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Objective: Systemic sclerosis (SSc) is a complex autoimmune disease with a strong genetic component. However, most of the genes associated with the disease are still unknown because associated variants affect mostly noncoding intergenic elements of the genome. We used functional genomics to translate the genetic findings into a better understanding of the disease., Methods: Promoter capture Hi-C and RNA-sequencing experiments were performed in CD4+ T cells and CD14+ monocytes from 10 SSc patients and 5 healthy controls to link SSc-associated variants with their target genes, followed by differential expression and differential interaction analyses between cell types., Results: We linked SSc-associated loci to 39 new potential target genes and confirmed 7 previously known SSc-associated genes. We highlight novel causal genes, such as CXCR5, as the most probable candidate gene for the DDX6 locus. Some previously known SSc-associated genes, such as IRF8, STAT4, and CD247, showed cell type-specific interactions. We also identified 15 potential drug targets already in use in other similar immune-mediated diseases that could be repurposed for SSc treatment. Furthermore, we observed that interactions were directly correlated with the expression of important genes implicated in cell type-specific pathways and found evidence that chromatin conformation is associated with genotype., Conclusion: Our study revealed potential causal genes for SSc-associated loci, some of them acting in a cell type-specific manner, suggesting novel biologic mechanisms that might mediate SSc pathogenesis., (© 2022 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Background: Many genes associated with asthma explain only a fraction of its heritability. Most genome-wide association studies (GWASs) used a broad definition of 'doctor-diagnosed asthma', thereby diluting genetic signals by not considering asthma heterogeneity. The objective of our study was to identify genetic associates of childhood wheezing phenotypes., Methods: We conducted a novel multivariate GWAS meta-analysis of wheezing phenotypes jointly derived using unbiased analysis of data collected from birth to 18 years in 9568 individuals from five UK birth cohorts., Results: Forty-four independent SNPs were associated with early-onset persistent, 25 with pre-school remitting, 33 with mid-childhood remitting, and 32 with late-onset wheeze. We identified a novel locus on chr9q21.13 (close to annexin 1 [ ANXA1 ], p<6.7 × 10 -9 ), associated exclusively with early-onset persistent wheeze. We identified rs75260654 as the most likely causative single nucleotide polymorphism (SNP) using Promoter Capture Hi-C loops, and then showed that the risk allele (T) confers a reduction in ANXA1 expression. Finally, in a murine model of house dust mite (HDM)-induced allergic airway disease, we demonstrated that anxa1 protein expression increased and anxa1 mRNA was significantly induced in lung tissue following HDM exposure. Using anxa1 -/- deficient mice, we showed that loss of anxa1 results in heightened airway hyperreactivity and Th2 inflammation upon allergen challenge., Conclusions: Targeting this pathway in persistent disease may represent an exciting therapeutic prospect., Funding: UK Medical Research Council Programme Grant MR/S025340/1 and the Wellcome Trust Strategic Award (108818/15/Z) provided most of the funding for this study., Competing Interests: RG, JC, SH, NK, SM, LG, LY, MT, JH, MP, JV, HA, PC, SF, ST No competing interests declared, GR MRC grant to my institution; President of the British Society of Allergy and Clinical Immunology, GK Dutch Lung Foundation, Ubbo Emmius Foundation (Money to insititution); Dutch Lung Foundation, Vertex, TEVA the Netherlands, GSK, ZON-MW (VICI grant), European Union (Money to institution); Astra Zeneca, Pure IMS, GSK (Money to institution); Sanofi, Boehringer Ingelheim (Money to institution), AS Medical research council Research grant; JP Moulton Charitable Foundation Research grant; Asthma UK Research grant, CM has received grants from Asthma Uk, the National Institute for Health Research, the Moulton Charitable Foundation and the North West Lung Centre Charity (to the Institution). They received lecture fees from GSK and Novartis, and received a travel grant from Sanofi. The authors has no other competing interests to declare, CL Wellcome Trust 107059/Z/15/Z, JH Medial Research Council grant MR/S025340/1 (to institution); American Academy of Allergy Asthma and Immunology (AAAI) (Support for speaker travel to AAAAI annual congress), AC MRC (research grants); EPSRC (research grant); Wellcome Trust (research grant); Worg Pharmaceoticals (Personal payment), (© 2023, Granell et al.)

Background: Asthma-associated single nucleotide polymorphisms from large genome-wide association studies only explain a fraction of genetic heritability. Likely causes of the missing heritability include broad phenotype definitions and gene-environment interactions (GxE). The mechanisms underlying GxE in asthma are poorly understood. Previous GxE studies on pet ownership showed discordant results., Objectives: We sought to study the GxE between the 17q12-21 locus and pet ownership in infancy in relation to wheeze., Methods: Wheezing classes derived from 5 UK-based birth cohorts (latent class analysis) were used to study GxE between the 17q12-21 asthma-risk variant rs2305480 and dog and cat ownership in infancy, using multinomial logistic regression. A total of 9149 children had both pet ownership and genotype data available. Summary statistics from individual analyses were meta-analyzed., Results: rs2305480 G allele was associated with increased risk of persistent wheeze (additive model odds ratio, 1.37; 95% CI, 1.25-1.51). There was no evidence of an association between dog or cat ownership and wheeze. We found significant evidence of a GxE interaction between rs2305480 and dog ownership (P = 8.3 × 10 -4 ) on persistent wheeze; among dog owners, the G allele was no longer associated with an increased risk of persistent wheeze (additive model odds ratio, 0.95; 95% CI, 0.73-1.24). For those without pets, G allele was associated with increased risk of persistent wheeze (odds ratio, 1.61; 95% CI, 1.40-1.86). Among cat owners, no such dampening of the genetic effect was observed., Conclusions: Among dog owners, rs2305480 G was no longer associated with an increased risk of persistent wheeze (or asthma). Early-life environmental exposures may therefore attenuate likelihood of asthma in those carrying 17q12-21 risk alleles., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Patterns of human immune responses to viruses and bacteria and how this impacts risk of infections or onset/exacerbation of chronic respiratory diseases are poorly understood. In a population-based birth cohort, we measured peripheral blood mononuclear cell responses (28 cytokines) to respiratory viruses and bacteria, Toll-like receptor ligands and phytohemagglutinin, in 307 children. Cytokine responses were highly variable with > 1000-fold differences between children. Machine learning revealed clear distinction between virus-associated and bacteria-associated stimuli. Cytokines clustered into three functional groups (anti-viral, pro-inflammatory and T-cell derived). To investigate mechanisms potentially explaining such variable responses, we investigated cytokine Quantitative Trait Loci (cQTLs) of IL-6 responses to bacteria and identified nine (eight novel) loci. Our integrative approach describing stimuli, cytokines and children as variables revealed robust immunologically and microbiologically plausible clustering, providing a framework for a greater understanding of host-responses to infection, including novel genetic associations with respiratory disease., (© 2022. The Author(s).)

Background: The aim of this study was to evaluate the prognostic value of perinuclear antineutrophil cytoplasmic antibodies (p-ANCA) in subjects with primary sclerosing cholangitis (PSC) and in particular whether it is associated with inflammatory bowel disease (IBD)., Methods: In the last 9 years, 64 patients were admitted to our Hospital with PSC: 34 males, mean age 53 years, range 17-90. All the patients had a cholestatic pattern of elevated serum enzymes. The diagnosis was made in most cases with magnetic resonance and in small percentages with endoscopic retrograde cholangiopancreatography (ERCP) or liver biopsy. In 33 patients with PSC, colonoscopy and p-ANCA assays were possible., Results: Thirteen patients showed p-ANCA positivity: 8 had ulcerative colitis (UC), with associated colon cancer (CC) in 3 cases, 3 had Crohn's disease (CD), 2 had no inflammatory bowel disease (IBD). Twenty patients were p-ANCA negative: only 1 with indeterminate IBD, while 19 had no IBD., Conclusions: IBD, or especially UC, is present in85% of patients with CSP and p-ANCA positivity, whereas 95% of patients with PSC who test negative for p-ANCA do not have IBD.

The ability to form biofilms is a common feature of microorganisms, which can colonize a variety of surfaces, such as host tissues and medical devices, resulting in infections highly resistant to conventional drugs. This aspect is particularly critical in polymicrobial biofilms involving both fungi and bacteria, therefore, to eradicate such severe infections, new and effective anti-biofilm strategies are needed. The efficacy of pentadecanal and pentadecanoic acid as anti-biofilm agents has been recently reported against different bacterial strains. Their chemical similarity with diffusible signal factors (DSFs), plus the already known ability of fatty acids to act as anti-biofilm agents, suggested to explore their use against Candida albicans and Klebsiella pneumoniae mixed biofilm. In this work, we demonstrated the ability of both molecules to prevent the formation and destabilize the structure of the dual-species biofilm. Moreover, the pentadecanoic acid anti-biofilm coating, previously developed through the adsorption of the fatty acid on polydimethylsiloxane (PDMS), was proved to prevent the polymicrobial biofilm formation in dynamic conditions by confocal laser scanning microscopy analysis. Finally, the evaluation of the expression levels of some biofilm-related genes of C. albicans and K. pneumoniae treated with pentadecanoic acid provided some insights into the molecular mechanisms underpinning its anti-biofilm effect., Competing Interests: Declaration of competing interest All authors declare that they have no conflict of interest., (Copyright © 2021 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Micronuclei (MN) are biomarkers of early biological effect often used for detecting DNA damage in human population exposed to genotoxic agents. The aim of this study was to evaluate the frequency of MN in exfoliated buccal cells of children living in an industrialized (impacted) area compared with that found in children living in a control area without significant anthropogenic impacts. A total of 462 6-8-year-old children (206 in the impacted area, 256 in the control area) attending primary school were enrolled. A questionnaire was administered to the parents of the recruited children to obtain information about personal data, lifestyles, and food habits of their children. Atmospheric particulate fractions were collected near the involved schools to assess the level of environmental exposure of the children. The presence of MN was highlighted in 68.4% of children living in the impacted area with a mean MN frequency of 0.66‱ ± 0.61‱. MN positivity and frequency were significantly lower in the control area (37.1% and 0.27‱ ± 0.43‱, respectively). The frequency of MN was positively associated with quasi-ultrafine particulate matter (PM 0.5 ), traffic near the home, and consuming barbecued food; while adherence to the Mediterranean diet and practicing sport were negatively associated., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analysis, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Background: Particulate matter (PM) is the most efficient vehicle for the inhalation and absorption of toxic substances into the body., Method: The present study was aimed at testing the hypothesis that PM10 samples collected on quartz filters exert an angiogenic activity in vivo in the chick embryo chorioallantoic membrane (CAM) assay., Results: When the low, medium, and high PM10 concentrations filters were tested in the CAM assay, an increasing number of microvessels was detectable after 4 days of applications of the filters. Moreover, at histological level, numerous microvessels and a dense inflammatory infiltrate were recognizable in the CAM mesenchyme., Conclusion: Our data show a clear dose-response relationship between the dose variable (PM10 and Bap) and the outcome variable. So far, the PM10 target value is determined on the basis of regulatory agreements and is not health-based. In addition, the mere gravimetric measure of PM10 cannot be considered a fully reliable surrogate of the overall toxicity of the mixture., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Nowadays, no a standard method for the determination of particulate bound nitro-PAHs (NPAHs) has been developed. Existing methods include complex sampling and extraction procedures. Moreover, their sensitivity does not allow to analyze daily PM10 samples, affecting the temporal resolution of NPAH concentrations. In this study an analytical method for the quantification of NPAHs on half 47 mm-filter samples of daily PM10 was developed and validated. NPAHs were recovered by microwave-assisted extraction, and analyzed by using a gas chromatography-triple quadrupole mass spectrometry in MRM mode. The analytical performance for 14 NPAHs (2-nitrofluorene, 9-nitroanthracene, 9-nitrophenantrene, 3-nitrophenantrene, 2-nitroanthracene, 3-nitrofluoranthene, 1-nitropyrene, 2,7-dinitrofluorene, 7-nitrobenzo[a]anthracene, 6-nitrochrysene, 1,3-dinitropyrene, 1,8-dinitropyrene, 1,6-dinitropyrene, 6-nitrobenza[a]pyrene) was investigated. Recovery extraction percentage exceeded 95% for all target compounds in the range between 0.25 and 10 ng/mL. The repeatability, expressed as Relative Standard Deviation percentage (RSD%) of five determinations, was less than 10% for target compounds except for 2,7-dinitrofluorene, 1,3- and 1,8-dinitropyrene (RSD% < 15%). The limit of detection (LOD) ranged from 12 to 84 pg/mL for most of NPAHs, except for dinitro-pyrenes and nitro-benzo(a)anthracene for which the LOD reached 1.8 ng/mL. The method developed was applied to real samples in order to evaluate the levels of NPAHs in the urban and industrial area of Taranto (South of Italy). The analysis of PM10 samples collected at four industrial and one urban sites, highlighted that in proximity of critical emission source as the biggest European steel plant and under certain weather conditions, combustion processes were the main source of NPAHs in atmosphere., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Around 50% of the world's population, particularly in developing countries, uses biomass as one of the most common fuels. Biomass combustion releases a considerable amount of various incomplete combustion products, including particulate matter (PM) and polycyclic aromatic hydrocarbons (PAHs). The paper presents the results of Indoor Air Quality (IAQ) measurements in six houses equipped with wood burning stoves or fireplaces as heating systems. The houses were monitored for 48-h periods in order to collect PM10 samples and measure PAH concentrations. The average, the maximum and the lowest values of the 12-h PM10 concentration were 68.6 μg/m³, 350.7 μg/m³ and 16.8 μg/m³ respectively. The average benzo[a]pyrene 12-h concentration was 9.4 ng/m³, while the maximum and the minimum values were 24.0 ng/m³ and 1.5 ng/m³, respectively. Continuous monitoring of PM10, PAHs, Ultra Fine Particle (UFP) and Total Volatile Organic Compounds (TVOC) was performed in order to study the progress of pollution phenomena due to biomass burning, their trends and contributions to IAQ. The results show a great heterogeneity of impacts on IAQ in terms of magnitude and behavior of the considered pollutants' concentrations. This variability is determined by not only different combustion technologies or biomass quality, but overall by different ignition mode, feeding and flame management, which can also be different for the same house. Moreover, room dimensions and ventilation were significant factors for pollution dispersion. The increase of PM10, UFP and PAH concentrations, during lighting, was always detected and relevant. Continuous monitoring allowed singling out contributions of other domestic sources of considered pollutants such as cooking and cigarettes. Cooking contribution produced an impact on IAQ in same cases higher than that of the biomass heating system.

Objective: The aim of this study was to determine whether the volatile organic compounds (VOCs) pattern in colorectal cancer (CRC) patients is modified by curative surgery for a potential application in the oncologic follow-up., Background: CRC has been proved to induce metabolic derangements detectable by high through-output techniques in exhaled breath showing a specific pattern of VOCs., Methods: Forty-eight CRC patients and 55 healthy controls (HC) entered the study. Thirty-two patients (M/F: 1.4; mean age 63 years) attended the oncologic follow-up (mean 24 months) and were found disease-free. Breath samples were collected under similar environmental conditions into a Tedlar bags and processed offline by thermal-desorption gas chromatography-mass spectrometry (TD-GC-MS). VOCs were selected by U test to build a Probabilistic Neural Network (PNN) model to set-up a training phase, which was cross-validated using the leave-one out method., Results: A total of 11 VOCs were finally selected for their excellent discriminant performance in identifying disease-free patients in follow-up from CRC patients before surgery, (sensitivity 100%, specificity 97.92%, accuracy 98.75%, and AUC: 1). The same VOCs pattern discriminated follow-up patients from HC, with a sensitivity of 100%, specificity of 90.91%, accuracy of 94.25%, and AUC 0.959., Conclusions: Exhaled VOCs pattern from CRC patients is modified by cancer removal confirming the tight relationship between tumor metabolism and exhaled VOCs. PNN analysis provides a high discriminatory tool to identify patients disease-free after curative surgery suggesting potential implications in CRC screening and secondary prevention.

Exhaled breath contains thousands of volatile organic compounds (VOCs) in gaseous form, which may be used as markers of airway inflammation and lung disease. Electronic noses enable quick and real-time pattern analysis of VOC spectra. It has been shown that the exhaled breath of patients with obstructive sleep apnoea (OSA) differs from that of non-obese controls. We aimed to assess the influence of obesity in the composition of exhaled VOCs by comparing obese subjects with and without OSA. Moreover, we aimed to identify the discriminant VOCs in the two groups.19 obese patients with established OSA (OO; age 51.2 ± 6.8; body mass index (BMI) 34.3 ± 3.5), 14 obese controls without OSA (ONO; age 46.5 ± 7.6; BMI 33.5 ± 4.1) and 20 non-obese healthy controls (HC; age 41.1 ± 12.6; BMI 24.9 ± 3.8) participated in a cross-sectional study. Exhaled breath was collected by a previously described method and sampled by using an electronic nose (Cyranose 320) and by gas chromatography-mass spectrometry (GC-MS) analysis. Breathprints were analyzed by canonical discriminant analysis on principal component reduction. Cross-validation accuracy (CVA) was calculated. Breathprints from the HC group were separated from those of OO (CVA = 97.4%) and ONO (CVA = 94.1%). Breathprints from OO were moderately separated from those of ONO (CVA = 67.6%).The presence of OSA alters the exhaled VOC pattern in obese subjects. The incomplete separation of breathprints between OO and ONO may be due to the same underlying inflammation caused by obesity.

Staphylococcus epidermidis is recognized as cause of biofilm-associated infections and interest in the development of new approaches for S. epidermidis biofilm treatment has increased. In a previous paper we reported that the supernatant of Antarctic bacterium Pseudoalteromonas haloplanktis TAC125 presents an anti-biofilm activity against S. epidermidis and preliminary physico-chemical characterization of the supernatant suggested that this activity is due to a polysaccharide. In this work we further investigated the chemical nature of the anti-biofilm P. haloplanktis TAC125 molecule. The production of the molecule was evaluated in different conditions, and reported data demonstrated that it is produced in all P. haloplanktis TAC125 biofilm growth stages, also in minimal medium and at different temperatures. By using a surface coating assay, the surfactant nature of the anti-biofilm compound was excluded. Moreover, a purification procedure was set up and the analysis of an enriched fraction demonstrated that the anti-biofilm activity is not due to a polysaccharide molecule but that it is due to small hydrophobic molecules that likely work as signal. The enriched fraction was also used to evaluate the effect on S. epidermidis biofilm formation in dynamic condition by BioFlux system., (© The Author(s) 2015.)

This study shows the direct effect of atmospheric particulate matter on plant growth. Tomato (Solanum lycopersicum L.) plants were grown for 18d directly on PM10 collected on quartz fiber filters. Organic and elemental carbon and polycyclic aromatic hydrocarbons (PAHs) contents were analyzed on all the tested filters. The toxicity indicators (i.e., seed germination, root elongation, shoot and/or fresh root weight, chlorophyll and carotenoids content) were quantified to study the negative and/or positive effects in the plants via root uptake. Substantial differences were found in the growth of the root apparatus with respect to that of the control plants. A 17-58% decrease of primary root elongation, a large amount of secondary roots and a decrease in shoot (32%) and root (53-70%) weights were found. Quantitative analysis of the reactive oxygen species (ROS) indicated that an oxidative burst in response to abiotic stress occurred in roots directly grown on PM10, and this detrimental effect was also confirmed by the findings on the chlorophyll content and chlorophyll-to-carotenoid ratio., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The gas chromatography-olfactometry (GC-O) technique couples traditional gas chromatographic analysis with sensory detection in order to study complex mixtures of odorous substances and to identify odor active compounds. The GC-O technique is already widely used for the evaluation of food aromas and its application in environmental fields is increasing, thus moving the odor emission assessment from the solely olfactometric evaluations to the characterization of the volatile components responsible for odor nuisance. The aim of this paper is to describe the state of the art of gas chromatography-olfactometry methodology, considering the different approaches regarding the operational conditions and the different methods for evaluating the olfactometric detection of odor compounds. The potentials of GC-O are described highlighting the improvements in this methodology relative to other conventional approaches used for odor detection, such as sensoristic, sensorial and the traditional gas chromatographic methods. The paper also provides an examination of the different fields of application of the GC-O, principally related to fragrances and food aromas, odor nuisance produced by anthropic activities and odorous compounds emitted by materials and medical applications.

Children are more sensitive to pollutants than adults and yet they spend large amounts of time in school environments where they are exposed to unknown levels of indoor pollutants. This study investigated the concentrations of the most abundant volatile organic compounds (VOCs) in eight naturally ventilated school buildings in Italy. The schools were chosen to include areas with different urbanization and traffic density characteristics in order to gather a more diverse picture of exposure risks in the different areas of the city. VOCs were sampled for one week in the presence/absence of pupils using diffusive samplers suitable for thermal desorption inside three classrooms at each school. The samples were then analyzed with thermal desorption-gas chromatography-mass spectrometry (TD-GC-MS). In addition, outdoor measurements were carried out in the yard at each school. VOC identification and quantification, and indoor/outdoor concentration plots were used to identify pollutant sources. While some classrooms were found to have very low VOC levels, others had a significant indoor contribution or a prevalent outdoor contribution. High concentrations of terpenes were found in all monitored classrooms: a-pinene and limonene were in the range of 6.55-34.18 µg/m3 and 11.11-25.42 µg/m3 respectively. Outdoor concentrations were lower than indoors for each monitored school. Indicators based on health risk assessment for chronic health effects associated with VOCs (either carcinogenic or non-carcinogenic) were proposed to rank sites according to their hazard level.

An annual monitoring campaign of VOCs, consisting of twelve sampling periods, was carried out from June 2008 to June 2009 in Modugno, a city located in the Apulia region (Southern Italy), in order to assess the urban air quality, identify the main emission sources, and quantify the cancer and no-cancer risk attributable to inhalation exposures. Monitoring, carried out by using the Radiello diffusive samplers, was conducted in eleven sampling sites throughout the city taking into account the traffic density and the architecture of the city. From the study of the data, it was found that, among all considered VOCs, benzene, toluene, ethylbenzene, and xylenes (BTEX) are the pollutants at higher concentration. The analysis of VOC concentrations, the study of the topography of the city, and the use of different diagnostic ratios between the BTEX species showed that the vehicular traffic emissions were the predominant source of VOCs in the urban area of Modugno. Despite that the annual concentration of benzene is lower than the regulatory limit, the estimation of cancer risk showed that the global lifetime cancer risk attributed to the investigated VOC exposure was not negligible and therefore should be taken into account in future regulatory approaches.

Microorganisms encounter diverse stress conditions in their native habitats but also during fermentation processes, which have an impact on industrial process performance. These environmental stresses and the physiological reactions they trigger, including changes in the protein folding/secretion machinery, are highly interrelated. Thus, the investigation of environmental factors, which influence protein expression and secretion is still of great importance. Among all the possible stresses, temperature appears particularly important for bioreactor cultivation of recombinant hosts, as reductions of growth temperature have been reported to increase recombinant protein production in various host organisms. Therefore, the impact of temperature on the secretion of proteins with therapeutic interest, exemplified by a model antibody Fab fragment, was analyzed in five different microbial protein production hosts growing under steady-state conditions in carbon-limited chemostat cultivations. Secretory expression of the heterodimeric antibody Fab fragment was successful in all five microbial host systems, namely Saccharomyces cerevisiae, Pichia pastoris, Trichoderma reesei, Escherichia coli and Pseudoalteromonas haloplanktis. In this comparative analysis we show that a reduction of cultivation temperature during growth at constant growth rate had a positive effect on Fab 3H6 production in three of four analyzed microorganisms, indicating common physiological responses, which favor recombinant protein production in prokaryotic as well as eukaryotic microbes., (Copyright © 2010 American Institute of Chemical Engineers (AIChE).)

A BTEX monitoring campaign, consisting of two weekly periods, was carried out in Bari, south-eastern Italy, in order to evaluate the impact of the vehicular traffic on the air quality at the main access roads of the city. Twenty-one sampling sites were selected: the pollution produced by the traffic in the vicinity of all exits from the ring road and some access roads to the city, those with higher traffic density, were monitored. Contemporarily the main meteorological parameters (ambient temperature, wind, atmospheric pressure and natural radioactivity) were investigated. It was found that in the same traffic conditions, barriers, buildings and local meteorological conditions can have important effects on the atmospheric dispersion of pollutants. This situation is more critical in downtown where narrow roads and high buildings avoid an efficient dispersion producing higher levels of BTEX. High spatial resolution monitoring allowed both detecting the most critical areas of the city with high precision and obtaining information on the mean level of pollution, meaning air quality standard of the city. The same concentration pattern and the correlation among BTEX levels in all sites confirmed the presence of a single source, the vehicular traffic, having a strong impact on air quality., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

The present work studied how much the meteorological parameters and the emission sources can influence the particulate polycyclic aromatic hydrocarbons (Invalid Journal Information PAHs) concentrations in two areas located in Southern Italy (Bari and Taranto). It was found that when the vehicular traffic is the main source of PAHs, there is a negative correlation between ambient temperature, wind speed and PAHs concentration (Bari). This is because these parameters are generally correlated with the dispersion capacity of the atmosphere. In the presence of a large industrial area, the wind direction becomes an important parameter able to determinate large changes in PAHs concentrations. This happened in Taranto where PAHs concentrations are exceptionally high. During the study the seasonal trend of particulate PAHs and PM10 was compared. PM10 did not show a significant seasonal cycle during the year because it is conditioned from a high regional aerosol background, especially during the summertime. On the contrary, particulate PAHs exerted distinct seasonal variation with higher concentrations in the winter and lower concentration during other months of the year. This evidence suggested that PAHs concentrations can be considered a more reliable index for air-quality assessment. In order to identify an index that considers the contributions of other particulate PAHs, it is necessary to calculate the carcinogenic potency of total PAHs (i.e., total BaPeq) obtained by the sum of the benzo[a]pyrene equivalent concentration (BaPeq) for each PAH.

Mean volatile organic compound (VOC) concentrations in 16 newspaper stands and in two printing shops were monitored for the purpose of quantifying the various VOCs in these areas and to relate the results. In each site halogenated, oxygenated, aliphatic, and aromatic compounds were monitored during one workweek. They were sampled with diffusive samplers for thermal desorption and analysed by GC-MS. The results showed that in all newspaper stands the indoor levels of toluene were much higher than the outdoor levels; some sites had toluene indoor concentrations 100 times higher than their correspondent outdoor levels. The investigations in two printing shops confirmed that newspapers, in particular the inks, are the main sources of toluene in the newspaper stands.

Micro-organisms that thrive at low temperatures produce cold-adapted enzymes which display high catalytic efficiency, generally associated with low thermal stability. In the recent past, researchers and industries have focused the attention on cold-adapted enzymes, whose peculiar properties make them particularly interesting either for investigating stability/flexibility relationships, or for their potential application in industrial processes. Among these enzymes, lipases and esterases, have potential utilisations in a broad range of biotechnological applications. In fact, these biocatalysts represent the most widely used enzymes in biotechnology and organic chemistry. Modern methods of genetic engineering combined with growing knowledge of structure and function allow further adaptation to industrial needs and exploration of novel applications. Hence, in this review we attempt to offer an overview on some psychrophilic esterases and lipases; major details will be presented for ORF PSHAa0051 from Pseudoalteromonas haloplanktis TAC125, recently investigated by our team. In addition, potential biotechnological applications will be discussed.

Aim: In literature there are many reports on hepatitis C virus (HCV) and type 2 diabetes mellitus association. However, many authors have proved this association in anti-HCV positive patients affected by cirrhosis. Thus, type 2 diabetes mellitus has been associated to cirrhosis rather than to HCV., Methods: We wanted to verify the type 2 diabetes mellitus prevalence in 3 606 anti-HCV positive patients both cirrhotic and noncirrhotic. The results obtained have been compared with those of 1 053 HBsAg positive patients. All the patients were hospitalised for the first time in our institute between January 1991 and December 2003., Results: Type 2 diabetes mellitus is more frequently associated to cirrhotic rather than to noncirrhotic patients, but between the 2 groups of patients (anti-HCV and HBsAg positive) HCV increases type 2 diabetes mellitus association significantly., Conclusions: Hepatic cirrhosis and HCV make easier the onset of type 2 diabetes mellitus.

An aspect of early Mexican surgery in the sixteenth century is presented. The treatment of facial wounds by Alonso Lopez de Hinojosos and Agustin Farfán is reviewed. Farfán proposed total nose reconstruction, with a cutaneous arm flap, 18 years before its description in De Curtorum Chirurgia, by Tagliacozzi, in 1597 in Venice, Italy. The chapter on facial wounds by Lopez de Hinojosos and Farfán shows their concern for the final aesthetic results and should be considered the first Mexican publication in the field of plastic surgery.

Background: Notwithstanding the presence of numerous examinations for screening coeliac disease, it may still escape timely diagnosis. For this reason we carried out an investigation to see whether simple haematochemical anomalies (as revealed in what are now routine examinations carried out during hospitalisation) might make diagnosis quicker or at least trigger the suspicion of coeliac disease., Methods: Retrospectively, of 21 adult patients admitted to our hospital for the first time and who were diagnosed with coeliac disease, we considered haemoglobin, iron, calcium, potassium, albumin and RDW (part of the normal blood count)., Results: We found that elevated RDW was the most frequent anomaly (67% of patients) of the six haematochemical parameters observed. In addition, it became normal in most patients after a gluten-free diet., Conclusions: Elevated RDW was more frequent than sideropenic anaemia in patients with coeliac disease. In addition, RDW indicates a response to diet therapy because it became normal after a gluten-free diet.

Genetic manipulation of Antarctic bacteria has been very limited so far. This article reports the isolation and molecular characterization of a novel plasmid, pMtBL, from the Antarctic gram-negative bacterium Pseudoalteromonas haloplanktis TAC 125. This genetic element, 4,081 bp long, appeared to be a multicopy cryptic replicon with no detectable transcriptional activity. By an in vivo assay, the pMtBL autonomous replication sequence was functionally limited to an AluI plasmid fragment of about 850 bp. This novel cold-adapted replication element showed quite a broad host range profile: it was cloned into a mesophilic genetic construction, obtaining a cold-adapted expression vector that was able to promote the production of P. haloplanktis A23 alpha-amylase in a psychrophilic bacterium. This study represents the first report of successful recombinant production of a cold-adapted protein in an Antarctic host.

The history of craniofacial surgery and the use of intentional cranial deformation is a long and varied one. Researching some of the earliest medical writings and reviews of early terracotta and stone figures from throughout the world clearly revealed that these two forms of treatment were widely extant. Intentional cranial deformation was used for a number of reasons including beautification, tribal identification, and social stature. The development of craniofacial surgery is a more modern practice and its historical evolution is reviewed in the context of techniques and the personalities involved.

The first published account of a neurosurgical intervention performed on the North American continent is described. The operation took place in Mexico City in 1561. The neurosurgical intervention was performed by a Spanish surgeon, Pedro Arias de Benavides, on a 13-year-old boy who had sustained head trauma that caused an open depressed cranial fracture and exposed the cerebrum. A description of this case was first published in Valladolid, Spain, 6 years after the event, in a book entitled Secretos de Chirurgia ("Secrets of Surgery").

Endoscopic techniques are now an accepted part of the surgical armamentarium and are used routinely in a number of aesthetic and reconstructive procedures. Endoscopic techniques are now being used commonly by plastic surgeons in forehead and face lifts. In both craniofacial surgery and in neurosurgery, the application of endoscopy potentially allows the surgical team to perform wide dissection of the dura mater in a minimally invasive fashion, thereby potentially reducing the risk of dural and brain injury. Also reduced by this surgical approach is potential injury to the major venous structures, such as the sagittal sinus, along with overall reduced bleeding. After an extensive laboratory study of 10 cadaveric dissections, the authors have refined a new endoscopic technique for completing an endoscopic intracranial craniofacial osteotomy. This study was conducted in the Department of Pathology at the University of Brno (Czech Republic), and was performed as a cooperative multicenter project between the University of Palermo, the Albert Einstein College of Medicine/ Montefiore Medical Center, the Hospital Infantil de Mexico, "Federico Gomez," and the Medtronic Midas Rex Institute, (Fort Worth, TX). During this cadaveric anatomic study and using small trephinations and skin incisions the authors were able to develop several different craniofacial and endoscopic monobloc procedures. To accomplish intracranial and facial osteotomies, a new malleable high-speed drill was designed for use in the endoscopic craniofacial approach. Using these newly developed cadaveric techniques and instrumentation, the authors performed two intracranial craniofacial procedures on children with congenital craniofacial anomalies. There would appear to be several significant advantages for the craniofacial patient as result of these new techniques: reduced surgical trauma, operative bleeding, surgical time, and hospitalization, along with a reduced risk of infection. It became quickly apparent, as a result of these cadaveric studies, that the learning curve for this endoscopic procedure is quite steep. Tutino M, Chico F, Tutino M, Goodrich JT, Ortiz Monasterio F. Endoscopic intracranial craniofacial and monobloc osteotomies with the aid of a malleable high-speed pneumatic drill: a cadaveric and clinical study.

The first nine clinical cases using endoscopic dissection of dura and craniotomy with minimal trephines were performed from June to August 1997 after trial dissection of 19 fresh cadavers conducted at the University of Brno's Pathology Institute in the Czech Republic. These procedures involved the refinement of craniofacial and intracranial surgical techniques using the endoscope and prototype instruments. These dissections demonstrated that intracranial structures can be explored using an endoscope without encumbrance, and that major craniofacial surgeries may also be performed with minor incisions and minimal craniotomies. Furthermore, we seek to illustrate that use of the endoscope in craniofacial surgery provides improved visualization and protection of vital structures while simultaneously allowing the surgeon to perform delicate maneuvers. This permits minimal brain retraction with less subsequent morbidity. This minimally invasive craniofacial-intracranial surgical technique using the endoscope is performed with minimal cutaneous incisions, avoiding wide exposure of subcutaneous tissue, cranium, and meningeal structures. The ultimate goal is to perform endoscopic intracranial osteotomies and obtain advancement of craniofacial skeleton with gradual distraction. Potential neurosurgical advantages include improved postoperative recovery, decreased cerebral edema, and decreased risk of hemorrhage and infection.

A study was conducted from February 29, 1996, to March 28, 1996, at the University of Brno's Pathology Institute in the Czech Republic to explore the possible application of craniofacial intracranial endoscopic techniques through minimal skin incisions and trephines in fresh cadavers (3 to 12 hours old). Through the trephines the dura was totally dissected from the bone. After this dissection a standard bicoronal incision and a full craniotomy was performed to assess the integrity of the meninges. This minimally invasive dissection of the skull base with the aid of an endoscope is characterized by fewer skin incisions, thereby avoiding the exposure of subcutaneous tissue, muscle, cranial bone, and meninges. We find that it is possible to accomplish an accurate and extensive intracranial dissection with the aid of an endoscope. The potential of this technique is important for craniofacial surgery as well as for neurosurgery. The objectives of this study were [1] to explore endoscopically the craniofacial anatomy to determine the best approach and the optimal method for dissecting endocranial structures, and [2] to achieve a safer and more accurate dissection of the skull base, evaluating advantages of endoscopic surgery as an alternative method for the treatment of craniofacial and neurosurgical pathologies.

The genes trpE and trpG of the hyperthermophilic archaeon Sulfolobus solfataricus, encoding the components I and II of anthranilate synthase, were cloned and co-expressed in Escherichia coli. The properties of the recombinant protein were determined and compared to those of the wild type complex. Gel filtration chromatography revealed an alpha2beta2 composition. The heteromeric enzyme is fully active above 85 degrees C and can be considered to be an "extremozyme" according to Adams et al.[1]. Sulfolobus solfataricus anthranilate synthase is subject to feedback inhibition by L-tryptophan even if it lacks the co-operativity that has been observed for all the other tetrameric anthranilate synthases.

This study brings to light the potential use of intracranial endoscopic techniques that can be combined with osteotomies and bone distraction to improve precision and reduce complications in craniofacial surgery. It also anticipates the widespread use of endoscopic techniques to reduce the morbidity and mortality of plastic surgical and neurosurgical intracranial surgery.

Indole-3-glycerol-phosphate synthase, a thermophilic and thermostable enzyme from the archaeon Sulfolobus solfataricus, was purified and characterized. The sequence of the thermophilic enzyme was compared to the sequence of a homologous mesophilic enzyme from Escherichia coli. The secondary structure of the thermophilic enzyme was predicted taking into account the patterns of hydropathy, chain flexibility and amphipathicity and the CD spectrum. From this analysis it turned out that indole-3-glycerol-phosphate synthase from S. solfataricus can be considered a model for studying thermostable TIM-barrel enzymes. Some peculiarities of the amino-acid sequence of indole-3-glycerol-phosphate synthase from S. solfataricus are discussed in relation to the thermostability of the enzyme.