Characterization of extracellular vesicles in osteoporotic patients compared to osteopenic and healthy controls

Extracellular vesicles (EVs) are mediators of a range of pathological conditions. However, their role in bone loss disease has not been well understood. In this study we characterized plasma EVs of 54 osteoporotic (OP) postmenopausal women compared to 48 osteopenic (OPN) and 44 healthy controls (CN), and we investigated their effects on osteoclasts and osteoblasts. We found no differences between the three groups in terms of anthropometric measurements and biochemical evaluation of serum calcium, phosphate, creatinine, PTH, 25-hydroxy vitamin D and bone biomarkers, except for an increase of CTX level in OP group. FACS analysis revealed that OP patients presented a significantly increased number of EVs and RANKL(+) EVs compared with both CN and OPN subjects. Total EVs are negatively associated with the lumbar spine T-score and femoral neck T-score. Only in the OPN patients we observed a positive association between the total number of EVs and RANKL(+) EVs with the serum RANKL. In vitro studies revealed that OP EVs supported osteoclastogenesis of healthy donor peripheral blood mononuclear cells at the same level observed following RANKL and M-CSF treatment, reduced the ability of mesenchymal stem cells to differentiate into osteoblasts, while inducing an increase of OSTERIX and RANKL expression in mature osteoblasts. The analysis of miRNome revealed that miR-1246 and miR-1224-5p were the most upregulated and downregulated in OP EVs; the modulated EV-miRNAs in OP and OPN compared to CN are related to osteoclast differentiation, interleukin-13 production and regulation of canonical WNT pathway. A proteomic comparison between OPN and CN EVs evidenced a decrease in fibrinogen, vitronectin, and clusterin and an increase in coagulation factors and apolipoprotein, which was also upregulated in OP EVs. Interestingly, an increase in RANKL(+) EVs and exosomal miR-1246 was also observed in samples from patients affected by Gorham-Stout disease, suggesting that EVs could be good candidate as bone loss disease biomarkers. (c) 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)

First-Line Pharmacotherapies and Survival among Patients Diagnosed with Non-Resectable NSCLC: A Real-Life Setting Study with Gender Prospective

(1) Purpose: To describe first-line pharmacotherapy and overall survival in non-resectable non-small cell lung cancer (nrNSCLC) patients by gender. (2) Methods: Incident cases of nrNSCLC recorded between 2009 and 2019 (cohort entry) in the pathology registry of the regional administrative healthcare database of Tuscany were identified. Records of antineoplastic therapies delivered up to 4 months following cohort entry were classified as chemotherapy, target therapies, immunotherapies, and undefined monoclonal antibodies. First-line treatment and survival of patients receiving drug treatment was described. Analyses were stratified according to histology, gender, and cohort entry year. (3) Results: 4393 incident cases of nrNSCLC were included. Women with non-squamous-NSCLC received target-therapy more frequently than men (14.9% vs. 6.5%). Immunotherapy incidence of use varied between 3.8% (2017) and 9.1% (2019). The 2-year survival rate increased over time: for non-squamous-NSCLC, it was 22.3% (2009-2011) and 30.6% (2018-2019), while for squamous-NSCLC, it was 13.5% and 22.5%, respectively. After multivariate analysis, a low reduction in mortality risk in 2018-2019 vs. 2009-2011 was found (non-squamous: HR: 0.95 CI95%: 0.92-0.98; squamous: HR: 0.94 CI95%: 0.90-0.98). Among non-squamous NSCLC, median survival was longer in women than in men (389 vs. 276 days). (4) Conclusion: In light of sex-related biomolecular differences, among non-squamous NSCLC, women received target-therapy more frequently than men. Survival seemed to slightly improve over the study period for both histologies, despite a poor reduction in mortality risk was still observed

Malignant mesothelioma due to non-occupational asbestos exposure from the Italian national surveillance system (ReNaM): epidemiology and public health issues

Italy produced and imported a large amount of raw asbestos, up to the ban in 1992, with a peak in the period between 1976 and 1980 at about 160\u2005000 tons/year. The National Register of Mesotheliomas (ReNaM, "Registro Nazionale dei Mesoteliomi" in Italian), a surveillance system of mesothelioma incidence, has been active since 2002, operating through a regional structure

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

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

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

Road Asphalt Pavements Analyzed by Airborne Thermal Remote Sensing: Preliminary Results of the Venice Highway

This paper describes a fast procedure for evaluating asphalt pavement surface defects using airborne emissivity data. To develop this procedure, we used airborne multispectral emissivity data covering an urban test area close to Venice (Italy).For this study, we first identify and select the roads’ asphalt pavements on Multispectral Infrared Visible Imaging Spectrometer (MIVIS) imagery using a segmentation procedure. Next, since in asphalt pavements the surface defects are strictly related to the decrease of oily components that cause an increase of the abundance of surfacing limestone, the diagnostic absorption emissivity peak at 11.2μm of the limestone was used for retrieving from MIVIS emissivity data the areas exhibiting defects on asphalt pavements surface.The results showed that MIVIS emissivity allows establishing a threshold that points out those asphalt road sites on which a check for a maintenance intervention is required. Therefore, this technique can supply local government authorities an efficient, rapid and repeatable road mapping procedure providing the location of the asphalt pavements to be checked

Understanding the role of value chain formation in the scaling of crop diversification

Significant detrimental effects of agricultural intensification and specialization are becoming increasingly evident. Reliance on monocultures, few varieties, and intensive use of agrochemicals is a major factor in climate change, biodiversity decline, soil health deterioration, and pollution, putting our food system at risk. This requires sustainable agricultural processes, such as crop diversification, to be more rapidly and effectively tested, adopted, and scaled. While these processes are typically introduced at niche level, they often struggle to scale and to induce broader sustainability transitions. In this study, we investigate how scaling may occur, focusing on institutional logics, their changes, and realignment over time. In particular, we applied an abductive research strategy to collect empirical evidence from two in-depth, longitudinal case studies of innovation niches related to crop diversification. Doing so, we show for the first time that, despite their many differences, scaling processes of crop diversification in both niches converge, presenting similar progressions in terms of institutional dimensions, and facing similar obstacles when it comes to value chain formation. While initial experimentation could still be implemented using organizational forms familiar to the lead actors, we discover that a systemic lack of adequate value chain arrangements obstructed the scaling process of crop diversification in both cases. These findings have been used to reflect on the role of value chain relations in scaling processes in sustainability transitions in agriculture

Pharmaco-epidemiological description of the population of the Marche Region (central Italy) treated with the antipsychotic drug olanzapine

BACKGROUND: In Italy, even though olanzapine has been discouraged for treatment of behaviour disorders in older patients affected by dementia, some physicians chose to prescribe for them. In response to this situation, the Italian Drug Agency (Agenzia Italiana del Farmaco, AIFA) promulgated a cautionary note. MATERIALS AND METHODS: This study examined epidemiological indices for olanzapine prescriptions between 2004 and 2007 in the Marche Region of central Italy and in its provinces, to assess physician compliance with the AIFA note, and to determine whether there were differences in drug prescription between populations of the same territory, or differences based on gender or age group. RESULTS: Our analyses revealed high olanzapine use among young men and mature women, suggesting that these groups are most prone to psychotic symptoms. Analysis revealed that olanzapine prescription in elderly patients was reduced in some provinces, in line with the AIFA note. CONCLUSIONS: Prudent use of olanzapine prescription, in compliance with the AIFA note, was noted throughout the Region. Furthermore, this work offers details that may be useful in future studies of adverse drug reactions

Thymidine phosphorylase expression in metastatic sites is predictive for response in patients with colorectal cancer treated with continuous oral capecitabine and biweekly oxaliplatin

The primary objective of this study was to determine the activity and safety profile of biweekly oxaliplatin combined with continuous oral capecitabine in the first-line treatment of metastatic colorectal cancer. A secondary endpoint was to investigate the correlation between thymidylate synthase and thymidine phosphorylase (TP) expression in metastatic tissues and tumor response. Forty-one patients received oral capecitabine 1331 mg/m every day combined with intravenous oxaliplatin 85 mg/m every 2 weeks. The overall response rate was 58.5% [95% confidence interval (CI): 43.3-73.6%], the median progression-free survival 9.4 months (95% CI: 7.7-11.2 months) and the median survival 22.3 months (95% CI: 16.1-27.5 months). There were no grade 4 toxicities, and grade 3 toxicity was also uncommon. High TP expression in metastatic tissue was significantly associated with response to treatment (P=0.019), and also with a trend towards a better median progression-free survival and overall survival compared with patients expressing low TP (P=0.056; P=0.073). This study suggests that biweekly oxaliplatin and continuous oral capecitabine is an active and well-tolerated chemotherapy regimen in the first-line treatment of metastatic colorectal cancer. Moreover, these findings add to a growing body of evidence that patients with high levels of intratumoral TP expression are the ideal candidates for capecitabine-based chemotherap