Polychlorinated Biphenyls and Semen Quality in Healthy Young Men Living in a Contaminated Area

Polychlorinated biphenyls (PCBs) are persistent organic pollutants and endocrine disruptors that have been implicated in potential damage to human semen. However, the studies conducted so far provide contrasting results. Our study aimed to investigate the associations between PCB serum and semen levels and semen quality in high school and university students living in a highly PCB-polluted area of Italy. Subjects with a normal body mass index who did not make daily use of tobacco, alcohol, drugs, or medication were selected. All participants provided a fasting blood and a semen sample. Gas chromatography-mass spectrometry was used to determine the concentrations of 26 PCB congeners. The concentrations of PCB functional groups and total PCBs were also computed. A total of 143 subjects (median age 20, range 18–22 years) were enrolled. The median total PCB concentrations were 3.85 ng/mL (range 3.43–4.56 ng/mL) and 0.29 ng/mL (range 0.26–0.32 ng/mL) in serum and semen, respectively. The analysis of the associations between sperm PCB concentration and semen parameters showed (a) negative associations between some PCB congeners, functional groups and total PCBs and sperm total motility; (b) negative associations of total PCBs with sperm normal morphology; and (c) no association of PCBs with sperm concentration. Subjects at the highest quartile of semen total PCB concentration had 19% and 23% mean reductions in total motility and normal morphology, respectively, compared to those at the lowest quartile. The analysis of the associations of serum PCB levels with sperm parameters yielded null or mixed (some positive, other negative) results. In conclusion, the present study provides evidence of a negative effect of some PCB congeners and total PCBs in semen on sperm motility and normal morphology. However, the associations between the concentration of serum and semen PCB congeners and functional groups and sperm quality parameters were inconsistent

A comparison of populations vaccinated in a public service and in a private hospital setting in the same area

<p>Abstract</p> <p>Background</p> <p>Improving immunisation rates in risk groups is one of the main objectives in vaccination strategies. However, achieving high vaccination rates in children with chronic conditions is difficult. Different types of vaccine providers may differently attract high risk children.</p> <p>Aim</p> <p>To describe the characteristics of two populations of children who attended a private and a public immunisation provider in the same area. Secondarily, to determine if prevalence of patients with underlying diseases by type of provider differs and to study if the choice of different providers influences timeliness in immunisation.</p> <p>Methods</p> <p>We performed a cross-sectional study on parents of children 2 – 36 months of age who attended a private hospital immunisation service or a public immunisation office serving the same metropolitan area of Rome, Italy. Data on personal characteristics and immunisation history were collected through a face to face interview with parents of vaccinees, and compared by type of provider. Prevalence of underlying conditions was compared in the two populations. Timeliness in immunisation and its determinants were analysed through a logistic regression model.</p> <p>Results</p> <p>A total of 202 parents of children 2–36 months of age were interviewed; 104 were in the public office, and 98 in the hospital practice. Children immunised in the hospital were more frequently firstborn female children, breast fed for a longer period, with a lower birthweight, and more frequently with a previous hospitalisation. The prevalence of high risk children immunised in the hospital was 9.2 vs 0% in the public service (P = 0.001). Immunisation delay for due vaccines was higher in the hospital practice than in the public service (DTP, polio, HBV, and Hib: 39.8% vs 22.1%; P = 0.005). Anyway multivariate analyses did not reveal differences in timeliness between the public and private hospital settings.</p> <p>Conclusion</p> <p>Children with underlying diseases or a low birthweight were more frequently immunised in the hospital. This finding suggests that offering immunisations in a hospital setting may facilitate vaccination uptake in high risk groups. An integration between public and hospital practices and an effort to improve communication on vaccines to parents, may significantly increase immunisation rates in high risk groups and in the general population, and prevent immunisation delays.</p

Immunological and Molecular Correlates of Disease Recurrence after Liver Resection for Hepatocellular Carcinoma

The definition of the risk of hepatocellular carcinoma (HCC) recurrence after resection represents a central issue to improve the clinical management of patients. In this study we examined the prognostic relevance of infiltrating immune cell subsets in the tumor (TIL) and in nontumorous (NT) liver (LIL), and the expression of immune-related and lineage-specific mRNAs in HCC and NT liver derived from 42 patients. The phenotype of infiltrating cells was analyzed by flow cytometry, and mRNA expression in liver tissue was examined by real-time reverse transcription (RT)-PCR. The tumor immune microenvironment was enriched in inhibitory and dysfunctional cell subsets. Enrichment in CD4+ T-cells and in particular CD4 and CD8+ memory subsets within TIL was predictive of better overall survival (OS) and time to recurrence (TTR). Increased programmed death ligand 1 (PDL1) mRNA content and higher prevalence of invariant NKT (iNKT) cells were associated with shorter OS and TTR, respectively. By combined evaluation of infiltrating cell subsets along with mRNA profiling of immune and tumor related genes, we identified the intratumoral frequency of memory T-cells and iNKT-cells as well as PDL1 expression as the best predictors of clinical outcome. HCC infiltrate is characterized by the expression of molecules with negative regulatory function that may favor tumor recurrence and poor survival

Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

A cross-ancestry genome-wide association meta-analysis of amyotrophic lateral sclerosis (ALS) including 29,612 patients with ALS and 122,656 controls identifies 15 risk loci with distinct genetic architectures and neuron-specific biology. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons

La certificabilità dei bilanci delle aziende sanitarie: modelli, stato dell’arte e implicazioni dei PAC regionali

Il capitolo affronta il tema dei Percorsi di Certificabilità (PAC) dei bilanci delle aziende sanitarie offrendo una mappatura aggiornata dello stato di implementazione dei percorsi e una lettura manageriale e strategica di quanto implementato fino ad oggi. I PAC derivano dalla più ampia riforma di armonizzazione contabile del D.lgs 118/20114 che ha riportato alla luce il tema dell’importanza del dato di bilancio per la gestione delle aziende pubbliche. Nel tempo questo si è abbinato anche all’esigenza di introdurre dei sistemi informativi e di controllo (interno ed esterno). Dopo aver analizzato tutti i documenti (normativi e non) delle regioni al fine di mappare lo stato di attuazione dei PAC, è stata condotta una analisi compartiva tra modelli regionali poi approfondita da tre casi studio. Tutte le regioni (con eccezione di PA Trento, Val d’Aosta e Friuli-Venezia Giulia) hanno avviato i PAC tra il 2013 e il 2017 seguendo le indicazioni ministeriali e avendo già previsto numerose rimodulazioni e aggiustamenti. I PAC regionali hanno assunto profili molto differenziati per quanto riguarda l’assegnazione della responsabilità e governance del processo; le connessioni previste con altri sistemi aziendali quali Sistemi di Controllo interno/audit o sistemi informativi; la predisposizione di Linee Guida o Manuali Regionali di Procedure contabili; l’attivazione di percorsi di formazione di supporto o l’avvio di sperimentazioni/progetti pilota legati al PAC. Questo fa emergere due diversi approcci: uno più tecnico, basato sui principi di revisione contabile e centrato sul governo delle procedure di bilancio; uno più strategico, basato sui principi organizzativi e sulla diffusione di una cultura manageriale. I tre casi studio (Lazio, Liguria, Umbria) evidenziano anche un diverso approccio tra regione e aziende sanitarie nella gestione del PAC, dove la prima può interpretare un ruolo di guida top-down nel caso in cui voglia stimolare le aziende verso l’introduzione di sistemi contabili di maggiore qualità, oppure un ruolo di regia e coordinamento lasciando che il processo si svolga in modalità bottom-down con le aziende sanitarie responsabili di monitorare e gestire il percorso

Performance economiche delle aziende ospedaliere: quali strategie per il risanamento aziendale?

Il capitolo ha l’obiettivo di fornire una rappresentazione e disamina delle performance economiche, patrimoniali e finanziarie delle Aziende Ospedaliere (AO) pubbliche attraverso un’analisi per indici di bilancio. L’analisi ha permesso di: i) analizzare le performance economiche, patrimoniale e finanziarie di tutte le AO pubbliche italiane per gli anni 2015, 2016, 2017; ii) individuare casi di AO che mostrano dei miglioramenti nelle performance economiche nel periodo temporale 2015-2017 identificando dei casi di risanamento aziendale; ii) discutere quali siano stati i principali driver di performance e di risanamento. L’analisi è stata condotta a partire dai dati di bilancio come da modelli ministeriali Conto Economico e Stato Patrimoniale e include sia indici economici sia indici patrimoniali. Il quadro complessivo sulla redditività aziendale segnala un trend positivo di miglioramento dei risultati economici delle AO, con una progressiva riduzione del numero delle aziende con risultato negativo nel periodo analizzato. L’analisi mostra tuttavia come la gestione operativa presenti alcune criticità che mettono in luce come il sistema di finanziamento delle AO possa ancora essere distorsivo rispetto alla capacità di queste di mettere in relazione ricavi e costi al fine di ottenere una gestione economica ed efficiente: da un lato, i risultati di esercizio complessivamente migliori dei risultati operativi continuano a segnalare un ruolo rilevante delle gestioni straordinaria e finanziaria; dall’altro, guardando alla scomposizione dei ricavi, si evince come i contributi indistinti continuino a giocare un importante ruolo di risanamento. Sul lato costi della produzione si conferma un generale trend di contenimento dei costi per beni e servizi e del personale. Nonostante ciò questi continuano a essere superiori ai ricavi della produzione. Rispetto alle performance patrimoniali e finanziarie si segnala un trend di miglioramento del livello di indebitamento e performance non critiche per quanto riguarda la gestione della liquidità. Preoccupante è invece l’obsolescenza di macchinari e attrezzature sanitarie. Guardando alle aziende i cui risultati mostrano percorsi di miglioramento (o risanamento) del risultato operativo nel periodo analizzato, si riscontra che questo fenomeno sia stato maggiormente significativo le aziende caratterizzate nel periodo da situazioni di performance particolarmente negativa (ROS < -10%). Nonostante i dati di bilancio non siano sufficienti per comprendere appieno come si sia raggiunto il miglioramento, gli indici evidenziano che queste aziende più di altre hanno lavorato su un trend di riduzione dei costi per beni e servizi e per il personale, il miglioramento del rapporto di indebitamento, della copertura delle immobilizzazioni e dei propri livelli di liquidità e di obsolescenza

A serially coupled stationary phase method for the determination of urinary 8-oxo-7,8-dihydro-2′-deoxyguanosine by liquid chromatography ion trap tandem mass spectrometry

Oxidative attack to DNA is of particular interest since DNA modifications can lead to heritable mutations. The most studied product of DNA oxidation is 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG). While 8-oxodG determination in blood and tissue cells is prone to artifacts, its measurement in urine employing liquid chromatography tandem mass spectrometry (LC-MS/MS) has gained more and more interest for increased reliability. LC-MS/MS can be affected by matrix effects and this is particularly true when ion trap is used as MS analyzer, due to ion accumulation in the trap and related space charge effect. In the present work, we have developed a LC-MS/MS method where the combination of cation exchange and reverse phase solid phases resulted in LC separation optimization. This together with the employment of an isotopically labeled internal standard, allowed the usage of ion trap LC-MS/MS, typically not employed for quantitative measurement in biological samples, for the measurement of 8-oxodG in urine samples from control populations. Four different urine matrices were employed for method validation. Limit of quantitation was set at least at 0.5 ng/ml. While analyzing urine samples from healthy volunteers, 8-oxodG levels reported as ng/ml were statistically different comparing males with females (p<0.05, Mann Whitney test); while comparing results normalized for creatinine no statistical significant difference was found. Mean urinary 8-oxodG level found in healthy volunteers was 1.16±0.46 nmol/mmol creatinine. The present method by enhancing at best the chromatographic performances allows the usage of ion trap LC-MS/MS for the measurement of 8-oxodG in urine samples from control populations

AFM-based tribological study of nanopatterned surfaces: The influence of contact area instabilities

Although the importance of morphology on the tribological properties of surfaces has long been proved, an exhaustive understanding of nanopatterning effects is still lacking due to the difficulty in both fabricating 'really nano-' structures and detecting their tribological properties. In the present work we show how the probe-surface contact area can be a critical parameter due to its remarkable local variability, making a correct interpretation of the data very difficult in the case of extremely small nanofeatures. Regular arrays of parallel 1D straight nanoprotrusions were fabricated by means of a low-dose focused ion beam, taking advantage of the amorphization-related swelling effect. The tribological properties of the patterns were detected in the presence of air and in vacuum (dry ambient) by atomic force microscopy. We have introduced a novel procedure and data analysis to reduce the uncertainties related to contact instabilities. The real time estimation of the radius of curvature of the contacting asperity enables us to study the dependence of the tribological properties of the patterns from their geometrical characteristics. The effect of the patterns on both adhesion and the coefficient of friction strongly depends on the contact area, which is linked to the local radius of curvature of the probe. However, a detectable hydrophobic character induced on the hydrophilic native SiO2 has been observed as well. The results suggest a scenario for capillary formation on the patterns