Changes in serum PSA after endoscopic enucleation of the prostate are predictive for the future diagnosis of prostate cancer.

PURPOSE: After Endoscopic Enucleation of the Prostate (EEP) for benign prostatic obstruction (BPO), men remain at risk for prostate cancer (PCa). Significant PSA changes occur after enucleation, which interfere with later screening for PCa. It remains unclear which patients need further diagnostic investigations for PCa after EEP. The goal of this study was to identify an independent predictor for PCa diagnosis after Holmium Laser Enucleation of the Prostate (HoLEP) in patients whose HoLEP resection specimen did not show PCa. METHODS: Data of 773 patients who underwent HoLEP for BPO between 2010 and 2018 in a referral center were analyzed. Exclusion criteria were PCa detection in the HoLEP specimen or absence of post-operative PSA values. Patients were divided in a PCa group and Control group depending on whether or not PCa was detected during follow-up after HoLEP. The predictive value for future diagnosis of PCa of different forms of PSA-change after HoLEP was analyzed by multivariate Cox regression and ROC analysis. RESULTS: Overall, 24 (4.2%) patients developed PCa after HoLEP. At 5 year follow-up, the PCa-free survival rate was 85%. First post-operative PSA was an independent predictor of PCa diagnosis after HoLEP (HR 1.106, 95% CI 1.074-1.139, p < 0.001, ROC AUC 0.903) with an optimal cut-off value of 1.73 ng/ml (sensitivity 83.3%, specificity 82.3%). CONCLUSIONS: For patients who underwent HoLEP for BPO, post-operative PSA after HoLEP is an independent predictor for future PCa diagnosis. When PSA is > 1.73 ng/ml within the first year after HoLEP, rigorous follow-up and diagnostic investigations for PCa are indicated.

Development and usability of a computer-tailored pedometer-based physical activity advice for breast cancer survivors.

This observational study aimed to adapt a computer-tailored step advice for the general population into a feasible advice for breast cancer survivors and to test its usability. First, several adaptations were made to the original design (adding cancer-related physical activity (PA) barriers and beliefs, and self-management strategies to improve survivors' personal control). Second, the adapted advice was evaluated in two phases: (1) a usability testing in healthy women (n = 3) and survivors (n = 6); and (2) a process evaluation during 3 weeks in breast cancer survivors (n = 8). Preliminary usability testing revealed no problems during logging-in; however, three survivors misinterpreted some questions. After refining the questionnaire and advice, survivors evaluated the advice as interesting, attractive to read, comprehensible and credible. Inactive survivors found the advice novel, but too long. The process evaluation indicated that the majority of the women (n = 5/8) reported increased steps. Monitoring step counts by using a pedometer was perceived as an important motivator to be more active. To conclude, this study provides initial support for the usability and acceptability of a computer-tailored pedometer-based PA advice for breast cancer survivors. After testing efficacy and effectiveness of this intervention, this tool can broaden the reach of PA promotion in breast cancer survivors.

EFFICACY OF FUNGICIDES AGAINST CALONECTRIA PAUCIRAMOSA IN POT AZALEA.

Calonectria (formerly Cylindrocladium) infection of pot azalea (Rhododendron simsii Planch) is an important disease problem in which usually one or two of the four plants per pot show progressing leaf and especially stem lesions, leading to mortality of the respective plant and rendering the pot unmarketable. This may occur in a later stage of the growing season, leading to significant commercial losses. The main objective of this study was to test a range of fungicides for their efficacy against this pathogen. To test the fungicides, a bioassay was first developed in which mycelium and conidiospores of the pathogen were produced on Potato Dextrose Agar, blended in water, and dilutions of the resulting suspension inoculated at the base of 11-week-old cuttings three weeks after they had been trimmed. Disease progression was monitored up to 7 weeks post inoculation and a disease index on a scale of 0 to 3 was established. In the actual efficacy trial, the following fungicides (with corresponding active ingredient(s)) were tested as preventive treatments: Topsin M 70 WG (thiophanate-methyl), Sporgon (prochloraz), Signum (boscalid+pyraclostrobin), Switch (cyprodinyl+fludioxonil), Flint 50WG (trifloxystrobin), Ortiva Top (azoxystrobin+difenoconazole) and Fungaflor (imazalil). Disease expression started after about 2 weeks, increased approximately 1 index level, and leveled off 5 weeks after inoculation. The best control was observed with Sporgon, Ortiva Top and Signum. Switch produced intermediate effects and insufficient control was observed with Topsin, Flint and Fungaflor. These results explain why specific standard fungicide treatments, such as those with Topsin, fail to control the disease, while they can be effective against a different Calonectria species such as C. pseudonaviculata, the cause of boxwood blight.

THE EFFECT OF COLD STORAGE OF POTTED AZALEA ON BROAD MITE INFECTION.

In potted azalea (Rhododendron simsii hybrids) the broad mite Polyphagotarsonemus latus (Banks) is considered a severe pest with an important economic impact. Although chemical control is available, permitted acaricides are limited and have a restricted number of applications. Therefore, growers have a keen interest in alternative control measures. Recently, research on the behaviour and population dynamics of P. latus on azalea leaf disks stored at different temperatures indicated that survival and reproductive capacity of broad mite is reduced drastically when temperature drops below 7°C. In Flanders, storage of azalea plants at 3°C is common practice to pause flower development (in function of the date that plants have to be ready for sale) before forcing them to flower in a heated greenhouse. Hence, an experiment was set-up to verify and quantify the effect of cold storage of azalea on broad mite infection. Azalea plants were infected with P. latus and stored at 3°C for 2, 3 or 4 weeks. Then, plants were transferred to a heated greenhouse for 2 weeks to check whether surviving female broad mites were still able to reproduce. The number of P. latus on azalea was assessed before cold treatment, immediately after treatment, and 2 weeks after transfer to the heated greenhouse. Results confirmed that cold storage can play a role in broad mite control as the P. latus population was significantly reduced (up to 90%) immediately after treatment. A further decrease in the number of P. latus during storage in the heated greenhouse indicated that cold treatment during 4 weeks had also an effect on the reproduction capacity of P. latus. We conclude that cold storage of azalea plants (at least 4 weeks at maximum 3°C) should be considered as an additional and alternative control method for P. latus at the end of the azalea production cycle.

EDART, a discrete algebraic reconstructing technique for experimental data obtained with high resolution computed tomography.

A novel reconstruction method is presented to improve the image quality of three dimensional (3D) datasets for samples consisting of only one material and surrounding air, obtained with high resolution X-ray Computed Tomography (µCT). It combines discrete tomography with iterative reconstruction algorithms, it is applicable for routine µCT applications and is referred to as the Experimental Discrete Algebraic Reconstruction Technique (EDART). A fast and intuitive method to estimate the attenuation coefficient and segmentation threshold, in case these are unknown, is included. Experimental results illustrate that EDART allows the improvement of the reconstruction quality as compared to standard iterative reconstruction when few projections are available, without significantly increasing the reconstruction time.

CLIMATE CONDITIONS AFFECTING THE WITHIN-PLANT SPREAD OF BROAD MITES ON AZALEA.

The broad mite Polyphagotarsonemus latus (Banks) is considered a major pest in potted azalea, Flanders' flagship ornamental crop of Rhododendron simsii hybrids. In addition to severe economic damage, the broad mite is dreaded for its increasing resistance to acaricides. Due to restrictions in the use of broad spectrum acaricides, Belgian azalea growers are left with only three compounds, belonging to two mode of action groups and restricted in their number of applications, for broad mite control: abamectin, milbemectin and pyrethrin. Although P. latus can be controlled with predatory mites, the high cost of this system makes it (not yet) feasible for integration into standard azalea pest management systems. Hence, a maximum efficacy of treatments with available compounds is essential. Because abamectin, milbemectin and pyrethrin are contact acaricides with limited trans laminar flow, only broad mites located on shoot tips of azalea plants will be controlled after spraying. Consequently, the efficacy of chemical treatments is influenced by the location and spread of P. latus on the plant. Unfortunately, little is known on broad mites' within-plant spread or how it is affected by climatic conditions like temperature and relative humidity. Therefore, experiments were set up to verify whether climate conditions have an effect on the location and migration of broad mites on azalea. Broad mite infected azalea plants were placed in standard growth chambers under different temperature (T:2.5-25°C) and relative humidity (RH:55-80%) treatments. Within-plant spread was determined by counting mites on the shoot tips and inner leaves of azalea plants. Results indicate that temperature and relative humidity have no significant effect on the within-plant spread of P. latus. To formulate recommendations for optimal spray conditions to maximize the efficacy of broad mite control with acaricides, further experiments on the effect of light intensity and rain are scheduled.

Cold storage to overcome dormancy affects the carbon balance of azalea.

Flower bud dormancy in azalea (Rhododendron simsii) is broken by artificial cold treatment and this will have its consequences on carbon reserves and photosynthesis. The effect of cold storage at 7 °C on carbohydrate and starch content in leaves and flower buds of an early ('Nordlicht') and semi-early ('M. Marie) flowering cultivar was quantified. Carbon loss due to respiration was lowest for 'M. Marie'. Photosynthetic measurements on 'Nordlicht' showed that photosynthesis 3 days after cold treatment (plants ready to flower) was improved compared to before cold treatment (plants with dormant flower buds).

In silico Mechanics of Stem Cells Intramyocardially Transplanted with a Biomaterial Injectate for Treatment of Myocardial Infarction.

PURPOSE: Biomaterial and stem cell delivery are promising approaches to treating myocardial infarction. However, the mechanical and biochemical mechanisms underlying the therapeutic benefits require further clarification. This study aimed to assess the deformation of stem cells injected with the biomaterial into the infarcted heart. METHODS: A microstructural finite element model of a mid-wall infarcted myocardial region was developed from ex vivo microcomputed tomography data of a rat heart with left ventricular infarct and intramyocardial biomaterial injectate. Nine cells were numerically seeded in the injectate of the microstructural model. The microstructural and a previously developed biventricular finite element model of the same rat heart were used to quantify the deformation of the cells during a cardiac cycle for a biomaterial elastic modulus (Einj) ranging between 4.1 and 405,900 kPa. RESULTS: The transplanted cells' deformation was largest for Einj = 7.4 kPa, matching that of the cells, and decreased for an increase and decrease in Einj. The cell deformation was more sensitive to Einj changes for softer (Einj ≤ 738 kPa) than stiffer biomaterials. CONCLUSIONS: Combining the microstructural and biventricular finite element models enables quantifying micromechanics of transplanted cells in the heart. The approach offers a broader scope for in silico investigations of biomaterial and cell therapies for myocardial infarction and other cardiac pathologies.

An exploratory study of contrast agents for soft tissue visualization by means of high resolution X-ray computed tomography imaging.

High resolution X-ray computed tomography (CT), or microCT, is a promising and already widely used technique in various scientific fields. Also for histological purposes it has great potential. Although microCT has proven to be a valuable technique for the imaging of bone structures, the visualization of soft tissue structures is still an important challenge due to their low inherent X-ray contrast. One way to achieve contrast enhancement is to make use of contrast agents. However, contrary to light and electron microscopy, knowledge about contrast agents and staining procedures is limited for X-ray CT. The purpose of this paper is to identify useful X-ray contrast agents for soft tissue visualization, which can be applied in a simple way and are also suited for samples larger than (1 cm)(3) . And 28 chemical substances have been investigated. All chemicals were applied in the form of concentrated aqueous solutions in which the samples were immersed. First, strips of green Bacon were stained to evaluate contrast enhancement between muscle and adipose tissue. Furthermore it was also tested whether the contrast agents remained fixed in the tissue after staining by re-immersing them in water. Based on the results, 12 contrast agents were selected for further testing on postmortem mice hind legs, containing a variety of different tissues, including muscle, fat, bone, cartilage and tendons. It was evaluated whether the contrast agents allowed a clearer distinction between the different soft tissue structures present. Finally also penetration depth was measured. And 26 chemicals resulted in contrast enhancement between muscle and adipose tissue in the Bacon strips. Mercury(II)chloride (HgCl2 ), phosphotungstic acid (PTA), phosphomolybdic acid (PMA) and ammonium orthomolybdate ((NH4 )2 MoO4 ) remained fixed after re-immersion in water. The penetration tests showed that potassium iodide (KI) and sodium tungstate can be most efficiently used for large samples of the order of several tens of cm(3) . PMA, PTA, HgCl2 and also to a lesser extent Na2 WO4 and (NH4 )2 MoO4 allowed a clearer distinction between the different soft tissue structures present.

Effect of biomaterial stiffness on cardiac mechanics in a biventricular infarcted rat heart model with microstructural representation of in situ intramyocardial injectate.

Intramyocardial delivery of biomaterials is a promising concept for treating myocardial infarction. The delivered biomaterial provides mechanical support and attenuates wall thinning and elevated wall stress in the infarct region. This study aimed at developing a biventricular finite element model of an infarcted rat heart with a microstructural representation of an in situ biomaterial injectate, and a parametric investigation of the effect of the injectate stiffness on the cardiac mechanics. A three-dimensional subject-specific biventricular finite element model of a rat heart with left ventricular infarct and microstructurally dispersed biomaterial delivered 1 week after infarct induction was developed from ex vivo microcomputed tomography data. The volumetric mesh density varied between 303 mm-3 in the myocardium and 3852 mm-3 in the injectate region due to the microstructural intramyocardial dispersion. Parametric simulations were conducted with the injectate's elastic modulus varying from 4.1 to 405,900 kPa, and myocardial and injectate strains were recorded. With increasing injectate stiffness, the end-diastolic median myocardial fibre and cross-fibre strain decreased in magnitude from 3.6% to 1.1% and from -6.0% to -2.9%, respectively. At end-systole, the myocardial fibre and cross-fibre strain decreased in magnitude from -20.4% to -11.8% and from 6.5% to 4.6%, respectively. In the injectate, the maximum and minimum principal strains decreased in magnitude from 5.4% to 0.001% and from -5.4% to -0.001%, respectively, at end-diastole and from 38.5% to 0.06% and from -39.0% to -0.06%, respectively, at end-systole. With the microstructural injectate geometry, the developed subject-specific cardiac finite element model offers potential for extension to cellular injectates and in silico studies of mechanotransduction and therapeutic signalling in the infarcted heart with an infarct animal model extensively used in preclinical research.

Accurate spin-orbit and spin-other-orbit contributions to the g-tensor for transition metal containing systems.

In this paper an overview is presented of several approximations within Density Functional Theory (DFT) to calculate g-tensors in transition metal containing systems and a new accurate description of the spin-other-orbit contribution for high spin systems is suggested. Various implementations in a broad variety of software packages (ORCA, ADF, Gaussian, CP2K, GIPAW and BAND) are critically assessed on various aspects including (i) non-relativistic versus relativistic Hamiltonians, (ii) spin-orbit coupling contributions and (iii) the gauge. Particular attention is given to the level of accuracy that can be achieved for codes that allow g-tensor calculations under periodic boundary conditions, as these are ideally suited to efficiently describe extended condensed-phase systems containing transition metals. In periodic codes like CP2K and GIPAW, the g-tensor calculation schemes currently suffer from an incorrect treatment of the exchange spin-orbit interaction and a deficient description of the spin-other-orbit term. In this paper a protocol is proposed, making the predictions of the exchange part to the g-tensor shift more plausible. Focus is also put on the influence of the spin-other-orbit interaction which becomes of higher importance for high-spin systems. In a revisited derivation of the various terms arising from the two-electron spin-orbit and spin-other-orbit interaction (SOO), new insight has been obtained revealing amongst other issues new terms for the SOO contribution. The periodic CP2K code has been adapted in view of this new development. One of the objectives of this study is indeed a serious enhancement of the performance of periodic codes in predicting g-tensors in transition metal containing systems at the same level of accuracy as the most advanced but time consuming spin-orbit mean-field approach. The methods are first applied on rhodium carbide but afterwards extended to a broad test set of molecules containing transition metals from the fourth, fifth and sixth row of the periodic table. The set contains doublets as well as high-spin molecules.

Physical activity levels and supportive care needs for physical activity among breast cancer survivors with different psychosocial profiles: a cluster-analytical approach.

The transition from breast cancer patient to survivor is associated with many treatment-related and psychosocial factors, which can influence health behaviour and associated needs. First, this study aimed to identify clusters of treatment-related and psychosocial factors among breast cancer survivors. Second, clusters' physical activity levels and care needs for physical activity were evaluated. Breast cancer survivors (n= 440; 52 ± 8 years) (3 weeks to 6 months post treatment) completed self-reports on physical and psychological symptoms; illness representations; social support and coping; physical activity and care needs for physical activity. Analyses identified four clusters: (1) a low distress-active approach group; (2) a low distress-resigned approach group; (3) a high distress-active approach group; and (4) a high distress-emotional approach group. Physical activity levels were higher in the low distress groups than in the high distress-emotional approach group. However, women with low distress and an active approach reported equal care needs for physical activity than women with high distress and an emotional approach. These findings suggest that care needs for physical activity are unrelated to distress and actual physical activity levels. The results emphasise the importance of screening for needs and provide a framework supporting the referral of breast cancer survivors to tailored interventions.

Contribution of VANGL2 mutations to isolated neural tube defects.

Vangl2 was identified as the gene defective in the Looptail (Lp) mouse model for neural tube defects (NTDs). This gene forms part of the planar cell polarity (PCP) pathway, also called the non-canonical Frizzled/Dishevelled pathway, which mediates the morphogenetic process of convergent extension essential for proper gastrulation and neural tube formation in vertebrates. Genetic defects in PCP signaling have strongly been associated with NTDs in mouse models. To assess the role of VANGL2 in the complex etiology of NTDs in humans, we resequenced this gene in a large multi-ethnic cohort of 673 familial and sporadic NTD patients, including 453 open spina bifida and 202 closed spinal NTD cases. Six novel rare missense mutations were identified in seven patients, five of which were affected with closed spinal NTDs. This suggests that VANGL2 mutations may predispose to NTDs in approximately 2.5% of closed spinal NTDs (5 in 202), at a frequency that is significantly different from that of 0.4% (2 in 453) detected in open spina bifida patients (p = 0.027). Our findings strongly implicate VANGL2 in the genetic causation of spinal NTDs in a subset of patients and provide additional evidence for a pathogenic role of PCP signaling in these malformations.

Assessment of periodic and cluster-in-vacuo models for first principles calculation of EPR parameters of paramagnetic defects in crystals: Rh2+ defects in NaCl as case study.

In order to find a reliable and efficient calculation scheme for electron paramagnetic resonance (EPR) spectroscopic parameters for transition metal complexes in ionic solids from first principles, periodic and finite cluster-in-vacuo density functional theory (DFT) simulations are performed for g tensors, ligand hyperfine tensors (A), and quadrupole tensors (Q) for Rh(2+)-related centers in NaCl. EPR experiments on NaCl:Rh single crystals identified three Rh(2+) monomer centers, only differing in the number of charge compensating vacancies in their local environment, and one dimer center. Periodic and cluster calculations, both based on periodically optimized structures, are able to reproduce experimentally observed trends in the ligand A and Q tensors and render very satisfactory numerical agreement with experiment. Taking also computation time into account as a criterion, a full periodic approach emerges as most appropriate for these parameters.The g tensor calculations, on the other hand, prove to be insufficiently accurate for model assessment. The calculations also reveal parameters of the complexes which are not directly accessible through experiments, in particular related to their geometry.

Molecular environment and temperature dependence of hyperfine interactions in sugar crystal radicals from first principles.

The effect of the molecular environment and the temperature dependence of hyperfine parameters in first principles calculations in alpha-d-glucose and beta-d-fructose crystal radicals have been investigated. More specifically, we show how static (0 K) cluster in vacuo hyperfine calculations, commonly used today, deviate from more advanced molecular dynamics calculations at the experimental temperature using periodic boundary conditions. From the latter approach, more useful information can be extracted, allowing us to ascertain the validity of proposed molecular models.

Identification and conformational study of stable radiation-induced defects in sucrose single crystals using density functional theory calculations of electron magnetic resonance parameters.

One of the major stable radiation-induced radicals in sucrose single crystals (radical T2) has been identified by means of density functional theory (DFT) calculations of electron magnetic resonance parameters. The radical is formed by a net glycosidic bond cleavage, giving rise to a glucose-centered radical with the major part of the spin density residing at the C 1 carbon atom. A concerted formation of a carbonyl group at the C 2 carbon accounts for the relatively small spin density at C 1 and the enhanced g factor anisotropy of the radical, both well-known properties of this radical from several previous experimental investigations. The experimentally determined and DFT calculated proton hyperfine coupling tensors agree very well on all accounts. The influence of the exact geometrical configuration of the radical and its environment on the tensors is explored in an attempt to explain the occurrence and characteristics of radical T3, another major species that is most likely another conformation of T2. No definitive conclusions with regard to the actual structure of T3 could be arrived at from this study. However, the results indicate that, most likely, T3 is identical in chemical structure to T2 and that changes in the orientation of neighboring hydroxy groups or changes in the configuration of the neighboring fructose ring can probably not account for the type and size of the discrepancies between T2 and T3.

Radiation-induced defects in sucrose single crystals, revisited: a combined electron magnetic resonance and density functional theory study.

The results are presented of an electron magnetic resonance analysis at 110 K of radiation-induced defects in sucrose single crystals X-irradiated at room temperature, yielding a total of nine (1)H hyperfine coupling tensors assigned to three different radical species. Comparisons are made with results previously reported in the literature. By means of electron paramagnetic resonance and electron nuclear double resonance temperature variation scans, most of the discrepancies between the present 110 K study and a previous 295 K study by Sagstuen and co-workers are shown to originate from the temperature dependence of proton relaxation times and hyperfine coupling constants. Finally, radical models previously suggested in the literature are convincingly refuted by means of quantum chemical density functional theory calculations.

Antibacterial activity of human neutrophil defensins in experimental infections in mice is accompanied by increased leukocyte accumulation.

Neutrophil defensins (or human neutrophil peptides-HNP) are major constituents of the azurophilic granules of human neutrophils and have been shown to display broad-spectrum antimicrobial activity. Other activities of these defensins, which are released from stimulated neutrophils, include cytotoxic, stimulatory, and chemotactic activities toward a variety of target cells. We studied the potential use of HNP-1 for antibacterial therapy of experimental bacterial infections in mice. In experimental peritoneal Klebsiella pneumoniae infections in mice, HNP-1 injection was shown to markedly reduce bacterial numbers in the infected peritoneal cavity 24 h after infection. This antibacterial effect was found to be associated with an increased influx of macrophages, granulocytes, and lymphocytes into the peritoneal cavity. These leukocytes appeared to be a requirement for the antibacterial effect, since in leukocytopenic mice administration of HNP-1 did not display antibacterial activity. HNP-1 treatment also reduced bacterial numbers in experimental K. pneumoniae or Staphylococcus aureus thigh muscle infections. In this model, radiolabeled HNP-1 was found to accumulate at the site of infection, whereas most of the injected HNP-1 was rapidly removed from the circulation via renal excretion. These results demonstrate that neutrophil defensins display marked in vivo antibacterial activity in experimental infections in mice and that this activity appears to be mediated, at least in part, by local leukocyte accumulation.

X- (X = O, S) ions in alkali halide lattices through density functional calculations. 1. Substitutional defect models.

Monoatomic X- (X = O, S) chalcogen centers in MZ (M = Na, K, Rb and Z = Cl, Br, I) alkali halide lattices are investigated within the framework of density functional theory with the principal aim to establish defect models. In electron paramagnetic resonance (EPR) experiments, X- defects with tetragonal, orthorhombic, and monoclinic g-tensor symmetry have been observed. In this paper, models in which X- replaces a single halide ion, with a next nearest neighbor and a nearest neighbor halide vacancy, are validated for the X- centers with tetragonal and orthorhombic symmetry, respectively. As such defect models are extended, the ability to reproduce experimental data is a stringent test for various computational approaches. Cluster in vacuo and embedded cluster schemes are used to calculate energy and EPR parameters for the two vacancy configurations. The final assignment of a defect structure is based on the qualitative and quantitative reproduction of experimental g and (super)hyperfine tensors.

X- (X = O, S, Se) Ions in alkali halide lattices through density functional calculations. 2. Interstitial defect models.

Density functional theory techniques are used to investigate the defect structure of X- (X = O, S, Se) ions in MZ (M = Na, K, Rb and Z = Cl, Br) alkali halides which exhibit monoclinic-I g-tensor symmetry, using cluster in vacuo, embedded cluster, and periodic embedding schemes. Although a perturbed interstitial defect model was suggested from electron paramagnetic resonance experiments (EPR), the nature of the perturbation is still unknown. An appropriate defect model is developed theoretically by comparing structural and energetical properties of various defect configurations. Further validation is achieved by cross referencing experimental and computed EPR data. On the basis of the computational results, the following defect model is proposed: the X- ion is located interstitially with a charge compensating halide vacancy in its first coordination shell.