Assessment of a Wearable Device for Minute Ventilation in Detecting Different States of Ventilation

Introduction: Minute ventilation (MV) and breathing status are valuable vital signs to measure in patients clinically such as in detecting opioid induced respiratory depression. However, there are few devices capable of continuously monitoring MV in an accurate fashion. RTM Vital Signs, LLC and TJU are developing a non-invasive wearable Tracheal Sound Sensor to determine if a device can accurately and continuously measure respiratory rate (RR), tidal volume (TV), MV, and changes in ventilation patterns based on sound recordings of breathing. Methods: Tracheal breathing sounds were recorded in six researchers using a prototype sensor placed on the skin above the sternal notch. Simultaneously, researcher’s RR and MV were recorded in minute long intervals using a pneumotach. Researchers were asked to mimic various breathing patterns by adjusting breathing rate and breathing depth. A variety of signal processing methods and algorithms were used to analyze the data to produce RR, TV, and breathing pattern estimates. Results: Researchers tolerated use of the sensor and breathing apparatus system without difficulty and data was successfully obtained. Initial signal processing and analysis methods applied to this data were able to accurately measure the respiratory rate (~ 98% sensitivity/specificity), and accurately characterize normal breathing from hyperventilation and hypoventilation (~ 98% sensitivity/specificity). The sensor’s algorithm estimated tidal volume with ± 100 ml accuracy compared with the commercial pneumotach. Discussion: Based on the results, a non-invasive wearable device could obtain accurate measures of RR and classify breathing patterns based solely on measurements of breathing sounds. Although the TV results were not as accurate as we expected, this may be due in part to systematic error from the pneumotach device used for the reference TV. With the satisfactory sensor and data acquisition system, future trials are planned in volunteers and hospitalized patients using this system with more accurate pneumotach devices

Detecting Different States of Ventilation with a Wearable Device through Minute Ventilation

Introduction: Detecting changes in respiration are essential to monitoring a patient’s vital signs. Few devices accomplish this in a non-invasive manner. We are developing a wearable Trachea Sound Sensor that measures respiratory rate (RR), tidal volume (TV), minute ventilation (MV = RR x TV). A prototypical Trachea Sound Sensor (TSS) was created and compared to a reference pneumotachometer. Both were used to record the sounds of breathing with research team members. Methods:The TSS recording device was tested on six research team members and breath sounds were recorded. Simultaneously, the member’s RR and MV was recorded using a calibrated pneumotachometer. The researchers were instructed to adjust their breathing rate and depth while intervals were recorded. Signal processing techniques were used to analyze and produce measurements of RR, TV, and characterize hyperventilatory or hypoventilatory states. Results: Based on the results, we found that it is possible to obtain accurate measures of RR and identify breathing patterns through the TSS. Signal processing and analysis calculated RR, states of hyperventilation and hypoventilation with 98% sensitivity and specificity. Results obtained for measuring TV were less accurate (±100 mL). Discussion: Our results suggest that it is viable to obtain accurate measures of RR and classify breathing sounds solely on measurements of breathing sounds from the TSS. The inaccuracy in TV measurements may be partly due to the systematic error from the pneumotachometer used. The prototypical TSS are suitable for upcoming NIH-funded clinical trials to test the TSS in volunteers and hospitalized patients

Hypoxia induces dilated cardiomyopathy in the chick embryo: mechanism; intervention; and long-term consequences.

Background Intrauterine growth restriction is associated with an increased future risk for developing cardiovascular diseases. Hypoxia in utero is a common clinical cause of fetal growth restriction. We have previously shown that chronic hypoxia alters cardiovascular development in chick embryos. The aim of this study was to further characterize cardiac disease in hypoxic chick embryos. Methods Chick embryos were exposed to hypoxia and cardiac structure was examined by histological methods one day prior to hatching (E20) and at adulthood. Cardiac function was assessed in vivo by echocardiography and ex vivo by contractility measurements in isolated heart muscle bundles and isolated cardiomyocytes. Chick embryos were exposed to vascular endothelial growth factor (VEGF) and its scavenger soluble VEGF receptor-1 (sFlt-1) to investigate the potential role of this hypoxia-regulated cytokine. Principal Findings Growth restricted hypoxic chick embryos showed cardiomyopathy as evidenced by left ventricular (LV) dilatation, reduced ventricular wall mass and increased apoptosis. Hypoxic hearts displayed pump dysfunction with decreased LV ejection fractions, accompanied by signs of diastolic dysfunction. Cardiomyopathy caused by hypoxia persisted into adulthood. Hypoxic embryonic hearts showed increases in VEGF expression. Systemic administration of rhVEGF165 to normoxic chick embryos resulted in LV dilatation and a dose-dependent loss of LV wall mass. Lowering VEGF levels in hypoxic embryonic chick hearts by systemic administration of sFlt-1 yielded an almost complete normalization of the phenotype. Conclusions/Significance Our data show that hypoxia causes a decreased cardiac performance and cardiomyopathy in chick embryos, involving a significant VEGF-mediated component. This cardiomyopathy persists into adulthood

Hypoxia induces dilated cardiomyopathy in the chick embryo: mechanism, intervention, and long-term consequences

Background: Intrauterine growth restriction is associated with an increased future risk for developing cardiovascular diseases. Hypoxia in utero is a common clinical cause of fetal growth restriction. We have previously shown that chronic hypoxia alters cardiovascular development in chick embryos. The aim of this study was to further characterize cardiac disease in hypoxic chick embryos. Methods: Chick embryos were exposed to hypoxia and cardiac structure was examined by histological methods one day prior to hatching (E20) and at adulthood. Cardiac function was assessed in vivo by echocardiography and ex vivo by contractility measurements in isolated heart muscle bundles and isolated cardiomyocytes. Chick embryos were exposed to vascular endothelial growth factor (VEGF) and its scavenger soluble VEGF receptor-1 (sFlt-1) to investigate the potential role of this hypoxia-regulated cytokine. Principal Findings: Growth restricted hypoxic chick embryos showed cardiomyopathy as evidenced by left ventricular (LV) dilatation, reduced ventricular wall mass and increased apoptosis. Hypoxic hearts displayed pump dysfunction with decreased LV ejection fractions, accompanied by signs of diastolic dysfunction. Cardiomyopathy caused by hypoxia persisted into adulthood. Hypoxic embryonic hearts showed increases in VEGF expression. Systemic administration of rhVEGF165 to normoxic chick embryos resulted in LV dilatation and a dose-dependent loss of LV wall mass. Lowering VEGF levels in hypoxic embryonic chick hearts by systemic administration of sFlt-1 yielded an almost complete normalization of the phenotype. Conclusions/Significance: Our data show that hypoxia causes a decreased cardiac performance and cardiomyopathy in chick embryos, involving a significant VEGF-mediated component. This cardiomyopathy persists into adulthood

Château de Dourdan : étude du parement de la courtine sud-ouest et des salles sud-est (Île-de-France, Essonne, Dourdan): Rapport de fouille archéologique 2011

National audienceL’opération menée en 2011 sur le château de Dourdan (Essonne) et, plus précisément, l’étude des courtines sud-ouest a permis de relocaliser le logis royal (Philippe II Auguste : 1165-1223) détruit au cours du siège de 1591. Ces découvertes et l’intérêt qu’elles ont suscité vis-à-vis de l’ensemble de ce château prestigieux, avec la réalisation d’une maquette « numérique » en 2012, amènent quelques remarques complémentaires au rapport d’opération, en guise de prolongement méthodologique, sur l’interprétation des vestiges et les choix de « reconstitution »

Targeted DNA methylation by homology-directed repair in mammalian cells. Transcription reshapes methylation on the repaired gene

We report that homology-directed repair of a DNA double-strand break within a single copy Green Fluorescent Protein (GFP) gene in HeLa cells alters the methylation pattern at the site of recombination. DNA methyl transferase (DNMT)1, DNMT3a and two proteins that regulate methylation, Np95 and GADD45A, are recruited to the site of repair and are responsible for selective methylation of the promoter-distal segment of the repaired DNA. The initial methylation pattern of the locus is modified in a transcription-dependent fashion during the 15-20 days following repair, at which time no further changes in the methylation pattern occur. The variation in DNA modification generates stable clones with wide ranges of GFP expression. Collectively, our data indicate that somatic DNA methylation follows homologous repair and is subjected to remodeling by local transcription in a discrete time window during and after the damage. We propose that DNA methylation of repaired genes represents a DNA damage code and is source of variation of gene expression

Targeted DNA methylation by homology-directed repair in mammalian cells. Transcription reshapes methylation on the repaired gene

We report that homology-directed repair of a DNA double-strand break within a single copy Green Fluorescent Protein (GFP) gene in HeLa cells alters the methylation pattern at the site of recombination. DNA methyl transferase (DNMT)1, DNMT3a and two proteins that regulate methylation, Np95 and GADD45A, are recruited to the site of repair and are responsible for selective methylation of the promoter-distal segment of the repaired DNA. The initial methylation pattern of the locus is modified in a transcription-dependent fashion during the 15-20 days following repair, at which time no further changes in the methylation pattern occur. The variation in DNA modification generates stable clones with wide ranges of GFP expression. Collectively, our data indicate that somatic DNA methylation follows homologous repair and is subjected to remodeling by local transcription in a discrete time window during and after the damage. We propose that DNA methylation of repaired genes represents a DNA damage code and is source of variation of gene expression

Hypoxia induces dilated cardiomyopathy in the chick embryo: mechanism; intervention; and long-term consequences.

Background Intrauterine growth restriction is associated with an increased future risk for developing cardiovascular diseases. Hypoxia in utero is a common clinical cause of fetal growth restriction. We have previously shown that chronic hypoxia alters cardiovascular development in chick embryos. The aim of this study was to further characterize cardiac disease in hypoxic chick embryos. Methods Chick embryos were exposed to hypoxia and cardiac structure was examined by histological methods one day prior to hatching (E20) and at adulthood. Cardiac function was assessed in vivo by echocardiography and ex vivo by contractility measurements in isolated heart muscle bundles and isolated cardiomyocytes. Chick embryos were exposed to vascular endothelial growth factor (VEGF) and its scavenger soluble VEGF receptor-1 (sFlt-1) to investigate the potential role of this hypoxia-regulated cytokine. Principal Findings Growth restricted hypoxic chick embryos showed cardiomyopathy as evidenced by left ventricular (LV) dilatation, reduced ventricular wall mass and increased apoptosis. Hypoxic hearts displayed pump dysfunction with decreased LV ejection fractions, accompanied by signs of diastolic dysfunction. Cardiomyopathy caused by hypoxia persisted into adulthood. Hypoxic embryonic hearts showed increases in VEGF expression. Systemic administration of rhVEGF165 to normoxic chick embryos resulted in LV dilatation and a dose-dependent loss of LV wall mass. Lowering VEGF levels in hypoxic embryonic chick hearts by systemic administration of sFlt-1 yielded an almost complete normalization of the phenotype. Conclusions/Significance Our data show that hypoxia causes a decreased cardiac performance and cardiomyopathy in chick embryos, involving a significant VEGF-mediated component. This cardiomyopathy persists into adulthood

Expression of total titin, titin isoforms, titin isoforms/total titin ratios and titin/myosin ratios.

<p>a.u.: arbitrary units.</p>*<p>P<0.05.</p>**<p>P<0.01.</p