Genome-scale resources in the infant gut symbiont Bifidobacterium breve reveal genetic determinants of colonization and host-microbe interactions.

Bifidobacteria represent a dominant constituent of human gut microbiomes during infancy, influencing nutrition, immune development, and resistance to infection. Despite interest in bifidobacteria as a live biotic therapy, our understanding of colonization, host-microbe interactions, and the health-promoting effects of bifidobacteria is limited. To address these major knowledge gaps, we used a large-scale genetic approach to create a mutant fitness compendium in Bifidobacterium breve.

Neurocognitive and neurobehavioral mechanisms of change following psychological treatment for alcohol use disorder.

Background: Although modestly effective treatments exist for alcohol use disorder (AUD), many individuals return to heavy drinking after treatment, suggesting the need for better understanding of factors that contribute to maintaining abstinence or drinking reductions. Whereas past studies identified what treatments work for AUD, recent studies focus more on why particular treatments work, and the mechanisms by which treatment leads to change. This focus on mechanisms of behavior change (MOBC) may inform the process by which treatment leads to better outcomes, and also may lead to new treatments or modifications of existing treatments that target empirically supported mechanisms known to lead to change.

Randomly barcoded transposon mutant libraries for gut commensals II: Applying libraries for functional genetics.

The critical role of the intestinal microbiota in human health and disease is well recognized. Nevertheless, there are still large gaps in our understanding of the functions and mechanisms encoded in the genomes of most members of the gut microbiota. Genome-scale libraries of transposon mutants are a powerful tool to help us address this gap.

Randomly barcoded transposon mutant libraries for gut commensals I: Strategies for efficient library construction.

Randomly barcoded transposon mutant libraries are powerful tools for studying gene function and organization, assessing gene essentiality and pathways, discovering potential therapeutic targets, and understanding the physiology of gut bacteria and their interactions with the host. However, construction of high-quality libraries with uniform representation can be challenging. In this review, we survey various strategies for barcoded library construction, including transposition systems, methods of transposon delivery, optimal library size, and transconjugant selection schemes.

Intraoperative Challenges in Hand Surgery.

A wide array of intraoperative issues can arise during surgery involving the hand and upper extremity. An understanding of the common pitfalls within hand surgery may help practicing hand surgeons circumvent such issues. Within this manuscript, we first identify problems with the increasingly popular technique of wide-awake local anesthesia no tourniquet (WALANT).

A mutant fitness compendium in Bifidobacteria reveals molecular determinants of colonization and host-microbe interactions.

Bifidobacteria commonly represent a dominant constituent of human gut microbiomes during infancy, influencing nutrition, immune development, and resistance to infection. Despite interest as a probiotic therapy, predicting the nutritional requirements and health-promoting effects of Bifidobacteria is challenging due to major knowledge gaps. To overcome these deficiencies, we used large-scale genetics to create a compendium of mutant fitness in ().

Cutibacterium avidum Osteomyelitis Associated With Pediatric Hip Reconstruction.

are gram-positive, non-sporulating, anaerobic, or microaerophilic bacilli that are increasingly recognized in the setting of indolent post-operative infection. Clinically significant infection with in the pediatric population is rarely encountered. Herein, we report our experience with two pediatric cases of osteomyelitis and soft tissue abscess after femoral derotational osteotomy for congenital hip dysplasia.

The "Standing Peanut" Scaphoid View: A Semi-supinated Radiographic View for Intraoperative Evaluation of Screw Placement in Scaphoid Waist Fractures.

Scaphoid waist fractures are the most common fracture of the scaphoid. Operative management is indicated with unstable fractures and often for nondisplaced waist fractures to decrease time to union and return to work/sport. Screw placement within the central axis of the scaphoid is paramount and correlates with outcomes.

Intramedullary Threaded Nail Fixation Versus Plate and Screw Construct in Metacarpal Neck Fractures: A Biomechanical Study.

Background: Indicated surgical management of metacarpal neck fractures varies with techniques, including Kirschner wire fixation, plate fixation, intramedullary fixation, and headless compression screw fixation, without demonstrated superiority. This study compares intramedullary threaded nail (ITN) fixation with a locking plate construct.

Methods: Index through small finger metacarpals were harvested from 10 embalmed cadavers.

Benefits and challenges of consolidating public health functions into a National Public Health Institute: a policy analysis.

National Public Health Institutes (NPHIs) around the world vary in composition. Consolidated organizational models can bring together critical functions such as disease surveillance, emergency preparedness and response, public health research, workforce development and laboratory diagnosis within a single focal point. This can lead to enhanced coordination and management of resources and enable more efficient and effective public health operations.

Construction and characterization of a genome-scale ordered mutant collection of Bacteroides thetaiotaomicron.

Background: Ordered transposon-insertion collections, in which specific transposon-insertion mutants are stored as monocultures in a genome-scale collection, represent a promising tool for genetic dissection of human gut microbiota members. However, publicly available collections are scarce and the construction methodology remains in early stages of development.

Results: Here, we describe the assembly of a genome-scale ordered collection of transposon-insertion mutants in the model gut anaerobe Bacteroides thetaiotaomicron VPI-5482 that we created as a resource for the research community.

Design, construction, and in vivo augmentation of a complex gut microbiome.

Efforts to model the human gut microbiome in mice have led to important insights into the mechanisms of host-microbe interactions. However, the model communities studied to date have been defined or complex, but not both, limiting their utility. Here, we construct and characterize in vitro a defined community of 104 bacterial species composed of the most common taxa from the human gut microbiota (hCom1).

M-TUBE enables large-volume bacterial gene delivery using a high-throughput microfluidic electroporation platform.

Conventional cuvette-based and microfluidics-based electroporation approaches for bacterial gene delivery have distinct advantages, but they are typically limited to relatively small sample volumes, reducing their utility for applications requiring high throughput such as the generation of mutant libraries. Here, we present a scalable, large-scale bacterial gene delivery approach enabled by a disposable, user-friendly microfluidic electroporation device requiring minimal device fabrication and straightforward operation. We demonstrate that the proposed device can outperform conventional cuvettes in a range of situations, including across Escherichia coli strains with a range of electroporation efficiencies, and we use its large-volume bacterial electroporation capability to generate a library of transposon mutants in the anaerobic gut commensal Bifidobacterium longum.

Bigger Is Not Always Better: Effects of Electrocautery Setting on Tissue Injury in a Porcine Model.

Introduction Electrosurgery for dissection and hemostasis remains one of the foundational tools for the field of surgery as a whole. Monopolar cautery remains the most utilized modality for achieving the aforementioned goals. Given the prolonged history and pre-modern development of "Bovie" cautery, there remains a paucity of data regarding appropriate settings and intensity for various tissue types, procedures, or locales.

Preventing Childhood Adversity Through Economic Support and Social Norm Strategies.

Through the Essentials for Childhood program, the Centers for Disease Control and Prevention funds 7 state health departments (states) to address the urgent public health problem of adverse childhood experiences and child abuse and neglect, in particular. Through interviews and document reviews, the paper highlights the early implementation of 2 primary prevention strategies from the Centers for Disease Control and Prevention's child abuse and neglect technical package with the greatest potential for broad public health impact to prevent adverse childhood experiences-strengthening economic supports and changing social norms. States are focused on advancing family-friendly work policies such as paid family and medical leave, livable wage policies, flexible and consistent work schedules, as well as programs and policies that strengthen household financial security such as increasing access to Earned Income Tax Credit.

Slipped Capital Femoral Epiphysis Associated with Endocrinopathy: A Narrative Review.

»: Slipped capital femoral epiphysis (SCFE) has a well-documented association with underlying endocrine conditions, including thyroid hormone aberrations and parathyroid dysfunction.

»: Recombinant growth hormone therapy has also been identified as a risk factor for the development of SCFE.

»: Presentation before their 10th birthday or after their 16th birthday along with height of <10th percentile are reliable risk factors for identifying children with an SCFE who are at a heightened risk for an underlying endocrinopathy and can been used to guide selective laboratory testing.

Rapid ordering of barcoded transposon insertion libraries of anaerobic bacteria.

Commensal bacteria from the human intestinal microbiota play important roles in health and disease. Research into the mechanisms by which these bacteria exert their effects is hampered by the complexity of the microbiota, the strict growth requirements of the individual species and a lack of genetic tools and resources. The assembly of ordered transposon insertion libraries, in which nearly all nonessential genes have been disrupted and the strains stored as independent monocultures, would be a transformative resource for research into many microbiota members.

Chemical-genetic interrogation of RNA polymerase mutants reveals structure-function relationships and physiological tradeoffs.

The multi-subunit bacterial RNA polymerase (RNAP) and its associated regulators carry out transcription and integrate myriad regulatory signals. Numerous studies have interrogated RNAP mechanism, and RNAP mutations drive Escherichia coli adaptation to many health- and industry-relevant environments, yet a paucity of systematic analyses hampers our understanding of the fitness trade-offs from altering RNAP function. Here, we conduct a chemical-genetic analysis of a library of RNAP mutants.

Functional genetics of human gut commensal Bacteroides thetaiotaomicron reveals metabolic requirements for growth across environments.

Harnessing the microbiota for beneficial outcomes is limited by our poor understanding of the constituent bacteria, as the functions of most of their genes are unknown. Here, we measure the growth of a barcoded transposon mutant library of the gut commensal Bacteroides thetaiotaomicron on 48 carbon sources, in the presence of 56 stress-inducing compounds, and during mono-colonization of gnotobiotic mice. We identify 516 genes with a specific phenotype under only one or a few conditions, enabling informed predictions of gene function.

Genetic interaction mapping informs integrative structure determination of protein complexes.

Determining structures of protein complexes is crucial for understanding cellular functions. Here, we describe an integrative structure determination approach that relies on in vivo measurements of genetic interactions. We construct phenotypic profiles for point mutations crossed against gene deletions or exposed to environmental perturbations, followed by converting similarities between two profiles into an upper bound on the distance between the mutated residues.

Mechanically resolved imaging of bacteria using expansion microscopy.

Imaging dense and diverse microbial communities has broad applications in basic microbiology and medicine, but remains a grand challenge due to the fact that many species adopt similar morphologies. While prior studies have relied on techniques involving spectral labeling, we have developed an expansion microscopy method (μExM) in which bacterial cells are physically expanded prior to imaging. We find that expansion patterns depend on the structural and mechanical properties of the cell wall, which vary across species and conditions.

Cutting the Gordian Knot of the Microbiota.

The gut microbiota plays a central role in human health. Studies by Tramontano et al. (2018) and Maier et al.

A genome-wide screen in reveals that ubiquinone is a key antioxidant for metabolism of long-chain fatty acids.

Long-chain fatty acids (LCFAs) are used as a rich source of metabolic energy by several bacteria including important pathogens. Because LCFAs also induce oxidative stress, which may be detrimental to bacterial growth, it is imperative to understand the strategies employed by bacteria to counteract such stresses. Here, we performed a genetic screen in on the LCFA, oleate, and compared our results with published genome-wide screens of multiple non-fermentable carbon sources.

Correction: A Chemical-Genomic Screen of Neglected Antibiotics Reveals Illicit Transport of Kasugamycin and Blasticidin S.

[This corrects the article DOI: 10.1371/journal.pgen.

Role for dithiolopyrrolones in disrupting bacterial metal homeostasis.

Natural products harbor unique and complex structures that provide valuable antibiotic scaffolds. With an increase in antibiotic resistance, natural products once again hold promise for new antimicrobial therapies, especially those with unique scaffolds that have been overlooked due to a lack of understanding of how they function. Dithiolopyrrolones (DTPs) are an underexplored class of disulfide-containing natural products, which exhibit potent antimicrobial activities against multidrug-resistant pathogens.