Novel insights into pivotal risk factors for rectal carriage of extended-spectrum-beta-lactamase-producing enterobacterales within the general population in Lower Saxony, Germany

AIMS: To estimate the prevalence of extended-spectrum-β-lactamase (ESBL)-producing enterobacterales (ESBL-E) carriage in the general population of Lower Saxony, Germany, and to identify risk factors for being colonised. METHODS AND RESULTS: Participants were recruited through local press and information events. Detection of ESBL-E by culture was conducted using ESBL-selective chromagar plates containing third generation cephalosporins. Identification of pathogens was performed using Matrix Assisted Laser Desorption Ionization Time-of-Flight-Technology on Vitek mass spectrometry. Antibiotic susceptibility testing was conducted by microdilution (Vitek II) and an ESBL confirmation assay was carried out using a combination disk test. Of 527 randomly collected stool samples from healthy volunteers, 5.5% were tested positive for ESBL-E. Post-stratification for age and gender yielded a similar population estimate (5.9%). People traveling abroad and taking antibiotics had the greatest rectal ESBL-E carriage. CONCLUSIONS: Potential risk factors (e.g., working in healthcare facilities, recent inpatient stay) did not attribute to rectal ESBL-E carriage as other factors (e.g., traveling, taking antibiotics). Rectal ESBL-E carriage within the general population seems to be high. SIGNIFICANCE AND IMPACT OF STUDY: The known risk factors for carriage with MDRO might not be fully applicable to ESBL-E and require further examination in order to develop effective strategies for the prevention of ESBL-E dissemination within the general population

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

Ein großes Werk zum Abschluss bringen

After a short history of the Akademie-Ausgabe der Werke Immanuel Kants, it is shown that the edition is incomplete in some essential parts: The central topic of the first part of the article is the Opus postumum. Here we have a new critical transcription which differs not only in the composition but even in many details. The second project is focused on Nachschriften of Kant’s lectures on Physische Geographie. The three volumes will show that Kant continually actualized the material for this complex area of problems, for which he presented the outlines of a new academic discipline (as he did too in his Anthropology). The other central topic is the new edition of the three Critiques. The second part of the article demonstrates principle steps of critical editing using the example of Kant’s third Critique, the Critique of Judgment.Peer Reviewe

Soils in mountain and upland regions of southwestern Norway nitrogen leaching and critical loads

Soil data were collected from 36 points in mountain and upland areas of southwestern Norway. Samling was at cross-points on the NIJOS`9x9 km grid used for forest and soil monitoring. The soils were linked to water chemistry and deposition data from the Norwegian critical load database (12x12 km grid). Together the data were tested for relationships between N deposition, C/N ratio in soil, and NO3 concentrations in surface waters. The absence of significant relationships was ascribed to soil heterogeneity and the cource-scale of the samling. Critical loads for soils were calculated using the MAGIC model and the criterion that Ca/Al molar ratio in soil solution does not exceed 1.0. Critical loads were lowest for sites somewhat inland. With full implementation of the Gothenburg protocol by 2010, and assuming no increase in % N leached, only at a few of the sites will the critical load for soils continue to be exceeded in the long run

Sammenhenger mellom trær vitalitet og næringsstatus i nåler og i humus i Sørøst-Norge

Nåleprøver ble innsamlet fra 180 grantrær på 45 flater i Sørøst-Norge. Det var generelt lavere konsentrasjon av kationer og mineralnæringsstoffer henholdsvis i humuslaget og i nåler i den sørligste del av landet, samt et høyere innhold av N. Ved fortsatt tilførsel av N, er det sannsynlig at det i trærne vil oppstå sterkere mangel på næringsstoffer som K og P. På grunn av den geografiske spredningen i materialet styres trærnes vitalitet i hovedsak av de naturlige vekstbetingelsene, samt av konsentrasjonen av nitrogen i nålene og pH i humuslaget, og viser ingen geografiske trender

Contribution of islet and intestinal neprilysin in modulating beta-cell function

peer reviewe

Sense and antisense RNA are not toxic in <i>Drosophila </i>models of <i>C9orf72</i>-associated ALS/FTD

A GGGGCC hexanucleotide repeat expansion in the C9orf72 gene is the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia. Neurodegeneration may occur via transcription of the repeats into inherently toxic repetitive sense and antisense RNA species, or via repeat-associated non-ATG initiated translation (RANT) of sense and antisense RNA into toxic dipeptide repeat proteins. We have previously demonstrated that regular interspersion of repeat RNA with stop codons prevents RANT (RNA-only models), allowing us to study the role of repeat RNA in isolation. Here we have created novel RNA-only Drosophila models, including the first models of antisense repeat toxicity, and flies expressing extremely large repeats, within the range observed in patients. We generated flies expressing ~ 100 repeat sense or antisense RNA either as part of a processed polyadenylated transcript or intronic sequence. We additionally created Drosophila expressing > 1000 RNA-only repeats in the sense direction. When expressed in adult Drosophila neurons polyadenylated repeat RNA is largely cytoplasmic in localisation, whilst intronic repeat RNA forms intranuclear RNA foci, as does > 1000 repeat RNA, thus allowing us to investigate both nuclear and cytoplasmic RNA toxicity. We confirmed that these RNA foci are capable of sequestering endogenous Drosophila RNA-binding proteins, and that the production of dipeptide proteins (poly-glycine-proline, and poly-glycine-arginine) is suppressed in our models. We find that neither cytoplasmic nor nuclear sense or antisense RNA are toxic when expressed in adult Drosophila neurons, suggesting they have a limited role in disease pathogenesis

The Genome of the Amoeba Symbiont “Candidatus Amoebophilus asiaticus” Reveals Common Mechanisms for Host Cell Interaction among Amoeba-Associated Bacteria ▿ †‡

Protozoa play host for many intracellular bacteria and are important for the adaptation of pathogenic bacteria to eukaryotic cells. We analyzed the genome sequence of “Candidatus Amoebophilus asiaticus,” an obligate intracellular amoeba symbiont belonging to the Bacteroidetes. The genome has a size of 1.89 Mbp, encodes 1,557 proteins, and shows massive proliferation of IS elements (24% of all genes), although the genome seems to be evolutionarily relatively stable. The genome does not encode pathways for de novo biosynthesis of cofactors, nucleotides, and almost all amino acids. “Ca. Amoebophilus asiaticus” encodes a variety of proteins with predicted importance for host cell interaction; in particular, an arsenal of proteins with eukaryotic domains, including ankyrin-, TPR/SEL1-, and leucine-rich repeats, which is hitherto unmatched among prokaryotes, is remarkable. Unexpectedly, 26 proteins that can interfere with the host ubiquitin system were identified in the genome. These proteins include F- and U-box domain proteins and two ubiquitin-specific proteases of the CA clan C19 family, representing the first prokaryotic members of this protein family. Consequently, interference with the host ubiquitin system is an important host cell interaction mechanism of “Ca. Amoebophilus asiaticus”. More generally, we show that the eukaryotic domains identified in “Ca. Amoebophilus asiaticus” are also significantly enriched in the genomes of other amoeba-associated bacteria (including chlamydiae, Legionella pneumophila, Rickettsia bellii, Francisella tularensis, and Mycobacterium avium). This indicates that phylogenetically and ecologically diverse bacteria which thrive inside amoebae exploit common mechanisms for interaction with their hosts, and it provides further evidence for the role of amoebae as training grounds for bacterial pathogens of humans

Previous antibiotic therapy as independent risk factor for the presence of vancomycin-resistant enterococci in surgical inpatients. Results from a matched case-control study

Abstract Background Investigation of risk factors for the presence of vancomycin-resistant enterococci (VRE) in inpatients on surgical wards and associated intensive care units of a German tertiary care hospital. Methods A single-centre retrospective matched case-control study was performed with surgical inpatients admitted between July 2013 and December 2016. Patients with in-hospital detection of VRE later than 48 h after admission were included and comprised 116 VRE-positive cases and 116 VRE-negative matched controls. VRE isolates of cases were typed by multi-locus sequence typing. Results ST117 was identified as the dominant VRE sequence type. Next to length of stay in hospital or on an intensive care unit and previous dialysis the case-control study revealed previous antibiotic therapy as a risk factor for the in-hospital detection of VRE. The antibiotics piperacillin/tazobactam, meropenem, and vancomycin were associated with the highest risks. After taking into account length of stay in hospital as possible confounder other potential contact-related risk factors such as previous sonography, radiology, central venous catheter, and endoscopy were not significant. Conclusions Previous dialysis and previous antibiotic therapy were identified as independent risk factors for the presence of VRE in surgical inpatients