Lymph Node Thyroglobulin Measurement in Diagnosis of Neck Metastases of Differentiated Thyroid Carcinoma

Aim. Enlarged cervical lymph nodes (LNs) in patients with thyroid cancer are usually assessed by fine-needle aspiration cytology (FNAC). Thyroglobulin (Tg) is frequently elevated in malignant FNAC needle wash specimens (FNAC-Tg). The objectives of the study were to (1) determine an appropriate diagnostic cut-off for FNAC-Tg levels (2) compare FNAC and FNAC-Tg results in a group of 108 patients affected by differentiated thyroid carcinoma (DTC). Methods. A total of 126 consecutive FNACs were performed on enlarged LNs and the final diagnosis was confirmed by surgical pathology examination or clinical follow-up. The best FNAC-Tg cut-off level was selected by receiver operating curve analysis, and diagnostic performances of FNAC and FNAC-Tg were compared. Results. The rate of FNAC samples adequate for cytological examination was 77% in contrast FNAC-Tg available in 100% of aspirates (<.01). The sensitivity, specificity, and accuracy of FNAC were 71%, 80%, 74%, 100%, 80%, and 94%, respectively. The most appropriate cut-off value for the diagnosis of thyroid cancer metastatic LN was 1.1 ng/mL (sensitivity 100%, specificity 100%). Conclusions. The diagnostic performance of needle washout FNAC-Tg measurement with a cut-off of 1.1 ng/mL compared favorably with cytology in detecting DTC node metastases

Preliminary studies on environmental pollutants in chamois and wild boar from Eastern Piedmont, Italy.

Organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) are synthetic chlorinated compounds classified as POPs whereas only the penta e tetra-brominated polybromodiphenyl ethers (PBDEs) are so defined by the Stockolm Convention (Stockholm Convention, 2005) in order to elimitate or restrict the use of POPs. Organophosphorus insecticides (OCPs) represent important environmental and food contamination sources, widely used in agriculture. Among polyciclic aromatic hydrocarbons (PAHs), benzo[a]pirene is classified by IARC in Group 1, as cancerogen  and Benzo[a]fluoranthene as a Group 2B, as possible cancerogen (IARC, 2012; IARC, 2010).  EFSA (European Food Safety Authority) has released a scientific opinion on the risks to public health related to the presence of brominated flame retardants in food (EFSA, 2011) and in 2014 European commission has asked Member States to monitor the presence of brominated flame retardants (BFRs) in food over the next two years (EC, 2014). Due to their heir n-octanol/water partition coefficient (log Kow), they accumulate in fat tissue, bioconcentrate and biomagnify in the animals at the higher trophic levels, possibly causing, through chronic exposure, endocrine disruption and cancer (Wania et al., 1995; Vallack et al., 1998). The aim of this study is to evaluate the presence of OCPs, PCBs, PBDEs and PAHs in chamois and wild boar from Eastern Piedmont, Italy. A total of 20 chamois and 20 wild boar muscle samples were collected during the hunting season 2017, from Verbania Cusio Ossola (VCO) (Fig 1). The chemical analysis for the detection of OCPs, PCBs, PBDEs, and PAHs   was performed by GC-MS/MS on muscle samples purified and extracted using a QuEChERS technique, validated according to SANTE 2017 (SANTE/11183/2017). These preliminary results show the ubiquitary presence of the studied contaminants. PCBs have been found more in chamois (45%) than in wild boar (35%). No PBDEs were detected in wild boar but in chamois were found with a prevalence of 35%  and  concentration 0.25-1.52 ng g-1. About OCPs, phorate and demeton were found in wild boar (55%-15%) and chamois (32%- 35%) with range concentrations 0.21-20.1 ng g-1. No PAHs were detected, expect antharacene for one samples in wild boar (0.53 ng g-1). Further studies are in progress in order to correlate environmental contamination and game animals

Metals in mussels from Italian mollusc culture plants

The beneficial effects on human health of seafood are well known. However, seafood is a major source of exposition for consumers of most of the contaminants due to human activities such as breeding, industries, mining and agriculture: the overall level in biota, therefore seafood and particularly molluscs, dramatically increased over this last two centuries. This study evaluates the presence of Lead, Mercury, Cadmium, Arsenic, Nickel and Chromium in mussels from the Italian mussel culture plants, and estimate the risk that Italian consumer undergoes eating these molluscs. Mussels where collected at the wholesale fish market of Milan, the most important wholesale Italian fish market. The molluscs belonged to the   37 FAO marine area (corresponding to Mediterranean Sea), particularly from FAO 37.2.1 Ligury, 37.2.2. North Adriatic, middle Adriatic, Puglia, 37.2.3 Lazio and Sardinia, and were collected from July 2016 to February 2017. (FIG1). Analyses were carried out through inductively coupled plasma-mass spectrometry (ICP-MS) according to the Environmental Protection Agency (EPA) 3050B method. The sample concentrations were below the Maximum Levels (ML) given by Commission Regulation (EC) No 1881/2006 for Cadmium, Lead and Mercury, except one sample from south Adriatic sea, that showed Mercury concentration of 0.528 mg kg-1. Arsenic, Nickel and Chromium ML are not stated by EU. Arsenic concentration ranged from 2.05 to 13.35 mg kg-1, with the highest values found in Italian molluscs, Nickel concentration ranged from 0.00 to 3.98 mg kg-1. Chromium was found only in 5 of 30 sample analysed with a maximum concentration of 0.590 g kg-1. The tolerable intakes recommended by EFSA and on EU maximum levels, indicate that Italian mussels do not pose a risk consumers

Utility of baseline 18FDG-PET/CT functional parameters in defining prognosis of primary mediastinal (thymic) large B-cell lymphoma

The International Extranodal Lymphoma Study Group (IELSG) 26 study was designed to evaluate the role of (18)F-fluorodeoxyglucose (18FDG) positron emission tomography/computed tomography (PET/CT) in the management of primary mediastinal (thymic) large B-cell lymphoma (PMBCL). We examined the prognostic impact of functional PET parameters at diagnosis. Metabolic activity defined by the maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) was measured on baseline 18FDG PET/CT following a standard protocol in a prospectively enrolled cohort of 103 PMBCL patients. All received combination chemoimmunotherapy with doxorubicin- and rituximab-based regimens; 93 had consolidation radiotherapy. Cutoff values were determined using the receiver-operating characteristic curve. At a median follow-up of 36 months, progression-free survival (PFS) and overall survival (OS) were 87% and 94%, respectively. In univariate analysis, elevated MTV and TLG were significantly associated with worse PFS and OS. Only TLG retained statistical significance for both OS (P = .001) and PFS (P &lt; .001) in multivariate analysis. At 5 years, OS was 100% for patients with low TLG vs 80% for those with high TLG (P = .0001), whereas PFS was 99% vs 64%, respectively (P &lt; .0001). TLG on baseline PET appeared to be a powerful predictor of PMBCL outcomes and warrants further validation as a biomarker. The IELSG 26 study was registered at www.clinicaltrials.gov as #NCT00944567

Escenarios regionalizados de cambio climático sobre España

Seminario del Departamento de Desarrollo y Aplicaciones impartido en la sede central de AEMET el 20 de marzo de 201

Environmental Footprint: Update of Life Cycle Impact Assessment methods – Ecotoxicity freshwater, human toxicity cancer, and non-cancer

In 2011 the EC-JRC published the International Reference Life Cycle Data System (ILCD) Handbook recommendations on the use of Impact Assessment models for use in LCA (EC-JRC 2011a). This created the basis for the Product and Organisation Environmental Footprint (PEF/OEF) recommendations for impact categories and models as per Recommendation 2013/179/EU on the use of common methods to measure and communicate the life cycle environmental performance of products and organisations (EC 2013a). This Commission Recommendation is expected to contribute to the Building the Single Market for Green Products (EC 2013b) by supporting a level playing field regarding the measurement of environmental performance of products and organisations. In the context of the PEF, the model retained and recommended for assessing the impact of elementary flows on freshwater aquatic ecosystems and human cancer and non-cancer toxicity was the model USEtox 1.01. However, due to the difficulties encountered in using the model and in interpretation the results, the PEF Technical Advisory Board (TAB) has decided not to include the freshwater aquatic toxicity, human cancer and human non-cancer toxicity impact categories in the list of mandatory impact categories to be used for hotspot analysis and for communication to consumer of to business. The Joint Research Centre (JRC-Ispra) was then mandated by DG environment to conduct an in-depth evaluation of the model and data used to calculate CFs and to come with a proposal to 1) address the issue reported by the Pilots and 2) increase the number of available CFs. Using the physicochemical and toxicity data available in the REACH, EFSA and PPDB database, and building on the feedback collected during a PEF stakeholder workshop organised in February 2018 and on the preliminary outcomes of the UNEP-SETAC Pellston workshop organised in June 2018, JRC has new aquatic toxicity characterisation factors for about 6000 substances and about 3500 for human toxicity non-cancer. The report describes the methodology followed to generate those new characterisation factors. Furthermore, a contribution analysis has been performed comparing the contribution to this new CFs versus old ones used in the PEF pilots.JRC.D.1 - Bio-econom

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Design and Characterization of a Human Monoclonal Antibody that Modulates Mutant Connexin 26 Hemichannels Implicated in Deafness and Skin Disorders

Background: Mutations leading to changes in properties, regulation, or expression of connexin-made channels have been implicated in 28 distinct human hereditary diseases. Eight of these result from variants of connexin 26 (Cx26), a protein critically involved in cell-cell signaling in the inner ear and skin. Lack of non-toxic drugs with defined mechanisms of action poses a serious obstacle to therapeutic interventions for diseases caused by mutant connexins. In particular, molecules that specifically modulate connexin hemichannel function without affecting gap junction channels are considered of primary importance for the study of connexin hemichannel role in physiological as well as pathological conditions. Monoclonal antibodies developed in the last three decades have become the most important class of therapeutic biologicals. Recombinant methods permit rapid selection and improvement of monoclonal antibodies from libraries with large diversity.Methods: By screening a combinatorial library of human single-chain fragment variable (scFv) antibodies expressed in phage, we identified a candidate that binds an extracellular epitope of Cx26. We characterized antibody action using a variety of biochemical and biophysical assays in HeLa cells, organotypic cultures of mouse cochlea and human keratinocyte-derived cells.Results: We determined that the antibody is a remarkably efficient, non-toxic, and completely reversible inhibitor of hemichannels formed by connexin 26 and does not affect direct cell-cell communication via gap junction channels. Importantly, we also demonstrate that the antibody efficiently inhibits hyperative mutant Cx26 hemichannels implicated in autosomal dominant non-syndromic hearing impairment accompanied by keratitis and hystrix-like ichthyosis-deafness (KID/HID) syndrome. We solved the crystal structure of the antibody, identified residues that are critical for binding and used molecular dynamics to uncover its mechanism of action.Conclusions: Although further studies will be necessary to validate the effect of the antibody in vivo, the methodology described here can be extended to select antibodies against hemichannels composed by other connexin isoforms and, consequently, to target other pathologies associated with hyperactive hemichannels. Our study highlights the potential of this approach and identifies connexins as therapeutic targets addressable by screening phage display libraries expressing human randomized antibodies

Patient Age Is an Independent Risk Factor of Relapse of Differentiated Thyroid Carcinoma and Improves the Performance of the American Thyroid Association Stratification System

Background: The 2015 American Thyroid Association (ATA) guidelines proposed a three-category system for estimating the risk of recurrence of differentiated thyroid carcinoma (DTC). This system includes several perioperative features, but not age at diagnosis. However, age has traditionally been recognized as a critical factor in the survival of DTC patients, and the eighth edition of TNM stated that patients older than 55 years were at higher risk of death. In this study, we raised the question of whether age at DTC diagnosis impacts on its risk of recurrence. Specifically, the present study aimed to (i) evaluate the association between age at diagnosis and structural recurrence and (ii) investigate whether age at diagnosis could improve the performance of the ATA system. Methods: During the study period, four institutions selected DTC patients treated with both thyroidectomy and radioiodine and who had follow-up for at least one year. Patients with proven structural evidence of disease during follow-up were identified, and disease-free survival (DFS) was calculated accordingly. Results: The study involved 1603 DTC patients with a median age of 49 years and DFS of 44 months. Disease recurred in 8%. The shortest DFS was found in the oldest patients. The Kaplan-Meier curves were calculated for each decade of age, and there was a significant association with DFS (p = 0.0014). Patients older than 55 years had significantly higher risk (hazard ratio [HR] 1.78, 95% confidence interval [CI 1.23-2.56]). The Kaplan-Meier curves of DFS in high-, intermediate-and low-risk groups showed a significant association only in the high-risk group (p = 0.0058). Patients older than 55 years had significantly higher risk of relapse over time only in the high-risk group (HR 2.15 [CI 2.01-4.53]). Cox's proportional analysis showed that the age cutoff of 55 years and the ATA system were significant predictors of relapse. Adding age at diagnosis above 55 years to the ATA system identified a subgroup of patients at highest risk for relapse. Conclusions: The age threshold adopted in the eighth edition of TNM staging system for DTC patients' prognosis also identifies cases at higher risk of relapse. Applying age at diagnosis, with a cutoff of 55 years, to the ATA risk stratification system identifies cases at highest risk of relapse