Telomerase subunit Est2 marks internal sites that are prone to accumulate DNA damage

BACKGROUND: The main function of telomerase is at the telomeres but under adverse conditions telomerase can bind to internal regions causing deleterious effects as observed in cancer cells. RESULTS: By mapping the global occupancy of the catalytic subunit of telomerase (Est2) in the budding yeast Saccharomyces cerevisiae, we reveal that it binds to multiple guanine-rich genomic loci, which we termed “non-telomeric binding sites” (NTBS). We characterize Est2 binding to NTBS. Contrary to telomeres, Est2 binds to NTBS in G1 and G2 phase independently of Est1 and Est3. The absence of Est1 and Est3 renders telomerase inactive at NTBS. However, upon global DNA damage, Est1 and Est3 join Est2 at NTBS and telomere addition can be observed indicating that Est2 occupancy marks NTBS regions as particular risks for genome stability. CONCLUSIONS: Our results provide a novel model of telomerase regulation in the cell cycle using internal regions as “parking spots” of Est2 but marking them as hotspots for telomere addition. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12915-021-01167-1

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Delphi study to derive expert consensus on a set of criteria to evaluate discharge readiness for adult ICU patients to be discharged to a general ward—European perspective

Abstract Background/purpose Discharge decisions in Intensive Care Unit (ICU) patients are frequently taken under pressure to free up ICU beds. In the absence of established guidelines, the evaluation of discharge readiness commonly underlies subjective judgements. The challenge is to come to the right decision at the right time for the right patient. A premature care transition puts patients at risk of readmission to the ICU. Delayed discharge is a waste of resources and may result in over-treatment and suboptimal patient flow. More objective decision support is required to assess the individual patient’s discharge readiness but also the current care capabilities of the receiving unit. Methods In a modified online Delphi process, an international panel of 27 intensive care experts reached consensus on a set of 28 intensive care discharge criteria. An initial evidence-based proposal was developed further through the panelists’ edits, adding, comments and voting over a course of 5 rounds. Consensus was defined as achieved when ≥ 90% of the experts voted for a given option on the Likert scale or in a multiple-choice survey. Round 1 to 3 focused on inclusion and exclusion of the criteria based on the consensus threshold, where round 3 was a reiteration to establish stability. Round 4 and 5 focused on the exact phrasing, values, decision makers and evaluation time frames per criterion. Results Consensus was reached on a standard set of 28 ICU discharge criteria for adult ICU patients, that reflect the patient’s organ systems ((respiratory (7), cardiovascular (9), central nervous (1), and urogenital system (2)), pain (1), fluid loss and drainages (1), medication and nutrition (1), patient diagnosis, prognosis and preferences (2) and institution-specific criteria (4). All criteria have been specified in a binary decision metric (fit for ICU discharge vs. needs further intensive therapy/monitoring), with consented value calculation methods where applicable and a criterion importance rank with “mandatory to be met” flags and applicable exceptions. Conclusion For a timely identification of stable intensive care patients and safe and efficient care transitions, a standardized discharge readiness evaluation should be based on patient factors as well as organizational boundary conditions and involve multiple stakeholders

Additional file 4 of Delphi study to derive expert consensus on a set of criteria to evaluate discharge readiness for adult ICU patients to be discharged to a general ward—European perspective

Additional file 4

Additional file 4 of Delphi study to derive expert consensus on a set of criteria to evaluate discharge readiness for adult ICU patients to be discharged to a general ward—European perspective

Additional file 4

Genetic Characterization of Carbapenem-Resistant Klebsiella spp. from Municipal and Slaughterhouse Wastewater

Currently, human and veterinary medicine are threatened worldwide by an increasing resistance to carbapenems, particularly present in opportunistic Enterobacterales pathogens (e.g., Klebsiella spp.). However, there is a lack of comprehensive and comparable data on their occurrence in wastewater, as well as on the phenotypic and genotypic characteristics for various countries including Germany. Thus, this study aims to characterize carbapenem-resistant Klebsiella spp. isolated from municipal wastewater treatment plants (mWWTPs) and their receiving water bodies, as well as from wastewater and process waters from poultry and pig slaughterhouses. After isolation using selective media and determination of carbapenem (i.e., ertapenem) resistance using broth microdilution to apply epidemiological breakpoints, the selected isolates (n = 30) were subjected to WGS. The vast majority of the isolates (80.0%) originated from the mWWTPs and their receiving water bodies. In addition to ertapenem, Klebsiella spp. isolates exhibited resistance to meropenem (40.0%) and imipenem (16.7%), as well as to piperacillin-tazobactam (50.0%) and ceftolozan-tazobactam (50.0%). A high diversity of antibiotic-resistance genes (n = 68), in particular those encoding β-lactamases, was revealed. However, with the exception of blaGES-5-like, no acquired carbapenemase-resistance genes were detected. Virulence factors such as siderophores (e.g., enterobactin) and fimbriae type 1 were present in almost all isolates. A wide genetic diversity was indicated by assigning 66.7% of the isolates to 12 different sequence types (STs), including clinically relevant ones (e.g., ST16, ST252, ST219, ST268, ST307, ST789, ST873, and ST2459). Our study provides information on the occurrence of carbapenem-resistant, ESBL-producing Klebsiella spp., which is of clinical importance in wastewater and surface water in Germany. These findings indicate their possible dissemination in the environment and the potential risk of colonization and/or infection of humans, livestock and wildlife associated with exposure to contaminated water sources

Additional file 9 of Telomerase subunit Est2 marks internal sites that are prone to accumulate DNA damage

Supplementary Table 4. List of yeast strains used in this study