural defects and chemical heterogeneity, the ζ plot shifted towards the typical shape of pure quartz and the membranolytic activity was reduced. We conclude that the ζ plot is a useful readout to measure the acid-base behavior of quartz surfaces and to describe the chemical heterogeneity of quartz silanols. Surface heterogeneity, here induced by metal contamination, is proposed as the main cause of quartz membranolytic activity, further supporting the hypothesis that surface silanol disorganization determines silica pathogenicity., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Magnetite-containing glass-ceramics are promising bio-materials for replacing bone tissue after tumour resection. Thanks to their ferrimagnetic properties, they generate heat when subjected to an alternated magnetic field. In virtue of this they can be employed for the hyperthermic treatment of cancer. Moreover, grafting anti-cancer drugs onto their surface produces specific anti-neoplastic activity in these biomaterials. Gallic acid (GA) exhibits antiproliferative activity which renders it a promising candidate for anticancer applications. In the present paper, the reactivity of ferrimagnetic glass-ceramic SC-45 grafted with GA (SC-45+GA) was studied in terms of ROS release, rupture of the C-H bond of the formate molecule and Fenton reactivity by EPR/spin trapping in acellular systems. The ability of these materials to cause lipid peroxidation was assessed by UV-vis/TBA assay employing linoleic acid as a model of membrane lipid. The results, compared to those obtained with SC-45, showed that GA grafting (i) significantly enhanced the Fenton reactivity and (ii) restored the former reactivity of SC-45 towards both the C-H bond and linoleic acid which had been completely suppressed by prolonged contact with water. Fe 2+ centres at the surface are probably implicated. GA, acting as a pro-oxidant, reduces Fe 3+ to Fe 2+ by maintaining a supply of Fe 2+ at the surface of SC-45+GA., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Several studies suggest that population-based breast cancer screening programmes might help reduce social inequalities in breast cancer survival both by increasing early diagnosis and by improving access to effective treatments. To start disentangling the two effects, we evaluated social inequalities in quality of treatment of screen-detected breast cancer in the city of Turin (Italy). Combining data from the Audit System on Quality of Breast Cancer Treatment and the Turin Longitudinal Study, we analysed 2700 cases in the screening target age class 50-69 diagnosed in the period 1995-2008. We selected 10 indicators of the pathway of care, relative to timeliness and appropriateness of diagnosis and treatment, and three indicators of socioeconomic position: education, occupational status and housing characteristics. For each indicator of care, relative risks of failure were estimated by robust Poisson regression models, controlling for calendar period of diagnosis, size of tumour and activity volume of the surgery units. The principal predictor of failure of the good care indicators was the calendar period of diagnosis, with a general improvement with time in the quality of diagnosis and treatment, followed by size of the tumour and volume of activity. Socioeconomic indicators show only a marginal independent effect on timeliness indicators. The observed associations of quality indicators with socioeconomic characteristics are lower than expected, suggesting a possible role of the screening programme in reducing disparities in the access to good-quality treatments thanks to its capability to enter screen-detected women into a protected pathway of care.

New outbursts of silicosis were recently reported among workers manufacturing an engineered material known as "artificial stone," composed by high percentages of quartz (up to 98%) agglomerated with pigments and polymeric resins. Dusts released by abrasion during artificial stone polishing were characterized for particle size, morphology, and elemental composition and studied for (1) ability to catalyze free radical generation in acellular tests, (2) membranolytic potential on human erythrocytes, (3) cytotoxic activity (lactate dehydrogenase release) on murine alveolar macrophages (MH-S) and human bronchial epithelial (BEAS-2B) cell lines, (4) induction of epithelial-mesenchymal transition (EMT) in BEAS-2B cells. Min-U-Sil 5 was used as reference quartz. Artificial stone dusts exhibited morphological features close to quartz, but contained larger amount of metal transition ions (mainly, Fe, Cu, and Ti), potentially responsible for the high reactivity in free radical generation observed. Opposite to Min-U-Sil 5, they were neither hemolytic nor cytotoxic on MH-S cells, a low cytotoxicity only being observed with BEAS-2B cells. The presence on the particle surface of residues of the resin accounts for this attenuated behavior, as hemolysis appeared and cytotoxicity increased after thermal degradation of the resin, when the free quartz surface was exposed. All dusts induced EMT with loss of E-cadherin expression and increased the expression of mesenchymal proteins (α-smooth muscle actin and vimentin). This may contribute to explain the development of fibrosis on workers exposed to artificial stone dusts., (© The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Industrial processing of materials containing quartz induces physico-chemical modifications that contribute to the variability of quartz hazard in different plants. Here, modifications affecting a quartz-rich sand during cast iron production, have been investigated. Composition, morphology, presence of radicals associated to quartz and reactivity in free radical generation were studied on a raw sand and on a dust recovered after mould dismantling. Additionally, cytotoxicity of the processed dust and ROS and NO generation were evaluated on MH-S macrophages. Particle morphology and size were marginally affected by casting processing, which caused only a slight increase of the amount of respirable fraction. The raw sand was able to catalyze OH and CO2(-) generation in cell-free test, even if in a lesser extent than the reference quartz (Min-U-Sil), and shows hAl radicals, conventionally found in any quartz-bearing raw materials. Enrichment in iron and extensive coverage with amorphous carbon were observed during processing. They likely contributed, respectively, to increasing the ability of processed dust to release CO2- and to suppressing OH generation respect to the raw sand. Carbon coverage and repeated thermal treatments during industrial processing also caused annealing of radiogenic hAl defects. Finally, no cellular responses were observed with the respirable fraction of the processed powder., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Exposure to some - but not all - quartz particles is associated to silicosis, lung cancer and autoimmune diseases. What imparts pathogenicity to any single quartz source is however still unclear. Crystallinity and various surface features are implied in toxicity. Quartz dusts used so far in particle toxicology have been obtained by grinding rocks containing natural quartz, a process which affects crystallinity and yields dusts with variable surface states. To clarify the role of crystallinity in quartz pathogenicity we have grown intact quartz crystals in respirable size., Methods: Quartz crystals were grown and compared with a fractured specimen obtained by grinding the largest synthetic crystals and a mineral quartz (positive control). The key physico-chemical features relevant to particle toxicity - particle size distribution, micromorphology, crystallinity, surface charge, cell-free oxidative potential - were evaluated. Membranolysis was assessed on biological and artificial membranes. Endpoints of cellular stress were evaluated on RAW 264.7 murine macrophages by High Content Analysis after ascertaining cellular uptake by bio-TEM imaging of quartz-exposed cells., Results: Quartz crystals were grown in the submicron (n-Qz-syn) or micron (μ-Qz-syn) range by modulating the synthetic procedure. Independently from size as-grown quartz crystals with regular intact faces did not elicit cellular toxicity and lysosomal stress on RAW 264.7 macrophages, and were non-membranolytic on liposome and red blood cells. When fractured, synthetic quartz (μ-Qz-syn-f) attained particle morphology and size close to the mineral quartz dust (Qz-f, positive control) and similarly induced cellular toxicity and membranolysis. Fracturing imparted a higher heterogeneity of silanol acidic sites and radical species at the quartz surface., Conclusions: Our data support the hypothesis that the biological activity of quartz dust is not due to crystallinity but to crystal fragmentation, when conchoidal fractures are formed. Besides radical generation, fracturing upsets the expected long-range order of non-radical surface moieties - silanols, silanolates, siloxanes - which disrupt membranes and induce cellular toxicity, both outcomes associated to the inflammatory response to quartz.

The natural occurrence of asbestos (NOA) in rural areas is a serious concern for human health and the dispersion route of asbestos in the proximity of natural asbestos-rich settings has been marginally evaluated so far. NOA may affect air, but also water and soil quality. In rural areas population may be exposed to asbestos with a largely unknown impact on human health. This work investigates the potential exposure of a farmer cultivating a field nearby the largest former asbestos mine of Western Europe (Balangero, Italy). The concentration of waterborne asbestos in the stream used to water the field was measured (ca. 2×10(5) fibers per liter, ff/L) and the cultivated ultramafic topsoil characterized, evidencing a remarkable occurrence of chrysotile. The worker's personal exposure and the environmental fiber dispersion during a simulated agricultural activity (tillage) were quantified in two independent trials. During the trials, the worker was exposed to average concentrations of 16 and 26 ff/L, with a peak of 40 ff/L. These data inform about the possible exposure of an agricultural worker to asbestos concentration higher than the accepted threshold of 2 ff/L. The release of asbestos fibers into the environment was negligible (0-2 ff/L)., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objective: The aim of this study is to assess age-specific compliance to quality indicators (QIs) regarding the treatment of breast cancer as defined by European Society of Breast Cancer Specialists (EUSOMA) for patients across Europe., Methods: All patients entered into this study were affected by in situ or invasive breast cancer, diagnosed and treated between 2003 and 2012 at 27 Breast Units across Europe, who were entered into the EUSOMA database. Patients were categorised according to age; compliance to thirteen QIs was assessed for each age group and per time period (2003-2007 and 2008-2012). Compliance to QIs was tested by multivariable logistic regression models adjusted for breast unit, incidence year and tumour characteristics., Results: Overall, 41,871 patients with a mean age of 59.6years were available for analysis. The highest compliance was reached for patients aged 55-64years and in the time period 2008-2012, whilst the lowest compliance was observed for women aged over 74 or under 40years and in the earlier time period. In multivariable logistic regression models, a significant difference between age categories was shown for 12 out of 13 QIs (P<0.001). Compliance to the QIs for patients aged ⩾75years was significantly lower when compared to patients aged 55-64years for ten QIs, whilst for patients in the youngest age group this was true for seven QIs., Conclusion: In conclusion, we found that among the 27 included breast units across Europe, compliance to QIs for breast cancer treatment is often lower in the youngest and oldest breast cancer patients, with a tendency to overtreatment in the youngest patients, and to under-treatment in the elderly., (Copyright © 2015. Published by Elsevier Ltd.)

Objectives: evaluation of a centralised collection of clinical data (Service) within cancer screening programmes in Piedmont based on a hub&spoke model and its impact on process indicators., Design: assessment of an organisational intervention, through a non-controlled pre-post design., Setting and Participants: organised screening programmes within the Piedmont Region, divided into 9 departments., Main Outcome Measures: clinical data (extracted from medical charts for mammography screening and from excision histology reports for cervical screening) obtained through the Service were quantified and their completeness was assessed. The Service impact on the detection rate (DR) was evaluated, comparing the DR pre- (2005-2008) and post-Service (2009- 2012) within breast screening; the DR was computed through histological diagnosis made during colposcopy (pre-Service method) or through the worst diagnosis between the latter and that reported from excision histology (post-Service method) within cervical screening (data available for department 1, year 2013). Some hints on human resources employed in pre- and post-Service periods were reported., Results: within mammography screening, the Service obtained 53.1% of extra-department medical charts and 45.8% of extra-region ones; the percentage of missing diagnoses changed from 5.5% (pre- Service) to 3.7% (post-Service). The age standardised DR for malignant tumours in the post-Service period is 1.3 times the DR of the pre-Service period per 1,000 screening tests. Within cervical screening, 51.7% of histological reports was recorded. Crude DR for high-grade lesions changed from 3.9 (pre-Service) to 4.7 (post-Service) per 1,000 screened women. The system centralisation did not imply an increase in the dedicated personnel., Conclusion: the Service is an operational core which coordinates the collection of clinical data, impacting on process indicators without an increase in human resources at departmental level.

This annual survey, conducted by the Italian group for mammography screening (GISMa), collects individual data on diagnosis and treatment of about 50% of screen-detected, operated lesions in Italy. The 2011-2012 results show good overall quality and an improving trend over time. A number of critical issues have been identified, including waiting times (which have had a worsening trend over the years) and compliance with the recommendation of not performing frozen section examination on small lesions. Pre-operative diagnosis improved constantly over time, but there is still a large variation between Regions and programmes. For almost 90% of screen-detected invasive cancers a sentinel lymph node (SLN) biopsy was performed on the axilla, avoiding a large number of potentially harmful dissections. On the other hand, potential overuse of SLN dissection for ductal carcinoma in situ, although apparently starting to decline, deserves further investigation. The detailed results have been distributed, among other ways by means of a web-based data-warehouse, to regional and local screening programmes, in order to allow multidisciplinary discussion and identification of the appropriate solutions to any issues documented by the data. The problem of waiting times should be assigned priority. Specialist Breast Units with adequate case volume and enough resources would provide the best setting for making monitoring effective in producing quality improvements with shorter waiting times.

Background: The hemolytic activity of inhaled particles such as silica has been widely investigated in the past and represents a usual toxicological endpoint to characterize particle reactivity despite the fact that red blood cells (RBCs) are not involved in the pathogenesis of pulmonary inflammation or fibrosis caused by some inhaled particles. The inflammatory process induced by silica starts with the activation of the inflammasome, which leads to the release of mature IL-1β. One of the upstream mechanisms causing activation of the inflammasome is the labilization of the phagolysosomal membrane after particle phagocytosis. Considering RBC lysis as a model of membrane damage, we evaluated the relationship between hemolytic activity and inflammasome-dependent release of IL-1β for a panel of selected silica particles, in search of the toxicological significance of the hemolytic activity of an inhaled particle., Methods: Well-characterized silica particles, including four quartz samples and a vitreous silica, with different surface properties and hemolytic potential were tested for their capacity to induce inflammasome-dependent release of IL-1β in LPS-primed primary murine peritoneal macrophages by ELISA and Western blot analysis. The mechanisms of IL-1β maturation and release were clarified by using ASC-deficient cells and inhibitors of phagocytosis and cathepsin B., Results: The silica samples induced dose-dependent hemolysis and IL-1β release of different amplitudes. A significant correlation between IL-1β release and hemolytic activity was evidenced (r = 0.827) by linear regression analysis. IL-1β release was completely abolished in ASC-deficient cells and reduced by inhibitors, confirming the involvement of the inflammasome and the requirement of phagocytosis and cathepsin B for activation., Conclusions: The same physico-chemical properties of silica particles which are relevant for the lysis of the RBC membrane also appear implicated in the labilization of the phagolysosome, leading to inflammasome activation and release of the pro-inflammatory cytokine IL-1β. These findings strengthen the relevance of the hemolysis assay to predict the pro-inflammatory activity of silica dusts.

Silicon carbide (SiC) an industrial-scale product manufactured through the Acheson process, is largely employed in various applications. Its toxicity has been poorly investigated. Our study aims at characterizing the physico-chemical features and the in vitro impact on biological activity of five manufactured SiC powders: two coarse powders (SiC C1/C2), two fine powders (SiC F1/F2) and a powder rich in iron impurities (SiC I). RAW 264.7 macrophages were exposed to the different SiC particles and the cellular responses were evaluated. Contrary to what happens with silica, no SiC cytotoxicity was observed but pro-oxidative and pro-inflammatory responses of variable intensity were evidenced. Oxidative stress (H₂O₂ production) appeared related to SiC particle size, while iron level regulated pro-inflammatory response (TNFα production). To investigate the impact of surface reactivity on the biological responses, coarse SiC C1 and fine SiC F1 powders were submitted to different thermal treatments (650-1400 °C) in order to alter the oxidation state of the particle surface. At 1400 °C a decrease in TNFα production and an increase in HO·, COO(·-) radicals production were observed in correlation with the formation of a surface layer of crystalline silica. Finally, a strong correlation was observed between surface oxidation state and in vitro toxicity., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Boehmite (γ-AlOOH) nanoparticles (NPs) are used in a wide range of industrial applications. However, little is known about their potential toxicity. This study aimed at a better understanding of the relationship between the physico-chemical properties of these NPs and their in vitro biological activity. After an extensive physico-chemical characterization, the cytotoxicity, pro-inflammatory response and oxidative stress induced by a bulk industrial powder and its ultrafine fraction were assessed using RAW264.7 macrophages. Although the bulk powder did not trigger a significant biological activity, pro-inflammatory response was highly enhanced with the ultrafine fraction. This observation was confirmed with boehmite NPs synthesized at the laboratory scale, with well-defined and tightly controlled physico-chemical features: toxicity was increased when NPs were dispersed. In conclusion, the agglomerates size of boehmite NPs has a major impact on their toxicity, highlighting the need to study not only raw industrial powders containing NPs but also the ultrafine fractions representative of respirable particles.