Postoperative impairment of motor function at train-of-four ratio ≥0.9 cannot be improved by sugammadex (1 mg kg-1).

BACKGROUND: A train-of-four ratio (TOFR) ≥0.9 measured by quantitative neuromuscular monitoring is accepted as an indication of sufficient neuromuscular recovery for extubation, even though many postsynaptic acetylcholine receptors may still be inhibited. We investigated whether antagonism with sugammadex after spontaneous recovery to TOFR≥0.9 further improves muscle function or subjective well-being. METHODS: Following recovery to TOFR≥0.9 and emergence from anaesthesia, 300 patients randomly received either sugammadex 1.0 mg kg(-1) or placebo. Fine motor function (Purdue Pegboard Test) and maximal voluntary grip strength were measured before and after surgery (before and after test drug administration). At discharge from the postanaesthesia care unit, well-being was assessed with numerical analogue scales and the Quality-of-Recovery Score 40 (QoR-40). RESULTS: Patients' fine motor function [6 (sd 4) vs 15 (3) pegs (30 s)(-1), P<0.05] and maximal voluntary grip strength (284 (126) vs 386 (125) N, P<0.05) were significantly lower after anaesthesia compared with the pre-anaesthesia baseline. After sugammadex or placebo, motor function was significantly improved in both groups but did not reach the preoperative level. There was no difference between groups at any time. Global well-being was unaffected (QoR-40: placebo, 174 vs 185; sugammadex, 175 vs 186, P>0.05). CONCLUSIONS: Antagonizing rocuronium at TOF≥0.9 with sugammadex 1.0 mg kg(-) (1) did not improve patients' motor function or well-being when compared with placebo. Our data support the view that TOFR≥0.9 measured by electromyography signifies sufficient recovery of neuromuscular function. CLINICAL TRIAL REGISTRATION: The trial is registered at ClinicalTrials.gov (NCT01101139).

Clostridium perfringens is not suitable for the indication of fecal pollution from ruminant wildlife but is associated with excreta from nonherbivorous animals and human sewage.

During a 3-year study, Clostridium perfringens was investigated in defined fecal sources from a temperate alluvial backwater area of a large river system. The results reveal that using C. perfringens as a conservative water quality indicator for total fecal pollution monitoring is no longer justified but suggest that it can be used as a tracer for excreta from nonherbivorous wildlife and human sewage.

Gastrointestinal chemosensation: chemosensory cells in the alimentary tract.

Sensing potentially beneficial or harmful constituents in the luminal content by specialized cells in the gastrointestinal mucosa is an essential prerequisite for governing digestive processes, initiating protective responses and regulating food intake. Until recently, it was poorly understood how the gastrointestinal tract senses and responds to nutrients and non-nutrients in the diet; however, the enormous progress in unraveling the molecular machinery underlying the responsiveness of gustatory cells in the lingual taste buds to these compounds has been an important starting point for studying intestinal chemosensation. Currently, the field of nutrient sensing in the gastrointestinal tract is evolving rapidly and is benefiting from the deorphanization of previously unliganded G-protein-coupled receptors which respond to important nutrients, such as protein degradation products and free fatty acids as well as from the FACS-assisted isolation of distinct cell populations. This review focuses on mechanisms and principles underlying the chemosensory responsiveness of the alimentary tract. It describes the cell types which might potentially contribute to chemosensation within the gut: cells that can operate as specialized sensors and transducers for luminal factors and which communicate information from the gut lumen by releasing paracrine or endocrine acting messenger molecules. Furthermore, it addresses the current knowledge regarding the expression and localization of molecular elements that may be part of the chemosensory machinery which render some of the mucosal cells responsive to constituents of the luminal content, concentrating on candidate receptors and transporters for sensing nutrients.

Clinical feasibility evaluation of digital dental articulation for three-piece maxillary orthognathic surgery: a proof-of-concept study.

Digital dental articulation for three-piece maxillary orthognathic surgery is challenging. The purpose of this proof-of-concept study was to evaluate the clinical feasibility of a newly developed mathematical algorithm to digitally establish the final occlusion for three-piece maxillary surgery. Five patients with jaw deformities who had undergone a three-piece double-jaw surgery that was planned virtually were randomly selected for this study. The final occlusion had been hand-articulated using stone casts, scanned into the computer and used in the surgery. These hand-articulated occlusions served as the control group. To form the experimental group, the three-piece maxillary dental arch was articulated again automatically from the patient's original occlusion using the mathematical algorithm. The hand- and algorithm-articulated occlusions were then evaluated qualitatively by two experienced orthodontists. A quantitative evaluation was also performed. The results of the qualitative evaluation showed that all of the three-piece occlusions, hand- and algorithm-articulated, were clinically acceptable based on the American Board of Orthodontics grading system. When compared, two of the algorithm-articulated occlusions were clearly better (40%), one was the same (20%), and two were slightly worse (40%) than the hand-articulated occlusions. All of the quantitative measurements were comparable between the two articulation methods. In conclusion, the results of this study demonstrate that it is clinically feasible to digitally articulate the three-piece maxillary arch to the intact mandibular dental arch.

Maternal obesity in pregnancy impacts offspring cardiometabolic health: Systematic review and meta-analysis of animal studies.

Obesity before and during pregnancy leads to reduced offspring cardiometabolic health. Here, we systematically reviewed animal experimental evidence of maternal obesity before and during pregnancy and offspring anthropometry and cardiometabolic health. We systematically searched Embase and Medline from inception until January 2018. Eligible publications compared offspring of mothers with obesity to mothers with a normal weight. We performed meta-analyses and subgroup analyses. We also examined methodological quality and publication bias. We screened 2543 publications and included 145 publications (N = 21 048 animals, five species). Essential methodological details were not reported in the majority of studies. We found evidence of publication bias for birth weight. Offspring of mothers with obesity had higher body weight (standardized mean difference (SMD) 0.76 [95% CI 0.60;0.93]), fat percentage (0.99 [0.64;1.35]), systolic blood pressure (1.33 [0.75;1.91]), triglycerides (0.64 [0.42;0.86], total cholesterol (0.46 [0.18;0.73]), glucose level (0.43 [0.24;0.63]), and insulin level (0.81 [0.61;1.02]) than offspring of control mothers, but similar birth weight. Sex, age, or species did not influence the effect of maternal obesity on offspring's cardiometabolic health. Obesity before and during pregnancy reduces offspring cardiometabolic health in animals. Future intervention studies should investigate whether reducing obesity prior to conception could prevent these detrimental programming effects and improve cardiometabolic health of future generations.

Progression of dysautonomia in multiple system atrophy: a prospective study of self-perceived impairment.

To assess severity and progression of self-perceived dysautonomia and their impact on health-related quality of life (Hr-QoL) in multiple system atrophy (MSA), twenty-seven patients were recruited by the European MSA Study Group (EMSA-SG). At baseline, all patients completed the Composite Autonomic Symptom Scale (COMPASS) and the 36 item Short Form Health Survey (SF-36), and they were assessed using the 3-point global disease severity scale (SS-3) and the Unified MSA Rating Scale (UMSARS). After 6 months follow-up, the self completed COMPASS Change Scale (CCS), the SF-36, SS-3, and UMSARS were obtained. MSA patients showed marked self-perceived dysautonomia at baseline visit and pronounced worsening of dysautonomia severity on the CCS at follow-up. Severity and progression of dysautonomia did not correlate with age, disease duration, motor impairment and overall disease severity at baseline. There were no significant differences between genders and motor subtypes. Baseline COMPASS scores were, however, inversely correlated with SF-36 scores. Progression of self-perceived dysautonomia did not correlate with global disease progression. Hr-QoL scores were stable during follow-up. This is the first study to investigate self-perceived dysautonomia severity in MSA and its evolution over time. Our data suggest that dysautonomia should be recognized as a key target for therapeutic intervention in MSA.

Molecular basis for the insensitivity of the Monarch (Danaus plexippus) to cardiac glycosides.

The Monarch (Danaus plexippus) sequesters cardiac glycosides for its chemical defence against predators. Larvae and adults of this butterfly are insensitive towards dietary cardiac glycosides, whereas other Lepidoptera, such as Manduca sexta and Creatonotos transiens are sensitive and intoxicated by ouabain. Ouabain inhibits the Na+,K(+)-ATPase by binding to its alpha-subunit. We have amplified and cloned the DNA sequence encoding the respective ouabain binding site. Instead of the amino acid asparagine at position 122 in ouabain-sensitive insects, the Monarch has a histidine in the putative ouabain binding site, which consists of about 12 amino acids. This change may explain the ouabain insensitivity.

Acid phosphatase test proves superior to standard phenotypic identification procedure for Clostridium perfringens strains isolated from water.

Clostridium perfringens is used as an indicator for persistent faecal pollution as well as to monitor the efficacy of water treatment processes. For these purposes, differentiation between C. perfringens and other Clostridia is essential and is routinely carried out by phenotypic standard tests as proposed in the ISO/CD 6461-2:2002 (ISO_LGMN: lactose fermentation, gelatine liquidation, motility and nitrate reduction). Because the ISO_LGMN procedure is time consuming and labour intensive, the acid phosphatase test was investigated as a possible and much more rapid alternative method for confirmation. The aim of our study was to evaluate and compare confirmation results obtained by these two phenotypic methods using genotypically identified strains, what to our knowledge has not been accomplished before. For this purpose, a species specific PCR method was selected based on the results received for type strains and genotypically characterised environmental strains. For the comparative investigation type strains as well as presumptive C. perfringens isolates from water and faeces samples were used. The acid phosphatase test revealed higher percentage (92%) of correctly identified environmental strains (n=127) than the ISO_LGMN procedure (83%) and proved to be a sensitive and reliable confirmation method.

Correlation between critical temperature and strength of small-scale bcc pillars.

Microcompression tests were performed on focused-ion-beam-machined micropillars of several body-centered-cubic metals (W, Mo, Ta, and Nb) at room temperature. The relationship between yield strength and pillar diameter as well as the deformation morphologies were found to correlate with a parameter specific for bcc metals, i.e., the critical temperature T(c). This finding sheds new light on the phenomenon of small-scale plasticity in largely unexplored non-fcc metals.

Vagus nerve stimulation for depression: efficacy and safety in a European study.

BACKGROUND: Vagus nerve stimulation (VNS) therapy is associated with a decrease in seizure frequency in partial-onset seizure patients. Initial trials suggest that it may be an effective treatment, with few side-effects, for intractable depression. METHOD: An open, uncontrolled European multi-centre study (D03) of VNS therapy was conducted, in addition to stable pharmacotherapy, in 74 patients with treatment-resistant depression (TRD). Treatment remained unchanged for the first 3 months; in the subsequent 9 months, medications and VNS dosing parameters were altered as indicated clinically. RESULTS: The baseline 28-item Hamilton Depression Rating Scale (HAMD-28) score averaged 34. After 3 months of VNS, response rates (> or = 50% reduction in baseline scores) reached 37% and remission rates (HAMD-28 score <10) 17%. Response rates increased to 53% after 1 year of VNS, and remission rates reached 33%. Response was defined as sustained if no relapse occurred during the first year of VNS after response onset; 44% of patients met these criteria. Median time to response was 9 months. Most frequent side-effects were voice alteration (63% at 3 months of stimulation) and coughing (23%). CONCLUSIONS: VNS therapy was effective in reducing severity of depression; efficacy increased over time. Efficacy ratings were in the same range as those previously reported from a USA study using a similar protocol; at 12 months, reduction of symptom severity was significantly higher in the European sample. This might be explained by a small but significant difference in the baseline HAMD-28 score and the lower number of treatments in the current episode in the European study.

Uptake and sequestration of ouabain and other cardiac glycosides inDanaus plexippus (Lepidoptera: Danaidae): Evidence for a carrier-mediated process.

Larvae ofDanaus plexippus feed almost exclusively on milkweed species of the genusAsclepias, whose characteristic secondary metabolites are cardiac glycosides (CGs). Aposematic last-instar larvae were fed with ouabain and other cardiac glycosides of differing polarities. Time course experiments show that ouabain is sequestered in the integument within 48 hr after feeding, whereas midgut tissue and hemolymph function as transient CG storage compartments. About 63% of ouabain was transferred from larvae to the butterflies, whereas 37% of ouabain was lost with larval and pupal exuviae and with the meconium. The main sites of storage in imagines are wings and integument. If mixtures of CGs are fed toD. plexippus larvae, differential sequestration can be observed: The polar ouabain contributes 58.8% of total CGs, followed by digitoxin (19.6%), oleandrin (10.6%), digoxin (4.9%), digoxigenin (4.6%) and proscillaridin A (1.5%). Thus, uptake and sequestration must be selective processes. Uptake of [(3)H]ouabain in vitro by isolated larval midguts was time-, pH-, and temperature-dependent and displayed an activation energy of 49 kJ/mol. Furthermore, the in vitro uptake of ouabain was inhibited (probably competitively) by the structurally similar convallatoxin. These data provide first evidence that ouabain uptake does not proceed by simple diffusion but with the aid of a carrier mechanism, which would explain the differential cardenolide uptake observed in living larvae.

The weight of the evidence among group C carcinogens.

Pesticide chemicals (more than 40) with limited evidence for carcinogenicity in animal experiments, and assigned to Group C according to the EPA Guidelines for Carcinogen Risk Assessment, were further analyzed and ranked by refining the weight of the evidence evaluation. For some of these chemicals there were considerable concern with respect to their potential as human carcinogens and for others there was minimal concern. A clear tumor response at several doses, malignancy of the tumors, the tumor type (rare versus common), the timing of the tumor, and the observance of tumors in both sexes raised the concern for potential human carcinogenicity, as did ancillary information such as the structure-activity relationship and genotoxicity. The design and quality of the studies used in the evaluation were significant factors in reaching a conclusion concerning the carcinogenic potential of the chemicals. Potency factors (Q1*) calculated for these chemicals indicated no correlation with the level of biological evidence for carcinogenicity.

[The growth and lipopolysaccharide production of Escherichia coli and Pseudomonas aeruginosa]. / Vermehrung und Lipopolysaccharidbildung von Escherichia coli und Pseudomonas aeruginosa.

The course of growth and LPS production of two strains of type cultures of Escherichia coli (ATCC 11229, ATCC 25922), one E. coli mutant strain P400 and one type strain of Pseudomonas aeruginosa (ATCC 15442), grown partly by repeated cultures in BHI and partly also in minimal medium or in 1:10 diluted PC broth in a gyratory shaker (60 rpm) at 30 degrees C, was monitored respectively by counting the cfu and by simultaneous determination of LPS by means of the three miniaturized LAL-tests, i.e. the capillary test, the "Mini" endotoxin test and the Coatest endotoxin method. All three tests yielded generally comparable and reproducible results. The LPS content for a defined number of cfu was virtually in the same order of magnitude in all cases, regardless of the nutrient content of the culture medium. The quantity of LPS was relatively high in the initial phases of growth but then decreased significantly to constant levels in the stationary phase. There was a remarkable increase in the yield of LPS in the mid- and late stages of the exponential phase in the three strains, in contrast to the mutant in which the LPS content declined continuously. A possible explanation for this variation could be due to the fact that specific cell membrane proteins, which are lacking in the mutant, react differently with the LPS and thus with the Limulus Amoebocyte lysate. When the LAL tests are used for the rapid determination of the gram negative bacterial load of in particular perishable fresh foods, in which generally bacterial cells are at different stages of the exponential growth phase, then it is necessary to standardize each method specifically both for the product and for the storage conditions.

[Comparison of three miniaturized Limulus-amoebocyte-lysate methods]. / Vergleich von drei miniaturisierten Limulus-Amoebocyten-Lysat Methoden.

Comparative examinations with three different micro-models for the LAL-test methods,--namely the capillary test, Endotoxin-test "Mini" and Coatest-Endotoxin-method-, tested with 11 Enterobacteriaceae- and 6 Pseudomonas-type-strains and isolates from foods gave only slight differences for the endotoxin content. Out of 250 single measurements per test method the capillary test as well as the Coatest-Endotoxin-method gave count limits between 2.8 X 10(1) and 7.4 X 10(3) CFU/ml. For the endotoxin-test method "Mini" the limits were one log unit higher-namely between 8.6 X 10(2) and 5.0 X 10(4) CFU/ml. The maximum values for count limits of all three methods correspond to approximately 1 ng Endotoxin. For the two gel test methods a relative error of +/- 15% has to be taken into account; for the chromogen method however, the relative error lies within +/- 25%, if the concentration is 0.0125 ng LPS/ml or lower. Between 0.025 and 0.1 ng LPS/ml or 0.075 and 0.1 ng LPS/ml the relative error is reduced to +/- 16% and +/- 5% respectively. The study has shown that the three micro tests in question as tested with pure cultures give comparable and reproducible results; inspite of the high relative error.

[The effect of temperature on the growth and lipopolysaccharide production of gram-negative bacteria]. / Einfluss der Temperatur auf Vermehrung und Lipopolysaccharidbildung von Gram-negativen Bakterien.

5 strains of Pseudomonas and 7 of Enterobacteriaceae were cultivated in a Temperature Gradient Incubator (TGI) in intervals of 5 degrees C over a linear temperature gradient of 4 to 48 degrees C. After attaining the stationary growth phase the amount of lipopolysaccharides (LPS) formed was determined by means of the three LAL tests, i.e. the Capillary test, the "Mini" Endotoxin test and the Coatest endotoxin method. Simultaneously, the colony count was carried out. The same was done for one strain of E. coli in the exponential growth phase after continuous cultivation in 5 degrees C intervals over the range 10 to 35 degrees C. With the exception of the E. coli mutant P400, the lowest amounts of LPS produced in the stationary phase per 10(9) cfu was determined between 20 and 30 degrees C. Increasing or decreasing temperatures caused a more or less sharp rise in the quantity of LPS formed in the stationary phase. This was also demonstrated for E. coli in the exponential phase. For the E. coli mutant P400, however, the LPS content was highest at lower growth temperatures but decreased with increasing temperatures. Changes in the composition of fatty acids and sugars of the LPS and of membrane protein, which are dependent on the temperature of growth apparently alter the steric structure of the LPS which react with the LAL system, and could thus be responsible for the increased LPS found at the lower and higher growth temperatures. In the use of the LAL-tests methods for the assessment of the bacterial load of foods with gram negative bacteria, it is necessary, especially for cold stored products, to test for and determine the LPS-cfu relationship beforehand.

[Colony count and LPS content of gram-negative bacteria in cold storage foods and water]. / Koloniezahlen und LPS-Gehalte Gram-Negativer Bakterien in kühlgelagerten Lebensmitteln und Wasser.

In storage trials, the multiplication of gram negative bacteria was monitored by means of both colony counts and LPS-formation as determined by the three LAL tests methods (the Capillary test, the "Mini" Endotoxin test and the Coatest endotoxin method). The detection limits of the colony forming units which could be determined by the three LAL tests were initially set in model experiments in which beef (M. cleidooccipitalis) was variously inoculated with stationary-phase cells of Pseudomonas sp. previously grown at 30 degrees C. In all three methods, measurable amounts of LPS were possible only at colony counts above 10(3)/ml, g or cm2. The detection limits for colony counts of vacuum packed, aerobically stored beef muscle (Caput long. of M. triceps brachii) were found to lie between 1.0 x 10(3) and 1.0 x 10(4)/g for the Capillary test and the Coatest endotoxin method, and 5.0 x 10(4)/g for the "Mini" Endotoxin test. In the case of poultry carcasses the detection limits lay between 2.0 x 10(1) and 7.0 x 10(2)/cm2 and were thus considerably lower than for beef. With very low levels of bacterial loads, substrate interference in the LPS-LAL reaction must be taken into account. Linear regression analysis gave satisfactory correlation between the concentration of LPS and colony forming units for beef, poultry carcasses, ground beef and mixed salad. An acceptable proportionality was established only for beef and poultry carcasses. Potable water, stagnant for a fortnight in an experimental piping system and sampled at five different points, showed significant regrowth of oligocarbotolerant aquatic bacteria. However, only very low levels of LPS could be determined. All three LAL test methods can be recommended for rapid determination of the load of gram negative bacteria in meat and meat products.

The gene encoding IFP 53/tryptophanyl-tRNA synthetase is regulated by the gamma-interferon activation factor.

We have obtained genomic DNA encoding the interferon-gamma (IFN-gamma)-inducible IFP 53/tryptophanyl-tRNA synthetase. Comparison with several different IFP 53 cDNA clones revealed a complex pattern of alternatively spliced 5'-untranslated regions. The interferon-responsive region within the IFP 53 promoter was found to contain a gamma-interferon activation site (GAS) but not the interferon-stimulated response element and to bind the gamma-interferon activation factor (GAF). GAF.GAS complexes contained the IFN-regulated 91-kDa protein. Competition experiments defined the GAS boundaries and showed that GAF binding to the IFP 53 GAS could be prevented by an excess of the IFN-gamma response regions of several other IFN-gamma-inducible genes. We thus provide evidence for a central role of GAS.GAF in gene transcription mediated by IFN-gamma and suggest a consensus sequence defining more precisely the requirements for GAF binding to DNA.