COVID-19 outbreak in healthcare workers in hospitals in Trieste, North-east Italy

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p53 overexpression is associated with cytoreduction and response to chemotherapy in ovarian cancer

The aim of this study was to assess the association of p53 status with primary cytoreduction, response to chemotherapy and outcome in stage III–IV primary ovarian cancer patients. Immunohistochemical analysis of p53 was performed on formalin-fixed, paraffin-embedded specimens from 168 primary ovarian carcinomas by using the DO-7 monoclonal antibody. p53 nuclear positivity was found in 84 out of 162 (52%) malignant tumours. A higher percentage of p53 nuclear positivity was observed in patients with advanced stage of disease than in stage I–II (57% vs 23% respectively; P = 0.0022) and in poorly differentiated versus well/moderately differentiated tumours (59% vs 32% respectively; P = 0.0038). The multivariate analysis aimed to investigate the association of FIGO stage, grade and p53 status with primary cytoreduction in 136 stage III–IV patients showed that stage IV disease may influence the possibility to perform primary cytoreduction in ovarian cancer patients. p53-positivity also maintained a trend to be associated with poor chance of cytoreduction. In patients who underwent pathologic assessment of response, cases who did not respond to chemotherapy were much more frequently p53-positive than p53-negative (86% vs 14% respectively; P = 0.012). Moreover, patients with stage III disease and < 2-cm residual tumour were more likely to respond to treatment. In multivariate analysis, FIGO stage and p53 expression were independently correlated with pathologic response to chemotherapy. Time to progression and survival rates were shown not to be different in p53-positive versus p53-negative patients. © 1999 Cancer Research Campaig

SARS-CoV-2 Breakthrough Infections: Incidence and Risk Factors in a Large European Multicentric Cohort of Health Workers.

Background: The research aimed to investigate the incidence of SARS-CoV-2 breakthrough infections and their determinants in a large European cohort of more than 60,000 health workers. Methods: A multicentric retrospective cohort study, involving 12 European centers, was carried out within the ORCHESTRA project, collecting data up to 18 November 2021 on fully vaccinated health workers. The cumulative incidence of SARS-CoV-2 breakthrough infections was investigated with its association with occupational and social-demographic characteristics (age, sex, job title, previous SARS-CoV-2 infection, antibody titer levels, and time from the vaccination course completion). Results: Among 64,172 health workers from 12 European health centers, 797 breakthrough infections were observed (cumulative incidence of 1.2%). The primary analysis using individual data on 8 out of 12 centers showed that age and previous infection significantly modified breakthrough infection rates. In the meta-analysis of aggregated data from all centers, previous SARS-CoV-2 infection and the standardized antibody titer were inversely related to the risk of breakthrough infection (p = 0.008 and p = 0.007, respectively). Conclusion: The inverse correlation of antibody titer with the risk of breakthrough infection supports the evidence that vaccination plays a primary role in infection prevention, especially in health workers. Cellular immunity, previous clinical conditions, and vaccination timing should be further investigated

Epidemiological patterns of asbestos exposure and spatial clusters of incident cases of malignant mesothelioma from the Italian national registry

Abstract BACKGROUND: Previous ecological spatial studies of malignant mesothelioma cases, mostly based on mortality data, lack reliable data on individual exposure to asbestos, thus failing to assess the contribution of different occupational and environmental sources in the determination of risk excess in specific areas. This study aims to identify territorial clusters of malignant mesothelioma through a Bayesian spatial analysis and to characterize them by the integrated use of asbestos exposure information retrieved from the Italian national mesothelioma registry (ReNaM). METHODS: In the period 1993 to 2008, 15,322 incident cases of all-site malignant mesothelioma were recorded and 11,852 occupational, residential and familial histories were obtained by individual interviews. Observed cases were assigned to the municipality of residence at the time of diagnosis and compared to those expected based on the age-specific rates of the respective geographical area. A spatial cluster analysis was performed for each area applying a Bayesian hierarchical model. Information about modalities and economic sectors of asbestos exposure was analyzed for each cluster. RESULTS: Thirty-two clusters of malignant mesothelioma were identified and characterized using the exposure data. Asbestos cement manufacturing industries and shipbuilding and repair facilities represented the main sources of asbestos exposure, but a major contribution to asbestos exposure was also provided by sectors with no direct use of asbestos, such as non-asbestos textile industries, metal engineering and construction. A high proportion of cases with environmental exposure was found in clusters where asbestos cement plants were located or a natural source of asbestos (or asbestos-like) fibers was identifiable. Differences in type and sources of exposure can also explain the varying percentage of cases occurring in women among clusters. CONCLUSIONS: Our study demonstrates shared exposure patterns in territorial clusters of malignant mesothelioma due to single or multiple industrial sources, with major implications for public health policies, health surveillance, compensation procedures and site remediation programs

Induction of MDR1 gene expression by anthracycline analogues in a human drug resistant leukaemia cell line

The effects of 4-demethoxydaunorubicin (idarubicin, IDA) and MX2, a new morpholino-anthracycline, on up-regulation of the MDR1 gene in the low-level multidrug resistant (MDR) cell line CEM/A7R were compared at similar concentrations (IC10, IC50and IC90) over a short time exposure (4 and 24 h). The chemosensitivity of each drug was determined by a 3-day cell growth inhibition assay. Compared with epirubicin (EPI), IDA and MX2 were 17- and eightfold more effective in the CEM/A7R line respectively. No cross-resistance to 5-FU was seen in the CEM/A7R line. Verapamil (5 μM) and PSC 833 (1 μM), which dramatically reversed resistance to EPI in the CEM/A7R line, had no sensitizing effect on the resistance of this line to MX2, but slightly decreased resistance to IDA. The sensitivity to 5-FU was unchanged by these modulators. The induction of MDR1 mRNA expression by IDA, MX2 and 5-FU was analysed by Northern blotting and semiquantitatively assessed by scanning Northern blots on a phosphorimager. The relative level of MDR1 expression was expressed as a ratio of MDR1 mRNA to the internal RNA control glyceraldehyde-3-phosphate dehydrogenase (GAPDH). IDA, MX2 and 5-FU differentially up-regulated MDR1 mRNA in the CEM/A7R line in a dose-dependent manner. Both IDA and MX2 induced MDR1 expression within 4 h. 5-FU up-regulated MDR1 expression only when drug exposure was prolonged to 24 h. Based on MRK 16 binding, flow cytometric analysis of P-glycoprotein (Pgp) expression paralleled the increase in MDR1 mRNA levels. For the three anthracyclines, the increase in MDR1 expression was stable in cells grown in the absence of drug for more than 3 weeks after drug treatment. The induction of MDR1 expression by 5-FU was transient, associated with a rapid decrease in the increased Pgp levels which returned to baseline 72 h after the removal of 5-FU. This study demonstrates that MDR1 expression can be induced by analogues of anthracyclies not pumped by Pgp, and that this induction appears to be stable despite a 3-week drug-free period. © 1999 Cancer Research Campaig

Magic-factor 1, a partial agonist of Met, induces muscle hypertrophy by protecting myogenic progenitors from apoptosis.

Hepatocyte Growth Factor (HGF) is a pleiotropic cytokine of mesenchymal origin that mediates a characteristic array of biological activities including cell proliferation, survival, motility and morphogenesis. Its high affinity receptor, the tyrosine kinase Met, is expressed by a wide range of tissues and can be activated by either paracrine or autocrine stimulation. Adult myogenic precursor cells, the so called satellite cells, express both HGF and Met. Following muscle injury, autocrine HGF-Met stimulation plays a key role in promoting activation and early division of satellite cells, but is shut off in a second phase to allow myogenic differentiation. In culture, HGF stimulation promotes proliferation of muscle precursors thereby inhibiting their differentiation

MeMoVolc report on classification and dynamics of volcanic explosive eruptions

Classifications of volcanic eruptions were first introduced in the early twentieth century mostly based on qualitative observations of eruptive activity, and over time, they have gradually been developed to incorporate more quantitative descriptions of the eruptive products from both deposits and observations of active volcanoes. Progress in physical volcanology, and increased capability in monitoring, measuring and modelling of explosive eruptions, has highlighted shortcomings in the way we classify eruptions and triggered a debate around the need for eruption classification and the advantages and disadvantages of existing classification schemes. Here, we (i) review and assess existing classification schemes, focussing on subaerial eruptions; (ii) summarize the fundamental processes that drive and parameters that characterize explosive volcanism; (iii) identify and prioritize the main research that will improve the understanding, characterization and classification of volcanic eruptions and (iv) provide a roadmap for producing a rational and comprehensive classification scheme. In particular, classification schemes need to be objective-driven and simple enough to permit scientific exchange and promote transfer of knowledge beyond the scientific community. Schemes should be comprehensive and encompass a variety of products, eruptive styles and processes, including for example, lava flows, pyroclastic density currents, gas emissions and cinder cone or caldera formation. Open questions, processes and parameters that need to be addressed and better characterized in order to develop more comprehensive classification schemes and to advance our understanding of volcanic eruptions include conduit processes and dynamics, abrupt transitions in eruption regime, unsteadiness, eruption energy and energy balance

Controls on explosive-effusive volcanic eruption styles

One of the biggest challenges in volcanic hazard assessment is to understand how and why eruptive style changes within the same eruptive period or even from one eruption to the next at a given volcano. This review evaluates the competing processes that lead to explosive and effusive eruptions of silicic magmas. Eruptive style depends on a set of feedbacks involving interrelated magmatic properties and processes. Foremost of these are magma viscosity, gas loss, and external properties such as conduit geometry. Ultimately, these parameters control the speed at which magmas ascend, decompress and outgas en route to the surface, and thus determine eruptive style and evolution