Nitric oxide regulation of fetal and newborn lung development and function.

In the developing lung, nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) signaling are essential in regulating lung formation and vascular tone. Animal studies have linked many anatomical and pathophysiological features of newborn lung disease to abnormalities in the NO/cGMP signaling system. They have demonstrated that driving this system with agonists and antagonists alleviates many of them.

Open-source software for respiratory rate estimation using single-lead electrocardiograms.

Respiratory rate (RR) is a critical vital sign used to assess pulmonary function. Currently, RR estimating instrumentation is specialized and bulky, therefore unsuitable for remote health monitoring. Previously, RR was estimated using proprietary software that extract surface electrocardiogram (ECG) waveform features obtained at several thoracic locations.

Osteosarcoma in Pediatric and Adult Populations: Are Adults Just Big Kids?

Malignant bone tumors are commonly classified as pediatric or adolescent malignancies, and clinical trials for these diseases have generally focused on these populations. Of primary bone cancers, osteosarcoma is among the most common. Osteosarcoma has a bimodal age distribution, with the first peak occurring in patients from 10 to 14 years old, and the second peak occurring in patients older than 65, with about 25% of cases occurring in adults between 20 and 59 years old.

Optimization of an Allysine-Targeted PET Probe for Quantifying Fibrogenesis in a Mouse Model of Pulmonary Fibrosis.

Purpose: Idiopathic pulmonary fibrosis (IPF) is a destructive lung disease with a poor prognosis, an unpredictable clinical course, and inadequate therapies. There are currently no measures of disease activity to guide clinicians making treatment decisions. The aim of this study was to develop a PET probe to identify lung fibrogenesis using a pre-clinical model of pulmonary fibrosis, with potential for translation into clinical use to predict disease progression and inform treatment decisions.

Graphene as a rational interface for enhanced adsorption of microcystin-LR from water.

Cyanotoxins such as microcystin-LR (MC-LR) represent a global environmental threat to ecosystems and drinking water supplies. The study investigated the direct use of graphene as a rational interface for removal of MC-LR via interactions with the aromatic ring of the ADDA chain of MC-LR and the sp hybridized carbon network of graphene. Intra-particle diffusion model fit indicated the high mesoporosity of graphene provided significant enhancements to both adsorption capacities and kinetics when benchmarked against microporous granular activated carbon (GAC).

LungElast-an open-source, flexible, low-cost, microprocessor-controlled mouse lung elastometer.

The study of mouse lung mechanics provides essential insights into the physiological mechanisms of pulmonary disease. Consequently, investigators assemble custom systems comprising infusion-withdrawal syringe pumps and analog pressure sensors to investigate the lung function of these animals. But these systems are expensive and require ongoing regulation, making them challenging to use.

Molecular MRI quantification of extracellular aldehyde pairs for early detection of liver fibrogenesis and response to treatment.

Liver fibrosis plays a critical role in the evolution of most chronic liver diseases and is characterized by a buildup of extracellular matrix, which can progress to cirrhosis, hepatocellular carcinoma, liver failure, or death. Now, there are no noninvasive methods available to accurately assess disease activity (fibrogenesis) to sensitively detect early onset of fibrosis or to detect early response to treatment. Here, we hypothesized that extracellular allysine aldehyde (Lys) pairs formed by collagen oxidation during active fibrosis could be a target for assessing fibrogenesis with a molecular probe.

Biodegradable microneedle patch for delivery of meloxicam for managing pain in cattle.

Microneedle patches are a promising source for transdermal diffusion of macromolecules and are designed to painlessly penetrate the skin. In this study, a biodegradable chitosan microneedle patch to deliver meloxicam for managing pain in cattle was tested. The potential of reuse of the polymeric solution to fabricate the patches, optimization of fabrication, morphological analysis of the microneedle patch and analysis of preservation of the chemical composition after sterilization were evaluated.

RespiCo: A novel, flexible, and stand-alone electronic respiratory coaching device.

Conscious respiratory pattern and rate control is desired by patients with some forms of pulmonary disease that are undergoing respiratory muscle conditioning and rehabilitation, by practitioners of meditation hoping to improve mindfulness and wellbeing, by athletes striving to obtain breathing control in order to increase competitiveness, and by engineers and scientists that wish to use the data from breathing subjects to test hypotheses and develop physiological monitoring systems. Although prerecorded audio sources and computer applications are available that guide breathing exercises, they often suffer from being inflexible and allow only limited customization of the breathing cues. Here we describe a small, lightweight, battery-powered, microprocessor-based respiratory coaching device (RespiCo), which through wireless or wired connections, can be easily customized to precisely guide subjects to breathe at desired respiratory rates using specific breathing patterns through visual, auditory, or haptic cues.

Graphene-Mediated removal of Microcystin-LR in chitosan/graphene composites for treatment of harmful algal blooms.

Water quality can be severely impacted by algal blooms alone, yet cyanotoxins, such as microcystin (MC), are potent underlying hazards produced by various species of cyanobacteria. Currently there is a need for environmentally compatible and economically viable media to address large scale application for HAB impacted waters. This study evaluated the interactions of chitosan/graphene (CSG) composites with three different species of cyanobacteria: Anabaena sp, Synechocystis sp, and Microcystis aeruginosa for both removal of algal optical density and toxins.

Lysyl oxidase regulation and protein aldehydes in the injured newborn lung.

During newborn lung injury, excessive activity of lysyl oxidases (LOXs) disrupts extracellular matrix (ECM) formation. Previous studies indicate that TGFβ activation in the O-injured mouse pup lung increases lysyl oxidase (LOX) expression. But how TGFβ regulates this, and whether the LOXs generate excess pulmonary aldehydes are unknown.

Ambulatory monitoring promises equitable personalized healthcare delivery in underrepresented patients.

The pandemic has brought to everybody's attention the apparent need of remote monitoring, highlighting hitherto unseen challenges in healthcare. Today, mobile monitoring and real-time data collection, processing and decision-making, can drastically improve the cardiorespiratory-haemodynamic health diagnosis and care, not only in the rural communities, but urban ones with limited healthcare access as well. Disparities in socioeconomic status and geographic variances resulting in regional inequity in access to healthcare delivery, and significant differences in mortality rates between rural and urban communities have been a growing concern.

Utility of a Smartphone-Based System (cvrPhone) in Estimating Minute Ventilation from Electrocardiographic Signals.

We investigated the ability of a novel stand-alone, smartphone-based system, the cvrPhone, in estimating the minute ventilation (MV) from body surface electrocardiographic (ECG) signals. Twelve lead ECG signals were collected from anesthetized and mechanically ventilated swine ( = 9) using standard surface electrodes and the cvrPhone. The tidal volume delivered to the animals was varied between 0, 250, 500, and 750 mL at respiration rates of 6 and 14 breaths/min.

IL-1β dysregulates cGMP signaling in the newborn lung.

Cyclic guanosine monophosphate (cGMP) signaling is an important regulator of newborn lung function and development. Although cGMP signaling is decreased in many models of newborn lung injury, the mechanisms are poorly understood. We determined how IL-1β regulates the expression of the α1-subunit of soluble guanylate cyclase (sGCα1), a prime effector of pulmonary cGMP signaling.

Low Fouling, Peptoid-Coated Polysulfone Hollow Fiber Membranes-the Effect of Grafting Density and Number of Side Chains.

The development of low fouling membranes to minimize protein adsorption has relevance in various biomedical applications. Here, electrically neutral peptoids containing 2-methoxyethyl glycine (NMEG) side chains were attached to polysulfone hollow fiber membranes via polydopamine. The number of side chains and grafting density were varied to determine the effect on coating properties and the ability to prevent fouling.

cGMP-dependent protein kinase I in vascular smooth muscle cells improves ischemic stroke outcome in mice.

Recent works highlight the therapeutic potential of targeting cyclic guanosine monophosphate (cGMP)-dependent pathways in the context of brain ischemia/reperfusion injury (IRI). Although cGMP-dependent protein kinase I (cGKI) has emerged as a key mediator of the protective effects of nitric oxide (NO) and cGMP, the mechanisms by which cGKI attenuates IRI remain poorly understood. We used a novel, conditional cGKI knockout mouse model to study its role in cerebral IRI.

Utility of a smartphone based system (cvrphone) to accurately determine apneic events from electrocardiographic signals.

Background: Sleep disordered breathing manifested as sleep apnea (SA) is prevalent in the general population, and while it is associated with increased morbidity and mortality risk in some patient populations, it remains under-diagnosed. The objective of this study was to assess the accuracy of respiration-rate (RR) and tidal-volume (TV) estimation algorithms, from body-surface ECG signals, using a smartphone based ambulatory respiration monitoring system (cvrPhone).

Methods: Twelve lead ECG signals were collected using the cvrPhone from anesthetized and mechanically ventilated swine (n = 9).

Peptoid microsphere coatings: The effects of helicity, temperature, pH, and ionic strength.

Peptoids are peptidomimetic oligomers that predominantly harness similarities to peptides for biomimetic functionality. They have potential for use in biomedical applications and biosensors due to resistance to proteolytic degradation and low immunogenicity. The incorporation of chiral, aromatic side chains in the peptoid sequence allows for the formation of distinct secondary structures and self-assembly into supramolecular assemblies, including microspheres.

Transforming growth factor-β downregulates sGC subunit expression in pulmonary artery smooth muscle cells via MEK and ERK signaling.

TGFβ activation during newborn lung injury decreases the expression of pulmonary artery smooth muscle cell (PASMC)-soluble guanylate cyclase (sGC), a critical mediator of nitric oxide signaling. Using a rat PASMC line (CS54 cells), we determined how TGFβ downregulates sGC expression. We found that TGFβ decreases sGC expression through stimulating its type I receptor; TGFβ type I receptor (TGFβR1) inhibitors prevented TGFβ-1-mediated decrease in sGCα1 subunit mRNA levels in the cells.

Medial Compartment Decompression by Proximal Fibular Osteotomy: A Biomechanical Cadaver Study.

Medial compartment knee osteoarthritis is a painful and debilitating disease. A proximal fibular osteotomy is a novel, simple surgical technique that may reduce pain and improve function for patients with osteoarthritis. The purpose of this biomechanical cadaver study was to determine what effect proximal fibular osteotomy had on knee joint and ankle pressures and tibia strain.

Transforming growth factor-β stimulates Smad1/5 signaling in pulmonary artery smooth muscle cells and fibroblasts of the newborn mouse through ALK1.

The intracellular signaling mechanisms through which TGF-β regulates pulmonary development are incompletely understood. Canonical TGF-β signaling involves Smad2/3 phosphorylation, Smad2/3·Smad4 complex formation and nuclear localization, and gene regulation. Here, we show that physiologically relevant TGF-β1 levels also stimulate Smad1/5 phosphorylation, which is typically a mediator of bone morphogenetic protein (BMP) signaling, in mouse pup pulmonary artery smooth muscle cells (mPASMC) and lung fibroblasts and other interstitial lung cell lines.

Clinical Care Guideline for Improving Pediatric Acute Musculoskeletal Infection Outcomes.

Background: Acute pediatric musculoskeletal infections are common, leading to significant use of resources and antimicrobial exposure. In order to decrease variability and improve the quality of care, Children's Hospital Colorado implemented a clinical care guideline (CCG) for these infections. The purpose of this study is to evaluate clinical and resource outcomes PRE and POST this CCG.