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Abstract: Chimeric antigen receptor (CAR) T-cell therapy targeting CD19 (CART-19) represents a significant advance in the treatment of patients with relapsed or refractory CD19+ B-cell lymphomas. However, a significant portion of patients either relapse or fail to respond. Moreover, many patients have symptomatic disease, requiring bridging radiation therapy (RT) during the period of CAR T-cell manufacturing. To investigate the impact of 1 to 2 fractions of low-dose RT on CART-19 treatment response, we developed a mouse model using A20 lymphoma cells for CART-19 therapy. We found that low-dose fractionated RT had a positive effect on generating abscopal systemic antitumor responses beyond the irradiated site. The combination of RT with CART-19 therapy resulted in additive effects on tumor growth in irradiated masses. Notably, a significant additional increase in antitumor effect was observed in nonirradiated tumors. Mechanistically, our results validate activation of the cyclic guanosine adenosine synthetase/stimulator of interferon genes pathway, tumor-associated antigen crosspriming, and elicitation of epitope spreading. Collectively, our findings suggest that RT may serve as an optimal priming and bridging modality for CAR T-cell therapy, overcoming treatment resistance and improving clinical outcomes in patients with CD19+ hematologic malignancies., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Carbonaceous aerosols (CA), composed of black carbon (BC) and organic matter (OM), significantly impact the climate. Light absorption properties of CA, particularly of BC and brown carbon (BrC), are crucial due to their contribution to global and regional warming. We present the absorption properties of BC (b Abs,BC ) and BrC (b Abs,BrC ) inferred using Aethalometer data from 44 European sites covering different environments (traffic (TR), urban (UB), suburban (SUB), regional background (RB) and mountain (M)). Absorption coefficients showed a clear relationship with station setting decreasing as follows: TR > UB > SUB > RB > M, with exceptions. The contribution of b Abs,BrC to total absorption (b Abs ), i.e. %Abs BrC , was lower at traffic sites (11-20 %), exceeding 30 % at some SUB and RB sites. Low AAE values were observed at TR sites, due to the dominance of internal combustion emissions, and at some remote RB/M sites, likely due to the lack of proximity to BrC sources, insufficient secondary processes generating BrC or the effect of photobleaching during transport. Higher b Abs and AAE were observed in Central/Eastern Europe compared to Western/Northern Europe, due to higher coal and biomass burning emissions in the east. Seasonal analysis showed increased b Abs , b Abs,BC , b Abs,BrC in winter, with stronger %Abs BrC , leading to higher AAE. Diel cycles of b Abs,BC peaked during morning and evening rush hours, whereas b Abs,BrC , %Abs BrC , AAE, and AAE BrC peaked at night when emissions from household activities accumulated. Decade-long trends analyses demonstrated a decrease in b Abs , due to reduction of BC emissions, while b Abs,BrC and AAE increased, suggesting a shift in CA composition, with a relative increase in BrC over BC. This study provides a unique dataset to assess the BrC effects on climate and confirms that BrC can contribute significantly to UV-VIS radiation presenting highly variable absorption properties in Europe., 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. Griša Močnik, Asta Gregorič, Matic Ivančič and Martin Rigler were or are employed by the manufacturer of the instruments used in this study., (Copyright © 2024. Published by Elsevier Ltd.)

Air pollution and particulate matter (PM) are the leading environmental cause of death worldwide. Exposure limits have lowered to increase the protection of human health; accordingly, it becomes increasingly important to understand the toxicological mechanisms on cellular models at low airborne PM concentrations which are relevant for actual human exposure. The use of air liquid interface (ALI) models, which mimic the interaction between airborne pollutants and lung epithelia, is also gaining importance in inhalation toxicological studies. This study reports the effects of ALI direct exposure of bronchial epithelial cells BEAS-2B to ambient PM 1 (i.e. particles with aerodynamic diameter lower than 1 μm). Gene expression (HMOX, Cxcl-8, ATM, Gadd45-a and NQO1), interleukin (IL)-8 release, and DNA damage (Comet assay) were evaluated after 24 h of exposure. We report the dose-response curves of the selected toxicological outcomes, together with the concentration-response association and we show that the two curves differ for specific responses highlighting that concentration-response association may be not relevant for understanding toxicological outcomes. Noteworthy, we show that pro-oxidant effects may be driven by the deposition of freshly emitted particles, regardless of the airborne PM 1 mass concentration. Furthermore, we show that reference airborne PM 1 metrics, namely airborne mass concentration, may not always reflect the toxicological process triggered by the aerosol. These findings underscore the importance of considering different aerosol metrics to assess the toxicological potency of fine and ultrafine particles. To better protect human health additional metrics should be defined, than account for the properties of the entire aerosol mixture including specific as particle size (i.e. particles with aerodynamic diameter lower than 20 nm), the relevant aerosol sources (e.g., traffic combustion, secondary organic aerosol …) as well as their atmospheric processing (freshly emitted vs aged ones)., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Maurizio Gualtieri reports financial support was provided by Italian Ministry of the University. Maurizio Gualtieri reports financial support was provided by European Union NextGenerationEU, National Recovery and Resilience Plan (NRRP) Mission 4. If there are other authors, they 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 © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Associations between indoor air pollution from fine particulate matter (PM with aerodynamic diameter d p  < 2.5 μm) and human health are poorly understood. Here, we analyse the concentration-response curves for fine and ultrafine PM, the gene expression, and the methylation patterns in human bronchial epithelial cells (BEAS-2B) exposed at the air-liquid interface (ALI) within a classroom in downtown Rome. Our results document the upregulation of aryl hydrocarbon receptor (AhR) and genes associated with xenobiotic metabolism (CYP1A1 and CYP1B1) in response to single exposure of cells to fresh urban aerosols at low fine PM mass concentrations within the classroom. This is evidenced by concentrations of ultrafine particles (UFPs, dp < 0.1 μm), polycyclic aromatic hydrocarbons (PAH), and ratios of black carbon (BC) to organic aerosol (OA). Additionally, an interleukin 18 (IL-18) down-regulation was found during periods of high human occupancy. Despite the observed gene expression dysregulation, no changes were detected in the methylation levels of the promoter regions of these genes, indicating that the altered gene expression is not linked to changes in DNA methylation and suggesting the involvement of another epigenetic mechanism in the gene regulation. Gene expression changes at low exposure doses have been previously reported. Here, we add the possibility that lung epithelial cells, when singly exposed to real environmental concentrations of fine PM that translate into ultra-low doses of treatment, may undergo epigenetic alteration in the expression of genes related to xenobiotic metabolism. Our findings provide a perspective for future indoor air quality regulations. We underscore the potential role of indoor UFPs as carriers of toxic molecules with low-pressure weather conditions, when rainfall and strong winds may favour low levels of fine PM., 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 © 2024 National reserch Council of Italy - CNR. Published by Elsevier Ltd.. All rights reserved.)

Background: Oxidative stress has emerged as a key contributor to numerous NCDs (non-communicable diseases), including cardiovascular diseases, cancer, and diabetes. This study aims to explore the potential of targeted interventions to mitigate oxidative stress as part of a primary prevention strategy., Methods: The study included 32 healthy participants (11 men, 21 women) aged 45-65 who completed both the initial and follow-up assessments of the Healthy Days Initiative, a community-based wellness program organized by the non-profit Associazione O.R.A. ETS. Through blood analysis, vital sign assessment, lifestyle questionnaires, and individualized recommendations, participants received guidance on improving their health and reducing disease risk. The initiative also offered the opportunity for participants to consume a flavonoid supplement containing quercitrin, rutin, and hesperidin, with the goal of reducing oxidative stress. Participants who opted for supplementation were instructed to take 1-2 tablets daily for two weeks. Data collected included demographic information, anthropometric measurements, vital signs, dietary and lifestyle habits, medical history, WHO-5 Well-Being Index scores, and blood parameters., Results: Significant reductions were observed in glucose levels (from 82 to 74.5 mg/dL), reactive oxygen metabolites (d-ROMs) (from 394.5 to 365.5 U.CARR), and systolic blood pressure (from 133 to 122 mmHg) after the two-week flavonoid intervention. Most participants (26/31) reported no side effects, and the majority (30/31) expressed a willingness to continue using a product combination of quercitrin, rutin, and hesperidin or a similar product long-term., Conclusions: While limited in scope and duration, the PREVES-FLAVON study contributes valuable insights to the growing body of evidence suggesting that flavonoid supplementation may play a significant role in reducing risk factors associated with NCDs in primary prevention settings. By targeting novel risk factors such as oxidative stress, this intervention holds promise for mitigating the global burden of NCDs and promoting healthy aging.

Competing Interests: Declaration of Competing Interest The authors declare that they have no relevant financial or non-financial interests to disclose that are relevant to the content of this article.

Particulate Matter (PM) is a complex and heterogeneous mixture of atmospheric particles recognized as a threat to human health. Oxidative Potential (OP) measurement is a promising and integrative method for estimating PM-induced health impacts since it is recognized as more closely associated with adverse health effects than ordinarily used PM mass concentrations. OP measurements could be introduced in the air quality monitoring, along with the parameters currently evaluated. PM deposition in the lungs induces oxidative stress, inflammation, and DNA damage. The study aimed to compare the OP measurements with toxicological effects on BEAS-2B and THP-1 cells of winter and summer PM 1 collected in the Po Valley (Italy) during 2021. PM 1 was extracted in deionized water by mechanical agitation and tested for OP and, in parallel, used to treat cells. Cytotoxicity, genotoxicity, oxidative stress, and inflammatory responses were assessed by MTT test, DCFH-DA assay, micronucleus, γ-H2AX, comet assay modified with endonucleases, ELISA, and Real-Time PCR. The evaluation of OP was performed by applying three different assays: dithiothreitol (OP DTT ), ascorbic acid (OP AA ), and 2',7'-dichlorofluorescein (OP DCFH ), in addition, the reducing potential was also analysed (RP DPPH ). Seasonal differences were detected in all the parameters investigated. The amount of DNA damage detected with the Comet assay and ROS formation highlights the presence of oxidative damage both in winter and in summer samples, while DNA damage (micronucleus) and genes regulation were mainly detected in winter samples. A positive correlation with OP DCFH (Spearman's analysis, p < 0.05) was detected for IL-8 secretion and γ-H2AX. These results provide a biological support to the implementation in air quality monitoring of OP measurements as a useful proxy to estimate PM-induced cellular toxicological responses. In addition, these results provide new insights for the assessment of the ability of secondary aerosol in the background atmosphere to induce oxidative stress and health effects., 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 © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: This retrospective study investigates the efficacy of cemiplimab, a monoclonal antibody targeting the PD-1 receptor, in treating squamous cell carcinoma (SCC) of the skin., Methods: The study analyzes data from 50 patients with SCC, focusing on various clinical parameters, including patient demographics, tumor characteristics, treatment history, disease status at the beginning of therapy, and survival outcomes., Results: Of the patients who received at least one cycle of cemiplimab, 42% showed a clinical response. Adverse reactions were generally low, with the safety profile deemed excellent. During a median follow-up of 9.6 months, 17 patients experienced progression or death. Among these, 15 patients had died at the time of the analysis. The median progression-free survival (PFS) for the entire cohort was approximately 20.8 months, while median overall survival (OS) was not reached. Univariate Cox regression analysis for PFS showed that tumors in the arms and legs were associated with higher progression risk, while age above 65 years was not statistically significant. Distant metastasis exhibited a trend towards improved PFS. In terms of OS, distant metastasis was a significant predictor of reduced survival, while age above 65 years was not statistically significant. In a multivariate model, only the absence of distant metastasis remained significant, with an adjusted odds ratio (OR) of 12.3 (95% confidence interval 1.3-112.1)., Conclusion: These findings provide valuable insights into the real-world effectiveness of cemiplimab in SCC management., (© 2023. The Author(s).)

A reliable determination of equivalent black carbon (eBC) mass concentrations derived from filter absorption photometers (FAPs) measurements depends on the appropriate quantification of the mass absorption cross-section (MAC) for converting the absorption coefficient (b abs ) to eBC. This study investigates the spatial-temporal variability of the MAC obtained from simultaneous elemental carbon (EC) and b abs measurements performed at 22 sites. We compared different methodologies for retrieving eBC integrating different options for calculating MAC including: locally derived, median value calculated from 22 sites, and site-specific rolling MAC. The eBC concentrations that underwent correction using these methods were identified as LeBC (local MAC), MeBC (median MAC), and ReBC (Rolling MAC) respectively. Pronounced differences (up to more than 50 %) were observed between eBC as directly provided by FAPs (NeBC; Nominal instrumental MAC) and ReBC due to the differences observed between the experimental and nominal MAC values. The median MAC was 7.8 ± 3.4 m 2 g -1 from 12 aethalometers at 880 nm, and 10.6 ± 4.7 m 2 g -1 from 10 MAAPs at 637 nm. The experimental MAC showed significant site and seasonal dependencies, with heterogeneous patterns between summer and winter in different regions. In addition, long-term trend analysis revealed statistically significant (s.s.) decreasing trends in EC. Interestingly, we showed that the corresponding corrected eBC trends are not independent of the way eBC is calculated due to the variability of MAC. NeBC and EC decreasing trends were consistent at sites with no significant trend in experimental MAC. Conversely, where MAC showed s.s. trend, the NeBC and EC trends were not consistent while ReBC concentration followed the same pattern as EC. These results underscore the importance of accounting for MAC variations when deriving eBC measurements from FAPs and emphasize the necessity of incorporating EC observations to constrain the uncertainty associated with eBC., Competing Interests: Declaration of competing interest Griša Močnik is employed by Haze Instruments d.o.o., the manufacturer of the aerosol instrumentation., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Parkin is an E3 ubiquitin ligase, which plays a key role in the development of Parkinson disease. Parkin defects also occur in numerous cancers, and a growing body of evidence indicates that Parkin functions as a tumor suppressor that impedes a number of cellular processes involved in tumorigenesis. Here, we generated murine and human models that closely mimic the advanced-stage tumors where Parkin deficiencies are found to provide deeper insights into the tumor suppressive functions of Parkin. Loss of Parkin expression led to aggressive tumor growth, which was associated with poor tumor antigen presentation and limited antitumor CD8+ T-cell infiltration and activation. The effect of Parkin deficiency on tumor growth was lost following depletion of CD8+ T cells. In line with previous findings, Parkin deficiency was linked with mitochondria-associated metabolic stress, PTEN degradation, and enhanced Akt activation. Increased Akt signaling led to dysregulation of antigen presentation, and treatment with the Akt inhibitor MK2206-2HCl restored antigen presentation in Parkin-deficient tumors. Analysis of data from patients with clear cell renal cell carcinoma indicated that Parkin expression was downregulated in tumors and that low expression correlated with reduced overall survival. Furthermore, low Parkin expression correlated with reduced patient response to immunotherapy. Overall, these results identify a role for Parkin deficiency in promoting tumor immune evasion that may explain the poor prognosis associated with loss of Parkin across multiple types of cancer., Significance: Parkin prevents immune evasion by regulating tumor antigen processing and presentation through the PTEN/Akt network, which has important implications for immunotherapy treatments in patients with Parkin-deficient tumors., (©2023 The Authors; Published by the American Association for Cancer Research.)

Exposures to fine particulate matter (PM[Formula: see text]) have been associated with health impacts, but the understanding of the PM[Formula: see text] concentration-response (PM[Formula: see text]-CR) relationships, especially at low PM[Formula: see text], remains incomplete. Here, we present novel data using a methodology to mimic lung exposure to ambient air (2[Formula: see text] 60 [Formula: see text]g m[Formula: see text]), with minimized sampling artifacts for nanoparticles. A reference model (Air Liquid Interface cultures of human bronchial epithelial cells, BEAS-2B) was used for aerosol exposure. Non-linearities observed in PM[Formula: see text]-CR curves are interpreted as a result of the interplay between the aerosol total oxidative potential (OP[Formula: see text]) and its distribution across particle size (d[Formula: see text]). A d[Formula: see text]-dependent condensation sink (CS) is assessed together with the distribution with d[Formula: see text] of reactive species . Urban ambient aerosol high in OP[Formula: see text], as indicated by the DTT assay, with (possibly copper-containing) nanoparticles, shows higher pro-inflammatory and oxidative responses, this occurring at lower PM[Formula: see text] concentrations (< 5 [Formula: see text]g m[Formula: see text]). Among the implications of this work, there are recommendations for global efforts to go toward the refinement of actual air quality standards with metrics considering the distribution of OP[Formula: see text] with d[Formula: see text] also at relatively low PM[Formula: see text]., (© 2023. The Author(s).)

Nasal vestibule squamous cell carcinoma (SCC) is a rare malignancy with limited treatment options. This case report presents an 83-year-old female with SCC of the nasal vestibule who was ineligible for surgery or radiotherapy due to various factors. The patient was successfully treated with cemiplimab, a systemic anti-PD-1 antibody, resulting in a remarkable tumor reduction without any observed side effects. This is the first reported case of nasal vestibule SCC treated with cemiplimab, highlighting its potential as a promising therapeutic option., Competing Interests: The authors have no conflicts of interest to declare., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

This study analyzed the variability of equivalent black carbon (eBC) mass concentrations and their sources in urban Europe to provide insights into the use of eBC as an advanced air quality (AQ) parameter for AQ standards. This study compiled eBC mass concentration datasets covering the period between 2006 and 2022 from 50 measurement stations, including 23 urban background (UB), 18 traffic (TR), 7 suburban (SUB), and 2 regional background (RB) sites. The results highlighted the need for the harmonization of eBC measurements to allow for direct comparisons between eBC mass concentrations measured across urban Europe. The eBC mass concentrations exhibited a decreasing trend as follows: TR > UB > SUB > RB. Furthermore, a clear decreasing trend in eBC concentrations was observed in the UB sites moving from Southern to Northern Europe. The eBC mass concentrations exhibited significant spatiotemporal heterogeneity, including marked differences in eBC mass concentration and variable contributions of pollution sources to bulk eBC between different cities. Seasonal patterns in eBC concentrations were also evident, with higher winter concentrations observed in a large proportion of cities, especially at UB and SUB sites. The contribution of eBC from fossil fuel combustion, mostly traffic (eBC T ) was higher than that of residential and commercial sources (eBC RC ) in all European sites studied. Nevertheless, eBC RC still had a substantial contribution to total eBC mass concentrations at a majority of the sites. eBC trend analysis revealed decreasing trends for eBC T over the last decade, while eBC RC remained relatively constant or even increased slightly in some cities., 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 Author(s). Published by Elsevier Ltd.. All rights reserved.)

Several studies have shown the influence of commensal microbes on T cell function, specifically in the setting of checkpoint immunotherapy for cancer. In this study, we investigated how vancomycin-induced gut microbiota dysbiosis affects chimeric antigen receptor (CAR) T immunotherapy using multiple preclinical models as well as clinical correlates. In two murine tumor models, hematopoietic CD19 + -A20 lymphoma and CD19 + -B16 melanoma, mice receiving vancomycin in combination with CD19-directed CAR T cell (CART-19) therapy displayed increased tumor control and tumor-associated antigens (TAAs) cross-presentation compared with CART-19 alone. Fecal microbiota transplant from human healthy donors to pre-conditioned mice recapitulated the results obtained in naive gut microbiota mice. Last, B cell acute lymphoblastic leukemia patients treated with CART-19 and exposed to oral vancomycin showed higher CART-19 peak expansion compared with unexposed patients. These results substantiate the role of the gut microbiota on CAR T cell therapy and suggest that modulation of the gut microbiota using vancomycin may improve outcomes after CAR T cell therapy across tumor types., Competing Interests: Declaration of interests M.R.: BMS, BAYER, GSK, consultancy; Novartis, patents and royalties; AbClon, consultancy, research funding; Tmunity, patents and royalties; viTToria Biotherapeutics, research funding. N.F.: Sana Biotechnology, consultancy; Novartis, research funding; Kite Pharma, consultancy; Syndax Pharmaceuticals, consultancy. C.H.J.: Tmunity, DeCART, BluesphereBio, Carisma, Cellares, Celldex, Cabaletta, Poseida, Verismo, and Ziopharm, current equity holder in publicly traded company; AC Immune, DeCART, BluesphereBio, Carisma, Cellares, Celldex, Cabaletta, Poseida, Verismo, Ziopharm, consultancy; Novartis, patents and royalties. D.L.P.: American Society for Transplantation and Cellular Therapy, honoraria; ASH and DeCart, membership on the Board of Directors or advisory committee; Genentech, current employment, current equity holder in publicly traded company; Incyte and Janssen, Kite/Gilead, and National Marrow Donor Program, membership on an entity’s board of directors or advisory committee; Novartis, membership on an entity’s board of directors or advisory committee, patents and royalties, and research funding; Unity, patents and royalties; and Wiley and Sons Publishing, honoraria. S.J.S.: TG Therapeutics, research funding; Incyte, research funding; Adaptive Biotechnologies, research funding; Pharmacyclics, research funding; Merck, research funding; Genentech/Roche, consultancy, research funding; Tessa Therapeutics, consultancy; Loxo Oncology, consultancy; Juno Therapeutics, consultancy, research funding; BeiGene, consultancy; Alimera Sciences, consultancy; Acerta Pharma/AstraZeneca, consultancy; Novartis, consultancy, honoraria, patents and royalties, research funding; AbbVie, consultancy, research funding; Nordic Nanovector, consultancy; Celgene, consultancy, honoraria, research funding., (Copyright © 2023. Published by Elsevier Inc.)

Introduction: Approximately a third of cancer-related deaths are attributable to modifiable factors., Methods: As a pilot experience, a cross-sectional survey was conducted in 8,000 citizens residing in four different municipalities of the Salerno province (Sarno, Pagani, San Valentino Torio, and San Marzano sul Sarno) to investigate key lifestyle and dietary habits., Results: A total of 703 of participants (8.7%) reported a history of malignancy. Alarmingly, 30.5% declared to be a current smoker, while 78.8% did not report any kind of physical activity. Encouragingly, 64.5% declared to be abstemious, and 83.0% declared to consume fruit and vegetables every day, while 4.7% and 31.9% declared not to consume meat and fried food, respectively, at any time. Never-consumers of fruit and vegetables had higher odds of having a history of colorectal cancer (OR = 5.01; 95% CI = 1.46-17.15; p = 0.01)., Conclusions: The PREVES study has served to prove the validity of an operational model allowing to integrate hospital and territorial healthcare services, which we expect to be applied at a larger scale. Key information regarding dietary and lifestyle habits of the investigated population was obtained. Larger studies conducted using more accurate approaches to investigate diet, such as 24-h recalls and food frequency questionnaires, are warranted., (© 2023 S. Karger AG, Basel.)

Introduction: Cancer aggravates COVID-19 prognosis. Nosocomial transmission of SARS-CoV-2 is particularly frequent in cancer patients, who need to attend hospitals regularly. Since March 2020, all cancer patients having access to the Oncology Unit at the "Andrea Tortora" Hospital (Pagani, Salerno - referred to as "the Hospital") as inpatients or outpatients receiving intravenous therapy have been screened for SARS-CoV-2 using RT-PCR nasal swab. The ongoing COICA (COVID-19 infection in cancer patients) study is an ambispective, multicenter, observational study designed to assess the prognosis of SARS-CoV-2 infection in cancer patients. The aim of the study presented here was to explore potential differences in COVID-19-related outcomes among screening-detected versus nonscreening-detected SARS-CoV-2-infected patients. Methods: The COICA study enrolled cancer patients who had received any anticancer systemic therapy within 3 months since the day they tested positive for SARS-CoV-2 on RT-PCR. The target accrual is 128 patients, and the study was approved by the competent Ethics Committee. Only the subgroup of patients enrolled at the Hospital was considered in this unplanned interim analysis. Logistic regression analysis was used to evaluate the association of screening-based versus nonscreening-based diagnosis. Results: Since March 15, 2020, until August 15, 2021, a total of 931 outpatients and 230 inpatients were repeatedly screened for SARS-CoV-2 using RT-PCR nasal swab at the Hospital. Among these, 71 asymptomatic patients were positive on routine screening and 5 patients were positive for SARS-CoV-2 outside the institutional screening. Seven patients died because of COVID-19. At univariate analysis, nonscreening- versus screening-detected SARS-CoV-2 infection was associated with significantly higher odds of O 2 therapy (OR = 16.2; 95% CI = 2.2-117.1; p = 0.006), hospital admission (OR = 31.5; 95% CI = 3.1-317.8; p = 0.003), admission to ICU (OR = 23.0; 95% CI = 2.4-223.8; p = 0.007), and death (OR = 8.8; 95% CI = 1.2-65.5; p = 0.034). Conclusion: Routine screening with RT-PCR may represent a feasible and effective strategy in reducing viral circulation and possibly COVID-19 mortality in patients with active cancer having repeated access to hospital facilities., (© 2021 S. Karger AG, Basel.)

Introduction: Metastatic castration-resistant prostate cancer (mCRPC) is a deadly disease. Enzalutamide is an oral second-generation anti-androgen that is active in mCRPC. Circulating tumor cells (CTC) count correlates with overall survival (OS) in mCRPC, whereas detection of the androgen-receptor splice variant 7 (AR-V7) in CTC predicts poor response to oral second-generation anti-androgens. Also, loss of PTEN (phosphatase and tensin homolog) in CTC is a biomarker of poor prognosis in mCRPC., Patients and Methods: In this translational study, we employed flow cytometry to assess total, PTEN - , and AR-V7 + CTC count per 7.5 mL of whole blood in a prospective cohort of patients with mCRPC receiving enzalutamide., Results: CTCs were assessed in a total of 45 men with mCRPC at baseline and at 12 weeks. Overall, CTC, PTEN - CTC, and AR-V7 + CTC detection rate was high, at baseline, with 84.4%, 71.1%, and 51.1% of samples showing at least 1 cell/7.5-mL blood, respectively, and after 3 months, with 93.3%, 64.4%, and 77.7% of samples showing at least 1 cell/7.5-mL blood, respectively. Median radiographic progression-free survival (rPFS) and OS were 6 (95% confidence interval [CI], 5.6-9) and 14.3 (95% CI, 12.8-20.3) months, respectively. Median (interquartile range) total CTC count at baseline was 5 (3; 8), whereas median (interquartile range) PTEN - CTC count was 2 (0; 4) and median (interquartile range) AR-V7 + CTC count was 1 (0; 3). At baseline, ≥ 5 versus < 5 total CTC count was associated with worse rPFS (hazard ratio [HR], 2.35; 95% CI, 1.14-4.84; P= .021) and OS (HR, 3.08; 95% CI, 1.45-6.54; P = .003), whereas ≥ 2 versus < 2 PTEN - CTC count was associated with worse rPFS (HR, 3.96; 95% CI, 1.8-8.72; P= .001) and OS (HR, 2.36; 95% CI, 1.12-5; P= .025). Finally, ≥ 1 versus < 1 AR-V7 + CTC count was also associated with worse rPFS (HR, 5.05; 95% CI, 2.4-10.64; P< .001) and OS (HR, 2.25; 95% CI, 1.1-4.58; P= .026)., Conclusions: Despite multiple limitations, including the small sample size, our preliminary study suggests that assessment of CTC via flow cytometry may provide potentially useful prognostic and predictive information in advanced prostate cancer. Further studies are warranted. Micro-Abstract: In this study, men with metastatic castration-resistant prostate cancer, scheduled to start enzalutamide, were assessed for circulating tumor cell count and molecular characterization (total, PTEN - , and AR-V7 + circulating tumor cell count) by the use of flow cytometry. We found that flow cytometry could be used to enumerate circulating tumor cells, but also to assess molecular biomarkers on their surface., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Head and neck squamous cell carcinoma (HNSCC) has a poor clinical outcome despite the presence of a rich CD8+ T cell tumor infiltrate in the majority of patients. This may be due to alterations of tumor infiltrating CD8+ T cells. Here, we performed a characterization of HNSCC infiltrating CD8+ T cells in a cohort of 30 patients. The results showed that differential intratumoral frequency of CD8+CD28+ T cells, CD8+CD28- T cells, and CD8+CD28-CD127-CD39+ Treg distinguished between HNSCC patients who did or did not respond to treatment. Moreover, high PD1 expression identified a CD8+CD28- T cell subpopulation, phenotypically/functionally corresponding to CD8+CD28-CD127-CD39+ Treg, which showed a high expression of markers of exhaustion. This observation suggests that development of exhaustion and acquisition of regulatory properties may configure the late differentiation stage for intratumoral effector T cells, a phenomenon we define as effector-to-regulatory T cell transition.

Background: Tumor endothelial marker 1 (TEM1) is a protein expressed in the tumor-associated endothelium and/or stroma of various types of cancer. We previously demonstrated that immunization with a plasmid-DNA vaccine targeting TEM1 reduced tumor progression in three murine cancer models. Radiation therapy (RT) is an established cancer modality used in more than 50% of patients with solid tumors. RT can induce tumor-associated vasculature injury, triggering immunogenic cell death and inhibition of the irradiated tumor and distant non-irradiated tumor growth (abscopal effect). Combination treatment of RT with TEM1 immunotherapy may complement and augment established immune checkpoint blockade., Methods: Mice bearing bilateral subcutaneous CT26 colorectal or TC1 lung tumors were treated with a novel heterologous TEM1-based vaccine, in combination with RT, and anti-programmed death-ligand 1 (PD-L1) antibody or combinations of these therapies, tumor growth of irradiated and abscopal tumors was subsequently assessed. Analysis of tumor blood perfusion was evaluated by CD31 staining and Doppler ultrasound imaging. Immunophenotyping of peripheral and tumor-infiltrating immune cells as well as functional analysis was analyzed by flow cytometry, ELISpot assay and adoptive cell transfer (ACT) experiments., Results: We demonstrate that addition of RT to heterologous TEM1 vaccination reduces progression of CT26 and TC1 irradiated and abscopal distant tumors as compared with either single treatment. Mechanistically, RT increased major histocompatibility complex class I molecule (MHCI) expression on endothelial cells and improved immune recognition of the endothelium by anti-TEM1 T cells with subsequent severe vascular damage as measured by reduced microvascular density and tumor blood perfusion. Heterologous TEM1 vaccine and RT combination therapy boosted tumor-associated antigen (TAA) cross-priming (ie, anti-gp70) and augmented programmed cell death protein 1 (PD-1)/PD-L1 signaling within CT26 tumor. Blocking the PD-1/PD-L1 axis in combination with dual therapy further increased the antitumor effect and gp70-specific immune responses. ACT experiments show that anti-gp70 T cells are required for the antitumor effects of the combination therapy., Conclusion: Our findings describe novel cooperative mechanisms between heterologous TEM1 vaccination and RT, highlighting the pivotal role that TAA cross-priming plays for an effective antitumor strategy. Furthermore, we provide rationale for using heterologous TEM1 vaccination and RT as an add-on to immune checkpoint blockade as triple combination therapy into early-phase clinical trials., 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.)

Background: Merkel cell carcinoma (MCC) is a rare neuroendocrine skin cancer. It frequently emerges in the presence of immunosuppression states such as myeloproliferative syndrome (MS). MS is treated with ruxolitinib, a selective JAK1 and JAK2 inhibitor. Avelumab, an anti PDL-1 inhibitor, is the standard treatment for MCC. To date it is unknown if avelumab and ruxolitinib have a synergistic or antagonistic effect when used together. Methods: We have identified all patients diagnosed with MCC, treated with avelumab, concomitant ruxolitinib, belonging to Tortora Hospital, Pagani and Santa Maria La Pietà Hospital, Nola, Italy between June 1 2019 and April 1 2020. Results: Among six MCC patients, we have found two patients in treatment with concomitant drugs. Both patients were being treated with ruxolitinib for MS as a standard regimen without suffering any hematological side effects. After starting doses of avelumab, we found thrombocytopenia, leukopenia, and anemia after cycle 1 and cycle 4, respectively, and decided to suspend both treatments. Following the suspension, the hematological values improved allowing us to restart treatment with avelumab without the need to resume ruxolitinib treatment. Conclusions: The combined treatment of ruxolitinib and avelumab demonstrated severe toxicity. Modifying the schedule or reducing the dose of both drugs needs to be studied in order to be able to treat both pathologies., (Copyright © 2020 Buonerba, Di Trolio, Grimaldi, Tucci, Leo, Ingenito, Costabile, Ragone, Savastano, Uzzauto, Belsito Petrizzi and Di Lorenzo.)

In the framework of the 2017 "carbonaceous aerosol in Rome and Environs" (CARE) experiment, particle number size distributions have been continuously measured on February 2017 in downtown Rome. These data have been used to estimate, through MPPD model, size and time resolved particle mass, surface area and number doses deposited into the respiratory system. Dosimetry estimates are presented for PM 10 , PM 2.5 , PM 1 and Ultrafine Particles (UFPs), in relation to the aerosol sources peculiar to the Mediterranean basin and to the atmospheric conditions. Particular emphasis is focused on UFPs and their fraction deposited on the olfactory bulb, in view of their possible translocation to the brain. The site of PM 10 deposition within the respiratory system considerably changes, depending on the aerosol sources and then on its different size distributions. On making associations between health endpoints and aerosol mass concentrations, the relevant coarse and fine fractions would be more properly adopted, because they have different sources, different capability of penetrating deep into the respiratory system and different toxicological implications. The separation between them should be set at 1 µm, rather than at 2.5 µm, because the fine fraction is considerably less affected by the contribution of the natural sources. Mass dose is a suitable metric to describe coarse aerosol events but gives a poor representation of combustion aerosol. This fraction of particles, made of UFPs and of accumulation mode particles (mainly with size below 0.2 µm), is of high health relevance. It elicited the highest oxidative activity in the CARE experiment and is properly described by the particle surface area and by the number metrics. Such metrics are even more relevant for the UFP doses deposited on the olfactory bulb, in consideration of the role recognized to oxidative stress in the progression of neurodegenerative diseases. Such metrics would be more appropriate, rather than PM x mass concentrations, to correlate neurodegenerative pathologies with aerosol pollution., 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 The Authors. Published by Elsevier Ltd.. All rights reserved.)

: Immunotherapy based on anti PD-1/PD-L1 inhibitors has proven to be more effective than sunitinib in the first-line setting of advanced renal cell carcinoma (RCC). RCC patients with sarcomatoid histology (sRCC) have a poor prognosis and limited therapeutic options. We performed a systematic review and a meta-analysis of randomized-controlled trials (RCTs) of first-line anti PD-1/PDL-1 agents vs. sunitinib, presenting efficacy data in the sub-group of sRCC patients. The systematic research was conducted on Google Scholar, Cochrane Library, PubMed and Embase and updated until 31th January, 2020. Abstracts from ESMO and ASCO (2010-2019) were also reviewed. Full texts and abstracts reporting about RCTs testing first-line anti-PD-1/ PD-L1 agents vs. sunitinib in RCC were included if sRCC sub-group analyses of either PFS (progression-free survival), OS (overall survival) or radiological response rate were available. Pooled data from 3814 RCC patients in the ITT (intention-to-treat) population and from 512 sRCC patients were included in the quantitative synthesis. In the sRCC sub-group vs. the ITT population, pooled estimates of the PFS-HRs were 0.57 (95%: 0.45-0.74) vs. 0.79 (95% CI: 0.70-0.89), respectively, with a statistically meaningful interaction favoring the sRCC sub-group (pooled ratio of the PFS-HRs = 0.64; 95% CI: 0.50-0.82; p < 0.001). Pooled estimates of the difference in CR-R (complete response-rate) achieved with anti-PD-1/PDL-1 agents vs. sunitinib were + 0.10 (95% CI: 0.04-0.16) vs. + 0.04 (95% CI: 0.00-0.07) in the sRCC vs. the non-sRCC sub groups, with a statistically meaningful difference of + 0.06 (95% CI: 0.02-0.10; p = 0.007) favoring the sRCC sub-group. Sarcomatoid histology may be associated with improved efficacy of anti PD-1/PDL-1 agents vs. sunitinib in terms of PFS and CR-R., Competing Interests: The authors declare no conflict of interest.

Some commonly available patient or disease characteristics may be associated with progression-free survival (PFS) and overall survival (OS) in EGFR-mutant non-small cell lung cancer (NSCLC) patients receiving EGFR-TKIs (epidermal growth factor receptor - tyrosine kinase inhibitors). We performed a systematic review and meta-analysis of randomized control trials (RCTs) to explore differences in outcomes associated with EGFR-TKIs among subgroups of EGFR-mutant NSCLC patients. Pooled HRs for progression or death (PFS-HRs) and pooled HRs for death (OS-HRs) were compared among sub-groups defined according to baseline clinical and demographic variables as well as type of EGFR mutation. In the entire assessable population of 4465 EGFR-mutant NSCLC patients, significant interactions with PFS were found for gender (males vs. females; pooled ratio of the PFS-HRs = 1.2; 95% CI 1.12-1.56), smoking history (smokers vs. non-smokers; pooled ratio of the PFS-HRs = 1.26; 95% CI 1.05-1.51), and type of EGFR mutation (patients with exon 21 L858R mutation vs. exon 19 deletion; pooled ratio of the PFS-HRs = 1.39; 95% CI 1.18-1.63). Male patients, smokers and patients with EGFR exon 21 L858R mutation may derive less benefit from EGFR-TKIs compared to female patients, non-smokers and patients with EGFR exon 19 deletion.

(1) Background : The products of guanine oxidation in DNA and RNA excreted in urine are 8-oxo-7,8-dihydroguanine (8-oxoGua), 8-oxo-7,8-dihydroguanosine (8-oxoGuo), and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo). Despite intra and inter-individual variability, it is possible to identify situations that significantly increase the levels of these compounds when comparing urinary concentrations of some workers to those of the general population. (2) Methods : urines from gasoline pump attendants (58 from Saudi Arabia and 102 from Italy), 24 workers of a fiberglass reinforced plastics plant, 17 painters and 6 divers were analyzed by HPLC/MS-MS. To test the individual variability, two subjects provided daily samples for one month, and 132 urine samples from the general population were analyzed. (3) Results : We summarized the results for each biomarker, and found the following were statistically higher than in the general population: 8-oxoGua in fiberglass and Italian gasoline workers; 8-oxodGuo in fiberglass and both Saudi Arabian and Italian gasoline workers; 8-oxoGuo in fiberglass workers, both Saudi Arabian and Italian gasoline workers, and painters after the working shift. (4) Conclusions : these results confirm that both 8-oxodGuo and 8-oxoGuo are valuable biomarkers for occupational exposures to dangerous chemicals and seem to suggest that 8-oxoGuo, related to RNA oxidation, is a suitable biomarker to evaluate short term, reversible effects of occupational exposures even within the health-based limit values.

An essential advantage during eukaryotic cell evolution was the acquisition of a network of mitochondria as a source of energy for cell metabolism and contrary to conventional wisdom, functional mitochondria are essential for the cancer cell. Multiple aspects of mitochondrial biology beyond bioenergetics support transformation including mitochondrial biogenesis, fission and fusion dynamics, cell death susceptibility, oxidative stress regulation, metabolism, and signaling. In cancer, the metabolism of cells is reprogrammed for energy generation from oxidative phosphorylation to aerobic glycolysis and impacts cancer mitochondrial function. Furthermore cancer cells can also modulate energy metabolism within the cancer microenvironment including immune cells and induce "metabolic anergy" of antitumor immune response. Classical approaches targeting the mitochondria of cancer cells usually aim at inducing changing energy metabolism or directly affecting functions of mitochondrial antiapoptotic proteins but most of such approaches miss the required specificity of action and carry important side effects. Several types of cancers harbor somatic mitochondrial DNA mutations and specific immune response to mutated mitochondrial proteins has been observed. An attractive alternative way to target the mitochondria in cancer cells is the induction of an adaptive immune response against mutated mitochondrial proteins. Here, we review the cancer cell-intrinsic and cell-extrinsic mechanisms through which mitochondria influence all steps of oncogenesis, with a focus on the therapeutic potential of targeting mitochondrial DNA mutations or Tumor Associated Mitochondria Antigens using the immune system., (Copyright © 2018. Published by Elsevier Inc.)

Sphingosine 1-phosphate (S1P) has a role in many cellular processes. S1P is involved in cell growth and apoptosis, regulation of cell trafficking, production of cytokines and chemokines. The kinases SphK1 and SphK2 (SphKs) phosphorilate Sphingosine (Sph) to S1P and several phosphatases revert S1P to sphingosine, thus assuring a balanced pool that can be depleted by a Sphingosine lyase in hexadecenal compounds and aldehydes. There are evidences that SphK1 and 2 may per se control cellular processes. Here, we report that Sph kinases regulate IL-17 expression in human T cells. SphKs inhibition impairs the production of IL-17, while their overexpression up-regulates expression of the cytokine through acetylation of IL-17 promoter. SphKs were up-regulated also in PBMCs of patients affected by IL-17 related diseases. Thus, S1P/S1P kinases axis is a mechanism likely to promote IL-17 expression in human T cells, representing a possible therapeutic target in human inflammatory diseases.

Air pollution and particulate matter are recognised cause of increased disease incidence in exposed population. The toxicological processes underlying air pollution associated effects have been investigated by in vivo and/or in vitro experimentation. The latter is usually performed by exposing cells cultured under submerged condition to particulate matter concentration quite far from environmental exposure expected in humans. Here we report for the first time the feasibility of a direct exposure of air liquid interface cultured cells to environmental concentration of particulate matter. Inflammatory proteins release was analysed in cell medium while differential expression of selected genes was analysed in cells. Significant association of anti-oxidant genes was observed with secondary and aged aerosol, while cytochrome activation with primary and PAHs enriched ultrafine particles. The results obtained clearly show the opportunity to move from the lab bench to the field for properly understanding the toxicological effects also of ultrafine particles on selected in vitro models., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The mechanisms leading to the formation of secondary organic aerosol (SOA) are an important subject of ongoing research for both air quality and climate. Recent laboratory experiments suggest that reactions taking place in the atmospheric liquid phase represent a potentially significant source of SOA mass. Here, we report direct ambient observations of SOA mass formation from processing of biomass-burning emissions in the aqueous phase. Aqueous SOA (aqSOA) formation is observed both in fog water and in wet aerosol. The aqSOA from biomass burning contributes to the "brown" carbon (BrC) budget and exhibits light absorption wavelength dependence close to the upper bound of the values observed in laboratory experiments for fresh and processed biomass-burning emissions. We estimate that the aqSOA from residential wood combustion can account for up to 0.1-0.5 Tg of organic aerosol (OA) per y in Europe, equivalent to 4-20% of the total OA emissions. Our findings highlight the importance of aqSOA from anthropogenic emissions on air quality and climate., Competing Interests: The authors declare no conflict of interest.

Current knowledge of daytime HONO sources remains incomplete. A large missing daytime HONO source has been found in many places around the world, including polluted regions in China. Conventional understanding and recent studies attributed this missing source mainly to ground surface processes or gas-phase chemistry, while assuming aerosols to be an insignificant media for HONO production. We analyze in situ observations of HONO and its precursors at an urban site in Beijing, China, and report an apparent dependence of the missing HONO source strength on aerosol surface area and solar ultraviolet radiation. Based on extensive correlation analysis and process-modeling, we propose that the rapid daytime HONO production in Beijing can be explained by enhanced hydrolytic disproportionation of NO2 on aqueous aerosol surfaces due to catalysis by dicarboxylic acid anions. The combination of high abundance of NO2, aromatic hydrocarbons, and aerosols over broad regions in China likely leads to elevated HONO levels, rapid OH production, and enhanced oxidizing capacity on a regional basis. Our findings call for attention to aerosols as a media for daytime heterogeneous HONO production in polluted regions like Beijing. This study also highlights the complex and uncertain heterogeneous chemistry in China, which merits future efforts of reconciling regional modeling and laboratory experiments, in order to understand and mitigate the regional particulate and O3 pollutions over China.

Objectives: to assess air pollution spatial and temporal variability in the urban area nearby the Ciampino International Airport (Rome) and to investigate the airport-related emissions contribute., Design and Setting: the study domain was a 64 km2 area around the airport. Two fifteen-day monitoring campaigns (late spring, winter) were carried out. Results were evaluated using several runs outputs of an airport-related sources Lagrangian particle model and a photochemical model (the Flexible Air quality Regional Model, FARM)., Main Outcome Measures: both standard and high time resolution air pollutant concentrations measurements: CO, NO, NO2, C6H6, mass and number concentration of several PM fractions. 46 fixed points (spread over the study area) of NO2 and volatile organic compounds concentrations (fifteen days averages); deterministic models outputs., Results: standard time resolution measurements, as well as model outputs, showed the airport contribution to air pollution levels being little compared to the main source in the area (i.e. vehicular traffic). However, using high time resolution measurements, peaks of particles associated with aircraft takeoff (total number concentration and soot mass concentration), and landing (coarse mass concentration) were observed, when the site measurement was downwind to the runway., Conclusions: the frequently observed transient spikes associated with aircraft movements could lead to a not negligible contribute to ultrafine, soot and coarse particles exposure of people living around the airport. Such contribute and its spatial and temporal variability should be investigated when assessing the airports air quality impact.

Purpose: This paper presents a novel approach to interpret ground-level O(3) with the measured atmospheric stability index (ASI)., Methods: O(3) concentrations were monitored by automatic analysers at three types of stations: traffic site, residential site and regional background site in 2005, and the ASI was simultaneously measured by observing radon and its short-lived decay products., Results: The observed results showed a clear annual variation of O(3) concentrations with a maximum in spring, relatively high at the regional background site over 120 ppb, and lower at the residential and traffic sites at about 70 ppb. ASI gives information about the dilution properties of the lower boundary layer and allows to highlight the relevant role of the dilution factor in determining atmospheric pollution events. We demonstrated the analysis of O(3) night peak episodes with vertical wind and ASI., Conclusions: With the advantage of ASI and vertical wind profiles, it was possible to isolate particular photochemical pollution phenomena of O(3) peaks from the free troposphere reservoir or formed by local reactions. This shows that the index constitutes a powerful and valuable tool for describing O(3) night-peak episodes at background station.

We analyze the observations of near-surface peroxy acetyl nitrate (PAN) and its precursors in Beijing, China in August of 2007. The levels of PAN are remarkably high (up to 14 ppbv), surpassing those measured over other urban regions in recent years. Analyses employing a 1-D version of a chemical transport model (Regional chEmical and trAnsport Model, REAM) indicate that aromatic non-methane hydrocarbons (NMHCs) are the dominant (55-75%) PAN source. The major oxidation product of aromatics that produces acetyl peroxy radicals is methylglyoxal (MGLY). PAN and O(3) in the observations are correlated at daytime; aromatic NMHCs appear to play an important role in O(3) photochemistry. Previous NMHC measurements indicate the presence of reactive aromatics at high levels over broad polluted regions of China. Aromatics are often ignored in global and (to a lesser degree) regional 3D photochemical transport models; their emissions over China as well as photochemistry are quite uncertain. Our findings suggest that critical assessments of aromatics emissions and chemistry (such as the yields of MGLY) are necessary to understand and assess ozone photochemistry and regional pollution export in China.

Within the Sino-Italian environmental protection cooperation framework established in 2002, a comprehensive air quality monitoring network has been developed in urban Suzhou, a medium-sized Chinese city, in compliance with European standards (Directive 96/62/EC). This paper is among the first attempts to present a systematic and scientific analysis of benzene, toluene, and xylenes (BTX) pollution in China. It presents our analysis of BTX space-related and time-related measurement results. Background BTX concentrations were investigated by passive sampler Analyst(R) in 2003. We depicted the spatial distribution of average BTX concentrations collected from three 15-day campaigns on isoconcentration maps. This is the first time such detailed BTX concentration maps have been developed in China in a city scale. Continuous measurement of BTX by automatic gas chromatography was carried out at two fixed monitoring stations, one in an urban residential zone and one in a heavy traffic zone, from April to December 2005. The results show similar seasonal trends at both sites, the similarities reaching their greatest level in December and their lowest level in August. The average daily profile of BTX shows greater fluctuation in spring and winter with clear morning and evening peaks. Daily average benzene, toluene, and m,p-xylenes concentrations for the study period were 2.64, 11.52, and 3.52 microg m(-3), respectively. The benzene/toluene ratio we found was lower in Suzhou than those published in studies of other worldwide cities, which indicates serious levels of toluene pollution from local stationary sources. The similarities in seasonal trend and spatial distribution in these manual and automatic measurement results were compared with each other, though the concentration values differed.

Based on an air pollution modeling system coupling with the non-hydrostatic fifth generation mesoscale meteorological model (MM5) and the regional modeling system for aerosols and deposition (REMSAD), the forecast results of NOx and SO2 in August and September 2002 in Nanjing were assimilated with the optimal interpolation method and the ensemble Kalman filter. The results show that the improvement rates of deviation mean value of NOx and SO2 after assimilated with the optimal interpolation method are 34.20% and 47.53%, and the improvement rates of root mean square errors are 31.95% and 42.04% respectively. It is also demonstrated that the improvement rates of deviation mean value of NOx and SO2 after assimilated with the ensemble Kalman filter with 30 ensemble members are 26.73% and 60.75%, and the improvement rates of root mean square errors are 25.20% and 55.16% respectively. So, the optimal interpolation method and the ensemble Kalman filter both can improve the quality of the initial state from the air pollution numerical prediction model. The comparative experiments on the assimilation performance with the optimal interpolation method and the ensemble Kalman filter with 61 ensemble members were performed, and the experiments demonstrate that the assimilation performance of the ensemble Kalman filter with 61 ensemble members were improved compared with 30 ensemble members, and with the increase of the ensemble members, the improvement to the initial state of NOx and SO2 with the ensemble Kalman filter will be better than the optimal interpolation method.

Background: The relationship between ankle plantar flexor biomechanical properties and gait pattern following surgery for acute rupture of the Achilles tendon has not yet been fully investigated., Methods: Forty-nine young adults (27 men and 22 women) who underwent surgical repair of a complete Achilles tendon rupture were evaluated at 3, 6, 12 and 24 months by clinical assessment, biomechanical evaluation and gait analysis., Findings: Ankle range of motion, plantar flexor passive stiffness and concentric strength were recovered within 12 months. Gait abnormalities related to these factors took longer to disappear owing to the presence of anomalous muscle patterns. At 24 months, a deficit in calf-muscle eccentric strength was still present, determining adaptive changes in gait strategy that involved ankle motion and coordinated muscular activity., Interpretation: Improvement of gait pattern is slower than recovery of plantar flexor mechanical properties. Persisting mechanical impairment resulting in gait adaptations may be detrimental to the healing structures by increasing stress on the Achilles tendon. Restoration of calf-muscle eccentric strength and coordinated antagonist muscle activity should be key points in postoperative rehabilitation following surgical repair of Achilles tendon rupture.

Incidental detection of a mediastinal mass in a asymptomatic patient poses a not easy diagnostic problem. For solid masses or cysts, histology or cytology is often necessary. Although substernal extension of a cervical goiter is common, totally intrathoracic primary thyroidal mass is unusual. We describe a rare case of heterotopic accessory mediastinal thyroid in a patient completely asymptomatic both for signs of thyroid dysfunction and mechanical compression. Radiological and hormonal 6 and 12 months follow-up is reported.

Descriptive data on occupational accidents and diseases in the field of construction and particularly among builders are reported. They derive from publications of the National Insurance Institute for Occupational Accidents (INAIL) and refer to the Italian and Umbrian situation. Data show that the number and the severity of the accidents in this field are of great concern. The characteristics of the building work in our areas are too peculiar as the work is carried out in small building sites and lasts for a short period of time; subcontracting and piecework are widely diffused; health surveillance is nearly absent. One must take into account all of these characteristics when prevention programs are to be planned. Intervention priority must be given to a) information on occupational risks of contractors and workers; b) first level prevention; c) control and inspection activity. In this respect the A.A. report the results of the watch activity in 703 erecting yards by one to health unit's Department for the health security, safety and welfare of persons at work (period May 1985 - May 1988). The A.A. define a type of organization to achieve a continual intervention in the erecting yards.

The present report is a research on air samples taken in the operating theatres environment in the hospitals of Umbria to control in order the concentration of anaesthetics in use and to define ambient pollution and to propose changes. The A.A. have divided operating theatres in for groups to analyze the data: 1) operating theatres where there were both systems: air change system and air intake system; 2) operating theatres where there was only the air-change system; 3) operating theatres where there was only the air intake system; 4) operating theatres where there were no systems. These data have been compared with the limit values advised by N.I.O.S.H. The lowest value of pollution have been recorded in those operating theatres with both systems. The A.A. have also compared the ethrane or other alogenated anaesthetics values in the air-change system equipped operating theatres with those (values) found in the intake-air system equipped operating theatres. The lowest values have been recorded in those operating theatres with normal air-change system. Where changes have been made to improve the operating theatres environment, the A.A. have effectuated new controls and found lower values of the anaesthetics levels. The concentration of anaesthetics appeared lower then before.

The authors, in view of the continuously changing contagious diseases outline, deal with the problem of a better qualification and reorganization of the direct interventions in the contagious diseases prophylaxis. In this respect, the authors deem that the reporting of the cases must assume a primary importance and that all the locally operating health and social services, where the general medicine practitioners have an integrating part, ought to be redefined in their tasks and reorganized in view of the new outlines. So, it is necessary to found a more flexible reporting system. A bidirectional information flux model is also proposed between the public health-services and the general medicine practitioners.