Effectiveness, safety and quality-of-life effects of guselkumab and ustekinumab in patients with psoriasis: Week 104 results from the non-interventional, prospective, German multicentre PERSIST study.

BACKGROUND: PERSIST was a prospective, non-interventional, real-world study of guselkumab and ustekinumab in adult patients with moderate-to-severe plaque psoriasis in Germany. OBJECTIVES: To examine effectiveness, safety and quality-of-life (QoL) outcomes to Week (W) 104 of treatment with guselkumab and ustekinumab in patients with moderate-to-severe plaque psoriasis. METHODS: Patients (≥18 years of age) received guselkumab or ustekinumab as per routine clinical practice. Outcomes to W104 were examined separately in guselkumab and ustekinumab recipients. An ad hoc exploratory analysis of outcomes with guselkumab versus ustekinumab was also performed following propensity score matching. RESULTS: Overall, 302 and 313 patients received guselkumab and ustekinumab, respectively. Patients in both cohorts experienced improvements in disease activity and QoL that were maintained to W104, with 64.7% and 63.6% of guselkumab- and 54.6% and 64.4% of ustekinumab-treated patients achieving a Psoriasis Area and Severity Index (PASI) 90 response and a Dermatology Life Quality Index (DLQI) 0/1 score, respectively. Propensity score matching yielded well-balanced baseline characteristics except for prior biologic use, which was higher in guselkumab versus ustekinumab recipients (51.7% vs. 32.0%). Achievement of PASI ≤1 at W104 was more common in guselkumab versus ustekinumab recipients (58.7% vs. 49.7%). The W104 PASI90 response rate was 65.6% with guselkumab and 56.0% with ustekinumab; corresponding rates for PASI100 were 44.3% and 28.5%. In guselkumab recipients, response rates were higher in biologic-naïve versus biologic-experienced patients (PASI90, 77.1% vs. 53.4%; PASI100, 55.0% vs. 33.0%). A high level of response for QoL outcomes was observed for both treatments. CONCLUSIONS: Ustekinumab and guselkumab led to improvements in physician-assessed and patient-reported outcomes that were sustained for up to 2 years, with no new safety signals identified. Following propensity score matching, greater improvements in PASI outcomes were observed with guselkumab versus ustekinumab. Improvements with guselkumab were highest in biologic-naïve patients, highlighting the value of early treatment.

GABA (γ-Aminobutyric Acid) Uptake Via the GABA Permease GabP Represses Virulence Gene Expression in Pseudomonas syringae pv. tomato DC3000.

The nonprotein amino acid γ-aminobutyric acid (GABA) is the most abundant amino acid in the tomato (Solanum lycopersicum) leaf apoplast and is synthesized by Arabidopsis thaliana in response to infection by the bacterial pathogen Pseudomonas syringae pv. tomato DC3000 (hereafter called DC3000). High levels of exogenous GABA have previously been shown to repress the expression of the type III secretion system (T3SS) in DC3000, resulting in reduced elicitation of the hypersensitive response (HR) in the nonhost plant tobacco (Nicotiana tabacum). This study demonstrates that the GABA permease GabP provides the primary mechanism for GABA uptake by DC3000 and that the gabP deletion mutant ΔgabP is insensitive to GABA-mediated repression of T3SS expression. ΔgabP displayed an enhanced ability to elicit the HR in young tobacco leaves and in tobacco plants engineered to produce increased levels of GABA, which supports the hypothesis that GABA uptake via GabP acts to regulate T3SS expression in planta. The observation that P. syringae can be rendered insensitive to GABA through loss of gabP but that gabP is retained by this bacterium suggests that GabP is important for DC3000 in a natural setting, either for nutrition or as a mechanism for regulating gene expression. [Formula: see text] Copyright © 2016 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .

[Body contouring]. / Körperkonturierung.

In our contemporary postmodern society, a modified perception of the human body is accompanied by an increasing demand for body shaping procedures. The treatment needs to be effective but it is just as important that they are safe and can be easily integrated into the daily working and routine schedule. While the options for minimally invasive volume addition are largely limited to injectable implants based on hyaluronic acid or autologous fat, a multitude of options are available for volume reduction. Before deciding on the method of choice, the following needs to be considered: which indications need to be treated, the extent of the reduction in volume and how much pain and possible undesired reactions the patient is prepared to accept.

Tracheostomy, ventilation and anterior cervical surgery: Timing and Complications.

BACKGROUND: Cervical spine injured patients often require prolonged ventilatory support due to intercostal paralysis and recurrent chest infections. This may necessitate tracheotomy. Concern exists around increased complications when anterior cervical spine surgery and tracheotomies are performed. OBJECTIVE: The primary aim of this study was to evaluate the effect of tracheostomy in anterior cervical surgery patients in term of complications. In addition, the aetiology of trauma and incidence of anterior surgery and ventilation in this patient group was assessed. METHOD: Patients undergoing anterior cervical surgery and requiring ventilation were identified from the unit's prospectively maintained database. These patients were further sub-divided into whether they had a tracheotomy or not. The aetiology of injury and incidence of complications were noted both from the database and a case note review. RESULTS: Of the 1829 admissions over an 8.5 year period, 444 underwent anterior cervical surgery. Of the 112 that required ventilation, 72 underwent tracheotomy. Motor vehicle accidents, followed by falls, were the most frequent cause of injury. There was a bimodal incidence of tracheostomy insertion, the day of spine surgery and 6-8 days later. There was no difference in the general complication rate between the two groups. With regards to specific complications attributable to the surgical approach/tracheotomy, there was no statistically significant difference. The timing of the tracheotomy also had no effect on complication rate. Although the complications occurred mostly in the formal insertion group as opposed to the percutaneous insertion group, this was most likely due to selection bias. CONCLUSION: Anterior cervical surgery and subsequent tracheostomy are safe despite the intuitive concerns. Timing does not affect the incidence of complications and there is no reason to delay the insertion of the tracheostomy. Ventilation in general is associated with increased complications rather than the tracheostomy tube per se.

Pathways and fluxes: exploring the plant metabolic network.

The transition from a pathway-centred view of plant metabolism to a network-wide perspective is still incomplete. Further progress in this direction requires tools to facilitate the structural description of the network on the basis of fully annotated genomes, techniques for modelling the properties of the network, and experimental methods for constraining the models and verifying their outputs. It also requires a focus on metabolic flux as the key to understanding the regulation of metabolic activity and the relationship between the inputs and outputs of the network. Progress is being made on several fronts and this Special Issue on 'Pathways and fluxes: exploring the plant metabolic network' describes current developments in the genomic reconstruction of metabolic networks, the application of flux-balance analysis to such networks, kinetic modelling, and both steady-state-and non-steady state isotope-based measurements of multiple fluxes in the network of central carbon metabolism. The papers also highlight insights that can be obtained from pathway analysis, particularly in relation to the thermodynamic and kinetic efficiency of the predicted and observed flux distributions.

Strategies for investigating the plant metabolic network with steady-state metabolic flux analysis: lessons from an Arabidopsis cell culture and other systems.

Steady-state (13)C metabolic flux analysis (MFA) is currently the experimental method of choice for generating flux maps of the compartmented network of primary metabolism in heterotrophic and mixotrophic plant tissues. While statistically robust protocols for the application of steady-state MFA to plant tissues have been developed by several research groups, the implementation of the method is still far from routine. The effort required to produce a flux map is more than justified by the information that it contains about the metabolic phenotype of the system, but it remains the case that steady-state MFA is both analytically and computationally demanding. This article provides an overview of principles that underpin the implementation of steady-state MFA, focusing on the definition of the metabolic network responsible for redistribution of the label, experimental considerations relating to data collection, the modelling process that allows a set of metabolic fluxes to be deduced from the labelling data, and the interpretation of flux maps. The article draws on published studies of Arabidopsis cell cultures and other systems, including developing oilseeds, with the aim of providing practical guidance and strategies for handling the issues that arise when applying steady-state MFA to the complex metabolic networks encountered in plants.

Quo vadis? - Monitoring Campylobacter in Germany.

Campylobacter is a poorly recognized foodborne pathogen, leading the statistics of bacterially caused human diarrhoea in Europe during the last years. In this review, we present qualitative and quantitative German data obtained in the framework of specific monitoring programs and from routine surveillance. These also comprise recent data on antimicrobial resistances of food isolates. Due to the considerable reduction of in vitro growth capabilities of stressed bacteria, there is a clear discrepancy between the detection limit of Campylobacter by cultivation and its infection potential. Moreover, antimicrobial resistances of Campylobacter isolates established during fattening of livestock are alarming, since they constitute an additional threat to human health. The European Food Safety Authority (EFSA) discusses the establishment of a quantitative limit for Campylobacter contamination of broiler carcasses in order to achieve an appropriate level of protection for consumers. Currently, a considerable amount of German broiler carcasses would not comply with this future criterion. We recommend Campylobacter reduction strategies to be focussed on the prevention of fecal contamination during slaughter. Decontamination is only a sparse option, since the reduction efficiency is low and its success depends on the initial contamination concentration.

Genetic influences on the pharmacokinetics of orally and intravenously administered digoxin as exhibited by monozygotic twins.

The expression and function of the drug transporter P-glycoprotein are highly variable. Environmental and genetic factors contribute to this variation. We studied the disposition of digoxin, a frequently used probe drug for P-glycoprotein function in humans, in monozygotic (MZ) twins and found that digoxin pharmacokinetics after oral and intravenous administration are highly correlated within MZ twins, supporting the hypothesis of a robust contribution from genetic variance. Our study suggests that studies involving twins could be more widely applied to elucidate pharmacogenetics.

Response of cytoplasmic pH to anoxia in plant tissues with altered activities of fermentation enzymes: application of methyl phosphonate as an NMR pH probe.

BACKGROUND AND AIMS: Acidification of the cytoplasm is a commonly observed response to oxygen deprivation in plant tissues that are intolerant of anoxia. The response was monitored in plant tissues with altered levels of lactate dehydrogenase (LDH) and pyruvate decarboxylase (PDC) with the aim of assessing the contribution of the targeted enzymes to cytoplasmic pH (pH(cyt)) regulation. METHODS: The pH(cyt) was measured by in vivo (31)P nuclear magnetic resonance (NMR) spectroscopy using methyl phosphonate (MeP) as a pH probe. The potential toxicity of MeP was investigated by analysing its effect on the metabolism of radiolabelled glucose. KEY RESULTS: MeP accumulated to detectable levels in the cytoplasm and vacuole of plant tissues exposed to millimolar concentrations of MeP, and the pH-dependent (31)P NMR signals provided a convenient method for measuring pH(cyt) values in tissues with poorly defined signals from the cytoplasmic inorganic phosphate pool. Pretreatment of potato (Solanum tuberosum) tuber slices with 5 mm MeP for 24 h did not affect the metabolism of [U-(14)C]glucose or the pattern of (14)CO(2) release from specifically labelled [(14)C]-substrates. Time-courses of pH(cyt) measured before, during and after an anoxic episode in potato tuber tissues with reduced activities of LDH, or in tobacco (Nicotiana tabacum) leaves with increased activities of PDC, were indistinguishable from their respective controls. CONCLUSIONS: MeP can be used as a low toxicity (31)P NMR probe for measuring intracellular pH values in plant tissues with altered levels of fermentation enzymes. The measurements on transgenic tobacco leaves suggest that the changes in pH(cyt) during an anoxic episode are not dominated by fermentation processes; while the pH changes in the potato tuber tissue with reduced LDH activity show that the affected isozymes do not influence the anoxic pH response.

First-order and second-order statistical analysis of 3D and 2D image structure.

In the first part of this article, we analyze the relation between local image structures (i.e., homogeneous, edge-like, corner-like or texture-like structures) and the underlying local 3D structure (represented in terms of continuous surfaces and different kinds of 3D discontinuities) using range data with real-world color images. We find that homogeneous image structures correspond to continuous surfaces, and discontinuities are mainly formed by edge-like or corner-like structures, which we discuss regarding potential computer vision applications and existing assumptions about the 3D world. In the second part, we utilize the measurements developed in the first part to investigate how the depth at homogeneous image structures is related to the depth of neighbor edges. For this, we first extract the local 3D structure of regularly sampled points, and then, analyze the coplanarity relation between these local 3D structures. We show that the likelihood to find a certain depth at a homogeneous image patch depends on the distance between the image patch and a neighbor edge. We find that this dependence is higher when there is a second neighbor edge which is coplanar with the first neighbor edge. These results allow deriving statistically based prediction models for depth interpolation on homogeneous image structures.

[Effect of urea nail lacquer on nail quality. Clinical evaluation and biophysical measurements]. / Einfluss eines ureahaltigen Lackes auf die Nagelqualität: Evaluation mittels klinischer Scores und biophysikalischer Parameter.

BACKGROUND: Urea is a well-known humectant. The aim of our study was to evaluate the in vivo effect of 10% urea lacquer on nail quality. METHODS: 60 healthy probands with brittle nails were included in a randomized, controlled study. The nail lacquer was applied once (n=30) or twice daily (n=30) on one hand for 28 days, while the other hand served as untreated control. Assessments included clinical evaluations and bioengineering measurements. RESULTS: Application of the nail lacquer was well-tolerated and led to a significant clinical improvement of nail surface morphology, nail plate consistency, reflection of the nail plate surface, appearance of the cuticle and the nail fold. Sonographic nail density was slightly increased. No relevant changes were found in nail thickness and transonychial water loss. CONCLUSIONS: Nail lacquer containing urea improves the cosmetic appearance of fingernails.

Metabolite fingerprinting and profiling in plants using NMR.

Although less sensitive than mass spectrometry (MS), nuclear magnetic resonance (NMR) spectroscopy provides a powerful complementary technique for the identification and quantitative analysis of plant metabolites either in vivo or in tissue extracts. In one approach, metabolite fingerprinting, multivariate analysis of unassigned 1H NMR spectra is used to compare the overall metabolic composition of wild-type, mutant, and transgenic plant material, and to assess the impact of stress conditions on the plant metabolome. Metabolite fingerprinting by NMR is a fast, convenient, and effective tool for discriminating between groups of related samples and it identifies the most important regions of the spectrum for further analysis. In a second approach, metabolite profiling, the 1H NMR spectra of tissue extracts are assigned, a process that typically identifies 20-40 metabolites in an unfractionated extract. These profiles may also be used to compare groups of samples, and significant differences in metabolite concentrations provide the basis for hypotheses on the underlying causes for the observed segregation of the groups. Both approaches generate a metabolic phenotype for a plant, based on a system-wide but incomplete analysis of the plant metabolome. However, a review of the literature suggests that the emphasis so far has been on the accumulation of analytical data and sample classification, and that the potential of 1H NMR spectroscopy as a tool for probing the operation of metabolic networks, or as a functional genomics tool for identifying gene function, is largely untapped.

Biologically motivated space-variant filtering for robust optic flow processing.

We describe and test a biologically motivated space-variant filtering method for decreasing the noise in optic flow fields. Our filter model adopts certain properties of a particular motion-sensitive area of the brain (area MT), which averages the incoming motion signals over receptive fields, the sizes of which increase with the distance from the center of the projection. We use heading estimation from optic flow as a criterion to evaluate the improvement of the filtered flow field. The tests are conducted on flow fields calculated with a standard flow algorithm from image sequences. We use two different sets of image sequences. The first set is recorded by a camera which is installed in a moving car. The second set is derived from a database containing three dimensional data and reflectance information from natural scenes. The latter set guarantees full control of the camera motion and ground truth about the flow field and the heading. We test the space-variant filtering method by comparing heading estimation results between space-variant filtered flow, flow filtered by averaging over domains of the visual field with constant size (constant filtering) and raw unfiltered flow. Because of noise and the aperture problem the heading estimates obtained from the raw flows are often unreliable. Estimated heading differs widely for different sub-sampled calculations. In contrast, the results obtained from the filtered flows are much less variable and therefore more consistent. Furthermore, we find a significant improvement of the results obtained from the space-variant filtered flow compared to the constant filtered flow. We suggest extensions to the space-variant filtering procedure that take other properties of motion representation in area MT into account.

Local image structures and optic flow estimation.

Different kinds of local image structures (such as homogeneous, edge-like and junction-like patches) can be distinguished by the intrinsic dimensionality of the local signals. Intrinsic dimensionality makes use of variance from a point and a line in spectral representation of the signal in order to classify it as homogeneous, edge-like or junction-like. The concept of intrinsic dimensionality has been mostly exercised using discrete formulations; however, recent work has introduced a continuous definition. The current study analyzes the distribution of local patches in natural images according to this continuous understanding of intrinsic dimensionality. This distribution reveals specific patterns than can be also associated to local image structures established in computer vision and which can be related to orientation and optic flow features. In particular, we link quantitative and qualitative properties of optic-flow error estimates to these patterns. In this way, we also introduce a new tool for better analysis of optic flow algorithms.

Joint positive control testing in guinea pig skin sensitization tests. A harmonized approach.

A scheme for the performance of positive control studies within a coordinated group of laboratories was proposed (joint positive control testing). The procedure has been described, as well as the first results of the validation phase of this joint positive control testing project. Adoption of this proposal within the participating six laboratories would lead to a reduction in the number of guinea pigs required for reliability and sensitivity checks from current approximate 12 studies per year down to 2 studies, i.e., 150-300 fewer animals per year. Another benefit would be the use of a harmonized, and therefore more comparable, method to perform guinea pig tests and interpret the data. In the validation phase of joint reading of the positive control studies, the congruency of reading could clearly be demonstrated. From the experience gained up to now, it was possible to draw the conclusion that a coordinated interlaboratory approach for positive control testing was fully acceptable and an improvement with regard to animal welfare.

A linkage analysis of sex determination in Bombus terrestris (L.) (Hymenoptera: Apidae).

We constructed a linkage map of Bombus terrestris (Hymenoptera, Apidae) phase unknown. The map contains 79 markers (six microsatellite and 73 RAPD markers) in 21 linkage groups and spans over 953.1 cM. The minimal recombinational size of the B. terrestris genome was estimated to be 1073 cM. Using flow cytometry, the physical size of the haploid genome of B. terrestris was calculated to be 274 Mb. This is the second linkage map for a social insect species. Bombus terrestris has on average five times less recombinational events per kb than the honey bee Apis mellifera. Male haploidy, chromosome size, and eusociality can now be excluded as reasons for the high recombination frequency of Apis mellifera. Finally, the sex determination locus of B. terrestris was placed on the map using bulked segregant analysis.

Multiple, distinct isoforms of sucrose synthase in pea.

Genes encoding three isoforms of sucrose synthase (Sus1, Sus2, and Sus3) have been cloned from pea (Pisum sativum). The genes have distinct patterns of expression in different organs of the plant, and during organ development. Studies of the isoforms expressed as recombinant proteins in Escherichia coli show that they differ in kinetic properties. Although not of great magnitude, the differences in properties are consistent with some differentiation of physiological function between the isoforms. Evidence for differentiation of function in vivo comes from the phenotypes of rug4 mutants of pea, which carry mutations in the gene encoding Sus1. One mutant line (rug4-c) lacks detectable Sus1 protein in both the soluble and membrane-associated fractions of the embryo, and Sus activity in the embryo is reduced by 95%. The starch content of the embryo is reduced by 30%, but the cellulose content is unaffected. The results imply that different isoforms of Sus may channel carbon from sucrose towards different metabolic fates within the cell.

Starch synthesis in transgenic potato tubers with increased 3-phosphoglyceric acid content as a consequence of increased 6-phosphofructokinase activity.

The aim of this work was to test the hypothesis that changes in cytosolic 3-phosphoglyceric acid (3-PGA) content can regulate the rate of starch synthesis in potato (Solanum tuberosum L.) tubers. The amount of 3-PGA was increased by expressing bacterial phosphofructokinase (PFK; EC 2.7.1.11) in transgenic potato tubers. The resultant 3-fold increase in PFK activity was accompanied by an increase in metabolites downstream of PFK, including a 3-fold increase in 3-PGA. There was also a decrease in metabolites upstream of PFK, most notably of glucose-6-phosphate. The increase in 3-PGA did not affect the amount of starch that accumulated in developing tubers, nor its rate of synthesis in tuber discs cut from developing tubers. This suggests that changes in cytosolic 3-PGA may not affect the rate of starch synthesis under all circumstances. We propose that in this case, a decrease in glucose-6-phosphate (which is transported into the amyloplast as a substrate for starch synthesis) may be sufficient to counteract the effect of increased 3-PGA.