Trivalent immunization with metal-binding proteins confers protection against enterococci in a mouse infection model.

is ranked among the top five bacterial pathogens responsible for catheter-associated urinary tract infections, wound infections, secondary root canal infections, and infective endocarditis. Previously, we showed that inactivation of either the manganese- and iron-binding (EfaA) or zinc-binding (AdcA and AdcAII) lipoproteins significantly reduced virulence. Here, we explored whether immunization using a multi-valent approach induces protective immunity against systemic enterococcal infections.

Structural Assessment of Major Outer Membrane Protein (MOMP)-Derived Vaccine Antigens and Immunological Profiling in Mice with Different Genetic Backgrounds.

() is the most common cause of bacterial sexually transmitted infections (STIs) worldwide. infections are often asymptomatic in women, leading to severe reproductive tract sequelae. Development of a vaccine against is crucial.

Predicting the Long-Term Effects of Therapeutic Neutralization of Oncostatin M on Human Hematopoiesis.

Therapeutic neutralization of Oncostatin M (OSM) causes mechanism-driven anemia and thrombocytopenia, which narrows the therapeutic window complicating the selection of doses (and dosing intervals) that optimize efficacy and safety. We utilized clinical data from studies of an anti-OSM monoclonal antibody (GSK2330811) in healthy volunteers (n = 49) and systemic sclerosis patients (n = 35), to quantitatively determine the link between OSM and alterations in red blood cell (RBC) and platelet production. Longitudinal changes in hematopoietic variables (including RBCs, reticulocytes, platelets, erythropoietin, and thrombopoietin) were linked in a physiology-based model, to capture the long-term effects and variability of therapeutic OSM neutralization on human hematopoiesis.

Murine Model of Airway Fibrosis has Anatomic, Physiologic, and Molecular Congruency to Human iSGS.

Objective: To narrow knowledge gaps in the pathophysiology of idiopathic subglottic stenosis (iSGS) through comparison of a murine subglottic stenosis model with iSGS.

Study Design: In vivo animal study.

Setting: Academic institution.

Dysfunctional Epithelial Barrier Is Characterized by Reduced E-Cadherin in Idiopathic Subglottic Stenosis.

Objectives: To aim of the study was to characterize the molecular profile and functional phenotype of idiopathic subglottic stenosis (iSGS)-scar epithelium.

Methods: Human tracheal biopsies from iSGS scar (n = 6) and matched non-scar (n = 6) regions were analyzed using single-cell RNA sequencing (scRNA-seq). Separate specimens were used for epithelial cell expansion in vitro to assess average growth rate and functional capabilities using transepithelial-electrical resistance (TEER), fluorescein isothiocyanate-dextran flux permeability assay, ciliary coverage, and cilia beating frequency (CBF).

Myeloid Phenotypes in Tracheostomy-Associated Granulation Tissue.

Objective(s): Tracheostomy-associated granulation tissue is a common, recurrent problem occurring secondary to chronic mucosal irritation. Although granulation tissue is composed of predominantly innate immune cells, the phenotype of monocytes and macrophages in tracheostomy-associated granulation tissue is unknown. This study aims to define the myeloid cell population in granulation tissue secondary to tracheostomy.

Characterizing the Macrophage Population in Patients With Idiopathic Subglottic Stenosis.

Objectives: Idiopathic subglottic stenosis (iSGS) is characterized by progressive fibrosis and subglottic luminal narrowing. Currently, immune characterization has focused on T-cells; however, macrophages remain largely unexplored. The goals of this study are to characterize the transcriptome of iSGS macrophages and the fibrogenic nature of identifed biomarkers.

Addition of Lauryldimethylamine -Oxide (LDAO) to a Copper-Free Click Chemistry Reaction Improves the Conjugation Efficiency of a Cell-Free Generated CRM197 Variant to Clinically Important Serotypes.

Strain-promoted azide-alkyne cycloaddition (SPAAC) reactions like click chemistry have the potential to be highly scalable, robust, and cost-effective methods for generating small- and large-molecule conjugates for a variety of applications. However, despite method improvements, the rates of copper-based click chemistry reactions continue to be much faster than the rates of copper-free click chemistry reactions, which makes broader deployment of click chemistry challenging from a safety and compatibility standpoint. In this study, we used a zwitterionic detergent, namely, lauryldimethylamine -oxide (LDAO), in a copper-free click chemistry reaction to investigate its impact on the generation of conjugate vaccines (CVs).

Impact of Low-Volume, Low-Pressure Tracheostomy Cuffs on Acute Mucosal Injury in Swine.

Objective: Tapered low-volume, low-pressure (LVLP) cuffs have been introduced to improve sealing and reduce injury from tracheostomy and endotracheal intubation compared to traditional cylindrical high-volume, low-pressure (HVLP) cuffs. The objective of this study is to develop a swine model of tracheostomy injury and to compare live tissue response following LVLP and HVLP tracheostomy placement.

Study Design: In vivo animal study.

Analysis of molecular photomechanical performance using a one-dimensional harmonic model.

The photochemical reaction of a molecule leads to a change in the position of its nuclei that can be harnessed to perform mechanical work. Photomechanical materials use this effect to act as light-powered actuators. In this paper, a one-dimensional model based on coupled harmonic potential energy surfaces is developed to describe the photomechanical response of a molecule.

DescePrep Significantly Increases Descemet Membrane Endothelial Keratoplasty Processing Efficiency and Success Rate in Diabetic Human Donor Corneas in Comparison With Manual Dissection.

Purpose: The purpose of this study was to compare the safety, efficacy, and efficiency of a Descemet membrane endothelial keratoplasty (DMEK) graft processing device, DescePrep, with a manual dissection technique through the measurement of tissue yield, processing time, and graft viability in nondiabetic and diabetic donor corneas.

Methods: Nondiabetic (n = 20) and diabetic (n = 20) donor corneas were processed using DescePrep, which standardizes the liquid bubble technique. Nondiabetic (n = 20) and diabetic (n = 24) donor corneas were also processed through manual dissection.

Tungstacyclopentane Ring Contraction Yields Olefin Metathesis Catalysts.

Exposure of a solution of the square pyramidal tungstacyclopentane complex W(NAr)(OSiPh)(CH) (Ar = 2,6--PrCH) to ethylene at 22 °C in ambient (fluorescent) light slowly leads to the formation of propylene and the square pyramidal tungstacyclobutane complex W(NAr)(OSiPh)(CH). No reaction takes place in the dark, but the reaction is >90% complete in ∼15 min under blue LED light (∼450 nm λ). The intermediates are proposed to be (first) an α methyl tungstacyclobutane complex (W(NAr)(OSiPh)(αMeCH)), and then from it, a β methyl version.

Eye Tracking and Motion Data Predict Endoscopic Sinus Surgery Skill.

Objective: Endoscopic surgery has a considerable learning curve due to dissociation of the visual-motor axes, coupled with decreased tactile feedback and mobility. In particular, endoscopic sinus surgery (ESS) lacks objective skill assessment metrics to provide specific feedback to trainees. This study aims to identify summary metrics from eye tracking, endoscope motion, and tool motion to objectively assess surgeons' ESS skill.

Phenotypic Epithelial Changes in Laryngotracheal Stenosis.

Objective: Characterize and quantify epithelium in multiple etiologies of laryngotracheal stenosis (LTS) to better understand its role in pathogenesis.

Study Design: Controlled in vitro cohort study.

Methods: Endoscopic brush biopsy samples of both normal (non-scar) and scar were obtained in four patients with idiopathic subglottic stenosis (iSGS) and four patients with iatrogenic LTS (iLTS).

A Capsule-Conjugate Vaccine Protects From Experimental Oral Bone Loss.

Periodontal diseases are chronic inflammatory diseases of the periodontium that result in progressive destruction of the soft and hard tissues supporting the teeth, and it is the most common cause of tooth loss among adults. In the US alone, over 100 million individuals are estimated to have periodontal disease. Subgingival bacteria initiate and sustain inflammation, and, although several bacteria have been associated with periodontitis, has emerged as the key etiological organism significantly contributing to the disease.

A survey of patients with laryngotracheal stenosis on future clinical trial design.

Background/aims: Laryngotracheal stenosis is a rare but devastating proximal airway fibrosis that restricts a patient's ability to breathe. Treatment is primarily surgical and to date, there has never been a multi-institutional, randomized, prospective, and interventional clinical trial for a medical therapy to treat laryngotracheal stenosis. Therefore, we aimed to obtain patient feedback to guide successful trial design, recruitment, retention, and for identifying potential barriers to study participation.

Efficient production of immunologically active Shigella invasion plasmid antigens IpaB and IpaH using a cell-free expression system.

Shigella spp. invade the colonic epithelium and cause bacillary dysentery in humans. Individuals living in areas that lack access to clean water and sanitation are the most affected.

Virtual Reality Simulation Has Weak Correlation with Overall Trainee Robot-Assisted Laparoscopic Hysterectomy Performance.

Study Objective: Both simulator practice and intraoperative performance serve to inform surgical trainee training, but the skill transfer from simulation to the intraoperative setting remains unclear. This study evaluates the correlation between trainee performance on virtual reality simulation and (1) overall intraoperative performance during robotic-assisted laparoscopic hysterectomy (RALH) procedures and (2) suturing performance during vaginal cuff closure portion of the case.

Design: Retrospective subgroup analysis of randomized controlled trial.

Chemical Tuning of Exciton versus Charge-Transfer Excited States in Conformationally Restricted Arylene Cages.

Covalent assemblies of conjugated organic chromophores provide the opportunity to engineer new excited states with novel properties. In this work, a newly developed triple-stranded cage architecture, in which meta-substituted aromatic caps serve as covalent linking groups that attach to both top and bottom of the conjugated molecule walls, is used to tune the properties of thiophene oligomer assemblies. Benzene-capped and triazine-capped 5,5'-(2,2-bithiophene)-containing arylene cages are synthesized and characterized using steady-state and time-resolved spectroscopic methods.

Evaluation of Efficacy, Efficiency, and Cell Viability of a Novel Descemet Membrane Endothelial Keratoplasty Graft Preparation Device, DescePrep, in Nondiabetic and Diabetic Human Donor Corneas.

Purpose: The purpose of this study was to evaluate the safety, efficacy, and efficiency of a Descemet membrane endothelial keratoplasty (DMEK) graft preparation device, DescePrep, through measurement of graft viability, yield, and preparation time in both healthy and diabetic (high-risk) donor eyes.

Methods: Twenty nondiabetic and 10 diabetic donor corneas were processed using DescePrep, which standardizes the liquid bubble technique. Corneas were stained with trypan blue and then processed.

Concentration-QT modelling in early clinical oncology settings: Simulation evaluation of performance.

Aims: Concentration-QT modelling (C-QTc) of first-in-human data has been rapidly adopted as the primary evaluation of QTc interval prolongation risk. Here, we evaluate the performance of C-QTc in early oncology settings (i.e.

Delayed Diagnosis of Idiopathic Subglottic Stenosis.

Objective: Idiopathic subglottic stenosis (iSGS) is a rare disease, causing life-threatening dyspnea secondary to scarring. Perhaps because it is rarely encountered, there is often a delay in diagnosing iSGS. The objective of this study is to characterize diagnostic delay of iSGS, factors that prolong delay, and its impact on iSGS patients.

Ceralasertib (AZD6738), an Oral ATR Kinase Inhibitor, in Combination with Carboplatin in Patients with Advanced Solid Tumors: A Phase I Study.

Purpose: This study reports the safety, tolerability, MTD, recommended phase II dose (RP2D), pharmacokinetic/pharmacodynamic profile, and preliminary antitumor activity of ceralasertib combined with carboplatin in patients with advanced solid tumors. It also examined exploratory predictive and pharmacodynamic biomarkers.

Patients And Methods: Eligible patients (n = 36) received a fixed dose of carboplatin (AUC5) with escalating doses of ceralasertib (20 mg twice daily to 60 mg once daily) in 21-day cycles.

Quantifying Viral Particle Aerosolization Risk During Tracheostomy Surgery and Tracheostomy Care.

Importance: During respiratory disease outbreaks such as the COVID-19 pandemic, aerosol-generating procedures, including tracheostomy, are associated with the risk of viral transmission to health care workers.

Objective: To quantify particle aerosolization during tracheostomy surgery and tracheostomy care and to evaluate interventions that minimize the risk of viral particle exposure.

Design, Setting, And Participants: This comparative effectiveness study was conducted from August 2020 to January 2021 at a tertiary care academic institution.