First attempt to quantify microplastics in Mediterranean Sabellaria spinulosa (Annelida, Polychaeta) bioconstructions.

This work focuses on the arenaceous reefs by the polychaete Sabellaria spinulosa and addresses microplastics pollution. The main aim is to assess microplastics amount in a bioconstruction located in the Adriatic coast of Italy (Mediterranean Sea) through a comparative approach: sea-floor sediment and bioconstruction samples were analysed to quantify microplastics absolute abundance in both substrates. A total of 431 MPs were found in the investigated substrates: respectively 85 % fibers and 15 % fragments. Multivariate analysis indicates that MPs within bioconstruction occur in higher abundances and with different morphologies than in sediment samples. The analysis of bioconstruction polished sections allowed for observation of MPs agglutinated in their original position: higher concentration is reported in inter-tube areas. Results suggest that physical characteristics of MPs could play a key-role in bioconstruction inclusion processes and raise questions on effective role of sabellariid bioconstructions as a trap for this pollutant in the littoral environment.

Effect of Lactoferrin on Clinical Outcomes of Hospitalized Patients with COVID-19: The LAC Randomized Clinical Trial.

As lactoferrin is a nutritional supplement with proven antiviral and immunomodulatory abilities, it may be used to improve the clinical course of COVID-19. The clinical efficacy and safety of bovine lactoferrin were evaluated in the LAC randomized double-blind placebo-controlled trial. A total of 218 hospitalized adult patients with moderate-to-severe COVID-19 were randomized to receive 800 mg/die oral bovine lactoferrin (n = 113) or placebo (n = 105), both given in combination with standard COVID-19 therapy. No differences in lactoferrin vs. placebo were observed in the primary outcomes: the proportion of death or intensive care unit admission (risk ratio of 1.06 (95% CI 0.63-1.79)) or proportion of discharge or National Early Warning Score 2 (NEWS2) ≤ 2 within 14 days from enrollment (RR of 0.85 (95% CI 0.70-1.04)). Lactoferrin showed an excellent safety and tolerability profile. Even though bovine lactoferrin is safe and tolerable, our results do not support its use in hospitalized patients with moderate-to-severe COVID-19.

Baseline Plasma Osteopontin Protein Elevation Predicts Adverse Outcomes in Hospitalized COVID-19 Patients.

More than three years have passed since the first case, and COVID-19 is still a health concern, with several open issues such as the lack of reliable predictors of a patient's outcome. Osteopontin (OPN) is involved in inflammatory response to infection and in thrombosis driven by chronic inflammation, thus being a potential biomarker for COVID-19. The aim of the study was to evaluate OPN for predicting negative (death or need of ICU admission) or positive (discharge and/or clinical resolution within the first 14 days of hospitalization) outcome. We enrolled 133 hospitalized, moderate-to-severe COVID-19 patients in a prospective observational study between January and May 2021. Circulating OPN levels were measured by ELISA at admission and at day 7. The results showed a significant correlation between higher plasma concentrations of OPN at hospital admission and a worsening clinical condition. At multivariate analysis, after correction for demographic (age and gender) and variables of disease severity (NEWS2 and PiO2/FiO2), OPN measured at baseline predicted an adverse prognosis with an odds ratio of 1.01 (C.I. 1.0-1.01). At ROC curve analysis, baseline OPN levels higher than 437 ng/mL predicted a severe disease evolution with 53% sensitivity and 83% specificity (area under the curve 0.649, p = 0.011, likelihood ratio of 1.76, (95% confidence interval (CI): 1.35-2.28)). Our data show that OPN levels determined at the admission to hospital wards might represent a promising biomarker for early stratification of patients' COVID-19 severity. Taken together, these results highlight the involvement of OPN in COVID-19 evolution, especially in dysregulated immune response conditions, and the possible use of OPN measurements as a prognostic tool in COVID-19.

CGRP Plasma Levels Correlate with the Clinical Evolution and Prognosis of Hospitalized Acute COVID-19 Patients.

SARS-CoV-2 is the etiological agent of COVID-19, an extremely heterogenous disease that can cause severe respiratory failure and critical illness. To date, reliable biomarkers allowing for early patient stratification according to disease severity are still lacking. Calcitonin gene-related peptide (CGRP) is a vasoactive neuropeptide involved in lung pathophysiology and immune modulation and is poorly investigated in the COVID-19 context. In this observational, prospective cohort study, we investigated the correlation between CGRP and clinical disease evolution in hospitalized moderate to severe COVID-19 patients. Between January and May 2021 (Italian third pandemic wave), 135 consecutive SARS-CoV-2 patients were diagnosed as being eligible for the study. Plasma CGRP level evaluation and routine laboratory tests were performed on blood samples collected at baseline and after 7 days of hospitalization. At baseline, the majority our patients had a moderate to severe clinical presentation, and higher plasma CGRP levels predicted a higher risk of in-hospital negative evolution (odds-ratio OR 2.84 [IQR 1.07-7.51]) and were correlated with pulmonary intravascular coagulopathy (OR 2.92 [IQR 1.19-7.17]). Finally, plasma CGRP levels were also correlated with plasma IP10 levels. Our data support a possible crosstalk between the lung and the neuroimmune axis, highlighting a crucial role for plasma CGRP in sustaining COVID-19-related hyperinflammation.

Baseline plasma SARS-CoV-2 RNA detection predicts an adverse COVID-19 evolution in moderate to severe hospitalized patients.

BACKGROUND: SARS-CoV-2 is a single-stranded RNA virus, known to be the causative agent of COVID-19. As the resulting disease shows a very heterogeneous range of clinical manifestations, the identification of early biomarkers allowing patients stratification according to the expected disease severity is still an unmet clinical need. METHODS: In this observational prospective cohort study, 137 consecutive patients, testing positive for SARS-CoV-2 infection by nasopharyngeal swab RT-PCR or antigenic test, were enrolled to evaluate their plasma viral load at the time of hospitalization. RESULTS: Even if all of them had a molecular diagnosis of COVID-19, only 29 patients showed a detectable plasma SARS-CoV-2 RNAemia. Such viremic patients also showed other clinical and laboratory finding alterations (increased troponin I, IL-6, RDW-CV, and creatinine levels along with decreased platelet count and glomerular filtration rate). A plasma detectable RNA viral load predicted in hospital death or ICU admission with an odds ratio of 3.53 (CI: 1.44-8.64, P=0.0058), while the lack of a detectable viral load was associated with a faster recovery, with an odds ratio of 4.06 (CI: 1.72-9.59, P=0.0014). These findings were confirmed in multivariate models including age, sex and baseline National Early Warning Score 2 and arterial oxygen tension over inspired oxygen fraction ratio. CONCLUSIONS: Our data thus suggest that plasma viral RNA load at the time of hospital admission could represent a useful independent biomarker allowing early patients' stratification according to the expected disease evolution, and driving clinical decisions tailored on the specific needs of the individual patient.

Baseline Plasma Gas6 Protein Elevation Predicts Adverse Outcomes in Hospitalized COVID-19 Patients.

Reliable biomarkers allowing early patients' stratification for the risk of adverse outcomes in COVID-19 are lacking. Gas6, together with its tyrosine kinase receptors named TAM, is involved in the regulation of immune homeostasis, fibrosis, and thrombosis. Our aim was to evaluate whether Gas6, sAxl, and sMerTK could represent early predictors of disease evolution either towards a negative (death or need of ICU admission) or a positive (discharge and/or clinical resolution within the first 14 days of hospitalization) outcome. To this purpose, between January and May 2021 (corresponding to third pandemic wave in Italy), 139 consecutive SARS-CoV-2 positive patients were enrolled in a prospective observational study. Plasma levels of these molecules were measured by ELISA at the time of hospitalization and after 7 and 14 days. We observed that higher plasma Gas6 concentrations at hospital admission were associated with a worsening in clinical conditions while lower sMerTK concentrations at baseline and after 7 days of hospitalization were associated with a more favorable outcome. At multivariate analysis, after correction for demographic and COVID-19 severity variables (NEWS2 and PiO2/FiO2), only Gas6 measured at baseline predicted an adverse prognosis with an odds ratio of 1.03 (C.I. 1.01-10.5). At ROC curve analysis, baseline Gas6 levels higher than 58.0 ng/ml predicted a severe disease evolution with 53.3% sensitivity and 77.6% specificity (area under the curve 0.653, p = 0.01, likelihood ratio of 2.38, IQR: 1.46-3.87). Taken together, these results support the hypothesis that a dysregulation in the Gas6/TAM axis could play a relevant role in modulating the course of COVID-19 and suggest that plasma Gas6 may represent a promising prognostic laboratory parameter for this condition.

Prognostic Markers in Hospitalized COVID-19 Patients: The Role of IP-10 and C-Reactive Protein.

BACKGROUND: SARS-CoV-2 is responsible for COVID-19, a clinically heterogeneous disease, ranging from being completely asymptomatic to life-threating manifestations. An unmet clinical need is the identification at disease onset or during its course of reliable biomarkers allowing patients' stratification according to disease severity. In this observational prospective cohort study, patients' immunologic and laboratory signatures were analyzed to identify independent predictors of unfavorable (either death or intensive care unit admission need) or favorable (discharge and/or clinical resolution within the first 14 days of hospitalization) outcome. METHODS: Between January and May 2021 (third wave of the pandemic), we enrolled 139 consecutive SARS-CoV-2 positive patients hospitalized in Northern Italy to study their immunological and laboratory signatures. Multiplex cytokine, chemokine, and growth factor analysis, along with routine laboratory tests, were performed at baseline and after 7 days of hospital stay. RESULTS: According to their baseline characteristics, the majority of our patients experienced a moderate to severe illness. At multivariate analysis, the only independent predictors of disease evolution were the serum concentrations of IP-10 (at baseline) and of C-reactive protein (CRP) after 7 days of hospitalization. Receiver-operating characteristic (ROC) curve analysis confirmed that baseline IP - 10 > 4271 pg/mL and CRP > 2.3 mg/dL at 7 days predict a worsening in clinical conditions (87% sensitivity, 66% specificity, area under the curve (AUC) 0.772, p < 0.001 and 83% sensitivity, 73% specificity, AUC 0.826, p < 0.001, respectively). CONCLUSIONS: According to our results, baseline IP-10 and CRP after 7 days of hospitalization could be useful in driving clinical decisions tailored to the expected disease trajectory in hospitalized COVID-19 patients.

Respiratory and Psychophysical Sequelae Among Patients With COVID-19 Four Months After Hospital Discharge.

Importance: Although plenty of data exist regarding clinical manifestations, course, case fatality rate, and risk factors associated with mortality in severe coronavirus disease 2019 (COVID-19), long-term respiratory and functional sequelae in survivors of COVID-19 are unknown. Objective: To evaluate the prevalence of lung function anomalies, exercise function impairment, and psychological sequelae among patients hospitalized for COVID-19, 4 months after discharge. Design, Setting, and Participants: This prospective cohort study at an academic hospital in Northern Italy was conducted among a consecutive series of patients aged 18 years and older (or their caregivers) who had received a confirmed diagnosis of severe acute respiratory coronavirus 2 (SARS-CoV-2) infection severe enough to require hospital admission from March 1 to June 29, 2020. SARS-CoV-2 infection was confirmed via reverse transcription-polymerase chain reaction testing, bronchial swab, serological testing, or suggestive computed tomography results. Exposure: Severe COVID-19 requiring hospitalization. Main Outcomes and Measures: The primary outcome of the study was to describe the proportion of patients with a diffusing lung capacity for carbon monoxide (Dlco) less than 80% of expected value. Secondary outcomes included proportion of patients with severe lung function impairment (defined as Dlco <60% expected value); proportion of patients with posttraumatic stress symptoms (measured using the Impact of Event Scale-Revised total score); proportion of patients with functional impairment (assessed using the Short Physical Performance Battery [SPPB] score and 2-minute walking test); and identification of factors associated with Dlco reduction and psychological or functional sequelae. Results: Among 767 patients hospitalized for severe COVID-19, 494 (64.4%) refused to participate, and 35 (4.6%) died during follow-up. A total of 238 patients (31.0%) (median [interquartile range] age, 61 [50-71] years; 142 [59.7%] men; median [interquartile range] comorbidities, 2 [1-3]) consented to participate to the study. Of these, 219 patients were able to complete both pulmonary function tests and Dlco measurement. Dlco was reduced to less than 80% of the estimated value in 113 patients (51.6%) and less than 60% in 34 patients (15.5%). The SPPB score was suggested limited mobility (score <11) in 53 patients (22.3%). Patients with SPPB scores within reference range underwent a 2-minute walk test, which was outside reference ranges of expected performance for age and sex in 75 patients (40.5%); thus, a total of 128 patients (53.8%) had functional impairment. Posttraumatic stress symptoms were reported in a total of 41 patients (17.2%). Conclusions and Relevance: These findings suggest that at 4 months after discharge, respiratory, physical, and psychological sequelae were common among patients who had been hospitalized for COVID-19.

Unusual presentation of fatal disseminated varicella zoster virus infection in a patient with lupus nephritis: a case report.

BACKGROUND: The risk of life-threatening complications, such as visceral disseminated varicella zoster virus (VZV) infection, is greater in immunosuppressed individuals, such as systemic lupus erythematosus (SLE) patients. CASE PRESENTATION: Here, a case is reported of a Caucasian woman diagnosed with lupus nephritis and anti-phospholipid syndrome, who was subjected to mycophenolate mofetil and high-dose steroid remission-induction therapy. Two months later she developed abdominal pain followed by a fatal rapid multi-organ failure. As no typical skin rashes were evident, death was initially attributed to catastrophic anti-phospholipid syndrome. However, autopsy and virological examinations on archival material revealed a disseminated VZV infection. CONCLUSIONS: Overall, this case highlights the importance of having a high clinical suspicion of fatal VZV infections in heavily immunosuppressed SLE patients even when typical signs and symptoms are lacking.

Ecotoxicological effects of atmospheric particulate produced by braking systems on aquatic and edaphic organisms.

Vehicles generate particulate matter (PM) in significant amounts as their brake systems wear. These particles can influence air quality and their transport/deposition may affect the edaphic and aquatic ecosystems. As part of the LOWBRASYS H2020 project, new more eco-friendly brake disc and pad formulations were developed. PMs generated from traditional (FM1-BD1) and innovative (FM4-BD2, FMB-BD7) brake systems in bench tests were studied. The PMs' physical/chemical characteristics were preliminarily investigated. To study the possible environmental impact of the nano-micro particulate, we used a battery of ecotoxicological tests. We employed the microalga Pseudokirchneriella subcapitata, the crustacean Daphnia magna and the bacteria Vibrio fischeri as aquatic bioindicators, while for the edaphic ecosystem we used the seeds of Lepidium sativum and Sorghum saccharatum, the nematode Caenorhabditis elegans, the earthworm Eisenia andrei and the ameba Dictyostelium discoideum. The results showed a higher sensitivity of the freshwater organisms exposed to the soluble PM fraction, with respect to the edaphic ones. FM4-BD2 brake formulation was slightly more toxic for algae (200 mg/L) than FM1-BD1 (500 mg/L). The new system FMB-BD7 particulate was not harmful for crustacean survival, and resulted weakly toxic for algal reproduction only at 500 mg/L. The particulate material per se was found to affect the algal reproduction. No toxic effects were found on nematodes, earthworms and seeds up to 1000 mg/L. However, in D. discoideum the reproduction rate was significantly reduced starting from 100 mg/L; and the lysosomal membrane stability showed a relevant alteration also at minimal concentration (0.1 mg/L). The results demonstrated a minimal risk for biodiversity of the particulates from the different brake systems and highlighted a more eco-friendly performance the new brake-pad FMB-BD7. However, the occurrence of sublethal effects should be considered as a possible contribution of the particle toxicity to the biological effects of the environmental pollution.

Role of positron emission tomography in the assessment of disease burden and risk of relapse in patients affected by giant cell arteritis.

Giant cell arteritis (GCA) is characterized by two subsets: cranial GCA and large-vessel GCA (LV-GCA); positron emission tomography (PET) is an essential tool in the diagnosis of LV-GCA. In this study, we aimed to investigate its potential prognostic value in the stratification of relapse risk. We retrospectively revised all the clinical records of patients who received a diagnosis of GCA at an immuno-rheumatology clinic of a University Hospital along 6 years and who underwent to a PET-CT examination at diagnosis. Clinical, laboratory, and imaging data were collected. Relapses were recorded. The study population included 19 patients (10 females, 52.6%; median age 74.0 [65.5-76.0] years), 12 with typical cranial GCA (63%) and 7 (37%) with LV-GCA. Based on PET findings, a diagnosis of aortitis was made in 15/19 patients, including 8/12 patients with a classical cranial GCA (58%). Along a median follow-up of 15 months [4.5-26.5], 4 relapses were observed. All relapsers were male; indeed, the difference in gender distribution was the only variable reaching statistical difference between relapsers and non-relapsers. Specifically, aortitis was not more frequent among relapsers. Our study confirms PET as a valid tool in the identification of LV-GCA with no cranial involvement. We failed to demonstrate a role for PET in the prognostic stratification of GCA, while male gender is suggested as a potential risk factor for GCA relapse.Key Points• A significant proportion of patients with GCA presents with non-cranial disease, the identification of which requires imaging studies, among which PET is particularly useful.• Aortitis might be detected also in patients with the classical, cranial GCA type but does not seem to have prognostic implications, at least in terms of relapse risk.• Male gender is suggested as a risk factor for relapse in GCA.

A 28-Year-Old Woman with Ascites and Multiple Focal Spleen Lesions.

Serous effusions complicating the course of lymphomas occur commonly in the pleural space but seldom in the peritoneum, where they most often present as chylous ascites with diagnostic cytology. Almost invariably, in these rare cases, the serum to ascites albumin gradient is low. We describe a 28-year-old woman with anasarca, ascites and a serum to ascites albumin gradient of 1.1 g/dl, consistent with portal hypertension. No tumour cells were detected in the ascitic fluid. However, a CT scan of the chest and abdomen disclosed liver and spleen enlargement and multiple enlarged retroperitoneal lymph nodes, suspicious for a lymphoproliferative disorder. Bone marrow aspiration and biopsy were not diagnostic, so a decision was made to proceed with a splenectomy despite the onset of low-grade disseminated intravascular coagulation. Surgery was uneventful. Diffuse large B cell lymphoma was diagnosed. A liver biopsy taken at the time of surgery demonstrated that the liver parenchyma was massively infiltrated by reactive T lymphocytes surrounding rare large CD20+ tumour cells. This infiltrate had likely led to increased portal pressure attended by ascites formation, which resolved completely after chemotherapy. The case emphasizes the rewards of pursuing a diagnosis supported by a high prior probability even in the presence of apparently discordant laboratory findings, as well as the importance of performing a diagnostic splenectomy in case of splenomegaly with unexplained focal lesions. LEARNING POINTS: Lymphomas may present with serous effusion, which is usually chylous and with positive cytology when represented by ascites accumulation; non-chylous effusions can be due to altered lymphatic drainage, extrinsic compression of the portal vein by enlarged lymph nodes as well as massive infiltration of the liver by lymphoma.If the cause of splenomegaly is unclear, diagnostic splenectomy remains a viable option.The diagnosis of lymphoma should always be pursued, even if it requires apparently unwise surgery, since this type of cancer can be treated effectively only if thoroughly characterized pathologically and molecularly.

Asbestos fiber identification in liver from cholangiocarcinoma patients living in an asbestos polluted area: a preliminary study.

PURPOSE: To assess whether asbestos fibers may be observed in liver tissue of patients with cholangiocarcinoma (CC) with environmental or working asbestos exposure. METHODS: Detection of fibers was performed directly on histologic sections of liver from 7 patients with CC using optical microscope and variable pressure scanning electron microscopy equipped with energy-dispersive spectroscopy (VP-SEM/EDS). All patients were from Casale Monferrato, Italy, a highly asbestos-polluted town. Due to ethical constraints, observers were blinded to patients' clinical features. RESULTS: Fibers/bundles of fibers of chrysotile were detected in 5 out of 7 patients (71%). The boundary between healthy and neoplastic tissue or the fibrocollagen tissue produced by the neoplasia were identified as areas of fiber incorporation. CONCLUSIONS: This study is the first report about the detection of chrysotile asbestos fibers in the liver of patients with CC. Further studies on larger cohorts are needed to corroborate our preliminary findings.

First reported human case of meningitis by Staphylococcus condimenti.

Staphylococcus condimenti (S. condimenti) is a coagulase-negative bacterium, generally regarded as not pathogenic. Indeed, S. condimenti owes its name to having been isolated from starter cultures of fermented sausage, as well as from fish and soy sauces. To the best of our knowledge, only two cases of human infection caused by this bacterium have been reported. Here, we present a case of meningitis by S. condimenti in a 65-year-old woman who was brought to hospital after having been found unconscious at home. At her arrival, she had a Glasgow coma scale = 3, fever, and hypoxic-normocapnic respiratory failure. Examination of her cerebrospinal fluid showed a slightly increased white blood cell count, normal glucose and protein concentrations. Paired cultures on blood and liquor samples yielded S. condimenti. Targeted antibiotic treatment with ceftriaxone led to a complete recovery. This unique case expands our knowledge on S. condimenti as a pathogenic bacterium.

Asbestos fibre burden in gallbladder: A case study.

The methods conventionally used to determine the burden of asbestos fibres inhaled/incorporated in lung require chemical digestion of the biological matrix before counting/characterising the inorganic fibrous phases under scanning electron microscopy and energy dispersive spectroscopy (SEM/EDS). Asbestos fibres can also be present in extra-pulmonary organs, and we set out to quantify the fibres in gallbladder. Although the standardised procedure requires approximately 5 × 10-1 g of wet tissue, this amount of tissue is not always available. We applied the procedure on about 9 × 10-4 g of gallbladder from a patient with known environmental and workplace exposure to asbestos. The patient died of malignant pleural mesothelioma and was also affected by severe bile-tract problems. The traditional procedure of digesting tissue samples in NaClO and filtering the resulting suspension was carried out. The filter was then examined under SEM/EDS using two methods 1. following the standardised procedure to assess the fibre burden in lung by investigating only 2 mm2 of the filter (660 microscopic fields), and 2. analysing all the microscopic fields in one-quarter of the filter (about 82 mm2). In parallel, histological sections (prepared in the usual way for medical diagnosis) were analysed without digestion or manipulation of the sample using variable pressure SEM/EDS. The fibre counts obtained using the two methods were of the same order of magnitude, i.e., ∼105 fibres/g of wet tissue. We showed that the counting of fibres in human tissue may be successfully carried out even when a limited amount of tissue is available. We also found that, when exposure to asbestos is considerable, the number of asbestos fibres accumulating in the gallbladder may be significant.

Stability of mineral fibres in contact with human cell cultures. An in situ µXANES, µXRD and XRF iron mapping study.

Relevant mineral fibres of social and economic importance (chrysotile UICC, crocidolite UICC and a fibrous erionite from Jersey, Nevada, USA) were put in contact with cultured diploid human non-tumorigenic bronchial epithelial (Beas2B) and pleural transformed mesothelial (MeT5A) cells to test their cytotoxicity. Slides of each sample at different contact times up to 96 h were studied in situ using synchrotron XRF, µ-XRD and µ-XAS (I18 beamline, Diamond Light Source, UK) and TEM investigations. XRF maps of samples treated for 96 h evidenced that iron is still present within the chrysotile and crocidolite fibres and retained at the surface of the erionite fibres, indicating its null to minor mobilization in contact with cell media; this picture was confirmed by the results of XANES pre-edge analyses. µ-XRD and TEM data indicate greater morphological and crystallinity modifications occurring in chrysotile, whereas crocidolite and erionite show to be resistant in the biological environment. The contact of chrysotile with the cell cultures seems to lead to earlier amorphization, interpreted as the first dissolution step of these fibres. The formation of such silica-rich fibre skeleton may prompt the production of HO in synergy with surface iron species and could indicate that chrysotile may be much more reactive and cytotoxic in vitro in the (very) short term whereas the activity of crocidolite and erionite would be much more sluggish but persistent in the long term.

Numerous Iron-Rich Particles Lie on the Surface of Erionite Fibers from Rome (Oregon, USA) and Karlik (Cappadocia, Turkey).

Erionite samples from Rome, Oregon (USA) and Karlik, Cappadocia (Turkey) were analyzed by environmental scanning electron microscopy (E-SEM) coupled with energy-dispersive spectroscopy (EDS) to verify the chemical composition of this mineral phase, and the presence of iron in particular. By means of backscattered electron images, a large number of particles/grains were observed on the surface of the erionite fibers from both locations. The particles were found to be micrometric on samples from Rome and submicrometric on samples from Karlik, and always lighter than the hosting crystal in appearance. In different areas of the same fiber or bundle of fibers, several EDS spectra were recorded. Iron was detected only when a light particle was lying in the path of the electron beam. Iron was never identified in the EDS spectra acquired on the flat erionite surface. The results from E-SEM/EDS were confirmed by micro-Raman spectroscopy, showing bands ascribing to hematite­Fe2O3, goethite­FeO(OH), or jarosite­KFe3(3+)(SO4)2(OH)6 when the laser beam was addressed on the light particles observed on the fiber surface. The evidence that iron is on the surface of erionite fibers, rather than being part of the crystalline structure, may be relevant for the carcinogenic potential of these fibers.

Asbestos fibers in the gallbladder of patients affected by benign biliary tract diseases.

PURPOSE: This exploratory study aimed to evaluate the presence of asbestos fibers in the biliary tract of patients living in an asbestos-polluted area using scanning electron microscopy. METHODS: Thin gallbladder sections were obtained from five patients who were operated on for gallbladder stones and the bile fluid of one of the patients was analyzed using variable-pressure scanning electron microscopy coupled with energy-dispersive spectroscopy. All patients were from Casale Monferrato, Italy, a well-known asbestos-polluted city, where the Eternit factory had operated since the beginning of the century until 1985. RESULTS: All the inorganic phases found in the gallbladder were analyzed for morphology and chemistry. Fibers and particles consistent with minerals defined by law as 'asbestos' were detected in three out of five patients. CONCLUSION: These findings suggest that asbestos fibers can be found in the gallbladder of patients exposed to asbestos, although how they reach the biliary tract remains unknown. Further studies to confirm these results are under way.

Continuous exposure to chrysotile asbestos can cause transformation of human mesothelial cells via HMGB1 and TNF-α signaling.

Malignant mesothelioma is strongly associated with asbestos exposure. Among asbestos fibers, crocidolite is considered the most and chrysotile the least oncogenic. Chrysotile accounts for more than 90% of the asbestos used worldwide, but its capacity to induce malignant mesothelioma is still debated. We found that chrysotile and crocidolite exposures have similar effects on human mesothelial cells. Morphological and molecular alterations suggestive of epithelial-mesenchymal transition, such as E-cadherin down-regulation and ß-catenin phosphorylation followed by nuclear translocation, were induced by both chrysotile and crocidolite. Gene expression profiling revealed high-mobility group box-1 protein (HMGB1) as a key regulator of the transcriptional alterations induced by both types of asbestos. Crocidolite and chrysotile induced differential expression of 438 out of 28,869 genes interrogated by oligonucleotide microarrays. Out of these 438 genes, 57 were associated with inflammatory and immune response and cancer, and 14 were HMGB1 targeted genes. Crocidolite-induced gene alterations were sustained, whereas chrysotile-induced gene alterations returned to background levels within 5 weeks. Similarly, HMGB1 release in vivo progressively increased for 10 or more weeks after crocidolite exposure, but returned to background levels within 8 weeks after chrysotile exposure. Continuous administration of chrysotile was required for sustained high serum levels of HMGB1. These data support the hypothesis that differences in biopersistence influence the biological activities of these two asbestos fibers.