Fish stock study on the Ridge of Santa Croce

Il presente studio è stato finalizzato alla caratterizzazione del Dosso di Santa Croce (Golfo di Trieste – Alto Adriatico) in termini di morfobatimetria e di distribuzione dei banchi di pesce presenti in questa zona. A tal fine è stato utilizzato un “echosounder” che permette, tramite riflessione degli impulsi acustici inviati, di individuare banchi di pecse o plankon, valutandone la relativa taglia, stimare abbondanza e densità dei medesimi organismi, studiarne il comportamento e le dinamiche migratorie e mappare il fondale. Lo strumento ha permesso, nel presente lavoro, di valutare in maniera semplice la densità e l’abbondanza relative dei banchi di pesce, ma la conversione in valori assoluti è stata resa difficoltosa dall’impossibilità di prelevare specie nell’area, sottoposta a protezione. Pertanto uno strumento utile da utilizzare in abbinamento all’echosounder sembrerebbe poter essere il “visual census” (campionamento visivo) per valutare le specie presenti nei banchi

Bird populations as sentinels of endocrine disrupting chemicals

Exposure to endocrine disrupting chemicals (EDCs) is a widespread phenomenon in nature. Although the mechanisms of action of EDCs are actively studied, the consequences of endocrine disruption (ED) at the population level and the adaptations evolved to cope with chronic EDC exposure have been overlooked. Birds probably represent the animal taxon most successfully adapted to synanthropic life. Hence, birds share with humans a similar pattern of exposure to xenobiotics. In this article, we review case studies on patterns of behaviour that deviate from the expectation in bird species exposed to EDCs. We provide behavioural and ecological parameters to be used as endpoints of ED; methodological requirements and caveats based on species-specific life-history traits, behavioural repertoires, developmental styles, and possibility of captive breeding; a list of species that could be used as sentinels to assess the quality of man-made environment

When sarcoidosis hits down: a case of prostatic sarcoidosis.

A 69-year-old North African male with established diagnosis of sarcoidosis underwent a stereotactic prostate biopsy with fusion technique. At the histological analysis, non-necrotizing microgranulomas were highlighted in 2 samples, while the immunohistochemical staining resulted negative for CK903/p63/racemase. To the best of our knowledge, only 16 cases of prostatic sarcoidosis have been reported in literature. With this case report we describe an incidental diagnosis of prostatic involvement of sarcoidotic disease and briefly review and discuss the available literature on the topic

Human lung adenocarcinoma cell cultures derived from malignant pleural effusions as model system to predict patients chemosensitivity

BACKGROUND: Lung cancer is the leading cause of cancer related deaths and Malignant Pleural Effusion (MPE) is a frequent complication. Current therapies suffer from lack of efficacy in a great percentage of cases, especially when cancer is diagnosed at a late stage. Moreover patients' responses vary and the outcome is unpredictable. Therefore, the identification of patients who will benefit most of chemotherapy treatment is important for accurate prognostication and better outcome. In this study, using malignant pleural effusions (MPE) from non-small cell lung cancer (NSCLC) patients, we established a collection of patient-derived Adenocarcinoma cultures which were characterized for their sensitivity to chemotherapeutic drugs used in the clinical practice. METHODS: Tumor cells present in MPEs of patients with NSCLC were isolated by density gradient centrifugation, placed in culture and genotyped by next generation sequencing. In a subset of cases patient derived xenografts (PDX) were obtained upon tumor cell inoculation in rag2/IL2 knock-out mice. Isolated primary cultures were characterized and tested for drug sensitivity by in vitro proliferation assays. Additivity, antagonism or synergy for combinatorial treatments were determined by analysis with the Calcusyn software. RESULTS: We have optimized isolation procedures and culture conditions to expand in vitro primary cultures from Malignant Pleural Effusions (MPEs) of patients affected by lung adenocarcinomas, the most frequent form of non small cell lung cancer. Using this approach we have been able to establish 16 primary cultures from MPEs. Cells were banked at low passages and were characterized for their mutational pattern by next generation sequencing for most common driver mutations in lung cancer. Moreover, amplified cultures were shown to engraft with high efficiency when injected in immunocompromised mice. Cancer cell sensitivity to drugs used in standard chemotherapy regimens was assessed either individually or in combination. Differential chemosensitivity and different mutation profiles were observed which suggests that this isolation method could provide a platform for predicting the efficacy of chemotherapy in the clinical setting. Most importantly for six patients it was possible to establish a correlation between drug response in vitro and response to therapy in the clinic. CONCLUSIONS: Results obtained using primary cultured cells from MPEs underscore the heterogeneity of NSCLC in advanced stage as indicated by drug response and mutation profile. Comparison of data obtained from in vitro assays with patients' responses to therapy leads to the conclusion that this strategy may provide a potentially useful approach for evaluating individual chemosensitivity profile and tailor the therapy accordingly. Furthermore, combining MPE-derived primary cultures with their genomic testing allows to identify patients eligible to trials with novel targeted agents

Immunotoxicity and Sensitizing Capacity of Metal Compounds Depend on Speciation

Immunotoxicity of metal compounds is an issue of great importance due to the recent industrial application of metals with unknown toxicity on the immune system and the discovery of metal intermediary compounds not sufficiently studied yet. In this report we show results of our study on the immunotoxicity of the following metals: the Platinum group elements (Platinum, Palladium, Rhodium), Titanium and Arsenic. We applied functional and non functional assays and investigated both innate and adaptive immune systems, in particular, cell proliferation, cytokine production by PBMCs and O−2 production by neutrophils. We obtained the following results: only some Ti compounds (Titanocene, Ti ascorbate and Ti oxalate) show immunotoxicity. Trivalent As compounds (Sodium arsenite and tetraphenyl arsonium chloride) are more immunotoxic than the other investigated As compounds. Genotoxicity of Pt group compounds is in the following order: Pt < Rh < Pd. Immunotoxicity of Pt group compounds is in the following order: Pd < Pt < Rh. Lymphocytes and macrophages show a different reaction of neutrophils to metal toxicity. We can conclude that these studies show that metal immunotoxicity depends on speciation. In general speciation provides additional and often essential information in evaluating metal toxicity. However, there are many difficulties in applying speciation in investigating toxico-kinetic aspects to many metals, mainly due to the lack of information about the existence and significance of species and to the lack of analytical methods for measuring species in biological samples

Phenotypic drug discovery: a case for thymosin alpha-1

Phenotypic drug discovery (PDD) involves screening compounds for their effects on cells, tissues, or whole organisms without necessarily understanding the underlying molecular targets. PDD differs from target-based strategies as it does not require knowledge of a specific drug target or its role in the disease. This approach can lead to the discovery of drugs with unexpected therapeutic effects or applications and allows for the identification of drugs based on their functional effects, rather than through a predefined target-based approach. Ultimately, disease definitions are mostly symptom-based rather than mechanism-based, and the therapeutics should be likewise. In recent years, there has been a renewed interest in PDD due to its potential to address the complexity of human diseases, including the holistic picture of multiple metabolites engaging with multiple targets constituting the central hub of the metabolic host–microbe interactions. Although PDD presents challenges such as hit validation and target deconvolution, significant achievements have been reached in the era of big data. This article explores the experiences of researchers testing the effect of a thymic peptide hormone, thymosin alpha-1, in preclinical and clinical settings and discuss how its therapeutic utility in the precision medicine era can be accommodated within the PDD framework

BRCA1 and BRCA2 mutations in central and southern Italian patients.

Protein truncation test (PTT) and single-strand conformation polymorphism (SSCP) assay were used to scan the BRCA1 and BRCA2 genes in 136 unrelated Italian breast/ovarian cancer patients. In the sample tested, BRCA1 and BRCA2 equally contributed to site-specific breast cancer patients who reported one to two breast cancer-affected first-/ second-degree relative(s) or who were diagnosed before age 40 years in the absence of a family history of breast/ovarian cancer. BRCA1 and BRCA2 mutations were mostly found in patients with disease diagnosis before and after age 50 years, respectively. Moreover, in cases with familial clustering of site-specific breast cancer, BRCA1 mostly accounted for tumours diagnosed before age 40 years and BRCA2 for tumours diagnosed after age 50 years. The BRCA1 and BRCA2 mutation spectrum was consistent with a lack of significant founder effects in the sample of patients studied

BRCA1 and BRCA2 mutations in central and southern Italian patients

INTRODUCTION: Germline BRCA1 and BRCA2 mutations account for most hereditary breast/ovarian cancers and are associated with male breast cancer. Furthermore, constitutional mutations in these genes may occur in breast/ovarian cancer patients that do not meet stringent criteria of autosomal-dominant predisposition. The relevance of BRCA1 and BRCA2 mutations in such patients is still debated. OBJECTIVES: We sought to determine the impact of BRCA1 and BRCA2 mutations in a population of patients from central and southern Italy. We analyzed the BRCA1 and BRCA2 coding regions in 136 unrelated probands: 117 females with breast/ovarian cancer and 19 males with breast cancer. This population of patients was mostly representative of cases who are at risk for hereditary susceptibility, but who do not meet stringent criteria of autosomal-dominant predisposition. METHODS: Probands, subclassified as follows, were consecutively recruited depending on informed consent from patients attending breast cancer clinics in Rome and Naples. Selection criteria for females were as follows: breast cancer with breast cancer family history [one to two first-/second-degree relative(s), n = 55]; breast cancer diagnosed before age 40 years (no breast/ovarian cancer family history, n = 28); bilateral breast cancer (regardless of age and family history, n =10); breast cancer associated with gastrointestinal, pancreatic or uterine cancers [synchronous/metachronous or in first-degree relative(s), n = 9]; breast or ovarian cancer with family history of breast-ovarian/ovarian cancer (at least 1 first-/ second-degree relative, n = 10); and ovarian cancer with no breast/ovarian cancer family history (n = 5). Males with breast cancer were recruited regardless of age and family history. BRCA1 exon 11 and BRCA2 exons 10 and 11 were screened by PTT. Coding BRCA1 exons 2, 3, 5-10 and 12-24 and BRCA2 exons 2-9 and 12-27 were screened by SSCP. Primers are listed in Table 1. In 27 cases, analyzed by PTT along the entire BRCA1 coding sequence, BRCA1 SSCP analysis was limited to exons 2, 5, 20 and 24. Mutations were verified by sequence analysis on two independent blood samples. RESULTS: Deleterious germline BRCA1/BRCA2 mutations were detected in 11 out of 136 cases (8%). Only three BRCA2 mutations were novel. One BRCA2 mutation recurred in two unrelated probands. Table 2 shows the mutations and data concerning carriers and their families. Table 3 shows correlations between BRCA1/BRCA2 mutations and sex, age at disease diagnosis and familial clustering of breast/ovarian cancer in the total patient population. Table 4 shows the proportions of BRCA1 and BRCA2 mutations in females with site-specific breast and breast-ovarian/ovarian cancer. Table 5 shows the frequency of BRCA1/BRCA2 mutations in males. BRCA1 and BRCA2 mutations, respectively, accounted for four out of 68 (6%) and one out of 68 (1%) cases diagnosed before age 50 years, and for one out of 68 (1%) and five out of 68 (7%) cases diagnosed after age 50 years. BRCA1 mutations were found in five out of 117 females (4%) and in none of 19 males (0%), and BRCA2 mutations were found in four out of 117 females (3%) and in two out of 19 males (10%). The proportions of BRCA1 and BRCA2 mutations coincided in site-specific female breast cancers (four out of 102; ie 4% each). BRCA1 and BRCA2 equally contributed to female breast cancers, with no familial clustering in those diagnosed before age 40 years (one out of 28; 4% each), and to female breast cancers, all ages, with familial clustering in one to two relatives (three out of 55; ie 5% each). In the latter subset of cases, BRCA1 mostly accounted for tumours diagnosed before age 40 years (two out of eight; 25%), and BRCA2 for tumours diagnosed after age 50 years (three out of 34; 9%). Regardless of family history, the respective contributions of BRCA1 and BRCA2 to site-specific female breast cancers diagnosed before age 40 years were 8% (three out of 36) and 3% (one out of 36). One BRCA1 mutation was detected among the 15 female probands from breast-ovarian/ovarian cancer families (7%). Among male breast cancers, BRCA2 mutations were identified in one out of five (20%) cases with family history and in one out of 14 (7%) apparently sporadic cases. No BRCA1 or BRCA2 mutations were found in female probands with nonfamilial bilateral breast cancer (10 cases) or in those with breast cancer associated with gastrointestinal, pancreatic or uterine cancers, synchronous/metachronous or in first-degree relative(s) (nine cases). These cases were all diagnosed after age 40 years. DISCUSSION: Our results indicate a lack of relevant founder effects for BRCA1- and BRCA2-related disease in the sample of patients studied, which is consistent with other Italian studies and with ethnical and historical data. Overall, the contribution of BRCA1 and BRCA2 to breast/ovarian cancer in Italian patients appears to be less significant than in patients from communities with founder mutations. The present study is in agreement with direct estimates on other outbred populations, indicating that 7-10% of all female breast cancers that occur in patients aged under 40 years are due to BRCA1/BRCA2. We found that BRCA1 and BRCA2 equally contributed to site-specific breast cancers who had one/two breast cancer-affected first-/second-degree relative(s) or who were diagnosed within age 40 years in the absence of family history. This is consistent with recent data that indicated that the respective frequencies of BRCA1 and BRCA2 mutations are comparable in early onset breast cancer. Considering the total population of patients analyzed here, however, BRCA1 and BRCA2 mutations were mostly found in cases with disease diagnosis before and after age 50 years, respectively. Moreover, in cases with familial clustering of site-specific breast cancer, BRCA1 mostly accounted for tumours diagnosed before age 40 years, and BRCA2 for tumours diagnosed after age 50 years. This is in agreement with a trend, which has been observed in other populations, for the proportion of cases with BRCA2 mutations to increase, and the proportion with mutations in BRCA1 to decrease, as the age at cancer onset increases. As in other studies, the frequency of BRCA1/BRCA2 mutations taken together was lower than the estimated frequencies at comparable ages for all susceptibility alleles derived from the Contraceptive and Steroid Hormones (CASH) study. The discrepancy between direct data deriving from BRCA1/BRCA2 mutational analysis and CASH estimates could be due to several factors, including contribution of gene(s) other than BRCA1/BRCA2, differences between populations and relative insensitivity of mutational screening. Only BRCA1 mutations were found in breast/ovarian and site-specific ovarian cancer families. BRCA2, but not BRCA1 mutations were found in the male breast cancers. The overall proportion of males with BRCA2 mutations was high when compared with data from other studies on outbred populations, but was low compared with data from populations with founder effects. The present results should be regarded as an approximation, because the following types of mutation are predicted to escape detection by the screening strategy used: mutations in noncoding regions; missense mutations within BRCA1 exon 11 and BRCA2 exons 10 and 11; large gene deletions; and mutations within the first and last 180 nucleotides of the amplicons analyzed by PTT

Evaluation of HIV Transmission Clusters Among Natives and Foreigners Living in Italy

We aimed at evaluating the characteristics of HIV-1 molecular transmission clusters (MTCs) among natives and migrants living in Italy, diagnosed between 1998 and 2018. Phylogenetic analyses were performed on HIV-1 polymerase (pol) sequences to characterise subtypes and identify MTCs, divided into small (SMTCs, 2\u20133 sequences), medium (MMTCs, 4\u20139 sequences) and large (LMTCs, 6510 sequences). Among 3499 drug-na\uefve individuals enrolled in the Italian Cohort Naive Antiretroviral (ICONA) cohort (2804 natives; 695 migrants), 726 (20.8%; 644 natives, 82 migrants) were involved in 228 MTCs (6 LMTCs, 36 MMTCs, 186 SMTCs). Migrants contributed 14.4% to SMTCs, 7.6% to MMTCs and 7.1% to LMTCs, respectively. HIV-1 non-B subtypes were found in 51 MTCs; noteworthy was that non-B infections involved in MTCs were more commonly found in natives (n = 47) than in migrants (n = 4). Factors such as Italian origin, being men who have sex with men (MSM), younger age, more recent diagnosis and a higher CD4 count were significantly associated with MTCs. Our findings show that HIV-1 clustering transmission among newly diagnosed individuals living in Italy is prevalently driven by natives, mainly MSM, with a more recent diagnosis and frequently infected with HIV-1 non-B subtypes. These results can contribute to monitoring of the HIV epidemic and guiding the public health response to prevent new HIV infections