[Cancer figures in Italy: an overview]. / Panoramica sui numeri del cancro in Italia.

BACKGROUND: the description of the geographical distribution and temporal trends of cancer is relevant for prevention and improving the quality of care. This is primarily achieved through the incidence measures derived from population cancer registries (CRs). In recent years, in Italy there has been a prevalence of 'real-time' estimates and projections, although based on rather dated data. Given the significant increase in registration activity and still in absence of a national cancer registry network, the recent publication of Volume 12 of Cancer Incidence in Five Continents (CI5) provides a valuable opportunity to update cancer incidence estimates in Italy and to provide national and macroarea reference estimates. OBJECTIVES: to explore the pattern of cancer in Italy by reviewing and reorganizing the most recent data from cancer registries. MATERIALS AND METHODS: data from Italian cancer registries included in CI5 for the years 2013-2017 were obtained. Populations were verified, corrected for errors, and normalized to Italian National census reconstruction. The completeness of CR data was assessed using the mortality/incidence ratio applied to potential outlier data. Age-specific rates, Age standardized rates (ASRs), and truncated rates for adults (35-64 years) were calculated for 79 different neoplasms. Analyses were performed for individual CRs and macroareas. Temporal comparisons were made for 23 CRs with data from 2008-2012. RESULTS: the observed incidence rates show extreme heterogeneity. Among males, the overall ASR ranges from 584 per 100,000 in the province of Reggio Calabria to 809.9 per 100,000 in the province of Sondrio. Among women, ASR is highest in Emilia-Romagna (540.5) and lowest in the province of Avellino (409.9). The gradient with decreasing rates from North to South is clearly visible only for female breast cancer. Higher rates of lung cancer are observed for the city of Naples in both genders. In adult males (35-64 years), ASRs of lung cancer are maximum in the provinces of Caserta and Naples, where they are more than double the ASRs observed in the Veneto Region. In general, a significant decline in male ASRs is observed in Northern Italy compared to the previous five-year period. A significant part of this trend is influenced by lung cancer that is significantly decreasing throughout the Centre-North among men and substantially increasing among women. The database and tables with details of all calculated indicators are provided as supplementary material. CONCLUSIONS: the analysis has shown the importance of a review of real CR data and, in general, working with real data to not only develop specific estimates of cancers in Italy, but also to share reference rates and basic data for further analysis. The present review has also revealed critical issues with data submitted to the IARC. The comparison and verification of data quality through control and audit processes must represent a concrete operational perspective of the national cancer registry network. From the perspective of cancer epidemiology, important indications emerge regarding the distribution of cancers that can fuel aetiological research, as well as the planning of prevention and care activities. The data also show that it is advisable to separate the provinces of Caserta and Naples from the South in estimation and projection models. The comparison and verification of data quality through control and audit processes must represent a concrete operational perspective of the national cancer registry network.

COVID-19 in liver transplant recipients: incidence, hospitalization and outcome in an Italian prospective double-centre study.

Liver transplant (LT) recipients are vulnerable to SARS-CoV-2-infection (COVID-19), due to immunosuppression and comorbidities. This study aimed to evaluate the impact of COVID-19 on LT recipients compared to general population in the Campania region. In this prospective double-centre study, we enrolled all consecutive adult LT recipients with confirmed SARS-CoV-2-infection. Data were collected at diagnosis of COVID-19 and during follow-up and compared with the regional population. Thirty LT recipients (3.28%) developed SARS-CoV-2-infection (76.66% male, median age 62.61 years). Sixteen (53.33%) were symptomatic. Common symptoms were fever, cough, fatigue, and anosmia. Twenty-five (83.33%) were outpatients, 5 (16.66%) required hospitalization (6.66% admitted to Intensive Care Unit, 6.62% developed Acute Respiratory Distress Syndrome and 6.66% died). Immunosuppressors were in 3 (10%) patients. Incidence rate of COVID-19 was similar between LT patients and general population (3.28% vs 4.37%, p = 0.142) with higher rate of symptoms in LT patients (53.33% vs 15.87%, p < 0.000). At univariate analysis, hospitalization and case fatality rates were higher in LT patients compared to general population (16.66% vs 4.54%, p = 0.001; and 6.66% vs 1.76%, p = 0.041, respectively). At multivariable logistic regression analysis, LT patients with COVID-19 were more frequently symptomatic (OR 5.447 [95% CI 2.437-12.177], p < 0.000), whereas hospitalization and death for COVID-19 were not significatively associated with LT condition (p = 0.724 and p = 0.462, respectively) and were comparable with general population. LT is not a risk factor for acquiring COVID-19. Nonetheless, LT patients are more frequently symptomatic, although comparable to the general population for hospitalization rate and mortality.

Effects of deployment of electric vehicles on air quality in the urban area of Turin (Italy).

This study aims to evaluate and quantify the environmental, health, and economic benefits due to the penetration of electric vehicles in the fleet composition by replacing conventional vehicles in an urban area. This study has been performed for the city of Turin, where road transport represents one of the main primary emission sources. Air pollution data were evaluated by ADMS-Roads, the flow traffic data used for simulation come from a real-time monitoring. Instead, statistics on mortality and hospitalizations due to cardiovascular and respiratory diseases were collected from the regional health information system and the National Health Institute and implemented in the BenMap software to evaluate the health and economic impacts. In both cases, two scenarios to evaluate the annual benefits of reducing PM10, PM2.5 and NO2 were used: reduction to the levels gained by the assumptions of 2025 and 2030 Scenario and the PM10, PM2.5 and NO2 concentrations were considered for evaluating short-term and long-term effects. The analysis performed doesn't include background pollution levels, i.e. the concentrations percentage reductions are only related to the local contribution, therefore derived from the contribution only of traffic source. The results show that fleet electrification has a potential benefit for concentrations reduction in comparison to the base Scenario, especially related to NO2, less for PM10 and PM2.5. Regarding 2025 Scenario (4 % (passenger car) and 5 % (light-duty vehicles) electric vehicles), reductions of 52 % of NO2, 35 % of PM10 and 49 % of PM2.5 are observed. Meanwhile, as regards 2030 Scenario reductions of 87 % of NO2, 36 % of PM10 and 50 % of PM2.5 are reached. Also, in terms of social costs a decrease of 47 % for the 2025 Scenario and 66 % for the 2030 Scenario in comparison to the base Scenario is arise.

Evaluation of a method based on coherence in aqueous systems and resonance-based isotherapeutic remedy in the treatment of chronic psoriasis vulgaris.

Psoriasis is a chronic skin disorder that exhibits three main features: lymphocytic infiltration into the dermis and epidermis, uncontrolled proliferation and abnormal differentiation of keratinocytes. In this study we have evaluated the effect of treatment with WHITE Holographic Bioresonance Method and a resonance-based isotherapeutic remedy on patients affected by chronic psoriasis vulgaris. The WHITE Holographic Bioresonance Method is based on the principles of electrodynamic coherence. By exploiting the phenomenon of bio-resonance, it uses a transfer plate to produce resonance- and light-based isotherapeutic coherent acqueous remedies and gels that emit coherent oscillations which "imprint" the area of psoriasis-affected skin. Levels of proinflammatory cytokines have been evaluated in the plasma of psoriatic patients treated with isotherapeutic remedies. The obtained results demonstrate a positive effect on the natural course of the disease and matched the results obtained by psoriatic patients treated with narrow band UVB. A significant reduction in plasma levels of cytokines involved in pathogenesis of psoriasis has been observed. Our findings may suggest that WHITE Holographic Bioresonance method used in combination with resonance-based isotherapeutic remedy could well be a new useful treatment option for patients with limited psoriatic plaques.

Mesothelioma incidence in the neighbourhood of an asbestos-cement plant located in a national priority contaminated site.

BACKGROUND: An epidemic of asbestos-related disease is ongoing in most industrialized countries, mainly attributable to past occupational exposure but partly due to environmental exposure. In this perspective, the incidence of pleural mesothelioma close to a former asbestos-cement plant in a national contaminated site was estimated. METHODS: The census-tracts interested by atmospheric dispersion of facilities in the contaminated site were identified. Two subareas with different estimated environmental asbestos impact were distinguished. An ecological study at micro-geographic level was performed. The standardized incidence ratios (SIR) for study area and the two subareas, in comparison with region and municipality were computed. The standardized incidence rate ratio (IRR) between the two subareas was computed. RESULTS: Mesothelioma incidence in the study area was increased: 46 cases were observed with respect to 22.23 expected (SIR: 2.02). The increase was confirmed in analysis considering only the subjects without an occupationally exposure to asbestos: 19 cases among men (SIR = 2.48; 95% CI: 1.49-3.88); 11 case among women (SIR = 1.34; 95% CI: 0.67-2.40). The IRR between the two subareas is less than one in overall population considering all age-classes and of 3 fold (IRR = 3.14, 95% CI: 0.65-9.17) in the age-classes below 55 years. CONCLUSIONS: The findings indicate an increased incidence of pleural mesothelioma in the neighbourhood of asbestos-cement plant, and a possible etiological contribution of asbestos environmental exposure in detected risks.

Alterations of skin innate immunity in lymphedematous limbs: Correlations with opportunistic diseases.

Lymphedematous areas are sites of regional immune destabilization depicting a typical example of an immunocompromised cutaneous district (ICD). This study evaluates the expression of some components of the skin innate immunity on lymphedematous limbs with the aim to clarify some facets of the ICD. Patients selected underwent two skin biopsies: One was obtained from the limb affected by lymphedema, another from the contralateral healthy limb. Expression of some components of the skin innate immunity was analyzed by reverse transcription-polymerase chain reaction. Stronger gene expression of Toll-like receptor 2 (TLR-2), human ß-defensin 2 (HBD-2), desmoglein 1, desmoglein 3, matrix metallopeptidase 9 (MMP-9), and interleukin 10 (IL-10) was found in keratinocytes derived from the affected limb compared with that of keratinocytes derived from contralateral healthy limb. Downregulation of survivin and vasoactive intestinal polypeptide (VIP) gene expression was found in the affected limbs. No induction of IL-1α and tumor necrosis factor α (TNF-α) was detectable in keratinocyte cultures obtained from both lymphedematous and normal limbs. Different phases and components of skin innate immunity turned out to be altered in the lymphedematous sites. Molecular alterations were similar in all patients recruited in the study. These changes might favor the local appearance or progression of opportunistic diseases such as tumors, infections, and immune-mediated skin disorders.

AlphaVBeta5 integrins mediates Pseudomonas fluorescens interaction with A549 cells

Interaction of pathogenic bacteria with human cells is usually an essential step in the infection process. The bacterial invasion is stimulated by microbial binding to mammalian extracellular matrix proteins such as vitronectin, fibronectin or integrins. We have recently shown that some strains isolated from a clinical environment are able to grow at/or above 37°C. In particular, we demonstrated that P. fluorescens AF181 binds specifically to the surface of A549 human respiratory epithelial cells and that adhesiveness modulates the inflammatory response. In this study, the involvement of Alpha(v)Beta5 integrins and its respective natural ligand vitronectin (VN) in P. fluorescens AF181 adherence and invasion was examined. The host cell cytoskeleton and cellular tyrosine kinases seem to be solicited during the P. fluorescens-respiratory cell interaction; consequently, cytochalasin D and genistein decreased the bacterial adherence and internalization. Gene silencing of α(v), ß5 integrins and vitronectin reduced P. fluorescens adherence and internalization to A549 cells. Taken together, these findings suggest that Alpha(v)Beta5 integrins and their natural ligand VN are involved in P. fluorescens adherence and invasion in human epithelial cells.

Polydatin, a natural precursor of resveratrol, induces ß-defensin production and reduces inflammatory response.

It is well known that human keratinocytes produce the anti-microbial peptide ß-defensin 2. Its production is enhanced by pathogenic microorganisms or other environmental stressors. In this study, we evaluated the effect of resveratrol, a polyphenol found in several dietary source as grape seed, and its natural precursor, polydatin on heat-stressed human keratinocytes. By reverse transcription-polymerase chain reaction and enzyme-linked immunoadsorbent assay, we demonstrated that resveratrol used in combination with polydatin was able to modulate interleukin (IL)-6, IL-8 and tumor necrosis factor-alpha gene expression. In addition, our data show that resveratrol and polydatin increased the heat shock protein (Hsp)70B' gene expression, a Hsp that plays an important role in the cytoprotection and repair of cells and tissues. Worthy of note, polydatin used alone or in combination with resveratrol, increased the release of human ß-defensin 2. These results highlighted the ability of polydatin and resveratrol to reinforce cytoprotective response in stress conditions and suggest their use in cosmetic or pharmaceutical preparations.

pEGFR-Tyr 845 expression as prognostic factors in oral squamous cell carcinoma: a tissue-microarray study with clinic-pathological correlations.

The EGFR (epidermal growth factor receptor) a member of the family of transmembrane protein kinase receptors known as the erbB family shows a significant correlation with the presence of metastases and poorly differentiated oral cancer. Aim of the present work is to define the key-role of EGFR in oral cancer prognosis. We have analyzed the EGFR expression on 149 cases of oral squamous cell cancers (OSCC) and we have found that it was poorly expressed in normal oral epithelium, but its expression was significantly increased in OSCCs. Moreover, we have recorded that both pEGFR-Tyr 845 and pEGFR-Tyr 1068 were mainly distributed in high histological grading and in advanced stages. Western blotting has confirmed the total absence of EGFR phosphorylation in normal oral epithelium and the higher level of protein phosphorylation in representative cases of OSCCs. The EGF-R amplification was found by fluorescence in situ hybridization (FISH) in 14% of OSCC; interestingly, EGF-R amplification was mainly observed in OSCC with higher histological grading (G2 and G3) and advanced stage (pT4) sub-groups. Kaplan-Meyer survival analysis suggested that patients with positive pEGFR-Tyr 845 tumors had a worse prognosis and were bad responders to chemotherapy. These results confirm the central role of EGF-R activation status as a prognostic biomarker in OSCC.

Dynamic clustering detection through multi-valued descriptors of dermoscopic images.

This paper introduces a dynamic clustering methodology based on multi-valued descriptors of dermoscopic images. The main idea is to support medical diagnosis to decide if pigmented skin lesions belonging to an uncertain set are nearer to malignant melanoma or to benign nevi. Melanoma is the most deadly skin cancer, and early diagnosis is a current challenge for clinicians. Most data analysis algorithms for skin lesions discrimination focus on segmentation and extraction of features of categorical or numerical type. As an alternative approach, this paper introduces two new concepts: first, it considers multi-valued data that scalar variables not only describe but also intervals or histogram variables; second, it introduces a dynamic clustering method based on Wasserstein distance to compare multi-valued data. The overall strategy of analysis can be summarized into the following steps: first, a segmentation of dermoscopic images allows to identify a set of multi-valued descriptors; second, we performed a discriminant analysis on a set of images where there is an a priori classification so that it is possible to detect which features discriminate the benign and malignant lesions; and third, we performed the proposed dynamic clustering method on the uncertain cases, which need to be associated to one of the two previously mentioned groups. Results based on clinical data show that the grading of specific descriptors associated to dermoscopic characteristics provides a novel way to characterize uncertain lesions that can help the dermatologist's diagnosis.

Captopril modulates acetylcholinesterase in human keratinocytes.

Human keratinocytes synthesize and secrete non-neuronal acetylcholine, which acts as a local cell signaling molecule, regulating functions like proliferation, cell adhesion, motility, desmosomal cell contact, and glandular activity. The keratinocyte acetylcholine axis is composed of the enzymes mediating acetylcholine synthesis (acetyltransferase) and degradation (acetylcholinesterase), and two classes of acetylcholine receptors. In this study we investigated the effect of captopril, an ACE-inhibitor, on acetylcholinesterase and acetylcholine secretion in human keratinocytes. We analyzed the level of acetylcholinesterase in HaCat and NHEK cells by RT-PCR and Western blotting analysis. In addition, the effect of captopril on AChE activity was evaluated. We found that captopril induces a strong AChE up-regulation leading to ACh degradation and reduced secretion. Our results suggest that acantholysis induced by ACE-inhibitors might be linked to altered level of Ach.

Anti-inflammatory effects of moxifloxacin and human beta-defensin 2 association in human lung epithelial cell line (A549) stimulated with lipopolysaccharide.

Epithelia in the human airways, from the nasal aperture to the alveoli, are covered in a protective film of fluid containing a number of antimicrobial proteins. Defensins are single-chain, strongly cationic peptides and are one of the most extensively studied classes of antimicrobial peptides. Moxifloxacin (MXF) is a fluoroquinolone that acts against both Gram positive and Gram negative bacteria. In this study, we evaluated the effects of HBD2, MXF and the association MXF/HBD2 on some cytokines and on the ICAM-1 expression in LPS-stimulated A549 cells. Our results suggest that by lowering the epithelial cell-derived IL-1beta, IL-6, IL-8 and ICAM-1 expression, the MXF/HBD2 association interferes with the multifunctional cytokine network evolving during inflammatory processes of the respiratory tract; this anti-inflammatory potential could be of great value in the treatment of inflammatory disorders.

Effects of AV119, a natural sugar from avocado, on Malassezia furfur invasiveness and on the expression of HBD-2 and cytokines in human keratinocytes.

AV119 is a patented blend of two sugars from avocado that can induce human beta-defensin-2 production by normal human keratinocytes. In this study, we analysed the effect of AV119 on growth and invasiveness of Malassezia furfur, a dimorphic, lipid-dependent yeast that is part of the normal human cutaneous commensal flora. The ability to modulate the expression of the proinflammatory and immunomodulatory cytokines in normal human keratinocytes was also investigated. Microbiological assay demonstrated that this sugar induced the aggregation of yeast cells and inhibited the invasiveness of M. furfur, without affecting its growth. Real-time PCR analysis demonstrated that AV119 was able to modulate the HBD-2 response in treated keratinocytes, reaching a maximum after 48-h treatment, and to induce the recovery of a satisfactory proinflammatory response in human keratinocytes. As AV119 can induce aggregation of yeast cells, thus inhibiting their penetration into the keratinocytes, the sugar could be used in the preparation of cosmetics or pharmacological drugs to inhibit colonization of the skin by pathogenic strains of M. furfur.

3-O-methylfunicone produced by penicillium pinophilum affects cell motility of breast cancer cells, downregulating alphavbeta5 integrin and inhibiting metalloproteinase-9 secretion.

Recent evidence assigns integrins and metalloproteinases (MMPs) an important role in regulating tumor cell progression. Here, we demonstrate that 3-O-methylfunicone (OMF), a secondary metabolite produced by Penicillium pinophilum, affects cell proliferation and motility of breast cancer MCF-7 cells, downregulating alphavbeta5 integrin, and inhibiting MMP-9 secretion. This effect was absent when the non-tumoral MCF-10 cell line was used. Inhibition of cell motility was also associated to modifications in cell shape and in the distribution of tubulin fibers of OMF-treated MCF-7 cells. In addition, a possible effect on survivin and hTERT was also investigated. We found that OMF strongly inhibits survivin and hTERT gene expression. The results of this study indicate that OMF-induced inhibition of cell motility may be mediated through the modulation of alphavbeta5 integrin and MMP-9 secretion. In addition, the inhibition of typical markers of tumor progression such as hTERT and survivin in MCF-7 and their inactivity towards MCF10 provide strong evidence for a potential use of OMF in anticancer therapy.