Exploring colistin pharmacodynamics against Klebsiella pneumoniae: A need to revise current susceptibility breakpoints

Objectives: Because the pharmacokinetic/pharmacodynamic (PK/PD) characteristics of colistin against Enterobacteriaceae are not well explored, we studied the activity of colistin against K. pneumoniae in an in vitro PK/PD model simulating different dosing regimens. Methods: Three clinical isolates of K. pneumoniae with MICs of 0.5, 1 and 4mg/L were tested in an in vitro PK/PD model following a dose-fractionation design over a period of 24h. A high and low inoculumof 107 and 104 cfu/mL with and without a heteroresistant subpopulation, respectively, were used. PK/PD indices associated with colistin activity were explored and Monte Carlo analysis was performed in order to determine the PTA for achieving a bactericidal effect (2 log kill). Results: The fAUC/MIC (R2"0.64-0.68) followed by fCmax/MIC (R2=0.55-0.63) best described colistin's 24 h log10 cfu/mL reduction for both low and high inocula. Dosing regimens with fCmax/MIC≥6 were always associated with a bactericidal effect (P=0.0025). However, at clinically achievable concentrations, usually below fCmax/MIC=6, an fAUC/MIC ≤25 was more predictive of a bactericidal effect. Using a dosing regimen of 9 MU/ day, the PTA for this pharmacodynamic target was 100%, 5%-70%and 0%, for isolates with MICs of ≤0.5, 1 and ≥2 mg/L, respectively. Dosing regimens that aim for a trough level of 1 mg/L achieve coverage of strains up to 0.5 mg/L (target trough/MIC=2 mg/L). Conclusions: Characterization of the pharmacodynamics of colistin against Enterobacteriaceae in an in vitro model of infection indicates that a revision of current susceptibility breakpoints is needed. Therapeutic drug monitoring of colistin to achieve pharmacodynamic targets in individual patients is highly recommended

Reperfusion therapy for ST elevation acute myocardial infarction 2010/2011: current status in 37 ESC countries

Aims Primary percutaneous coronary intervention (PPCI) is the preferred reperfusion therapy in ST-elevation myocardial infarction (STEMI). We conducted this study to evaluate the contemporary status on the use and type of reperfusion therapy in patients admitted with STEMI in the European Society of Cardiology (ESC) member countries. Methods and results A cross-sectional descriptive study based on aggregated country-level data on the use of reperfusion therapy in patients admitted with STEMI during 2010 or 2011. Thirty-seven ESC countries were able to provide data from existing national or regional registries. In countries where no such registries exist, data were based on best expert estimates. Data were collected on the use of STEMI reperfusion treatment and mortality, the numbers of cardiologists, and the availability of PPCI facilities in each country. Our survey provides a brief data summary of the degree of variation in reperfusion therapy across Europe. The number of PPCI procedures varied between countries, ranging from 23 to 884 per million inhabitants. Primary percutaneous coronary intervention and thrombolysis were the dominant reperfusion strategy in 33 and 4 countries, respectively. The mean population served by a single PPCI centre with a 24-h service 7 days a week ranged from 31 300 inhabitants per centre to 6 533 000 inhabitants per centre. Twenty-seven of the total 37 countries participated in a former survey from 2007, and major increases in PPCI utilization were observed in 13 of these countries. Conclusion Large variations in reperfusion treatment are still present across Europe. Countries in Eastern and Southern Europe reported that a substantial number of STEMI patients are not receiving any reperfusion therapy. Implementation of the best reperfusion therapy as recommended in the guidelines should be encourage

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

Το ηλεκτρονικό έγγραφο στις συναλλαγές

Η παρούσα διπλωματική εργασία πραγματεύεται τη φύση του ηλεκτρονικού εγγράφου και την αξιοποίησή του στις καθημερινές συναλλαγές, τόσο ως συστατικός όσο και ως αποδεικτικός τύπος. Θα ασχοληθούμε με τα ηλεκτρονικά έγγραφα εν στενή εννοία, δηλαδή αυτά που έχουν αμιγώς ηλεκτρονική μορφή, καθώς μόνο αυτά ρυθμίζονται από τον Κανονισμό 910/2014 και το προϊσχύον δίκαιο. Συνακόλουθα, μία βασική έννοια που θα μας απασχολήσει είναι αυτή της ηλεκτρονικής υπογραφής, καθώς από το είδος αυτής εξαρτάται και η αποδεικτική ισχύς του ηλεκτρονικού εγγράφου. Σε πρώτο στάδιο, θα επιχειρηθεί μια παρουσίαση των ηλεκτρονικών δηλώσεων βουλήσεως, καθώς τέτοιες δηλώσεις περιέχονται στα ηλεκτρονικά έγγραφα και θα αναζητηθεί επίσης ο ρόλος που διαδραματίζει ο ηλεκτρονικός υπολογιστής στη διαβίβαση ή και τη διαμόρφωση των ηλεκτρονικών εγγράφων.The present thesis deals with the nature of the electronic document and its exploitation in daily transactions, both as a constitutive and as a proof form. We will deal with electronic documents in a narrow sense, that is, those that are purely electronic, as only those are regulated by Regulation 910/2014 and the previous law. Consequently, a basic concept that will concern us is that of the electronic signature, since the probative value of the electronic document depends on the kind of the electronic signature that is attached to it. In the first instance, a presentation of the electronic declarations of intent will be attempted, as such statements are contained in the electronic documents, and we will also examine the role of the computer in the transmission and / or the configuration of the electronic documents

Model Application for Estimation of Agri-Environmental Indicators of Kiwi Production: A Case Study in Northern Greece

Due to the sensitivity of kiwifruit to soil water and nutrient availability, kiwi production is often associated with over-watering and over-fertilization, especially with nitrogen (N), resulting in increased environmental risks. Crop models are powerful tools for simulating crop production and environmental impact of given management practices. In this study, the CropSyst model was applied to estimate soil N budget and environmental effects of kiwi production, with particular regard to N losses, in two grower-managed kiwi orchards in northern Greece, involving two seasons and different management practices. Management options included N fertilization and irrigation. Model estimates were compared with yield and soil mineral N content (0–90 cm depths) measured three times within the growing season. Agri-environmental indicators were calculated based on the N budget simulation results to assess the environmental consequences (focusing on N losses and water use efficiency) of the different management practices in kiwi production. According to model simulation results, kiwifruit yield and N uptake were similar in both orchards. N losses to the environment, however, were estimated on average to be 10.3% higher in the orchard with the higher inputs of irrigation water and N fertilizer. The orchard with the lower inputs showed better water and N use efficiency. N leaching losses were estimated to be higher than 70% of total available soil N in both study sites, indicating potential impact on groundwater quality. These findings demonstrate the necessity for improved irrigation and N fertilization management in kiwi production in the area

Early phenotypic detection of fluconazole- and anidulafungin-resistant Candida glabrata isolates

Background: Increased fluconazole and echinocandin resistance in Candida glabrata requires prompt detection in routine settings. A phenotypic test based on the EUCAST E.DEF 7.3.2 protocol was developed for the detection of fluconazole- and anidulafungin-resistant isolates utilizing the colorimetric dye XTT. Methods: Thirty-one clinical C. glabrata isolates, 11 anidulafungin resistant and 14 fluconazole resistant, were tested. After optimization studies, 0.5-2.5 × 105 cfu/mL of each isolate in RPMI 1640 + 2% d-glucose medium containing 100 mg/L XTT + 0.78 μΜ menadione and 0.06 mg/L anidulafungin (S breakpoint) or 16 mg/L fluconazole (I breakpoint) in 96-well flat-bottom microtitration plates were incubated at 37°C for 18 h; we also included drug-free wells. XTT absorbance was measured at 450 nm every 15 min. Differences between the drug-free and the drug-treated wells were assessed using Student's t-test at different timepoints. ROC curves were used in order to identify the best timepoint and cut-off. Results: The XTT absorbance differences between fluconazole-containing and drug-free wells were significantly lower for the resistant isolates compared with susceptible increased exposure isolates (0.08 ± 0.05 versus 0.25 ± 0.06, respectively, P = 0.005) at 7.5 h, with a difference of &lt;0.157 corresponding to 100% sensitivity and 94% specificity for detection of resistance. The XTT absorbance differences between anidulafungin-containing and drug-free wells were significantly lower for the resistant isolates compared with susceptible isolates (0.08 ± 0.07 versus 0.200 ± 0.03, respectively, P &lt; 0.001) at 5 h, with a difference of &lt;0.145 corresponding to 91% sensitivity and 100% specificity, irrespective of underlying mutations. Conclusions: A simple, cheap and fast phenotypic test was developed for detection of fluconazole- and anidulafungin-resistant C. glabrata isolates.</p

Early phenotypic detection of fluconazole- and anidulafungin-resistant Candida glabrata isolates

Background: Increased fluconazole and echinocandin resistance in Candida glabrata requires prompt detection in routine settings. A phenotypic test based on the EUCAST E.DEF 7.3.2 protocol was developed for the detection of fluconazole- and anidulafungin-resistant isolates utilizing the colorimetric dye XTT. Methods: Thirty-one clinical C. glabrata isolates, 11 anidulafungin resistant and 14 fluconazole resistant, were tested. After optimization studies, 0.5-2.5 × 105 cfu/mL of each isolate in RPMI 1640 + 2% d-glucose medium containing 100 mg/L XTT + 0.78 μΜ menadione and 0.06 mg/L anidulafungin (S breakpoint) or 16 mg/L fluconazole (I breakpoint) in 96-well flat-bottom microtitration plates were incubated at 37°C for 18 h; we also included drug-free wells. XTT absorbance was measured at 450 nm every 15 min. Differences between the drug-free and the drug-treated wells were assessed using Student's t-test at different timepoints. ROC curves were used in order to identify the best timepoint and cut-off. Results: The XTT absorbance differences between fluconazole-containing and drug-free wells were significantly lower for the resistant isolates compared with susceptible increased exposure isolates (0.08 ± 0.05 versus 0.25 ± 0.06, respectively, P = 0.005) at 7.5 h, with a difference of <0.157 corresponding to 100% sensitivity and 94% specificity for detection of resistance. The XTT absorbance differences between anidulafungin-containing and drug-free wells were significantly lower for the resistant isolates compared with susceptible isolates (0.08 ± 0.07 versus 0.200 ± 0.03, respectively, P < 0.001) at 5 h, with a difference of <0.145 corresponding to 91% sensitivity and 100% specificity, irrespective of underlying mutations. Conclusions: A simple, cheap and fast phenotypic test was developed for detection of fluconazole- and anidulafungin-resistant C. glabrata isolates

Research for intervention programs to address the prepubertal and adolescent obesity. Their role in controlling weight

Introduction: According to the definition of the World Health Organization about obesity and considering the way that nurses handle it as consultants, we noted that literature focuses mainly on the prevention of the phenomenon rather than to its confrontation. Aim: The aim of the present systematic review was the study of the role of diet to the pubertal obesity prevention and the control of weight. Method: To prepare this systematic review we collected data from primary quantitative surveys, qualitative surveys and meta-analysis. The search was made in the databases PubMed Advanced, Medline Complete (EBSCOHost), Cinahl (EBSCOHost) and Scopus and resulted 1080 surveys (N 1080). Finally, studies obtained for further evaluation following the blockades, were 24 (N: 24). From them, 11 were meta-analysis, 9 quantitative, 4 were systematic reviews and one was qualitative study. Results: The results of this study concluded on the effect of diet in combating prepubertal and adolescent obesity and analyzed factors contributing the adoption of healthy eating in young people. It also analyzed the role played by the family and school environment to the prevention and proposals for intervention programs. Most studies conducted to date, confuse combat with prevention as two interconnected phenomena. Conclusion: This review concluded that to assess any level of food risk which may lead to obesity should take into account the dietary behavior of modern people

Assessment of Minimum Water Level in Lakes and Reservoirs Based on Their Morphological and Hydrological Features

The sustainable management of lakes and reservoirs requires the determination of their minimum environmental water level. Even though the assessment of minimum water level depends on a number of biotic and abiotic factors of the lake ecosystem, in many cases these factors are not entirely known and, furthermore, their evaluation is usually a challenging and laborious task. On the other hand, the lakes/reservoirs may comprise an important water resource to meet the requirements arising from economic activities. In this paper, the morphological and hydrological features of four lakes of northern Greece were analysed in order to assess their minimum environmental water level. The hydromorphological analysis was based on the relationship of the lake surface area and volume with water level as well as the water inflow from the lake&rsquo;s hydrological catchment area, considering as the lake&rsquo;s critical volume storage, the annual water volume flowing into a lake from its hydrological catchment area with a probability of exceedance 50% of a long time series of hydrological years. By combining morphological and hydrological features, the proposed methodology aimed to extend the analysis based solely on morphological features, and assess more comprehensively the minimum environmental water level in the four lakes, ensuring also the rising from the minimum level to the maximum (overflow) level for most of the hydrological years