Activity of imipenem/relebactam against Enterobacterales and Pseudomonas aeruginosa in Spain. SMART 2016-2020.

OBJECTIVE: To determine susceptibility to the novel ß-lactam/ß-lactamase inhibitor combination imipenem/relebactam in clinical isolates recovered from intra-abdominal (IAI), urinary (UTI), respiratory (RTI) and bloodstream (BSI) infections in the SMART (Study for Monitoring Antimicrobial Resistance Trends) study in SPAIN during 2016 - 2020. METHODS: Broth microdilution MICs for imipenem/relebactam and comparators were determined by a central laboratory against isolates of Enterobacterales and Pseudomonas aeruginosa. MICs were interpreted using EUCAST-2021 breakpoints. RESULTS: In total, 5,210 Enterobacterales and 1,418 P. aeruginosa clinical isolates were analyzed. Imipenem/relebactam inhibited 98.8% of Enterobacterales. Distinguishing by source of infection susceptibility was 99.1% in BSI, 99.2% in IAI, 97.9% in RTI, and 99.2% in UTI. Of intensive care unit isolates (ICU) 97.4% were susceptible and of non-ICU isolates 99.2% were susceptible. In Enterobacterales, activity against Class A, Class B and Class D carbapenemases was 96.2%, 15.4% and 73.2%, respectively. In P. aeruginosa, imipenem/relebactam was active in 92.2% of isolates. By source of infection it was 94.8% in BSI, 92.9% in IAI, 91.7% in RTI, and 93.1% in UTI. An 88.7% of ICU isolates and 93.6% of non-ICU isolates were susceptible to imipenem/relebactam. Imipenem/relebactam remained active against P. aeruginosa ceftazidime-resistant (76.3%), cefepime-resistant (73.6%), imipenem-resistant (71.5%) and piperacillin-resistant (78.7%) isolates. Of all multidrug-resistant or difficult-to-treat resistance P. aeruginosa isolates, 75.1% and 46.2%, respectively, were susceptible to imipenem/relebactam. CONCLUSIONS: Imipenem/relebactam showed high rates of susceptibility in Enterobacterales and P. aeruginosa isolates from different sources of infection as well as depending on patients' location (ICU or non-ICU scenarios).

[Unexpected out-of-hospital deliveries: Management and risk factors]. / Accouchement inopiné extrahospitalier : prise en charge et facteur de risque.

OBJECTIVES: To estimate the frequency of accidental out-of-hospital deliveries (OHDs), to describe the home care and the complications occurred, and to identify risk factors. MATERIALS AND METHODS: A retrospective case-control study from 1st January 2012 to 31 December 2012 in Lyon urban area. Cases were identified from the Emergency Medical Aid Service 69 (SAMU 69) registry and control from the birth registry of the maternity corresponding to the case, recruiting two controls per case. RESULTS: The frequency of the OHDs was 0.3% [0.2-0.4]. At home, the prophylactic administration of oxytocin was performed in 18.3% [9.31-27.3] of cases and prevention of neonatal hypothermia was performed in 45.7% [34.1%-57.3%] of cases. Multiparity [OR: 3.43 (1.65-7.23)], a precarious situation [OR: 37.63 (5.02-7.81)], and lack of antenatal care [OR: 3.36 (2.72-4.15)] were OHDs' risk factors. CONCLUSION: The practical prevention of postpartum hemorrhage, and that of the home neonatal hypothermia could be improved. Points of vigilance for the medical teams to look for during the pregnancy monitoring are precariousness and less than 3 consultations scheduled.

Flexible attosecond beamline for high harmonic spectroscopy and XUV/near-IR pump probe experiments requiring long acquisition times.

We describe the versatile features of the attosecond beamline recently installed at CEA-Saclay on the PLFA kHz laser. It combines a fine and very complete set of diagnostics enabling high harmonic spectroscopy (HHS) through the advanced characterization of the amplitude, phase, and polarization of the harmonic emission. It also allows a variety of photo-ionization experiments using magnetic bottle and COLTRIMS (COLd Target Recoil Ion Momentum Microscopy) electron spectrometers that may be used simultaneously, thanks to a two-foci configuration. Using both passive and active stabilization, special care was paid to the long term stability of the system to allow, using both experimental approaches, time resolved studies with attosecond precision, typically over several hours of acquisition times. As an illustration, applications to multi-orbital HHS and electron-ion coincidence time resolved spectroscopy are presented.

Single-shot diffractive imaging with a table-top femtosecond soft x-ray laser-harmonics source.

Coherent x-ray diffractive imaging is a powerful method for studies on nonperiodic structures on the nanoscale. Access to femtosecond dynamics in major physical, chemical, and biological processes requires single-shot diffraction data. Up to now, this has been limited to intense coherent pulses from a free electron laser. Here we show that laser-driven ultrashort x-ray sources offer a comparatively inexpensive alternative. We present measurements of single-shot diffraction patterns from isolated nano-objects with a single 20 fs pulse from a table-top high-harmonic x-ray laser. Images were reconstructed with a resolution of 119 nm from the single shot and 62 nm from multiple shots.

Detection of DNA hybridization by ABEI electrochemiluminescence in DNA-chip compatible assembly.

The electrochemiluminescence (ECL) of a luminol derivate (ABEI) generated both by a carbon electrode and a polypyrrole-coated carbon electrode was examined. It was found that the polypyrrole film (ppy) did not inhibit the ECL. After that, ABEI anchored on a single stranded DNA target (ODNt) has been used for the ECL detection of the hybridization between a complementary single stranded DNA probe (ODNp) covalently linked to a polypyrrole support and the ODNt. The ECL detection has been performed using a DNA sensor having a low surface concentration of ODNp probes, constituted of a polypyrrole copolymer electrosynthesized from a pyrrole-ODNp/pyrrole monomer ratio of 1/20,000.

Comparison by QCM and photometric enzymatic test of the biotin-avidin recognition on a biotinylated polypyrrole.

By gravimetric measurements using a quartz cristal microbalance (QCM), we have studied the immobilization of biotinylated glucose oxidase enzymes (B-GOx) bound through on an intermediate avidin layer to a biotinylated polypyrrole film. The aim is to assess the amount of B-GOx specifically anchored on the biotinylated polypyrrole/avidin assembly thank to the biotin/avidin interaction between avidin and B-GOx. Indeed the estimated amount from the QCM measurement corresponds to the specific recognition of avidin/B-GOx added to a non-specific recognition (adsorption) of B-GOx. In order to discriminate these two phenomena, we have carried out a study by QCM of the anchoring of B-GOx on an avidin layer linked by adsorption to a polypyrrole free from biotin units. From QCM measurements we have deduced for the biotinylated polypyrrole/avidin assembly that the amount of B-GOx bound via the biotin/avidin interaction and those due to the avidin adsorption process correspond to 3.9 pmol cm(-2) (1.3 equivalent of B-Gox monolayer) and 1.4 pmol cm(-2) (0.46 equivalent of B-GOx monolayer) respectively. These values have been corroborated by measurements of the enzymatic activity of GOx.

The dynamics of human isometric pointing movements under varying accuracy requirements.

The goal of the present study was to explore the relation between speed-accuracy trade-off phenomena and action kinematics in the case of pointing under isometric conditions. Increasing task difficulty resulted in a linear increase in movement time (as predicted by Fitts' law) and in systematic changes in the spatio-temporal patterning of force production. The observed changes in motion topology were similar to those reported for isotonic tasks and adequately captured by a limit cycle model derived for the latter type of task. These results indicate that, for isometric force control as for isotonic position control, the reasons underlying the emergence of Fitts' law might be sought in dynamic trajectory formation processes.

Electropolymerization as a versatile route for immobilizing biological species onto surfaces. Application to DNA biochips.

Biosensors based on electronic conducting polymers appear particularly well suited to the requirements of modern biological analysis--multi-parametric assays, high information density, and miniaturization. We describe a new methodology for the preparation of addressed DNA matrices. The process includes an electrochemically directed copolymerization of pyrrole and oligonucleotides bearing on their 5' end a pyrrole moiety. The resulting polymer film deposited on the addressed electrode consists of pyrrole chains bearing covalently linked oligonucleotides (ODN). An oligonucleotide array was constructed on a silicon device bearing a matrix of 48 addressable 50 x 50 microns gold microelectrodes. This technology was successfully applied to the genotyping of hepatitis C virus in blood samples. Fluorescence detection results show good sensitivity and a high degree of spatial resolution. In addition, gravimetric studies carried out by the quartz crystal microbalance technique provide quantitative data on the amount of surface-immobilized species. In the case of ODN, it allows discrimination between hybridization and nonspecific adsorption. The need for versatile processes for the immobilization of biological species on surfaces led us to extend our methodology. A biotinylated surface was obtained by coelectropolymerization of pyrrole and biotin-pyrrole monomers. The efficiency for recognition (and consequently immobilization) of R-phycoerythrin-avidin was demonstrated by fluorescence detection. Copolymerization of decreasing ratios of pyrrole-biotin over pyrrole allowed us to obtain a decreasing scale of fluorescence.

The Timing Effects of Accent Production in Periodic Finger-Tapping Sequences.

When subjects are required to produce short sequences of equally paced finger taps and to accentuate one of the taps, the interval preceding the forceful tap is shortened and the one that immediately follows the accent is lengthened. Assuming that the tapping movements are triggered by an internal clock, one explanation attributes the rnistiming of the taps to central factors: The momentary rate of the clock is accelerated or decelerated as a function of motor preparation to, respectively, increase or decrease the movement force. This hypothesis predicts that the interresponse intervals measured between either tap movement onsets or movement terminations (taps) will show the same timing pattern. A second explanation for the observed interval effects is that the tapping movements are triggered by a regular internal clock but the timing of the successive taps is altered because the forceful movement is completed in less time than the other tap movements are. This "peripheral" hypothesis predicts regular timing of movement onsets but distorted timing of movement terminations. In the present study, the trajectories of the movements performed by subjects were recorded and the interresponse intervals were measured at the beginning and the end of the tapping movements. The results of Experiment 1 showed that neither model can fully explain the interval effects: The fast forceful movements were initiated with an additional delay that took into account the small execution time of these movements. Experiment 2 reproduced this finding and showed that the timing of the onset and contact intervals did not evolve with the repetition of trial blocks. Therefore, the assumption of an internal clock that would trigger the successive movements must be rejected. The results are discussed in the framework of a modified two-stage model in which the internal clock, instead of triggering the tapping movements, provides target time points at which the movements have to produce their meaningful effects, that is, contacts with the response key. The timing distortions are likely to reflect both peripheral and central components.

The role of sensory information in the production of periodic finger-tapping sequences.

A subject lacking proprioceptive and tactile sensibility below the neck and a group of control subjects performed sequences of periodic finger taps involving a pattern of accentuation. The required intertap interval was 700 ms. In some situations, the taps were synchronized with the clicks of a metronome. Feedback conditions were manipulated by either allowing or not allowing the subjects to hear the taps and see their finger movements. We recorded the trajectory of the subjects' finger displacement in the vertical plane, and the force and moment of contact of the finger with the response key. The control subjects achieved precise timing of the finger taps by trading off downstroke onset for movement duration, e.g., they initiated shorter-duration tapping movements with a delay. This strategy did not vary depending on task demands (e.g., synchronization) or feedback conditions. The deafferented patient produced intertap intervals on average close to the required value. However, his tap timing was characterized by increased variability and severe distortion (lengthening) after the accentuated tap, regardless of feedback conditions. He did not manifest the compensatory strategy whereby, in control subjects, movement onset was adjusted to movement duration. Thus, such a strategy in controls seems to depend on intact proprioceptive and/or tactile information from the moving limb. Upon withdrawal of visual and acoustic feedback, the deafferented subject increased the force of the taps and the amplitude of tapping movements; his mean synchronization error with the metronome also increased. However, he did not lose correct phasing between the taps and the clicks of the metronome. These findings suggest that, under normal circumstances, sequential movements are timed by an internal timekeeper which paces sensory consequences relating to the occurrence of behaviorally important events (e.g., finger taps), and not the onset of the movements eliciting those events. In the synchronization task, the timekeeper may be phase locked to the periodic acoustic stimuli by direct entrainment. Feedback information may be needed, however, for keeping any synchronization error as small as possible.

Ability of different flavonoids to inhibit the procoagulant activity of adherent human monocytes.

Sixty-five natural flavonoids of various chemical classes were screened for their ability to inhibit the procoagulant activity of adherent human monocytes stimulated by endotoxin and interleukin-1 beta in vitro. Eighteen of these compounds inhibited the interleukin-1 beta-induced expression of tissue factor on human monocytes, but the most active compound was a biflavonoid: hinokiflavone.

Adrenergic regulation of glycogenolysis in rat liver after cholestasis. Modulation of the balance between alpha 1 and beta 2 receptors.

The effects of extrahepatic cholestasis upon adrenergic regulation of glycogenolysis and upon the numbers of adrenoceptors in rat liver were studied using isolated hepatocytes and plasma membranes, respectively. A 60% decrease in the number of alpha 1 adrenoceptors (285 vs. 680 fmol/mg protein) and a simultaneous 2.7-fold increase in the number of beta adrenergic sites (67 vs. 25 fmol/mg protein) were observed beginning 36 h after bile flow obstruction and persisted for at least 68 h. The reciprocal modification of the numbers of alpha 1 and beta adrenoceptors was accompanied by a change in the manner of stimulation of glycogen phosphorylase by catecholamines in hepatocytes; originally alpha 1 adrenergic in normal rats (phenylephrine Ka = 0.9 microM, isoproterenol Ka = 7.1 microM), the stimulation became predominantly beta adrenergic in cholestatic animals (phenylephrine Ka = 3.7 microM, isoproterenol Ka = 0.06 microM). In normal rats, activation of the enzyme by epinephrine was inhibited by the alpha blocker phentolamine, without inhibition by the beta blocker propranolol. In contrast, propranolol was more effective than phentolamine in cholestatic rat hepatocytes. Modification of the regulation of glycogenolysis after cholestasis did not seem to be secondary to an alteration in the metabolism of thyroid hormones or in the action of glucocorticoids. However, cholestasis provoked a 10-fold increase in the number of hepatic mitoses and in the incorporation of thymidine into liver DNA of cholestatic animals. Similar changes were observed in regenerating livers, following two-thirds hepatectomy. We propose that the changes following extrahepatic cholestasis might, as well, be explained by a regenerative process.

The hormonal induction of gamma glutamyltransferase in rat liver and in a hepatoma cell line.

Gamma glutamyltransferase (GGT) is a membrane-bound enzyme that is involved in glutathione metabolism and aminoacids uptake. GGT activity is stimulated by a number of hormones and pharmacological agents in certain animal tissues. In rat liver, adrenalectomy causes a 2-fold decrease in GGT activity and hydrocortisone treatment of adrenalectomized animals specifically stimulates this enzyme activity. In a highly differentiated hepatoma cell line, Fao, GGT activity is similar to rat liver and is under glucocorticoids control. These hormones specifically stimulate GGT activity (2- to 3-fold). Translation and transcription inhibitors prevent the hormonal effect. The stimulation of GGT activity is therefore probably due to an increase in GGT mRNA synthesis. The results reported suggest that the Fao cell line is a very convenient system for the study of the molecular mechanisms of both the glucocorticoid effects on differentiated cells as well as the modulation of membrane-bound enzymes biosynthesis.

Glucocorticoid hormones increase the activity of gamma-glutamyltransferase in a highly differentiated hepatoma cell line.

Gamma-Glutamyltransferase activity was detected in the plasma membrane of the highly differentiated hepatoma cell line Fao, (0.93 mU/mg cell protein). Dexamethasone (1 microM) provoked a 2-3-fold increase in the activity of the enzyme in the presence of fetal calf serum. Maximal induction occurred 48-72 h after addition of the glucocorticoid to the cell culture medium. The hormonal specificity was demonstrated by the relative potencies of several glucocorticoids and sex steroids: hydrocortisone and corticosterone increased gamma-glutamyltransferase activity while tetrahydrocorticosterone and all sex steroids tested were ineffective. The effect of dexamethasone on gamma-glutamyltransferase activity wa specific since the activities of several other plasma membrane enzymes were not modified. The mechanism of the dexamethasone-induced increase in gamma-glutamyltransferase activity was neither by modification of the affinity of the enzyme for its substrates nor by alteration of the subcellular distribution of the enzyme. This increase was prevented by cycloheximide and actinomycin D. The data presented are consistent with a specific glucocorticoid receptor-mediated induction of gamma-glutamyltransferase activity in Fao cells. The kinetic parameters of the induction process by glucocorticoids are very similar to those found in adult rat liver. These results suggest that the Fao cell line is a very convenient system for the study of the molecular mechanisms of glucocorticoid effects on differentiated cells.

In vivo modulation of rat hepatic gamma-glutamyltransferase activity by glucocorticoids.

The gamma-glutamyltransferase (gamma-GT) activity decreased by 50% following adrenalectomy of female rats, in homogenate as well as in a purified plasma membrane preparation from liver. In contrast, such a variation was not found in the kidney. None of 3 other enzyme activities of the plasma membrane, namely 5'-nucleotidase, alkaline phosphatase, and alkaline phosphodiesterase I, was decreased by adrenalectomy. Administration of hydrocortisone (5 mg/100 g body weight) resulted in a 2.6-fold increase in hepatic gamma-GT activity from adrenalectomized rats. The hydrocortisone-mediated stimulation of gamma-GT activity was dose- and time-dependent. The 5'-nucleotidase and leucine aminopeptidase activities were not modified by the hydrocortisone treatment. The activity of gamma-GT was mainly associated with nuclear fractions (nuclei and plasma membranes) obtained from liver homogenates of either control, adrenalectomized or adrenalectomized hydrocortisone-treated animals, and this activity was purified 18-fold in a plasma-membrane preparation as compared to homogenate. These data suggest that adrenalectomy and conversely hydrocortisone treatment modulate specifically the hepatic plasma-membrane gamma-GT activity. This represents one of the first demonstrations of a specific modulation by glucocorticoids of an enzyme activity typical of the plasma membrane.

Levels of asbestos air pollution in some environmental situations.

Asbestos contamination of the outside aid in Paris and suburbs has been monitored in some environmental situations, namely, "typical" urban sites removed from known sources of asbestos emissions, crossroad locations, the vicinity of a freeway, areas with buildings under construction, and areas around asbestos factories. In the same manner, measurements have been performed inside buildings of various types: those sprayed with asbestos-containing materials, those fitted with asbestos products, and control buildings. Air has been sampled by use of 0.45 micrometer pore size Millipore filters. After low-temperature ashing, ultrasonicated ashes were transferred to carbon film on 200-mesh gold grids examined under an analytic transmission electron microscope. Levels of pollution were expressed in terms of gravimetric concentrations. Inside buildings, when the air was in contact with significant amounts of asbestos-containing materials (spray, sheets), the levels were in the range 0.1--1000 10(-9) g m-3. In the vicinities of asbestos plants, the concentrations were higher: 1000--3000 10(-9) g m-3. Under other circumstances, the levels were of the same order of magnitude: 99% of the values were below 7 X 10(-9) g m-3. The Conseil Supérieur d'Hygiène Publique de France proposed a numerical ambient air quality standard of 50 X 10(-9) g m-3 inside buildings sprayed with asbestos.