Dissemination of ESBL-producing E. coli ST131 through wastewater and environmental water in Switzerland

The E. coli lineage ST131 is a major cause of multidrug-resistant urinary tract and bloodstream infections worldwide. Recently emerged ST131 sublineages spread globally within few years, but their dissemination routes are incompletely understood. In this study, we investigate the potential role of wastewater and surface water in the spread of extended-spectrum β-lactamase (ESBL)-producing ST131. Streams, lakes, and two wastewater treatment plants (WWTPs) in the canton of Zug, Switzerland, were consecutively sampled over 1.5 years. ST131 was detected in 38% of the samples taken downstream (1-5 km) of WWTP discharge sites, but usually absent in water bodies distant from urban areas or WWTP discharge. Specific strains were repeatedly isolated (≤5 pairwise cgSNP distance) from wastewater or river sites downstream of effluent discharge, indicating their repeated entry or persistence in WWTPs in large concentrations. Genetic characterization of the ESBL-producing water isolates revealed a predominance of clades A and C1 and an emerging ciprofloxacin-resistant sublineage with mutations in quinolone resistance determining regions (QRDR) within clade A. Multiple isolates belonged to internationally circulating sublineages, including C1-M27 and papGII + sublineages with chromosomally encoded ESBLs. This study demonstrates that the clinically relevant E. coli lineage ST131 pollutes river ecosystems, representing a significant challenge to public health and to technologies to minimize their entry into the water environment

Complete Genome Sequence of Hafnia paralvei Isolate AVS0177, Harboring mcr−9mcr-9 on a Plasmid

Here, we report the complete genome sequence of a Hafnia paralvei strain isolated from a lake in Switzerland in 2020. The genome consists of a 4.7-Mbp chromosome, a large plasmid (213 kb) harboring mcr-9, and a small plasmid (6 kb)

Complete Genome Sequence of Colistin-Resistant, mcr-10-Harboring, Enterobacter cloacae Isolate AVS0889, Recovered from River Water in Switzerland

Here, we report the complete genome sequence of colistin-resistant Enterobacter cloacae sequence type 1 (ST1) isolate AVS0889, which was recovered from a river in Switzerland in 2021. The genome consists of a 4.95-Mbp chromosome and five plasmids, including a large plasmid (90.8 kb) harboring a disrupted mcr-10 gene

Anthropometric Criteria for Identifying Infants Under 6 Months of Age at Risk of Morbidity and Mortality: A Systematic Review.

BACKGROUND: There is increasing global focus on small and nutritionally at-risk infants aged <6 months (<6 m). Current WHO guidelines recommend weight-for-length z-score (WLZ) for enrolment to malnutrition treatment programmes but acknowledge a weak evidence-base. This review aims to inform future guidelines by examining which anthropometric criteria best identify infants <6 m at high risk of mortality/morbidity. METHODS: We searched Medline, EMBASE, CINAHL, Global Health, Cochrane Library and POPLINE for studies conducted in low- and middle-income countries and published between 1990 and October 2020. We included studies reporting anthropometric assessment of nutritional status in infants <6 m and assessed the association with subsequent morbidity or mortality. RESULTS: A total of 19 studies were included in the final review, covering 20 countries, predominantly in sub-Saharan Africa. WLZ had poor reliability and poor prognostic ability to identify infants at risk of death. Mid-upper arm circumference (MUAC) and weight-for-age z-score (WAZ) were better at identifying infants at risk of mortality/morbidity. MUAC-for-age z-score did not perform better than using a single MUAC cut-off. Suggested MUAC cut-offs for this age group varied by context, ranging from 10.5 to 11.5 cm. The assessment for reliability showed that length was difficult to measure, making WLZ the least reliable indicator overall. CONCLUSION: Evidence from our review suggests that a change in current practice is necessary. To better identify small and nutritionally at-risk infants <6 m WAZ and/or MUAC rather than WLZ should be used. Future research should explore possible benefits for programme coverage, impact and cost-effectiveness. Research should also examine if context-specific MUAC thresholds are needed

In Vivo Tracking of Human Neural Stem Cells with 19F Magnetic Resonance Imaging

(c)The Author

Stem Cell Mediation of Functional Recovery after Stroke in the Rat

This is an open-access article distributed under the terms of the Creative Commons Attribution License.[Background]: Regenerative strategies of stem cell grafting have been demonstrated to be effective in animal models of stroke. In those studies, the effectiveness of stem cells promoting functional recovery was assessed by behavioral testing. These behavioral studies do, however, not provide access to the understanding of the mechanisms underlying the observed functional outcome improvement. [Methodology/Principal Findings]: In order to address the underlying mechanisms of stem cell mediated functional improvement, this functional improvement after stroke in the rat was investigated for six months after stroke by use of fMRI, somatosensory evoked potentials by electrophysiology, and sensorimotor behavior testing. Stem cells were grafted ipsilateral to the ischemic lesion. Rigorous exclusion of spontaneous recovery as confounding factor permitted to observe graft-related functional improvement beginning after 7 weeks and continuously increasing during the 6-month observation period. The major findings were i) functional improvement causally related to the stem cells grafting; ii) tissue replacement can be excluded as dominant factor for stem cell mediated functional improvement; iii) functional improvement occurs by exclusive restitution of the function in the original representation field, without clear contributions from reorganization processes, and iv) stem cells were not detectable any longer after six months. [Conclusions/Significance]: A delayed functional improvement due to stem cell implantation has been documented by electrophysiology, fMRI and behavioral testing. This functional improvement occurred without cells acting as a tissue replacement for the necrotic tissue after the ischemic event. Combination of disappearance of grafted cells after six months on histological sections with persistent functional recovery was interpreted as paracrine effects by the grafted stem cells being the dominant mechanism of cell activity underlying the observed functional restitution of the original activation sites. Future studies will have to investigate whether the stem cell mediated improvement reactivates the original representation target field by using original connectivity pathways or by generating/activating new ones for the stimulus.Financial support from the Hertie Foundation (Germany), and EU grants of the FP-6: DiMI (LSHB-CT-2005-512146), EMIL (LSHC-CT-2004-503569) and Stem Stroke (LSHB-CT-2006-037526) are gratefully acknowledged.Peer Reviewe

Soluble Beta-Amyloid Precursor Protein Is Related to Disease Progression in Amyotrophic Lateral Sclerosis

Background: Biomarkers of disease progression in amyotrophic lateral sclerosis (ALS) could support the identification of beneficial drugs in clinical trials. We aimed to test whether soluble fragments of beta-amyloid precursor protein (sAPPa and sAPPß) correlated with clinical subtypes of ALS and were of prognostic value. Methodology/Principal Findings: In a cross-sectional study including patients with ALS (N = 68) with clinical follow-up data over 6 months, Parkinson’s disease (PD, N = 20), and age-matched controls (N = 40), cerebrospinal fluid (CSF) levels of sAPPa a, sAPPß and neurofilaments (NfH SMI35) were measured by multiplex assay, Progranulin by ELISA. CSF sAPPa and sAPPß levels were lower in ALS with a rapidly-progressive disease course (p = 0.03, and p = 0.02) and with longer disease duration (p = 0.01 and p = 0.01, respectively). CSF NfH SMI35 was elevated in ALS compared to PD and controls, with highest concentrations found in patients with rapid disease progression (p,0.01). High CSF NfH SMI3 was linked to low CSF sAPPa and sAPPß (p = 0.001, and p = 0.007, respectively). The ratios CSF NfH SMI35 /CSF sAPPa,-ß were elevated in patients with fast progression of disease (p = 0.002 each). CSF Progranulin decreased with ongoing disease (p = 0.04). Conclusions: This study provides new CSF candidate markers associated with progression of disease in ALS. The data suggest that a deficiency of cellular neuroprotective mechanisms (decrease of sAPP) is linked to progressive neuro-axona

Spatiotemporal Correlations between Blood-Brain Barrier Permeability and Apparent Diffusion Coefficient in a Rat Model of Ischemic Stroke

Variations in apparent diffusion coefficient of water (ADC) and blood-brain barrier (BBB) permeability after ischemia have been suggested, though the correlation between ADC alterations and BBB opening remains to be studied. We hypothesized that there are correlations between the alteration of ADC and BBB permeability. Rats were subjected to 2 h of transient middle cerebral artery occlusion and studied at 3 and 48 h of reperfusion, which are crucial times of BBB opening. BBB permeability and ADC values were measured by dynamic contrast-enhanced MRI and diffusion-weighted imaging, respectively. Temporal and spatial analyses of the evolution of BBB permeability and ADC alteration in cortical and subcortical regions were conducted along with the correlation between ADC and BBB permeability data. We found significant increases in BBB leakage and reduction in ADC values between 3 and 48 h of reperfusion. We identified three MR tissue signature models: high Ki and low ADC, high Ki and normal ADC, and normal Ki and low ADC. Over time, areas with normal Ki and low ADC transformed into areas with high Ki. We observed a pattern of lesion evolution where the extent of initial ischemic injury reflected by ADC abnormalities determines vascular integrity. Our results suggest that regions with vasogenic edema alone are not likely to develop low ADC by 48 h and may undergo recovery

Epidemic Microclusters of Blood-Culture Proven Sepsis in Very-Low-Birth Weight Infants: Experience of the German Neonatal Network

INTRODUCTION: We evaluated blood culture-proven sepsis episodes occurring in microclusters in very-low-birth-weight infants born in the German Neonatal Network (GNN) during 2009-2010. METHODS: Thirty-seven centers participated in GNN; 23 centers enrolled ≥50 VLBW infants in the study period. Data quality was approved by on-site monitoring. Microclusters of sepsis were defined as occurrence of at least two blood-culture proven sepsis events in different patients of one center within 3 months with the same bacterial species. For microcluster analysis, we selected sepsis episodes with typically cross-transmitted bacteria of high clinical significance including gram-negative rods and Enterococcus spp. RESULTS: In our cohort, 12/2110 (0.6%) infants were documented with an early-onset sepsis and 235 late-onset sepsis episodes (≥72 h of age) occurred in 203/2110 (9.6%) VLBW infants. In 182/235 (77.4%) late-onset sepsis episodes gram-positive bacteria were documented, while coagulase negative staphylococci were found to be the most predominant pathogens (48.5%, 95%CI: 42.01-55.01). Candida spp. and gram-negative bacilli caused 10/235 (4.3%, 95%CI: 1.68% -6.83%) and 43/235 (18.5%) late-onset sepsis episodes, respectively. Eleven microclusters of blood-culture proven sepsis were detected in 7 hospitals involving a total 26 infants. 16/26 cluster patients suffered from Klebsiella spp. sepsis. The median time interval between the first patient's Klebsiella spp. sepsis and cluster cases was 14.1 days (interquartile range: 1-27 days). First patients in the cluster, their linked cases and sporadic sepsis events did not show significant differences in short term outcome parameters. DISCUSSION: Microclusters of infection are an important phenomenon for late-onset sepsis. Most gram-negative cluster infections occur within 30 days after the first patient was diagnosed and Klebsiella spp. play a major role. It is essential to monitor epidemic microclusters of sepsis in surveillance networks to adapt clinical practice, inform policy and further improve quality of care

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery