Role of key-regulator genes in melanoma susceptibility and pathogenesis among patients from South Italy

Background. Several genetic alterations have been demonstrated to contribute to the development and progression of melanoma. In this study, we further investigated the impact of key-regulator genes in susceptibility and pathogenesis of such a disease. Methods. A large series (N = 846) of sporadic and familial cases originating from South Italy was screened for germline mutations in p16CDKN2A, BRCA2, and MC1R genes by DHPLC analysis and automated DNA sequencing. Paired primary melanomas and lymph node metastases from same patients (N = 35) as well as melanoma cell lines (N = 18) were analyzed for somatic mutations in NRAS, BRAF, and p16CDKN2A genes. Results. For melanoma susceptibility, investigations at germline level indicated that p16CDKN2A was exclusively mutated in 16/545 (2.9%) non-Sardinian patients, whereas BRCA2 germline mutations were observed in 4/91 (4.4%) patients from North Sardinia only. Two MC1R germline variants, Arg151Cys and Asp294His, were significantly associated with melanoma in Sardinia. Regarding genetic events involved in melanoma pathogenesis at somatic level, mutually-exclusive mutations of NRAS and BRAF genes were observed at quite same rate (about two thirds) in cultured and in vivo melanomas (either primary or metastatic lesions). Conversely, p16CDKN2A gene alterations were observed at increased rates moving from primary to metastatic melanomas and melanoma cell lines. Activation of the ERK gene product was demonstrated to be consistently induced by a combination of molecular alterations (NRAS/BRAF mutations and p16CDKN2A silencing). Conclusion. Our findings further clarified that: a) mutation prevalence in melanoma susceptibility genes may vary within each specific geographical area; b) multiple molecular events are accumulating during melanomagenesis

Ecological risk and estimates of organophosphate pesticides loads into the Central Mediterranean Sea from Volturno River, the river of the “Land of Fires” area, southern Italy

The organophosphate pesticides pollution in the Volturno River and its environmental impact on the Tyrrhenian Sea (Central Mediterranean Sea) were estimated. Eight selected organophosphate pesticides (diazinon, dimethoate, malathion, chlorpyrifos, pirimiphos-methyl, fenitrothion, methidathion and tolclofos-methyl) were determined in the water dissolved phase, suspended particulate matter and sediment samples collected from 10 sites in different seasons. Total organophosphate pesticides concentrations ranged from 0.12 to 65.09 ng L-1 in water (as the sum of the water dissolved phase and suspended particulate matter) and from 1.19 to 23.17 ng g-1 in sediment samples. It has been calculated that the discharge of pollutants from the Volturno river into the Tyrrhenian Sea was about 71.815, 31 g year-1; for this reason the river is to be considered one of the main mouths of organophosphate pesticides in the Tyrrhenian Sea. In relation to environmental risk assessment, the concentrations of most OPPs in water and sediments from the Volturno River and its estuary were lower than guideline values, but the mean concentration of chlorpyrifos (5.41 ng L-1) in the Volturno River and Estuary has been shown that the ecological integrity of the river watercourse is possibly at risk

Caratterizzazione geochimica del porto di Napoli

Quello che viene presentato in questo lavoro, rappresenta un primo tentativo di sintesi del dataset chimico-fisico a disposizione per il Porto di Napoli che, a sua volta, rappresenta un interessante caso studio per l’indagine di aree fortemente sottoposte ad impatto antropico e pressione da parte di aree urbane importanti

A qualitative analysis and development of a conceptual model assessing financial toxicity in cancer patients accessing the universal healthcare system

Purpose: This paper illustrates a conceptual model for a new patient-reported outcome measure (PROM) aimed at measuring financial toxicity (FT) in oncological setting in Italy, where citizens are provided universal healthcare coverage. Methods: Focus groups with overall 34 patients/caregivers in three different Italian centers (from Northern, Centre, and Southern Italy) and an open-ended survey with 97 medical oncologists were undertaken. Transcripts from focus groups and the open-ended survey were analyzed to identify themes and links between themes. Themes from the qualitative research were supplemented with those reported in the literature; concepts identified formed the basis for item development that were then tested through the importance analysis (with 45 patients) and the cognitive debriefing (with other 45 patients) to test relevance and comprehension of the first draft PRO instrument. Results: Ten domains were extracted by analyzing 156 concepts generated from focus groups and the open-ended survey. After controlling for redundancy, 55 items were generated and tested through the importance analysis. After controlling comprehension and feasibility through cognitive debriefing interviews, a first version of the questionnaire consisting of 30 items was devised. Conclusions: This qualitative study represents the first part of a study conducted to develop a new PROM to assess FT in Italy, by using a bottom-up approach that makes the most of patients’ experiences and the health system analysis. Trial registration: clinicaltrials.gov NCT03473379 first posted on March 22, 2018

Correction to: Tocilizumab for patients with COVID-19 pneumonia. The single-arm TOCIVID-19 prospective trial (Journal of Translational Medicine, (2020), 18, 1, (405), 10.1186/s12967-020-02573-9)

Following publication of the original article [1] the authors identified that the collaborators of the TOCIVID-19 investigators, Italy were only available in the supplementary file. The original article has been updated so that the collaborators are correctly acknowledged. For clarity, all collaborators are listed in this correction article