Identifying high-risk central lines in critically ill children: A novel nurse-driven screening and mitigation intervention to reduce CLABSI.

Background: Despite strong adherence to central line-associated bloodstream infection (CLABSI) infection prevention bundles, the CLABSI rate in our academic pediatric intensive care unit (PICU) and pediatric cardiac intensive unit (PCICU) remained high.

Methods: We developed a novel screening tool that stratified patients' risk for CLABSI and considered risk mitigation strategies.

Results: Of 1,583 screenings, 30% were classified as high-risk, 27% as moderate-risk, and 43% as low-risk.

Evaluation of a Comprehensive Algorithm for PICU Patients With New Fever or Instability: Association of Clinical Decision Support With Testing Practices.

Objectives: Previously, we implemented a comprehensive decision support tool, a "New Fever Algorithm," to support the evaluation of PICU patients with new fever or instability. This tool was associated with a decline in culture rates without safety concerns. We assessed the impact of the algorithm on testing practices by identifying the proportion of cultures pre- vs.

A Novel Comprehensive Algorithm for Evaluation of PICU Patients With New Fever or Instability.

Objectives: There is variation in microbiology testing among PICU patients with fever offering opportunities to reduce avoidable testing and treatment. Our objective is to describe the development and assess the impact of a novel comprehensive testing algorithm to support judicious testing practices and expanded diagnostic differentials for PICU patients with new fever or instability.

Design: A mixed-methods quality improvement study.

Males induce premature demise of the opposite sex by multifaceted strategies.

Interactions between the sexes negatively impact health in many species. In Caenorhabditis, males shorten the lifespan of the opposite sex-hermaphrodites or females. Here we use transcriptomic profiling and targeted screens to systematically uncover conserved genes involved in male-induced demise in C.

Biology of Stress Responses in Aging.

On April 28, 2022, a group of scientific leaders gathered virtually to discuss molecular and cellular mechanisms of responses to stress. Conditions of acute, high-intensity stress are well documented to induce a series of adaptive responses that aim to promote survival until the stress has dissipated and then guide recovery. However, high-intensity or persistent stress that goes beyond the cell's compensatory capacity are countered with resilience strategies that are not completely understood.

Culture Ordering for Patients with New-onset Fever: A Survey of Pediatric Intensive Care Unit Clinician Practices.

Introduction: Accurate assessment of infection in critically ill patients is vital to their care. Both indiscretion and under-utilization of diagnostic microbiology testing can contribute to inappropriate antibiotic administration or delays in diagnosis. However, indiscretion in diagnostic microbiology cultures may also lead to unnecessary tests that, if false-positive, would incur additional costs and unhelpful evaluations.

Coordination of Substrate Binding and Protonation in the MtrD Efflux Pump Controls the Functionally Rotating Transport Mechanism.

Multidrug resistance is a serious problem that threatens the effective treatment of the widespread sexually transmitted disease gonorrhea, caused by the Gram-negative bacterium . The drug efflux pump primarily implicated in antimicrobial resistance is the inner membrane transporter MtrD, which forms part of the tripartite multiple transferable resistance (Mtr) CDE efflux system. A structure of MtrD was first solved in 2014 as a symmetrical homotrimer, and then, recently, as an asymmetrical homotrimer.

Program evaluation of trauma-informed yoga for vulnerable populations.

Background: Trauma is highly prevalent among vulnerable populations, including those who are incarcerated, in treatment for substance use, or seeking mental health services. Trauma-informed yoga seeks to create a safer yoga practice for individuals with a trauma history and may improve emotional and physical wellbeing. Thus, we conducted an evaluation of a trauma-informed yoga program to gain insight into participant experiences.

Multidrug Resistance in Neisseria gonorrhoeae: Identification of Functionally Important Residues in the MtrD Efflux Protein.

A key mechanism that uses to achieve multidrug resistance is the expulsion of structurally different antimicrobials by the MtrD multidrug efflux protein. MtrD resembles the homologous AcrB efflux protein with several common structural features, including an open cleft containing putative access and deep binding pockets proposed to interact with substrates. A highly discriminating strain, with the MtrD and NorM multidrug efflux pumps inactivated, was constructed and used to confirm and extend the substrate profile of MtrD to include 14 new compounds.

Self-sperm induce resistance to the detrimental effects of sexual encounters with males in hermaphroditic nematodes.

Sexual interactions have a potent influence on health in several species, including mammals. Previous work in identified strategies used by males to accelerate the demise of the opposite sex (hermaphrodites). But whether hermaphrodites evolved counter-strategies against males remains unknown.

Insulin-like peptides and the mTOR-TFEB pathway protect hermaphrodites from mating-induced death.

Lifespan is shortened by mating, but these deleterious effects must be delayed long enough for successful reproduction. Susceptibility to brief mating-induced death is caused by the loss of protection upon self-sperm depletion. Self-sperm maintains the expression of a DAF-2 insulin-like antagonist, INS-37, which promotes the nuclear localization of intestinal HLH-30/TFEB, a key pro-longevity regulator.

AlloMAPS: allosteric mutation analysis and polymorphism of signaling database.

AlloMAPS database provides data on the causality and energetics of allosteric communication obtained with the structure-based statistical mechanical model of allostery (SBSMMA). The database contains data on allosteric signaling in three sets of proteins and protein chains: (i) 46 proteins with comprehensively annotated functional and allosteric sites; (ii) 1908 protein chains from PDBselect set of chains with low (<25%) sequence identity; (iii) 33 proteins with more than 50 known pathological SNPs in each molecule. In addition to energetics of allosteric signaling between known functional and regulatory sites, allosteric modulation caused by the binding to these sites, by SNPs, and by mutations designated by the user can be explored.

The Aging Epigenome.

During aging, the mechanisms that normally maintain health and stress resistance strikingly decline, resulting in decrepitude, frailty, and ultimately death. Exactly when and how this decline occurs is unknown. Changes in transcriptional networks and chromatin state lie at the heart of age-dependent decline.

Shockingly Early: Chromatin-Mediated Loss of the Heat Shock Response.

In this issue of Molecular Cell, Labbadia and Morimoto (2015) show that there is a precipitous decline in stress resistance at the onset of reproduction in C. elegans and that this transition is regulated by changes in repressive chromatin marks.

Intersecting transcription networks constrain gene regulatory evolution.

Epistasis-the non-additive interactions between different genetic loci-constrains evolutionary pathways, blocking some and permitting others. For biological networks such as transcription circuits, the nature of these constraints and their consequences are largely unknown. Here we describe the evolutionary pathways of a transcription network that controls the response to mating pheromone in yeast.

Males shorten the life span of C. elegans hermaphrodites via secreted compounds.

How an individual's longevity is affected by the opposite sex is still largely unclear. In the nematode Caenorhabditis elegans, the presence of males accelerated aging and shortened the life span of individuals of the opposite sex (hermaphrodites), including long-lived or sterile hermaphrodites. The male-induced demise could occur without mating and required only exposure of hermaphrodites to medium in which males were once present.

Protein modularity, cooperative binding, and hybrid regulatory states underlie transcriptional network diversification.

We examine how different transcriptional network structures can evolve from an ancestral network. By characterizing how the ancestral mode of gene regulation for genes specific to a-type cells in yeast species evolved from an activating paradigm to a repressing one, we show that regulatory protein modularity, conversion of one cis-regulatory sequence to another, distribution of binding energy among protein-protein and protein-DNA interactions, and exploitation of ancestral network features all contribute to the evolution of a novel regulatory mode. The formation of this derived mode of regulation did not disrupt the ancestral mode and thereby created a hybrid regulatory state where both means of transcription regulation (ancestral and derived) contribute to the conserved expression pattern of the network.

Intercalation of a new tier of transcription regulation into an ancient circuit.

Changes in gene regulatory networks are a major source of evolutionary novelty. Here we describe a specific type of network rewiring event, one that intercalates a new level of transcriptional control into an ancient circuit. We deduce that, over evolutionary time, the direct ancestral connections between a regulator and its target genes were broken and replaced by indirect connections, preserving the overall logic of the ancestral circuit but producing a new behaviour.

Arginine-rich motifs present multiple interfaces for specific binding by RNA.

A number of proteins containing arginine-rich motifs (ARMs) are known to bind RNA and are involved in regulating RNA processing in viruses and cells. Using automated selection methods we have generated a number of aptamers against ARM peptides from various natural proteins. Aptamers bind tightly to their cognate ARMs, with K(d) values in the nanomolar range, and frequently show no propensity to bind to other ARMs or even to single amino acid variants of the cognate ARM.