Noncontact Detection of Sleep Apnea Using Radar and Expectation-Maximization Algorithm

Sleep apnea syndrome requires early diagnosis because this syndrome can lead to a variety of health problems. If sleep apnea events can be detected in a noncontact manner using radar, we can then avoid the discomfort caused by the contact-type sensors that are used in conventional polysomnography. This study proposes a novel radar-based method for accurate detection of sleep apnea events. The proposed method uses the expectation-maximization algorithm to extract the respiratory features that form normal and abnormal breathing patterns, resulting in an adaptive apnea detection capability without any requirement for empirical parameters. We conducted an experimental quantitative evaluation of the proposed method by performing polysomnography and radar measurements simultaneously in five patients with the symptoms of sleep apnea syndrome. Through these experiments, we show that the proposed method can detect the number of apnea and hypopnea events per hour with an error of 4.8 times/hour; this represents an improvement in the accuracy by 1.8 times when compared with the conventional threshold-based method and demonstrates the effectiveness of our proposed method.Comment: 8 pages, 12 figures, 3 tables. This work is going to be submitted to the IEEE for possible publicatio

Inhibition of Plasminogen Activator Inhibitor- 1 Attenuates Transforming Growth Factor- β-Dependent Epithelial Mesenchymal Transition and Differentiation of Fibroblasts to Myofibroblasts

Transforming growth factor-β (TGF-β) is central during the pathogenesis of pulmonary fibrosis, in which the plasminogen activator inhibitor-1 (PAI-1) also has an established role. TGF-β is also known to be the strongest inducer of PAI-1. To investigate the link between PAI-1 and TGF-β in fibrotic processes, we evaluated the effect of SK-216, a PAI-1-specific inhibitor, in TGF-β-dependent epithelial-mesenchymal transition (EMT) and fibroblast to myofibroblast differentiation. In human alveolar epithelial A549 cells, treatment with TGF-β induced EMT, whereas co-treatment with SK-216 attenuated the occurrence of EMT. The inhibition of TGF-β-induced EMT by SK-216 was also confirmed in the experiment using murine epithelial LA-4 cells. Blocking EMT by SK-216 inhibited TGF-β-induced endogenous production of PAI-1 and TGF-β in A549 cells as well. These effects of SK-216 were not likely mediated by suppressing either Smad or ERK pathways. Using human lung fibroblast MRC-5 cells, we demonstrated that SK-216 inhibited TGF-β-dependent differentiation of fibroblasts to myofibroblasts. We also observed this inhibition by SK-216 in human primary lung fibroblasts. Following these in vitro results, we tested oral administration of SK-216 into mice injected intratracheally with bleomycin.We found that SK-216 reduced the degree of bleomycin-induced pulmonary fibrosis in mice. Although the precise mechanisms underlying the link between TGF-β and PAI-1 regarding fibrotic process were not determined, PAI-1 seems to act as a potent downstream effector on the pro-fibrotic property of TGF-β. In addition, inhibition of PAI-1 activity by a PAI-1 inhibitor exerts an antifibrotic effect even in vivo. These data suggest that targeting PAI-1 as a downstream effector of TGF-β could be a promising therapeutic strategy for pulmonary fibrosis

Reduced endogenous secretory RAGE in blood and bronchoalveolar lavage fluid is associated with poor prognosis in idiopathic pulmonary fibrosis

Background The endogenous secretory receptor for advanced glycation end products (esRAGE) is a soluble isoform produced by alternative splicing of the RAGE gene. The isoform has anti-inflammatory properties due to its inhibition of the RAGE/ligand interaction and is reduced in the lung tissue of patients with idiopathic pulmonary fibrosis (IPF). This study aimed to investigate the association of esRAGE serum and bronchoalveolar lavage fluid (BALF) levels with progression of IPF. Methods This study included 79 IPF patients and 90 healthy controls. IPF and control serum esRAGE levels were compared, and the correlation between serum and BALF esRAGE levels was analyzed in 57 IPF patient samples. We also investigated the relationship of esRAGE serum and BALF levels with prognoses and lung function parameters in patients with IPF. Results Serum esRAGE levels in IPF patients were significantly lower than those in healthy controls (162.0 +/- 102.4 ng/ml and 200.7 +/- 107.3 ng/ml,p = 0.009), although the baseline characteristics of age and smoking history were not matched. Serum levels of esRAGE were correlated with BALF esRAGE levels (r(s) = 0.317). The BALF esRAGE levels were also correlated with diffusion capacity for carbon monoxide (r(s) = 0.406). A Kaplan-Meier curve analysis and univariate/multivariate Cox hazard proportion analysis revealed that lower levels of esRAGE in blood and BALF were significantly associated with poorer prognoses in patients with IPF. Conclusions Decreased esRAGE levels in BALF and blood were associated with poor prognoses in patients with IPF. These results suggest that esRAGE could be related to the pathophysiology of IPF and serum esRAGE could be a potential prognostic marker of IPF.Peer reviewe

MUC1 in lung adenocarcinoma: cross-sectional genetic and serological study

[Background]Mucin 1 (MUC1) contributes to the growth and metastasis of various cancers, including lung cancer, and MUC1 gene length polymorphisms are associated with susceptibility to lung cancer and its prognosis. In contrast, the association between rs4072037, a single nucleotide polymorphism in MUC1, and lung cancer has not been well studied. [Methods]In the present study, we determined the rs4072037 genotype and measured serum KL-6 levels to evaluate the association between lung adenocarcinoma (ADC) and rs4072037 or serum KL-6 levels. DNA samples were available for 172 patients and these were included in the genomic analyses. In addition, 304 patients were included in the serum analyses. Furthermore, 276 healthy volunteers were included in both genomic and serum analyses. [Results]The rs4072037 genotype was not associated with susceptibility to lung ADC or its prognosis. Interestingly, serum KL-6 levels significantly differed according to rs4072037 genotype in those with T1 or T2 (P < 0.001), N0 or N1 (P = 0.002) and M0 (P < 0.001), but not in those with T3 or T4 (P = 0.882), N2 or N3 (P = 0.616) and M1a or M1b (P = 0.501). Serum KL-6 levels were significantly associated with the presence of lung ADC, as well as with its progression and prognosis, indicating the crucial involvement of KL-6/MUC1 in the development of lung cancer and its progression. [Conclusion]Based on these findings, we conclude that rs4072037 does not have a significant impact on the pathogenesis or prognosis of lung ADC, whereas serum KL-6 levels, which might reflecting the molecular length of MUC1, are significantly associated with lung ADC.This work was partly supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan. The funders had no role in study design, collection, analysis and interpretation of data and in writing the manuscript

Intracrine activity involving NAD-dependent circadian steroidogenic activity governs age-associated meibomian gland dysfunction

新たなイントラクライン機構を用いた加齢性眼疾患治療へ --眼局所のホルモンの加齢変化とサーカディアンリズムが鍵--. 京都大学プレスリリース. 2022-02-14.Canonically, hormones are produced in the endocrine organs and delivered to target tissues. However, for steroids, the concept of tissue intracrinology, whereby hormones are produced in the tissues where they exert their effect without release into circulation, has been proposed, but its role in physiology/disease remains unclear. The meibomian glands in the eyelids produce oil to prevent tear evaporation, which reduces with aging. Here, we demonstrate that (re)activation of local intracrine activity through nicotinamide adenine dinucleotide (NAD+)-dependent circadian 3β-hydroxyl-steroid dehydrogenase (3β-HSD) activity ameliorates age-associated meibomian gland dysfunction and accompanying evaporative dry eye disease. Genetic ablation of 3β-HSD nullified local steroidogenesis and led to atrophy of the meibomian gland. Conversely, reactivation of 3β-HSD activity by boosting its coenzyme NAD+ availability improved glandular cell proliferation and alleviated the dry eye disease phenotype. Both women and men express 3β-HSD in the meibomian gland. Enhancing local steroidogenesis may help combat age-associated meibomian gland dysfunction

Development of new experimental platform ‘MARS’—Multiple Artificial-gravity Research System—to elucidate the impacts of micro/partial gravity on mice

This Japan Aerospace Exploration Agency project focused on elucidating the impacts of partial gravity (partial g) and microgravity (μg) on mice using newly developed mouse habitat cage units (HCU) that can be installed in the Centrifuge-equipped Biological Experiment Facility in the International Space Station. In the first mission, 12 C57BL/6 J male mice were housed under μg or artificial earth-gravity (1 g). Mouse activity was monitored daily via downlinked videos; μg mice floated inside the HCU, whereas artificial 1 g mice were on their feet on the floor. After 35 days of habitation, all mice were returned to the Earth and processed. Significant decreases were evident in femur bone density and the soleus/gastrocnemius muscle weights of μg mice, whereas artificial 1 g mice maintained the same bone density and muscle weight as mice in the ground control experiment, in which housing conditions in the flight experiment were replicated. These data indicate that these changes were particularly because of gravity. They also present the first evidence that the addition of gravity can prevent decreases in bone density and muscle mass, and that the new platform ‘MARS’ may provide novel insights on the molecular-mechanisms regulating biological processes controlled by partial g/μg