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A surveillance study was performed throughout Germany from November 2001 to June 2002 to assess the prevalence of linezolid-resistant isolates among Gram-positive bacteria from routine susceptibility data and to compare the in-vitro activity of linezolid to that of other antibacterial agents. Each of 86 laboratories provided routine susceptibility data for 100 consecutive isolates. Most laboratories (c. 60%) used the disk diffusion test. Laboratories were also requested to send a representative sample of their isolates, as well as all isolates reported as intermediate or resistant to linezolid, to a reference laboratory for MIC determination. Susceptibility data for 8594 isolates were evaluated. Sites of infection were skin and soft tissue (29.9%), upper and lower respiratory tract (19.1%), foreign body or catheter (10.5%), or urinary tract (9.8%). Routine linezolid susceptibility data were reported for 6433 isolates. The prevalence of linezolid resistance, as reported to the clinician, was 0.4% inStaphylococcus aureus, 0.3% inStaphylococcus epidermidis, 2.9% inEnterococcus faecalis, 2.3% inEnterococcus faecium, 1.4% inStreptococcus pyogenesand 2.9% inStreptococcus agalactiae.Linezolid resistance was not detected inStreptococcus pneumoniaeor in viridans group streptococci. Sixty-nine of 115 isolates reported as intermediate or resistant to linezolid were retested, but none was resistant to linezolid. Linezolid exhibited excellent in-vitro activity against representative isolates of the six most frequently encountered species (MIC90, 1–2 mg/L). The prevalence of resistance to linezolid was very low in Germany. Organisms reported as linezolid-resistant should be retested, either in the same laboratory with an alternative method or in a reference laboratory. [ABSTRACT FROM AUTHOR]

Materials with multiple superconducting phases are rare. Here, we report the discovery of two-phase unconventional superconductivity in CeRh2As2. Using thermodynamic probes, we establish that the superconducting critical field of its high-field phase is as high as 14 tesla, even though the transition temperature is only 0.26 kelvin. Furthermore, a transition between two different superconducting phases is observed in a c axis magnetic field. Local inversion-symmetry breaking at the cerium sites enables Rashba spin-orbit coupling alternating between the cerium sublayers. The staggered Rashba coupling introduces a layer degree of freedom to which the field-induced transition and high critical field seen in experiment are likely related. [ABSTRACT FROM AUTHOR]

The current generation of ground-based imaging atmospheric Cherenkov telescopes (IACTs) operate in the very-high-energy (VHE) domain from ~100 GeV to ~100 TeV. They use electronic digital trigger systems to discern the Cherenkov light flashes emitted by extensive air showers (EASs), from the overwhelming light of the night sky (LoNS) background. Near the telescope energy threshold, the number of emitted Cherenkov photons by gamma-ray-induced EASs is comparable to the fluctuations of the LoNS and the photon distribution at the Cherenkov-imaging camera plane becomes patchy. This results in a severe loss of effectiveness of the digital triggers based on combinatorial logic of thresholded signals. A stereoscopic analog trigger system has been developed for improving the detection capabilities of the Major Atmospheric Gamma-ray Imaging Cherenkov (MAGIC) telescopes at the lowest energies. It is based on the analog sum of the photosensor electrical signals. In this article, the architectural design, technical performances, and configuration of this stereoscopic analog trigger, dubbed “Sum-Trigger-II,” are described. [ABSTRACT FROM AUTHOR]

Empiric initial antibiotic therapy of bacterial infections is based primarily upon the susceptibility of the most common causative pathogens. The purpose of this study was to provide susceptibility data on six bacterial species known to cause ear, nose and throat (ENT) infections. A total of 1066 isolates collected during a nationwide laboratory-based surveillance study were analysed. All Streptococcus pyogenes isolates were penicillin (PEN)-susceptible, indicating that natural penicillins can still be recommended as the first-line treatment for group A streptococcal tonsillopharyngitis. Of the S. pneumoniae isolates, 92.9% were PEN-susceptible and of the Haemophilus influenzae isolates, 89.7% were amoxicillin-susceptible, retaining aminopenicillins as the first-line treatment for acute otitis media (AOM) and acute rhinosinusitis (ARS), in case antibiotic therapy is considered. In contrast, cefuroxime axetil seems less likely to be suitable for the treatment of AOM or ARS, as all Moraxella catarrhalis and >99% of the H. influenzae isolates were categorised as intermediate or resistant. The susceptibility rates of Pseudomonas aeruginosa were 97-100% for the drugs tested, except for the fluoroquinolones (87.6%). Overall, bacterial isolates from outpatients presenting with ENT infections showed low frequencies of resistance in Germany. However, given the emergence of multidrug resistance to standard antibiotics in Escherichia coli and other pathogens, inappropriate use of broad-spectrum antibiotics for the treatment of ENT infections has to be avoided. [ABSTRACT FROM AUTHOR]

Körber-Irrgang, B., Wetzstein, H.-G., Bagel-Trah, S., Hafner, D., Kresken, M. Comparative activity of pradofloxacin and marbofloxacin against coagulase-positive staphylococci in a pharmacokinetic-pharmacodynamic model based on canine pharmacokinetics. J. vet. Pharmacol. Therap. 35, 571-579. Pradofloxacin (PRA), a novel veterinary 8-cyano-fluoroquinolone (FQ), is active against Staphylococcus pseudintermedius, the primary cause of canine pyoderma. An in vitro pharmacokinetic-pharmacodynamic model was used to compare the activities of PRA and marbofloxacin (MAR) against three clinical isolates of S. pseudintermedius and reference strain Staphylococcus aureus ATCC 6538. Experiments were performed involving populations of 1010 CFU corresponding to an inoculum density of approximately 5 × 107 CFU/mL. The time course of free drug concentrations in canine serum was modelled, resulting from once daily standard oral dosing of 3 mg of PRA/kg and 2 mg of MAR/kg. In addition, experimentally high doses of 6 mg of PRA/kg and 16 mg of MAR/kg were tested against the least susceptible strain. Viable counts were monitored over 24 h. At concentrations associated with standard doses, PRA caused a faster and more sustained killing than MAR of all strains. The ratios of free drug under the concentration-time curve for 24 h over MIC and the maximum concentration of free drug over MIC were at least 90 and 26, and 8.5 and 2.1 for PRA and MAR, respectively. At experimentally high doses, PRA was superior to MAR in terms of immediate killing. Subpopulations with reduced susceptibility to either FQ did not emerge. We conclude that PRA is likely to be an efficacious therapy of canine staphylococcal infections. [ABSTRACT FROM AUTHOR]

Kavain metabolism in humans was the target of this current investigation. In the present study a high-performance liquid chromatographic (HPLC–DAD) assay method for the simultaneous determination of kavain and its main metabolites (p-hydroxykavain, p-hydroxy-5,6-dehydrokavain and p-hydroxy-7,8-dihydrokavain) in serum and urine was developed and validated. The metabolites were mainly excreted in the form of their conjugates. All kavain metabolites were detectable in serum and urine, except for p-hydroxy-7,8-dihydrokavain, which was found in urine only. Confirmation of the results and identification of the metabolites were performed by LC–MS or LC–MS–MS. Kinetics of kavain and its metabolites in serum were investigated after administration of a single oral dose (800 mg kavain). Within 1 and 4 h after uptake, the serum concentrations ranged between 40 and 10 ng/ml for kavain, 300 and 125 ng/ml for p-hydroxykavain, 90 and 40 ng/ml for o-desmethyl-hydroxy-5,6-dehydrokavain, and 50 and 30 ng/ml for 5,6-dehydrokavain. [Copyright &y& Elsevier]

Oral mucositis (OM) is a common side effect in patients undergoing chemotherapy (CT), especially in children due to their rapid epithelial mitotic rate. It has been associated with a significant reduction in life quality since it leads to pain, an inadequate intake of nutrients, an increased risk of opportunistic infections, and interruptions of CT. Photobiomodulation (PMB) with low-level laser therapy (LLLT) has shown faster healing, reduction in pain, and the reduced use of analgesic compared to placebo groups. The purpose of this review is to analyze and compare the existing clinical trials and identify their shortcomings in hope to make future research easier. Using MeSH terms and keywords, the Embase, Medline, and PubMed databases we searched for the period of the last 5 years. We identified a total of 15 clinical trials, with a total of 929 pediatric patients analyzed in this review. We compared different light sources and other laser technique characteristics used in clinical trials such as wavelength, energy and power density, spot size, irradiation time, PBM protocol, and OM evaluation. The main findings show inconsistent laser parameter quotations, differences in the PBM protocol along with a laser application technique, and a lack of clinical trials. Based on that, more studies with a high methodological quality should be conducted in order to provide a unified PBM protocol suitable for the pediatric population.

The aim of this study was to investigate and compare the molecular epidemiology and carbapenem resistance determinants in clinical Acinetobacter baumannii isolates collected during four multicentre surveillance studies conducted by the Paul-Ehrlich-Society for Infection Therapy. Isolates were collected prospectively from hospital in-patients at 17 medical centres in Germany over four periods of three- to six-months starting in October of each of 2010, 2013, 2016 and 2019. Species identification was performed by MALDI-TOF, gyrB multiplex polymerase chain reaction (PCR), and detection of the intrinsic bla OXA-51-like gene. Minimum inhibitory concentrations were determined by broth microdilution. The prevalence of carbapenemase-encoding genes was investigated by OXA-multiplex PCR and whole-genome sequencing. Molecular epidemiology was examined by rep-PCR and core-genome multi-locus sequence typing. A total of 302 A. baumannii isolates were collected. Resistance to imipenem and/or meropenem was detected in 58 isolates (19.2%) from 14 centres. The proportion of carbapenem-resistant isolates increased from 21.3% in 2010 to 33.3% in 2013, and then decreased to 13.8% in 2016 and 12.3% in 2019. Forty-six of these isolates were associated with the international clonal lineage IC2 and five with IC1. The most prevalent carbapenemase gene detected was bla OXA-23-like (n=51). Further carbapenem-resistance determinants were bla OXA-40-like (n=1), bla OXA-58-like (n=3) and bla NDM-1 (n=2). In one isolate, ISAba1 was detected upstream of bla OXA-51-like . In conclusion, IC2 was the most prevalent clonal lineage detected in this study. Interestingly, in Germany, carbapenem resistance seems to have decreased in A. baumannii between 2013 and 2019., Competing Interests: Declaration of Competing Interest M.K. was an acting partner of Antiinfectives Intelligence GmbH, a research organisation providing services to pharmaceutical companies. E.W. is the head of the laboratory at Antiinfectives Intelligence GmbH and the novel acting partner. H.S. has received grants or research support from the German Center for Infection Research (DZIF), and has been a consultant for Debiopharm, Eumedica, Gilead, MSD, and Shionogi. Other authors: none to declare., (Copyright © 2022. Published by Elsevier Ltd.)

The success of monocular depth estimation relies on large and diverse training sets. Due to the challenges associated with acquiring dense ground-truth depth across different environments at scale, a number of datasets with distinct characteristics and biases have emerged. We develop tools that enable mixing multiple datasets during training, even if their annotations are incompatible. In particular, we propose a robust training objective that is invariant to changes in depth range and scale, advocate the use of principled multi-objective learning to combine data from different sources, and highlight the importance of pretraining encoders on auxiliary tasks. Armed with these tools, we experiment with five diverse training datasets, including a new, massive data source: 3D films. To demonstrate the generalization power of our approach we use zero-shot cross-dataset transfer, i.e. we evaluate on datasets that were not seen during training. The experiments confirm that mixing data from complementary sources greatly improves monocular depth estimation. Our approach clearly outperforms competing methods across diverse datasets, setting a new state of the art for monocular depth estimation.

The impact of individual scientists is commonly quantified using citation-based measures. The most common such measure is the h-index. A scientist's h-index affects hiring, promotion, and funding decisions, and thus shapes the progress of science. Here we report a large-scale study of scientometric measures, analyzing millions of articles and hundreds of millions of citations across four scientific fields and two data platforms. We find that the correlation of the h-index with awards that indicate recognition by the scientific community has substantially declined. These trends are associated with changing authorship patterns. We show that these declines can be mitigated by fractional allocation of citations among authors, which has been discussed in the literature but not implemented at scale. We find that a fractional analogue of the h-index outperforms other measures as a correlate and predictor of scientific awards. Our results suggest that the use of the h-index in ranking scientists should be reconsidered, and that fractional allocation measures such as h-frac provide more robust alternatives., Competing Interests: The authors were supported by Intel Corporation. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Active inference offers a first principle account of sentient behavior, from which special and important cases-for example, reinforcement learning, active learning, Bayes optimal inference, Bayes optimal design-can be derived. Active inference finesses the exploitation-exploration dilemma in relation to prior preferences by placing information gain on the same footing as reward or value. In brief, active inference replaces value functions with functionals of (Bayesian) beliefs, in the form of an expected (variational) free energy. In this letter, we consider a sophisticated kind of active inference using a recursive form of expected free energy. Sophistication describes the degree to which an agent has beliefs about beliefs. We consider agents with beliefs about the counterfactual consequences of action for states of affairs and beliefs about those latent states. In other words, we move from simply considering beliefs about "what would happen if I did that" to "what I would believe about what would happen if I did that." The recursive form of the free energy functional effectively implements a deep tree search over actions and outcomes in the future. Crucially, this search is over sequences of belief states as opposed to states per se. We illustrate the competence of this scheme using numerical simulations of deep decision problems.

Poly(2-oxazoline)s (POx) bottle-brush brushes have excellent biocompatible and lubricious properties, which are promising for the functionalization of surfaces for biomedical devices. Herein, a facile synthesis of POx is reported which is based bottle-brush brushes (BBBs) on solid substrates. Initially, backbone brushes of poly(2-isopropenyl-2-oxazoline) (PIPOx) were fabricated via surface initiated Cu 0 plate-mediated controlled radical polymerization (SI-Cu 0 CRP). Poly(2-methyl-2-oxazoline) (PMeOx) side chains were subsequently grafted from the PIPOx backbone via living cationic ring opening polymerization (LCROP), which result in ≈100 % increase in brush thickness (from 58 to 110 nm). The resultant BBBs shows tunable thickness up to 300 nm and high grafting density (σ) with 0.42 chains nm -2 . The synthetic procedure of POx BBBs can be further simplified by using SI-Cu 0 CRP with POx molecular brush as macromonomer (M n =536 g mol -1 , PDI=1.10), which results in BBBs surface up to 60 nm with well-defined molecular structure. Both procedures are significantly superior to the state-of-art approaches for the synthesis of POx BBBs, which are promising to design bio-functional surfaces., (© 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

Background and Aims: The treatment options for eosinophilic esophagitis (EoE) patients include drugs (proton pump inhibitors [PPIs], swallowed topical corticosteroids [STCs]), elimination diets, and dilation. Given the lack of data, we aimed to assess adult EoE patients' satisfaction with different EoE-specific treatment modalities., Patients and Methods: We evaluated therapy satisfaction recalled over a 12-month period using the validated Treatment Satisfaction Questionnaire for Medication that assesses effectiveness, side effects, convenience, and overall satisfaction. The score for each scale ranges from 0 (dissatisfied) to 100 (satisfied). To evaluate satisfaction with nonpharmacologic therapies, the questionnaire was modified and debriefed into three focus groups. The final questionnaire was sent to 147 patients., Results: The patient response rate was 74%. In the last 12 months, 24, 75, 19, and 9% were treated with PPIs, STCs, elimination diet, and dilation, respectively. Patients identified the following considerations as important for therapy choice: effect on symptoms (89%), effect on esophageal inflammation (76%), side effects (69%), and ease of use (58%). Patients found STCs to be effective (83 points), convenient (83 points), and experienced no side effects when using this therapy. When using STCs alone (43%), overall patient satisfaction was high (86 points). Patients judged PPIs to be most convenient (89 points), STCs to be a bit less convenient (83 points), and diet to be most inconvenient (46 points) of the three therapies examined., Conclusions: Adult EoE patients consider both therapy effect on symptoms and esophageal inflammation as important criteria when choosing EoE therapy and appear to be satisfied with STC use., (© 2019 S. Karger AG, Basel.)

Systems neuroscience seeks explanations for how the brain implements a wide variety of perceptual, cognitive and motor tasks. Conversely, artificial intelligence attempts to design computational systems based on the tasks they will have to solve. In artificial neural networks, the three components specified by design are the objective functions, the learning rules and the architectures. With the growing success of deep learning, which utilizes brain-inspired architectures, these three designed components have increasingly become central to how we model, engineer and optimize complex artificial learning systems. Here we argue that a greater focus on these components would also benefit systems neuroscience. We give examples of how this optimization-based framework can drive theoretical and experimental progress in neuroscience. We contend that this principled perspective on systems neuroscience will help to generate more rapid progress.

The shape of nanoparticles is known recently as an important design parameter influencing considerably the fate of nanoparticles with and in biological systems. Several manufacturing techniques to generate nonspherical nanoparticles as well as studies on in vitro and in vivo effects thereof have been described. However, nonspherical nanoparticle shape stability in physiological-related conditions and the impact of formulation parameters on nonspherical nanoparticle resistance still need to be investigated. To address these issues, different nanoparticle fabrication methods using biodegradable polymers are explored to produce nonspherical nanoparticles via the prevailing film-stretching method. In addition, systematic comparisons to other nanoparticle systems prepared by different manufacturing techniques and less biodegradable materials (but still commonly utilized for drug delivery and targeting) are conducted. The study evinces that the strong interplay from multiple nanoparticle properties (i.e., internal structure, Young's modulus, surface roughness, liquefaction temperature [glass transition (T g ) or melting (T m )], porosity, and surface hydrophobicity) is present. It is not possible to predict the nonsphericity longevity by merely one or two factor(s). The most influential features in preserving the nonsphericity of nanoparticles are existence of internal structure and low surface hydrophobicity (i.e., surface-free energy (SFE) > ≈55 mN m -1 , material-water interfacial tension <6 mN m -1 ), especially if the nanoparticles are soft (<1 GPa), rough (R rms > 10 nm), porous (>1 m 2 g -1 ), and in possession of low bulk liquefaction temperature (<100 °C). Interestingly, low surface hydrophobicity of nanoparticles can be obtained indirectly by the significant presence of residual stabilizers. Therefore, it is strongly suggested that nonsphericity of particle systems is highly dependent on surface chemistry but cannot be appraised separately from other factors. These results and reviews allot valuable guidelines for the design and manufacturing of nonspherical nanoparticles having adequate shape stability, thereby appropriate with their usage purposes. Furthermore, they can assist in understanding and explaining the possible mechanisms of nonspherical nanoparticles effectivity loss and distinctive material behavior at the nanoscale., (© 2019 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background & Aims: Eosinophilic esophagitis (EoE) is assessed endoscopically (endoscopic activity), based on grades of edema, rings, exudates, furrows, and strictures (EREFS). We examined variations in endoscopic assessments of severity, developed and validated 3 EREFS-based scoring systems, and assessed responsiveness of these systems using data from a randomized placebo-controlled trial of patients with EoE., Methods: For the development set, 5 gastroenterologists reviewed EREFS findings from 266 adults with EoE and provided endoscopist global assessment scores (EndoGA, scale of 0 to 10); variation (ΔEndoGA) was assessed using linear regression. We evaluated simple scores (features given arbitrary values from 0 to 3) and developed 2 scoring systems (adjusted score range, 0-100). We then fitted our linear regression model with mean EndoGA to data from 146 adults recruited in centers in Switzerland and the United States between April 2011 and December 2012. For the validation set, we collected data from 120 separate adults (recruited in centers in Switzerland and the United States between May 2013 and July 2014), assessing regression coefficient-based scores using Bland-Altman method. We assessed the responsiveness of our scoring systems using data from a randomized trial of patients with EoE given fluticasone (n=16) or placebo (n=8)., Results: The distribution of EndoGA values differed among endoscopists (mean ΔEndoGA, 2.6±1.8; range 0-6.6). We developed 2 regression-based scoring systems to assess overall and proximal and distal esophageal findings; variation in endoscopic features accounted for more than 90% of the mean EndoGA variation. In the validation group, differences between mean EndoGA and regression-based scores were small (ranging from -4.70 to 2.03), indicating good agreement. In analyses of data from the randomized trial, the baseline to end of study change in patients given fluticasone was a reduction of 24.3 in simple score (reduction of 4.6 in patients given placebo, P=.052); a reduction of 23.5 in regression-based overall score (reduction of 6.56 in patients given placebo, P=.12), and a reduction of 23.8 (reduction of 8.44 in patients given placebo, P=.11)., Conclusion: Assessments of endoscopic activity in patients with EoE vary among endoscopists. In an analysis of data from a randomized controlled trial, we found that newly developed scoring systems are no better than simple scoring system in detecting changes in endoscopic activity. These results support the use of a simple scoring system in evaluation of endoscopic activity in patients with EoE. clinicaltrials.gov no: NCT00939263 and NCT01386112., (Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Well informed patients who are in cohesive partnership with physicians and who have realistic expectations towards therapy are more likely to be adherent, which results in better disease control., Aim: To assess which therapy goals adults with eosinophilic oesophagitis consider relevant., Methods: Following refinement during three focus groups, a study brochure and questionnaire were sent to 148 patients. Patients ranked the importance (five levels) of short-term (in the next 3 months) and long-term (≥1 year) treatment effect on symptoms, quality of life (QoL), histologically-detected inflammation and fibrosis, endoscopically-detected inflammation, and stricture formation as well as achieving histological remission while asymptomatic. Patients' characteristics associated with treatment goals were identified using logistic regression., Results: Of 109 respondents (mean age 43 years), 85 were men. Over 90% chose symptoms and QoL improvement as important short- and long-term therapy goals. A greater proportion attributed more importance to long-term reduction in endoscopic (90% vs 73%, P < 0.001) and histological (81% vs 62%, P = 0.002) inflammation, and histologically-detected fibrosis (79% vs 64%, P = 0.018) when compared to short-term reduction in these features. Patients (88%) ranked achieving histological remission while being asymptomatic as important. Gender, therapy use, education level, QoL, symptom severity, and history of dilation were associated with patients' choice of treatment goals., Conclusions: Patients attributed most importance to improvement in symptoms and QoL. Reduction in biological activity was judged less important, but more relevant in the long- compared to the short-term., (© 2018 John Wiley & Sons Ltd.)

The aim of this study was to analyse the presence of vascular endothelial growth factor (VEGF) and interferon alpha (IFN-α) in the follicular fluid (FF) and their possible influence, as pro-angiogenic or anti-angiogenic factors, on in vitro fertilization outcome. The concentrations of VEGF and IFN-α were correlated with oocyte and embryo quality, concentrations of hormones in the serum, perifollicular blood flow and endometrial thickness. VEGF was detected in all FF samples (median 706.6 pg/ml, range 182.9-6638 pg/ml). IFN-α was detected in 60% of the samples (median 6.5 pg/ml, range 0-79.4 pg/ml), while in 40% of the samples its levels were below the test detection limit. VEGF and IFN-α concentrations did not correlate with the cause of infertility, concentrations of FSH, LH, E2 and prolactin, oocyte or embryo quality. Significantly higher concentrations of VEGF have been found in women with primary compared with secondary infertility (p = 0.011, Mann Whitney test). The concentrations of VEGF and IFN-α did not correlate with the resistance index (RI) on days of hCG administration, follicular aspiration and embryo transfer. However, the concentrations of IFN-α correlated with endometrial thickness on the day of embryo transfer (Spearman correlation coefficient ρ = 0.4107; P < 0.05) but not on days of hCG administration and follicular aspiration. The mechanism of VEGF association with the previous ability of having a child needs to be clarified in future studies. The results of this study indicate a possible role of IFN-α in pathways of endometrial remodelling., (Copyright © 2018 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier B.V. All rights reserved.)

This work describes a new approach based on multiple light scattering to study red wine clarification processes. The whole spectral signal (1933 backscattering points along the length of each sample vial) were fitted by a multivariate kinetic model that was built with a three-step mechanism, implying (1) adsorption of wine colloids to fining agents, (2) aggregation into larger particles, and (3) sedimentation. Each step is characterized by a reaction rate constant. According to the first reaction, the results showed that gelatin was the most efficient fining agent, concerning the main objective, which was the clarification of the wine, and consequently the increase in its limpidity. Such a trend was also discussed in relation to the results achieved by nephelometry, total phenols, ζ-potential, color, sensory, and electronic nose analyses. Also, higher concentrations of the fining agent (from 5 to 30 g/100 L) or higher temperatures (from 10 to 20 °C) sped up the process. Finally, the advantage of using the whole spectral signal vs classical univariate approaches was demonstrated by comparing the uncertainty associated with the rate constants of the proposed kinetic model. Overall, multiple light scattering technique showed a great potential for studying fining processes compared to classical univariate approaches.

2D mussel-inspired polydopamine (PDA) nanosheets are prepared and exploited as a functional surface for grafting various polymer brushes. The PDA nanosheet and its polymer-brush derivatives show lateral integrity and are robust; therefore, they can be detached from their substrates. Cell-adhesion tests show that the PDA nanosheet promotes cell growth and attachment, while a PDA-based poly(3-sulfopropyl methacrylate) carpet exhibits nonfouling behavior., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The in vitro activities of fosfomycin and seven other antibiotics commonly used for oral treatment of urinary tract infections (UTIs) were evaluated for 499 Escherichia coli isolated from urine samples during a nationwide laboratory-based surveillance study in 2010. Overall, the highest resistance rates were found for amoxicillin (42.9%), followed by amoxicillin/clavulanic acid (32.7%), trimethoprim/sulfamethoxazole (SXT) (30.9%), ciprofloxacin (19.8%), cefuroxime (10.0%), cefpodoxime (8.6%) and cefixime (8.2%). One-half of the isolates (n=252; 50.5%) were fully susceptible to the eight drugs, whilst only 6 strains (1.2%) were resistant to fosfomycin. Combined resistance to amoxicillin, cefuroxime, ciprofloxacin and SXT was detected in 29 isolates (5.8%). Moreover, 40 isolates (8.0%) produced an extended-spectrum β-lactamase (ESBL), including CTX-M-type ESBLs detected in 39/40 isolates (97.5%) and a TEM-52 ESBL in 1 strain (2.5%). The predominant CTX-M-type ESBL was CTX-M-15 (27/39; 69.2%). Of the 27 CTX-M-15 producers, 19 (70.4%) belonged to the clonal lineage E. coli O25b-ST131. All but one ESBL-producing strains were fosfomycin-susceptible. In view of the emergence of multidrug resistance to standard oral antibiotics, these data support that oral fosfomycin (trometamol salt) may represent a valuable option in the treatment of uncomplicated UTIs., (Copyright © 2014 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.)

Objectives: This study evaluates the safety, principal feasibility and restoration potential of laser-supported CD133+ intramyocardial cell transplantation in patients with ischemic cardiomyopathy., Methods: Forty-two patients with severe ischemic cardiomyopathy (left ventricular ejection fraction (LVEF) >15% and <35%) were included in this prospective multicenter phase I trial. They underwent coronary artery bypass grafting (CABG) with subsequent transepicardial low-energy laser treatment and autologous CD133+ cell transplantation, and were followed up for 12 months. To evaluate segmental myocardial contractility as well as perfusion and to identify the areas of scar tissue, cardiac MRI was performed at 6 months and compared to the preoperative baseline. In addition, clinical assessment comprising of CCS scoring, blood and physical examination was performed at 3, 6 and 12 months, respectively., Results: Intraoperative cell isolation resulted in a mean cell count of 9.7±1.2×106. Laser treatment and subsequent CD133+ cell therapy were successfully and safely carried out in all patients and no procedure-related complications occurred. At 6 months, the LVEF was significantly increased (29.7±1.9% versus 24.6±1.5% with p = 0.004). In addition, freedom from angina was achieved, and quality of life significantly improved after therapy (p<0.0001). Interestingly, an extended area of transmural delayed enhancement (>3 myocardial segments) determined in the preoperative MRI was inversely correlated with a LVEF increase after laser-supported cell therapy (p = 0.024)., Conclusions: This multicenter trial demonstrates that laser-supported CD133+ cell transplantation is safe and feasible in patients with ischemic cardiomyopathy undergoing CABG, and in most cases, it appears to significantly improve the myocardial function. Importantly, our data show that the beneficial effect was significantly related to the extent of transmural delayed enhancement, suggesting that MRI-guided selection of patients is mandatory to ensure the effectiveness of the therapy., Trial Registration: EudraCT 2005-004051-35) Controlled-Trials.com ISRCTN49998633.

We present a method to measure the absolute surface resistance of conductive samples at a set of GHz frequencies with superconducting lead stripline resonators at temperatures 1-6 K. The stripline structure can easily be applied for bulk samples and allows direct calculation of the surface resistance without the requirement of additional calibration measurements or sample reference points. We further describe a correction method to reduce experimental background on high-Q resonance modes by exploiting TEM-properties of the external cabling. We then show applications of this method to the reference materials gold, tantalum, and tin, which include the anomalous skin effect and conventional superconductivity. Furthermore, we extract the complex optical conductivity for an all-lead stripline resonator to find a coherence peak and the superconducting gap of lead.

T-2 toxin is the most acutely toxic trichothecene mycotoxin: it inhibits protein, DNA and RNA synthesis. The main goal of this study was to evaluate the rate of DNA damage caused by T-2 toxin in porcine mononuclear cells in increasing concentrations (0.1, 0.5 and 1.0 μmol) and after two different incubation periods (24 and 42 h). The lowest concentration caused DNA damage and about 50% of the treated cells could be categorised as having 1 to 4 scores in comet assay. In parallel with the increase of T-2 toxin concentration, the frequency of intact lymphocytes decreased from 50.2% (0.1 μM) to 36.3% (1.0 μM) in the first 24 h. In case of score 3, the highest concentration of T-2 toxin resulted in a 5-fold change, as compared to the lowest dose. Cells with score 4 were found only after exposure to 1.0 μM T-2 toxin. The exposure time did not have a significant effect on the results, while concentration did (P < 0.0001). However, a significant interaction between concentration and time as fixed factors (P < 0.0001) was found. When these were combined as a single factor, the results showed a significant toxin treatment effect on the results. It was concluded that a time- and dose-dependent DNA damaging effect of T-2 toxin could be demonstrated using peripheral blood mononuclear cells from healthy pigs by comet assay.

Background: Snail1 is a transcription regulator of E-cadherin. The loss of E-cadherin seems to be a crucial step in the process of Epithelial-mesenchymal transition (EMT). EMT initiates invasion and proliferation in many tumours. Overexpression of Snail1 is known to be associated with poor outcome in several solid tumours. The aim of this study was to analyse its expression profile and prognostic significance in colorectal cancer., Methods: Tissue microarrays (TMA) containing paraffin-embedded primary colorectal cancer (CRC) tissue samples from 251 patients were used in this study. The expression of Snail1 and E-cadherin was assessed by immunohistochemistry in different tumour compartments, corresponding lymph node metastases and normal colonic mucosa. Intensity of staining was classified according to the Remmele score (standardized scoring system) as well as the semiquantitative score established by Blechschmidt et al., Results: Snail1 expression was observed in 76% of the CRC. Loss of E-cadherin was noted in 87% of the CRC. Snail1 positive tumours were significantly correlated with Snail1 positive lymph node metastases (p=0.03). There was no significant correlation between loss of E-cadherin and Snail1 expression, or between N-stage or grading and Snail1 expression. Kaplan-Meier survival analysis identified no prognostic impact of Snail1 expression on overall survival., Conclusion: Snail1 expression was detectable in most of the CRC but showed no significant association with E-cadherin loss, clinical pathological characteristics or overall survival. The observed loss of E-cadherin could be explained by effects of other important EMT pathways, such as the Wnt-signalling cascade.

Many patients with Anorexia and Bulimia Nervosa (AN, BN) engage in sport and physical activity in an excessive and compulsive manner, mostly to influence weight and shape. Many of them experience guilt in case of not exercising. However, sport and physical exercise can also have a positive effect on mental illness by influencing mood, sense of self-esteem and body experience. Until now, only few programs for eating disorder patients exist which aim at changing physical activity behavior and use sport and exercise activities in a therapeutic way. We developed a sport-therapeutic program designed for outpatients with eating disorders. It supervises sport and physical exercise and helps patients to use sport and exercise in a healthy manner. This report presents the program's manual and first experiences based on half-standardized interviews., (© Georg Thieme Verlag KG Stuttgart · New York.)

Introduction: Conservative treatment of a heterotopic cervical pregnancy was performed with a modification of the fixation of a Foley catheter at the level of the external cervical os, followed by the ligature of the descending cervical branches of the uterine arteries and systemic methotrexate application., Case Presentation: A 34-year-old Caucasian woman was diagnosed with double gestation after 6 weeks of in vitro fertilization treatment. A gynecological examination and color Doppler ultrasound scan revealed intra-uterine and cervical gestational sacs both containing live fetuses. A Foley catheter balloon was inserted into the cervical canal, inflated and fixed by a cerclage suture at the level of the external cervical os, followed by ligation of the descending cervical branches of the uterine arteries. Systemic methotrexate was applied. Three days after removal of the Foley catheter, an evacuation of the intra-uterine gestational sac was performed. Hemorrhage from the implantation site was controlled immediately and a pregnancy termination was successfully performed. The procedure was uneventful and our patient was discharged with a preserved uterus., Conclusions: Conservative treatment of cervical pregnancy using a Foley catheter balloon is more efficacious if the Foley catheter balloon is attached in the correct position with a cerclage suture at the level of the external os, followed by ligation of the descending cervical branches of the uterine arteries, thereby exerting maximal pressure on the bleeding vessels.

The aim of the present investigation was to determine the expression of the Fas-receptor/ligand system in established cell lines of squamous cell carcinomas of the head and neck (SCCHN), and to study it's functional impact on chemotherapy-induced apoptosis in these SCCHN cell lines. We observed constitutive expression of Fas and FasL in 13 SCCHN cell lines by RT-PCR, Southern-blotting and immunocytochemistry, respectively. Administration of the agonistic Fas-antibody CH-11 led to a significant reduction of viable cells in the colorimetric MTT-assay in 5 out of 13 (38%) cell lines tested and preincubation with Interferon-gamma (IFN-gamma) rendered 3 (23%) primarily resistant cell lines sensitive. Cisplatin (cDDP) and bleomycin (BLM) caused dose-dependent cytotoxicity in all cell lines as determined by the 50% inhibitory concentration (IC(50)) and induction of apoptosis. Furthermore, both antineoplastic agents led to an enhanced surface expression of Fas and FasL in all cell lines, and this effect was independent of the respective p53-status. This upregulation of Fas/FasL surface expression increased preexisting Fas-sensitivity only, but failed to make primarily resistant cell lines undergo Fas-mediated growth reduction or apoptosis. Vice versa, blockade of Fas-receptor-ligand-interactions by monoclonal antibodies directed against FasL was able to attenuate the cytotoxic effect of cDDP and BLM in 2 out of 5 (40%) cell lines tested only. In conclusion, in contrast to many other solid tumors, the Fas/FasL-system does not seem to play an exclusive role in anticancer drug mediated apoptosis in SCCHN.

Chemotherapy and/or radiotherapy are established measures in treatment protocols of head and neck squamous cell carcinoma (HNSCC). However, we still lack reliable predictive markers for the response to radio- and chemotherapy. The p53 pathway is involved in stress response and thus might influence chemo-/radiosensitivity. Using 29 HNSCC cell lines previously characterized for p53 mutations, we simultaneously analyzed several key players in the p53 pathway by RT-PCR, transcript sequencing and immunohistochemistry, and investigated their association with chemosensitivity and radiosensitivity. Cell lines with p53 mutations were slightly more sensitive to cisplatin than those with wild-type p53. The type of mutation did not influence radio- or chemosensitivity. p14(ARF), an activator of p53, was lost or mutated in all cell lines. Three cell lines showed overexpression of HDM-2, a major negative regulator of p53; however, HDM-2 levels did not correlate with radio- or chemosensitivity. HPV-16 oncoproteins were detected in one highly chemoresistant cell line. Our findings suggest that molecular events resulting in the inactivation of the p53 pathway occur in all HNSCC cell lines. However, single alterations in the p53 pathway are not reliable predictors for the response to radio- or chemotherapy in HNSCC.

Background: Although bradykinin is known to play a major role in the pathophysiology of hereditary and angiotensin-converting enzyme inhibitor (ACEi)-induced angioedema, other factors acting as triggers or enhancers are likely important as well., Objective: We hypothesized that fibrinogen might contribute to ACEi-induced angioedema (eg, through direct actions on vascular tone)., Methods: Plasma levels of fibrinogen were determined in 59 patients with acute angioedema. Vascular activity of human and bovine fibrinogen and its effects on bradykinin-induced vasodilation and phosphorylation of vasodilator-stimulated phosphoprotein were investigated in small (0.8-1.4 mm in diameter) porcine coronary artery and human internal thoracic artery (ITA) segments., Results: In patients with ACEi-induced angioedema, fibrinogen levels (481 +/- 22 mg/dL, n = 39) were significantly higher than in patients with idiopathic angioedema (302 +/- 15 mg/dL, P < .001). Fibrinogen (1-15 mumol/L) induced a concentration-dependent vasodilation in preconstricted small porcine coronary arteries (n = 13), reaching a maximum vasodilator effect of 70% +/- 4.7%. Likewise, fibrinogen induced a 52.1% +/- 9.1% (n = 7) vasodilation in ITA rings. Fibrinogen vasorelaxations were completely inhibited by abciximab and diminished by endothelial denudation and treatment with the nitric oxide synthase inhibitor L-nitroargininemethylester and glibenclamide (P < .01). Importantly, fibrinogen increased the vasodilator potency of bradykinin by 10-fold (P < .0001) and increased bradykinin-induced vasodilator-stimulated phosphoprotein phosphorylation (P < .01)., Conclusion: The increase of plasma fibrinogen levels, its vasodilator activity in human ITAs, and the potentiation of bradykinin-induced vasodilation suggest that fibrinogen might contribute to the pathophysiology of ACEi-induced angioedema. Thus acute-phase proteins, such as fibrinogen, might be viewed as risk factors for bradykinin-induced angioedema.

To study the energetic costs of incubation in relation to clutch size, clutch sizes were manipulated and the metabolic rate of female great tits, Parus major (Linnaeus), during nocturnal incubation (MR(inc)) was measured using mobile oxygen analysers. Individuals were measured on consecutive nights while incubating their own or manipulated clutches. The experiment was performed under field conditions in order to place possible effects of clutch size manipulation within the context of other factors explaining variation in MR(inc). Females spent more energy when incubating enlarged clutches as compared with controls (6-10% more energy for three additional eggs) but did not spend significantly less energy when incubating reduced clutches. MR(inc) was strongly negatively related to ambient temperature. The effect of clutch enlargement is consistent with previous studies whereas the absence of an effect of clutch reduction is not. The small effect of clutch enlargement on MR(inc) highlights the need for further studies to include measurements of daily energy expenditure in order to judge how important energy expenditure can be in explaining fitness consequences of incubating experimentally enlarged clutches.

Objective: The objective was to compare the results of a complete chromosomal, genetic and histological investigation in 13 azoospermic men with the results of the intracytoplasmic sperm injection (ICSI) procedure., Study Design: Peripheral blood samples were used for the measurement of follicle-stimulating hormone (FSH) levels, chromosomal analysis, microdeletions in the azoospermia factor (AZF) region of the Y chromosome and cystic fibrosis transmembrane conductance regulator (CFTR) mutation analysis. Testicular tissue was used for histological scoring and cytogenetic evaluation., Results: Peripheral blood cytogenetic analysis revealed a normal male karyotype in all cases. Chromosomal analysis from testicular tissue revealed a mosaicism for the terminal deletion of chromosome 22 with a breakpoint site at 22q13 in one patient with congenital bilateral absence of the vas deferens (CBAVD). Deletions in the AZFa, ATFb, and AZFc regions were not detected. The CFTR mutational analysis showed normal results in all patients., Conclusions: Cytogenetic evaluation of testicular tissue should be performed in non-obstructive and obstructive azoospermic patients as well as in patients with multiple failed IVF and recurrent spontaneous abortion.

Objective: To compare efficacy and efficiency of ovarian stimulation therapy., Study Design: Retrospective study compares ovarian response as number of retrieved oocytes, fertilization rates, endometrial patterns, number of pregnancies and pregnancy rates to different stimulation protocols., Results: The least number of cancelled cycles was in long protocols with buserelin. There was no difference in overall number of retrieved oocytes between the rFSH and HMG protocols, but 75% of the patients undergoing both protocols had higher number of oocytes after rFSH. The highest pregnancy rate (35.13%) was with rFSH. There was no statistical correlation between endometrial pattern and type of protocol used. Data showed the 9 mm cut-off value for endometrial thickness, and RI = 0.58 for subendometrial blood flow between the pregnant and non-pregnant group of patients. Nitriderm patches significantly decreased (P < 0.05) subendometrial RI of the patients with impaired uterine perfusion, increased endometrial thickness and achieved better morphology., Conclusions: These findings demonstrate that rFSH alone and in long protocol gives better results in wide patient population. Nitriderm patches seem to have good impact on pregnancy rate, but further studies are necessary before making any statements.

A multicentre surveillance study comprising 26 laboratories located in Austria, Germany, and Switzerland was carried out in November 2001. A total of 787 isolates of Staphylococcus aureus and 456 isolates of Staphylococcus epidermidis mainly recovered from hospitalised patients, were tested. MICs for mupirocin were determined using the broth microdilution procedure. Breakpoints were < or = 4 mg/l (susceptible), 8-256 mg/l (low-level resistance) and > or = 512 mg/l (high-level resistance). Rates of low- and high-level resistances were 2.9 and 0.9% in S. aureus, and 9.4 and 3.3% in S. epidermidis, respectively. Mupirocin resistance was almost exclusively observed in oxacillin-resistant isolates of S. aureus (MRSA) and S. epidermidis (MRSE). High-level mupirocin resistance was detected in 3.1 and 4.5% of MRSA and MRSE, respectively., (Copyright 2004 Elsevier B.V.)

We determined the toxin-gene profiles of 239 endemic, invasive group A streptococcal (GAS) isolates that circulated, within a 5-year period, in European university hospitals. Profiling was performed by use of multiplex polymerase chain reaction that screened for 9 streptococcal pyrogenic exotoxins (speA, speB, speC, speF, speG, speH, speJ, ssa, and smeZ). Analysis revealed that invasive GAS isolates do not share a common toxin-gene profile. Although all emm types were characterized by several different toxin-gene profiles, a predominance of 1 or 2 toxin-gene profiles could be observed, reflecting that a few invasive clones have spread successfully throughout the world. Remarkably, statistical pair-wise analysis of individual toxin genes revealed that strains that did not share the predominant profile still showed a nonrandom distribution of key toxin genes characteristic of the specific emm type. This could indicate that M proteins function, directly or indirectly, as barriers for horizontal gene exchange.

Aims: Large oral doses of betaine have proved effective in lowering plasma homocysteine in severe hyperhomocysteinaemia. The pharmacokinetic characteristics and metabolism of betaine in humans have not been assessed and drug monitoring for betaine therapy is not available. We studied the pharmacokinetics of betaine and its metabolite dimethylglycine (DMG) in healthy subjects and in three patients with homocystinuria., Methods: Twelve male volunteers underwent an open-label study. After one single administration of 50 mg betaine kg-1 body weight and during continuous intake of twice daily 50 mg kg-1 body weight, serial blood samples and 24 h urines were collected to determine betaine and DMG plasma concentrations and urinary excretion, respectively. Patients were evaluated after one single dose of betaine., Results: We found rapid absorption (t(1/2),abs 00.28 h, s.d. 0.17) and distribution (t(1/2), lambda1 00.59 h, s.d. 0.22) of betaine. A Cmax of 0.94 mmol l-1 (s.d. 0.19) was reached after tmax 00.90 h (s.d. 0.33). The elimination half life t(1/2), z was 14.38 h (s.d. 7.17). After repeated dosage, t(1/2), lambda1 (01.77 h, s.d. 0.75) and t(1/2), z (41.17 h, s.d. 13.50) increased significantly (95% CI 0.73, 01.64 h and 19.90, 33.70 h, respectively), whereas absorption remained unchanged. DMG concentrations increased significantly after betaine administration and accumulation occurred to the same extent as with betaine. Renal clearance was low and urinary excretion of betaine was equivalent to 4% of the ingested dose. Distribution and elimination kinetics in homocystinuric patients appeared to be accelerated., Conclusions: Betaine plasma concentrations change rapidly after ingestion. Elimination half-life increased during continuous dosing over 5 days. Betaine is mainly eliminated by metabolism. More pharmacokinetic and pharmacodynamic studies in hyperhomocysteinaemic patients are needed to refine the current treatment with betaine.

Protein kinase C (PKC) plays a pivotal role in signal transduction involved in the control of cell proliferation, differentiation and apoptosis. Interference with such signaling pathways may result in altered tumor cell response to antineoplastic drugs. We investigated the effects of two selective PKC inhibitors as single agents and in combination with cisplatin in cell lines derived from squamous cell carcinomas of the head and neck (SCCHN). Safingol (Saf) is directed against the regulatory domain, whereas chelerythrine (Che) interacts with the catalytic domain of PKC. In six SCCHN cell lines (UM-SCC 11B, 14A, 14C and 22B, 8029NA, and a 5-fold cisplatin-resistant subline 8029DDP). PKC activities ranged between 1 and 158 IU/1 x 10(7) cells, and they were inversely proportional to the amount of cellular epidermal growth factor receptor. Using the colorimetric MTT assay, PKC inhibitors Saf and Che showed comparable dose-dependent growth inhibition. The 50% inhibitory concentrations (IC50) were between 3.8-8.6 microM for Saf and 8.5-13.6 microM for Che with no relationship to PKC activity or cisplatin sensitivity of the respective cell lines. Combinations of cisplatin (IC50 = 0.4-5.8 microg/ml) and either PKC inhibitor (5 microM Saf, 10 microM Che) led to a significant decrease of cisplatin IC50 values in most cell lines. However, comparison with theoretical additive dose-response curves showed additive rather than synergistic effects for both PKC inhibitors.

The prevalence of integrons in five enterobacterial species was analyzed in 900 blood culture isolates from 1993, 1996, and 1999. Remarkably, the prevalence increased from 4.7% in 1993 to 9.7% in 1996 and finally to 17.4% in 1999 (P < 0.01). Within 7 years the combined percentage of P1 strong promoters and P1 weak plus P2 active promoters with high transcription efficacies has increased from 23.1 to 33.3 and finally 60% (P < 0.05).

In a prospective multicenter study (1996 to 1999), 156 episodes of bacteremic streptococcal infections of neutropenic patients were evaluated. Streptococcus oralis (26.3%), S. pneumoniae (26.3%), S. agalactiae (11.5%), S. mitis (9%), and S. pyogenes (5.8%) were the predominant species. Four strains (2.6%) were found to be intermediately resistant to penicillin. One strain (0.6%) was found to be highly resistant to penicillin (MIC, 8 mg/liter). Reduced susceptibility to penicillin was detected among S. oralis (14.6%), S. mitis (7.1%), and S. pneumoniae (4.9%) isolates but was not recorded among S. agalactiae and S. pyogenes. Resistance rates and intermediate resistance rates for other antimicrobials were as follows (all species): amoxicillin, 1.3 and 3.2%; erythromycin, 16 and 2.6%; clindamycin, 5.8 and 0%; ciprofloxacin, 1.9 and 7.7%. Quinupristin-dalfopristin showed good in vitro activity against most streptococcal isolates (MIC at which 50% of the isolates were inhibited [MIC(50)], 0.5 mg/liter; MIC(90), 1 mg/liter, MIC range, 0.25 to 4 mg/liter).