Cromemia e cromuria: valori a confronto tra soggetti professionalmente esposti al cromo e popolazione generale

Aim of present study is the valutation and quantification of chromium in blood and urine. We compared 3 groups of persons formed by building workers, in particular masons, because cement contains potassium chromate that is dangerous for health, and by common people: urban population and outside the town population. In fact, exposure to CrVI risk is high for people who live near chromate industries. We maked a medical examination, blood and instrumental tests, chromium measuring in blood (recent exposure indicator) and urine (recent and previous indicator). Then we used statistical methods to estimate obtained values of blood and urine chromium among professional exposed people and common people. At the end we think that preventive measures in working environment reduced exposure to CrVI but environmental exposure (for example road dust from catalytic converter erosion, from brake lining erosion, cement dust and tobacco smoke), in the last years, has increased. So there are no difference between urban population and outside the town population and there are also no difference with professional exposed people for work prevention according to law in force, that let down professional risk using safe limits

Influence of CYP3A5 and ABCB1 gene polymorphisms and other factors on tacrolimus dosing in Caucasian liver and kidney transplant patients

n/

Pharmacogenetic considerations for optimizing tacrolimus dosing in liver and kidney transplant patients

The introduction of tacrolimus in clinical practice has improved patient survival after organ transplant. However, despite the long use of tacrolimus in clinical practice, the best way to use this agent is still a matter of intense debate. The start of the genomic era has generated new research areas, such as pharmacogenetics, which studies the variability of drug response in relation to the genetic factors involved in the processes responsible for the pharmacokinetics and/or the action mechanism of a drug in the body. This variability seems to be correlated with the presence of genetic polymorphisms. Genotyping is an attractive option especially for the initiation of the dosing of tacrolimus; also, unlike phenotypic tests, the genotype is a stable characteristic that needs to be determined only once for any given gene. However, prospective clinical studies must show that genotype determination before transplantation allows for better use of a given drug and improves the safety and clinical efficacy of that medication. At present, research has been able to reliably show that the CYP3A5 genotype, but not the CYP3A4 or ABCB1 ones, can modify the pharmacokinetics of tacrolimus. However, it has not been possible to incontrovertibly show that the corresponding changes in the pharmacokinetic profile are linked with different patient outcomes regarding tacrolimus efficacy and toxicity. For these reasons, pharmacogenetics and individualized medicine remain a fascinating area for further study and may ultimately become the face of future medical practice and drug dosing

Analisi del tasso di crescita in Pinna nobilis (Molluschia Bivalvia): confronto fra una popolazione profonda e due superficiali del parco Nazionale di Cabrera (Isole Baleari, Spagna)

Il tasso di crescita di tre popolazioni di Pinna nobilis all’interno del Parco Nazionale di Cabrera (Isole Baleari) è stato analizzato per stimare l’età degli individui al fine di una migliore comprensione della biologia e dell’ecologia di questa specie sempre più minacciata. In questa tesi il tasso di crescita di una popolazione profonda, quella delle Baleari (20-30m), è stato confrontato con quello di due popolazioni superficiali: Freus e Gandulf (5-10m). L’obiettivo è valutare l’effetto della profondità e del sito sulle modalità di accrescimento degli individui. Sono state prelevate alcune valve di individui morti di P. nobilis a varie profondità. Lo studio della sclerocronologia ci ha permesso di studiare l’origine dei registri interni di crescita e le modalità di accrescimento. I risultati hanno mostrato una chiara differenziazione della taglia fra le tre popolazioni. Gli individui della popolazione profonda raggiungono dimensioni maggiori elevate e vivono più a lungo. Ma la popolazione di Gandulf ha un tasso di crescita simile a quello della popolazione delle Baleari essendo entrambe caratterizzate da individui di grandi dimensioni (Lmax Baleari= 65,1cm; Lmax Gandulf=62,4cm) e più longevi (età max=27anni). La popolazione di Freus è caratterizzata invece da individui di dimensioni minori e giovani di età (età max=14anni). Anche la velocità di crescita che porta a raggiungere la dimensione asintotica massima risulta simile nella popolazione di Gandulf (K=0,19) e nella popolazione delle Baleari (K=0,14), ed in entrambe è inferiore ai valori rilevati a Freus (K=0,21). Tali risultati evidenziano l’esistenza di una forte variabilità del tasso di accrescimento fra popolazioni collocate sia a profondità che in siti diversi. La differenza riscontrata tra la popolazione di Freus e quella di Gandulf è che la prima si trova in un sito esposto, mentre l’altra è collocata in una cala protetta subendo, quindi, un minor stress idrodinamico

Benthic foraminifera as environmental indicators in extreme environments. The marine cave of Bue Marino (Sardinia, Italy)

The coast of the Gulf of Orosei (Sardinia, Italy) consists of impressive cliffs set up on dolostones and limestones characterized by wide karst systems connected to the sea. Marine caves, which are part of these system flooded by seawater through marine entrances, may be considered as extreme environments because of wide spatial and temporal environmental variability due to changing marine and terrestrial contributions. This study presents the results of the third survey carried out in summer 2016 in the Bue Marino cave, as part of a research project started in 2014 aimed at the application of Benthic Foraminifera (BF) as ecological indicators in Mediterranean marine caves for the identification of different habitats and their environmental interpretation. Sediment and water samples were collected from a total of 25 stations from two distinct sectors of the cave (North Branch and Middle Branch); sediments were analysed for living and dead BF and grain size, while Temperature, Salinity, pH and Dissolved Oxygen were measured in water samples collected close to sediment water interface. Two main foraminiferal assemblages, with distinct characteristics with respect to the typical Mediterranean shallow-water ones, were recognized by means of Hierarchical Cluster Analysis and Non-metric Multidimensional Scaling, and a Canonical Correspondence Analysis deduced their environmental significance. A well oxygenated, less saline environment with coarse bottom sediment, correlated with a mixed calcareous-agglutinated assemblage (Gavelinopsis praegeri, Rosalina spp., Eggerelloides advenus and Reophax dentaliniformis) with high species diversity (H-index 2.32–3.57) and low foraminiferal density, was exclusive of the North Branch. A scarcely oxygenated, more saline environment with fine bottom sediment enriched in vegetal debris was related to a prevalently agglutinated assemblage characterized by low species diversity (H-index 1.60–2.68), with high dominance of E. advenus (up to 83.6%) associated to Ammonia tepida, and high foraminiferal density, recognized in the Middle Branch. These different environments were interpreted considering the different modes of feeding the karst systems of the two branches. They also corresponded to two distinct ecozones, Entrance and Confluence, already recognized in earlier studies. The environmental significance of the foraminiferal ecozones recognized in this study and their comparison with the ones identified in the previous years, helped to consider the ecological zonation as a tool for detecting seasonal and, possibly, long term annual environmental variability in the marine system

Proteome-wide characterization of the RNA-binding protein RALY-interactome using the in vivo-biotinylation-pulldown-quant (iBioPQ) approach

RALY is a member of the heterogeneous nuclear ribonucleoproteins, a family of RNA-binding proteins generally involved in many processes of mRNA metabolism. No quantitative proteomic analysis of RALY-containing ribonucleoparticles (RNPs) has been performed so far, and the biological role of RALY remains elusive. Here, we present a workflow for the characterization of RALY's interaction partners, termed iBioPQ, that involves in vivo biotinylation of biotin acceptor peptide (BAP)-fused protein in the presence of the prokaryotic biotin holoenzyme synthetase of BirA so that it can be purified using streptavidin-coated magnetic beads, circumventing the need for specific antibodies and providing efficient pulldowns. Protein eluates were subjected to tryptic digestion and identified using data-independent acquisition on an ion-mobility enabled high-resolution nanoUPLC-QTOF system. Using label-free quantification, we identified 143 proteins displaying at least 2-fold difference in pulldown compared to controls. Gene Ontology overrepresentation analysis revealed an enrichment of proteins involved in mRNA metabolism and translational control. Among the most abundant interacting proteins, we confirmed RNA-dependent interactions of RALY with MATR3, PABP1 and ELAVL1. Comparative analysis of pulldowns after RNase treatment revealed a protein-protein interaction of RALY with eIF4AIII, FMRP, and hnRNP-C. Our data show that RALY-containing RNPs are much more heterogeneous than previously hypothesized

Immobilization of proteolytic enzymes on replica-molded thiol-ene micropillar reactors via thiol-gold interaction

Julkaistaan OA-artikkelina.We introduce rapid replica molding of ordered, high-aspect-ratio, thiol-ene micropillar arrays for implementation of microfluidic immobilized enzyme reactors (IMERs). By exploiting the abundance of free surface thiols of off-stoichiometric thiol-ene compositions, we were able to functionalize the native thiol-ene micropillars with gold nanoparticles (GNPs) and these with proteolytic alpha-chymotrypsin (CHT) via thiol-gold interaction. The micropillar arrays were replicated via PDMS soft lithography, which facilitated thiol-ene curing without the photoinitiators, and thus straightforward bonding and good control over the surface chemistry (number of free surface thiols). The specificity of thiol-gold interaction was demonstrated over allyl-rich thiol-ene surfaces and the robustness of the CHT-IMERs at different flow rates and reaction temperatures using bradykinin hydrolysis as the model reaction. The product conversion rate was shown to increase as a function of decreasing flow rate (increasing residence time) and upon heating of the IMER to physiological temperature. Owing to the effective enzyme immobilization onto the micropillar array by GNPs, no further purification of the reaction solution was required prior to mass spectrometric detection of the bradykinin hydrolysis products and no clogging problems, commonly associated with conventional capillary packings, were observed. The activity of the IMER remained stable for at least 1.5 h (continuous use), suggesting that the developed protocol may provide a robust, new approach to implementation of IMER technology for proteomics research.Peer reviewe

Incidence of potential drug interactions in a transplant centre setting and relevance of electronic alerts for clinical practice support

Background Adverse drug events may occur as a result of drug–drug interactions (DDIs). Information technology (IT) systems can be an important decision-making tool for healthcare workers to identify DDIs.Objective The aim of the study is to analyse drug prescriptions in our main hospital units, in order to measure the incidence and severity of potential DDIs. The utility of clinical decision-support systems (CDSSs) and computerised physician order entry (CPOE) in term of alerts adherence was also assessed. DDIs were assessed using a Micromedex healthcare series database.Methods The system, adopted by the hospital, generates alerts for prescriptions with negative interactions and thanks to an 'acknowledgement function' it is possible to verify physician adherence to alerts. This function, although used previously, became mandatory from September 2010. Physician adherence to alerts and mean monthly incidence of potential DDIs in analysed units, before and after the mandatory 'acknowledgement function', were calculated.Results The intensive care unit (ICU) registered the greatest incidence of potential DDIs (49.0%), followed by the abdominal surgery unit and dialysis (43.4 and 42.0%, respectively). The cardiothoracic surgery unit (41.6%), step-down unit (38.3%) and post-anaesthesia care unit (30.0%) were comparable. The operating theatre and endoscopy registered the fewest potential DDIs (28.2 and 22.7%, respectively). Adherence to alerts after the 'acknowledgement function' increased by 25.0% in the ICU, 54.0% in the cardiothoracic surgery unit, 52.5% in the abdominal surgery unit, 58.0% in the stepdown unit, 67.0% in dialysis, 51.0% in endoscopy and 48.0% in the post-anaesthesia care unit. In the operating theatre, adherence to alerts decreased from 34.0 to 30.0%. The incidence of potential DDIs after mandatory use of the 'acknowledgement function' decreased slightly in endoscopy (–2.9%), the abdominal surgery unit (–2.7%), dialysis (–1.9%) and the step-down unit (–1.4%).Conclusions Improving DDI alerts will improved patient safety by more appropriately alerting clinicians

Physical Health and Transition to Psychosis in People at Clinical High Risk

Background: The clinical high risk for psychosis (CHR-P) construct represents an opportunity for prevention and early intervention in young adults, but the relationship between risk for psychosis and physical health in these patients remains unclear. Methods: We conducted a RECORD-compliant clinical register-based cohort study, selecting the long-term cumulative risk of developing a persistent psychotic disorder as the primary outcome. We investigated associations between primary outcome and physical health data with Electronic Health Records at the South London and Maudsley (SLaM) NHS Trust, UK (January 2013–October 2020). We performed survival analyses using Kaplan-Meier curves, log-rank tests, and Cox proportional hazard models. Results: The database included 137 CHR-P subjects; 21 CHR-P developed psychosis during follow-up, and the cumulative incidence of psychosis risk was 4.9% at 1 year and 56.3% at 7 years. Log-rank tests suggested that psychosis risk might change between different levels of nicotine and alcohol dependence. Kaplan-Meier curve analyses indicated that non-hazardous drinkers may have a lower psychosis risk than non-drinkers. In the Cox proportional hazard model, nicotine dependence presented a hazard ratio of 1.34 (95% CI: 1.1–1.64) (p = 0.01), indicating a 34% increase in psychosis risk for every additional point on the Fagerström Test for Nicotine Dependence. Conclusions: Our findings suggest that a comprehensive assessment of tobacco and alcohol use, diet, and physical activity in CHR-P subjects is key to understanding how physical health contributes to psychosis risk