197,681 research outputs found

    The impact of heat waves on mortality.

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    BACKGROUND: Heat waves have been linked with an increase in mortality, but the associated risk has been only partly characterized. METHODS: We examined this association by decomposing the risk for temperature into a "main effect" due to independent effects of daily high temperatures, and an "added" effect due to sustained duration of heat during waves, using data from 108 communities in the United States during 1987-2000. We adopted different definitions of heat-wave days on the basis of combinations of temperature thresholds and days of duration. The main effect was estimated through distributed lag nonlinear functions of temperature, which account for nonlinear delayed effects and short-time harvesting. We defined the main effect as the relative risk between the median city-specific temperature during heat-wave days and the 75th percentile of the year-round distribution. The added effect was defined first using a simple indicator, and then a function of consecutive heat-wave days. City-specific main and added effects were pooled through univariate and multivariate meta-analytic techniques. RESULTS: The added wave effect was small (0.2%-2.8% excess relative risk, depending on wave definition) compared with the main effect (4.9%-8.0%), and was apparent only after 4 consecutive heat-wave days. CONCLUSIONS: Most of the excess risk with heat waves in the United States can be simply summarized as the independent effects of individual days' temperatures. A smaller added effect arises in heat waves lasting more than 4 days

    Exploring the potential of zwitterionic teicoplanin-based CSPs by using macroporous superficially porous silica particles 2.7 μm 160Å and 3.4 μm 400Å

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    During the last years, the research in the enantioselective Ultra High Performance Chromatography (eUHPC) is going to push the limits of high efficient and ultrafast analyses. In this work, novel Chiral Stationary Phases (CSPs) were prepared by covalently bonding the teicoplanin selector (TE_A2-2) on Halo 2.7μm 160Å and 3.4μm 400Å Superficially Porous silica Particles (SPP). An innovative bonding protocol allowed to obtain a zwitterionic teicoplanin based CSP, which was used to produce the already known UHPC-FPP-Titan-Tzwitt CSP based on 1.9 μm 120Å Fully Porous monodispersed silica Particles (FPP) and UHPC-SPP-Halo90-Tzwitt CSP 2.0 μm [1-3]. Columns with an internal diameter of 4.6 mm and different lengths (50 and 100 mm) were packed with all CSPs and characterized in terms of permeability, efficiency and thermodynamic under HILIC conditions. The kinetic performance was evaluated through the use of van Deemter curves. The UHPC-SPP-Halo160-Tzwitt 2.7 μm column exhibited extremely high efficiencies on both achiral (>323,000 theoretical plates/meter, N/m; hr: 1.14) and chiral compounds (>240,000 N/m; hr: 1.53) under HILIC conditions, attesting the high potential of this CSP from the kinetic viewpoint. An extreme efficiency was recorded by using the HPC-SPP-Halo400-Tzwitt 3.4 μm column which allowed to achieve an efficiency of 280’000 N/m on naphthalene (hr: 1.05). Furthermore, taking into account the thermodynamic viewpoint, the UHPC-SPP-Halo160-Tzwitt 2.7 μm exhibited the highest resolution power (Rs/tr,2) thanks to its enantioselectivity values because of the higher selector density on the silica matrix. In conclusion, in this study we demonstrate the potential of the use of SPP macroporous silica particles in the UHPLC chiral field opening an interesting scenario in the chiral chromatography area. [1] O.H. Ismail, A. Ciogli, C. Villani, M. De Martino, M. Pierini, A. Cavazzini, D.S. Bell, F. Gasparrini, J. Chromatogr. A, 1427 (2016) 55–68. [2] O.H. Ismail, M. Antonelli, A. Ciogli, C. Villani, A. Cavazzini, M. Catani, F. Gasparrini, J. Chromatogr. A, 1520 (2017) 91–102 [3] O.H. Ismail, M. Antonelli, A. Ciogli, M. De Martino, M. Catani, C. Villani, A. Cavazzini, M. Ye, D.S. Bell, F. Gasparrini, J. Chromatogr. A., 1576 (2018), 42-50

    Diagenesis versus hydrothermalism and fluid–rock interaction within the Tuscan Nappe of the Monte Amiata CO2-rich geothermal area (Italy)

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    In southern Tuscany (central Italy), deep to shallow geothermal systems were active since the Pleistocene and comprise fluids carrying variable amounts of CO2. The Monte Amiata geothermal fields include two main reser- voirs: a deep one located in the Palaeozoic metamorphic succession (1300–3000 m deep) belonging to the Tus- can metamorphic ‘basement’ and a shallow one hosted in the Mesozoic sedimentary succession (500–1000 m deep) belonging to the Tuscan Nappe. Multiple sets of calcite veins were investigated in some outcrops of the Tuscan Nappe succession exposed in the Monte Amiata area and surroundings. Two main fluid systems were characterized: the former related to combined diagenetic syn-tectonic processes from highly saline fluids after interaction with the Late Triassic evaporites (Burano Fm) and the latter related to a fossil geothermal system, Pleistocene in age, fed by low-salinity meteoric fluids, carrying CO2, radiogenic Sr and heavy O isotopes after interaction with the subsurface rocks. Comparison with the present-day hydrothermal fluids allowed to sketch the thermal evolution of the system from past to present. Geochemical data proved that portions of the vein–host rocks were reset after interaction with CO2-rich fluids circulating in the past. Consequently, textural and mineral- ogical changes are expected to have occurred with respect to the undisturbed rock masses. Understanding these modifications, their location and extension, is a prerequisite to construct (i) geochemical models addressed to the comprehension of the diagenesis induced in sediments after long-term CO2 storage; and (ii) geological models applied to the prediction of rock heterogeneity distribution within the upper reservoirs, characterizing the shallow (500–1500 m) geothermal systems of southern Tuscany

    Characterization and applications in seconds time scale of new totally porous sub-2micron CSPs: brush-type and macrocyclic selectors.

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    Over the last ten years, the technological progress has led to the development of stationary phases on ever smaller silica particles and instruments (UHPLC/UHPSFC) with a reduced extra-column volume able to reach very high pressure. These innovations allow higher efficiencies, resolutions and permit to reduce the analysis time and the eluent consumption. For these reasons also chiral stationary phases (CSPs) are moving to sub-2μm particles diameter. This talk concerns the development of two different sub-2μm CSPs based on the WhelkO-1[1] and on the teicoplanin selectors[2]. The first selector was covalently bonded on fully porous 1.8 μm Kromasil and the second one on totally porous and monodispersed 1.9 μm Titan silica particles. Both CSPs were packed in columns with an I.D. of 4.6 mm and different lengths, from 10 cm down to 1 cm, the latter geometry permitting very short analysis time. The UHPLC columns packed with the WhelkO-1-CSP were evaluated using normal phase and supercritical fluid eluents. Kinetic performances were estimated using trans-stilbene oxide as a probe, and resulted in efficiencies up to 250’000 plates/m under normal phase conditions. To evaluate the thermodynamic performances a large library screening[3] was performed under sub-critical fluid conditions: in one working day, 81 out of 129 randomly collected racemates were resolved under identical eluting conditions. The new UHPC-Titan120-Chirobiotic-TZWIT-1.9 showed a broad field of application in different environments (reversed phase, polar organic mode, HILIC, sub-critical fluid and normal phase). The thermodynamic performances of the new TEICO-Titan 1.9 μm have been evaluated with several N-protected amino acids, aryloxy acids, pharmaceutical compounds, sulfoxides and phosphine oxides. This CSP frequently showed high enantio-selectivity values: downsizing in column length, from 10-cm down to 1-cm was easily possible maintain high efficiency obtaining baseline separations and providing a considerable reduction of the analysis time. Ultra-fast enantiomeric separations in less than 60 seconds could get a routine in the chiral screening methods. References [1] D. Kotoni, A. Ciogli, C. Molinaro, I. D’Acquarica, J. Kocergin, T. Szczerb, H. Ritchie, C. Villani, F. Gasparrini, Anal. Chem., 84 (2012), 6805 [2] Berthod A., Chen X., Kullman J.P., Armstrong D.W., Gasparrini F., D’Acquarica I., Villani C., Carotti A., Anal. Chem. 72 (2000) 1767-1780; [3] L. Sciascera, O. Ismail, A. Ciogli, D. Kotoni, A. Cavazzini, L. Botta, T. Szczerba, J. Kocergin, C. Villani, F. Gasparrini, JCA, 1383 (2015) 160–16

    L-carnitine during in vitro culture enhances the cryotolerance of buffalo (Bubalus bubalis) in vitro derived embryos.

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    In buffalo, in vitro embryo production (IVEP) technology is the best tool to improve the genetic merit through the maternal lineage. A major limitation of IVEP technology in buffalo species is the poor cryotolerance of the embryos, likely due to their high lipid content (Gasparrini 2002 Theriogenology 57, 237–256). It was previously demonstrated that supplementing bovine culture media with L-carnitine, a cofactor of β-oxidation, improves in vitro embryo development (Sutton-McDowall et al. 2012 Theriogenology 77, 1632–1641). The aim of this work was to evaluate whether L-carnitine supplementation during in vitro culture (IVC) improves blastocyst development and cryotolerance of in vitro produced buffalo embryos. After a preliminary dose response trial, we selected the concentration of 0.25 mM for the experiment. Cumulus–oocytes complexes (n = 288, over 4 replicates), recovered from slaughtered animals, were matured and fertilized in vitro according to our standard procedures (Gasparrini et al. 2006 Theriogenology 65, 275–287). On Day 1 (Day 0 = IVF), zygotes were cultured in SOF supplemented with 8 mg mL–1 BSA, in the absence (control, n = 143) or presence of 0.25 mM L-carnitine (n = 145). In vitro culture was carried out at 38.5°C under 5% CO2, 7% O2, and 88% N2. Cleavage rate was evaluated on Day 5, when the cleaved embryos were transferred into fresh medium for further 2 days. On Day 7 after IVF, embryo outcome was assessed and all the embryos were vitrified by cryotop in 16.5% ethylene glycol, 16.5% dimethyl sulfoxide (DMSO), and 0.5 M sucrose (De Rosa et al. 2007 Ital. J. Anim. Sci. 6(Suppl 2), 747–750). The resistance to cryopreservation was evaluated by assessing the survival rate, on the basis of morphological criteria, after 24 h culture. Data were analyzed by chi-square test. No differences were found in cleavage rates between the control (81.5%) and the L-carnitine group (78.8%). The blastocyst yields (calculated in relation to the cleaved embryos) were not significantly influenced by the L-carnitine treatment (40.2 and 52.9%, in the control and the L-carnitine groups, respectively). However, buffalo embryos cultured in the presence of L-carnitine showed an increased resistance to cryopreservation, as indicated by the higher survival rates recorded after 24 h culture (78.7 and 96.4%, in the control and the L-carnitine groups, respectively; P < 0.01). In conclusion, these results demonstrated that L-carnitine supplementation of culture medium improves the resistance to cryopreservation of in vitro produced buffalo embryos. We speculate that the increased cryotolerance observed in the presence of L-carnitine may be due to a better utilization of the endogenous lipid stores, resulting in improved embryo quality

    NAMPT: A critical driver and therapeutic target for cancer

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    Nicotinamide phosphoribosyltransferase (NAMPT) possesses a vital role in mammalian cells due to its activity as a rate-limiting enzyme in the biosynthesis of nicotinamide adenine dinucleotide (NAD) from nicotinamide. NAD is an essential redox cofactor, but it also functions as a substrate for NAD-consuming enzymes, regulating multiple cellular processes such as DNA repair and gene expression, fundamental to sustain tumor growth and survival and energetic needs. A common strategy that several tumor types adopt to sustain NAD synthesis is to over-express NAMPT. However, beside its intracellular functions, this enzyme has a second life outside of cells exerting cytokine-like functions and mediating pro-inflammatory conditions activating signaling pathways. While the effects of NAMPT/NAD axis on energetic metabolism in tumors has been well-established, increasing evidence demonstrated the impact of NAMPT over-expression (intra-/extra-cellular) on several tumor cellular processes, including DNA repair, gene expression, signaling pathways, proliferation, invasion, stemness, phenotype plasticity, metastatization, angiogenesis, immune regulation, and drug resistance. For all these reasons, NAMPT targeting has emerged as promising anti-cancer strategy to deplete NAD and impair cellular metabolism, but also to counteract the other NAMPT-related functions. In this review, we summarize the key role of NAMPT in multiple biological processes implicated in cancer biology and the impact of NAMPT inhibition as therapeutic strategy for cancer treatment
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