Influence of Sex, Age and Body Mass Index on an Algorithm for Electrocardiogram-derived Respiratory Rate.

Respiratory rate (RR) is an important biomarker of cardiopulmonary status. Its role is particularly evident in conditions like obstructive sleep apnea, which significantly increase risk of heart disease. Electrocardiogram (ECG)-derived RR is an emerging alternative to traditional RR measurement, which requires cumbersome and specialized equipment.

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.

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.

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.

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.

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.

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).

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.

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.

Lysophosphatidic Acid Signaling through the Lysophosphatidic Acid-1 Receptor Is Required for Alveolarization.

Lysophosphatidic acid (LPA) signaling through one of its receptors, LPA1, contributes to both the development and the pathological remodeling after injury of many organs. Because we found previously that LPA-LPA1 signaling contributes to pulmonary fibrosis, here we investigated whether this pathway is also involved in lung development. Quantitative assessment of lung architecture of LPA1-deficient knock-out (KO) and wild-type (WT) mice at 3, 12, and 24 weeks of age using design-based stereology suggested the presence of an alveolarization defect in LPA1 KO mice at 3 weeks, which persisted as alveolar numbers increased in WT mice into adulthood.

The Golgi apparatus regulates cGMP-dependent protein kinase I compartmentation and proteolysis.

cGMP-dependent protein kinase I (PKGI) is an important effector of cGMP signaling that regulates vascular smooth muscle cell (SMC) phenotype and proliferation. PKGI has been detected in the perinuclear region of cells, and recent data indicate that proprotein convertases (PCs) typically resident in the Golgi apparatus (GA) can stimulate PKGI proteolysis and generate a kinase fragment that localizes to the nucleus and regulates gene expression. However, the role of the endomembrane system in PKGI compartmentation and processing is unknown.

cGMP-dependent protein kinase I gamma encodes a nuclear localization signal that regulates nuclear compartmentation and function.

cGMP-dependent protein kinase I (PKGI) plays an important role in regulating how cGMP specifies vascular smooth muscle cell (SMC) phenotype. Although studies indicate that PKGI nuclear localization controls how cGMP regulates gene expression in SMC, information about the mechanisms that regulate PKGI nuclear compartmentation and its role in directly regulating cell phenotype is limited. Here we characterize a nuclear localization signal sequence (NLS) in PKGIγ, a proteolytically cleaved PKGI kinase fragment that translocates to the nucleus of SMC.

Continuous noninvasive cardiac output in children: is this the next generation of operating room monitors? Initial experience in 402 pediatric patients.

Background: Electrical Cardiometry(™) (EC) estimates cardiac parameters by measuring changes in thoracic electrical bioimpedance during the cardiac cycle. The ICON(®), using four electrocardiogram electrodes (EKG), estimates the maximum rate of change of impedance to peak aortic blood acceleration (based on the premise that red blood cells change from random orientation during diastole (high impedance) to an aligned state during systole (low impedance)).

Objective: To determine whether continuous cardiac output (CO) data provide additional information to current anesthesia monitors that is useful to practitioners.

Transglutaminase 2: a new player in bronchopulmonary dysplasia?

Aberrant remodelling of the extracellular matrix in the developing lung may underlie arrested alveolarisation associated with bronchopulmonary dysplasia (BPD). Transglutaminases are regulators of extracellular matrix remodelling. Therefore, the expression and activity of transglutaminases were assessed in lungs from human neonates with BPD and in a rodent model of BPD.

Deregulation of the lysyl hydroxylase matrix cross-linking system in experimental and clinical bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is a common and serious complication of premature birth, characterized by a pronounced arrest of alveolar development. The underlying pathophysiological mechanisms are poorly understood although perturbations to the maturation and remodeling of the extracellular matrix (ECM) are emerging as candidate disease pathomechanisms. In this study, the expression and regulation of three members of the lysyl hydroxylase family of ECM remodeling enzymes (Plod1, Plod2, and Plod3) in clinical BPD, as well as in an experimental animal model of BPD, were addressed.

A novel in vitro model to study alveologenesis.

Many pediatric pulmonary diseases are associated with significant morbidity and mortality due to impairment of alveolar development. The lack of an appropriate in vitro model system limits the identification of therapies aimed at improving alveolarization. Herein, we characterize an ex vivo lung culture model that facilitates investigation of signaling pathways that influence alveolar septation.

Soluble guanylate cyclase modulates alveolarization in the newborn lung.

Nitric oxide (NO) regulates lung development through incompletely understood mechanisms. NO controls pulmonary vascular smooth muscle cell (SMC) differentiation largely through stimulating soluble guanylate cyclase (sGC) to produce cGMP and increase cGMP-mediated signaling. To examine the role of sGC in regulating pulmonary development, we tested whether decreased sGC activity reduces alveolarization in the normal and injured newborn lung.

Proprotein convertases play an important role in regulating PKGI endoproteolytic cleavage and nuclear transport.

Nitric oxide and cGMP modulate vascular smooth muscle cell (SMC) phenotype by regulating cell differentiation and proliferation. Recent studies suggest that cGMP-dependent protein kinase I (PKGI) cleavage and the nuclear translocation of a constitutively active kinase fragment, PKGIγ, are required for nuclear cGMP signaling in SMC. However, the mechanisms that control PKGI proteolysis are unknown.