In-Vitro-Experiments on the Dissolution of Ca-Oxalate and Ca-Phosphate Renal Calculi by the Tricarboxylic Acids of the Krebs-Cycle. Results and in Vivo Perspectives

The nephrolithiasis is the most frequent urological disease.1•2 The stone incidence in general is 1-4°/o and can be compared with that of diabetes mellitus

Current status of MELCOR 2.2 for fusion safety analyses

MELCOR is an integral code developed by Sandia National Laboratories (SNL) for the US Nuclear Regulatory Commission (USNRC) to perform severe accident analyses of Light Water Reactors (LWR). More recently, MELCOR capabilities are being extended also to analyze non-LWR fission technologies. Within the European MELCOR User Group (EMUG), organized in the framework of USNRC Cooperative Severe Accident Research Program (CSARP), an activity on the evaluation of the applicability of MELCOR 2.2 for fusion safety analyses has been launched and it has been coordinated by ENEA. The aim of the activity was to identify the physical models to be possibly implemented in MELCOR 2.2 necessary for fusion safety analyses, and to check if those models are already available in MELCOR 1.8.6 for fusion version, developed by Idaho National Laboratory (INL). From this activity, a list of modeling needs emerged from the safety analyses of fusion-related installations have been identified and described. Then, the importance of the various needs, intended as the priority for model implementation in the MELCOR 2.2 code, has been evaluated according to the technical expert judgement of the authors. In the present paper, the identified modeling needs are discussed. The ultimate goal would be to propose to have a single integrated MELCOR 2.2 code release capable to cover both fission and fusion applications

Current status of Melcor 2.2 for fusion safety analyses

MELCOR is an integral code developed by Sandia National Laboratories (SNL) for the US Nuclear Regulatory Commission (USNRC) to perform severe accident analyses of Light Water Reactors (LWR). More recently, MELCOR capabilities are being extended also to analyze non-LWR fission technologies. Within the European MELCOR User Group (EMUG), organized in the framework of the USNRC Cooperative Severe Accident Research Program (CSARP), an activity on the evaluation of the applicability of MELCOR 2.2 for fusion safety analyses has been launched and it has been coordinated by ENEA. The aim of the activity was to identify the physical models to be possibly implemented in MELCOR 2.2 necessary for fusion safety analyses, and to check if those models are already available in MELCOR 1.8.6 fusion version, developed by Idaho National Laboratory (INL). From this activity, a list of modeling needs that emerged from the safety analyses of fusion-related installations has been identified and described. Then, the importance of the various needs, intended as the priority for model implementation in the MELCOR 2.2 code, has been evaluated according to the technical expert judgment of the authors. In the present paper, the identified modeling needs are discussed. The ultimate goal would be to propose to have a single integrated MELCOR 2.2 code release capable to cover both fission and fusion applications

Growth and nutrient absorption of Cape Gooseberry (Physalis Peruviana L.) in soilless culture

"This is an Author's Accepted Manuscript of an article published in [include the complete citation information for the final version of the article as published in the Journal of Plant Nutrition 2015 March, available online at: http://www.tandfonline.com/10.1080/01904167.2014.934474."Cape gooseberry (Physalis peruviana L.) is a solanaceous plant. The growth and time-course of nutrient accumulation of the plant and its partitioning between roots, stems, leaves, and fruits were examined. The study was conducted analyzing two nutrient solutions in soilless culture under greenhouse conditions during two consecutive seasons. The macronutrient contents were analyzed. On average, the yield was 8.9 t.ha(-1). Growth of the plant until 90 d after transplanting obeys an exponential function of time and the relative growth rate for this period was determined. Nitrogen (N) was the element that showed the highest concentration, corresponding to leaves (4.67%), followed by potassium (K) in stems (4.46%). The highest accumulations of N, phosphorous (P), calcium (Ca), and magnesium (Mg) were found in leaves and of K in the stems. Potassium showed the highest nutrient accumulation (29 g.plant(-1)) and the highest specific uptake rate.Torres Rubio, JF.; Pascual Seva, N.; San Bautista Primo, A.; Pascual España, B.; López Galarza, SV.; Alagarda Pardo, J.; Maroto Borrego, JV. (2015). Growth and nutrient absorption of Cape Gooseberry (Physalis Peruviana L.) in soilless culture. Journal of Plant Nutrition. 38(4):485-496. doi:10.1080/01904167.2014.934474S485496384Bellaloui, N., & Brown, P. H. (1998). Plant and Soil, 198(2), 153-158. doi:10.1023/a:1004343031242Bennett, J. P., Oshima, R. J., & Lippert, L. F. (1979). Effects of ozone on injury and dry matter partitioning in pepper plants. Environmental and Experimental Botany, 19(1), 33-39. doi:10.1016/0098-8472(79)90022-4CAUSTON, D. R. (1991). Plant Growth Analysis: The Variability of Relative Growth Rate Within a Sample. Annals of Botany, 67(2), 137-144. doi:10.1093/oxfordjournals.aob.a088112Convenio MAG-IICA (Ministerio de Agricultura y Ganadería. Institución Interamericana de Cooperación para la Agricultura). 2001. The cape gooseberry (Physalis peruvianaL.Physalis edulis). Subprograma de Cooperación Técnica, Ecuador. Available at: http://www.sica.gov.ec/agronegocios/Biblioteca/Convenio%20MAG%20IICA/productos/uvilla_mag.pdf (Accessed July 2007, in Spanish).El-Tohamy, W. A., El-Abagy, H. M., Abou-Hussein, S. D., & Gruda, N. (2009). Response of Cape gooseberry (Physalis peruviana L.) to nitrogen application under sandy soil conditions. Gesunde Pflanzen, 61(3-4), 123-127. doi:10.1007/s10343-009-0211-0Fresquet, J., Pascual, B., López-Galarza, S., Bautista, S., Baixauli, C., Gisbert, J. M., & Maroto, J. V. (2001). Nutrient uptake of pepino plants in soilless cultivation. The Journal of Horticultural Science and Biotechnology, 76(3), 338-343. doi:10.1080/14620316.2001.11511373Heuvelink, E., Bakker, M. J., Elings, A., Kaarsemaker, R. C., & Marcelis, L. F. M. (2005). EFFECT OF LEAF AREA ON TOMATO YIELD. Acta Horticulturae, (691), 43-50. doi:10.17660/actahortic.2005.691.2Leskovar, D. I., & Cantliffe, D. J. (1993). Comparison of Plant Establishment Method, Transplant, or Direct Seeding on Growth and Yield of Bell Pepper. Journal of the American Society for Horticultural Science, 118(1), 17-22. doi:10.21273/jashs.118.1.17Marcelis, L. F. M. (1993). Fruit growth and biomass allocation to the fruits in cucumber. 1. Effect of fruit load and temperature. Scientia Horticulturae, 54(2), 107-121. doi:10.1016/0304-4238(93)90059-yPuente, L. A., Pinto-Muñoz, C. A., Castro, E. S., & Cortés, M. (2011). Physalis peruviana Linnaeus, the multiple properties of a highly functional fruit: A review. Food Research International, 44(7), 1733-1740. doi:10.1016/j.foodres.2010.09.034Radford, P. J. (1967). Growth Analysis Formulae - Their Use and Abuse1. Crop Science, 7(3), 171. doi:10.2135/cropsci1967.0011183x000700030001xRamadan, M. F., & Moersel, J. T. (2007). Impact of enzymatic treatment on chemical composition, physicochemical properties and radical scavenging activity of goldenberry (Physalis peruviana L.) juice. Journal of the Science of Food and Agriculture, 87(3), 452-460. doi:10.1002/jsfa.2728Ramadan, M. F., & Moersel, J.-T. (2009). Oil extractability from enzymatically treated goldenberry (Physalis peruvianaL.) pomace: range of operational variables. International Journal of Food Science & Technology, 44(3), 435-444. doi:10.1111/j.1365-2621.2006.01511.xSalazar, M. R., Jones, J. W., Chaves, B., & Cooman, A. (2008). A model for the potential production and dry matter distribution of Cape gooseberry (Physalis peruviana L.). Scientia Horticulturae, 115(2), 142-148. doi:10.1016/j.scienta.2007.08.015Scholberg, J., McNeal, B. L., Jones, J. W., Boote, K. J., Stanley, C. D., & Obreza, T. A. (2000). Growth and Canopy Characteristics of Field-Grown Tomato. Agronomy Journal, 92(1), 152. doi:10.2134/agronj2000.921152xTrinchero, G. D., Sozzi, G. O., Cerri, A. M., Vilella, F., & Fraschina, A. A. (1999). Ripening-related changes in ethylene production, respiration rate and cell-wall enzyme activity in goldenberry (Physalis peruviana L.), a solanaceous species. Postharvest Biology and Technology, 16(2), 139-145. doi:10.1016/s0925-5214(99)00011-3Turner, A. (1994). Dry Matter Assimilation and Partitioning in Pepper Cultivars Differing in Susceptibility to Stress-induced Bud and Flower Abscission. Annals of Botany, 73(6), 617-622. doi:10.1006/anbo.1994.1077WILLIAMS, R. F. (1946). The Physiology of Plant Growth with Special Reference to the Concept of Net Assimilation Rate. Annals of Botany, 10(1), 41-72. doi:10.1093/oxfordjournals.aob.a083119Zapata, J.L., A. Saldarriaga, M. Londoño, and C. Díaz. 2002. Cape gooseberry Management in Colombia. Antioquia, Colombia: Rionegro, Programa Nacional de Transferencia de Tecnología Agropecuaria - Corpoica Regional Cuatro (in Spanish).Zerihun, A. (2000). Compensatory Roles of Nitrogen Uptake and Photosynthetic N-use Efficiency in Determining Plant Growth Response to Elevated CO2: Evaluation Using a Functional Balance Model. Annals of Botany, 86(4), 723-730. doi:10.1006/anbo.2000.123

Auditory ossicles: a potential biomarker for maternal and infant health in utero

YesBackground: Carbon (δ13C) and nitrogen (δ15N) isotope ratios of collagen from teeth and bone are used to study human nutrition and health. As bones are constantly remodelling throughout life, isotopic values of bone collagen represent an average of several years. In contrast, human teeth do not remodel and their primary dentine contains only the isotopic data from the time of formation. In contrast to all other bones, human auditory ossicles also appear not to remodel. As they develop in utero and finish formation in the first 2 years of life, their collagen should also represent isotopic values of these two relatively short periods. Aim: By comparing δ13C and δ15N data from ossicles and incremental dentine, this study aims to investigate how two developmental periods of the ossicles, in utero and the first 2 years of life, reflect in collagen obtained from the ossicles. Subject and methods: Ossicle and tooth samples of 12 individuals aged 0.5 ± 0.4 years to 13 ± 1 years from the nineteenth century St. Peter’s burial ground in Blackburn were collected and processed to obtain bulk bone and incremental dentine collagen which was measured for δ13C and δ15N. Results: Averaged δ13C and δ15N of ossicles are lower when compared to every age group except after 3 years of age. Average offset between ossicles and dentine of different groups ranges from 0.4–0.9‰ for δ13C and from 0.3–0.9‰ for δ15N, with highest counterbalance at birth and after the first 5 months after birth. Conclusions: There appears to be a systematic offset between the dentine and ossicle data. It seems that the second phase of development does not influence the isotopic values of collagen significantly and the data we are obtaining from ossicles represents the in utero period.Research grant from The Society for the Study of Human Biology

Exploring the Trypanosoma brucei Hsp83 Potential as a Target for Structure Guided Drug Design

Human African trypanosomiasis is a neglected parasitic disease that is fatal if untreated. The current drugs available to eliminate the causative agent Trypanosoma brucei have multiple liabilities, including toxicity, increasing problems due to treatment failure and limited efficacy. There are two approaches to discover novel antimicrobial drugs--whole-cell screening and target-based discovery. In the latter case, there is a need to identify and validate novel drug targets in Trypanosoma parasites. The heat shock proteins (Hsp), while best known as cancer targets with a number of drug candidates in clinical development, are a family of emerging targets for infectious diseases. In this paper, we report the exploration of T. brucei Hsp83--a homolog of human Hsp90--as a drug target using multiple biophysical and biochemical techniques. Our approach included the characterization of the chemical sensitivity of the parasitic chaperone against a library of known Hsp90 inhibitors by means of differential scanning fluorimetry (DSF). Several compounds identified by this screening procedure were further studied using isothermal titration calorimetry (ITC) and X-ray crystallography, as well as tested in parasite growth inhibitions assays. These experiments led us to the identification of a benzamide derivative compound capable of interacting with TbHsp83 more strongly than with its human homologs and structural rationalization of this selectivity. The results highlight the opportunities created by subtle structural differences to develop new series of compounds to selectively target the Trypanosoma brucei chaperone and effectively kill the sleeping sickness parasite

Association between loop diuretic dose changes and outcomes in chronic heart failure: observations from the ESC-EORP Heart Failure Long-Term Registry

[Abstract] Aims. Guidelines recommend down-titration of loop diuretics (LD) once euvolaemia is achieved. In outpatients with heart failure (HF), we investigated LD dose changes in daily cardiology practice, agreement with guideline recommendations, predictors of successful LD down-titration and association between dose changes and outcomes. Methods and results. We included 8130 HF patients from the ESC-EORP Heart Failure Long-Term Registry. Among patients who had dose decreased, successful decrease was defined as the decrease not followed by death, HF hospitalization, New York Heart Association class deterioration, or subsequent increase in LD dose. Mean age was 66±13 years, 71% men, 62% HF with reduced ejection fraction, 19% HF with mid-range ejection fraction, 19% HF with preserved ejection fraction. Median [interquartile range (IQR)] LD dose was 40 (25–80) mg. LD dose was increased in 16%, decreased in 8.3% and unchanged in 76%. Median (IQR) follow-up was 372 (363–419) days. Diuretic dose increase (vs. no change) was associated with HF death [hazard ratio (HR) 1.53, 95% confidence interval (CI) 1.12–2.08; P = 0.008] and nominally with cardiovascular death (HR 1.25, 95% CI 0.96–1.63; P = 0.103). Decrease of diuretic dose (vs. no change) was associated with nominally lower HF (HR 0.59, 95% CI 0.33–1.07; P = 0.083) and cardiovascular mortality (HR 0.62 95% CI 0.38–1.00; P = 0.052). Among patients who had LD dose decreased, systolic blood pressure [odds ratio (OR) 1.11 per 10 mmHg increase, 95% CI 1.01–1.22; P = 0.032], and absence of (i) sleep apnoea (OR 0.24, 95% CI 0.09–0.69; P = 0.008), (ii) peripheral congestion (OR 0.48, 95% CI 0.29–0.80; P = 0.005), and (iii) moderate/severe mitral regurgitation (OR 0.57, 95% CI 0.37–0.87; P = 0.008) were independently associated with successful decrease. Conclusion. Diuretic dose was unchanged in 76% and decreased in 8.3% of outpatients with chronic HF. LD dose increase was associated with worse outcomes, while the LD dose decrease group showed a trend for better outcomes compared with the no-change group. Higher systolic blood pressure, and absence of (i) sleep apnoea, (ii) peripheral congestion, and (iii) moderate/severe mitral regurgitation were independently associated with successful dose decrease

Sex- and age-related differences in the management and outcomes of chronic heart failure: an analysis of patients from the ESC HFA EORP Heart Failure Long-Term Registry

Aims: This study aimed to assess age- and sex-related differences in management and 1-year risk for all-cause mortality and hospitalization in chronic heart failure (HF) patients. Methods and results: Of 16 354 patients included in the European Society of Cardiology Heart Failure Long-Term Registry, 9428 chronic HF patients were analysed [median age: 66 years; 28.5% women; mean left ventricular ejection fraction (LVEF) 37%]. Rates of use of guideline-directed medical therapy (GDMT) were high (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers and mineralocorticoid receptor antagonists: 85.7%, 88.7% and 58.8%, respectively). Crude GDMT utilization rates were lower in women than in men (all differences: P\ua0 64 0.001), and GDMT use became lower with ageing in both sexes, at baseline and at 1-year follow-up. Sex was not an independent predictor of GDMT prescription; however, age >75 years was a significant predictor of GDMT underutilization. Rates of all-cause mortality were lower in women than in men (7.1% vs. 8.7%; P\ua0=\ua00.015), as were rates of all-cause hospitalization (21.9% vs. 27.3%; P\ua075 years. Conclusions: There was a decline in GDMT use with advanced age in both sexes. Sex was not an independent predictor of GDMT or adverse outcomes. However, age >75 years independently predicted lower GDMT use and higher all-cause mortality in patients with LVEF 6445%