Characterization of urban aerosol: Seasonal variation of genotoxicity of the water-soluble portion of PM2.5 and PM1.

Urban particulate matter (PM) is a complex mixture of several classes of chemicals: elemental carbon, ammonium, sulfates, nitrates, organic compounds and metals. For a long time, numerous studies had shown that PM causes health problems and, in 2013, it has been classified by the International Agency for Research on Cancer as carcinogenic to humans (group 1). Furthermore, it's known that the fine fraction of PM is the most genotoxic, and that smaller particles are retained by the lower respiratory system, making fine particles a public health concern. In this study we characterize the water-soluble portion of urban aerosol from Bologna, a county town of Emilia-Romagna in the north of Italy, by collecting the finest fractions of airborne particles, PM2.5 and PM1, in three different seasons (winter, summer and autumn) over a three-year period. The genotoxicity of the water-soluble extracts was evaluated, both by a standard and a enzyme-modified Comet assay and also by the Micronucleus test, with lung adenocarcinoma epithelial cells (A549). In the same extracts, water-soluble metals (V, Ni, Cu, Cr, Fe) were detected and associations between the physicochemical parameters of PM and genotoxicity were evaluated. DNA strand breaks were found in summer and winter samples in the Comet experiments, whereas oxidative damage was induced by autumn extracts; winter samples induced chromosome breakage or loss in A549 cells. Iron and copper were the most abundant transition metals in both fractions and both were associated with micronuclei induction, whereas chromium is linked with oxidative damage. This study also shows that the water-soluble fraction of PM contributes to global genotoxicity and that transition metals play a role, therefore both organic and water-soluble fractions should be considered in an air-quality monitoring program.

Genotoxicity of airborne PM2.5 assessed by salmonella and comet assays in five cities of the Emilia-Romagna (Italy) mutagenicity monitoring network.

Airborne particulate matter (PM) has long been recognized as a potential health hazard and in 2013 was classified as carcinogenic to humans by the International Agency for Research on Cancer. In this study we evaluate and compare mutagenic and genotoxic potencies of PM2.5 collected in three seasons, from 2012 to 2015, in five Italian cities. Mutagenicity was evaluated through the Ames test on TA98 and TA100 strains and, for the measurement of PM clastogenicity, Comet assay was carried out on cultured human lung cells (A549). Organic matter, extracted from urban particulate matter, was also characterized for polycyclic aromatic hydrocarbons (PAHs) and their derivatives content. Samples collected in the colder seasons show the presence of both base pair substitution and frameshift mutagens, with enhanced mutagenic response in the absence of enzyme activation. The highest DNA damage detected with the Comet assay was induced by winter extracts, but different from Salmonella, the relative increase per cubic meter in comet tail for November samples was comparable to July ones. Comparing mutagenicity and genotoxicity with chemical concentrations we found that data from the Salmonella assay correlate with mass concentration and, to a lesser extent, with PAHs, but no association was found with their derivatives, whereas DNA damage correlate only with PAHs measured at one site. These findings demonstrate that to assess the mutagenicity and genotoxicity of complex mixtures it's necessary to use bioassays and that the chemical analysis of pollutants does not take into account the possible inhibitory or synergic effects of exposure. Environ. Mol. Mutagen. 58:719-729, 2017. © 2017 Wiley Periodicals, Inc.

Characterization of urban aerosol: seasonal variation of mutagenicity and genotoxicity of PM2.5, PM1 and semi-volatile organic compounds.

Urban particulate matter (PM) is an environmental public health concern as it has been classified by the IARC as carcinogenic to humans (group 1) and it's well known that pollutants are more associated with the finest fractions of PM. In this study we characterize urban aerosol in Bologna, county town of Emilia-Romagna in the north of Italy, collecting PM2.5, PM1 and semi-volatile organic compounds using polyurethane foam. Samples were collected in three different seasons (winter, summer and autumn) and were extracted with acetone. On these three fractions we assessed mutagenicity using Salmonella reverse mutation test and genotoxicity by alkaline comet assay and micronucleus assay in human lung cancer cell line, A549. Organic extracts were also characterized for alkanes, polycyclic aromatic hydrocarbons (PAHs), nitrated and oxygenated PAHs. We also evaluated associations between the physicochemical parameters of samples and their genotoxicity. The particulate samples, collected in autumn and winter, indicated the presence of both base pair substitution and frameshift mutagens using TA98 and TA100 strains of Salmonella typhimurium and the mutagenicity was more associated with the finest fraction. Enhanced mutagenic response was observed in the absence of enzyme activation. Only a third of comet and a half of micronucleus assays gave positive results that, unlike Salmonella's ones, are not season-related. These results were compared with environmental chemicals concentrations and we found that Salmonella's data correlated with PAHs detected on PM filters and with mass concentrations, whereas the DNA damage correlate only with PAHs extracted from polyurethane foams. The use of different assays was sensitive to detect and identify different classes of airborne mutagenic/genotoxic compounds present in aerosol, showing that monitoring air quality using this methodology is relevant.

The classification of hospitalized patients with hyperglycemia and its implication on outcome: results from a prospective observational study in Internal Medicine.

The relevance of classifying hyperglycemic hospitalized subjects (HS) as known diabetes (D), newly discovered diabetes (ND), and stress hyperglycemia (SH) is unclear. The aim of this study was to determine the prevalence, in-hospital mortality, and length of stay (LOS) of three different phenotypes of HS. Fasting glucose ≥126 mg/dL (7 mmol/L) or random blood glucose ≥200 mg/dL (11.1 mmol/L) defined HS who were categorized into three groups: D; ND (no history of diabetes and HbA1c ≥48 mmol/mol); SH (no history of diabetes and HbA1c <48 mmol/mol). The end points of the study were in-hospital mortality and LOS. Of 1447 consecutive enrolled subjects, the prevalence of HS was 28.6 % (415/1447), of these 71.6 % had D, 21.2 % SH, and 7.2 % ND, respectively. In-hospital death was 3.9 % in normoglycemic and 6.0 % in hyperglycemic subjects. Individuals with SH had an increased risk of in-hospital death (7.9 %) (HR 2.17, 95 % CI 1.18-4.9; p = 0.039), while this was not observed for D and ND patients. The mean LOS was greater in ND and SH subjects. Hyperglycemia is common, and is associated with an increased risk of in-hospital mortality and extension of hospital stay. HbA1c along with clinical history is a useful tool to identify subgroups of hyperglycemic hospitalized subjects. Individuals with SH have a longer LOS, and a double risk of in-hospital mortality. Additionally, identifying previously unknown diabetes represents a remarkable opportunity for prevention of diabetes-related acute and chronic complications.

Time sequence of autonomic changes induced by daily slow-breathing sessions.

OBJECTIVE: Daily sessions of slow-breathing (6 breaths/min) significantly reduced 24-h ambulatory blood pressure (ABP) in patients with mild hypertension and this effect persisted at least 6 months after the interruption of sessions. The sequence of changes induced by slow-breathing (SB) daily sessions on the modulation of ambulatory blood pressure, renal resistive index, heart rate variability (HRV), and baroreflex sensitivity (BRS) was thus investigated in a randomized, controlled clinical trial. METHODS: Thirty-seven patients (30-75 years, grade I essential hypertension), untreated with antihypertensive drugs, were randomized to daily sessions (30 min) of music-guided SB (<10 breaths/min) (intervention, n = 24) or simple relaxation (control, n = 13). Office and ambulatory blood pressure monitoring renal Doppler ultrasound, assessment of BRS (sequence method and spectral analysis), and HRV (spectral power in the high- and low-frequency bands) were performed at baseline, and after 1, 4, and 8 weeks. Mixed model analysis was conducted on derived variables given by the difference between each measurement and the baseline value within subjects. RESULTS: After 1 week, the intervention enhanced the parasympathetic modulation (high-frequency power; at least p < 0.05 vs both control and baseline) and reduced renal vascular resistance (p < 0.05 for both comparisons); after 1 month, the enhancement of BRS (p < 0.05 for both comparisons at both methods) paralleled a significant reduction in 24 h ABP (p < 0.05 for all comparisons). INTERPRETATION: Repeated daily session of music-guided SB increased parasympathetic modulation and decreased renal resistive index early in the study. These changes were being followed by a positive modulation of BRS and blood pressure reduction.

A case of Candida glabrata severe urinary sepsis successfully treated with micafungin.

Candida glabrata is frequently resistant to fluconazole, and in advanced renal failure the safe use of this and other recommended drugs is limited. We report a case of a 56 years-old diabetic woman with renal failure and severe urinary sepsis from C. glabrata successfully treated with micafungin.

Psychological predictors of the antihypertensive effects of music-guided slow breathing.

BACKGROUND: The possibility that daily sessions of music-guided slow breathing may reduce 24-h ambulatory blood pressure (ABP), and predictors of efficacy were explored in a randomized, placebo-controlled trial with parallel design. METHODS: Age-matched and sex-matched hypertensive patients were randomized to music-guided slow breathing exercises (4-6 breaths/min; 1: 2 ratio of inspiration: expiration duration) (Intervention; n = 29) or to control groups who were thought to relax while either listening to slow music (Control-M; n = 26) or reading a book (Control-R; n = 31). At baseline and at follow-up visits (1 week and 1, 3 and 6 months), ABP monitoring was performed. RESULTS: At mixed model analysis, intervention was associated with a significant reduction of 24-h (P = 0.001) and night-time (0100-0600 h) (P < 0.0001) systolic ABP. The average reduction of systolic 24-h ABP at 6 months was 4.6 mmHg [confidence limits at 95% 1.93-7.35] and 4.1 mmHg (95% confidence limits 1.59-6.67) vs. Control-M and Control-R groups, respectively, (P < 0.001 for both). Antihypertensive treatment was selected as negative predictor of BP reduction at multivariate stepwise analysis. When antihypertensive treatment was inserted as covariate in a generalized linear model, psychological subscales assessed at baseline by the Mental Health Inventory questionnaire were found to affect systolic blood pressure reduction at 6-month follow-up (general positive affect P < 0.001; emotional ties, P < 0.001; loss of behavioral control, P = 0.035). In particular, a level of general positive affect higher than the 75th percentiles was found to be significantly associated with low treatment efficacy (odds ratio 0.09; 95% confidence limits 0.01-0.93). CONCLUSION: Daily sessions of voluntary music-guided slow breathing significantly reduce 24-h systolic ABP, and psychological predictors of efficacy can be identified.

Response of serum proteome in patients undergoing infrarenal aortic aneurysm repair.

BACKGROUND: Postoperative organ dysfunction in conventional surgery for abdominal aortic aneurysm (AAA) is associated with a complex inflammatory reaction, with activation of coagulation and fibrinolysis. A prospective,observational study was performed to define the complex plasma proteomic changes after AAA repair and to identify factor(s) that may affect myocardial function in uncomplicated procedures. METHODS: Ten patients undergoing infrarenal AAA repair were investigated. Eight subjects subjected to major abdominal surgery served as controls. Hemodynamic changes were continuously monitored by using the pressure recording analytical method technique. The time course of plasma proteins was investigated after induction of anesthesia and at different times after surgery (6 h, 12 h, 24 h, 36 h) by using two-dimensional difference gel electrophoresis, matrix-assisted laser desorption/ionization-time of flight mass spectrometry, and Western blot. The effects of plasma on the functional properties of isolated rat ventricular myocytes were also investigated. RESULTS: In AAA patients alone, 18 spots were found to change more than two-fold in expression level, spot identification revealing an increased thrombin generation 6 h after surgery. At the same time cardiac cycle efficiency significantly reduced versus baseline (-0.5 +/- 0.9 vs. 0.18 +/- 0.3 in AAA patients, P < 0.01; 0.4 +/- 0.1 vs. 0.2 +/- 0.3 in control surgery, not significant; P < 0.01 group x time interaction at ANOVA). Plasma obtained 6 h after AAA surgery dose-dependently inhibited contractile function of control rat myocytes (percent shortening fell by 51% with 10% of AAA plasma and was abolished with 20% of AAA plasma, P < 0.001 for both). The inhibitory response was abolished by thrombin antagonism. CONCLUSIONS: These findings show for the first time the possible role of thrombin generation within the complex activation of inflammatory response in causing hemodynamic instability in the early postoperative period after AAA surgery.

Point-of-care testing of cholesterol and triglycerides for epidemiologic studies: evaluation of the multicare-in system.

Cardiovascular disease is the leading cause of death in the world with 80% of cardiovascular events that occur in low- and middle-income countries. Reliable data on the prevalence of risk factors in developing countries can be obtained in door-to-door epidemiologic studies with the use of automatic instruments. This study was performed to assess the sensitivity and specificity of a low-cost and manageable point-of-care testing (POCT) instrument (HPS MultiCare-in, Italy) for cholesterol and triglyceride assays. Plasma blood samples were obtained from consecutive subjects referred to our clinic for diagnostic evaluation. The analyzer currently used in our central laboratory (ADVIA 2400; Siemens, Deerfield, Ill) was used as comparison method. The inter-assay imprecision (expressed as variation coefficient) of the MultiCare POCT system was 4.51% (range, 2.38%-8.54%) and was 3.29% (range, 1.06%-7.45%) for cholesterol and triglycerides systems, respectively. The mean percent bias for capillary samples was 3.5 +/- 4.3% for total cholesterol and -2.4 +/- 4.9% for triglycerides. The difference in results obtained by nonprofessionals compared with professionals (practicability testing) was 0.28 +/- 7.61% and 1.26 +/- 9.86%, respectively (P value was nonsignificant for both). Sensitivity and specificity measurements were 95.7% and 61.9% (threshold value of cholesterol 190 mg/dL) and 98% and 93.5% (threshold value of triglycerides 170 mg/dL), respectively. POCT instruments are essential to perform epidemiologic studies while avoiding transportation and storage of biologic material. The characteristics of sensitivity and specificity as well as diagnostic accuracy make the POCT instrument useful for obtaining an accurate stratification of a study population.

Intersystem crossing processes in nonplanar aromatic heterocyclic molecules.

A comprehensive study of the photophysical properties of a series of monoaza[5]helicenes is presented on the basis of joint optical spectroscopy and quantum chemistry investigations. The molecules have been characterized by absorption and CW/time-resolved luminescence measurements. All quantities related to spin-orbit-coupling processes, such as intersystem crossing rates and radiative phosphorescence lifetimes, were found to depend strongly on the nitrogen position within the carbon backbone. Density functional theory and semiempirical quantum-chemical methods were used to evaluate the molecular geometries, the characteristics of the excited singlet and triplet states, and the spin-orbit coupling matrix elements. We demonstrate that the magnitude of spin-orbit coupling is directly correlated with the degree of deviation from planarity. The trends from the calculated photophysical quantities, namely, radiative fluorescence and phosphorescence decay rates and intersystem crossing rates, of the mono-aza-helicenes are fully consistent with experiment.

Excited-state properties and emission spectra of nonplanar heterocyclic helicenes.

We discuss the electron-vibration coupling in mono-aza-[5]helicenes on the basis of a Franck-Condon analysis and density functional theory (DFT) calculations of the fluorescence and phosphorescence spectra measured in ethanol. The geometries of the initial states were obtained from time-dependent DFT (S(1)) and unrestricted DFT (T(1)) excited-state optimizations. In general, the position of the nitrogen atom has only a minor impact on the vibronic fine-structure in both absorption and emission. The shapes of the emission spectra from the lowest singlet and triplet states are found to be determined by contributions from multiple normal modes. The results of the calculations demonstrate how the interplay among these normal modes results in qualitatively and quantitatively different spectra for fluorescence and phosphorescence.