[A cohort study on mortality and morbidity in the area of Taranto, Southern Italy].

Introduction: the area of Taranto has been investigated in several environmental and epidemiological studies due to the presence of many industrial plants and shipyards. Results from many studies showed excesses of mortality and cancer incidence for the entire city of Taranto, but there are no studies for different geographical areas of the city that take into account the important confounding effect of socioeconomic position. Objective: to assess mortality and hospitalization rates of residents in Taranto, Statte and Massafra through a cohort study, with a particular focus on residents in the districts closest to the industrial complex, taking into account the socioeconomic position. Methods: a cohort of residents during the period 1998-2010 was enrolled. Individual follow-up for assessment of vital status at 31.01.2010 was performed using municipality data. The census-tract socioeconomic position level and the district of residence were assigned to each participant, on the basis of the geocoded addresses at the beginning of the follow-up. Standardized cause specific mortality/morbidity rates, adjusted for age, were calculated by gender and districts of residence. Mortality and morbidity Hazard Ratios (HR, CI95%) were calculated by districts and socioeconomic position using Cox models. All models were adjusted for age and calendar period, and were done separately for men and women. Results: 321.356 people were enrolled in the cohort (48.9% males). Mortality/morbidity risks for natural cause, cancers, cardiovascular and respiratory diseases were found to be higher in low socioeconomic position groups compared to high ones. The analyses by districts have shown several excess mortality/morbidity risks for residents in Tamburi (Tamburi, Isola, Porta Napoli and Lido Azzurro), Borgo, Paolo VI and the municipality of Statte. Conclusions: The results of this study showed a significant relationship between socioeconomic position and health status of people resident in Taranto. People living in the districts closest to the industrial zone have higher mortality/morbidity levels compared to the rest of the area also taking into account the socioeconomic position

Electron Transport Properties of Single-Molecule-Bearing Multiple Redox Levels Studied by EC-STM/STS

Multielectron systems as possible components of molecular electronics devices are attracting compelling experimental and theoretical interest. Here we studied by electrochemical scanning tunneling techniques (EC-STMicroscopy and EC-STSpectroscopy) the electron transport properties of a redox molecule endowed with two redox levels, namely, the hydroquinone/quinone (H2Q/Q) couple. By forming self-assembled monolayers on Au(111) of oligo-phenylene-vinylene (OPV) derivatized H2Q/Q moieties, we were able to explore the features of the tunneling current/overpotential relation in the EC-STS setup. The behavior of the tunneling current sheds light onto the mechanism of electron transport involving the redox levels of the H2Q/Q redox pair coupled to tip and substrate electrodes

GHEP-ISFG collaborative exercise on mixture profiles of autosomal STRs (GHEP-MIX01, GHEP-MIX02 and GHEP-MIX03): results and evaluation

One of the main objectives of the Spanish and Portuguese-Speaking Group of the International Society for Forensic Genetics (GHEP-ISFG) is to promote and contribute to the development and dissemination of scientific knowledge in the area of forensic genetics. Due to this fact, GHEP-ISFG holds different working commissions that are set up to develop activities in scientific aspects of general interest. One of them, the Mixture Commission of GHEP-ISFG, has organized annually, since 2009, a collaborative exercise on analysis and interpretation of autosomal short tandem repeat (STR) mixture profiles. Until now, three exercises have been organized (GHEP-MIX01, GHEP-MIX02 and GHEP-MIX03), with 32, 24 and 17 participant laboratories respectively. The exercise aims to give a general vision by addressing, through the proposal of mock cases, aspects related to the edition of mixture profiles and the statistical treatment. The main conclusions obtained from these exercises may be summarized as follows. Firstly, the data show an increased tendency of the laboratories toward validation of DNA mixture profiles analysis following international recommendations (ISO/IEC 17025:2005). Secondly, the majority of discrepancies are mainly encountered in stutters positions (53.4%, 96.0% and 74.9%, respectively for the three editions). On the other hand, the results submitted reveal the importance of performing duplicate analysis by using different kits in order to reduce errors as much as possible. Regarding the statistical aspect (GHEP-MIX02 and 03), all participants employed the likelihood ratio (LR) parameter to evaluate the statistical compatibility and the formulas employed were quite similar. When the hypotheses to evaluate the LR value were locked by the coordinators (GHEP-MIX02) the results revealed a minor number of discrepancies that were mainly due to clerical reasons. However, the GHEP-MIX03 exercise allowed the participants to freely come up with their own hypotheses to calculate the LR value. In this situation the laboratories reported several options to explain the mock cases proposed and therefore significant differences between the final LR values were obtained. Complete information concerning the background of the criminal case is a critical aspect in order to select the adequate hypotheses to calculate the LR value. Although this should be a task for the judicial court to decide, it is important for the expert to account for the different possibilities and scenarios, and also offer this expertise to the judge. In addition, continuing education in the analysis and interpretation of mixture DNA profiles may also be a priority for the vast majority of forensic laboratories.Fil: Sala, Adriana Andrea. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Servicio de Huellas Digitales Genéticas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Crespillo, M.. Instituto Nacional de Toxicología y Ciencias Forenses; EspañaFil: Barrio, P. A.. Instituto Nacional de Toxicología y Ciencias Forenses; EspañaFil: Luque, J. A.. Instituto Nacional de Toxicología y Ciencias Forenses; EspañaFil: Alves, Cíntia. Universidad de Porto; PortugalFil: Aler, M.. Servicio de Laboratorio. Sección de Genética Forense y Criminalística; EspañaFil: Alessandrini, F.. Università Politecnica delle Marche. Department of Biomedical Sciences and Public Health; ItaliaFil: Andrade, L.. Instituto Nacional de Medicina Legal e Ciências Forenses, Delegação do Centro. Serviço de Genética e Biologia Forenses; PortugalFil: Barretto, R. M.. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: Bofarull, A.. Instituto Nacional de Toxicología y Ciencias Forenses; EspañaFil: Costa, S.. Instituto Nacional de Medicina Legal y Ciencias Forenses; PortugalFil: García, M. A.. Servicio de Criminalística de la Guardia Civil. Laboratorio Central de Criminalística. Departamento de Biología; EspañaFil: García, O.. Basque Country Police. Forensic Genetics Section. Forensic Science Unit; EspañaFil: Gaviria, A.. Cruz Roja Ecuatoriana. Laboratorio de Genética Molecular; EcuadorFil: Gladys, A.. Corte Suprema de Justicia de la Nación; ArgentinaFil: Gorostiza, A.. Grupo Zeltia. Genomica S. A. U.. Laboratorio de Identificación Genética; EspañaFil: Hernández, A.. Instituto Nacional de Toxicología y Ciencias Forenses; EspañaFil: Herrera, M.. Laboratorio Genda S. A.; ArgentinaFil: Hombreiro, L.. Jefatura Superior de Policía de Galicia. Brigada de Policía Científica. Laboratorio Territorial de Biología – ADN; EspañaFil: Ibarra, A. A.. Universidad de Antioquia; ColombiaFil: Jiménez, M. J.. Policia de la Generalitat – Mossos d’Esquadra. Divisió de Policia Científica. Àrea Central de Criminalística. Unitat Central de Laboratori Biològic; EspañaFil: Luque, G. M.. Instituto Nacional de Toxicología y Ciencias Forenses; EspañaFil: Madero, P.. Centro de Análisis Genéticos; EspañaFil: Martínez Jarreta, B.. Universidad de Zaragoza; EspañaFil: Masciovecchio, M. Verónica. IACA Laboratorios; ArgentinaFil: Modesti, Nidia Maria. Provincia de Córdoba. Poder Judicial; ArgentinaFil: Moreno, F.. Servicio Médico Legal. Unidad de Genética Forense; ChileFil: Pagano, S.. Dirección Nacional de Policía Técnica. Laboratorio de Análisis de ADN para el CODIS; UruguayFil: Pedrosa, S.. Navarra de Servicios y Tecnologías S. A. U.; EspañaFil: Plaza, G.. Neodiagnostica S. L.; EspañaFil: Prat, E.. Comisaría General de Policía Científica. Laboratorio de ADN; EspañaFil: Puente, J.. Laboratorio de Genética Clínica S. L.; EspañaFil: Rendo, F.. Universidad del País Vasco; EspañaFil: Ribeiro, T.. Instituto Nacional de Medicina Legal e Ciências Forenses, Delegação Sul. Serviço de Genética e Biologia Forenses; PortugalFil: Santamaría, E.. Instituto Nacional de Toxicología y Ciencias Forenses; EspañaFil: Saragoni, V. G.. Servicio Médico Legal. Departamento de Laboratorios. Unidad de Genética Forense; ChileFil: Whittle, M. R.. Genomic Engenharia Molecular; Brasi

Exogenous HIV-1 Nef Upsets the IFN-γ-Induced Impairment of Human Intestinal Epithelial Integrity

The mucosal tissues play a central role in the transmission of HIV-1 infection as well as in the pathogenesis of AIDS. Despite several clinical studies reported intestinal dysfunction during HIV infection, the mechanisms underlying HIV-induced impairments of mucosal epithelial barrier are still unclear. It has been postulated that HIV-1 alters enterocytic function and HIV-1 proteins have been detected in several cell types of the intestinal mucosa. In the present study, we analyzed the effect of the accessory HIV-1 Nef protein on human epithelial cell line.We used unstimulated or IFN-γ-stimulated Caco-2 cells, as a model for homeostatic and inflamed gastrointestinal tracts, respectively. We investigated the effect of exogenous recombinant Nef on monolayer integrity analyzing its uptake, transepithelial electrical resistance, permeability to FITC-dextran and the expression of tight junction proteins. Moreover, we measured the induction of proinflammatory mediators. Exogenous Nef was taken up by Caco-2 cells, increased intestinal epithelial permeability and upset the IFN-γ-induced reduction of transepithelial resistance, interfering with tight junction protein expression. Moreover, Nef inhibited IFN-γ-induced apoptosis and up-regulated TNF-α, IL-6 and MIP-3α production by Caco-2 cells while down-regulated IL-10 production. The simultaneous exposure of Caco-2 cells to Nef and IFN-γ did not affect cytokine secretion respect to untreated cells. Finally, we found that Nef counteracted the IFN-γ induced arachidonic acid cascade.Our findings suggest that exogenous Nef, perturbing the IFN-γ-induced impairment of intestinal epithelial cells, could prolong cell survival, thus allowing for accumulation of viral particles. Our results may improve the understanding of AIDS pathogenesis, supporting the discovery of new therapeutic interventions

CNS Penetration of Intrathecal-Lumbar Idursulfase in the Monkey, Dog and Mouse: Implications for Neurological Outcomes of Lysosomal Storage Disorder

A major challenge for the treatment of many central nervous system (CNS) disorders is the lack of convenient and effective methods for delivering biological agents to the brain. Mucopolysaccharidosis II (Hunter syndrome) is a rare inherited lysosomal storage disorder resulting from a deficiency of iduronate-2-sulfatase (I2S). I2S is a large, highly glycosylated enzyme. Intravenous administration is not likely to be an effective therapy for disease-related neurological outcomes that require enzyme access to the brain cells, in particular neurons and oligodendrocytes. We demonstrate that intracerebroventricular and lumbar intrathecal administration of recombinant I2S in dogs and nonhuman primates resulted in widespread enzyme distribution in the brain parenchyma, including remarkable deposition in the lysosomes of both neurons and oligodendrocytes. Lumbar intrathecal administration also resulted in enzyme delivery to the spinal cord, whereas little enzyme was detected there after intraventricular administration. Mucopolysaccharidosis II model is available in mice. Lumbar administration of recombinant I2S to enzyme deficient animals reduced the storage of glycosaminoglycans in both superficial and deep brain tissues, with concurrent morphological improvements. The observed patterns of enzyme transport from cerebrospinal fluid to the CNS tissues and the resultant biological activity (a) warrant further investigation of intrathecal delivery of I2S via lumbar catheter as an experimental treatment for the neurological symptoms of Hunter syndrome and (b) may have broader implications for CNS treatment with biopharmaceuticals

Social cognition in people with schizophrenia: A cluster-analytic approach

Background The study aimed to subtype patients with schizophrenia on the basis of social cognition (SC), and to identify cut-offs that best discriminate among subtypes in 809 out-patients recruited in the context of the Italian Network for Research on Psychoses. Method A two-step cluster analysis of The Awareness of Social Inference Test (TASIT), the Facial Emotion Identification Test and Mayer-Salovey-Caruso Emotional Intelligence Test scores was performed. Classification and regression tree analysis was used to identify the cut-offs of variables that best discriminated among clusters. Results We identified three clusters, characterized by unimpaired (42%), impaired (50.4%) and very impaired (7.5%) SC. Three theory-of-mind domains were more important for the cluster definition as compared with emotion perception and emotional intelligence. Patients more able to understand simple sarcasm (14 for TASIT-SS) were very likely to belong to the unimpaired SC cluster. Compared with patients in the impaired SC cluster, those in the very impaired SC cluster performed significantly worse in lie scenes (TASIT-LI <10), but not in simple sarcasm. Moreover, functioning, neurocognition, disorganization and SC had a linear relationship across the three clusters, while positive symptoms were significantly lower in patients with unimpaired SC as compared with patients with impaired and very impaired SC. On the other hand, negative symptoms were highest in patients with impaired levels of SC. Conclusions If replicated, the identification of such subtypes in clinical practice may help in tailoring rehabilitation efforts to the person's strengths to gain more benefit to the person

Evaluation of the prognostic value of impaired renal function on clinical progression in a large cohort of HIV-infected people seen for care in Italy

Whilst renal dysfunction, especially mild impairment (60 die;ve (Icona) Foundation Study collected between January 2000 and February 2014 with at least two creatinine values available. eGFR (CKD-epi) and renal dysfunction defined using a priori cut-offs of 60 (severely impaired) and 90 ml/min/1.73m2 (mildly impaired). Characteristics of patients were described after stratification in these groups and compared using chi-square test (categorical variables) or Kruskal Wallis test comparing median values. Follow-up accrued from baseline up to the date of the CCVD or AIDS related events or death or last available visit. Kaplan Meier curves were used to estimate the cumulative probability of occurrence of the events over time. Adjusted analysis was performed using a proportional hazards Cox regression model. We included 7,385 patients, observed for a median follow-up of 43 months (interquartile range [IQR]: 21-93 months). Over this time, 130 cerebro-cardiovascular events (including 11 deaths due to CCVD) and 311 AIDS-related events (including 45 deaths) were observed. The rate of CCVD events among patients with eGFR &gt;90, 60-89, &lt;60 ml/min, was 2.91 (95% CI 2.30-3.67), 4.63 (95% CI 3.51-6.11) and 11.9 (95% CI 6.19-22.85) per 1,000 PYFU respectively, with an unadjusted hazard ratio (HR) of 4.14 (95%CI 2.07-8.29) for patients with eGFR &lt;60 ml/min and 1.58 (95%CI 1.10-2.27) for eGFR 60-89 compared to those with eGFR ≥90. Of note, these estimates are adjusted for traditional cardiovascular risk factors (e.g. smoking, diabetes, hypertension, dyslipidemia). Incidence of AIDS-related events was 9.51 (95%CI 8.35-10.83), 6.04 (95%CI 4.74-7.71) and 25.0 (95% CI 15.96-39.22) per 1,000 PYFU, among patients with eGFR &gt;90, 60-89, &lt;60 ml/min, respectively, with an unadjusted HR of 2.49 (95%CI 1.56-3.97) for patients with eGFR &lt;60 ml/min and 0.68 (95%CI 0.52-0.90) for eGFR 60-89. The risk of AIDS events was significantly lower in mild renal dysfunction group even after adjustment for HIV-related characteristics. Our data confirm that impaired renal function is an important risk marker for CCVD events in the HIV-population; importantly, even those with mild renal impairment (90&lt;60)&gt

Economic consequences of investing in anti-HCV antiviral treatment from the Italian NHS perspective : a real-world-based analysis of PITER data

OBJECTIVE: We estimated the cost consequence of Italian National Health System (NHS) investment in direct-acting antiviral (DAA) therapy according to hepatitis C virus (HCV) treatment access policies in Italy. METHODS: A multistate, 20-year time horizon Markov model of HCV liver disease progression was developed. Fibrosis stage, age and genotype distributions were derived from the Italian Platform for the Study of Viral Hepatitis Therapies (PITER) cohort. The treatment efficacy, disease progression probabilities and direct costs in each health state were obtained from the literature. The break-even point in time (BPT) was defined as the period of time required for the cumulative costs saved to recover the Italian NHS investment in DAA treatment. Three different PITER enrolment periods, which covered the full DAA access evolution in Italy, were considered. RESULTS: The disease stages of 2657 patients who consecutively underwent DAA therapy from January 2015 to December 2017 at 30 PITER clinical centres were standardized for 1000 patients. The investment in DAAs was considered to equal €25 million, €15 million, and €9 million in 2015, 2016, and 2017, respectively. For patients treated in 2015, the BPT was not achieved, because of the disease severity of the treated patients and high DAA prices. For 2016 and 2017, the estimated BPTs were 6.6 and 6.2 years, respectively. The total cost savings after 20 years were €50.13 and €55.50 million for 1000 patients treated in 2016 and 2017, respectively. CONCLUSIONS: This study may be a useful tool for public decision makers to understand how HCV clinical and epidemiological profiles influence the economic burden of HCV