The BrAID study protocol: integration of machine learning and transcriptomics for brugada syndrome recognition.

BACKGROUND: Type 1 Brugada syndrome (BrS) is a hereditary arrhythmogenic disease showing peculiar electrocardiographic (ECG) patterns, characterized by ST-segment elevation in the right precordial leads, and risk of Sudden Cardiac Death (SCD). Furthermore, although various ECG patterns are described in the literature, different individual ECG may show high-grade variability, making the diagnosis problematic. The study aims to develop an innovative system for an accurate diagnosis of Type 1 BrS based on ECG pattern recognition by Machine Learning (ML) models and blood markers analysis trough transcriptomic techniques. METHODS: The study is structured in 3 parts: (a) a retrospective study, with the first cohort of 300 anonymized ECG obtained in already diagnosed Type 1 BrS (75 spontaneous, 150 suspected) and 75 from control patients, which will be processed by ML analysis for pattern recognition; (b) a prospective study, with a cohort of 11 patients with spontaneous Type 1 BrS, 11 with drug-induced Type 1 BrS, 11 suspected BrS but negative to Na + channel blockers administration, and 11 controls, enrolled for ECG ML analysis and blood collection for transcriptomics and microvesicles analysis; (c) a validation study, with the third cohort of 100 patients (35 spontaneous and 35 drug-induced BrS, 30 controls) for ML algorithm and biomarkers testing. DISCUSSION: The BrAID system will help clinicians improve the diagnosis of Type 1 BrS by using multiple information, reducing the time between ECG recording and final diagnosis, integrating clinical, biochemical and ECG information thus favoring a more effective use of available resources. Trial registration Clinical Trial.gov, NCT04641585. Registered 17 November 2020, https://clinicaltrials.gov/ct2/show/NCT04641585.

Correlation between viral load, plasma levels of CD4 - CD8 T lymphocytes and AIDS-related oral diseases: a multicentre study on 30 HIV+ children in the HAART era.

This experimental retrospective multicenter study carried out on 30 seropositive children treated with Highly Active Antiretroviral Therapy (HAART), between the ages of 18 months and 14 years, in the clinical categories Centers for Disease Control (CDC) classification 1993 A (mildly symptomatic), B (moderately symptomatic) and C (severely symptomatic) aims to: 1) clinically and immunologically demonstrate the therapeutic benefits of HAART; 2) monitor the frequency of AIDS-related oral diseases in seropositive children with HAART therapy; 3) monitor the plasma levels of total CD4, CD4 percent, CD8 percent, CD4-CD8 lymphocytes and viral load from 1997 to 30 April, 2011. The statistic methods used are the analysis of covariance and the Bonferroni Test. More than 100 AIDS-related oral diseases were found in the study samples, the most frequent being: oral candidiasis, oropharyngeal candidiasis, HSV-1 herpetic esophagyitis, herpetic gingivolstomatitis (RHOG), recurrent aphthous stomatitis (RAS), parotid swelling, oral hairy leukoplakia (OHL), Herpes simplex 1 (HSV-1), linear gingival erythema (LGE), necrotizing gingivitis (NUG), facial lipodistrophy, facial-cervical lymphadenopathy (FCL), xerostomia, dysgeusia, hyposmia, oral mucosa hyperpigmentation (OMP). The Bonferroni test showed a significant difference between the mean plasma values (mpVTL) of total CD4, CD4 percentage, CD4-CD8 T lymphocytes and Viral Load (VL) of the various oral diseases found in the study samples. The therapeutic benefits of HAART are: immune reconstitution; reduction of the HIV/AIDS-related stomatology diseases; prevention and cure of the AIDS correlated neoplasias; reduction in maternal-fetal transmission of the HIV virus. The negative effects of HAART in relation to odontostomatolgy are: increase in oral lesions from HPV; xerostomia; dysgeusia/ageusia, hyposmia, perioral paresthesia; hyperpigmentation of oral mucosa; facial lipodystrophy, recurrent aphthous stomatitis (RAS). No case of immune reconstitution inflammatory syndrome or human papillomavirus (HPV)-related oral diseases were found in this study.

Retrospective mortality cohort study of Italian workers compensated for silicosis.

OBJECTIVES: To estimate cause specific mortality in a large cohort of Italian workers compensated for silicosis. METHODS: The cohort included 14 929 subjects (14,098 men and 831 women) compensated for silicosis between 1946 and 1979, alive on 1 January 1980, and resident in Tuscany (a region of central Italy with 3,547,000 inhabitants). Mortality follow up ranged from 1980 to 1999. Vital status and the causes of death were determined by linkage with the regional mortality registry and with the national mortality database. The cohort mortality rates were compared to the rates of the local reference population. SMRs and their 95% confidence intervals were computed assuming a Poisson distribution of the observed deaths. Specific SMR analyses were performed according to the level of disability, the year of compensation assignment, and the job type. RESULTS: A significant excess mortality was observed in male silicotics for cancer of the lung, trachea, and bronchus and cancer of the liver, respiratory diseases (silicosis, asbestosis, antracosilicosis, and other pneumoconiosis), and for tubercolosis. Statistically significant mortality excess was observed in female silicotics for respiratory diseases (specifically silicosis and other pneumoconiosis) and tuberculosis. Analyses for period of compensation assignment showed a twofold increased SMR for biliary tract cancer among female workers and for liver cancer among male workers compensated before 1970. CONCLUSIONS: The excess mortality from respiratory tract cancers and respiratory tract diseases detected in Italian compensated silicotics are in agreement with previous epidemiological studies. Although the twofold increased risk for liver cancer among males is suggestive of a possible association with silica dust exposure, the finding needs to be confirmed.

[A monitoring system for occupational cancer]. / Un sistema di monitoraggio per i tumori di origine professionale.

INTRODUCTION: The Italian Occupation and Safety Act (d.lgs 626/94) provided for the establishment of a nationwide occupational cancer registry, under the National Institute for Occupational Health and Safety (ISPESL), with the aim of detecting cancer cases of occupational origin and estimating the influence of occupation in cancer causation. METHODS: Information on cancer cases, drawn from six Italian population-based cancer registries (CRs of Friuli Venezia Giulia Region, Genoa Town and Genoa Province, Macerata Town, Umbria Region, Varese Town, Veneto Region), and on a random sample of population controls selected in each CRs area were linked with data on subjects employed in private enterprises that have been available in electronic form since 1974 at the National Institute for Social Security (INPS). In this way, both for cases and controls, the occupational histories of past employment were collected. A population-based case-control study covering the period 1990-1998 was carried out with the aim of estimating occupational cancer risk in the private sector by site and economic category in each area. Since one of the major drawbacks of this approach is the difficulty in distinguishing true occupational hazards from incidental findings derived from multiple comparisons, an extensive research of occupational literature was carried out, independently of the study results, to compare our results with existing knowledge on occupational risks. RESULTS: Pooled analysis of the most recent incidence data based on 36,379 cases and 29,572 controls was performed; 34 "statistically significant" associations were found for 11 economic categories. Using our literature review, 10 associations were supported by more than 5 publishedpapers, 14 by a number of papers between 1 and 5, and 10 associations had not been previously reported. CONCLUSIONS: This system appears suitable for assessing existing occupational cancer risks and can eventually lead to detecting occupational hazards in many areas of Italy. The system can also provide a list of cases suitable for in-depth search for past occupational exposures.

[Registry of the Italian Institute for Occupational Prevention and Safety of local productive units: methodology and structure]. / L'anagrafe ISPESL delle unità locali produttive: metodologia e struttura.

The Italian Institute for Occupational Prevention and Safety (ISPESL) carried out a register of enterprises operating in industry, services and agriculture sector to provide information on their location, economical activity and occupational data. This database has been built merging administrative files from the National Institute of Social Security (INPS) and the Computer Science Society of Italian Chambers of Commerce (InfoCamere). Enterprises have been classified by economic sector - in accordance with ISTAT (National Statistics Institute) "Ateco91" classification--and by accuracy level of the record linkage. In details, three different subsystems have been set up: (A) enterprises satisfying linkage; (B) enterprises in InfoCamere file not linked with INPS file; (C) enterprises in INPS file not linked with InfoCamere file. In the whole, 6.026.676 factories have been collected, of which 1.188.784 in group A, 4.543.091 in group B and 294.801 in group C. Establishing a database of information on industries may be useful to improve preventive programs and to plan health care surveillance systems.

Epidemiologic surveillance for primary prevention of malignant mesothelioma: the Italian experience.

BACKGROUND: The Italian National Mesothelioma Registry (ReNaM) was set up at the National Institute for Occupational Safety and Health (ISPESL) to estimate Italian incidence of malignant mesothelioma (MM), define modalities of asbestos exposures, assess impact and diffusion of MM, identify underestimated sources of environmental contamination. OBJECTIVES: To describe ReNaM activity, database dimension and epidemiological characteristics of the caselist. METHODS: Regional Operating Centers (COR) in 16 Italian regions were set up to identify and investigate all cases of MM diagnosed in each region, applying national guidelines. COR collect cases in health care institutions. Occupational history, lifestyle and residence are obtained by direct interview using a standard questionnaire. Exposure modalities are classified by industrial hygienists, evaluating whether work, private life or any particular environmental condition could have involved asbestos exposure. RESULTS: Data refer to 3,446 cases collected in 9 Italian regions during 1993-2001. Pleural mesothelioma affected 94% cases, pleural/peritoneal ratio was 16:1. Gender ratio (M/F) was 2.7:1 (1.3:1 for peritoneum). There was a variety of occupational exposures, some already known as high risk sectors and others unexpected. The most common exposures occurred in building and construction, metallurgy and steel, shipbuilding, and railway stock. High risk categories were encountered such as bricklayers, plumbers, carpenters, electricians, welders, installers and maintenance workers in metallurgy and the steel industry, general labourers, tool makers and painters in shipbuilding/repair/demolition. CONCLUSIONS: Despite some ReNam's limitations, identification of MM cases and analysis of modality of exposure, with standardized criteria, are a fundamental tool for primary prevention of asbestos related diseases.

[Epidemiologic surveillance in occupational carcinogenesis]. / La sorveglianza epidemiologica in tema di cancerogenesi professionale.

Research on occupational cancer epidemiology has been an important area of occupational health in Italy. While according to epidemiological estimates the proportion of all cancers attributable to occupational factor is about 4%, the number of compensated occupational cancers in Italy is remarkably lower. Re.Na.M., OCCAM and ISOD projects are example of epidemiological surveillance and can serve as basis for ad hoc studies.

Analysis of survival of mesothelioma cases in the Italian register (ReNaM).

The Italian National Mesothelioma Register (ReNaM) was set up at ISPESL (the National Institute for Occupational Safety and Prevention) in 1993. Five Italian regions (Piedmont, Liguria, Emilia-Romagna, Tuscany and Puglia, with a total of approximately 17500000 inhabitants) agreed to record mesothelioma cases according to guidelines established by ISPESL, to define exposure to asbestos and transmit the data to ISPESL. We describe an analysis of survival of 429 mesothelioma cases-392 pleural, 34 peritoneal and 3 in the pericardium-diagnosed during 1997, with variable follow-up from June 1999 to December 2001. The Kaplan-Meier method was used to estimate survival rates, the log rank non-parametric test and Cox proportional hazard model to assess the role of prognostic factors such as age, gender, morphology, level of diagnostic certainty and modality of exposure. Median survival was 275 days (95% confidence interval (CI) 241-309) for pleural mesotheliomas and 157 days (95% CI: 118-196) for peritoneal mesotheliomas. Survival after diagnosis of malignant pleural mesothelioma showed a statistically significant linear trend for age group at diagnosis, for males and females (P=0.006 and 0.008, respectively). The Cox proportional hazard model gave an adjusted relative risk (RR(adj)), for the fibrous histotype, of 2.96 (95% CI: 1.28-6.81; P=0.012) compared with cases with unspecified morphology; for epithelioid and biphasic morphologies, the risk was lower than unity. There was no significant difference in survival for cases with confirmed exposure (occupational, household or environmental) or without.

[Database of occupations and industrial activities that involve the risk of pulmonary tumors]. / Database di occupazioni e attività industriali che comportano rischio di tumore del polmone.

Lists of occupations and industries associated with lung cancer are a useful tool to estimate attributable risks for occupational exposures. They were first published in 1982, based on IARC Monographs. List A included industries, processes and occupations definitely entailing carcinogenic risk, list B those probably/possibly carcinogenic. In 1995 the lists had been updated. We carried out a further update, reviewing IARC Monographs Volumes 62-75, focusing on Group 1, 2 A, and 2 B agents, and coded the lists according to widely used classifications: ISIC Rev. 2, ISIC Rev. 3, NACE Rev. 1, and ISTAT ATECO 1991 (for economic activities); ILO-ISCO 1968 and ISTAT-Classificazione delle professioni 1991 (for occupations). In order to evaluate temporal and geographical variations in attributable risk, exposure assessment must be performed consistently across different studies and standard tools to identify exposures, such as the one we propose here, are needed. The lists can also help to develop maps of industrial activities entailing carcinogenic risk at local, regional, and national level, and to identify economic activities that deserve priority action to control occupational exposures to carcinogens. The classifications were originally developed for economic and demographic purposes, and some exposure circumstances cannot be coded with sufficient specificity. This applies to productions or processes (i.e.: PVC production) that could be classified only by codes corresponding to wide groups of economic activities and/or occupations: in these instances we associated no code, so as not to inflate the estimates of exposed workers. As a consequence, however, certain exposures are not represented in the coded version of the lists. Even keeping in mind such limitations, coding makes the lists easier to apply, and increases the comparability of studies on lung cancer and occupation, as well as of surveys on exposure prevalence.

Unusually high incidence of malignant pleural mesothelioma in a town of eastern Sicily: an epidemiological and environmental study.

In a recent epidemiological study, researchers investigated mortality from malignant pleural neoplasms in Italy, and they detected some geographic clusters of cases of this disease. We found a town located in a volcanic area of eastern Sicily to be of special interest. The residents, some of whom were diagnosed with pleural mesothelioma, had never had any relevant exposure to asbestos during their professional lives. The results of an environmental survey suggested that a possible cause of asbestos exposure was the stone quarries near the town. The products of the quarries contain fibrous amphiboles, which are used widely in the local building industry. These fibrous amphiboles were identified as intermediate phases between tremolite and actinolite. Samples were collected from buildings in the town, and concentrations of amphibole fibers were evaluated. Fibrous phases were detected in 71% of the samples, and fiber concentrations ranged from a few thousand to more than 4 x 10(4) fibers/mg of material. In addition, we conducted a study on the mineral fiber lung burden in a pleural mesothelioma case. Many mineral fibers that were classified as the same tremolite-actinolite fibrous amphibole found in the quarries and in the building materials were detected in the lung tissue. The results suggest that the inhabitants of the town we studied had been exposed for several decades to asbestos fibers that were present in the material extracted from the local stone quarries. The material was subsequently used in the building industry, and this has caused an increased risk of pleural mesothelioma in the area.

Confirmatory factor analysis of the Competitive State Anxiety Inventory-2.

The aim of this study was to evaluate the factor structure of the Competitive State Anxiety Inventory-2 (CSAI-2) using confirmatory factor analysis. Volunteer participants (n = 1213) completed the CSAI-2 approximately 1 h before competition and the data were analysed in two samples. The hypothesized model showed poor fit indices in both samples independently (Robust Comparative Fit Index: sample A = 0.82, sample B = 0.84) and simultaneously (Comparative Fit Index = 0.83), suggesting that the factor structure proposed by Martens et al. is flawed. Our findings suggest that a limitation of the Cognitive Anxiety scale derives from phrasing items around the word 'concerned' rather than 'worried'. We suggest that being concerned about an impending performance does not necessarily mean that an athlete is experiencing negative thoughts, but that the athlete is acknowledging the importance and difficulty of the challenge and is attempting to mobilize resources to cope. The present results question the use of the CSAI-2 as a valid measure of competitive state anxiety.

Cohort mortality study of women compensated for asbestosis in Italy.

BACKGROUND: The carcinogenic effect of asbestos is accepted for lung cancer and mesothelioma, while conflicting opinions exist for other cancer sites. The aim of the present investigation is to study cause-specific mortality of women compensated for asbestosis who had certainly been exposed to high levels of asbestos fibers. METHODS: The cause-specific mortality of all Italian women compensated for asbestosis and alive December 31, 1979, was investigated through October 30, 1997. In the total cohort, which included 631 subjects, 277 deaths occurred. Cause-specific SMRs (Standardized Mortality Ratio) were computed using the national rates for comparison. RESULTS: A significantly increased mortality for all diseases related to asbestos exposure was observed. Mortality for all causes, all neoplasms, lung cancer, uterine cancer, ovarian cancer, and non-neoplastic respiratory diseases was significantly increased. Separate analyses for textile (n = 276) and asbestos-cement (n = 278) workers were performed. Women employed in the textile industry, mainly exposed to chrysotile, who are compensated at a younger age, showed higher SMRs for lung cancer and asbestosis. Women in the asbestos-cement industry, mainly exposed to crocidolite containing asbestos mixtures, experienced higher mortality for pleural malignancies. CONCLUSIONS: The role of asbestos exposure in the development of gastrointestinal and genital neoplasms is discussed.

[Malignant Mesothelioma Registry from Piedmont. Incidence in 1990-1995]. / Il Registro dei Mesoteliomi Maligni del Piemonte. Incidenza nel periodo 1990-1995.

This paper describes methods and results of the Piedmont Malignant Mesothelioma Registry. The Registry is active since 1990 and collects all histologically confirmed incident cases of malignant mesothelioma (m.m.) occurring in the residents of Piedmont. In the period 1990-95, 346 cases of pleural m.m. (211 males and 135 females) and 41 (28 males and 13 females) of peritoneal m.m. have been observed. Amongst the inhabitants of the Local Health Authority of Casale Monferrato, where manufacturing of cement asbestos has determined serious asbestos exposures both in the work place and general environment, there have been 105 pleural m.m. and 17 peritoneal m.m. (incidence rate were 15.6 for men and 13.0 for women and 3.6 for men and 0.6 for women respectively). Leaving out the Local Health Authority (LHA) of Casale Monferrato, the annual incidence rate in Piedmont (for 10(5) person-years, age standardised on the 1981 Italian population), has been 1.0 in men and 0.6 in women for the pleural m.m. (respectively 154 and 87 cases) and 0.09 and 0.06 for peritoneal m.m. (14 and 10 cases). Possible cases of m.m. (cytological and/or x-ray diagnosis) have been searched in the file of hospital admission and discharges (SDO) in 1994-95: 46 additional cases were found, with a 25% increase in incidence rates. The analysis of incidence according to geographical aggregations (defined according to the LHA borders) has identified, besides some already known important sources of exposures, as Casale Monferrato and the LHA of Lanzo (Balangero mine), other areas with excess of incidence as the LHA's of Galliate and Caluso which show an increased incidence of pleural m.m. in men or Vercelli and Chieri with increased incidence of pleural m.m. in women. These observation deserves further analysis.

[Clinico-statistical investigation about cement dermatitis in Italy]. / Indagine clinico-statistica sulla dermatite da cemento in Italia.

To define the prevalence of cement dermatitis (allergic contact dermatitis-ACD-and irritant contact dermatitis-ICD), two retrospective studies have been carried out in Italy: the first one based on the analysis of dermatitis cases ascribable to cement as defined by INAIL (Italian Institute for Industrial Accidents Insurance) from 1984 to 1992; the second one by surveying cement dermatitis cases in workers in the building industry aged between 16 and 70 carried out by Istituto di Clinica Dermatologica dell'Università di Bari from 1988 to 1994. The survey on INAIL data showed that in the years take into account 5,290 dermatitis cases included in item 41 of the occupational diseases table have been defined. About 80% of these cases have been observed in workers working as bricklayers and floor-layers. Therefore, given the remarkable exposure to cement in these professions, the prevalence of cement dermatitis in Italy has been estimated to 6 cases/province/year, even though it has not been possible recognize the clinical form of cement dermatitis. Moreover, the study showed that disabling cutaneous after-effects eligible for compensation have been observed in 30% of the cases defined by INAIL. The allergologic study carried out by Clinica Dermatologica has not only defined the incidence of contact dermatitis (ACD and ICD), in building workers, but it has also extrapoled dermatitis cases due to cement. As a whole, in the years taken into account, 166 occupational or mixed ACD cases and 77 occupational or mixed ICD have been diagnosed. The incidence of contact dermatitis ascribable to cement has equalled 79% among ACD and 88% among ICD, with a ratio of about 2 to 1 in favour of allergic forms. Among the chemicals tested, potassium bichromate showed the highest frequency of cases positive to patch tests. The skin site the most affected by cement dermatitis is hand, followed by upper limbs, lower limbs and feet. In the province of Bari, in the years taken into account, an average incidence of 28.4 cases per year of the two forms of cement dermatitis has been observed.