A high-throughput approach to the culture-based estimation of plasmid transfer rates

Horizontal gene transfer is an essential component of bacterial evolution. Quantitative information on transfer rates is particularly useful to better understand and possibly predict the spread of antimicrobial resistance. A variety of methods has been proposed to estimate the rates of plasmid-mediated gene transfer all of which require substantial labor input or financial resources. A cheap but reliable method with high-throughput capabilities is yet to be developed in order to better capture the variability of plasmid transfer rates, e.g. among strains or in response to environmental cues. We explored a new approach to the culture-based estimation of plasmid transfer rates in liquid media allowing for a large number of parallel experiments. It deviates from established approaches in the fact that it exploits data on the absence/presence of transconjugant cells in the wells of a well plate observed over time. Specifically, the binary observations are compared to the probability of transconjugant detection as predicted by a dynamic model. The bulk transfer rate is found as the best-fit value of a designated model parameter. The feasibility of the approach is demonstrated on mating experiments where the RP4 plasmid is transfered from Serratia marcescens to several Escherichia coil recipients. The methods uncertainty is explored via split sampling and virtual experiments.Peer reviewe

The neurological manifestations of trauma: lessons from World War I

Changes in the clinical presentation of functional disorders and the influence of social and cultural factors can be investigated through the historical case notes from mental hospitals. World War I (WWI) was a potent trigger of functional disorders with neurological or psychiatric symptoms. We analysed 100 randomly selected case files of German servicemen admitted to the Department of Psychiatry of the Charité Medical School of Berlin University during WWI and classified them according to contemporaneous and retrospective modern diagnoses. We compared the clinical presentations with accounts in the German and British medical literature of the time. Most patients obtained the contemporaneous diagnosis of ‘psychopathic constitution’ or hysteria reflecting the general view of German psychiatrists that not the war but an individual predisposition was the basis for the development of symptoms. The clinical picture was dominated by pseudoneurological motor or sensory symptoms as well as pseudoseizures. Some soldiers relived combat experiences in dream-like dissociative states that partly resemble modern-day post-traumatic stress disorder. Most servicemen were classified as unfit for military service but very few of them were granted compensation. Severe functional disorders of a neurological character could develop even without traumatic exposure in combat, which is of interest for the current debate on triggers of stress disorders. The high incidence of pseudoseizures accords with the psychiatric literature of the time and contrasts with accounts of war-related disorders in Britain. The tendency of German psychiatrists not to send traumatised servicemen back to active duty also distinguished between German and British practice. Our data contribute to the debate on the changing patterns of human responses to traumatic experience and their historical and social context

The spread of the plasmid RP4 in a synthetic bacterial community is dependent on the particular donor strain

The rapid spread of antibiotic resistance challenges modern medicine. So far, mechanistic and quantitative knowledge concerning the spread of resistance genes mainly relies on laboratory experiments with simplified setups, e.g. two strain communities. Thus, the transferability of the obtained process rates might be limited. To investigate the role of a diverse community concerning the dissemination of the multidrug resistance plasmid RP4, an Escherichia coli harboring RP4 invaded a microbial community consisting of 21 species. Changes in the community composition as well as plasmid uptake by community members were monitored for 22 days. Special focus was laid on the question of whether the observed changes were dependent on the actual invading donor isolate and the ambient antibiotic concentration. In our microcosm experiment, the community composition was primarily influenced by the given environmental variables and only secondarily by the particular invader E. coli. The establishment of resistance within the community, however, was directly dependent on the donor identity. The extent to which ambient conditions influence the spread of RP4 depended on the E. coli donor strain. These results emphasize that even within one species there are great differences in the ability to conquer an ecological niche and to spread antibiotic resistance.Peer reviewe

Sewage from Airplanes Exhibits High Abundance and Diversity of Antibiotic Resistance Genes

Airplane sanitary facilities are shared by an international audience. We hypothesized the corresponding sewage to be an extraordinary source of antibiotic-resistant bacteria (ARB) and resistance genes (ARG) in terms of diversity and quantity. Accordingly, we analyzed ARG and ARB in airplane-borne sewage using complementary approaches: metagenomics, quantitative polymerase chain reaction (qPCR), and cultivation. For the purpose of comparison, we also quantified ARG and ARB in the inlets of municipal treatment plants with and without connection to airports. As expected, airplane sewage contained an extraordinarily rich set of mobile ARG, and the relative abundances of genes were mostly increased compared to typical raw sewage of municipal origin. Moreover, combined resistance against third-generation cephalosporins, fluorochinolones, and aminoglycosides was unusually common (28.9%) among Escherichia coli isolated from airplane sewage. This percentage exceeds the one reported for German clinical isolates by a factor of 8. Our findings suggest that airplane-borne sewage can effectively contribute to the fast and global spread of antibiotic resistance.Peer reviewe

IAB-Haushaltspanel Lebensqualität und soziale Sicherung : Interviewerhandbuch Welle 5 - 2011

"Im Zeitraum von Februar bis Juni 2011 werden ca. 12.000 Haushalte und etwa 20.000 Personen in Deutschland zu ihrer sozialen Sicherung und Lebensqualität befragt. Es handelt sich hierbei um die fünfte Befragungswelle der IAB-Panelstudie PASS. Der größte Teil der Haushalte wurde bereits viermal befragt und hat das Einverständnis für ein weiteres Interview gegeben. Daneben wurden in jeder Welle auch neue Haushalte für die Langzeitstudie ausgewählt. Diese ca. 1.000 Haushalte werden jeweils zum ersten Mal befragt." Der Methodenreport gibt den Interviewern Hinweise zu den Hintergründen der Studie, zur Durchführung der Befragung, zur Kontaktaufnahme mit den Befragungshaushalten und zum Interviewer-Verhalten. Weiterhin werden Informationen zum Fragebogen gegeben. (IAB2)IAB-Haushaltspanel, Befragung - Handbuch, Durchführungsanweisung, Datengewinnung

Multidrug-Resistant and Clinically Relevant Gram-Negative Bacteria Are Present in German Surface Waters

Water is considered to play a role in the dissemination of antibiotic-resistant Gram-negative bacteria including those encoding Extended-spectrum beta-lactamases (ESBL) and carbapenemases. To investigate the role of water for their spread in more detail, we characterized ESBL/Carbapenemase-producing bacteria from surface water and sediment samples using phenotypic and genotypic approaches. ESBL/Carbapenemase-producing isolates were obtained from water/sediment samples. Species and antibiotic resistance were determined. A subset of these isolates (n = 33) was whole-genome-sequenced and analyzed for the presence of antibiotic resistance genes and virulence determinants. Their relatedness to isolates associated with human infections was investigated using multilocus sequence type and cgMLST-based analysis. Eighty-nine percent of the isolates comprised of clinically relevant species. Fifty-eight percent exhibited a multidrug-resistance phenotype. Two isolates harbored the mobile colistin resistance gene mcr-1. One carbapenemase-producing isolate identified as Enterobacter kobei harbored bla(VIM-)(1). Two Escherichia coli isolates had sequence types (ST) associated with human infections (ST131 and ST1485) and a Klebsiella pneumoniae isolate was classified as hypervirulent. A multidrug-resistant (MDR) Pseudomonas aeruginosa isolate encoding known virulence genes associated with severe lung infections in cystic fibrosis patients was also detected. The presence of MDR and clinically relevant isolates in recreational and surface water underlines the role of aquatic environments as both reservoirs and hot spots for MDR bacteria. Future assessment of water quality should include the examination of the multidrug resistance of clinically relevant bacterial species and thus provide an important link regarding the spread of MDR bacteria in a One Health context.Peer reviewe

Soil microbiome indicators can predict crop growth response to large-scale inoculation with arbuscular mycorrhizal fungi

Alternative solutions to mineral fertilizers and pesticides that reduce the environmental impact of agriculture are urgently needed. Arbuscular mycorrhizal fungi (AMF) can enhance plant nutrient uptake and reduce plant stress; yet, large-scale field inoculation trials with AMF are missing, and so far, results remain unpredictable. We conducted on-farm experiments in 54 fields in Switzerland and quantified the effects on maize growth. Growth response to AMF inoculation was highly variable, ranging from -12% to +40%. With few soil parameters and mainly soil microbiome indicators, we could successfully predict 86% of the variation in plant growth response to inoculation. The abundance of pathogenic fungi, rather than nutrient availability, best predicted (33%) AMF inoculation success. Our results indicate that soil microbiome indicators offer a sustainable biotechnological perspective to predict inoculation success at the beginning of the growing season. This predictability increases the profitability of microbiome engineering as a tool for sustainable agricultural management

Continuous glucose monitoring in older adults with diabetes : data from the diabetes prospective follow-up (DPV) registry

Aims: To analyse predictors for continuous glucose monitoring (CGM) use in people with diabetes aged ≥60 years using insulin therapy and to assess the rates of CGM use during recent years (2019–2021). Research Design and Methods: Prospective study including 6849 individuals with diabetes and insulin therapy (type 2 diabetes: n = 5320; type 1 diabetes: n = 1529) aged ≥60 years. Data from 129 treatment centres were retrieved from the Diabetes Prospective Follow-up Registry (DPV) in March 2023. Results: Sensor use in individuals aged ≥60 years has increased in type 1 (2019: 28%, 2020: 39%, 2021: 45%) and type 2 diabetes (2019: 10%, 2020: 16%, 2021: 18%). Predictors for sensor use in older individuals with type 1 diabetes are younger age and CSII use (p < 0.001). Predictors in older individuals with type 2 diabetes are younger age, longer diabetes duration, higher BMI and CSII use (p < 0.001). Conclusions: CGM has become more common in older adults with diabetes and will presumably increase further. Age is a predictor for sensor use in older adults with diabetes. Age-related physical barriers and insufficient usability of devices, lack of interest in technologies, but possibly also effects of prejudice on the grounds of age may contribute to this finding

SchussenAktivplus: reduction of micropollutants and of potentially pathogenic bacteria for further water quality improvement of the river Schussen, a tributary of Lake Constance, Germany

The project focuses on the efficiency of combined technologies to reduce the release of micropollutants and bacteria into surface waters via sewage treatment plants of different size and via stormwater overflow basins of different types. As a model river in a highly populated catchment area, the river Schussen and, as a control, the river Argen, two tributaries of Lake Constance, Southern Germany, are under investigation in this project. The efficiency of the different cleaning technologies is monitored by a wide range of exposure and effect analyses including chemical and microbiological techniques as well as effect studies ranging from molecules to communities

Population pharmacokinetics of TLD-1, a novel liposomal doxorubicin, in a phase I trial.

STUDY OBJECTIVES TLD-1 is a novel pegylated liposomal doxorubicin (PLD) formulation aiming to optimise the PLD efficacy-toxicity ratio. We aimed to characterise TLD-1's population pharmacokinetics using non-compartmental analysis and nonlinear mixed-effects modelling. METHODS The PK of TLD-1 was analysed by performing a non-compartmental analysis of longitudinal doxorubicin plasma concentration measurements obtained from a clinical trial in 30 patients with advanced solid tumours across a 4.5-fold dose range. Furthermore, a joint parent-metabolite PK model of doxorubicinentrapped, doxorubicinfree, and metabolite doxorubicinol was developed. Interindividual and interoccasion variability around the typical PK parameters and potential covariates to explain parts of this variability were explored. RESULTS Medians  standard deviations of dose-normalised doxorubicinentrapped+free Cmax and AUC0-∞ were 0.342 0.134 mg/L and 40.1 18.9 mg·h/L, respectively. The median half-life (95 h) was 23.5 h longer than the half-life of currently marketed PLD. The novel joint parent-metabolite model comprised a one-compartment model with linear release (doxorubicinentrapped), a two-compartment model with linear elimination (doxorubicinfree), and a one-compartment model with linear elimination for doxorubicinol. Body surface area on the volumes of distribution for free doxorubicin was the only significant covariate. CONCLUSION The population PK of TLD-1, including its release and main metabolite, were successfully characterised using non-compartmental and compartmental analyses. Based on its long half-life, TLD-1 presents a promising candidate for further clinical development. The PK characteristics form the basis to investigate TLD-1 exposure-response (i.e., clinical efficacy) and exposure-toxicity relationships in the future. Once such relationships have been established, the developed population PK model can be further used in model-informed precision dosing strategies. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov-NCT03387917-January 2, 2018