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Regulatory T lymphocytes expressing the forkhead/winged helix transcription factor Foxp3 (Treg) play a vital role in the protection of the organism from autoimmune disease and other immunopathologies. The antigen specificity of Treg plays an important role in their in vivo activity. We therefore assessed the diversity of the T-cell receptors (TCRs) for antigen expressed by Treg newly developed in the thymus of autoimmune type 1 diabetes-prone NOD mice and compared it to the control mouse strain C57BL/6. Our results demonstrate that use of the TCRα and TCRβ variable (V) and joining (J) segments, length of the complementarity determining region (CDR) 3, and the diversity of the TCRα and TCRβ chains are comparable between NOD and C57BL/6 mice. Genetic defects affecting the diversity of the TCR expressed by newly developed Treg therefore do not appear to be involved in the etiology of type 1 diabetes in the NOD mouse.

As tool for identifying the pollution sources and their impact on human health, chemical signature of airborne particulates and deposition dusts is a subject of study since decades. Usually, three complementary ways are adopted for this purpose; they are: specific source markers, concentration ratios of pairs of congeners, and percent distributions of homologues within groups. After presenting the state-of-the-art about non-polar aliphatic (i.e., alkanes and alkenes), aromatic (PAHs, Nitro-PAHs) and polar (fatty acids, organic halides, polysaccharides) compounds associated with emissions, some unusual molecular signatures of non-polar organics are discussed, as possible tracers of emission sources. Non-polar organic fraction of particulates comprises short/medium-chain alkenes and alkanes (with carbon numbers ranging from 12 to 23), which display distinct relative abundances in petrol-derived spills and exhausts, release by microorganisms and high vegetation leaf debris. Long-chain alkanes associated with tobacco smoke show a peculiar iso/anteiso/normal homologue fingerprint and n-hentriacontane percentages higher than other emissions. Several concentration ratios of PAHs were analyzed in scientific literature as diagnostic of nature of emissions; meanwhile, the possible sources of uncertainty were elucidated. Due to its intrinsic limits (e.g., diagnostic ratios variability caused by decomposition and gas/particle exchange), the identification of sources exploiting molecular signature is overall restricted to qualitative purposes. Nevertheless, parameterizing molecular signatures through numerical indexes can aid in apportioning the pollution sources providing preliminary information for modeling. Future investigations would allow understanding the sources of uncommon molecular fingerprints (e.g., alkane/alkene distributions) and elucidating the role of humans as actual emitters of chemicals affecting internal environments.

Tobacco smoke (TS) is the source of a number of toxicants affecting the atmosphere and poses a threat to smokers and the whole community. Chemical, physical, and toxicological features of smoking products (vapors as well as mainstream, side stream, and third-hand smoke) have been investigated extensively. Special attention is paid to organic compounds (individually or in combination giving rise to peculiar molecular fingerprints), potentially able to act as “chemical signature” of TS. In this regard, the percent distribution of long-chainnormal, iso, and anteiso alkanes was ascertained as typical of TS. Nevertheless, until now no indexes have been identified as suitable for assessing the global TS contribution to environmental pollution, e.g., the TS percentage in carbonaceous aerosol and in deposited dusts, the only exception consisting in the use of nicotelline as tracer. This paper describes the results of an extensive study aimed at chemically characterizing the nonpolar lipid fraction associated to suspended particulates (PMs) and deposition dusts (DDs) collected at indoor and outdoor locations. Based on the iso, anteiso, and normal C29–C34 alkane profile in the samples as well in tobacco smoke- and no-TS-related emissions (literature data), various parameters describing the distribution of compounds were investigated. Finally, a cumulative variable was identified as the tobacco smoke impact index (TS%) suitable for estimating the TS percentage occurring in the particulate matter. The TS% rates were plotted vs. the exceedance of normal C31 alkane with respect to the average of C29 and C33 homologs, which results higher in TS than in most other emissions, revealing a link in the case of suspended particulates but not of deposited dusts. According to back analysis carried out on all particulate matter sets, it was found that traces of TS affect even remote areas, while inside the smokers’ homes the contributions of TS to PM could account for up to ~61% and ~10%, respectively, in PM and DD. This confirms the need of valuing the health risk posed by TS to humans, by means of tools easy to apply in extensive investigations. Supplementary Information The online version contains supplementary material available at 10.1007/s11356-021-16617-0.

Regulatory T lymphocytes expressing the forkhead/winged helix transcription factor Foxp3 (Treg) play a vital role in the protection of the organism from autoimmune disease and other immunopathologies. The antigen-specificity of Treg plays an important role in their in vivo activity. We therefore assessed the diversity of the T cell receptors for antigen (TCR) expressed by Treg newly developed in the thymus of autoimmune type I diabetes-prone NOD mice and compared it to the control mouse strain C57BL/6. Our results demonstrate that usage of the TCRa and TCRb variable (V) and joining (J) segments, length of the complementarity determining region (CDR) 3, and the diversity of the TCRa and TCRb chains are comparable between NOD and C57BL/6 mice. Genetic defects affecting the diversity of the TCR expressed by newly developed Treg therefore do not appear to be involved in the etiology of type I diabetes in the NOD mouse.

The composition of organic fraction associated to particulate emissions depends on their nature as well as on contour conditions. Therefore, many Authors have investigated the chemical signature of airborne particulate matter and dusts with the goal of identifying the pollution sources and assessing their impact on the environment and health. Usually, Authors use three complementary tools for this goal; they are specific source markers, concentration ratios of pairs of congeners, and percent distributions of homologues within a group. After the presentation of the state-of-the-art about non-polar aliphatic (alkanes and alkenes), aromatic (PAHs, Nitro-PAHs) and polar (fatty acids, organic halides, polysaccharides) compounds associated to emissions, this paper provides new information with regard to chemical signature non-polar fraction, suitable to trace the impact of sources on airborne particulate matter and settled dust. Non-polar organic fraction comprises short/medium-chain alkenes and alkanes (with carbon numbers ranging from 12 to 23), which display distinct relative abundances in petrol-derived exhausts, microorganism residues and high vegetation leaf debris. Meanwhile, long-chain alkanes associated to tobacco smoke show a peculiar iso/anteiso/normal homologues fingerprint as well as n-hentriacontane percentages higher than other emissions. Based on this particular alkane distribution, two indexes (ATSR and AICR) have tentatively identified and tested though comparing their rates in some sets of particulate samples. Until now, the study of molecular signature has overall limited to qualitative purposes and seldom exploited to achieve quantitative estimates of contributions of sources to air pollution. Future investigations will reach this goal through further clarifying the nature and behavior of organic contaminants associated to airborne and settled particulate matters.

The composition of organic fraction released in emissions varies with its nature and contour conditions; hence, the chemical signature of atmospheric particulate matter and dusts are investigated to identify the pollution sources and assess the respective aftermaths on environment and health. For this purpose, three complementary tools are usually adopted, i.e. specific source markers, concentration ratios of pairs of congeners, and percent distribution profiles of homologues (including derived “carbon preference indexes”). This paper provides an overview of investigations dealing with chemical signature of emission sources, applied to non-polar aliphatic (alkanes), aromatic (PAHs, Nitro-PAHs) and polar (fatty acids, organic halides, polysaccharides) organics affecting atmospheric particulate matter and deposition dust. Despite a rich literature is nowadays available, further investigations seem necessary to clarify the nature, sources and behaviors of mid-volatile, non-polar organic contaminants. More sophisticated investigations have gained importance recently (principal component analysis, source factorization modelling), nevertheless molecular fingerprints remain suitable to draw primary insights about the nature and impact of sources of environmental pollution.

Size distribution of toxicants in airborne particulates remains insufficiently investigated in Algeria. A 1-year campaign was performed at Bab Ezzouar, Algiers (Algeria), aimed at characterizing particulates for their physical and chemical features. For this purpose, scanning electronic microscopy (SEM), Raman spectroscopy (RaS), and GC-MS methodologies were applied. The samples were collected on daily basis by means of a high-volume sampling (HVS) system equipped with cascade impactor separating three size fractions, i.e., particles with aerodynamic diameters d < 1.0 mu m (PM1), 1.0 mu m

International audience; Regulatory T lymphocytes (Treg) play a vital role in the protection of the organism against autoimmune pathology. It is therefore paradoxical that comparatively large numbers of Treg were found in the thymus of type I diabetes-prone NOD mice. The Treg population in the thymus is composed of newly developing cells and cells that had recirculated from the periphery back to the thymus. We here demonstrate that exceptionally large numbers of Treg develop in the thymus of young, but not adult, NOD mice. Once emigrated from the thymus, an unusually large proportion of these Treg is activated in the periphery, which causes a particularly abundant accumulation of recirculating Treg in the thymus. These cells then rapidly inhibit de novo development of Treg. The proportions of developing Treg thus reach levels similar to or lower than those found in most other, type 1 diabetes-resistant, inbred mouse strains. Thus, in adult NOD mice the particularly large Treg-niche is actually composed of mostly recirculating cells and only few newly developing Treg.

Laboratory and field studies were carried out to assess the effects of oxidative degradation and volatilization on PM10 bound polycyclic aromatic hydrocarbons (PAHs), collected at low volume condition according to the EU sampling reference method EN12341:2014 (flow rate 2.3 m(3) h(-1)), on 47 mm quartz filters. For the laboratory experiments, pairs of twin samples were collected in field and, after treatments favoring decomposition or/and volatilization of PAHs on one sample, the PAH amount was compared with that of the corresponding untreated sample. Ozone exposure caused a general PAHs decay with more marked effects on benzo [a]pyrene, perylene and benz [a]anthracene; these compounds showed, similarly to benzo [ghi]perylene, correlations between ozone dose and losses. Treatments with zero air exhibited losses due to volatilization even for 5-ring PAHs up to benzo [a]pyrene, whereas a linear dependence was observed between filter PAH load and losses for benzo [a]anthracene, chrysene and benzofluoranthenes. Concentrations on samples collected simultaneously over 48, 24, 12 and 6 h were compared. Results confirmed a lack of temporal auto-consistency in the PAHs sampling methodology here adopted. In particular higher atmospheric PAH concentrations were ascertained on samples constituted by cumulative filters exposed over shorter sampling times. When 24 h and 2 x 12-h samples were compared, comparable losses were evaluated in the hot and cold seasons. This finding shows that, although in summer meteorology conditions favor sampling artifacts, the effectiveness of these phenomena continue in the winter, probably due to the larger amount of PAH available on the sampling filter (total PAHs similar to 10 vs 0.5 ng m(-3)). (C) 2018 Elsevier Ltd. All rights reserved.

Adenomatous polyps are precancerous lesions associated with a higher risk of colorectal cancer (CRC). Curcumin and anthocyanins have shown promising CRC-preventive activity in preclinical and epidemiological studies. The objective of this window-of-opportunity, proof-of principle trial was to evaluate the effect of curcumin combined with anthocyanin supplements on tissue biomarkers of colorectal adenomatous polyps. Eligible patients received either anthocyanin and curcumin supplementation or related matching placebo for 4–6 weeks before polyp removal. Adenomatous polyps and adjacent tissue biopsies were collected at baseline and after supplementation for immunohistochemical assessment of β-catenin, NF-kappa B (NF-κB), Ki-67, P53, and dysplasia. No differences were observed in baseline biomarker expression between normal and dysplastic tissues. The combination of anthocyanins and curcumin resulted in a significant borderline reduction of NF-κB immunohistochemistry (IHC) expression in adenoma tissue (geometric mean ratio (GMR): 0.72, 95% confidence interval (CI): 0.51–1.00, p-value: 0.05) and a trend to a reduction of Ki-67 (GMR: 0.73, 95% CI: 0.50–1.08, p-value: 0.11). No significant modulation of biomarkers in normal adjacent mucosa was observed. We concluded that the combined supplementation of anthocyanins and curcumin seems to lead to a potentially favorable modulation of tissue biomarkers of inflammation and proliferation in colon adenomas.

Psychotropic substances (PSs) are known to affect air and waters, while scarce attention has been paid to their occurrence in settled dusts although they can reach important concentrations there; moreover, no procedures have been developed for this specific purpose. In this study, a list of PSs (i.e., nicotine, cotinine, caffeine, cocaine, cannabinol, Δ9-tetrahydrocannabinol, cannabidiol, amphetamine, heroin, and methadone) were characterized in dusts from Rome and Fiumicino international airport, Italy, and from Ouargla city, Algeria. The analytical procedure, based on ultra-sonic bath extraction, silica column chromatography, and GC-MSD analysis, provided good recovery, uncertainty, sensitivity, and lack of interferences for all substances except amphetamine. In NIST SRM-2585 house dust, nicotine, cotinine, caffeine, cocaine, and cannabinol accounted for ~5.95, 0.87, 4.17, 7.0, and 2.2 μg/g, respectively; on the other hand, methadone, tetrahydrocannabinol, cannabidiol, and heroin (all

Immunosuppressive regulatory T lymphocytes (Treg) expressing the transcription factor Foxp3 play a vital role in the maintenance of tolerance of the immune-system to self and innocuous non-self. Most Treg that are critical for the maintenance of tolerance to self, develop as an independent T-cell lineage from common T cell precursors in the thymus. In this organ, their differentiation requires signals from the T cell receptor for antigen, from co-stimulatory molecules, as well as from cytokine-receptors. Here we focus on the cytokines implicated in thymic development of Treg, with a particular emphasis on the roles of interleukin-2 (IL-2) and IL-15. The more recently appreciated involvement of TGF-β in thymic Treg development is also briefly discussed. Finally, we discuss how cytokine-dependence of Treg development allows for temporal, quantitative, and potentially qualitative modulation of this process.

This study reports the first investigation of atmospheric illicit drug concentrations in Northern Europe using measurements of cocaine and cannabinoids in Amsterdam, London and Stockholm. Further, these measurements were compared to those made in Rome to explore the geographical and inter-city variability. Co-located measurements of atmospheric particulate mass and PAHs were used to help describe and interpret the illicit drug measurements with respect to atmospheric dispersion. Cocaine concentrations ranged from 0.03 to 0.14 ng/m3 in Amsterdam, from 0.02 to 0.33 ng/m3 in London and were below quantification limit (3 pg/m3) in Stockholm. Cannabinol was the only cannabinoid molecule detected in the three cities. During this campaign, London reported the highest concentrations of cocaine and meaningful differences were detected between the urban background and city centre London sites. Mean cocaine concentrations measured in Amsterdam during March 2011 were also compared with those measured simultaneously in eight Italian cities. The cocaine concentration in Amsterdam was comparable to that measured at an urban background in Milan and at a densely populated site in Florence. Although correlating atmospheric concentrations directly with drug prevalence is not possible using current data, links between concentrations of cocaine and estimates of abuse prevalence assessed by the more routinely used wastewater analysis were also examined. A statistically significant correlation was found between the two sets of data (R2 = 0.66; p = 0.00131). Results confirmed that meteorology, population rate and habits of consumption influence the atmospheric concentrations of drugs. If these confounding factors were better controlled for, the techniques described here could became an easy and cost effective tool to index the impact of cocaine abuse in the area; especially where local hot spots need to be identified. Keywords: Illicit drugs, Cocaine, Atmosphere, PM10, Wastewater analysis

The results of air quality monitoring carried out over several years (2008–2012) in two international airports near Rome (labelled as A and B) are reported and discussed. Airport A serves regular flights, airport B operates low-cost flights and, during the period investigated, had about 17% of airport A aircraft traffic load. Diffusive sampling of gaseous species (NO 2 , SO 2, BTX and O 3 ) was performed at several sites inside the airports. During 2012 the investigation was improved by including PM 10 and polycyclic aromatic hydrocarbons (PAHs). Higher concentrations of NO 2 (+18%) and lower of SO 2 (−20%) were found at airport B, compared to A, over the whole period investigated. The maximum concentrations of SO 2 were measured in 2011 at both airports (13.4 μg/m 3 and 10.8 μg/m 3 respectively for A and B), despite the decrease of aircraft traffic load recorded. Statistical analysis of PM 10 data showed that there was no significant difference between the average concentrations measured at the two airports (25.7 μg/m 3 and 27.4 μg/m 3 for A and B respectively) and among the sites investigated. The concentration of PAHs at airport B (4.3 ng/m 3 ) was almost twice that of airport A (2.2 ng/m 3 ), though the respective percentages of compounds were similar. Airport B seemed to be negatively influenced by its surroundings, in particular by vehicular traffic flows of two major roads, whereas airport A was positively influenced by the proximity to the seaside. PCA data analysis showed that airport A sites are differently impacted by the LTO flight phases according to their position, whereas at airport B it was impossible to find similar relationships.

Particulate polycyclic aromatic hydrocarbons, n-alkanes and polar organic compounds were investigated in the marine atmosphere of Southern and Eastern Mediterranean Sea, in the frame of the scientific cruise of Urania ship between 27 July and 11 August 2013. The PM10 fraction of aerosol to which most organic substances are associated, were collected daily; contemporarily, gaseous regulated toxicants (ozone, nitrogen oxides and carbon oxide) and carbonyls were recorded. Samplings were carried out in front of Palermo and Messina, respectively the start and end harbors, and along the cruise, both in movement (transects, N =14) and at stops (N =11). Total PAHs ranged from 0.06 ng/m(3) up to 1.8 ng/m(3), with the maximums observed close to harbors. Unlike total concentrations that were in general comparable, the percent composition of PAHs was distinct for harbors, transects and stops, which allowed to draw insights about the pollution sources impact Concentrations of n-alkanes (C-18-C-35) ranging from 6.7 to 43 ng/m(3) were quantified. The carbonyls evaluation revealed relatively high concentrations of formaldehyde (similar to 4-24 mu g/m(3)) and acetone (similar to 5-35 mu g/m(3)) near harbors, and of acrolein (up to 12 mu g/m(3)) offshore, while benzaldehyde was quite independent of the site type (approximate to 0.5 mu g/m(3)). Nicotine and caffeine were detected, at different extents (0.0-2.2 ng/m(3) and 0.01-0.17 ng/m(3), respectively), in ca. 70% and 100% of samples. Alkyl phthalates ranged from 2.7 to 67 ng/m(3) and showed variable percentages in the samples. Finally, traces of N,N-diethyl-meta-toluene amide (up to 0.4 ng/m(3)) were found at all sites. (C) 2016 Elsevier Ltd. All rights reserved.

Regulatory T (Treg) lymphocytes play a central role in the control of immune responses and so maintain immune tolerance and homeostasis. In mice, expression of the CD8 co-receptor and low levels of the co-stimulatory molecule CD28 characterizes a Treg cell population that exerts potent suppressive function in vitro and efficiently controls experimental immunopathology in vivo. It has remained unclear if CD8(+) CD28(low) Treg cells develop in the thymus or represent a population of chronically activated conventional T cells differentiating into Treg cells in the periphery, as suggested by their CD28(low) phenotype. We demonstrate that functional CD8(+) CD28(low) Treg cells are present in the thymus and that these cells develop locally and are not recirculating from the periphery. Differentiation of CD8(+) CD28(low) Treg cells requires MHC class I expression on radioresistant but not on haematopoietic thymic stromal cells. In contrast to other Treg cells, CD8(+) CD28(low) Treg cells develop simultaneously with CD8(+) CD28(high) conventional T cells. We also identified a novel homologous naive CD8(+) CD28(low) T-cell population with immunosuppressive properties in human blood and thymus. Combined, our data demonstrate that CD8(+) CD28(low) cells can develop in the thymus of mice and suggest that the same is true in humans.

Hematopoietic precursors entering the thymus undergo a maturation process leading to the generation of a variety of T cell subsets that migrate to the periphery to perform their effector functions. This maturation process is strictly regulated by multiple interactions of developing T cells with thymic stroma cells. Signals received via the T cell receptor for antigen, co-stimulatory molecules and cytokines will determine, through thymic selection and lineage choice, thymocyte-fate. Recently, different populations of peripheral antigen presenting cells and T cells have been reported to enter the thymus. Here we review how these cells migrating from the periphery to the thymus modulate T cell development.

Antimicrobial resistance (AMR) became in the last two decades a global threat to public health systems in the world. Since the antibiotic era, with the discovery of the first antibiotics that provided consistent health benefits to human medicine, the misuse and abuse of antimicrobials in veterinary and human medicine have accelerated the growing worldwide phenomenon of AMR. This article presents an extensive overview of the epidemiology of AMR, with a focus on the link between food producing-animals and humans and on the legal framework and policies currently implemented at the EU level and globally. The ways of responding to the AMR challenges foresee an array of measures that include: designing more effective preventive measures at farm level to reduce the use of antimicrobials; development of novel antimicrobials; strengthening of AMR surveillance system in animal and human populations; better knowledge of the ecology of resistant bacteria and resistant genes; increased awareness of stakeholders on the prudent use of antibiotics in animal productions and clinical arena; and the public health and environmental consequences of AMR. Based on the global nature of AMR and considering that bacterial resistance does not recognize barriers and can spread to people and the environment, the article ends with specific recommendations structured around a holistic approach and targeted to different stakeholders.

International audience; Upon activation, naive CD4+ T cells differentiate into distinct T cell subsets via processes reliant on epigenetically regulated, lineage-specific developmental programs. Here, we examined the function of the histone methyltransferase SETDB1 in T helper (Th) cell differentiation. Setdb1-/- naive CD4+ T cells exhibited exacerbated Th1 priming, and when exposed to a Th1-instructive signal, Setdb1-/- Th2 cells crossed lineage boundaries and acquired a Th1 phenotype. SETDB1 did not directly control Th1 gene promoter activity but relied instead on deposition of the repressive H3K9me3 mark at a restricted and cell-type-specific set of endogenous retroviruses (ERVs) located in the vicinity of genes involved in immune processes. Refined bioinformatic analyses suggest that these retrotransposons regulate Th1 gene cis-regulatory elements or act as Th1 gene enhancers. Thus, H3K9me3 deposition by SETDB1 ensures Th cell lineage integrity by repressing a repertoire of ERVs that have been exapted into cis-regulatory modules to shape and control the Th1 gene network.

The artifacts induced by oxidative degradation and volatilization were assessed with regards to determination of particulate atmospheric PAHs collected at low volume conditions (2.3 m3 h−1) according to the EU Reference Method EN 12341:2014. In order to evaluate the oxidative degradation, PAH measures carried out through collecting airborne particulate with and without ozone denuders were examined. Simultaneously, the influence of volatilization was investigated by comparing concentrations of PAHs in particulate samples collected over 24-h and 12-h using conventional instruments. Summer and winter/spring campaigns were carried out in order to assess the influence of environmental contour on the artifact processes. Oxidative degradation led to a general decrease of PAH concentrations in both periods; in particular, the highest losses were observed for benzo[a]pyrene and perylene reaching, in average, ca. 20%. In the summer, the effect of volatilization exceeded that of oxidative degradation for light PAHs up to benzo[e]pyrene. In the winter/spring time, the influence of both artifact typologies could be mitigated by splitting the normal 24-h collection interval starting at midnight into two 12-h intervals. A mitigation of the losses could even be obtained by fixing the start time sampling fixed at noon or in the first hours of the day. Finally, the feasibility of collecting PAHs through prolonged sampling (>1 month) at the flow rate of 1.1 L min−1 was preliminarily investigated. Results indicated that this approach is unsuitable for minimizing the oxidative artifacts.

Nell'ambito del Progetto "Treno Verde 2017" di Legambiente e Ferrovie dello Stato (febbraio-aprile 2017), il ns. Istituto ha monitorato la qualità ambientale all'interno di undici istituti scolastici in altrettante città italiane: Asti, Bari, Bologna, Catania, Fabriano (PE), Milano, Paola (CS), Pescara, Potenza, Salerno e Vicenza. A tal fine, in ogni scuola sono stati esaminati due o tre ambienti interni (aule, mense o uffici), dove sono sti misurati gli idrocarburi aromatici gassosi benzene, toluene, etilbenzene e xileni (il benzene è un parametro di qualità dell'aria, la sua concentrazione media non deve superare 5,0 µg/m3). Misure comparative sono state effettuate all'esterno delle scuole. Contestualmente, in uno o più ambienti interni sono state esaminate le polveri di deposizione per il contenuto d'idrocarburi policiclici aromatici (IPA) e di esteri ftalici. Infatti, gli IPA sono riconosciuti cancerogeni e la normativa ambientale fissa un limite di 1,0 ng/m3 per la sua concentrazione media annua in aria; gli ftalati sono i più importanti e diffusi interferenti endocrini tra i contaminanti ambientali, essendo componenti fondamentali di plastiche, gomme, vernici, colle, polimeri e prodotti d'uso comune. Le polveri di deposizione degli ambienti interni hanno una composizione diversa dalle polveri sospese, soprattutto perché assai più ricche di ftalati e plastificanti, ritardanti di fiamma, anti-ossidanti, grassi, tensioattivi. Perciò, esse sono un importante veicolo d'esposizione umana a sostanze nocive, per contatto e ingestione. Per il monitoraggio, gli idrocarburi gassosi erano prelevati mediante campionatori diffusionali (tipo Analyst BTEX), esposti all'aria per un periodo mediamente compreso tra 10 e 15 gg. Le polveri di deposizione erano meccanicamente asportate con un filtro in fibra di quarzo da una superficie pari a 0,5 m2, posta orizzontalmente a 1,8-2,0 m di altezza. Le analisi chimiche erano eseguite con procedure e metodi strumentali consolidati, sviluppati in istituto. Nelle scuole il benzene (~2-12 µg/m3) eccedeva il limite di legge a Catania e Pescara e, tranne i due casi (Salerno e Vicenza) era più abbondante che in aria esterna; analogo comportamento mostravano gli idrocarburi totali BTEX (~7-43 230g/m3). Gli IPA delle polveri (~230-1800 ng/m2), con il massimo in Paola e Bari) erano prevalente-mente a 3-4 anelli (fenantrene-pirene), ma gli IPA cancerogeni raggiungevano 158 ng/m2 a Foligno. Il benzo[a]pirene in oltre la metà dei casi era assente e non superava mai 23 ng/m2. Le polveri erano ricche di ftalati (44-270 µg/m2, soprattutto diisobutilftalato e dietilesilftalato), ma contenevano anche dietilesiladipato, un altro plastificante. Infine, era presente DEET, un comune repellente d'insetti (fino a 570 ng/m2).

The environmental influence of biomass burning for civil uses was investigated through the determination of several air toxicants in the town of Leonessa and its surroundings, in the mountain region of central Italy. Attention was focussed on PM10, polycyclic aromatic hydrocarbons (PAHs) and regulated gaseous pollutants (nitrogen dioxide, ozone and benzene). Two in-field campaigns were carried out during the summer 2012 and the winter 2013. Contemporarily, air quality was monitored in Rome and other localities of Lazio region. In the summer, all pollutants, with the exception of ozone, were more abundant in Rome. On the other hand, in the winter, PAH concentration was higher in Leonessa (15.8 vs. 7.0 ng/m3), while PM10 was less concentrated (22 vs. 34 μg/m3). Due to lack of other important sources and to limited impact of vehicle traffic, biomass burning was identified as the major PAH source in Leonessa during the winter. This hypothesis was confirmed by PAH molecular signature of PM10 (i.e. concentration diagnostic ratios and 206 ion mass trace in the chromatograms). A similar phenomenon (i.e. airborne particulate levels similar to those of the capital city but higher PAH loads) was observed in other locations of the province, suggesting that uncontrolled biomass burning contributed to pollution across the Rome metropolitan area.

Nella letteratura scientifica sui farmaceutici, una sezione è dedicata alla presenza dei principi attivi, metaboliti e sotto-prodotti nell'ambiente. Tuttavia, il focus è sempre sugli organismi o sistemi acquosi che ricevono le sostanze dopo l'impiego sull'uomo o sugli animali (liquidi biologici, acque di scarico, fiumi). Il comparto atmosfera non è stato mai studiato; infatti, da una parte i farmaci sono molecole polari e a medio-alto peso formula, dall'altra raramente sono impiegate come spray o aerosol, ma sono ingerite, inoculate o spalmate come soluzioni, creme e pastiglie; inoltre, le quantità sono minori di quelle di prodotti industriali o per la casa. Perciò si pensa che i farmaci non si trovino né come vapori, né associati alle polveri ambientali. Invece, l'uso di sostanze di proprietà sanitarie (farmaci, disinfettanti e igienizzanti, stimolanti, ormoni) è diffuso anche in comparti insospettati. Esse sono impiegate, spesso senza conoscerne le contro-indicazioni, in quantità eccessive. Perciò, è facile che ogni ambiente (specie quelli interni) sia contaminato di farmaci. Il primo studio in assoluto è stato da noi eseguito esaminando le polveri PM10 di città (Roma, Rende e Amsterdam). Per lo sviluppo del metodo (basato sull'estrazione con solvente, reazione con un silanizzante e analisi GC-MSD), si è esaminata l'"house dust" SRM-2585 del NIST. Test preliminari confermavano la presenza di farmaci a concentrazioni comprese tra i ng e i µg per g di polvere. Le sostanze esaminate erano: a) ibuprofen, ketoprofen, fenoprofen, naproxen (antiinfiammatori); b) aspirina, paracetamolo, acido salicilico (analgesici, antipiretici); c) fenofibrato (antiipercolesterolo); d) diclofenac (antireumatico, antiinfiammatorio); e) furosemide (diuretico); f) acetilcisteina (mucolitico); g) sulfanilammide (antibiotico, antibatterico); h) parabeni, acido p-idrossibenzoico (antibatterici). I risultati sono riassunti in Figura 1. Figura 1

Till now, no attention has been paid to pharmaceuticals (PCs) in the air, though they are known to affect waters, soils, foods and biota. This paper describes the first attempt to characterize the PC occurrence in the air. Airborne particulates (PM10 or PM2.5 fractions, from Amsterdam, Netherland, Rome and Rende, Italy) were sampled on quartz fiber filter by means of pumping systems operating at medium-volume conditions (16 or 38.5 L min-1). The samples were solvent extracted through sonication with a dichloromethane:acetone:methanol mixture and reduced close to dryness; three fractions of the residue were separated through column chromatography; they comprised non polar, low polar and very polar organic compounds, respectively, and PCs were in the third one. Chemical analysis was performed by means of gas chromatography coupled with mass spectrometric detection (GC-MSD), after treatment of solutions with methyl,tertzbutylsilyl-trifluoroacetamide (MTBSTFA) to form silyl derivatives of most PCs. The following substances were investigated: acetaminophenol, ibuprofen, ketoprofen, fenoprefen, naproxen, fenofibrate, diclofenac, acetylcysteine and sulfanilamide; p-hydroxybenzoic acid and salicylic acid; and parabens (methyl, ethyl and propyl). Except aspirin, acetamidophenol, acetylcysteine and sulfanilamide, the target compounds could be quantified with good repeatability, reproducibility and percent recoveries (on the average, ∼7.5%, ∼7.1% and 91%, respectively). The PC concentrations ranged

Urban commuters are exposed to elevated levels of air pollutants, especially in heavily polluted areas and traffic congested roads. In order to assess the contribution of commuting to citizens’ exposure, measurements of fine particulate (PM2.5) and polycyclic aromatic hydrocarbons (PAHs) were carried out in cars, busses, and metro trains, within the LIFE+ EXPAH Project. Monitoring campaigns were performed in Rome, Italy, from April 2011 to August 2012. Inside the busses, the concentration of total PAHs ranged from 2.7 to 6.6 ng/m3 during the winter and from 0.34 to 1.51 ng/m3 in the summer. In cars, internal concentrations were in the range 2.2–7.3 and 0.46–0.82 ng/m3, respectively, in the 2-year time. Analogous differences between seasons were observed examining the benzo[a]pyrene-equivalent carcinogenicity. In the metro trains, total PAHs ranged from 1.19 to 2.35 ng/m3 and PM2.5 ranged from 17 to 31 μg/m3. The PM2.5 concentration in all transport modes ranged from 10 to 160 μg/m3 during the cold season and 15–48 μg/m3 during the warm time. The average inside-to-outside ratio (R I/O) was found to exceed 1.0 for PM2.5 only in busses, probably due to dust re-suspension caused by crowding and passenger activity. The molecular PAH signature suggests that vehicle emissions and biomass combustion were the major sources of commuters’ exposure to these toxicants in Rome. According to linear regression analysis, the PAH concentrations inside the vehicles were linked to those detected outside. Statistically significant differences (p

The presence of drugs in outdoor air has been established, but few investigations have been conducted indoors. This study focused on psychotropic substances (PSs) at three schools, four homes and one office in Rome, Italy. The indoor drug concentrations and the relationships with the outdoor atmosphere were investigated. The optimised monitoring procedure allowed for the determination of cocaine, cannabinoids and particulate fractions of nicotine and caffeine. In-field experiments were performed during the winter, spring and summer seasons. Psychotropic substances were observed in all indoor locations. The indoor concentrations often exceeded those recorded both outdoors at the same sites and at the atmospheric pollution control network stations, indicating that the drugs were released into the air at the inside sites or were more persistent. During winter, the relative concentrations of cannabinol, cannabidiol and tetrahydrocannabinol depended on site and indoor/outdoor location at the site. Keywords: Indoor environments, Airborne particulate, Psychotropic substances, Illicit drugs, Cocaine, Cannabis

Indoor and outdoor concentrations of polycyclic aromatic hydrocarbons (PAHs) associated with PM2.5 particles were monitored in three microenvironments (schools, homes and offices) in the city of Rome, Italy, between winter 2011 and summer 2012. Molecular signatures and indoor/outdoor concentration ratios of PAHs were investigated, with special emphasis on carcinogenic congeners. At indoor locations, total PAHs ranged, on average, from 1.8 to 8.4 ng/m3 in winter and from 0.30 to 1.35 ng/m3 in spring/summer. Outdoors, total PAH concentrations were found to reach 6.3–17.9 ng/m3 in winter and 0.42–1.74 ng/m3 in spring-summer. Indoors, the concentration of benzo[a]pyrene (BaP) was as high as 1.1 ng/m3 in winter and below 0.1 ng/m3 in the warm season, independently of site type; the yearly average remained below the European guideline value. The indoor/outdoor concentration ratios of individual compounds were lower than one for most of congeners, suggesting that outdoor sources were predominant. Nonetheless, the percentages of PAH compounds changed with sites and seasons; in particular, in spring/summer, the concentration of BaP at our sites was more than twice that recorded at the regional network stations.

Till now, the Sahara desert sands have scarcely characterized for their organic contents, despite they are known to heavily affect Europe and America when transported by winds. In this study, the composition of sands collected in ten oasis lying in two regions of the Algerian Sahara during 2011 was investigated with regards to organic fraction. Attention was paid to anthropogenic and biogenic sources of organics associated to sands, through the characterization of n-alkanes, n-alkanoic and n-alkanedioic acids, n-alkanols, sterols, PAHs and caffeine. The organic fraction load on sands associable to natural sources was higher in the Region of Biskra than in that of Ouargla. The biogenic contribution to the total amount of organics in sands exceeded that of the anthropogenic sources. The composition of sands from Hassi Messaoud, compared to that observed there in 2006, showed that the anthropic impact over the region was not changed. © 2014 Elsevier Ltd.

There is a lack of validated predictors on which to decide the timing of discharge in patients already hospitalized for upper nonvariceal bleeding.Identify factors that appear to protect nonvariceal bleeders from the development of negative outcome (rebleeding, surgery, death).Secondary analysis of two prospective multicenter studies. Multivariate analyses for each investigated outcome were performed; a single model was developed including all factors that were statistically significant in each sub-model. A final score was developed to predict favourable outcomes. Prognostic accuracy was tested with ROC curve analysis.Out of 2398 patients, 211 (8.8%) developed one or more adverse outcomes: 87 (3.63%) had rebleeding, 46 (1.92%) needed surgery and 107 (4.46%) died. Predictors of favourable prognosis were: ASA score 1 or 2, absence of neoplasia, outpatient bleeding, use of low-dose aspirin, no need for transfusions, clean-based ulcer, age70 years, no haemodynamic instability successful endoscopic diagnosis/therapy, no Dieulafoy's lesion at endoscopy, no hematemesis on presentation and no need for endoscopic treatment. Overall prognostic accuracy of the model was 83%. The final score accurately identified 20-30% of patients that eventually do not develop any negative outcome.The "good luck score" may be a useful tool in deciding when to discharge a patient already hospitalized for acute non-variceal bleeding.

Regulatory T (Treg) lymphocytes play a central role in the control of autoimmune pathology. Any alteration in Treg-cell biology in mouse strains used for the study of these disorders therefore raises the question of its direct link with disease susceptibility. Paradoxically, in non-obese diabetic (NOD) mice increased numbers of Treg cells develop in the thymus. In this report we identify a locus of

Psychotropic substances were monitored in eight big cities of Italy over one year, starting in May 2010, in the frame of the Ariadrugs Project. Yearly average concentrations ranged from 0.02 ± 0.01 to 0.26 ± 0.11 ng/m3 for cocaine, from 0.05 ± 0.05 to 0.96 ± 1.37 ng/m3 for cannabinoids, from 16 ± 6 to 61 ± 28 ng/m3 for nicotine, and from 1.0 ± 0.8 to 8 ± 7 ng/m3 for caffeine. Palermo and Turin were the cities suffering the lowest and the highest psychotropic substance concentrations, respectively. Nicotine and cocaine exhibited trends less seasonally modulated than common air toxicants. Caffeine and cannabinoids peaked in winter dropping close to zero from May to August. In Rome, where various anthropic contours were investigated in February 2011, differences were observed both in net concentrations and ratios of psychotropic substances vs. regulated toxicants. Ambient drugs look as a consequence of addiction and their burdens give insights about the corresponding consumes.

Gli Idrocarburi Policiclici Aromatici (IPA) sono una classe di composti riconosciuti come cancerogeni, per questo la Direttiva Europea 2008/50/EC fissa come media annua per la concentrazione del benzo(a)pirene nel PM10 un valore guida pari ad 1 ng/m3, inoltre impone il monitoraggio di altri sei congeneri. La misura degli IPA atmosferici può essere però inficiata già nella fase di campionamento. Due sono i processi principali di produzione degli artefatti: la perdita per evaporazione dal filtro di raccolta degli omologhi più leggeri e i fenomeni di decomposizione legati alla presenza di ossidanti atmosferici quali l'ozono. I metodi di riferimento per l'analisi degli IPA sottolineano che per ottenere un campione rappresentativo del reale contenuto di questi composti nel PM10 sarebbe necessario utilizzare un sistema di abbattimento dell'ozono (scrubber). Ciononostante, la mancanza di studi riguardanti l'applicazione in campo di questi sistemi ne impedisce l'inserimento nelle procedure della norma. Tramite l'utilizzo contemporaneo di 6 linee di prelievo, sono state svolte indagini sull'entità dei processi ossidativi e di volatilizzazione a carico degli IPA durante il campionamento secondo diverse condizioni meteorologiche, secondo diverse durate dei tempi di raccolta e anche variando gli orari di inizio del campionamento. I risultati hanno confermato che durante l'estate gli IPA campionati secondo la norma EN12341, ma senza lo scrubber, possono subire perdite fino al 30%. Le perdite indotte dall'evaporazione erano più importanti delle perdite dovute a decomposizione per gli IPA più leggeri, dimostrando che questo processo, seppur meno considerato, è molto rilevante. La durata del campionamento, ma anche l'orario di inizio, possono contribuire alla riduzione degli artifacts.

Per il progetto SELVA, un'indagine sull'impatto della combustione di biomassa, in specie di piccole centrali termiche a legna, è stata effettuata a Leonessa mediante la caratterizzazione d'idrocarburi policiclici aromatici IPA nelle polveri atmosferiche. A tal fine, la frazione PM10 è stata raccolta sia nell'area cittadina, sia nei dintorni rurali (Terzone), in due distinte stagioni (luglio 2012, febbraio 2013). Nell'area, situata nell'Appennino Laziale a 974 m di altitudine; la combustione biomassa è ampiamente utilizzata per gli usi domestici, soprattutto riscaldamento degli ambienti, e anche per alimentare una centrale termica collocata presso una scuola. Operativamente, le polveri erano raccolte su filtri in teflon, per due settimane, con campionatori sequenziali a medio flusso (38.2 L/min). I campioni erano pesati, raggruppati per settimane, estratti con solvente in bagno ultrasonico, purificati su colonna d'allumina e infine processati per gascromatografia - spettrometria di massa. I risultati sono stati analizzati con quelli d'indagini parallele in altre località.

Riassunto: Nell'ambito del progetto LIFE+EXPAH, misure d'idrocarburi policiclici aromatici IPA sono state effettuate presso scuole, case e uffici di Roma tra novembre 2011 e luglio 2012. Ogni sito è stato esaminato in due distinte stagioni dell'anno, per non meno di tre settimane. Operativamente, le polveri fini (PM2,5) in aria erano raccolte giornalmente, pesate e unite in gruppi settimanali per la valutazione degli IPA. La procedura adottata era basata sull'estrazione con solvente, frazionamento su colonna d'allumina e analisi strumentale GC-MSD. Le misure erano effettuate indoor, outdoor ai siti e presso alcune stazioni della rete regionale ARPA Lazio, allo scopo di valutare l'effettiva esposizione della popolazione alle polveri fini e gli IPA cancerogeni, di individuare l'eventuale impatto di sorgenti interne e anche di verificare l'attendibilità delle stime basate sulle misure alle stazioni ARPA. Quanto agli IPA, negli ambienti indoor la concentrazione del benzo[a]pirene poteva superare il valore limite di legge, quantunque questo sia valido come media annua; i valori indoor erano perlopiù inferiori a quelli outdoor ai siti di misura, ma non a quelli delle stazioni ARPA. Infatti, in primavera-estate le concentrazioni di BaP superavano d'un fattore 1.3 - 1.9 quelli ARPA. Gli IPA totali, invece, erano sempre inferiori nei siti indoor.

Per la prima volta sono state misurate le concentrazioni di cocaina e cannabinoidi nelle polveri atmosferiche di Amsterdam, Londra e Stoccolma. Per individuare le differenze all'interno delle rispettive città, a Londra sono stati investigati i siti di Marylebone Road (MR, sito di traffico) e North Kensington (NK, fondo urbano), ad Amsterdam 2 siti da traffico (Einsteinweg, EW e Jan van Galenstraat, GS) e un fondo urbano (Vondelpark, VP), mentre a Stoccolma le misure hanno riguardato un solo sito nell'area di Södermalm (fondo urbano). A Londra le misure sono state condotte sia in inverno che in estate in modo da individuare eventuali differenze stagionali. Per meglio osservare le differenze tra città del sud e del nord Europa, nel Marzo 2013 sono stati raccolti campioni di polveri contemporaneamente a Roma, Amsterdam e Londra. Come aspettato, dati i livelli di abuso stimati nel Regno Unito, a Londra sono state misurate le più alte concentrazioni di cocaina (0.15 ± 0.11 ng/m3), nonostante le avverse condizioni metereologiche avessero portato ad un abbattimento degli inquinanti. Ad Amsterdam i livelli di cocaina nello stesso periodo erano compresi tra i 0.05 e i 0,07 ng/m3 e a Roma la media su 4 siti (Francia, Villa Ada, Cipro e Cinecittà) era pari 0,09 ± 0,03 ng/m3. A Stoccolma tra Settembre e Novembre del 2014 sono state identificate solo tracce non quantificabili di cocaina. Nonostante i livelli di prevalenza del consumo di cannabis in Olanda e nel Regno Unito siano considerati tra i più alti in Europa, le concentrazioni atmosferiche dei cannabinoidi ad Amsterdam e a Londra sono risultate minori di quelle in genere misurate in Italia nello stesso periodo dell'anno, forse a causa del fatto che queste sostanze vengono prevalentemente consumate indoor nei paesi del Nord Europa.

Il trasporto marittimo e i porti sono importanti per lo sviluppo economico e occupazionale poiché in grado di attirare investimenti e risorse locali e nazionali ma, nel contempo generano rilevanti impatti ambientali. Nell'ambito del progetto "Green Ports" sono stati raccolti nella città di Crotone nel mese di ottobre 2015 campioni giornalieri di PM10, in tre siti: all'interno del porto precisamente sul molo, in un una postazione urbana "G. da Fiore" e in una stazione di monitoraggio dell'ARPA Calabria "Fermi". La caratterizzazione chimica delle polveri atmosferiche ha riguardato gli idrocarburi policiclici aromatici (IPA), gli n-alcani (C19-C36) e alcuni composti organici polari presenti nell'atmosfera (nicotina e cocaina, ftalati). Nel corso di tale attività la concentrazione media degli IPA totali variava da 0.33 ng/m3 calcolata nella stazione Fermi a 1.56 ng/m3 in G. Fiore. Il Benzo[a]pirene non eccedeva mai il valore annuale Europeo guida di 1.0 ng/m3, variando tra 0.03 e 0.09 ng/m3 rappresentando circa il 6% del totale presso la scuola e oltre il 10% al porto e a Fermi. La frazione percentuale dei singoli IPA e i rapporti diagnostici per i tre siti dimostravano distinte fonti di emissioni: industriali, attività portuali e di traffico veicolare. La distribuzione media risultava assai simile a Fermi e al porto ma distinta alla scuola; le differenze divenivano più marcate distinguendo i giorni 13-14 ottobre dagli altri; in tali campioni anche tra il porto e il sito Fermi (vedi figura) erano evidenti differenze di composizione. L'analisi degli alcani confermava, sebbene le concentrazioni totali non variassero nei tre siti, il differente contributo delle emissioni naturali e antropiche. In tutti e tre i casi si osserva la sovrapposizione del modello distributivo a campana (max in C24-C25) tipico degli esausti d'origine petrolifera (antropica), con quello a dente di sega (max in C29 e C31), d'origine vegetale (biogenica). In valore assoluto, le concentrazioni degli n-alcani erano coerenti con quelli misurate in aree poco inquinate (~10 ng/m3 a Fermi, ~13 ng/m3 alla scuola e al porto). Il contributo naturale si rivelava più importante in città e nella periferia (CPI = 5.5) rispetto al porto (CPI = 2.5). La concentrazione totale di ftalati presentava ampie variazioni giornaliere, ma i valori medi e la composizione percentuale non erano dissimili nei tre siti (~10-13 ng/m3). Ciò sembra indicare che, quantunque la circolazione dell'aria tenda a limitare l'accumulo degli inquinanti (valori assoluti simili al centro città), l'impatto delle fonti antropiche (attività portuali) non è trascurabile.

Durante la campagna oceanografica "Fenice 2013" condotta dal 27 luglio all' 11 agosto del 2013, sono stati analizzati gli idrocarburi policiclici aromatici (IPA), gli n-alcani e i composti organici polari presenti nell'atmosfera marina del Sud e del Mediterraneo orientale. Nel corso dell'intera crociera scientifica sono stati raccolti campioni di PM2.5, e di alcuni composti carbonilici contemporaneamente al monitoraggio automatico di gas tossici quali: O3, NO, NO2 e CO. Il campionamento dell'aerosol marino è avvenuto alla partenza e all'arrivo di fronte rispettivamente ai porti di Palermo e Messina, e in base alle soste (N=11) e ai trasferimenti intermedi durante la rotta (N=14, transetti) (Fig.1). Gli IPA totali erano compresi tra 0.06 e 1.80 ng/m3, in accordo con Mulder et al. (2014)[1], con i massimi osservati vicino ai porti. Le medie concentrazioni totali per le tre tipologie di sito erano comparabili, tuttavia la distribuzione percentuale dei congeneri era diversa dando importanti informazioni riguardo l'impatto e la tipologia delle sorgenti di inquinamento. Gli alcani totali (C18-C35) variavano tra 6.7 e 43 ng/m3. La nicotina e la caffeina (0.0-2.2 ng/m3 e 0.01- 0.17 rispettivamente) sono state rilevate in più del 70% dei campioni. Gli ftalati alchilici (2.7-67 ng/m3) mostravano una composizione variabile e tracce di N,N-dietil- meta-toluenammide sono state trovate in tutti i campioni. Erano presenti concentrazioni relativamente alte di carbonili volatili: la formaldeide (~ 2.5 vs 0.8 ?g/m3) e l'acetone (~ 4.4 vs 2.1 ?g/m3) risultavano elevati vicino ai porti, l'acroleina (~ 0.9 vs 0.1 ?g/m3) in mare aperto, mentre la benzaldeide rimaneva in ogni sito relativamente costante (~ 0.5 ?g/m3).

From an Italian Registry of patients with upper gastrointestinal hemorrhage (UGIH), we assessed the clinical outcomes and explored the roles of clinical, endoscopic, and therapeutic factors on 30-day mortality in a real life setting.Prospective analysis of consecutive patients endoscoped for UGIH at 23 community and tertiary care institutions from 2003 to 2004. Covariates and outcomes were defined a priori and 30-day follow-up obtained. Logistic regression analysis identified predictors of mortality.One thousand and twenty patients were included. A total of 46 patients died for an overall 4.5% mortality rate. In all, 85% of deaths were associated with one or more major comorbidity. Sixteen of 46 patients (35%) died within the first 24 h of the onset of bleeding. Of these, eight had been categorized as ASA class 1 or 2 and none of them was operated upon, despite a failure of endoscopic intention to treatment in four. Regression analysis showed advanced age, presence of severe comorbidity, low hemoglobin levels at presentation, and worsening health status as the only independent predictors of 30-day mortality (P0.001). The acute use of a PPI exerted a protective effect (OR 0.23, 95% CI 0.09-0.73). Recurrent bleeding was low (3.2%). Rebleeders accounted for only 11% of the total patients deceased (OR 3.27, 95% CI 1.5-11.2).These results indicate that 30-day mortality for nonvariceal bleeding is low. Deaths occurred predominantly in elderly patients with severe comorbidities or those with failure of endoscopic intention to treatment.

The air quality of three different microenvironments (school, dwelling, and coffee bar) located in the city of Rome, Italy, was assessed. Indoor and outdoor concentrations of polycyclic aromatic hydrocarbons (PAHs) associated with PM2.5 particles were determined during an intensive 3-week sampling campaign conducted in March 2013. In interiors, total particulate PAHs ranged from 1.53 to 4.96 ng/m(3) while outdoor air contained from 2.75 to 3.48 ng/m(3). In addition, gaseous toxicants, i.e., NO2, NOx , SO2, O3, and BTEX (benzene, toluene, ethyl-benzene, and xylene isomers), were determined both in internal and external air. To solve the origin of indoor and outdoor PAHs, several source apportionment methods were applied. Multivariate analysis revealed that emissions from motor vehicles, biomass burning for heating purposes, and soil resuspension were the major sources of PAHs in the city. No linear correlation was established between indoor and outdoor values for PM2.5 and BTEX; the respective indoor/outdoor concentration ratios exceed unity except for PM2.5 in the no smoking home and benzene in all school floors. This suggests that important internal sources such as tobacco smoking, cleaning products, and resuspension dust contributed to indoor pollution. Using the monitoring stations of ARPA Lazio regional network as reference, the percentage within PAH group of benzo[a]pyrene, which is the WHO marker for the carcinogenic risk estimates, was ca. 50% higher in all locations investigated.

Most T lymphocytes, including regulatory T cells (Treg cells), differentiate in the thymus. The age-dependent involution of this organ leads to decreasing production of T cells. Here we found that the output of new Treg cells from the thymus decreased substantially more than that of conventional T cells. Peripheral mouse and human Treg cells recirculated back to the thymus, where they constituted a large proportion of the pool of Treg cells and displayed an activated and differentiated phenotype. In the thymus, the recirculating cells exerted their regulatory function by inhibiting interleukin 2 (IL-2)-dependent de novo differentiation of Treg cells. Thus, Treg cell development is controlled by a negative feedback loop in which mature progeny cells return to the thymus and restrain development of precursors of Treg cells.

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CD4+CD25+Foxp3+ regulatory T lymphocytes are crucial for maintenance of immunological tolerance to self and innocuous non-self, are known to modulate immunity to tumors and infectious agents, and can induce transplantation tolerance. Surprisingly, only a single genetic polymorphism is known to modulate regulatory T cell development in the thymus, leading to a lethal autoimmune disorder. Here we show that considerably different levels of regulatory T cells are found in thymi of distinct common laboratory mouse strains. We demonstrate that distinct levels of phenotypically and functionally identical regulatory T cells develop with similar kinetics in the studied mice, that the responsible locus acts in a thymocyte intrinsic manner, and that levels of thymic Foxp3+ regulatory T cells correlate to those found in the periphery. Using several congenic mouse-strains we mapped one of the at least two genetic loci capable of quantitatively modulating thymic regulatory T cell development to a ≤ 2.2 Mbp region telomeric to the MHC. Our data indicate that polymorphic genes closely linked to the MHC locus substantially modulate differentiation of regulatory T cells. Identification of responsible genes should help in understanding mechanisms involved in commitment to the regulatory T cell lineage as well as selection of these cells in the thymus.

Natural CD4+CD25+ regulatory T lymphocytes (Treg) are key protagonists in the induction and maintenance of peripheral T cell tolerance. Their thymic origin and biased repertoire continue to raise important questions about the signals that mediate their development. We validated analysis of MHC class II capture by developing thymocytes from thymic stroma as a tool to study quantitative and qualitative aspects of the cellular interactions involved in thymic T cell development and used it to analyze Treg differentiation in wild-type mice. Our data indicate that APCs of bone marrow origin, but, surprisingly and importantly, not thymic epithelial cells, induce significant negative selection among the very autoreactive Treg precursors. This fundamental difference between thymic development of regulatory and effector T lymphocytes leads to the development of a Treg repertoire enriched in cells specific for a selected subpopulation of self-Ags, i.e., those specifically expressed by thymic epithelial cells.