Inter-rater reliability of muscle ultrasonography performed by multidisciplinary novice sonographers in the evaluation of critically ill patients with acute kidney injury requiring continuous kidney replacement therapy.

Early diagnosis of muscle wasting in critically ill patients with acute kidney injury requiring continuous kidney replacement therapy (AKI-CKRT) may improve outcomes timely rehabilitation and nutrition. Muscle ultrasound (MUS) has recently gained traction for assessing muscle atrophy in the intensive care unit (ICU) but requires training to achieve reproducibility. We evaluated the inter-rater reliability of MUS in patients with AKI-CKRT performed by multidisciplinary raters including nephrologists.

Exploring the principles behind antibiotics with limited resistance.

Antibiotics that target multiple cellular functions are anticipated to be less prone to bacterial resistance. Here we hypothesize that while dual targeting is crucial, it is not sufficient in preventing resistance. Only those antibiotics that simultaneously target membrane integrity and block another cellular pathway display reduced resistance development.

Amide Internucleoside Linkages Suppress the MicroRNA-like Off-Target Activity of Short Interfering RNA.

RNA interference (RNAi) has rapidly matured as a novel therapeutic approach. In this field, chemical modifications have been critical to the clinical success of short interfering RNAs (siRNAs). Notwithstanding the significant advances, achieving robust durability and gene silencing in extrahepatic tissues, as well as reducing off-target effects of siRNA, are areas where chemical modifications can still improve siRNA performance.

ESKAPE pathogens rapidly develop resistance against antibiotics in development in vitro.

Despite ongoing antibiotic development, evolution of resistance may render candidate antibiotics ineffective. Here we studied in vitro emergence of resistance to 13 antibiotics introduced after 2017 or currently in development, compared with in-use antibiotics. Laboratory evolution showed that clinically relevant resistance arises within 60 days of antibiotic exposure in Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa, priority Gram-negative ESKAPE pathogens.

Antibiotic candidates for Gram-positive bacterial infections induce multidrug resistance.

Several antibiotic candidates are in development against Gram-positive bacterial pathogens, but their long-term utility is unclear. To investigate this issue, we studied the laboratory evolution of resistance to antibiotics that have not yet reached the market. We found that, with the exception of compound SCH79797, antibiotic resistance generally readily evolves in .