Development of an Electronic Stethoscope and a Classification Algorithm for Cardiopulmonary Sounds.

With conventional stethoscopes, the auscultation results may vary from one doctor to another due to a decline in his/her hearing ability with age or his/her different professional training, and the problematic cardiopulmonary sound cannot be recorded for analysis. In this paper, to resolve the above-mentioned issues, an electronic stethoscope was developed consisting of a traditional stethoscope with a condenser microphone embedded in the head to collect cardiopulmonary sounds and an AI-based classifier for cardiopulmonary sounds was proposed. Different deployments of the microphone in the stethoscope head with amplification and filter circuits were explored and analyzed using fast Fourier transform (FFT) to evaluate the effects of noise reduction. After testing, the microphone placed in the stethoscope head surrounded by cork is found to have better noise reduction. For classifying normal (healthy) and abnormal (pathological) cardiopulmonary sounds, each sample of cardiopulmonary sound is first segmented into several small frames and then a principal component analysis is performed on each small frame. The difference signal is obtained by subtracting PCA from the original signal. MFCC (Mel-frequency cepstral coefficients) and statistics are used for feature extraction based on the difference signal, and ensemble learning is used as the classifier. The final results are determined by voting based on the classification results of each small frame. After the testing, two distinct classifiers, one for heart sounds and one for lung sounds, are proposed. The best voting for heart sounds falls at 5-45% and the best voting for lung sounds falls at 5-65%. The best accuracy of 86.9%, sensitivity of 81.9%, specificity of 91.8%, and F1 score of 86.1% are obtained for heart sounds using 2 s frame segmentation with a 20% overlap, whereas the best accuracy of 73.3%, sensitivity of 66.7%, specificity of 80%, and F1 score of 71.5% are yielded for lung sounds using 5 s frame segmentation with a 50% overlap.

Inhibition of p38 MAPK Mitigates Lung Ischemia Reperfusion Injury by Reducing Blood-Air Barrier Hyperpermeability.

Background: Lung ischemia reperfusion injury (LIRI) is a complex pathophysiological process activated by lung transplantation and acute lung injury. The p38 mitogen-activated protein kinase (MAPK) is involved in breakdown of the endothelial barrier during LIRI, but the mechanism is still unclear. Therefore, we investigated the function of p38 MAPK in LIRI in vivo and in vitro. Methods: Sprague-Dawley rats were subjected to ischemia reperfusion with or without pretreatment with a p38 MAPK inhibitor. Lung injury was assessed using hematoxylin and eosin staining, and pulmonary blood-air barrier permeability was evaluated using Evans blue staining. A rat pulmonary microvascular endothelial cell line was infected with lentiviral expressing short hairpin (sh)RNA targeting p38 MAPK and then cells were subjected to oxygen/glucose deprivation and reoxygenation (OGD/R). Markers of endothelial destruction were measured by western blot and immunofluorescence. Results: In vivo LIRI models showed structural changes indicative of lung injury and hyperpermeability of the blood-air barrier. Inhibiting p38 MAPK mitigated these effects. Oxygen/glucose deprivation and reoxygenation promoted hyperpermeability of the endothelial barrier in vitro, but knockdown of p38 MAPK attenuated cell injury; maintained endothelial barrier integrity; and partially reversed injury-induced downregulation of permeability protein AQP1, endothelial protective protein eNOS, and junction proteins ZO-1 and VE-cadherin while downregulating ICAM-1, a protein involved in destroying the endothelial barrier, and ET-1, a protein involved in endothelial dysfunction. Conclusion: Inhibition of p38 MAPK alleviates LIRI by decreasing blood-air hyperpermeability. Blocking p38 MAPK may be an effective treatment against acute lung injury.

Mitophagy-Mediated mtDNA Release Aggravates Stretching-Induced Inflammation and Lung Epithelial Cell Injury via the TLR9/MyD88/NF-κB Pathway.

BACKGROUND: In animal models of ventilation-induced lung injury, mitophagy triggers mitochondria damage and the release of mitochondrial (mt) DNA, which activates inflammation. However, the mechanism of this process is unclear. METHODS: A model of cyclic stretching (CS)-induced lung epithelial cell injury was established. The genetic intervention of phosphatase and tensin homolog-induced kinase 1 (PINK1) expression via lentivirus transfection was used to identify the relationship between PINK1-mediated mitophagy and mtDNA release in stretching-induced inflammatory response and injury. Pharmacological inhabitation of Toll-like receptor 9 (TLR9) and myeloid differentiation factor 88 (MyD88) expression was performed via their related inhibitors, while pre-treatment of exogenous mtDNA was used to verify the role of mtDNA in stretching-induced inflammatory response and injury. RESULTS: Using a cell culture model of CS, we found that knocking down PINK1 in lung epithelial cells reduced mitophagy activation and mtDNA release, leading to milder inflammatory response and injury; conversely, up-regulating PINK1 exacerbated stretching-induced inflammation and injury, and similar effects were observed by upregulating TLR9 to induce expression of MyD88 and nuclear factor-κB (NF-κB)/p65. Down-regulating MyD88 protected lung epithelial cells from stretching injury and decreased NF-κB/p65 expression. CONCLUSION: These findings suggest that PINK1-dependent mitophagy and associated TLR9 activation is indeed a major factor in stretch-induced cell injury via a mechanism in which released mtDNA activates TLR9 and thereby the MyD88/NF-κB pathway. Inhibiting this process may be a therapeutic approach to prevent inflammation and cell injury in patients on mechanical ventilation.

High Tidal Volume Induces Mitochondria Damage and Releases Mitochondrial DNA to Aggravate the Ventilator-Induced Lung Injury.

OBJECTIVE: This study aimed to determine whether high tidal volume (HTV) induce mitochondria damage and mitophagy, contributing to the release of mitochondrial DNA (mtDNA). Another aim of the present study was to investigate the role and mechanism of mtDNA in ventilator-induced lung injury (VILI) in rats. METHODS: Rats were tracheotomized and allowed to breathe spontaneously or mechanically ventilated for 4 h. After that, lung injury was assessed. Inhibition of toll-like receptor 9 (TLR9), named ODN2088, was used to determine the involvement of TLR9/myeloid differentiation factor 88 (MyD88)/nuclear factor-κB (NF-κB) signaling pathway in VILI. The mitochondrial damage and release of mtDNA were assessed. Pharmacological inhibition of mtDNA (chloroquine) was used to determine whether mtDNA trigger inflammation via TLR9 in VILI. EDU-labeled mtDNA deriving from mitophagy was assessed by immunofluorescence. The role of mitophagy in VILI was shown by administration of antimycin A and cyclosporine A. MAIN RESULTS: Rats subjected to HTV showed more severe pulmonary edema and inflammation than the other rats. The decreased expression of TLR9, MyD88, and NF-κB were observed following the use of ODN2088. Mechanical ventilation (MV) with HTV damaged mitochondria which resulted in dysfunctional ATP synthesis, accumulation of reactive oxygen species, and loss of mitochondrial membrane potential. Moreover, the results of distribution of fluorescence in rats upon HTV stimulation indicated that mtDNA cleavage was associated with mitophagy. The expression levels of mitophagy related genes (LC3B-II/LC3B-I, PINK1, Parkin, and mitofusin 1) in animals ventilated with HTV were significantly upregulated. Administration of antimycin A aggregated the histological changes and inflammation after MV, but these effects were attenuated when administered in the presence of cyclosporine A. CONCLUSION: MV with HTV induces mitochondrial damage and mitophagy, contributing to the release of mtDNA, which may be induced VILI in rat via TLR9/MyD88/NF-κB signaling pathway.

Determinants of emergency medical utilization among the elderly population in Taiwan: a national longitudinal cohort study.

The aim of this study was to evaluate the potential determinants for emergency medical utilization by elderly patients in Taiwan. The data were drawn from the 'Survey of Health and Living Status of the Elderly in Taiwan', a population-based, longitudinal study of a nationally representative random sample of older adults aged 60 years and older, which was conducted from 1989 to 2007. Face-to-face interviews were conducted at the respondents' homes by trained interviewers accompanied by local health workers. The Andersen Behavioral Model helped us to evaluate the potential determinants for emergency medical utilization that included predisposing factors, enabling factors, and need factors. The measurements of determinants were repeated five times in the period of this study, and the longitudinal data were analyzed through the generalized estimating equation (GEE) by SPSS 17.0 software. The eligibility criteria were that respondents had to be more than 65 years old at baseline in 1993, and then they had to be enrolled in a 14-year follow-up period from 1993 to 2007. At the beginning of this study in 1993, there were 2961 eligible respondents in total, and in 2007, there were 1136 survivors. The loss in follow-up was mainly due to death. The results demonstrated that the significant determinants of emergency medical utilization by the elderly population were gender, age, education, self-ranked health status, chronic disease, and medical accessibility. The GEE model provides a suitable method to predict the long-term trend of emergency medical utilization by the elderly.