Age-related remodeling of the vocal fold extracellular matrix composition, structure, and biomechanics during tissue maturation.

Purpose: The vocal folds (VFs) are among the most mechanically active connective tissues, vibrating between 80 and 250 hz during speech. Overall VF function is determined by the composition and structure of their extracellular matrix (ECM). During tissue maturation, the VFs remodel from a monolayer of collagen fibers to a tri-layered structure, affecting tissue biomechanics.

Azithromycin Prevents Subglottic Stenosis in Mice.

Objective: Pediatric subglottic stenosis (SGS) is characterized by subglottic narrowing which occurs when pathological fibroblasts deposit extracellular matrix that reduces airway patency. Recent clinical observations have suggested that azithromycin may have favorable impacts on SGS reduction while treating airway infections; furthermore, our recent work in mice demonstrated that the airway microbiome influences SGS. In this work, we characterize the protective effect of azithromycin as an immunomodulatory and antibacterial therapeutic against subglottic stenosis.

Amelioration of Subglottic Stenosis by Antimicrobial Peptide Eluting Endotracheal Tubes.

Introduction: Pediatric subglottic stenosis (SGS) results from prolonged intubation where scar tissue leads to airway narrowing that requires invasive surgery. We have recently discovered that modulating the laryngotracheal microbiome can prevent SGS. Herein, we show how our patent-pending antimicrobial peptide-eluting endotracheal tube (AMP-ET) effectively modulates the local airway microbiota resulting in reduced inflammation and stenosis resolution.

Modulated Fibrosis and Mechanosensing of Fibroblasts by SB525334 in Pediatric Subglottic Stenosis.

Objective: Subglottic stenosis (SGS) may result from prolonged intubation where fibrotic scar tissue narrows the airway. The scar forms by differentiated myofibroblasts secreting excessive extracellular matrix (ECM). TGF-β1 is widely accepted as a regulator of fibrosis; however, it is unclear how biomechanical pathways co-regulate fibrosis.

Effects of Brief Mental Skills Training on Emergency Medicine Residents' Stress Response During a Simulated Resuscitation: A Prospective Randomized Trial.

Background: Acute stress impairs physician decision-making and clinical performance in resuscitations. Mental skills training, a component of the multistep, cognitive-behavioral technique of stress inoculation, modulates stress response in high-performance fields.

Objective: We assessed the effects of mental skills training on emergency medicine (EM) residents' stress response in simulated resuscitations as well as residents' perceptions of this intervention.

Drug-Eluting Endotracheal Tubes for Preventing Bacterial Inflammation in Subglottic Stenosis.

Objectives/hypothesis: Subglottic stenosis (SGS) results from dysregulated extracellular matrix deposition by laryngotracheal fibroblasts causing scar tissue formation following intubation. Recent work has highlighted a relationship between this inflammatory state and imbalances in the upper airway microbiome. Herein, we engineer novel drug-eluting endotracheal (ET) tubes to deliver a model antimicrobial peptide Lasioglossin-III (Lasio) for the local modulation of the microbiome during intubation.

Drug delivery to the pediatric upper airway.

Pediatric upper airway disorders are frequently life-threatening and require precise assessment and intervention. Targeting these pathologies remains a challenge for clinicians due to the high complexity of pediatric upper airway anatomy and numerous potential etiologies; the most common treatments include systemic delivery of high dose steroids and antibiotics or complex and invasive surgeries. Furthermore, the majority of innovative airway management technologies are only designed and tested for adults, limiting their widespread implementation in the pediatric population.

Peptide functionalized liposomes for receptor targeted cancer therapy.

Most clinically approved cancer therapies are potent and toxic small molecules that are limited by severe off-target toxicities and poor tumor-specific localization. Over the past few decades, attempts have been made to load chemotherapies into liposomes, which act to deliver the therapeutic agent directly to the tumor. Although liposomal encapsulation has been shown to decrease toxicity in human patients, reliance on passive targeting via the enhanced permeability and retention (EPR) effect has left some of these issues unresolved.

Pathogen-specific antimicrobials engineered de novo through membrane-protein biomimicry.

Precision antimicrobials aim to kill pathogens without damaging commensal bacteria in the host, and thereby cure disease without antibiotic-associated dysbiosis. Here we report the de novo design of a synthetic host defence peptide that targets a specific pathogen by mimicking key molecular features of the pathogen's channel-forming membrane proteins. By exploiting physical and structural vulnerabilities within the pathogen's cellular envelope, we designed a peptide sequence that undergoes instructed tryptophan-zippered assembly within the mycolic acid-rich outer membrane of Mycobacterium tuberculosis to specifically kill the pathogen without collateral toxicity towards lung commensal bacteria or host tissue.

Re-engineering Antimicrobial Peptides into Oncolytics Targeting Drug-Resistant Ovarian Cancers.

Introduction: Bacteria and cancer cells share a common trait-both possess an electronegative surface that distinguishes them from healthy mammalian counterparts. This opens opportunities to repurpose antimicrobial peptides (AMPs), which are cationic amphiphiles that kill bacteria by disrupting their anionic cell envelope, into anticancer peptides (ACPs). To test this assertion, we investigate the mechanisms by which a pathogen-specific AMP, originally designed to kill bacterial Tuberculosis, potentiates the lytic destruction of drug-resistant cancers and synergistically enhances chemotherapeutic potency.

Supramolecular Peptide Assemblies as Antimicrobial Scaffolds.

Antimicrobial discovery in the age of antibiotic resistance has demanded the prioritization of non-conventional therapies that act on new targets or employ novel mechanisms. Among these, supramolecular antimicrobial peptide assemblies have emerged as attractive therapeutic platforms, operating as both the bactericidal agent and delivery vector for combinatorial antibiotics. Leveraging their programmable inter- and intra-molecular interactions, peptides can be engineered to form higher ordered monolithic or co-assembled structures, including nano-fibers, -nets, and -tubes, where their unique bifunctionalities often emerge from the supramolecular state.

Discovery of antitumor lectins from rainforest tree root transcriptomes.

Glycans are multi-branched sugars that are displayed from lipids and proteins. Through their diverse polysaccharide structures they can potentiate a myriad of cellular signaling pathways involved in development, growth, immuno-communication and survival. Not surprisingly, disruption of glycan synthesis is fundamental to various human diseases; including cancer, where aberrant glycosylation drives malignancy.

The Ca export pump PMCA clears near-membrane Ca to facilitate store-operated Ca entry and NFAT activation.

Ca signals, which facilitate pluripotent changes in cell fate, reflect the balance between cation entry and export. We found that overexpression of either isoform of the Ca-extruding plasma membrane calcium ATPase 4 (PMCA4) pump in Jurkat T cells unexpectedly increased activation of the Ca-dependent transcription factor nuclear factor of activated T cells (NFAT). Coexpression of the endoplasmic reticulum-resident Ca sensor stromal interaction molecule 1 (STIM1) with the PMCA4b splice variant further enhanced NFAT activity; however, coexpression with PMCA4a depressed NFAT.

Lipopeptisomes: Anticancer peptide-assembled particles for fusolytic oncotherapy.

Anticancer peptides (ACPs) are cationic amphiphiles that preferentially kill cancer cells through folding-dependent membrane disruption. Although ACPs represent attractive therapeutic candidates, particularly against drug-resistant cancers, their successful translation into clinical practice has gone unrealized due to their poor bioavailability, serum instability and, most importantly, severe hemolytic toxicity. Here, we exploit the membrane-specific interactions of ACPs to prepare a new class of peptide-lipid particle, we term a lipopeptisome (LP).

Surface effects on the structure and mobility of the ionic liquid C6C1ImTFSI in silica gels.

We report on how the dynamical and structural properties of the ionic liquid 1-hexyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide (C6C1ImTFSI) change upon different degrees of confinement in silica gels. The apparent diffusion coefficients of the individual ions are measured by (1)H and (19)F pulsed field gradient nuclear magnetic resonance (PFG-NMR) spectroscopy, while the intermolecular interactions in the ionogels are elucidated by Raman spectroscopy. In addition, the local structure of the ionic liquid at the silica interface is probed by solid-state NMR spectroscopy.

First principles derived, transferable force fields for CO2 adsorption in Na-exchanged cationic zeolites.

The development of accurate force fields is vital for predicting adsorption in porous materials. Previously, we introduced a first principles-based transferable force field for CO2 adsorption in siliceous zeolites (Fang et al., J.