Meconium Influences Pulmonary Short-Chain Fatty Acid Concentration in Porcine Meconium Aspiration Model.

Introduction: The factors influencing meconium aspiration syndrome (MAS) severity remain poorly understood. In a piglet model of MAS, we hypothesized the respiratory microbiome would reflect the bacterial signature of meconium with short-chain fatty acid (SCFA) accumulation as a byproduct of bacterial fermentation.

Methods: Cesarean section at approximately 115-day term was performed on two sows.

Design and Implementation of a Computer-Controlled Hybrid Oscillatory Ventilator.

During mechanical ventilation, lung function and gas exchange in structurally heterogeneous lungs may be improved when volume oscillations at the airway opening are applied at multiple frequencies simultaneously, a technique referred to as multifrequency oscillatory ventilation (MFOV). This is in contrast to conventional high-frequency oscillatory ventilation (HFOV), for which oscillatory volumes are applied at a single frequency. In the present study, as a means of fully realizing the potential of MFOV, we designed and tested a computer-controlled hybrid oscillatory ventilator capable of generating the flows, tidal volumes, and airway pressures required for MFOV, HFOV, conventional mechanical ventilation (CMV), as well as oscillometric measurements of respiratory impedance.

Phase I pilot safety and feasibility of a novel restraint device for critically ill patients requiring mechanical ventilation.

Background: Mechanically ventilated Intensive Care Unit (ICU) patients often require wrist restraints, contributing to immobility and agitation, over-sedation, and delirium. The ® ® (Healthy Design, LLC), a novel restraint alternative, may be safe and facilitate greater mobility than traditional restraints.

Objective: This National Institutes of Health Small Business Technology Transfer (STTR) Program Grant-funded single-site Phase I feasibility study evaluated ® safety and feasibility in anticipation of a multi-site Phase II randomized controlled trial (RCT).

Intratumoral Chemotherapy: The Effects of Drug Concentration and Dose Apportioning on Tumor Cell Injury.

The addition of intravenous (i.v.) chemotherapy to i.

The protein disulfide isomerase A3 and osteopontin axis promotes influenza-induced lung remodelling.

Background And Purpose: Fibrotic lung remodelling after a respiratory viral infection represents a debilitating clinical sequela. Studying or managing viral-fibrotic sequela remains challenging, due to limited therapeutic options and lack of understanding of mechanisms. This study determined whether protein disulfide isomerase A3 (PDIA3) and secreted phosphoprotein 1 (SPP1), which are associated with pulmonary fibrosis, can promote influenza-induced lung fibrotic remodelling and whether inhibition of PDIA3 or SPP1 can resolve viral-mediated fibrotic remodelling.

LDCT image biomarkers that matter most for the deep learning classification of indeterminate pulmonary nodules.

Background: Continued improvement in deep learning methodologies has increased the rate at which deep neural networks are being evaluated for medical applications, including diagnosis of lung cancer. However, there has been limited exploration of the underlying radiological characteristics that the network relies on to identify lung cancer in computed tomography (CT) images.

Objective: In this study, we used a combination of image masking and saliency activation maps to systematically explore the contributions of both parenchymal and tumor regions in a CT image to the classification of indeterminate lung nodules.

Elucidating the interaction between stretch and stiffness using an agent-based spring network model of progressive pulmonary fibrosis.

Pulmonary fibrosis is a deadly disease that involves the dysregulation of fibroblasts and myofibroblasts, which are mechanosensitive. Previous computational models have succeeded in modeling stiffness-mediated fibroblasts behaviors; however, these models have neglected to consider stretch-mediated behaviors, especially stretch-sensitive channels and the stretch-mediated release of latent TGF-β. Here, we develop and explore an agent-based model and spring network model hybrid that is capable of recapitulating both stiffness and stretch.

Time-Controlled Adaptive Ventilation (TCAV): a personalized strategy for lung protection.

Acute respiratory distress syndrome (ARDS) alters the dynamics of lung inflation during mechanical ventilation. Repetitive alveolar collapse and expansion (RACE) predisposes the lung to ventilator-induced lung injury (VILI). Two broad approaches are currently used to minimize VILI: (1) low tidal volume (LV) with low-moderate positive end-expiratory pressure (PEEP); and (2) open lung approach (OLA).

Ratchet recruitment in the acute respiratory distress syndrome: lessons from the newborn cry.

Patients with acute respiratory distress syndrome (ARDS) have few treatment options other than supportive mechanical ventilation. The mortality associated with ARDS remains unacceptably high, and mechanical ventilation itself has the potential to increase mortality further by unintended ventilator-induced lung injury (VILI). Thus, there is motivation to improve management of ventilation in patients with ARDS.

Full-lung simulations of mechanically ventilated lungs incorporating recruitment/derecruitment dynamics.

This study developed and investigated a comprehensive multiscale computational model of a mechanically ventilated ARDS lung to elucidate the underlying mechanisms contributing to the development or prevention of VILI. This model is built upon a healthy lung model that incorporates realistic airway and alveolar geometry, tissue distensibility, and surfactant dynamics. Key features of the ARDS model include recruitment and derecruitment (RD) dynamics, alveolar tissue viscoelasticity, and surfactant deficiency.

Chemical Kinetic Method for Active-Site Quantification in Fe-N-C Catalysts and Correlation with Molecular Probe and Spectroscopic Site-Counting Methods.

Mononuclear Fe ions ligated by nitrogen (FeN) dispersed on nitrogen-doped carbon (Fe-N-C) serve as active centers for electrocatalytic O reduction and thermocatalytic aerobic oxidations. Despite their promise as replacements for precious metals in a variety of practical applications, such as fuel cells, the discovery of new Fe-N-C catalysts has relied primarily on empirical approaches. In this context, the development of quantitative structure-reactivity relationships and benchmarking of catalysts prepared by different synthetic routes and by different laboratories would be facilitated by the broader adoption of methods to quantify atomically dispersed FeN active centers.

Sustained vs. Intratidal Recruitment in the Injured Lung During Airway Pressure Release Ventilation: A Computational Modeling Perspective.

Introduction: During mechanical ventilation, cyclic recruitment and derecruitment (R/D) of alveoli result in focal points of heterogeneous stress throughout the lung. In the acutely injured lung, the rates at which alveoli can be recruited or derecruited may also be altered, requiring longer times at higher pressure levels to be recruited during inspiration, but shorter times at lower pressure levels to minimize collapse during exhalation. In this study, we used a computational model to simulate the effects of airway pressure release ventilation (APRV) on acinar recruitment, with varying inspiratory pressure levels and durations of exhalation.

Local fractal dimension of collagen detects increased spatial complexity in fibrosis.

Increase of collagen content and reorganization characterizes fibrosis but quantifying the latter remains challenging. Spatially complex structures are often analyzed via the fractal dimension; however, established methods for calculating this quantity either provide a single dimension for an entire object or a spatially distributed dimension that only considers binary images. These neglect valuable information related to collagen density in images of fibrotic tissue.

An approach to study recruitment/derecruitment dynamics in a patient-specific computational model of an injured human lung.

We present a new approach for physics-based computational modeling of diseased human lungs. Our main object is the development of a model that takes the novel step of incorporating the dynamics of airway recruitment/derecruitment into an anatomically accurate, spatially resolved model of respiratory system mechanics, and the relation of these dynamics to airway dimensions and the biophysical properties of the lining fluid. The importance of our approach is that it potentially allows for more accurate predictions of where mechanical stress foci arise in the lungs, since it is at these locations that injury is thought to arise and propagate from.

Visualizing intratumoral injections in lung tumors by endobronchial ultrasound.

Real-time endobronchial ultrasound images are crucial for the accurate placement of the needle in peribronchial lung tumors and lymph nodes for diagnostic sampling. Beyond its role as a diagnostic tool, ultrasound-guided bronchoscopy can also aid the delivery of anti-cancer agents intratumorally, enabling diagnosis, staging, and treatment to occur within the same anesthesia, reducing the patient's burden. However, determining drug retention and distribution remains challenging, albeit pivotal in assessing the success or failure of the therapeutic intervention.

Effects of obesity, pneumoperitoneum, and body position on mechanical power of intraoperative ventilation: an observational study.

Mechanical power can describe the complex interaction between the respiratory system and the ventilator and may predict lung injury or pulmonary complications, but the power associated with injury of healthy human lungs is unknown. Body habitus and surgical conditions may alter mechanical power but the effects have not been measured. In a secondary analysis of an observational study of obesity and lung mechanics during robotic laparoscopic surgery, we comprehensively quantified the static elastic, dynamic elastic, and resistive energies comprising mechanical power of ventilation.

Ventilator-Induced Lung Injury as a Dynamic Balance Between Epithelial Cell Damage and Recovery.

Acute respiratory distress syndrome (ARDS) has a high mortality rate that is due in part to ventilator-induced lung injury (VILI). Nevertheless, the majority of patients eventually recover, which means that their innate reparative capacities eventually prevail. Since there are currently no medical therapies for ARDS, minimizing its mortality thus amounts to achieving an optimal balance between spontaneous tissue repair versus the generation of VILI.

Predicting alveolar ventilation heterogeneity in pulmonary fibrosis using a non-uniform polyhedral spring network model.

Pulmonary Fibrosis (PF) is a deadly disease that has limited treatment options and is caused by excessive deposition and cross-linking of collagen leading to stiffening of the lung parenchyma. The link between lung structure and function in PF remains poorly understood, although its spatially heterogeneous nature has important implications for alveolar ventilation. Computational models of lung parenchyma utilize uniform arrays of space-filling shapes to represent individual alveoli, but have inherent anisotropy, whereas actual lung tissue is isotropic on average.

An agent-based model of tissue maintenance and self-repair.

We hypothesized that a system that possesses the capacity for ongoing maintenance of its tissues will necessarily also have the capacity to self-heal following a perturbation. We used an agent-based model of tissue maintenance to investigate this idea, and in particular to determine the extent to which the current state of the tissue must influence cell behavior in order for tissue maintenance and self-healing to be stable. We show that a mean level of tissue density is robustly maintained when catabolic agents digest tissue at a rate proportional to local tissue density, but that the spatial heterogeneity of the tissue at homeostasis increases with the rate at which tissue is digested.