Long-term platinum retention after treatment with cisplatin and oxaliplatin

Background  

The aim of this study was to evaluate long-term platinum retention in patients treated with cisplatin and oxaliplatin.     

Pentacycloundecane lactam vs lactone norstatine type protease HIV inhibitors: binding energy calculations and DFT study

Background

Novel pentacycloundecane (PCU)-lactone-CO-EAIS peptide inhibitors were designed, synthesized, and evaluated against wild-type C-South African (C-SA) HIV-1 protease. Three compounds are reported herein, two of which displayed IC₅₀ values of less than 1.00 μM. A comparative MM-PB(GB)SA binding free energy of solvation values of PCU-lactam and lactone models and their enantiomers as well as the PCU-lactam-NH-EAIS and lactone-CO-EAIS peptide inhibitors and their corresponding diastereomers complexed with South African HIV protease (C-SA) was performed. This will enable us to rationalize the considerable difference between inhibitory concentration (IC₅₀) of PCU-lactam-NH-EAIS and PCU-lactone-CO-EAIS peptides.

Results

The PCU-lactam model exhibited more negative calculated binding free energies of solvation than the PCU-lactone model. The same trend was observed for the PCU-peptide inhibitors, which correspond to the experimental activities for the PCU-lactam-NH-EAIS peptide (IC₅₀ = 0.076 μM) and the PCU-lactone-CO-EAIS peptide inhibitors (IC₅₀ = 0.850 μM). Furthermore, a density functional theory (DFT) study on the natural atomic charges of the nitrogen and oxygen atoms of the three PCU-lactam, PCU-lactim and PCU-lactone models were performed using natural bond orbital (NBO) analysis. Electrostatic potential maps were also used to visualize the electron density around electron-rich regions. The asymmetry parameter (η) and quadrupole coupling constant (χ) values of the nitrogen and oxygen nuclei of the model compounds were calculated at the same level of theory. Electronic molecular properties including polarizability and electric dipole moments were also calculated and compared. The Gibbs theoretical free solvation energies of solvation (∆G_solv) were also considered.

Conclusions

A general trend is observed that the lactam species appears to have a larger negative charge distribution around the heteroatoms, larger quadrupole constant, dipole moment and better solvation energy, in comparison to the PCU-lactone model. It can be argued that these characteristics will ensure better eletronic interaction between the lactam and the receptor, corresponding to the observed HIV protease activities in terms of experimental IC₅₀ data.

Electronic supplementary material

The online version of this article (doi:10.1186/s12929-015-0115-5) contains supplementary material, which is available to authorized users.     

Controls of Evapotranspiration and CO2 Fluxes from Scots Pine by Surface Conductance and Abiotic Factors

Evapotranspiration (E) and CO₂ flux (F_c) in the growing season of an unusual dry year were measured continuously over a Scots pine forest in eastern Finland, by eddy covariance techniques. The aims were to gain an understanding of their biological and environmental control processes. As a result, there were obvious diurnal and seasonal changes in E, F_c, surface conductance (g_c), and decoupling coefficient (Ω), showing similar trends to those in radiation (PAR) and vapour pressure deficit (δ). The maximum mean daily values (24-h average) for E, F_c, g_c, and Ω were 1.78 mmol m⁻² s⁻¹, −11.18 µmol m⁻² s⁻¹, 6.27 mm s⁻¹, and 0.31, respectively, with seasonal averages of 0.71 mmol m⁻² s⁻¹, −4.61 µmol m⁻² s⁻¹, 3.3 mm s⁻¹, and 0.16. E and F_c were controlled by combined biological and environmental variables. There was curvilinear dependence of E on g_c and F_c on g_c. Among the environmental variables, PAR was the most important factor having a positive linear relationship to E and curvilinear relationship to F_c, while vapour pressure deficit was the most important environmental factor affecting g_c. Water use efficiency was slightly higher in the dry season, with mean monthly values ranging from 6.67 to 7.48 μmol CO₂ (mmol H₂O)⁻¹ and a seasonal average of 7.06 μmol CO₂ (μmol H₂O)⁻¹. Low Ω and its close positive relationship with g_c indicate that evapotranspiration was sensitive to surface conductance. Mid summer drought reduced surface conductance and decoupling coefficient, suggesting a more biotic control of evapotranspiration and a physiological acclimation to dry air. Surface conductance remained low and constant under dry condition, supporting that a constant value of surface constant can be used for modelling transpiration under drought condition.     

Comparison of the effects of symmetric and asymmetric temperature elevation and CO2 enrichment on yield and evapotranspiration of winter wheat (Triticum aestivum L.)

Under the changing climate, asymmetric warming pattern would be more likely during day and night time, instead of symmetric one. Concurrently, the growth responses and water use of plants may be different compared with those estimated based on symmetric warming. In this work, it was compared with the effects of symmetric (ETs) and asymmetric (ETa) elevation of temperature alone, and in interaction with elevated carbon dioxide concentration (EC), on the grain yield (GY) and evapotranspiration in winter wheat (Triticum aestivum L.) based on pot experiment in the North China Plain (NCP). The experiment was carried out in six enclosed‐top chambers with following climate treatments: (1) ambient temperature and ambient CO₂ (CON), (2) ambient temperature and elevated CO₂ (EC), (3) elevated temperature and ambient CO₂ (ETs; ETa), and (4) elevated temperature and elevated CO₂ (ECETs, ECETa). In symmetric warming, temperature was increased by 3°C and in asymmetric one by 3.5°C during night and 2.5°C during daytime, respectively. As a result, GY was in ETa and ETs 15.6 (P < 0.05) and 10.3% (P < 0.05) lower than that in CON. In ECETs and ECETa treatments, GY was 14.9 (P < 0.05) and 9.1% (P < 0.05) higher than that in CON. Opposite to GY, evapotranspiration was 7.8 (P < 0.05) and 17.9% (P < 0.05) higher in ETa and ETs treatments and 7.2 (P < 0.05) and 2.1% (P > 0.05) lower in ECETs and ECETa treatments compared with CON. Thus, GY of wheat could be expected to increase under the changing climate with concurrent elevation of CO₂ and temperature as a result of increased WUE under the elevated CO₂. However, the gain would be lower under ETa than that estimated based on ETs due to higher evapotranspiration.     

Net climate impacts of forest biomass production and utilization in managed boreal forests

In this work, we studied the potentials offered by managed boreal forests and forestry to mitigate the climate change using forest‐based materials and energy in substituting fossil‐based materials (concrete and plastic) and energy (coal and oil). For this purpose, we calculated the net climate impacts (radiative forcing) of forest biomass production and utilization in the managed Finnish boreal forests (60°–70°N) over a 90‐year period based on integrated use forest ecosystem model simulations (on carbon sequestration and biomass production of forests) and life‐cycle assessment (LCA) tool. When studying the effects of management on the radiative forcing in a system integrating the carbon sink/sources dynamics in both biosystem and technosystem, the current forest management (baseline management) was used a reference management. Our results showed that the use of forest‐based materials and energy in substituting fossil‐based materials and energy would provide an effective option for mitigating climate change. The negative climate impacts could be further decreased by maintaining forest stocking higher over the rotation compared to the baseline management and by harvesting stumps and coarse roots in addition to logging residues in the final felling. However, the climate impacts varied substantially over time depending on the prevailing forest structure and biomass assortment (timber, energy biomass) used in substitution.     

Accuracy and Feasibility of Point-Of-Care White Blood Cell Count and C-Reactive Protein Measurements at the Pediatric Emergency Department

Background

Several point-of-care (POC) tests are available for evaluation of febrile patients, but the data about their performance in acute care setting is sparse. We investigated the analytical accuracy and feasibility of POC tests for white blood cell (WBC) count and C-reactive protein (CRP) at the pediatric emergency department (ED).

Methods

In the first part of the study, HemoCue WBC and Afinion AS100 CRP POC analyzers were compared with laboratory’s routine WBC (Sysmex XE-2100) and CRP (Modular P) analyzers in the hospital central laboratory in 77 and 48 clinical blood samples, respectively. The POC tests were then adopted in use at the pediatric ED. In the second part of the study, we compared WBC and CRP levels measured by POC and routine methods during 171 ED patient visits by 168 febrile children and adolescents. Attending physicians performed POC tests in capillary fingerprick samples.

Results

In parallel measurements in the laboratory both WBC and CRP POC analyzers showed good agreement with the reference methods. In febrile children at the emergency department (median age 2.4 years), physician performed POC determinations in capillary blood gave comparable results with those in venous blood analyzed in the laboratory. The mean difference between POC and reference test result was 1.1 E9/L (95% limits of agreement from -6.5 to 8.8 E9/L) for WBC and -1.2 mg/L (95% limits of agreement from -29.6 to 27.2 mg/L) for CRP.

Conclusions

POC tests are feasible and relatively accurate methods to assess CRP level and WBC count among febrile children at the ED.     

<Emphasis Type="Italic">TRAF1/C5</Emphasis>polymorphism is not associated with increased mortality in rheumatoid arthritis: two large longitudinal studies

Introduction  

Recently an association between a genetic variation in TRAF1/C5 and mortality from sepsis or cancer was found in rheumatoid arthritis (RA). The most prevalent cause of death, cardiovascular disease, may have been missed in that study, since patients were enrolled at an advanced disease stage. Therefore, we used an inception cohort of RA patients to investigate the association between TRAF1/C5 and cardiovascular mortality, and replicate the findings on all-cause mortality. As TRAF1/C5 associated mortality may not be restricted to RA, we also studied a large cohort of non-RA patients.     

Isolation of toxigenic Nocardiopsis strains from indoor environments and description of two new Nocardiopsis Species, N. exhalans sp. nov. and N. umidischolae sp. nov

Nocardiopsis strains were isolated from water-damaged indoor environments. Two strains (N. alba subsp. alba 704a and a strain representing a novel species, ES10.1) as well as strains of N. prasina, N. lucentensis, and N. tropica produced methanol-soluble toxins that paralyzed the motility of boar spermatozoa at <30 microg of crude extract (dry weight) x ml(-1). N. prasina, N. lucentensis, N. tropica, and strain ES10.1 caused cessation of motility by dissipating the mitochondrial membrane potential, Deltapsi, of the boar spermatozoa. Indoor strain 704a produced a substance that destroyed cell membrane barrier function and depleted the sperm cells of ATP. Indoor strain 64/93 was antagonistic towards Corynebacterium renale. Two indoor Nocardiopsis strains were xerotolerant, and all five utilized a wide range of substrates. This combined with the production of toxic substances suggests good survival and potential hazard to human health in water-damaged indoor environments. Two new species, Nocardiopsis exhalans sp. nov. (ES10.1T) and Nocardiopsis umidischolae sp. nov. (66/93T), are proposed based on morphology, chemotaxonomic and physiological characters, phylogenetic analysis, and DNA-DNA reassociations.     

Modelling the distribution of diameter growth along the stem in Scots pine

This paper presents an empirical model for the distribution of diameter growth along the stem in Scots pine (Pinus sylvestris L.) and for the consequent stem form over time. First, the distribution of annual mass growth in the stem is determined as a function of the total annual growth in stem mass, current stem mass and the distribution of the latter along the stem. Second, the distribution of diameter growth is obtained by converting the fraction of annual growth in the stem mass at a given height in the stem into the thickness of the annual ring at the same height. Application of the model to Scots pine data sets including both young and mature trees not used in parameter estimation showed that the model was capable of reconstructing the distribution of diameter growth from the stem butt to the apex and from the pith to the stem surface at any height in the stem in both young and mature trees. The resulting empirical model was also linked to a physiological, process-based model in order to study its performance in a simulated stand. Simulations representing trees grown in unthinned and thinned Scots pine stands with trees of different status (from dominant to suppressed) showed that the response in tree growth to thinning in terms of the distribution of diameter growth along the stem was quite realistic relative to measured data.