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A targeted literature study was performed to assess the toxicological evidence for a selection of cardiotoxic chemicals, for which the results were collected in a data matrix. The objective of this document is to describe the methodology of the literature study, as well as to provide a summary and description of the main results collected in the data matrix. Chemicals for the literature study were selected from an earlier review. These chemicals elicited heart failure related effects in vitro, such as effects on cardiomyocyte viability, contractility, hypertrophy, and myopathy. The data matrix contains toxicological potency estimates for these relevant in vitro endpoints, as well as study results of in vivo toxicity assays. Relevant study characteristics were collected, such as species, cell type, dosing range, incubation time, and main outcome, facilitating comparison between chemicals and therefore prioritization efforts. The data matrix can therefore help the project in various stages, ranging from chemical selection to validation, while providing a framework with mechanistic data that can explain and integrate cardiotoxicity pathways with heart failure outcomes seen in exposed populations.

This document aims to provide an overview on the regulatory needs for cardiotoxicity methods and data that can be used for consultation of national and European Preliminary Assessment of REgulatory Relevance (PARERE) Networks. We provide a brief overview of 1) the scientific knowledge about cardiotoxicity induced by chemical stressors, 2) the current regulatory assessment frameworks for cardiotoxicity and their needs for improvement, and 3) specific New Approach Methodologies (NAMs)-based assessment tools, which are available or in development, with a specific focus on the work performed in the European project ALTERNATIVE (https://alternative-project.eu/). In addition, a set of questions for PARERE regulators is included and we aim to receive feedback on the regulatory relevance of these three aspects.

This deliverable represents the Data Management Plan for the ALTERNATIVE project. This document includes the prospects for the data that will be collected and created during the project, to ensure its correct implementation and addresses the project participation in the Pilot on Open Research Data for H2020 applicants. It includes the application of the FAIR principles and tackles aspects such as data security, allocation of resources and ethical aspects for data management.

In 2012, we conducted a retrospective cross-sectional study to assess the number of people living with HIV linked to care and, among these, the number of people on antiretroviral therapy. The health authority in each of the 20 Italian Regions provided the list of Public Infectious Diseases Clinics providing antiretroviral therapy and monitoring people with HIV infection. We asked every Public Infectious Diseases Clinic to report the number of HIV-positive people diagnosed and linked to care and the number of those on antiretroviral therapy during 2012. In 2012, 94,146 people diagnosed with HIV and linked to care were reported. The majority were males (70.1%), Italians (84.4%), and aged between 25 and 49 years (63.4%); the probable route of transmission was heterosexual contact in 37.5% of cases, injecting drug use in 28.1%, and male-to-male contact in 27.9%. Among people in care, 20.1% had less than 350 CD4 cells/μl, 87.6% received antiretroviral therapy, and among these, 62.4% had a CD4 cell count higher than 350 cells/μl. The overall estimated prevalence of individuals diagnosed and linked to care in 2012 in Italy was 0.16 per 100 residents (all ages). Adding the estimated proportion of undiagnosed people, the estimated HIV prevalence would range between 0.19 and 0.26 per 100 residents. In Italy, the majority of people diagnosed and linked to care receive antiretroviral therapy. A higher prevalence of individuals diagnosed and linked to care was observed in Northern Italy and among males. More information for developing the HIV care continuum is necessary to improve the entire engagement in care, focusing on test-and-treat strategies to substantially reduce the proportion of people still undiagnosed or with a detectable viral load.

The aim of an environmental and health sustainable management, decision-makers, particularly territorial planning authorities, need the appropriate information and tools to evaluate the best decisions to take, connected to the investigated problems. The study was carried out in the urban area of Pisa (Italy) assessing the environmental and health risk related to the incinerator located at Ospedaletto in the near suburbs of the city. The project included three main research branches: Public Health (i.e. state of health of the population living within 4 km radius circle around the incinerator, based on the health information system and an ad-hoc survey on respiratory symptoms and risk perception); Environment (i.e. investigation on the main pollutants: heavy metals dioxins in soils potentially produced by an incinerator, the soils have also been characterized for all the main physical and chemical properties); Georeferecing (i.e. all the environmental and health data collected have been transferred in thematic maps using GPS and GIS resources). The study carried out revealed the potential of a multidisciplinary team in this kind of investigations and allowed to elaborate a procedure aimed to the correct management of the public health. Some high concentration values detected for selected contaminants are interesting if the potentially toxic effects on community health, plants growth and quality of waters are considered. To integrate environmental and health knowledge a survey on the population health conditions before the possible contamination is necessary, since these information will be relevant in order to set up a monitoring system on the potential impacts.

The present study analyses the environment and health status of the population living near a municipal waste incinerator that have operated in the Pisa Southeast district for 20 years approximately. This area is located within a dense road network with heavy vehicle traffic. The local authorities are now evaluating a project for a new hazardous waste disposal plant to be located in the above district. The study area is defined by a 0-4 km zone around the site with a population of about 12,000 residents.

The present study analyses the environment and health status of the population living near a municipal waste incinerator that have operated in the Pisa Southeast district for 20 years approximately. This area is located within a dense road network with heavy vehicle traffic. The local authorities are now evaluating a project for a new hazardous waste disposal plant to be located in the above district. The study area is defined by a 0-4 km zone around the site with a population of about 12,000 residents.

In the aim of a sustainable management of environment and health, decision-makers, particularly territorial planning authorities, need appropriate information and tools in order to take the best decisions in relation to the investigated problems. Research to develop such tools must follow a multidisciplinary approach, and the main areas involved are related to biosciences (i.e. medicine, biology, environmental sciences, epidemiology, bio-statistics) and computer sciences. The project included three main research areas: · Public Health: state of health of the population living within a circle of 4 km radius around the incinerator, based on the existing health information system and an ad-hoc survey on respiratory symptoms and risk perception. · Environment: investigation of the main pollutants in water and soils that are potentially produced by an incinerator. The soils have been characterized for all the main physical and chemical properties. The main contaminants investigated were heavy metals, PAH and Dioxins. · Geo-referencing: all the environmental and health data collected were included in thematic maps using GPS and GIS resources. A survey of the health status of the population (e.g. mortality, morbidity, reproductive outcomes and other health indicators) of the time prior to possible contamination is necessary, if environmental data and health information are to be integrated. Such information is relevant for the setting up of a monitoring system on potential impacts, including also data on socio-economic features, life-styles, etc.

An abstract is not available.

To evaluate whether the detection of Toxoplasma gondii DNA in CSF could contribute to the differential diagnosis of AIDS-related focal brain lesions, CSF samples from 88 HIV-infected patients (56 with focal brain lesions and 32 without) were tested prospectively by a nested PCR for the B1 gene of T. gondii. The assay had a detection limit of 10 trophozoite equivalents. Six of 18 patients with toxoplasmic encephalitis, but none of the 70 patients with other disorders, were PCR-positive (33.3% sensitivity and 100% specificity). Considering only those patients with cerebral toxoplasmosis from whom CSF was collected before or during the first week of antitoxoplasmic therapy, sensitivity rose to 50%. This was higher than the sensitivity in patients whose CSF was collected after the first week of treatment (odds ratio (OR) of 7.0; 95% CI: 0.46-218.2). The administration of antitoxoplasmic prophylaxis did not affect the PCR results. Patients with a poor response to therapy had a higher probability of detectable T. gondii DNA in their CSF (OR of 5.0; 95% CI: 0.37-86.6). All patients with other central nervous system disorders were PCR-negative. Despite the moderate sensitivity, the high specificity and positive predictive value (100%) make this assay a useful tool in the differential diagnosis of AIDS-related focal brain lesions as part of a series of CSF and neuroradiological examinations.

Summary. Acquired immunodeficiency syndrome (AIDS)-related primary central nervous system lymphoma (PCNSL) is almost always associated with the Epstein-Barr virus (EBV), and EBV-DNA in cerebrospinal fluid (CSF) has been indicated as a useful tumour marker for this HIV-related neoplasm. AIDS lymphomas also show an enhanced production of IL-10 which is generally associated with the presence of EBV in lymphoma cells. We performed a prospective study in 19 HIV seropositive patients with brain mass lesions, and in 21 other AIDS patients with or without other neurological disorders, to assess the in vivo diagnostic value of EBV-DNA and of IL-10 levels in the CSF for primary lymphoma of the central nervous system (CNS). EBV-DNA was detected by a nested polymerase chain reaction (PCR) in the CSF from seven of eight patients with PCNSL, diagnosed by brain biopsy (875% sensitivity) and in none of the 11 controls with brain mass lesions (100% specificity) and of the other 21 AIDS patients with or without neurological disorders. The only patient with PCNSL without detectable EBV-DNA in the CSF was also negative for EBV-DNA in the lymphoma tissue, whereas the samples of the other seven brain lymphomas were all positive for EBV-DNA by nested PCR. Therefore 100% of patients with an EBV-positive primary CNS lymphoma had detectable EBV-DNA in the CSF. No patient from the control group without PCNSL with EBV-negative CSF developed a lymphoma after a mean follow-up of 157 ± 173 d. IL-10 levels in the CSF from the patients with PCNSL were not significantly different from those in the other groups of patients with AIDS. Due to uniformly high levels in the CSF from AIDS patients, IL-10 is not a useful diagnostic marker for AIDS-related brain lymphoma. The detection of EBV-DNA from the CSF by nested PCR is an extremely sensitive and specific diagnostic tool for AIDS-related PCNSL and should be further evaluated as a possible alternative in patients from whom brain biopsy is not advisable.