introduction to the special issue high resolution topography quantitative analysis and geomorphological mapping

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Pharmacogenetics of bisphosphonate-associated osteonecrosis of the jaw.

An undesirable effect associated with bisphosphonates is osteonecrosis of the jaw (ONJ). Case reports discussed ONJ development in patients with multiple myeloma or metastatic cancers receiving bisphosphonates as palliation for malignant bone disease. No causative relationship has been unequivocally demonstrated between ONJ and bisphosphonate therapy. To determine if a higher sensitivity to bisphosphonates could in part explain the development of ONJ, the segregation of A/C rs2297480 polymorphism of gene encoding for the farnesyl pyrophosphate synthase (FDPS) with ONJ was evaluated in a cohort of 68 Caucasian patients treated with zoledronic acid for multiple myeloma and metastatic mammary and prostate cancer. The AA and CC genotypes were highly differently distributed among ONJ patients and controls, matched for sex and type of malignant disease, with a positive correlation between AA carrier status and occurrence of ONJ (p=0.03) after 18-24 months of treatment. Because FDPS gene variants have been associated with bone morbidity, these pharmacogenetic association likely reflect the interaction of amino-bisphosphonates with germline sensitivity to drug actions, and might identify patients at highest risk to develop ONJ

JRC Ispra EMEP - GAW Regional Station for Atmospheric Research - 2006 Report

The aim of the JRC-Ispra station for atmospheric research (45°49'N, 8°38'E) is to monitor atmospheric parameters (pollutant concentrations and fluxes, atmospheric particle chemical composition, number size distribution and optical properties) to contribute in assessing the impact of European policies on air pollution and climate change. The station has been operated continuously since November 1985, with a gap in gas phase data due to a severe breakdown of the data acquisition system in 2003 though. The measurements performed in 2006 led to annual averages of ca. 41 µg m-3 O3, 1.1 µg m-3 SO2, 21 µg m-3 NO2 and 33 µg m-3 PM10. Carbonaceous species (organic matter plus elemental carbon) are the main constituents of PM2.5 (> 50 %) followed by (NH4)2SO4 (10-20 %) and NH4NO3 (20-30 %). The measurements confirmed the seasonal variations observed over the previous years, mainly driven by meteorology rather than by changes in emissions. Aerosol physical and optical properties were also measured in 2006. The average particle number (from 6 nm to 10 µm) was about 10000 cm-3 in 2006. The mean (close to dry) aerosol single scattering albedo (a key parameter for determining the aerosol direct radiative forcing) was 0.79. Long-term trends (over 20 years) show decreases in sulfur concentrations and deposition, and in extreme ozone value occurrence frequency, although the latter was higher in compared to the last two years The decreasing trends in nitrogen oxides, reduced nitrogen species, and PM concentrations are much less pronounced.JRC.H.2-Climate chang

JRC Ispra EMEP-GAW Regional Station for Atmospheric Research - 2007 Report

The aim of the JRC-Ispra station for atmospheric research (45°49'N, 8°38'E) is to monitor atmospheric parameters (pollutant concentrations and fluxes, atmospheric particle chemical composition, number size distribution and optical properties) to contribute in assessing the impact of European policies on air pollution and climate change. The station has been operated continuously since November 1985, with a gap in gas phase data due to a severe breakdown of the data acquisition system in 2003 though. The measurements performed in 2007 led to annual averages of ca. 32 µg m-3 O3, 0.8 µg m-3 SO2, 21 µg m-3 NO2 and 30 µg m-3 PM10. Carbonaceous species (organic matter plus elemental carbon) are the main constituents of PM2.5 (> 55 %) followed by NH4NO3 (20-30 %) and (NH4)2SO4 (10-20 %). The measurements confirmed the seasonal variations observed over the previous years, mainly driven by meteorology rather than by changes in emissions. Aerosol physical and optical properties were also measured in 2007. The average particle number (from 10 nm to 10 µm) was about 9200 cm-3 in 2007. The mean (close to dry) aerosol single scattering albedo (0.79) was low compared to the values generally observed in Europe, which means that the cooling effect of aerosols is reduced in our region compared to others. Long-term trends (over 20 years) show consistent decreases in sulfur concentrations and deposition, PM mass concentration (-0.9 µg m-3 yr-1) and in extreme ozone value occurrence frequency. The decreasing trends in oxidised and reduced nitrogen species are much less pronounced. However, historical minimum in NO3-, NH4+, (and SO42-) wet deposition, as well as in O3 pollution indicators (AOT40 and SOMO35) were observed in 2007.JRC.H.2-Climate chang

JRC Ispra EMEP - GAW Regional Station for Atmospheric Research 2008 Report

The aim of the JRC-Ispra station for atmospheric research (45°49'N, 8°38'E) is to monitor atmospheric parameters (pollutant concentrations and fluxes, atmospheric particle chemical composition, number size distribution and optical properties) to contribute in assessing the impact of European policies on air pollution and climate change. The station has been operated continuously since November 1985, with a gap in gas phase data due to a severe breakdown of the data acquisition system in 2003 though. The measurements performed in 2008 led to annual averages of ca. 34 µg m-3 O3, 0.7 µg m-3 SO2, 20 µg m-3 NO2 and 27 µg m-3 PM10. Carbonaceous species (organic matter plus elemental carbon) are the main constituents of PM2.5 (~57 %) followed by NH4NO3 (20-30 %) and (NH4)2SO4 (10-20 %). The data from 2008 confirmed the seasonal variations observed over the previous years, mainly driven by meteorology rather than by changes in emissions, as revealed by the lidar measurements. Aerosol physical and optical properties were also measured in 2008. The average particle number (from 10 nm to 10 µm) was about 8000 cm-3 in 2008. The mean (close to dry) aerosol single scattering albedo (0.75) was low compared to the values generally observed in Europe, which means that the cooling effect of aerosols is reduced in our region compared to others. Long-term trends (over 20 years) show consistent decreases in sulfur concentrations and deposition, PM mass concentration (-0.9 µg m-3 yr-1), and from 2003 in ozone concentrations too. The decreasing trends in oxidised and reduced nitrogen species are much less pronounced.JRC.H.2-Climate chang

JRC Ispra EMEP - GAW Regional Station for Atmospheric Research, 2009 Report

The aim of the JRC-Ispra station for atmospheric research (45°49¿N, 8°38¿E) is to monitor atmospheric parameters (pollutant concentrations and fluxes, atmospheric particle chemical composition, number size distribution and optical properties) to contribute in assessing the impact of European policies on air pollution and climate change. The station has been operated continuously since November 1985, with a gap in gas phase data in 2003 and 2009 due to a breakdown of the data acquisition system and lack of man-power, respectively. The measurements performed in 2009 led to annual average of 26.8 µg m-3 for PM10, well below the European annual limit value of 40 µg/m³ (the European directive 1999/30/EC for the year 2005 and onwards). In addition, the measurements performed in 2009 led to annual average of 19.0 µg m-3 for PM2.5, well below the future European annual limit value of 25 µg/m³ (European directive 2008/50/EC for the year 2015 and onwards). Carbonaceous species (organic matter plus elemental carbon) are the main constituents of PM2.5 (~57 %) followed by (NH4)2SO4 (24 %) and NH4NO3 (12 %). The data from 2009 confirmed the seasonal variations observed over the previous years, mainly driven by meteorology rather than by changes in emissions, as revealed by the lidar measurements. Aerosol physical and optical properties were also measured in 2009. The average particle number (from 10 nm to 10 µm) was about 7400 cm-3 and the mean geometric diameter was 70 nm. Their hygroscopic growth at 90% RH varies from <1.2 in December to 1.25 ¿ 1.35 (size dependent) in June. The mean (close to dry) aerosol single scattering albedo at ¿ = 550 nm was 0.76, and it was low compared to the values generally observed in Europe, which means that the cooling effect of aerosols is reduced in our region compared to others. Long-term trends (over 20 years) show consistent decreases in sulfur concentrations and deposition, PM mass concentration (about -0.9 µg m-3 yr-1), and from 2003 onwards also a slight decease in ozone concentrations too. The decreasing trends in oxidised and reduced nitrogen species are much less pronounced.JRC.DDG.H.2-Climate change and air qualit

L-Arginine-Derived Polyamidoamine Oligomers Bearing at Both Ends beta-Cyclodextrin Units as pH-Sensitive Curcumin Carriers

The aza-Michael polyaddition of L-arginine and N,N′-methylene-bis-acrylamide gives the biocompatible and easily cell-internalized polyamidoamine ARGO7. By controlled synthesis, two ARGO7 oligomers, namely a trimer and a pentamer, bearing acrylamide terminal units, were obtained as precursors of the β-cyclodextrin-end-terminated oligomers P3 and P5, which have been shown to encapsulate curcumin at both pH 7.4 and 4.5. After lyophilization, P3- and P5-curcumin complexes gave stable water solutions. The apparent solubility of encapsulated curcumin was in the range 20–51 μg mL(−1), that is, three orders of magnitude higher than the water solubility of free curcumin (0.011 μg mL(−1)). The drug release profiles showed induction periods both at pH levels 4.5 and 7.4, suggesting a diffusive release mechanism, as confirmed by kinetic studies. The release rate of curcumin was higher at pH 7.4 than at pH 4.5 and, in both cases, it was higher for the P5 complex. Encapsulated curcumin was more photostable than the free drug. Molecular mechanics and molecular dynamics simulations explain at atomistic level the formation of aggregates due to favorable van der Waals interactions. The drug molecules interact with the external surface of carriers or form inclusion complexes with the β-cyclodextrin cavities. The aggregate stability is higher at pH 4.5

Cyclodextrin-Based Nanohydrogels Containing Polyamidoamine Units: A New Dexamethasone Delivery System for Inflammatory Diseases

Glucocorticoids are widely prescribed in treatment of rheumatoid arthritis, asthma, systemic lupus erythematosus, lymphoid neoplasia, skin and eye inflammations. However, well-documented adverse effects offset their therapeutic advantages. In this work, novel nano-hydrogels for the sustained delivery of dexamethasone were designed to increase both bioavailability and duration of the administered drug and reducing the therapeutic dose. Hydrogels are soft materials consisting of water-swollen cross-linked polymers to which the insertion of cyclodextrin (CD) moieties adds hydrophobic drug-complexing sites. Polyamidoamines (PAAs) are biocompatible and biodegradable polymers apt to create CD moieties in hydrogels. In this work, β or γ-CD/PAA nanogels have been developed. In vitro studies showed that a pretreatment for 24–48 h with dexamethasone-loaded, β-CD/PAA nanogel (nanodexa) inhibits adhesion of Jurkat cells to human umbilical vein endothelial cells (HUVEC) in conditions mimicking inflammation. This inhibitory effect was faster and higher than that displayed by free dexamethasone. Moreover, nanodexa inhibited COX-2 expression induced by PMA+A23187 in Jurkat cells after 24–48 h incubation in the 10−8–10−5 M concentration range, while dexamethasone was effective only at 10−5 M after 48 h treatment. Hence, the novel nanogel-dexamethasone formulation combines faster action with lower doses, suggesting the potential for being more manageable than the free drug, reducing its adverse side effects

Effects of a dietary crude fibre concentrate on growth in weaned piglets

Many fibre sources can help the adaptation of piglets at weaning, improving the growth. In this study, the effects of a dietary crude fibre concentrate (CFC) on piglet’s growth was investigated. From 31 to 51 days of age, 108 weaned piglets (D×(Lw×L)), had access to two isofibrous, isoenergetic and isonitrogenous diets, supplemented with 1% of CFC (CFC group) or not (control (CON) group). From days 52 to 64 all piglets received the same starter diet. During the dietary treatment period the CFC group showed higher average daily gain, average daily feed intake and feed efficiency (P&lt;0.001) than CON group. At 64 days of age, BW was higher in CFC group compared with CON group (P&lt;0.001). Blood samples were collected at days 31, 38, 45 and 52 of age. From days 31 to 52 significant differences in the somatotropic axis between groups were observed. In particular, growth hormone levels were higher only at the end of the 1st week of dietary treatment (P&lt;0.05) in CFC group animals compared with CON group animals. The IGF-I trend was similar between groups even if the IGF-I levels were higher in the CFC group than CON group 1 week after starting treatment (P&lt;0.01). The IGF-binding protein 3 (IGFBP-3) levels were higher in the first 2 weeks of dietary treatment and lower in the 3rd week in CON group compared with CFC group (P&lt;0.01). Specifically, the IGFBP-3 profile was consistent with that of IGF-I in CFC group but not in CON group. At the same time, an increase of leptin in CFC compared with CON group was observed (P&lt;0.05). Piglets fed the CFC diet showed a lower diarrhoea incidence (P&lt;0.05) and a lower number of antibiotic interventions (P&lt;0.05) than CON diet from 31 to 51 days of age. Pig-major acute-phase protein plasma level (P&lt;0.01) and interleukin-6 gene expression (P&lt;0.05) were higher in CON group than CFC group at the end of 1st week of dietary treatment. In conclusion, this study showed that CFC diet influences the hormones related to energy balance enhancing the welfare and growth of piglets. Furthermore, the increase in feed intake during 3 weeks of dietary treatment improved the feed efficiency over the entire post-weaning period