High colonization rates of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli in Swiss Travellers to South Asia- a prospective observational multicentre cohort study looking at epidemiology, microbiology and risk factors.

BACKGROUND International travel contributes to the worldwide spread of multidrug resistant Gram-negative bacteria. Rates of travel-related faecal colonization with extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae vary for different destinations. Especially travellers returning from the Indian subcontinent show high colonization rates. So far, nothing is known about region-specific risk factors for becoming colonized. METHODS An observational prospective multicentre cohort study investigated travellers to South Asia. Before and after travelling, rectal swabs were screened for third-generation cephalosporin- and carbapenem-resistant Enterobacteriaceae. Participants completed questionnaires to identify risk factors for becoming colonized. Covariates were assessed univariately, followed by a multivariate regression. RESULTS Hundred and seventy persons were enrolled, the largest data set on travellers to the Indian subcontinent so far. The acquired colonization rate with ESBL-producing Escherichia coli overall was 69.4% (95% CI 62.1-75.9%), being highest in travellers returning from India (86.8%; 95% CI 78.5-95.0%) and lowest in travellers returning from Sri Lanka (34.7%; 95% CI 22.9-48.7%). Associated risk factors were travel destination, length of stay, visiting friends and relatives, and eating ice cream and pastry. CONCLUSIONS High colonization rates with ESBL-producing Enterobacteriaceae were found in travellers returning from South Asia. Though risk factors were identified, a more common source, i.e. environmental, appears to better explain the high colonization rates.

Extended duration of torsional loading reduced the survival of the NP cells of the intervertebral disc

Introduction Previous studies on the influence of torsion and combined torsion-compression loading revealed a positive effect on the cell viability when a repetitive short-term torsion was applied at a physiological magnitude to intervertebral disc organ culture.1 However, after an extended period (8 hours) of combined torsion-compression loading, substantial cell death was detected in the nucleus pulposus (NP).2 In this follow-up study, we aimed to investigate the relationship, if any, between the duration of torsion applied to the intervertebral disc (IVD) and the level of NP cell viability. Materials and Methods Bovine caudal discs were harvested and cultured in a custom-built multiaxis dynamic loading bioreactor.2 Torsion (± 2 degrees) was applied to the samples at a frequency of 0.2 Hz. Torsion was applied for durations of 0, 1, 4, and 8 h/d, repeated over 7 days. After the last day of loading, disc tissue was dissected for analysis of cell viability and gene expression. Results Disc NP cell viability remained above 85% after torsional loading for 0, 1, or 4 h/d. Viability was statistical significantly reduced to below 70% when torsion was applied for 8 h/d (p = 0.03) (Table 1). The daily duration of torsional loading did not affect the AF cell viability (> 80% for all loading durations). The trend of collagen 2 gene upregulation and matrix metalloproteases 13 downregulation with an increasing duration of torsion was observed in both NP and AF (Fig. 1).Conclusion We have demonstrated that an extended duration of torsion could inhibit the survival of NP cells within the IVD in organ culture. Acknowledgments Funds from the Orthopedic Department of the Insel University Hospital of Bern and a private donation from Prof. Dr. Paul Heini, Spine Surgeon, Sonnenhof Clinic Bern were received to support this work. Disclosure of Interest None declared References References 1 Chan SC, Ferguson SJ, Wuertz K, Gantenbein-Ritter B. Biological response of the intervertebral disc to repetitive short-term cyclic torsion. Spine 2011;36(24):2021–2030 2 Chan SC, Walser J, Käppeli P, Shamsollahi MJ, Ferguson SJ, Gantenbein-Ritter B. Region specific response of intervertebral disc cells to complex dynamic loading: an organ culture study using a dynamic torsion-compression bioreactor. PLoS ONE 2013;8(8):e72489

Lesion location predicts transient and extended risk of aspiration after supratentorial ischemic stroke

BACKGROUND AND PURPOSE To assess the association of lesion location and risk of aspiration and to establish predictors of transient versus extended risk of aspiration after supratentorial ischemic stroke. METHODS Atlas-based localization analysis was performed in consecutive patients with MRI-proven first-time acute supratentorial ischemic stroke. Standardized swallowing assessment was carried out within 8±18 hours and 7.8±1.2 days after admission. RESULTS In a prospective, longitudinal analysis, 34 of 94 patients (36%) were classified as having acute risk of aspiration, which was extended (≥7 days) or transient (<7 days) in 17 cases. There were no between-group differences in age, sex, cause of stroke, risk factors, prestroke disability, lesion side, or the degree of age-related white-matter changes. Correcting for stroke volume and National Institutes of Health Stroke Scale with a multiple logistic regression model, significant adjusted odds ratios in favor of acute risk of aspiration were demonstrated for the internal capsule (adjusted odds ratio, 6.2; P<0.002) and the insular cortex (adjusted odds ratio, 4.8; P<0.003). In a multivariate model of extended versus transient risk of aspiration, combined lesions of the frontal operculum and insular cortex was the only significant independent predictor of poor recovery (adjusted odds ratio, 33.8; P<0.008). CONCLUSIONS Lesions of the insular cortex and the internal capsule are significantly associated with acute risk of aspiration after stroke. Combined ischemic infarctions of the frontal operculum and the insular cortex are likely to cause extended risk of aspiration in stroke patients, whereas risk of aspiration tends to be transient in subcortical stroke.

HOMO Stabilisation in π-Extended Dibenzotetrathiafulvalene Derivatives for Their Application in Organic Field-Effect Transistors

Three new organic semiconductors, in which either two methoxy units are directly linked to a dibenzotetrathiafulvalene (DB-TTF) central core and a 2,1,3-chalcogendiazole is fused on the one side, or four methoxy groups are linked to the DB-TTF, have been synthesised as active materials for organic field-effect transistors (OFETs). Their electrochemical behaviour, electronic absorption and fluorescence emission as well as photoinduced intramolecular charge transfer were studied. The electron-withdrawing 2,1,3-chalcogendiazole unit significantly affects the electronic properties of these semiconductors, lowering both the HOMO and LUMO energy levels and hence increasing the stability of the semiconducting material. The solution-processed single-crystal transistors exhibit high performance with a hole mobility up to 0.04 cm2 V−1 s−1 as well as good ambient stability.

Nickel(II)-, cobalt(II)-, copper(II)-, and zinc(II)-phthalate and 1-methylimidazole coordination compounds: synthesis, crystal structures and magnetic properties

Three new coordination polymers [M(Pht)(1-MeIm)2]n (where M=Cu (1), Zn (2), Co (3); Pht2−=dianion of o-phthalic acid; 1-MeIm=1-methylimidazole) and two compounds [M(1-MeIm)6](HPht)2 · 2H2O (M=Co (4), Ni (5)) have been synthesized and characterized by X-ray crystallography. The structures of 1–3 (2 is isostructural to 3) consist of [M(1-MeIm)2] building units connected by 1,6-bridging phthalate ions to form infinite chains. In complex 1, each copper(II) center adopts a square coordination mode of N2O2 type by two O atoms from different phthalate ions and two N atoms of 1-MeIm, whereas in 3 two independent metal atoms are tetrahedrally (N2O2) coordinated to a pair of Pht ligands and a pair of 1-MeIm molecules. There are only van der Waals interactions between the chains in 1, while the three-dimensional network in 3 is assembled by C–H⋯O contacts. In contrast to polymers 1–3 the structures of 4 and 5 (complexes are also isostructural) are made up of the [M(1-MeIm)6]2+ cation, two hydrogen phthalate anions (HPht−) and two H2O solvate molecules. The coordination around each metal(II) atom is octahedral with six nitrogen atoms of 1-MeIm. Extended hydrogen bonding networks embracing the solvate water molecules and a phthalate residue as well as the weak C–H⋯O interactions stabilize the three-dimensional structures. Magnetic studies clearly show that the magnetic ions do not interact with each other. Furthermore, in compound 4 we have another example of a highly anisotropic Co2+ ion with a rhombic g-tensor and large zero-field-splitting. The complexes were also characterized by IR and 1H NMR spectroscopy, thermogravimetric analysis, and all data are discussed in the terms of known structures.

The Utilization of Classical Spin Monte Carlo Methods to Simulate the Magnetic Behavior of Extended Three-Dimensional Cubic Networks Incorporating M(II) Ions with an S = 5/2 Ground State Spin

The numerical simulations of the magnetic properties of extended three-dimensional networks containing M(II) ions with an S = 5/2 ground-state spin have been carried out within the framework of the isotropic Heisenberg model. Analytical expressions fitting the numerical simulations for the primitive cubic, diamond, together with (10−3) cubic networks have all been derived. With these empirical formulas in hands, we can now extract the interaction between the magnetic ions from the experimental data for these networks. In the case of the primitive cubic network, these expressions are directly compared with those from the high-temperature expansions of the partition function. A fit of the experimental data for three complexes, namely [(N(CH3)4][Mn(N3)] 1, [Mn(CN4)]n 2, and [FeII(bipy)3][MnII2(ox)3] 3, has been carried out. The best fits were those obtained using the following parameters, J = −3.5 cm-1, g = 2.01 (1); J = −8.3 cm-1, g = 1.95 (2); and J = −2.0 cm-1, g = 1.95 (3).

Oligodeoxynucleotide Duplexes Containing (5′S)-5′-C-Alkyl-Modified 2′-Deoxynucleosides: Can an Alkyl Zipper across the DNA Minor-Groove Enhance Duplex Stability?

10.1002/hlca.200390311.abs A series of oligonucleotides containing (5′S)-5′-C-butyl- and (5′S)-5′-C-isopentyl-substituted 2′-deoxyribonucleosides were designed, prepared, and characterized with the intention to explore alkyl-zipper formation between opposing alkyl chains across the minor groove of oligonucleotide duplexes as a means to modulate DNA-duplex stability. From four possible arrangements of the alkyl groups that differ in the density of packing of the alkyl chains across the minor groove, three (duplex types I–III, Fig. 2) could experimentally be realized and their duplex-forming properties analyzed by UV-melting curves, CD spectroscopy, and isothermal titration calorimetry (ITC), as well as by molecular modeling. The results show that all arrangements of alkyl residues within the minor groove of DNA are thermally destabilizing by 1.5–3°/modification in Tm. We found that, within the proposed duplexes with more loosely packed alkyl groups (type-III duplexes), accommodation of alkyl residues without extended distorsion of the helical parameters of B-DNA is possible but does not lead to higher thermodynamic stability. The more densely packed and more unevenly distributed arrangement (type-II duplexes) seems to suffer from ecliptic positioning of opposite alkyl groups, which might account for a systematic negative contribution to stability due to steric interactions. The decreased stability in the type-III duplexes described here may be due either to missing hydrophobic interactions of the alkyl groups (not bulky enough to make close contacts), or to an overcompensation of favorable alkyl-zipper formation presumably by loss of structured H2O in the minor groove.

High Prevalence of Extended-Spectrum β-Lactamase, Plasmid-Mediated AmpC and Carbapenemase genes in Food for Pets

We evaluated the pet food contained in thirty packages as potential origin of extended-spectrum cephalosporin-resistant Gram-negative organisms and β-lactamase genes (bla). Alive bacteria were not detected by selective culture. However, PCR investigations on food DNA extracts indicated that samples harbored blaCTX-M-15 (53.3%), blaCMY-4 (20%), and blaVEB-4-like (6.7%). Particularly worrisome was the presence of blaOXA-48-like carbapenemases (13.3%). Original pet food ingredients and/or the production process were highly contaminated with bacteria carrying clinically relevant acquired bla genes.

Long-term results of a prospective randomised trial assessing the impact of readaptation of the dorsolateral peritoneal layer following extended pelvic lymph node dissection and cystectomy.

OBJECTIVE To evaluate the long term oncological and functional outcomes after readaptation of the dorsolateral peritoneal layer following pelvic lymph node dissection (PLND) and cystectomy . PATIENTS AND METHODS A randomised, single-center, single-blinded, two-arm trial was conducted on 200 consecutive cystectomy patients who underwent PLND and cystectomy for bladder cancer (

The Plasmodium Class XIV Myosin, MyoB, Has a Distinct Subcellular Location in Invasive and Motile Stages of the Malaria Parasite and an Unusual Light Chain

Myosin B (MyoB) is one of the two short class XIV myosins encoded in the Plasmodium genome. Class XIV myosins are characterized by a catalytic "head," a modified "neck," and the absence of a "tail" region. Myosin A (MyoA), the other class XIV myosin in Plasmodium, has been established as a component of the glideosome complex important in motility and cell invasion, but MyoB is not well characterized. We analyzed the properties of MyoB using three parasite species as follows: Plasmodium falciparum, Plasmodium berghei, and Plasmodium knowlesi. MyoB is expressed in all invasive stages (merozoites, ookinetes, and sporozoites) of the life cycle, and the protein is found in a discrete apical location in these polarized cells. In P. falciparum, MyoB is synthesized very late in schizogony/merogony, and its location in merozoites is distinct from, and anterior to, that of a range of known proteins present in the rhoptries, rhoptry neck or micronemes. Unlike MyoA, MyoB is not associated with glideosome complex proteins, including the MyoA light chain, myosin A tail domain-interacting protein (MTIP). A unique MyoB light chain (MLC-B) was identified that contains a calmodulin-like domain at the C terminus and an extended N-terminal region. MLC-B localizes to the same extreme apical pole in the cell as MyoB, and the two proteins form a complex. We propose that MLC-B is a MyoB-specific light chain, and for the short class XIV myosins that lack a tail region, the atypical myosin light chains may fulfill that role.

In vivo Evolution of CMY-2 to CMY-33 β-Lactamase in Escherichia coli ST131: Characterization of an Acquired Extended-Spectrum AmpC (ESAC) Conferring Resistance to Cefepime.

Cefepime is frequently prescribed to treat infections caused by AmpC-producing Gram-negative bacteria. CMY-2 is the most common plasmid-mediated AmpC (pAmpC) β-lactamase. Unfortunately, CMY variants conferring enhanced cefepime resistance are reported. Here, we describe the evolution of CMY-2 to an extended-spectrum AmpC (ESAC) in clonally identical E. coli isolates obtained from a patient. The CMY-2-producing E. coli (CMY-2-Ec) was isolated from a wound. Thirty days later, one CMY-33-producing E. coli (CMY-33-Ec) was detected in bronchoalveolar lavage. Two weeks before the isolation of CMY-33-Ec, the patient received cefepime.CMY-33-Ec and CMY-2-Ec were identical by rep-PCR, being of hyperepidemic ST131, but showed different β-lactam MICs (e.g., cefepime 16 vs. ≤0.5 μg/ml). Identical CMY-2-Ec isolates were also found in a rectal swab. CMY-33 differs from CMY-2 by a Leu293-Ala294 deletion. Expressed in E. coli DH10B, both CMYs conferred resistance to ceftazidime (≥256 μg/ml), but cefepime MICs were higher for CMY-33 than CMY-2 (8 vs. 0.25 μg/ml). The kcat/Km or kinact/KI (μM(-1) s(-1)) indicated that CMY-33 possesses an ESBL-like spectrum compared to CMY-2 (cefoxitin: 0.2 vs. 0.4; ceftazidime: 0.2 vs. not measurable; cefepime: 0.2 vs. not measurable; tazobactam 0.0018 vs. 0.0009). Using molecular modeling, we show that a widened active site (∼4 Å shift) may play a significant role in enhancing cefepime hydrolysis. This is the first in vivo demonstration of a pAmpC that under cephalosporin treatment expands its substrate spectrum resembling an ESBL. The prevalence of CMY-2-Ec isolates is rapidly increasing worldwide, therefore awareness that cefepime treatment may select for resistant isolates is critical.

Development and validation of a novel pedometer algorithm to quantify extended characteristics of the locomotor behavior of dairy cows

Behavior is one of the most important indicators for assessing cattle health and well-being. The objective of this study was to develop and validate a novel algorithm to monitor locomotor behavior of loose-housed dairy cows based on the output of the RumiWatch pedometer (ITIN+HOCH GmbH, Fütterungstechnik, Liestal, Switzerland). Data of locomotion were acquired by simultaneous pedometer measurements at a sampling rate of 10 Hz and video recordings for manual observation later. The study consisted of 3 independent experiments. Experiment 1 was carried out to develop and validate the algorithm for lying behavior, experiment 2 for walking and standing behavior, and experiment 3 for stride duration and stride length. The final version was validated, using the raw data, collected from cows not included in the development of the algorithm. Spearman correlation coefficients were calculated between accelerometer variables and respective data derived from the video recordings (gold standard). Dichotomous data were expressed as the proportion of correctly detected events, and the overall difference for continuous data was expressed as the relative measurement error. The proportions for correctly detected events or bouts were 1 for stand ups, lie downs, standing bouts, and lying bouts and 0.99 for walking bouts. The relative measurement error and Spearman correlation coefficient for lying time were 0.09% and 1; for standing time, 4.7% and 0.96; for walking time, 17.12% and 0.96; for number of strides, 6.23% and 0.98; for stride duration, 6.65% and 0.75; and for stride length, 11.92% and 0.81, respectively. The strong to very high correlations of the variables between visual observation and converted pedometer data indicate that the novel RumiWatch algorithm may markedly improve automated livestock management systems for efficient health monitoring of dairy cows.

Occupational mobility chains and the role of job opportunities for upward, lateral and downward mobility in Switzerland

This paper addresses the rarely studied relationship between job vacancies and inter-firm upward, lateral, and downward status mobility in an occupationally segmented labor market, taking Switzerland as the example. To conceptualize mobility mechanisms in this type of labor market, we introduce the concept of “occupational mobility chains” and test its validity. This concept provides the backdrop for developing time-dependent measures of individual job opportunities based on Swiss Job Monitor data. We link these measures with career data taken from the Swiss Life History Study and employ event history analysis to test different propositions of the ways in which status mobility is contingent on the number and the status of vacant positions. Results support our assumption that in occupationally segmented labor markets vacant positions affect status mobility only to the degree that they are located within workers’ occupational mobility chains.