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Most studies focused on species coexistence have been directed at the differential use of habitat and food resources; nonetheless, the differential use of the diel cycle may enhance the coexistence of same-sized species. We investigated the activity patterns of mesocarnivores (red fox (Vulpes vulpes), European badger (Meles meles), pine marten (Martes martes), stone marten (M. foina)) in NW Italy via camera-trapping. We hypothesized that the smallest species would tend to avoid competition by selecting time periods when larger species were less active. Foxes, badgers, and stone martens were mainly nocturnal. In lowland areas overlap between coexisting species was generally low, while in Mediterranean habitats all activity patterns tended to be unimodal and overlap was generally high. The pine marten showed a cathemeral pattern. We suggest that the lower ability of the stone marten to avoid interference competition at community-level may play a major role in determining its widespread exclusion from forested areas by the pine marten. [ABSTRACT FROM AUTHOR]

The occurrence of iridoid glycosides in a number of Cymbalaria spp. collected in Italy is shown and chemo-systematic implications are discussed. [ABSTRACT FROM AUTHOR]

Abstract: The Italian Bone Marrow Donor Register is the institutional organization for management of unrelated hematopoietic stem cell donors. The law requires only a donor''s clinical history, but not a psychosocial profile for registration. We have studied the donor''s motivation for enlistment on the donor registry and the medical staff''s need for this information to interact correctly with the donor. For this purpose we distributed a questionnaire to new donors at the 20 centers in the Lombardy Region over a period of 1 year. The analysis of the responses revealed a prevalence of extrinsic motivations that would not ensure continued registration for donation. Therefore, it is necessary that the donor be well informed and better educated about all aspects of donation, in order to produce a shift to an intrinsic motivation. This objective can be facilitated via professional training of health workers in communication. [Copyright &y& Elsevier]

In this paper, the first phytochemical analysis of the ethanolic extract of Daphne sericea Vahl flowering aerial parts collected in Italy and its biological activities were reported. Eleven compounds were identified i.e., α-linolenic acid ( 1 ), tri-linoleoyl- sn -glycerol ( 2 ), pheophorbide a ethyl ester ( 3 ), pilloin ( 4 ), sinensetin ( 5 ), yuanhuanin ( 6 ), rutamontine ( 7 ), syringin ( 8 ), p -coumaric acid ( 9 ), p -anisic acid ( 10 ) and caffeic acid ( 11 ). To the best of our knowledge, compounds ( 1 - 4 , 7-8 and 10 ) were isolated from D. sericea for the first time during this work, whereas sinensetin ( 5 ) represents a newly identified component of the entire Thymelaeaceae family. The extract was found to possess radical scavenging against both DPPH • and 2,2'-azino- bis (3-thylbenzothiazoline-6-sulfonic acid (ABTS •+ ) radicals, with at least a 40-fold higher potency against the latter. Moreover, chelating abilities against both ferrous and ferric ions have been highlighted, thus suggesting a possible indirect antioxidant power of the extract. Although the precise bioactive compounds remain to be discovered, the polyphenolic constituents, including phenolic acids, tannins and flavonoids, seem to contribute to the antioxidant power of the phytocomplex. In addition, the extract produced cytotoxic effects in MDA-MB-231 and U87-MG cancer cell lines, especially at the concentration of 625 μg/mL and after 48-72 h. Further studies are required to clarify the contribution of the identified compounds in the bioactivities of the extract and to support possible future applications.

Despite its uniqueness, the Bargellini multicomponent reaction remains barely known by the most part of chemists. This can be ascribed to the fact that this transformation has not been adequately reviewed in the classic books of named reactions in organic chemistry. Nevertheless, several works on this reaction have been carried out over the years, many of them were written in Italian in the period 1929-1966. In this review article we extensively cover, in a chronological order, the most important applications of the Bargellini reaction reported to date, with the hope that this knowledge-sharing will help chemists to properly use this multicomponent transformation and imagine novel reactivities based on it.

Aging is a risk factor for the development of multiple chronic diseases, including cardiovascular disease, cancer and dementia. Life expectancy has increased in certain countries but this phenomenon is associated with a reduction of years of healthy life. Aging is associated with a number of physical and functional changes, especially sarcopenia. Sarcopenia is a clinical condition associated with a decrease in skeletal muscle and muscle strength, however, sarcopenia is a reversible condition. On the basis of the current scientific literature, sarcopenia could more appropriately capture an individual's vulnerability to negative health-related outcomes since it represents an early form of the chronic diseases. Recognition of this clinical condition can improve the management of older individuals in many different clinical settings. Despite the limitations of the indirect methods used to study body composition, the Italian College of the Academic Nutritionists ME/49 recommends that health authorities and health professionals around the world should make a greater effort to diagnose sarcopenia earlier and to manage it more effectively. In line with the development of cancer screening, the use of two diagnostic tools for sarcopenia (BIA and DXA) should be implemented.

Background: The European guidelines for quality assurance in colorectal cancer (CRC) screening recommend that interval cancer rate be expressed as a proportion of background incidence rate., Aim: To determine the crude and adjusted proportional incidence of interval CRC in an Italian regional two-yearly faecal immunochemical test (FIT) screening programme., Methods: The programme (year of implementation, 2005) is targeted at over 1,000,000 people aged 50-69 years. The test is a one-sample OC-Sensor (Eiken Chemical Co., Tokyo, Japan). The study covered one-third of the regional area. Excerpts of 434,295 eligible negative FIT records dated 2005-2012 from 193,193 subjects were retrieved from the regional CRC screening data warehouse. By 31 December 2013, the cohort accumulated 198,302 man-years and 235,370 woman-years. Interval CRCs were identified by record-linkage with the local population-based cancer registry. Their number was divided by the expected number, estimated with age-period-cohort models, to obtain the proportional incidence., Results: The proportional incidence of interval CRC for men and women was, respectively, 0.06 (95% confidence interval (CI), 0.04-0.09) and 0.17 (95% CI, 0.13-0.23) in the first interval year, and 0.21 (95% CI, 0.16-0.26) and 0.28 (95% CI, 0.22-0.36) in the second year., Conclusions: The results were acceptable and in line with previous studies., (Copyright © 2020 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

The meadow froghopper, Philaenus spumarius L., is endemic in Italy and was not considered a harmful species until 2014, when the olive quick decline syndrome (OQDS) showed up in Apulia (southern Italy). It was immediately suspected and then verified as the main vector of Xylella fastidiosa, the bacterium responsible for the disease. Currently, EU Directives consider the fight against P. spumarius compulsory in member states and recommend Integrated Pest Management (IPM), both in uncultivated and cultivated infested areas, to minimise the environmental impact of chemical pesticides. This should be based on an improved knowledge of the vector with its seasonal trends and feeding habits linked to specific herbaceous species. In this context, our field study was aimed to improve the understanding of the vector nutritional behaviour, especially at its critical nymph stage, by monitoring its presence on different herbaceous target species, using its typical feeding foams as key indicator. The study area was in Lazio region (central Italy), dedicated to olive growing and still unaffected by the X. fastidiosa plague. Over two years, during the nymph development period, field data have been acquired over the test area and then analysed by coupling statistical (ANOVA), geographical information system (GIS) and geo-referenced field sampling approaches. Results highlighted that P. spumarius exhibits significant preferences for specific herbaceous plants, especially at its early development stages, detectable by tenuous spittle. This indicates female oviposition activity, which seems also not influenced by olive tree proximity. Furthermore, the non-host plant species identified here could be suitable for creating green barriers for limiting the vector diffusion to contiguous areas where sensible plantations are growing. In the final section, applied implications arising from the present findings for P. spumarius population management are discussed.

An undescribed labdane-like diterpene with a rare spiro-β-lactone function was identified from the ethanol extract of the male cones of the coniferous tree Wollemia nobilis. This spirolabdadienolide (IUPAC name: syn-ent-8(17),13-labdadien-19,18-olid-15-oic acid methyl ester; trivial name: wollemolide), was isolated by means of traditional and high performance chromatography techniques and structurally elucidated through NMR and MS. In addition, six further known metabolites were evidenced in the extract. Wollemolide, which may be considered an additional chemotaxonomic marker, and 4'-O-methyl-scutellarein, a simple flavonoid, had not been isolated in our previous phytochemical study on the same plant organ. This demonstrates how the molecular pattern of a plant species is in continuous movement and changes with the passing of time according to the climate of the year., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: The objective of this study was to evaluate if mammography screening attendance is associated with a reduction in late-stage breast cancer incidence., Methods: The cohort included over 400,000 Italian women who were first invited to participate in regional screening programmes during the 1990s and were followed for breast cancer incidence for 13 years. We obtained individual data on their exposure to screening and correlated this with total and stage-specific breast cancer incidence. Socio-economic status and pre-screening incidence data were used to assess the presence of self-selection bias., Results: Overall, screening attendance was associated with a 10% excess risk of in situ and invasive breast cancer (IRR = 1.10; 95% confidence interval (CI): 1.06-1.14), which dropped to 5% for invasive cancers only (IRR = 1.05; 95% CI: 1.01-1.09). There were significant reductions among attenders for specific cancer stages; we observed a 39% reduction for T2 or larger (IRR = 0.61; 95% CI: 0.57-0.66), 19% for node positives (IRR = 0.81; 95% CI: 0.76-0.86) and 28% for stage II and higher (IRR = 0.72; 95% CI: 0.68-0.76). Our data suggest that the presence of self-selection bias is limited and, overall, invited women experienced a 17% reduction of advanced cancers compared with pre-screening rates., Conclusions: Comparing attenders' and non-attenders' stage-specific breast cancer incidence, we have estimated that screening attendance is associated with a reduction of nearly 30% for stages II+., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

In this work, we examined a sample of Parentucellia viscosa from Sardinia island, showing similarities and differences of the secondary metabolite content with respect to previous study conducted on an accession of continental origin, and also with Bellardia trixago, a species very close to Parentucellia. In this aspect, the proximity between these species, previously stated by a phylogenetic study, was confirmed by a phytochemical approach. Within the non-iridoidic fraction a chiral polyol (mannitol) and two aromatic acids (benzoic acid and gallic acid) were evidenced. These two acids are not common in Scropulariaceae since they have been reported only from a few species, and it is worth to note that gallic acid was never reported from the Orobanchaceae family.

Background and Aims: Oxidative processes have been related to atherosclerosis, but there is scanty information on the role of dietary antioxidants in the prevention of acute myocardial infarction (AMI)., Methods and Results: The relationship between non-enzymatic antioxidant capacity (NEAC) and the risk of nonfatal AMI was investigated in a case-control study conducted in Milan, Italy, between 1995 and 2003. Cases were 760 patients below 75 years with a first episode of AMI and controls were 682 patients admitted to hospitals for acute conditions, who completed an interviewer-administered food frequency questionnaire, tested for validity and reproducibility. NEAC (excluding coffee) was measured using Italian food composition tables in terms of ferric reducing-antioxidant power (FRAP), Trolox equivalent antioxidant capacity (TEAC) and total radical-trapping antioxidant parameter (TRAP). The odds ratios (OR) of AMI, and the corresponding 95% confidence intervals (CI), were obtained by multiple logistic regression models including terms for main risk factors of AMI and total energy intake. NEAC was inversely related with the risk of AMI. The ORs for the highest quintile compared with the lowest one were 0.41 (95% CI, 0.27-0.63) for FRAP, 0.42 (95% CI, 0.27-0.65) for TEAC and 0.41 (95% CI, 0.27-0.62) for TRAP, with significant trends in risk. The inverse relationship was apparently stronger in women and in subjects aged ≥ 60 years., Conclusions: Our results support a favorable role of dietary NEAC in the prevention of AMI, and encourage a high consumption of fruit and vegetables and a moderate consumption of wine and whole cereals., (Copyright © 2014 Elsevier B.V. All rights reserved.)

A favorable role of fruit and vegetables on colorectal cancer risk has been related to the antioxidant properties of their components. We used data from an Italian case-control study including 1,953 patients with incident, histologically confirmed colorectal cancer (1,225 colon and 728 rectal cancers). Controls were 4,154 patients admitted to hospital for acute, non-neoplastic conditions. A reproducible and valid food frequency questionnaire was used to assess subjects' usual diet. Total antioxidant capacity (TAC) was measured using Italian food composition tables in terms of ferric reducing-antioxidant power (FRAP), Trolox equivalent antioxidant capacity (TEAC) and total radical-trapping antioxidant parameter (TRAP). We estimated the odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) through multiple logistic regression models, including terms for potential confounding factors, and energy intake. TAC was inversely related with colorectal cancer risk: the OR for the highest versus the lowest quintile was 0.68 (95% CI, 0.57-0.82) for FRAP, 0.69 (95% CI, 0.57-0.83) for TEAC and 0.69 (95% CI, 0.57-0.83) for TRAP. Corresponding values, excluding TAC deriving from coffee, were 0.75 (95% CI, 0.61-0.93) for FRAP, 0.76 (95% CI, 0.61-0.93) for TEAC and 0.71 (95% CI, 0.57-0.89) for TRAP. The inverse association was apparently-though not significantly-stronger for rectal than for colon cancer. This is the first case-control study indicating consistent inverse relations between dietary TAC and colorectal cancer risk., (Copyright © 2013 UICC.)

A three-dimensional numerical model is used to simulate the thermal destratification caused by hypolimnetic jets releasing oxygen-rich water for lake restoration. Focussing on the case study described in the companion paper (Toffolon et al., 2013), i.e. the small, relatively shallow Lake Serraia (Trentino, Italy), a specific simplified sub-grid model is developed in the numerical model to reproduce jet entrainment with reduced computational costs, with the aim to simulate the whole lake dynamics along several weeks. The noticeable agreement between numerical results and available measurements suggests that the model can be used to understand the main effects of the hypolimnetic oxygenation in different scenarios. Therefore, different options can be evaluated and guidelines can be proposed for lake management, with the aim to preserve the typical thermal stratification while providing sufficient oxygen mass to proceed with the restoration phase., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background/objectives: Antioxidant-rich foods may favorably influence lung function. We examined possible associations between the total dietary antioxidant capacity (TAC) and pulmonary function in a healthy Italian population., Subjects/methods: Until May 2009, 22,300 persons were randomly recruited from the general population in the Moli-sani project. A sample only including healthy women (5824) and men (5848) was analyzed. TAC was measured in foods by three different assays and the ferric reducing-antioxidant power (FRAP) assay was selected as the better indicator of dietary TAC. The European Investigation into Cancer and Nutrition Food Frequency Questionnaire was used for dietary assessment. The association between quintiles of dietary FRAP and pulmonary indexes was assessed using analysis of variance separately for men and women., Results: After adjustment for confounders, women in the highest quintile of FRAP intake had +39 ml forced expiratory volume in the first second (FEV(1)) and +54 ml forced vital capacity, compared with those in the lowest quintile (P for trend ≤0.006). Stratified analysis showed that this relationship only occurred in women who were premenopausal/never smokers. In this subgroup, the observed effect of higher FRAP intake on FEV(1) was equivalent to an improvement in pulmonary age of 3.3 years. In men, all significant associations between pulmonary function and TAC were lost after adjustment for confounding., Conclusions: Dietary TAC may have a favorable role in respiratory health, particularly in premenopausal/never smoker women.

Glaucium flavum collected in Sardinia was studied using a phytochemical approach in order to evaluate its alkaloid composition and obtain a comparison with the alkaloid contents of the same species in populations of other geographic proveniences. In fact, different chemoecotypes of G. flavum have been identified, on the basis of their particular content and composition in alkaloids, in accordance with the different distribution areas. The analysis showed that Sardinian G. flavum contains a homogeneous alkaloid pattern of aporphyne type, significantly different from those reported for populations from other parts of Europe.

In this article we examined the role of HLA incompatibility, of KIR C1 and C2 ligands and of other clinical factors on 99 cord blood transplants performed using single units from Milano Cord Blood Bank (MICB). We analyzed the occurrence of rejection, overall patient survival (OS) and occurrence of acute GvHD >or= 2 grade (severe aGvHD). No correlation was found between the end points and the number of HLA-A,-B, -DRB1 and -DQB1 mismatches. Only HLA-C disparities are associated with the occurrence of rejection (P=0.03). Our results showed that the presence of the C1 ligand in the donor decreased the occurrence of aGvHD (grade >or= 2) in the recipient while recipients of donors expressing the C2 KIR ligand experienced more frequently aGvHD (P=0.03). The HLA-C1 ligand, therefore, proved to have a protective effect towards severe aGvHD. The probability of rejection increased in KIR epitope-mismatched recipient/donor pairs (P=0.01). Finally the stage of disease at transplantation and cell dose were important for patient survival (P=0.003, P=0.048 respectively)., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Secondary metabolite isolation and analysis of Plumbago europaea L. (Plumbaginaceae) is the aim of this work, which is included in a project of our groups on spontaneous and endemic Sardinian species. Plumbago europaea is the only specie of the genera that grows wild in Italy. Metabolites from leaves and roots of this specie were compared. Moreover, at present, literature on the phytochemical characterisation of P. europaea is poor. Plumbagin was isolated in both of the samples analysed, confirming its nature in the Plumbaginaceae family as chemotaxonomic marker of the Plumbaginae tribe. In this work, hydroplumbagin-4-O-glucoside and myricetin-3-O-rhamnoside are isolated for the first time in the genus.

The phytochemical study of Euphrasia genargentea, a rare species only present in Sardinia, led to the identification of iridoid glucosides, i.e. aucubin, catalpol, mussaenosidic acid and melampyroside, which allowed chemotaxonomic considerations on the genus. On the basis of iridoid distribution in the genus, E. genargentea does not show any particular analogy with other Italian Euphrasia spp. This study is also important considering the severe risk of extinction of E. genargentea.

To assess the adequacy of a routine screening to identify cervical intraepithelial neoplasia 2 or worse (CIN2+) in women over 50 years of age, a retrospective cohort was set in six Italian organised population-based screening programmes. In all, 287 330 women (1 714 550 person-years of observation, 1110 cases) screened at age 25-64, with at least two cytological screening tests, the first negative, were followed from their first negative smear until a biopsy proven CIN2+ lesion or their last negative smear. For women aged 25-49 and 50-64 years, crude and age-standardised detection rate (DR), cumulative risk (CR), adjusted hazard risk for number of previous negative screens, probability of false-positive CIN2+ after two or more smear tests were calculated. Detection rate is significantly lower over 50 years of age. Multivariable analysis shows a significant protective effect from four screening episodes (DR=0.70, 95% CI: 0.51-0.97); the effect of age >or=50 is 0.29 (95% CI: 0.24-0.35). The CR of CIN2+ is at least eightfold higher in women <50 (CR=2.06, 95% CI: 1.88-2.23) after one previous negative test than in women >or=50 years with four screens (CR=0.23, 95% CI: 0.00-0.46). Over 50 years of age, after four tests at least three false-positive cases are diagnosed for every true positive. Benefits arising from cytological screening is uncertain in well-screened older women.

The monoterpenoid fractions of three endemic Galium ssp. (Rubiaceae) from Sardinia Island were examined and compared with the iridoidic pattern yet known in Galium species. This comparison evidenced theirs endemic characters. In particular, in G.corsicum and in G. glaucophyllum loganic acid was isolated and identified for the first time in Galium genus. In G. schmidii a rare iridoid is present, 10-hydroxy-loganin, whose presence in this genus was evidenced only in G. mollugo and loganin isolated for the first time.

We describe the isolation and characterization of two novel HLA-DRB1*11 alleles, officially named DRB1*1161 and 110404. These two new variants were both identified in two Caucasoid individuals. The exon 2 sequence of DRB1*1161 is identical to that of DRB1*110101 except at codon 41, where a nucleotide substitution (GAC>AAC) is responsible for an amino-acidic change from Asp to Asn. The exon 2 sequence of the second novel allele described here, DRB1*110404, differs from that of DRB1*110401 only at codon 34 where the nucleotidic change CAA>CAG gives rise to a silent mutation.

The iridoidic composition of Stachys glutinosa L. was examined in comparison with the results obtained in the phytochemical studies on S. corsica Pers. The presence of the known harpagide and acetyl-harpagide were showed together with that of a new di-glycosidic iridoid. The structure of this new compound, the 5-allosyloxy-aucubin, was demonstrated by comparison with the spectroscopical data of monomelittoside and of its 5-O-glucosyl-derivative, the melittoside. The presence of allose in Stachys genus seems to be a chemotaxonomical character.

In this work the iridoidic fraction of Teucrium marum from Sardinia, was examined. A new clerodane, teumarin B, was isolated and identified by 1H- and 13C-NMR spectra analysis. The endemic character of this plant was further confirmed. Teumarin B showed cytotoxic properties.

During our systematic study on the species of genus Linaria (Scrophulariaceae) present in Italy, we examined the glycosidic fraction of Linaria capraria Moris et De Not., a species endemic of Tuscany archipelago. This fraction is particularly complex and we considered in this article only the medium polarity components. In accordance with previous studies, L. capraria shows acyl derivatives of antirrhinoside 1 as specific chemotaxonomic iridoidic markers. L. capraria exhibits a complex composition, with regard to iridoidic constituents, with several chromatographic problems to be resolved. We then isolated, besides the known antirrhinoside 1, two acyl derivatives of antirrhinoside, the 6'-O-senecioyl derivative, 2, and the 6'-O-angeloyl derivative, 3. In addition a glucoside of an acyclic monoterpene, 4, was also isolated, which may be correlated to the other monoterpenic glycosides isolated from other species of Scrophulariaceae.

Epidemiologic studies have demonstrated an inverse association between consumption of fruits and vegetables and morbidity and mortality from degenerative diseases. The antioxidant content of fruits and vegetables may contribute to the protection they offer from disease. Because plant foods contain many different classes and types of antioxidants, knowledge of their total antioxidant capacity (TAC), which is the cumulative capacity of food components to scavenge free radicals, would be useful for epidemiologic purposes. To accomplish this, a variety of foods commonly consumed in Italy, including 34 vegetables, 30 fruits, 34 beverages and 6 vegetable oils, were analyzed using three different assays, i.e., Trolox equivalent antioxidant capacity (TEAC), total radical-trapping antioxidant parameter (TRAP) and ferric reducing-antioxidant power (FRAP). These assays, based on different chemical mechanisms, were selected to take into account the wide variety and range of action of antioxidant compounds present in actual foods. Among vegetables, spinach had the highest antioxidant capacity in the TEAC and FRAP assays followed by peppers, whereas asparagus had the greatest antioxidant capacity in the TRAP assay. Among fruits, the highest antioxidant activities were found in berries (i.e., blackberry, redcurrant and raspberry) regardless of the assay used. Among beverages, coffee had the greatest TAC, regardless of the method of preparation or analysis, followed by citrus juices, which exhibited the highest value among soft beverages. Finally, of the oils, soybean oil had the highest antioxidant capacity, followed by extra virgin olive oil, whereas peanut oil was less effective. Such data, coupled with an appropriate questionnaire to estimate antioxidant intake, will allow the investigation of the relation between dietary antioxidants and oxidative stress-induced diseases.

The availability of published data from organized cervical screening programmes in southern Europe is scant. In the Italian area of Romagna, a first round of organized screening (based on a 3-yearly Pap smear for women aged 25-64 years) was initiated between December 1995 and January 1997 and was completed in an average of 42 months (range 36-48 months). The target population included 305 478 women. Of these, 253 949 were eligible and received a personal letter of invitation. Age-specific screening performance indicators were calculated according to standard methods. The response rate within 6 months of invitation was 49.1% (n=124 621). The total participation rate including women who presented later was 61.7% (n=156 735). The recall rate was 35.2 per 1000 of participants (n=5514). Positive cytology results were distributed as follows: atypical squamous cells of un-determined significance/atypical glandular cells of undetermined significance (ASCUS/AGUS) 40.1%, low-grade squamous intraepithelial neoplasia (LGSIL) 48.6%, high-grade squamous intraepithelial neoplasia (HGSIL) 10.7% and carcinoma 0.7%. Compliance to colposcopy follow-up was 93.4% (n=5149). The biopsy rate was 52.4% (n=2696) of patients undergoing colposcopy. The detection rate was 4.5 per 1000 of participants (n=707) for CIN2-3 and 0.5 (n=75) for invasive carcinoma. The proportion of microinvasive carcinomas was 36.0% (n=27). The positive predictive value for CIN2-3/carcinoma was 5.8% for the cytology reports of ASCUS/AGUS, 7.6% for those of LGSIL, 76.5% for those of HGSIL, and 100.0% for those of carcinoma (80.4% for combined HGSIL/carcinoma). The ratio of observed to expected (or prevalent to incident) cases of invasive carcinoma was 2.35 (95% confidence interval (CI) 1.85-2.95). In conclusion, most early results of the programme were compatible with an acceptable performance.

The integration of routine Pap smear practice based on self-referral into an organized programme based on personal invitation is the recommended approach to cervical cancer screening. In this study, the cytology archive of the integrated cervical screening programme implemented in the Faenza district (northern Italy) was used to compare the population of women responding to invitation with that of self-referred women for the cumulative probability of early (< 36 months) repeat Pap smear after a negative result. Between 1995 and 1998, women aged 25-64 living in five municipalities of the district were targeted by the first round of the programme. Eligible for the study were 2356 women responding to invitation for screening and 2221 women not invited because of self-referral for Pap smear at any other setting. The probability of early repeat Pap smear was estimated by the life table method. Differences were evaluated by the Gehan test. Multivariate determinants were assessed by the Cox regression analysis. At 36 months' follow-up, the cumulative probability of early repeat Pap smear was 44% among self-referred women and 6% among women responding to invitation (relative hazard = 4.8). For self-referred women, the probability was related to age (with a peak at 35-44 years), previous Pap smear history and municipality of residence. Among women responding to invitation, only an inverse association with age was demonstrated. In conclusion, the observed differences in overall probability and determinants of early repeat Pap smear between the two screening populations provided important information on Pap smear usage in the total target population.

Background: The poor accuracy of the clinical examination of pigmented skin lesions (PSLs) is a major limitation of secondary prevention strategies for cutaneous melanoma (CMM). In the last few years, the epiluminescence microscopy (ELM) technique has been used increasingly as an adjunct to clinical examination in the dermatology practice. Although the question of training has emerged as a priority, the diffusion, the effects, and the correlates of educational programmes in ELM have seldom been studied., Methods: Thirty ELM images of PSLs (11 CMMs, 14 melanocytic nevi (MN), and 5 nonmelanocytic lesions (NMLs) each matched with the corresponding clinical or plain photographic image were independently diagnosed before and after a one-day workshop by 83 Italian dermatologists participating in a nationwide educational programme on ELM. The original histology diagnosis was assumed as a gold standard. The overall effect of training on a set of accuracy measures by PSL type was evaluated. The association of the professional sector (public/private), number of years of general experience in dermatology (1-10/>10), average weekly number of PSLs seen (< or =10/11-20/>20), routine use of ELM (no/yes), and area of residence (northern/southern Italy) with the mean number of PSLs correctly diagnosed before and after training was evaluated with the general factorial analysis of variance. The factors associated with improvement between the two tests were evaluated with the analysis of variance for repeated measures., Results: Compared with pretraining data, the average percentage of exact diagnosis increased significantly for all PSLs (CMMs, 72% vs 55%; MN, 68% vs 64%; NMLs, 67% vs 58%; total lesions combined, 69% vs 60%). Baseline as well as final accuracy were independent from the professional sector and the years of experience but were greater among those subjects who reported >20 PSLs per week compared with the reference group (< or =10 PSLs). The routine use of ELM was associated with a slight advantage in pretraining accuracy. The area of residence was the strongest determinant of baseline as well as final accuracy. The effect of training was independent from all factors studied with the exception of the area of residence with a 13% increase in the frequency of exact diagnosis in northern Italy (from 66-79%) and 6% in southern Italy (from 55-61%)., Conclusions: Though insufficient in absolute terms, a measurable increase in ELM accuracy can be achieved even with intense training sessions of short duration. Medical education to ELM in southern Italy should be a priority.

Background: Treatment of cervical intraepithelial neoplasia grade 3 (CIN3) is one of the most unexplored issues of the monitoring of cervical cancer screening. We evaluated (1) the frequency of major patterns of diagnosis and treatment of CIN3 (ICD-O code 8070.2), (2) the determinants of hysterectomy as a first choice treatment, and (3) the determinants of invasive cervical squamous carcinoma (CSC) detection among CIN3 cases treated by hysterectomy., Methods: A population-based, retrospective, descriptive (objective 1) and analytical (objectives 2 and 3) study was conducted by the Romagna Cancer Registry (Northern Italy). Included were 316 CIN3 patients (median age, 38.5 years; range, 21-80) registered between 1986 and 1993 and meeting one of the following eligibility criteria: histological diagnosis of CIN3 on biopsy with any subsequent treatment, histological diagnosis of CIN3 on conization, histological diagnosis of CIN3 on hysterectomy with previous negative/benign (< or = CIN2) biopsy or conization. Multivariate associations were evaluated by the multiple logistic regression., Results: Of 316 patients, 264 (84%) were first diagnosed on biopsy, 39 (12%) on conization, and 13 (4%) on hysterectomy. Among the 264 patients diagnosed on biopsy, the first choice treatment was local destructive therapy for 16 (6%), conization for 155 (59%) and hysterectomy for 93 (35%). Age was the strongest uni/multivariate predictor of hysterectomy (the most frequent first choice treatment >40 years) followed by adequacy of biopsy (inverse association) and place of treatment (decreased probability for patients treated outside the area and in the private sector). Among the 93 CIN3 patients undergoing hysterectomy, 23 (25%) had a CSC diagnosed. Multivariate analysis showed that the probability of CSC detection was related to adequacy of biopsy (inverse association), year of registration, and biopsy-to-treatment interval (inverse association)., Conclusion: Hysterectomy was a common treatment for patients with CIN3 on biopsy. Only in a minority of hysterectomized patients was a CSC diagnosed. Difficulties and inefficiencies in the biopsy and assessment procedure were found to be important factors in the management and outcome of CIN3 patients.

Aims and Background: The accuracy of epiluminescence microscopy (ELM) for pigmented skin lesions (PSLs) is still unclear. The large scale utilization of the technique is generally discouraged. The present study was aimed at comparing the accuracy of ELM with that of clinical examination alone in a group of 20 practical dermatologists., Methods and Study Design: Thirty digital clinical images of benign and malignant PSLs and their digital ELM counterparts were used. A set of cumulative accuracy measures reported in the combined clinical/ELM diagnosis was compared with that reported in the clinical diagnosis alone., Results: The proportion of nonmelanocytic lesions (NMLs), melanocytic nevi, and melanomas correctly identified, the predictive value of such diagnoses, and the proportion of melanomas detected by referral for biopsy (irrespective of the diagnosis reported) increased significantly. The cases referred for biopsy despite a "benign" impression decreased significantly among NMLs., Conclusions: The observed tendency towards a greater accuracy suggests that even in the routine dermatology practice ELM has the potential to improve the clinical examination of PSLs.

Patients diagnosed with CIN3 on biopsy without a Pap smear are an inevitable correlate of the extensive utilization of colposcopy as a basic screening test. In a series of 248 CIN3 cases diagnosed on biopsy and notified to the Romagna Cancer Registry between 1986 and 1993, we evaluated the independent association between the Pap smear result and (1) the final histology diagnosis, (2) the first choice treatment, and (3) the appropriateness of hysterectomy. The patients were grouped into the following categories: (1) no smear, ie colposcopy only (n = 40 or 16%), (2) CIN1, CIN2, LGSIL, and minor changes, (3) CIN3 and HGSIL, and (4) carcinoma. In multiple logistic regression analysis, patients without a Pap smear were used as a reference category. Patients with smears reported as CIN1-2/LGSIL or less as well as CIN3/HGSIL had a significantly lower probability of invasive squamous carcinoma (odds ratio = 0.26 for both categories) compared with those not undergoing cytology. The Pap smear result was not a determinant of the first choice treatment. Hysterectomy had a greater probability of being unnecessary if performed in patients with smears reported as showing CIN3/HGSIL (odds ratio = 5.05) or less. In conclusion, this registry-based study demonstrated that the Pap smear had an independent but neglected value in the assessment of cases reported as CIN3 on colposcopy-guided biopsy.

Aims and Background: In southern European countries, the availability of epidemiologic data on cutaneous malignant melanoma is limited. A descriptive analysis was performed on melanoma cases diagnosed in the Italian region of Romagna (population 600,000), 1986-91., Methods: The main end point was the proportion of cases less than 1.5 mm thick by sex, age, and site., Results: A total of 297 incident cases was evaluated. The average annual age-standardized (World) incidence rates were 6.2 (95% CI 5.2-7.2) per 100,000 females and 4.5 (95% CI 3.6-5.3) per 100,000 males. Females presented with significantly thinner melanomas than males. The proportion of cases less than 1.5 mm thick decreased significantly with increasing age in both sexes, with the most pronounced decrease (approximately from 2/3 to 1/3) being observed above 60 years for females and above 40 for males. Comparing sexes by 10-year age groups, a significant F:M advantage in thickness distribution was found only at age 40-49 and 50-59 years. Among females under 60, melanomas of the legs and those of the trunk showed no difference in thickness distribution. In both sexes, incidence appeared to increase progressively with age. No apparent elevation in incidence rates was observed in the age groups with the highest frequency of thin melanomas., Conclusions: The major implication of these data is that in public education programs specific messages should be aimed at those subgroups that show the poorest levels of self-surveillance.

Aims and Background: Fineneedle aspiration cytology (FNAC) is a routine test in the evaluation of breast lesions. We assessed the diagnostic accuracy of mammography (MG), physical examination (PE), ultrasonography (US) and FNAC in 1064 histologically confirmed breast lesions (638 malignant, 426 benign) observed consecutively at the Cancer Prevention Center of Ravenna (Italy)., Methods: The performance of each test and the additional contribution of FNAC were determined., Results: FNAC was done in 69.6% of cancers and 39.7% of benign lesions (P = 0.00000), the frequency of aspiration being significantly associated with severity at MG, PE, and US. For FNAC, the true positive rate was 95.1% and the true negative rate 67.4%. Only one breast cancer case was detected by FNAC alone (additional true positive rate 0.2%). The positive predictive value of FNAC in the absence of other abnormalities was 5%. The negative predictive value of a benign report at MG, PE, US and FNAC was 100%., Conclusions: All breast lesions should be evaluated by all available techniques, especially FNAC, and open biopsy should be avoided for those reported as benign at all tests.

Cytologic and colposcopic histories of cases of invasive cervical cancer and cervical intraepithelial neoplasia grade III (CIN III) registered in Ravenna (northern Italy) between 1986 and 1990 were evaluated. During the 5 years prior to diagnosis, 10/49 invasive cancer patients and 25/61 CIN III patients had had at least one pap smear reported as negative. At the time of the most recent false-negative report, 9/10 and 17/25 of these cases had been recommended for a repeat smear within 2 to 6 months. Of the 9 patients with invasive cancer, 5 had also undergone an inconclusive colposcopy (with biopsy unperformed). Among invasive cancer patients aged under 50, half of incident cases (7/14) and most of those with some cytologic experience (7/8) had had a false-negative report; each of these patients (7/7) had been recommended for an early repeat smear. For invasive cancer patients as well as for CIN III patients, the suggested intervals for the early repeat were largely exceeded. Median delay in diagnosis was about 2 years. Although the frequency of negative reports recommending repeat smears within a few months was estimated to be some 10% of total screening patients, current concepts in cervical cytology suggest that cancer cases with such false-negative reports should be regarded as follow-up failures rather than laboratory errors. In fact, they passed quite unnoticed. In unplanned (spontaneous) cervical screening practice, sensitivity needs to be maximized, but even the occurrence of false-negative cases is not monitored. The present study points out what may result from such a contradiction.

The distribution of Breslow's thickness by sex, age and site of 95 of the 103 cases of primary cutaneous malignant melanoma (CMM) diagnosed in 1981-1990 in the Ravenna Health District (a low-incidence area in northern Italy) was studied. The median patient age was 57 years. The median tumor thickness was 1.33 mm in females and 2.15 mm in males (two-tailed Wilcoxon rank sum test, p = 0.153). Significantly thinner lesions were found among women up to the median age than among men of the same age group (1.05 mm vs. 1.80 mm, p = 0.034) and older women (2.20 mm, p = 0.035). The difference between males aged under 57 years and older than 57 was not significant (1.80 mm vs. 2.20 mm, p = 0.828). As a consequence, younger women compared favorably with the rest of the population as a whole (2.20 mm, p = 0.011). No significant differences in site-specific median tumor thickness were found between the sexes or between young and older males, whereas CMMs of the legs among females were thinner in the younger age group (0.67 mm vs. 2.20 mm, p = 0.007). The prevalence of younger women in the recognition of early CMM was entirely accounted for by a substantial shift observed in the most recent 5-year period (from 2.40 mm to 0.70 mm, p = 0.006). Specific educational activities have never been carried out in Ravenna.