Radiographic Measurements of Pes Planovalgus Do Not Predict Clinical Outcomes in Tarsal Coalition Excision.

Objective: Many patients who undergo tarsal coalition excision have persistent postoperative pain. Most studies have utilized cat scan (CT) scan parameters of pes planovalgus and heel valgus but have found this to be an inconsistent predictor of outcomes. Plain radiographic parameters have been less utilized in trying to predict outcomes after coalition excision.

Reducing Radiation Dermatitis for PBS Proton Therapy Breast Cancer Patients Using SpotDelete.

Purpose: The purpose of this work was to reduce the severity of radiation dermatitis for breast cancer patients receiving pencil beam scanning proton therapy. The hypothesis was that eliminating proton spots (SpotDelete) in the 0.5 cm skin rind would reduce the potentially higher relative biological effectiveness (RBE) known to occur at the Bragg Peak.

Salmonella re-engineers the intestinal environment to break colonization resistance in the presence of a compositionally intact microbiota.

The gut microbiota prevents harmful microbes from entering the body, a function known as colonization resistance. The enteric pathogen Salmonella enterica serovar (S.) Typhimurium uses its virulence factors to break colonization resistance through unknown mechanisms.

High fat intake sustains sorbitol intolerance after antibiotic-mediated Clostridia depletion from the gut microbiota.

Carbohydrate intolerance, commonly linked to the consumption of lactose, fructose, or sorbitol, affects up to 30% of the population in high-income countries. Although sorbitol intolerance is attributed to malabsorption, the underlying mechanism remains unresolved. Here, we show that a history of antibiotic exposure combined with high fat intake triggered long-lasting sorbitol intolerance in mice by reducing Clostridia abundance, which impaired microbial sorbitol catabolism.

Antimicrobial susceptibility testing to evaluate minimum inhibitory concentration values of clinically relevant antibiotics.

Antimicrobial susceptibility testing is used to determine the minimum inhibitory concentration (MIC), the standard measurement of antibiotic activity. Here, we present a protocol for evaluating MIC values of clinically relevant antibiotics against bacterial isolates cultured in standard bacteriologic medium and in mammalian cell culture medium. We describe steps for pathogen identification, culturing bacteria, preparing MIC plates, MIC assay incubation, and determining MIC.

Re-evaluation of FDA-approved antibiotics with increased diagnostic accuracy for assessment of antimicrobial resistance.

Accurate assessment of antibiotic susceptibility is critical for treatment of antimicrobial resistant (AMR) infections. Here, we examine whether antimicrobial susceptibility testing in media more physiologically representative of in vivo conditions improves prediction of clinical outcome relative to standard bacteriologic medium. This analysis reveals that ∼15% of minimum inhibitory concentration (MIC) values obtained in physiologic media predicted a change in susceptibility that crossed a clinical breakpoint used to categorize patient isolates as susceptible or resistant.

A broad-spectrum synthetic antibiotic that does not evoke bacterial resistance.

Background: Antimicrobial resistance (AMR) poses a critical threat to public health and disproportionately affects the health and well-being of persons in low-income and middle-income countries. Our aim was to identify synthetic antimicrobials termed conjugated oligoelectrolytes (COEs) that effectively treated AMR infections and whose structures could be readily modified to address current and anticipated patient needs.

Methods: Fifteen chemical variants were synthesized that contain specific alterations to the COE modular structure, and each variant was evaluated for broad-spectrum antibacterial activity and for in vitro cytotoxicity in cultured mammalian cells.

The IRE1α-XBP1 Signaling Axis Promotes Glycolytic Reprogramming in Response to Inflammatory Stimuli.

Immune cells must be able to adjust their metabolic programs to effectively carry out their effector functions. Here, we show that the endoplasmic reticulum (ER) stress sensor Inositol-requiring enzyme 1 alpha (IRE1α) and its downstream transcription factor X box binding protein 1 (XBP1) enhance the upregulation of glycolysis in classically activated macrophages (CAMs). The IRE1α-XBP1 signaling axis supports this glycolytic switch in macrophages when activated by lipopolysaccharide (LPS) stimulation or infection with the intracellular bacterial pathogen Brucella abortus.

Descriptive Epidemiology of Isolated Distal Radius Fractures in Children: Results From a Prospective Multicenter Registry.

Introduction: More than 1 in 4 pediatric fractures involves the distal radius. Most prior epidemiologic studies are limited to retrospective, single center investigations, and often include adults. This study aims to describe the contemporary epidemiology of pediatric distal radius fractures using prospectively collected data from a multicenter Pediatric Distal Radius Fracture Registry.

Fully displaced pediatric supracondylar humerus fractures: Which ones need to go at night?

Background: Challenges remain in determining which displaced supracondylar humerus fractures are safe to postpone surgical treatment until daylight hours. The purpose of this study is to determine which characteristics can be identified to guide the timing of treatment of supracondylar humerus fractures.

Methods: 225 completely displaced Gartland extension type 3/4 supracondylar humerus fractures in healthy patients that presented between 6 am and 7 am were identified.

Genealogy of an passaged isolate of western Canadian bovine respiratory syncytial virus.

Bovine respiratory syncytial virus (BRSV) is a primary respiratory pathogen in calves. Clinical infection with this pathogen has been experimentally modelled to assess vaccine efficacy using a field isolate (Asquith) of BRSV that has been sequentially passaged in neonatal calves to maintain virulence. The objective of this retrospective cumulative analysis of passages over approximately 20 years was to determine if there have been any changes in the viral genome of this isolate because of this process.

Host cells subdivide nutrient niches into discrete biogeographical microhabitats for gut microbes.

Changes in the microbiota composition are associated with many human diseases, but factors that govern strain abundance remain poorly defined. We show that a commensal Escherichia coli strain and a pathogenic Salmonella enterica serovar Typhimurium isolate both utilize nitrate for intestinal growth, but each accesses this resource in a distinct biogeographical niche. Commensal E.

miRNA/mRNA co-profiling identifies the miR-200 family as a central regulator of SMC quiescence.

miRNAs are versatile regulators of smooth muscle cell (SMC) fate and behavior in vascular development and disease. Targeted loss-of-function studies have established the relevance of specific miRNAs in controlling SMC differentiation or mediating phenotypic modulation. Our goal was to characterize SMC miRNAome and its contribution to transcriptome changes during phenotypic modulation.

Coagulation factor protein abundance in the pre-septic state predicts coagulopathic activities that arise during late-stage murine sepsis.

Background: Although sepsis accounts for 1 in 5 deaths globally, few molecular therapies exist for this condition. The development of effective biomarkers and treatments for sepsis requires a more complete understanding of host responses and pathogenic mechanisms at early stages of disease to minimize host-driven pathology.

Methods: An alternative to the current symptom-based approach used to diagnose sepsis is a precise assessment of blood proteomic changes during the onset and progression of Salmonella Typhimurium (ST) murine sepsis.

Development of inactivated heartwater (Ehrlichia ruminantium) vaccine in South Africa.

Heartwater, Ehrlichia ruminantium infection in cattle, sheep, goats, and some wild ruminants, is an economically important disease in Africa characterized by high mortality rates in susceptible populations. In South Africa, the current commercial heartwater vaccine is an infection and treatment type of immunization using virulent live E. ruminantium organisms generated from blood of infected sheep with subsequent treatment of the animals with antibiotics at specific times during the course of infection.

Assessment of a Smartphone-Based Loop-Mediated Isothermal Amplification Assay for Detection of SARS-CoV-2 and Influenza Viruses.

Importance: A critical need exists in low-income and middle-income countries for low-cost, low-tech, yet highly reliable and scalable testing for SARS-CoV-2 virus that is robust against circulating variants.

Objective: To assess whether a smartphone-based assay is suitable for SARS-CoV-2 and influenza virus testing without requiring specialized equipment, accessory devices, or custom reagents.

Design, Setting, And Participants: This cohort study enrolled 2 subgroups of participants (symptomatic and asymptomatic) at Santa Barbara Cottage Hospital.

Retrospective study of patterns of vitamin D testing and status at a single institution paediatric orthopaedics and sports clinics.

Objectives: There has been a recent increase in awareness of the importance of bone health in children treated by paediatric orthopaedic and sports medicine providers. The purpose of this study was to assess our utilisation of 25 hydroxy vitamin D (25(OH)Vit D) testing in the past 10 years, and to evaluate the level of 25(OH)Vit D sufficiency in various populations of patients seen.

Design: This is a single site, retrospective medical record review study.

Juvenile Hallux Valgus.

Treatment of juvenile hallux valgus can be challenging. Initial treatment with conservative measures is appropriate until exhausted. Surgical treatment should be delayed until after skeletal maturity when possible.

Epiphysiodesis for Leg Length Discrepancy: A Cost Analysis of Drill Versus Screw Technique.

Research has demonstrated similar efficacy of drill epiphysiodesis and percutaneous epiphysiodesis using transphyseal screws for the management of adolescent leg length discrepancy. A cost analysis was performed to determine which procedure is more cost-effective. Patients seen for epiphysiodesis of the distal femur and/or proximal tibia and fibula between 2004 and 2017 were reviewed.

H3K4 di-methylation governs smooth muscle lineage identity and promotes vascular homeostasis by restraining plasticity.

Epigenetic mechanisms contribute to the regulation of cell differentiation and function. Vascular smooth muscle cells (SMCs) are specialized contractile cells that retain phenotypic plasticity even after differentiation. Here, by performing selective demethylation of histone H3 lysine 4 di-methylation (H3K4me2) at SMC-specific genes, we uncovered that H3K4me2 governs SMC lineage identity.

Kinetic Detection of E3:PROTAC:Target Ternary Complexes Using NanoBRET Technology in Live Cells.

Heterobifunctional small-molecule degraders known as Proteolysis Targeting Chimeras (PROTACs) serve as a chemical bridge bringing into direct association a target protein with an active E3 ligase complex, called the ternary complex, to facilitate targeted protein degradation. This ternary complex formation is the first key mechanistic step in a cascade of events that results in ubiquitination and subsequent degradation of the target protein via the ubiquitin-proteasome pathway. The ternary complex, however, is a nonnative cellular complex; therefore, PROTAC compound design has many challenges to overcome to ensure successful formation, including achieving structural and electrostatic favorability among target and ligase.

Prospective Evaluation of Tarsal Coalition Excision Show Significant Improvements in Pain and Function.

Background: Excision of pediatric tarsal coalition has been successful in most patients. However, some patients have ongoing pain after coalition excision. This study prospectively assessed patient-based clinical outcomes before and after surgical excision of tarsal coalition, with particular emphasis on comparison to radiologic imaging.