Correlates and reference limits of plasma gamma-glutamyltransferase fractions from the Framingham Heart Study.

Background: We assessed GGT fractions correlates and their reference values in the Offspring Cohort of the Framingham Heart Study. Methods: Correlates of GGT fractions were assessed by multivariable regression analysis in 3203 individuals [47% men, mean age (SD): 59 (10) years]. GGT fractions reference values were established by empirical quantile analysis in a reference group of 432 healthy subjects [45% men, 57 (10) years]. Results: Fractional GGT levels were higher in men than in women (Pb0.0001). In both sexes, fractions were associated with: triglycerides were associated with b-GGT, alcohol consumption with m-, s- and f-GGT. C-reactive protein with m- and s-GGT, while plasminogen activator inhibitor-1 with b- and f-GGT. Body mass index, blood pressure, glucose and triglycerides correlated with b- and f-GGT. In comparison with the reference group [b-GGT/s-GGT median (Q1–Q3): 0.51 (0.35–0.79)U/L], subjects affected by cardiovascular disease or diabetes showed no change of b/s ratio [0.52 (0.34–0.79)U/L, 0.57 (0.40–0.83)U/L, respectively]. The b/s ratio was higher in presence of metabolic syndrome [0.61 (0.42–0.87)U/L, Pb0.0001], while lower in heavy alcohol consumers [0.41 (0.28–0.64)U/L, Pb0.0001]. Conclusions: Metabolic and cardiovascular risk markers are important correlates of GGT fractions, in particular of b-GGT

Evaluation of direct immunofluerescence test for Campylobacter fetus in bull experimentally infected and commensal bacteria from the reproductive tract of bulls

Campylobacter fetus is a Gram negative bacterium, with 2 relevant subspecies for cattle health: C. fetus subsp. fetus (Cff) and C. fetus subsp. venerealis (Cfv) which cause important reproductive losses. In the present work, four groups of bulls were used: one group to characterize the genital microbiota (G1; n=3) and the other three to evaluate the direct immunofluorescence (DIF) test for the diagnosis of bovine campylobacteriosis in preputial samples (PS) from experimentally infected bulls with Cff (G2; n=3) and Cfv (G3; n=3), and controls (G4; n=4). Seven bacterial strains of different genera were identified in the PS from G1. Other 11 laboratory bacterial strains were included: Cff, Cfv and Cfv biovar Intermedius, 3 Campylobacter non-fetus, 3 Gram negative and 2 Gram positive. Only the C. fetus strains presented positive immunostaining. The sensitivity and specificity of the DIF test were 79 % and 100 %, respectively. Concordance between DIF test and bacteriological culture was 83 % (Kappa index: 0.65). The present study shows the high specificity of the DIF test for detection of C. fetus using a fluorescent conjugate elaborated in Argentina, and highlights the relevance of no cross reaction against 15 bacterial strains normally present in bull preputial microbiota.Campylobacter fetus es una bacteria Gram negativa que incluye 2 subespecies de relevancia sanitaria para el bovino: C. fetus subsp. fetus (Cff) y C. fetus subsp. venerealis (Cfv), causantes de importantes pérdidas reproductivas. En el presente estudio, se utilizaron cuatro grupos de toros: un grupo (G1) para caracterizar la microbiota genital, y otros tres (G2, G3, G4) (n=10) para evaluar el test de inmunofluorescencia directa (IFD) para el diagnóstico de la campilobacteriosis bovina en esmegma prepucial (EP) de toros experimentalmente infectados con Cff y Cfv. Se identificaron siete cepas bacterianas de distinto género del G1. Otras 11 cepas bacterianas de laboratorio fueron incluidas: Cff, Cfv, Cfv biovar Intermedius, 3 Campylobacter no-fetus, 3 Gram negativo y 2 Gram positivo. Solo las cepas de C. fetus presentaron inmunofluorescencia positiva. La sensibilidad y especificidad de la IFD fue de 79 % y 100 %, respectivamente. La concordancia entre la IFD y el cultivo bacteriológico fue de 83 % (Kappa: 0,65). Se demuestra la alta especificidad de la IFD para la detección de C. fetus con un conjugado fluorescente elaborado en Argentina, y se destaca la no reacción cruzada contra 15 cepas bacterianas normalmente presentes en la microbiota prepucial del toro.Fil: García, Juan Agustín. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Innovación para la Producción Agropecuaria y el Desarrollo Sostenible - Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires Sur. Estación Experimental Agropecuaria Balcarce. Instituto de Innovación para la Producción Agropecuaria y el Desarrollo Sostenible; ArgentinaFil: Soto, J.. Laboratorio Biologico de Tandil ; ArgentinaFil: Soto, P.. Laboratorio Biologico de Tandil Srl.; ArgentinaFil: Malena, Rosana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Innovación para la Producción Agropecuaria y el Desarrollo Sostenible - Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires Sur. Estación Experimental Agropecuaria Balcarce. Instituto de Innovación para la Producción Agropecuaria y el Desarrollo Sostenible; ArgentinaFil: Morsella, Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Innovación para la Producción Agropecuaria y el Desarrollo Sostenible - Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires Sur. Estación Experimental Agropecuaria Balcarce. Instituto de Innovación para la Producción Agropecuaria y el Desarrollo Sostenible; ArgentinaFil: Méndez, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Innovación para la Producción Agropecuaria y el Desarrollo Sostenible - Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires Sur. Estación Experimental Agropecuaria Balcarce. Instituto de Innovación para la Producción Agropecuaria y el Desarrollo Sostenible; ArgentinaFil: Fiorentino, Maria Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Innovación para la Producción Agropecuaria y el Desarrollo Sostenible - Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires Sur. Estación Experimental Agropecuaria Balcarce. Instituto de Innovación para la Producción Agropecuaria y el Desarrollo Sostenible; ArgentinaFil: Paz Acuña, Joaquín Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Innovación para la Producción Agropecuaria y el Desarrollo Sostenible - Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires Sur. Estación Experimental Agropecuaria Balcarce. Instituto de Innovación para la Producción Agropecuaria y el Desarrollo Sostenible; ArgentinaFil: Lucchesi, Enrique. Laboratorio Biologico de Tandil ; ArgentinaFil: Paolicchi, Fernando Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Innovación para la Producción Agropecuaria y el Desarrollo Sostenible - Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires Sur. Estación Experimental Agropecuaria Balcarce. Instituto de Innovación para la Producción Agropecuaria y el Desarrollo Sostenible; Argentin

Collisional processes and size distribution in spatially extended debris discs

We present a new multi-annulus code for the study of collisionally evolving extended debris discs. We first aim to confirm results obtained for a single-annulus system, namely that the size distribution in "real" debris discs always departs from the theoretical collisional equilibrium dN\proptoR^{-3.5}dR power law, especially in the crucial size range of observable particles (<1cm), where it displays a characteristic wavy pattern. We also aim at studying how debris discs density distributions, scattered light luminosity profiles, and SEDs are affected by the coupled effect of collisions and radial mixing due to radiation pressure affected small grains. The size distribution evolution is modeled from micron-sized grains to 50km-sized bodies. The model takes into account the crucial influence of radiation pressure-affected small grains. We consider the collisional evolution of a fiducial a=120AU radius disc with an initial surface density in $\Sigma(a)\propto a^{\alpha}$. We show that the system's radial extension plays a crucial role: in most regions the collisional and size evolution of the dust is imposed by small particles on eccentric or unbound orbits produced further inside the disc. The spatial distribution of small grains strongly departs from the initial profile, while the bigger objects, containing most of the system's mass, still follow the initial distribution. This has consequences on the scattered--light radial profiles which get significantly flatter, and we propose an empirical law to trace back the distribution of large unseen parent bodies from the observed profiles. We finally provide empirical formula for the collisional size distribution and collision timescale that can be used for future debris disc modeling.Comment: Accepted for publication in Astronomy and Astrophysics (with better figures) (note: full abstract in the *.pdf file

MS-based targeted profiling of oxylipins in COVID-19: A new insight into inflammation regulation

The key role of inflammation in COVID-19 induced many authors to study the cytokine storm, whereas the role of other inflammatory mediators such as oxylipins is still poorly understood. IMPRECOVID was a monocentric retrospective observational pilot study with COVID-19 related pneumonia patients (n = 52) admitted to Pisa University Hospital between March and April 2020. Our MS-based analytical platform permitted the simultaneous determination of sixty plasma oxylipins in a single run at ppt levels for a comprehensive characterisation of the inflammatory cascade in COVID-19 patients. The datasets containing oxylipin and cytokine plasma levels were analysed by principal component analysis (PCA), computation of Fisher's canonical variable, and a multivariate receiver operating characteristic (ROC) curve. Differently from cytokines, the panel of oxylipins clearly differentiated samples collected in COVID-19 wards (n = 43) and Intensive Care Units (ICUs) (n = 27), as shown by the PCA and the multivariate ROC curve with a resulting AUC equal to 0.92. ICU patients showed lower (down to two orders of magnitude) plasma concentrations of anti-inflammatory and pro-resolving lipid mediators, suggesting an impaired inflammation response as part of a prolonged and unsolvable pro-inflammatory status. In conclusion, our targeted oxylipidomics platform helped shedding new light in this field. Targeting the lipid mediator class switching is extremely important for a timely picture of a patient's ability to respond to the viral attack. A prediction model exploiting selected lipid mediators as biomarkers seems to have good chances to classify patients at risk of severe COVID-19

A polymorphism in the promoter is associated with EZH2 expression but not with outcome in advanced pancreatic cancer patients

Aim: EZH2 expression is a prognostic marker in radically resected pancreatic ductal adenocarcinoma (PDAC) patients. Here we investigated its role in locally advanced/metastatic patients, as well as candidate polymorphisms. Materials &amp; methods: EZH2 expression and polymorphisms were evaluated by quantitative reverse transcription PCR in 32 laser microdissected tumors, while polymorphisms were also studied in blood samples from two additional cohorts treated with gemcitabine monotherapy (n = 93) or polychemotherapeutic regimens (n = 247). Results: EZH2 expression correlated with survival and with the rs6958683 polymorphism in the first cohort of patients, but this polymorphism was not associated with survival in our larger cohorts. Conclusion: EZH2 is a prognostic factor for locally advanced/metastatic PDACs, while candidate polymorphisms cannot predict clinical outcome. Other factors involved in EZH2 regulation, such as miR-101, should be investigated in accessible samples in order to improve the clinical management of advanced PDAC

Patient Perceptions and Knowledge of Ionizing Radiation from Medical Imaging

Importance: Although imaging has become a standard tool of modern medicine, its widespread use has been paralleled by an increasing cumulative radiation dose to patients despite technological advancements and campaigns calling for better awareness and minimization of unnecessary exposures. Objective: To assess patients' knowledge about medical radiation and related risks. Design, Setting, and Participants: A survey study of hospitals in Italy was conducted; all patients in waiting rooms for medical imaging procedures before undergoing imaging examinations at 16 teaching and nonteaching hospitals were approached to take the survey. The survey was performed from June 1, 2019, to May 31, 2020. Main Outcomes and Measures: Survey respondents' basic knowledge of ionizing radiation levels and health risks, earlier imaging tests performed, and information and communication about radiation protection issues. Results: Among 3039 patients invited to participate, the response rate was 94.3% (n = 2866). Participants included 1531 women (53.4%); mean (SD) age was 44.9 (17.3) years. Of the 2866 participants, 1529 (53.3%) were aware of the existence of natural sources of ionizing radiation. Mammography (1101 [38.4%]) and magnetic resonance imaging (1231 [43.0%]) were categorized as radiation-based imaging modalities. More than half of the 2866 patients (1579 [55.1%]; P =.03) did not know that chest computed tomography delivers a larger dose of radiation than chest radiography, and only 1499 (52.3%) knew that radiation can be emitted after nuclear medicine examinations (P =.004). A total of 667 patients (23.3%) believed that radiation risks were unrelated to age, 1273 (44.4%) deemed their knowledge about radiation risks inadequate, and 2305 (80.4%) preferred to be informed about radiation risks by medical staff. A better knowledge of radiation issues was associated with receiving information from health care professionals (odds ratio [OR], 1.71; 95% CI, 1.43-2.03; P &lt;.001) and having a higher educational level (intermediate vs low: OR, 1.48; 95% CI, 1.17-1.88; P &lt;.001; high vs low: OR, 2.68; 95% CI, 2.09-3.43; P &lt;.001). Conclusions and Relevance: The results of this survey suggest that patients undergoing medical imaging procedures have overall limited knowledge about medical radiation. Intervention to achieve better patient awareness of radiation risks related to medical exposures may be beneficial

Contribution by Polymorphonucleate Granulocytes to Elevated Gamma-Glutamyltransferase in Cystic Fibrosis Sputum

Background: Cystic fibrosis (CF) is an autosomal recessive disorder characterized by a chronic neutrophilic airways inflammation, increasing levels of oxidative stress and reduced levels of antioxidants such as glutathione (GSH). Gammaglutamyltransferase (GGT), an enzyme induced by oxidative stress and involved in the catabolism of GSH and its derivatives, is increased in the airways of CF patients with inflammation, but the possible implications of its increase have not yet been investigated in detail. Principal Findings: The present study was aimed to evaluate the origin and the biochemical characteristics of the GGT detectable in CF sputum. We found GGT activity both in neutrophils and in the fluid, the latter significantly correlating with myeloperoxidase expression. In neutrophils, GGT was associated with intracellular granules. In the fluid, gel-filtration chromatography showed the presence of two distinct GGT fractions, the first corresponding to the human plasma b-GGT fraction, the other to the free enzyme. The same fractions were also observed in the supernatant of ionomycin and fMLPactivated neutrophils. Western blot analysis confirmed the presence of a single band of GGT immunoreactive peptide in the CF sputum samples and in isolated neutrophils. Conclusions: In conclusion, our data indicate that neutrophils are able to transport and release GGT, thus increasing GGT activity in CF sputum. The prompt release of GGT may have consequences on all GGT substrates, including major inflammatory mediators such as S-nitrosoglutathione and leukotrienes, and could participate in early modulation of inflammatory response

Molecular and pathological characterization of the EZH2 rs3757441 single nucleotide polymorphism in colorectal cancer

Background The enhancer of zeste-homolog 2 (EZH2) is involved in cancer development through gene silencing by trimethylation of lysine 27 of histone 3 (H3K27me3). The C/C genotype for the EZH2 rs3757441 single-nucleotide polymorphism (SNP) is linked with poor prognosis in metastatic colorectal cancer (CRC), but molecular and pathological characterization of this SNP is lacking. Methods 119 primary CRCs were analyzed. SNP was evaluated by real-time PCR from colonic healthy tissue, while EZH2 and H3K27me3 expression were studied by immunohistochemistry. We primarily looked for correlation between EZH2 rs3757441 genotypes and EZH2/H3K27me3 expression. Potential associations between EZH2/H3K27me3 expression and clinico-pathological features or KRAS exon 2 and BRAF exon 15 mutations were secondary endpoints. Statistical analysis was performed by chi-square test, T-test or ANOVA. Results The C/C genotype was significantly associated with higher EZH2 (100 vs. 44 %; P = 0.019) and H3K27me3 (100 vs. 38 %; P = 0.009) staining intensity compared with C/T and T/T. EZH2 3+ staining significantly correlated with stronger H3K27me3 expression (P = 0.039). KRAS and BRAF mutations were not associated with EZH2 or H3K27me3 expression. Conclusion EZH2 rs3757441 C/C genotype is associated with stronger EZH2 and H3K27me3 immunoreactivity in primary CRC: this SNP may serve as a promising biomarker for EZH2-targeting agents and may add independent information to KRAS and BRAF testing

Asteroids. From Observations to Models

We will discuss some specific applications to the rotation state and the shapes of moderately large asteroids, and techniques of observations putting some emphasis on the HST/FGS instrument.Comment: to appear in LNP; 28pages; written in 2003; Winter School "Dynamique des Corps Celestes Non Ponctuels et des Anneaux", Lanslevillard (FRANCE