The current MLVA typing scheme for Enterococcus faecium is less discriminatory than MLST and PFGE for epidemic-virulent, hospital-adapted clonal types

BACKGROUND: MLVA (multiple-locus variable-number tandem repeat analysis) is a reliable typing technique introduced recently to differentiate also isolates of Enterococcus faecium. We used the established VNTR (variable number of tandem repeats) scheme to test its suitability to differentiate 58 E. faecium isolates representing mainly outbreaks and clusters of infections and colonizations among patients from 31 German hospitals. All isolates were vancomycin-resistant (vanA type). Typing results for MLVA are compared with results of macrorestriction analysis in PFGE (pulsed-field gel electrophoresis) and MLST (multi-locus sequence typing). RESULTS: All 51 but one hospital isolates from 1996–2006 were assigned to the clonal complex (CC) of epidemic-virulent, hospital-adapted lineages (MLST CC-17; MLVA CC-1) and differed from isolates of sporadic infections and colonizations (n = 7; 1991–1995) and other non-hospital origins (n = 27). Typing of all 58 hospital VRE revealed MLVA as the least discriminatory method (Simpson's diversity index 0.847) when compared to MLST (0.911) and PFGE (0.976). The two most common MLVA types MT-1 (n = 16) and MT-159 (n = 14) combined isolates of several MLST types including also major epidemic, hospital-adapted, clonal types (MT-1: ST-17, ST-18, ST-280, ST-282; MT-159: ST-78, ST-192, ST-203). These data clearly indicate that non-related E. faecium could possess an identical MLVA type being especially critical when MLVA is used to elucidate supposed outbreaks with E. faecium within a single or among different hospitals. Stability of a given MLVA profile MT-12 (ST-117) during an outbreak over a period of five years was also shown. CONCLUSION: MLVA is a suitable method to assign isolates of E. faecium into distinct clonal complexes. To investigate outbreaks the current MLVA typing scheme for E. faecium does not discriminate enough and cannot be recommended as a standard superior to PFGE

Vancomycin-resistant vanB-type Enterococcus faecium isolates expressing varying levels of vancomycin resistance and being highly prevalent among neonatal patients in a single ICU

Background: Vancomycin-resistant isolates of E. faecalis and E. faecium are of special concern and patients at risk of acquiring a VRE colonization/infection include also intensively-cared neonates. We describe here an ongoing high prevalence of VanB type E. faecium in a neonatal ICU hardly to identify by routine diagnostics. Methods: During a 10 months’ key period 71 E. faecium isolates including 67 vanB-type isolates from 61 patients were collected non-selectively. Vancomycin resistance was determined by different MIC methods (broth microdilution, Vitek® 2) including two Etest® protocols (McFarland 0.5/2.0. on Mueller-Hinton/Brain Heart Infusion agars). Performance of three chromogenic VRE agars to identify the vanB type outbreak VRE was evaluated (BrillianceTM VRE agar, chromIDTM VRE agar, CHROMagarTM VRE). Isolates were genotyped by SmaI- and CeuI-macrorestriction analysis in PFGE, plasmid profiling, vanB Southern hybridisations as well as MLST typing. Results: Majority of vanB isolates (n = 56, 79%) belonged to a single ST192 outbreak strain type showing an identical PFGE pattern and analyzed representative isolates revealed a chromosomal localization of a vanB2-Tn5382 cluster type. Vancomycin MICs in cation-adjusted MH broth revealed a susceptible value of ≤4 mg/L for 31 (55%) of the 56 outbreak VRE isolates. Etest® vancomycin on MH and BHI agars revealed only two vanB VRE isolates with a susceptible result; in general Etest® MIC results were about 1 to 2 doubling dilutions higher than MICs assessed in broth and values after the 48 h readout were 0.5 to 1 doubling dilutions higher for vanB VRE. Of all vanB type VRE only three, three and two isolates did not grow on BrillianceTM VRE agar, chromIDTM VRE agar and CHROMagarTM VRE, respectively. Permanent cross contamination via the patients’ surrounding appeared as a possible risk factor for permanent VRE colonization/infection. Conclusions: Low level expression of vanB resistance may complicate a proper routine diagnostics of vanB VRE and mask an ongoing high VRE prevalence. A high inoculum and growth on rich solid media showed the highest sensitivity in identifying vanB type resistance

Methicillin-resistant Staphylococcus aureus from infections in horses in Germany are frequent colonizers of veterinarians but rare among MRSA from infections in humans

AbstractA total of 272 methicillin-resistant Staphylococcus aureus (MRSA) from equine infections originating from 17 equine hospitals and 39 veterinary practices in Germany as well as 67 isolates from personnel working at equine clinics were subjected to molecular typing. The majority of isolates from horses was attributed to clonal complex (CC) 398 (82.7%). Within CC398, 66% of isolates belonged to a subpopulation (clade) of CC398, which is associated with equine clinics.MRSA attributed to CC8 (ST254, t009, t036, SCCmecIV; ST8, t064, SCCmecIV) were less frequent (16.5%). Single isolates were attributed to ST1, CC22, ST130, and ST1660. The emergence of MRSA CC22 and ST130 in horses was not reported so far. Nasal MRSA colonization was found in 19.5% of veterinary personnel with occupational exposure to horses. The typing characteristics of these isolates corresponded to isolates from equine infections.Comparing typing characteristics of equine isolates with those of a substantial number of isolates from human infections typed at the German Reference Center for Staphylococci and Enterococci (2006–2014; n=10864) yielded that the proportion of isolates exhibiting characteristics of MRSA from equine medicine is very low (<0.5%). As this low proportion was also found among MRSA originating from nasal screenings of human carriers not suffering from a staphylococcal infection (n=5546) transmission of MRSA from equine clinics to the community seems to be rare so far

An extra-heating mechanism in Doppler-cooling experiments

In this paper we experimentally and theoretically investigate laser cooling of Strontium 88 atoms in one dimensional optical molasses. In our case, since the optical cooling dipole transition involves a $J_g=0$ groundstate, no Sisyphus-type mechanisms can occur. We are thus able to test quantitatively the predictions of the Doppler-cooling theory. We have found, in agreement with other similar experiments, that the measured temperatures are systematically larger than the theoretical predictions. We quantitatively interpret this discrepancy by taking into consideration the extra-heating mechanism induced by transverse spatial intensity fluctuations of the optical molasses. Experimental data are in good agreement with Monte-Carlo simulations of our theoretical model. We thus confirm the important role played by intensity fluctuations in the dynamics of cooling and for the steady-state regime

Entanglement witnesses and geometry of entanglement of two--qutrit states

We construct entanglement witnesses with regard to the geometric structure of the Hilbert--Schmidt space and investigate the geometry of entanglement. In particular, for a two--parameter family of two--qutrit states that are part of the magic simplex we calculate the Hilbert--Schmidt measure of entanglement. We present a method to detect bound entanglement which is illustrated for a three--parameter family of states. In this way we discover new regions of bound entangled states. Furthermore we outline how to use our method to distinguish entangled from separable states.Comment: 23 pages, 8 figure

Early volumetric changes of hippocampus and medial prefrontal cortex following medial temporal lobe resection

Previous studies have shown that cognitive demands and physical exercise stimulate adult neurogenesis in the dentate gyrus and hippocampus. Recent observations in healthy humans and patients with mild cognitive impairment moreover suggest that training-induced increases in hippocampal volume may be associated with improved memory performance. The corresponding plasticity processes in hippocampal volume may occur on timescales of months to years. For patients with focal lesions in this region, previous functional imaging studies suggest that increased recruitment of the contralateral hippocampus and extratemporal regions may be an important part of the reorganization of episodic memory. However, it is currently unclear whether focal damage to the medial temporal lobe (MTL) induces gray matter (GM) volume changes in the intact contralateral hippocampus and in connected network regions on a shorter timescale. We therefore investigated whether unilateral resection of the MTL, including the hippocampus, induces measurable volumetric changes in the contralateral hippocampus and in the default mode network (DMN). We recruited 31 patients with unilateral left (N = 19) or right (N = 12) hippocampal sclerosis undergoing MTL resection for treatment of drug-resistant epilepsy. Structural MRI was acquired immediately before and 3 months after surgery. Longitudinal voxel-based morphometry (VBM) analysis revealed a significant increase of right hippocampal volume following resection of the left anterior MTL. Furthermore, this patient group showed GM volume increases in the DMN. These results demonstrate significant structural plasticity of the contralateral hippocampus, even in patients with a long-standing unilateral hippocampal dysfunction and structural reorganization processes extending to distant, but functionally connected brain regions

Dimethylfumarate Impairs Neutrophil Functions

Host defense against pathogens relies on neutrophil activation. Inadequate neutrophil activation is often associated with chronic inflammatory diseases. Neutrophils also constitute a significant portion of infiltrating cells in chronic inflammatory diseases, for example, psoriasis and multiple sclerosis. Fumarates improve the latter diseases, which so far has been attributed to the effects on lymphocytes and dendritic cells. Here, we focused on the effects of dimethylfumarate (DMF) on neutrophils. In vitro, DMF inhibited neutrophil activation, including changes in surface marker expression, reactive oxygen species production, formation of neutrophil extracellular traps, and migration. Phagocytic ability and autoantibody-induced, neutrophil-dependent tissue injury ex vivo was also impaired by DMF. Regarding the mode of action, DMF modulates—in a stimulus-dependent manner-neutrophil activation using the phosphoinositide 3-kinase/Akt-p38 mitogen-activated protein kinase and extracellular signal-regulated kinase 1/2 pathways. For in vivo validation, mouse models of epidermolysis bullosa acquisita, an organ-specific autoimmune disease caused by autoantibodies to type VII collagen, were employed. In the presence of DMF, blistering induced by injection of anti-type VII collagen antibodies into mice was significantly impaired. DMF treatment of mice with clinically already-manifested epidermolysis bullosa acquisita led to disease improvement. Collectively, we demonstrate a profound inhibitory activity of DMF on neutrophil functions. These findings encourage wider use of DMF in patients with neutrophil-mediated diseases

Impact of lattice dynamics on the phase stability of metamagnetic FeRh: Bulk and thin films

We present phonon dispersions, element-resolved vibrational density of states (VDOS) and corresponding thermodynamic properties obtained by a combination of density functional theory (DFT) and nuclear resonant inelastic X-ray scattering (NRIXS) across the metamagnetic transition of B2 FeRh in the bulk material and thin epitaxial films. We see distinct differences in the VDOS of the antiferromagnetic (AF) and ferromagnetic (FM) phase which provide a microscopic proof of strong spin-phonon coupling in FeRh. The FM VDOS exhibits a particular sensitivity to the slight tetragonal distortions present in epitaxial films, which is not encountered in the AF phase. This results in a notable change in lattice entropy, which is important for the comparison between thin film and bulk results. Our calculations confirm the recently reported lattice instability in the AF phase. The imaginary frequencies at the $X$-point depend critically on the Fe magnetic moment and atomic volume. Analyzing these non vibrational modes leads to the discovery of a stable monoclinic ground state structure which is robustly predicted from DFT but not verified in our thin film experiments. Specific heat, entropy and free energy calculated within the quasiharmonic approximation suggest that the new phase is possibly suppressed because of its relatively smaller lattice entropy. In the bulk phase, lattice degrees of freedom contribute with the same sign and in similar magnitude to the isostructural AF-FM phase transition as the electronic and magnetic subsystems and therefore needs to be included in thermodynamic modeling.Comment: 15 pages, 12 figure

Geometry of entangled states

Geometric properties of the set of quantum entangled states are investigated. We propose an explicit method to compute the dimension of local orbits for any mixed state of the general K x M problem and characterize the set of effectively different states (which cannot be related by local transformations). Thus we generalize earlier results obtained for the simplest 2 x 2 system, which lead to a stratification of the 6D set of N=4 pure states. We define the concept of absolutely separable states, for which all globally equivalent states are separable.Comment: 16 latex pages, 4 figures in epsf, minor corrections, references updated, to appear in Phys. Rev.