The ribosome lowers the entropic penalty of protein folding.

Most proteins fold during biosynthesis on the ribosome, and co-translational folding energetics, pathways and outcomes of many proteins have been found to differ considerably from those in refolding studies. The origin of this folding modulation by the ribosome has remained unknown. Here we have determined atomistic structures of the unfolded state of a model protein on and off the ribosome, which reveal that the ribosome structurally expands the unfolded nascent chain and increases its solvation, resulting in its entropic destabilization relative to the peptide chain in isolation.

Bayesian reweighting of biomolecular structural ensembles using heterogeneous cryo-EM maps with the cryoENsemble method.

Cryogenic electron microscopy (cryo-EM) has emerged as a powerful method for the determination of structures of complex biological molecules. The accurate characterisation of the dynamics of such systems, however, remains a challenge. To address this problem, we introduce cryoENsemble, a method that applies Bayesian reweighting to conformational ensembles derived from molecular dynamics simulations to improve their agreement with cryo-EM data, thus enabling the extraction of dynamics information.

Risk Evaluation in Occupational Safety and Health Research: Results From a Benchmarking Exercise of Federal and Academic IRBs.

Objective: Research involving working populations can pose unique ethical and risk evaluation challenges. The purpose of this benchmarking project was to assess how federal agencies and academic institutions approach the interpretation and application of key risk evaluation concepts in research involving workers in their places of employment.

Methods: Key informant interviews were conducted to ascertain current practices related to assessing soundness of research design, determining risk reasonableness and research relatedness of risks, and evaluating the risk of noninvasive clinical tests in occupational settings.

Preparing the occupational safety and health workforce for future disruptions.

Background: Despite some emerging lessons learned from the COVID-19 pandemic, evidence suggests the world remains largely underprepared for-and vulnerable to-similar threats in the future.

Methods: In 2022, researchers at the US National Institute for Occupational Safety and Health (NIOSH) led a team of volunteers to explore how future disruptions, such as pandemics, might impact work and the practice of occupational safety and health (OSH). This qualitative inquiry was framed as a strategic foresight project and included a series of activities designed to help better understand, prepare for, and influence the future.

Four Futures for Occupational Safety and Health.

Rapid changes to the nature of work have challenged the capacity of existing occupational safety and health (OSH) systems to ensure safe and productive workplaces. An effective response will require an expanded focus that includes new tools for anticipating and preparing for an uncertain future. Researchers at the U.

Contemporary Evaluation of Tebipenem Activity against Enterobacterales Clinical Isolates Causing Urinary Tract Infections in US Medical Centers (2019-2020).

Tebipenem pivoxil is an oral broad-spectrum carbapenem. This study evaluated the activity of tebipenem and comparators against UTI Enterobacterales from US hospitals (2019-2020). 3,576 Enterobacterales causing UTI in 52 centers in 9 US Census Divisions were included.

Expanding the Focus of Occupational Safety and Health: Lessons from a Series of Linked Scientific Meetings.

There is widespread recognition that the world of work is changing, and agreement is growing that the occupational safety and health (OSH) field must change to contribute to the protection of workers now and in the future. Discourse on the evolution of OSH has been active for many decades, but formalized support of an expanded focus for OSH has greatly increased over the past 20 years. Development of approaches such as the National Institute for Occupational Safety and Health (NIOSH)'s Total Worker Health concept and the World Health Organization (WHO)'s Healthy Workplace Framework are concrete examples of how OSH can incorporate a new focus with a wider view.

Activity of meropenem/vaborbactam and comparators against non-carbapenemase-producing carbapenem-resistant Enterobacterales isolates from Europe.

Background: Carbapenem-resistant Enterobacterales (CRE) isolates have disseminated worldwide. CREs usually produce a carbapenemase; however, some isolates are negative for known carbapenemases. In this study, we evaluated the activity of meropenem/vaborbactam and comparators against CREs without a carbapenemase (nonCP CREs) collected from European hospitals from 2016 to 2019.

Tedizolid in vitro activity against Gram-positive clinical isolates causing bone and joint infections in hospitals in the USA, Europe, Latin America, and the Asia-Pacific region (2015-2019).

As bone and joint infections (BJIs) frequently require prolonged, systemic antibiotic use, tedizolid is an attractive candidate for BJI therapy in adults and children. Tedizolid activity was evaluated against 1,193 Gram-positive isolates causing BJI in American (USA), European (EUR), Latin American (LATAM), and Asian-Pacific (APAC) medical centers. Isolates consecutively collected from 2015 to 2019 were susceptibility tested by CLSI broth microdilution.

Implementation of a surgical site infection prevention bundle: Patient adherence and experience.

We evaluated barriers and facilitators to patient adherence with a bundled intervention including chlorhexidine gluconate (CHG) bathing and decolonizing nasal carriers in a real-world setting. Survey data identified 85.5% adherence with home use of CHG as directed and 52.

Five-year analysis of the activity of tedizolid against a worldwide collection of indicated species causing clinical infections: results from the Surveillance of Tedizolid Activity and Resistance (STAR) programme.

Objectives: The Surveillance of Tedizolid Activity and Resistance (STAR) programme monitored the tedizolid activity against , , , and group. We evaluated the antimicrobial susceptibility of 47 400 unique Gram-positive clinical isolates from the STAR programme collected from USA (21 243), Europe (17 674), Asia-Pacific (4954) and Latin America (3529) medical centres (2015-19).

Methods: All isolates were tested for susceptibility by reference broth microdilution method.

Infigratinib Reduces Fibroblast Growth Factor 23 (FGF23) and Increases Blood Phosphate in Tumor-Induced Osteomalacia.

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by ectopic production of fibroblast growth factor 23 (FGF23) by phosphaturic mesenchymal tumors (PMTs). Acting on renal tubule cells, excess FGF23 decreases phosphate reabsorption and 1,25-dihydroxy-vitamin D (1,25D) production, leading to hypophosphatemia, impaired bone mineralization, pain, and fractures. Fibronectin 1-fibroblast growth factor receptor 1 (FN1-FGFR1) gene fusions have been identified as possible drivers in up to 40% of resected PMTs.

Activity of Ceftolozane-Tazobactam Against Gram-Negative Isolates from Australia and New Zealand as part of the PACTS Surveillance 2016-2018.

Objectives: Ceftolozane-tazobactam (C-T) is an anti-pseudomonal cephalosporin combined with a well-described β-lactamase inhibitor. Ceftolozane-tazobactam has enhanced activity against Pseudomonas aeruginosa, and activity against Enterobacterales isolates that produce extended-spectrum β-lactamases (ESBLs) or AmpC cephalosporinases. In this study, we analysed the susceptibility of Gram-negative isolates to C-T and comparators collected in Australia and New Zealand from 2016 to 2018 as part of the Program to Assess Ceftolozane-Tazobactam Susceptibility (PACTS) surveillance.

Resign or carry-on? District and principal leadership as drivers of change in teacher turnover intentions during the COVID-19 crisis: A latent growth model examination.

During the COVID-19 pandemic, teachers in the United States, an already at-risk occupation group, experienced new work-related stressors, safety concerns, and work-life challenges, magnifying on-going retention concerns. Integrating the crisis management literature with the unfolding model of turnover, we theorize that leader actions trigger initial employee responses but also set the stage for on-going crisis response that influence changes in teachers' turnover intentions. We apply latent growth curve modelling to test our hypotheses based on a sample of 617 K-12 teachers using nine waves of data, including a baseline survey at the start of the 2020-2021 school year and eight follow-up surveys (2-week lags) through the Fall 2020 semester.

The ribosome stabilizes partially folded intermediates of a nascent multi-domain protein.

Co-translational folding is crucial to ensure the production of biologically active proteins. The ribosome can alter the folding pathways of nascent polypeptide chains, yet a structural understanding remains largely inaccessible experimentally. We have developed site-specific labelling of nascent chains to detect and measure, using F nuclear magnetic resonance (NMR) spectroscopy, multiple states accessed by an immunoglobulin-like domain within a tandem repeat protein during biosynthesis.

Activity of Cefiderocol against U.S. and European Gram-Negative Clinical Isolates Collected in 2020 as Part of the SENTRY Antimicrobial Surveillance Program.

Cefiderocol is a siderophore-conjugated cephalosporin with broad activity against Gram-negative (GN) bacteria, including carbapenem-resistant (CRE), Pseudomonas aeruginosa, Acinetobacter spp., and Stenotrophomonas maltophilia. Cefiderocol was approved by the FDA for treatment of complicated urinary tract infection, hospital-acquired bacterial pneumonia, and ventilator-associated bacterial pneumonia and by the European Medicines Agency (EMA) for aerobic GN infections in adults with few treatment options.

Promising Occupational Safety, Health, and Well-Being Approaches to Explore the Future of Work in the USA: An Editorial.

The future of work continues to undergo profound and fundamental changes in response to shifting social, technological, economic, environmental, and political contexts [...

Clinical characteristics of COVID-19 in solid organ transplant recipients following COVID-19 vaccination: A multicenter case series.

Background: Solid organ transplant recipients (SOTR) have diminished humoral immune responses to COVID-19 vaccination and higher rates of COVID-19 vaccine breakthrough infection than the general population. Little is known about COVID-19 disease severity in SOTR with COVID-19 vaccine breakthrough infections.

Methods: Between 4/7/21 and 6/21/21, we requested case reports via the Emerging Infections Network (EIN) listserv of SARS-CoV-2 infection following COVID-19 vaccination in SOTR.

Activity of Oritavancin against Gram-Positive Pathogens Causing Bloodstream Infections in the United States over 10 Years: Focus on Drug-Resistant Enterococcal Subsets (2010-2019).

Oritavancin displayed potent and stable activity (MIC range of 0.06 to 0.5 mg/L) over a 10-year period (2010 to 2019) against Gram-positive pathogens that cause bloodstream infections (BSI), including methicillin-resistant Staphylococcus aureus (MRSA) and resistant subsets of spp.

Antimicrobial susceptibility of Gram-negative bacteria from intensive care unit and non-intensive care unit patients from United States hospitals (2018-2020).

We evaluated the antimicrobial susceptibility of Gram-negative bacteria recovered from ICU patients in US hospitals and compared them to those from non-ICU patients from the same hospitals during the same period. Overall, 4,680 isolates from ICU patients and 16,263 isolates from non-ICU patients were collected from 70 US medical centers in 2018-2020 and susceptibility tested by the broth microdilution method. Ceftazidime-avibactam and ceftolozane-tazobactam were the most active agents against P.

Frequency of occurrence and antimicrobial susceptibility of bacteria isolated from respiratory samples of patients hospitalized with pneumonia in Western Europe, Eastern Europe and the USA: results from the SENTRY Antimicrobial Surveillance Program (2016-19).

Background: The SENTRY Antimicrobial Surveillance Program monitors the frequency of occurrence and antimicrobial susceptibility of organisms from various infection types worldwide.

Objectives: To evaluate the SENTRY programme results for organisms isolated from respiratory samples of patients hospitalized with probable pneumonia.

Methods: A total of 28 918 bacterial isolates were consecutively collected (one per patient) in 2016-19 from 121 medical centres located in western Europe (W-EU; = 7966), eastern Europe (E-EU; = 3182) and the USA ( = 17 770) and then susceptibility tested by reference broth microdilution methods in a central laboratory.

Interactions between nascent proteins and the ribosome surface inhibit co-translational folding.

Most proteins begin to fold during biosynthesis on the ribosome. It has been suggested that interactions between the emerging polypeptide and the ribosome surface might allow the ribosome itself to modulate co-translational folding. Here we combine protein engineering and NMR spectroscopy to characterize a series of interactions between the ribosome surface and unfolded nascent chains of the immunoglobulin-like FLN5 filamin domain.

Activity of the Novel Aminomethylcycline KBP-7072 and Comparators against 1,057 Geographically Diverse Recent Clinical Isolates from the SENTRY Surveillance Program, 2019.

KBP-7072 is a novel broad-spectrum tetracycline (aminomethylcycline) antibacterial in clinical development (oral and intravenous formulations) for the treatment of acute bacterial skin and skin structure infections, community-acquired bacterial pneumonia, and complicated intra-abdominal infections. KBP-7072 is active against many of the World Health Organization priority pathogens. In this study, KBP-7072 and tetracycline class comparators were susceptibility tested against 1,057 geographically diverse surveillance isolates from 2019 according to Clinical and Laboratory Standards Institute (CLSI) guidelines.