Demographic fluctuations in bloodstream lineages configure the mobile gene pool and antimicrobial resistance.

in the bloodstream causes high morbidity and mortality, exacerbated by the spread of multidrug-resistant and methicillin-resistant (MRSA). We aimed to characterize the circulating lineages of from bloodstream infections and the contribution of individual lineages to resistance over time. Here, we generated 852 high-quality short-read draft genome sequences of isolates from patient blood cultures in a single hospital from 2010 to 2022.

Multi-host infection and phylogenetically diverse lineages shape the recombination and gene pool dynamics of Staphylococcus aureus.

Background: Staphylococcus aureus can infect and adapt to multiple host species. However, our understanding of the genetic and evolutionary drivers of its generalist lifestyle remains inadequate. This is particularly important when considering local populations of S.

Prophage-encoded immune evasion factors are critical for host infection, switching, and adaptation.

is a multi-host pathogen that causes infections in animals and humans globally. The specific genetic loci-and the extent to which they drive cross-species switching, transmissibility, and adaptation-are not well understood. Here, we conducted a population genomic study of 437 isolates to identify bacterial genetic variation that determines infection of human and animal hosts through a genome-wide association study (GWAS) using linear mixed models.

Quantifying the breadth of antibiotic exposure in sepsis and suspected infection using spectrum scores.

A retrospective cohort study. Studies to quantify the breadth of antibiotic exposure across populations remain limited. Therefore, we applied a validated method to describe the breadth of antimicrobial coverage in a multicenter cohort of patients with suspected infection and sepsis.

Genome Sequencing of Methicillin-Resistant and Methicillin-Susceptible from Diseased Animals.

Mammaliicoccus sciuri (previously Staphylococcus sciuri) is a frequent colonizer of mammals. We report the draft genomes of a methicillin-resistant strain (2254A) isolated from an armadillo and a methicillin-susceptible strain (6942A) from a cow. Genomes were sequenced using long-read Nanopore sequencing.

Genome characteristics of clinical Salmonella enterica population from a state public health laboratory, New Hampshire, USA, 2017-2020.

Background: The implementation of whole genome sequencing (WGS) by PulseNet, the molecular subtyping network for foodborne diseases, has transformed surveillance, outbreak detection, and public health laboratory practices in the United States. In 2017, the New Hampshire Public Health Laboratories, a member of PulseNet, commenced the use of WGS in tracking foodborne pathogens across the state. We present some of the initial results of New Hampshire's initiative to transition to WGS in tracking Salmonella enterica, a bacterial pathogen that is responsible for non-typhoidal foodborne infections and enteric fever.

Temporal Trends in Antimicrobial Prescribing During Hospitalization for Potential Infection and Sepsis.

Importance: Some experts have cautioned that national and health system emphasis on rapid administration of antimicrobials for sepsis may increase overall antimicrobial use even among patients without sepsis.

Objective: To assess whether temporal changes in antimicrobial timing for sepsis are associated with increasing antimicrobial use, days of therapy, or broadness of antimicrobial coverage among all hospitalized patients at risk for sepsis.

Design, Setting, And Participants: This is an observational cohort study of hospitalized patients at 152 hospitals in 2 health care systems during 2013 to 2018, admitted via the emergency department with 2 or more systemic inflammatory response syndrome (SIRS) criteria.

Genome Evolution of Invasive Methicillin-Resistant Staphylococcus aureus in the Americas.

Staphylococcus aureus causes a variety of debilitating and life-threatening diseases, and thus remains a challenging global health threat. S. aureus is remarkably diverse, yet only a minority of methicillin-resistant S.

Shared antibiotic resistance and virulence genes in Staphylococcus aureus from diverse animal hosts.

The emergence of methicillin-resistant Staphylococcus aureus (MRSA) poses an important threat in human and animal health. In this study, we ask whether resistance and virulence genes in S. aureus are homogeneously distributed or constrained by different animal hosts.

Accessory Genome Dynamics of Local and Global Populations.

is a major bacterial colonizer and opportunistic pathogen in dogs. Methicillin-resistant (MRSP) continues to emerge as a significant challenge to maintaining canine health. We sought to determine the phylogenetic relationships of across five states in the New England region of the United States and place them in a global context.

Outcomes After Implementation of a Benzodiazepine-Sparing Alcohol Withdrawal Order Set in an Integrated Health Care System.

Importance: Alcohol withdrawal syndrome (AWS) is a common inpatient diagnosis managed primarily with benzodiazepines. Concerns about the adverse effects associated with benzodiazepines have spurred interest in using benzodiazepine-sparing treatments.

Objective: To evaluate changes in outcomes after implementation of a benzodiazepine-sparing AWS inpatient order set that included adjunctive therapies (eg, gabapentin, valproic acid, clonidine, and dexmedetomidine).

Extensive Horizontal Gene Transfer within and between Species of Coagulase-Negative Staphylococcus.

Members of the gram-positive bacterial genus Staphylococcus have historically been classified into coagulase-positive Staphylococcus (CoPS) and coagulase-negative Staphylococcus (CoNS) based on the diagnostic presentation of the coagulase protein. Previous studies have noted the importance of horizontal gene transfer (HGT) and recombination in the more well-known CoPS species Staphylococcus aureus, yet little is known of the contributions of these processes in CoNS evolution. In this study, we aimed to elucidate the phylogenetic relationships, genomic characteristics, and frequencies of HGT in CoNS, which are now being recognized as major opportunistic pathogens of humans.

Retrospective Cohort Study Comparing Infliximab-dyyb and Infliximab in Biologic-Naive Patients With Inflammatory Bowel Disease in the United States.

Background: Real-world assessments of biosimilars are needed to understand their effectiveness and safety in practice settings that may differ from those seen in clinical trials or healthcare systems in different countries. To assess the effectiveness and safety of a biosimilar (infliximab-dyyb) and its reference product (infliximab) in patients with inflammatory bowel disease (IBD) in the United States.

Methods: We conducted a retrospective cohort study of biologic-naive patients with IBD who started treatment with infliximab-dyyb or infliximab.

Genomic epidemiology of methicillin-resistant and -susceptible Staphylococcus aureus from bloodstream infections.

Background: Bloodstream infections due to Staphylococcus aureus cause significant patient morbidity and mortality worldwide. Of major concern is the emergence and spread of methicillin-resistant S. aureus (MRSA) in bloodstream infections, which are associated with therapeutic failure and increased mortality.

Melanin pigments extracted from horsehair as antibacterial agents.

Here we present the important findings related to biologically derived pigments for potential use as antibacterial agents. Melanin biopigments extracted from Equus ferus hair exhibit a homogeneous elliptical microstructure with highly ordered semicrystalline features. Spectroscopic analysis indicates that melanin contains a high degree of redox active catechol groups, which can produce reactive oxygen species.

Deterministic Lateral Displacement: Challenges and Perspectives.

The advent of microfluidics in the 1990s promised a revolution in multiple industries from healthcare to chemical processing. Deterministic lateral displacement (DLD) is a continuous-flow microfluidic particle separation method discovered in 2004 that has been applied successfully and widely to the separation of blood cells, yeast, spores, bacteria, viruses, DNA, droplets, and more. Deterministic lateral displacement is conceptually simple and can deliver consistent performance over a wide range of flow rates and particle concentrations.

Population genomics of Staphylococcus pseudintermedius in companion animals in the United States.

Staphylococcus pseudintermedius is a commensal bacterium and a major opportunistic pathogen of dogs. The emergence of methicillin-resistant S. pseudintermedius (MRSP) is also becoming a serious concern.

exRNA Atlas Analysis Reveals Distinct Extracellular RNA Cargo Types and Their Carriers Present across Human Biofluids.

To develop a map of cell-cell communication mediated by extracellular RNA (exRNA), the NIH Extracellular RNA Communication Consortium created the exRNA Atlas resource (https://exrna-atlas.org). The Atlas version 4P1 hosts 5,309 exRNA-seq and exRNA qPCR profiles from 19 studies and a suite of analysis and visualization tools.

Gel-on-a-chip: continuous, velocity-dependent DNA separation using nanoscale lateral displacement.

We studied the trajectories of polymers being advected while diffusing in a pressure driven flow along a periodic pillar nanostructure known as nanoscale deterministic lateral displacement (nanoDLD) array. We found that polymers follow different trajectories depending on their length, flow velocity and pillar array geometry, demonstrating that nanoDLD devices can be used as a continuous polymer fractionation tool. As a model system, we used double-stranded DNA (dsDNA) with various contour lengths and demonstrated that dsDNA in the range of 100-10 000 base pairs (bp) can be separated with a size-selective resolution of 200 bp.

Integrated nanoscale deterministic lateral displacement arrays for separation of extracellular vesicles from clinically-relevant volumes of biological samples.

Extracellular vesicles (EVs) offer many opportunities in early-stage disease diagnosis, treatment monitoring, and precision therapy owing to their high abundance in bodily fluids, accessibility from liquid biopsy, and presence of nucleic acid and protein cargo from their cell of origin. Despite their growing promise, isolation of EVs for analysis remains a labor-intensive and time-consuming challenge given their nanoscale dimensions (30-200 nm) and low buoyant density. Here, we report a simple, size-based EV separation technology that integrates 1024 nanoscale deterministic lateral displacement (nanoDLD) arrays on a single chip capable of parallel processing sample fluids at rates of up to 900 μL h-1.

Broken flow symmetry explains the dynamics of small particles in deterministic lateral displacement arrays.

Deterministic lateral displacement (DLD) is a technique for size fractionation of particles in continuous flow that has shown great potential for biological applications. Several theoretical models have been proposed, but experimental evidence has demonstrated that a rich class of intermediate migration behavior exists, which is not predicted. We present a unified theoretical framework to infer the path of particles in the whole array on the basis of trajectories in a unit cell.

Nanoscale lateral displacement arrays for the separation of exosomes and colloids down to 20 nm.

Deterministic lateral displacement (DLD) pillar arrays are an efficient technology to sort, separate and enrich micrometre-scale particles, which include parasites, bacteria, blood cells and circulating tumour cells in blood. However, this technology has not been translated to the true nanoscale, where it could function on biocolloids, such as exosomes. Exosomes, a key target of 'liquid biopsies', are secreted by cells and contain nucleic acid and protein information about their originating tissue.

Hydrodynamics of diamond-shaped gradient nanopillar arrays for effective DNA translocation into nanochannels.

Effective DNA translocation into nanochannels is critical for advancing genome mapping and future single-molecule DNA sequencing technologies. We present the design and hydrodynamic study of a diamond-shaped gradient pillar array connected to nanochannels for enhancing the success of DNA translocation events. Single-molecule fluorescence imaging is utilized to interrogate the hydrodynamic interactions of the DNA with this unique structure, evaluate key DNA translocation parameters, including speed, extension, and translocation time, and provide a detailed mapping of the translocation events in nanopillar arrays coupled with 10 and 50 μm long channels.