Differential effects of dexamethasone and roflumilast on asthma in mice with or without short cigarette smoke exposure.

Appropriate drug treatment for smoking asthmatics is uncertain because most smokers with asthma are less sensitive to treatment with glucocorticoids compared with non-smokers with asthma. We hypothesized that roflumilast (Rof), a selective phosphodiesterases-4 inhibitor regarded as an add-on therapy for chronic obstructive pulmonary disease, might be more effective than glucocorticoids for improving asthma in smokers. To investigate this hypothesis, we compared the therapeutic effects of dexamethasone (Dex) and Rof in a mouse model of ovalbumin-induced asthma with or without concurrent cigarette smoke (CS) exposure for 2 weeks. We found that recurrent asthma attacks increased lung tissue resistance. CS exposure in asthmatic mice decreased the central airway resistance, increased lung compliance, and attenuated airway hyper-responsiveness (AHR). CS exposure in asthmatic mice also increased the number of neutrophils and macrophages in the bronchoalveolar fluid. Treatment with Dex in asthmatic mice without CS exposure reduced airway resistance, AHR and airway eosinophilia. In asthmatic mice with CS exposure, however, Dex treatment unexpectedly increased lung tissue resistance and restored AHR that had been otherwise suppressed. Dex treatment in asthmatic mice with CS exposure inhibited eosinophilic inflammation but conversely exacerbated neutrophilic inflammation. On the other hand, treatment with Rof in asthmatic mice without CS exposure reduced airway resistance and airway eosinophilia, although the inhibitory effect of Rof on AHR was unremarkable. In asthmatic mice with CS exposure, Rof treatment did not exacerbate lung tissue resistance but modestly restored AHR, without any significant effects on airway inflammation. These results suggest that CS exposure mitigates sensitivity to both Dex and Rof. In asthmatic mice with CS exposure, Dex is still effective in reducing eosinophilic inflammation but increases lung tissue resistance, AHR and neutrophilic inflammation. Rof is ineffective in improving lung function and inflammation in asthmatic mice with CS exposure. This study did not support our initial hypothesis that Rof might be more effective than glucocorticoids for improving asthma in smokers. However, glucocorticoids may have a detrimental effect on smoking asthmatics.

Arousal index as a marker of carotid artery atherosclerosis in patients with obstructive sleep apnea syndrome.

PURPOSE: It was shown in a previous cohort study that men with internal carotid artery (ICA) plaque, defined as focal wall thickness of ≥ 1.5 mm, had a threefold higher risk of stroke than those without plaque. We examined the relationship between arousal indices and sleep stages in patients with obstructive sleep apnea syndrome (OSAS) and carotid atherosclerosis. METHODS: Carotid atherosclerosis severity was evaluated using the maximal carotid wall intima-media thickness of the ICA (ICA-maxIMT) and plaque in 83 patients with OSAS. RESULTS: The ICA-maxIMT values were positively correlated with the apnea hypopnea index (AHI) (ρ = 0.294, P = 0.007), arousal index (ρ = 0.289, P = 0.008), oxygen desaturation index (ρ = 0.298, P = 0.006), percentage of visually scored total sleep time spent in nocturnal oxygen saturation < 90% (SpO2 < 90%) (ρ = 0.246, P = 0.025), and the percentage of visually scored total sleep time spent in non-REM sleep stage 1 (ρ = 0.326, P = 0.003) and were negatively correlated with the percentage of visually scored total sleep time spent in non-REM sleep stages 2 and 3. Arousal index, diabetes mellitus, and age were found to be independent predictors of ICA plaque presence (OR 1.052, P = 0.003; OR 8.705, P = 0.026; OR 1.064, P = 0.023, respectively). CONCLUSIONS: Several PSG variables that are indicative of sleep fragmentation, sleep disordered breathing, and poor sleep quality correlated with the occurrence of atherosclerosis, but total arousal index was the only independent predictive factor.

Multiferroic nanocomposite fabrication via liquid phase using anodic alumina template.

We report a novel and inexpensive fabrication process of multiferroic nanocomposite via liquid phase using an anodic alumina template. The sol-gel spin-coating technique was used to coat the template with ferrimagnetic CoFe2O4. By dissolving the template with NaOH aqueous solution, a unique nanotube array structure of CoFe2O4 was obtained. The CoFe2O4 nanotube arrays were filled with, and sandwiched in, ferroelectric BaTiO3 layers by a sol-gel spin-coating method to obtain the composite. Its multiferroicity was confirmed by measuring the magnetic and dielectric hysteresis loops.

Hypercapnia Accelerates Adipogenesis: A Novel Role of High CO2 in Exacerbating Obesity.

Obesity is a major risk factor for the development of obstructive sleep apnea (OSA) and obesity hypoventilation syndrome (OHS), which manifest as intermittent hypercapnia and sustained plus intermittent hypercapnia, respectively. In this study, we investigated whether CO2 affects adipocyte differentiation (adipogenesis) and maturation (hypertrophy). Human visceral or subcutaneous preadipocytes were grown to confluence and then induced to differentiate to adipocytes under hypocapnia, normocapnia, and hypercapnia with or without hypoxia. Adipogenesis was also induced under intermittent or sustained hypercapnia. Differentiated adipocytes were maintained to maturity under normocapnia or hypercapnia. Our main findings are as follows: (1) hypercapnia accelerated adipogenesis in visceral and subcutaneous preadipocytes, whereas hypocapnia inhibited adipogenesis; (2) hypercapnia did not affect adipocyte hypertrophy; (3) hypercapnia-accelerated adipogenesis was independent of extracellular acidosis, oxygen concentration, or either intermittent or sustained exposure to high CO2; and (4) the mechanisms underlying hypercapnia-accelerated adipogenesis involved increased production of cyclic adenosine monophosphate (cAMP) via soluble adenylyl cyclase, leading to the activation of protein kinase A and exchanger protein directly activated by cAMP, which, in turn, activated proadipogenic transcription factors, such as cAMP response element binding protein, CCAAT/enhancer binding protein ß, and peroxisome proliferator-activated receptor γ. This study reveals a novel role of high CO2 in promoting adipogenesis, which provides mechanistic clues to a pathoetiological interaction between OSA/OHS and obesity. Our data suggest a vicious cycle of disease progression via the following mechanism: OSA/OHS → hypoventilation → hypercapnia → increased adipogenesis → increased fat mass → exacerbated OSA/OHS.

Improvement of metabolic disorders by an EP2 receptor agonist via restoration of the subcutaneous adipose tissue in pulmonary emphysema.

Chronic obstructive pulmonary disease (COPD) is often associated with co-morbidities. Metabolic disorders like hyperlipidemia and diabetes occur also in underweight COPD patients, although the mechanism is uncertain. Subcutaneous adipose tissue (SAT) plays an important role in energy homeostasis, since restricted capacity to increase fat cell number with increase in fat cell size occurring instead, is associated with lipotoxicity and metabolic disorders. The aim of this study is to show the protective role of SAT for the metabolic disorders in pulmonary emphysema of a murine model. We found ectopic fat accumulation and impaired glucose homeostasis with wasting of SAT in a murine model of elastase-induced pulmonary emphysema (EIE mice) reared on a high-fat diet. ONO-AE1-259, a selective E-prostanoid (EP) 2 receptor agonist, improved angiogenesis and subsequently adipogenesis, and finally improved ectopic fat accumulation and glucose homeostasis with restoration of the capacity for storage of surplus energy in SAT. These results suggest that metabolic disorders like hyperlipidemia and diabetes occured in underweight COPD is partially due to the less capacity for storage of surplus energy in SAT, though the precise mechanism is uncertained. Our data pave the way for the development of therapeutic interventions for metabolic disorders in emphysema patients, e.g., use of pro-angiogenic agents targeting the capacity for storage of surplus energy in the subcutaneous adipose tissue.

Fast calculation method of computer generated hologram animation for viewpoint parallel shift and rotation using Fourier transform optical system.

Computer generated hologram (CGH) animations can be made by switching many CGHs on an electronic display. Some fast calculation methods for CGH animations have been proposed, but one for viewpoint movement has not been proposed. Therefore, we designed a fast calculation method of CGH animations for viewpoint parallel shifts and rotation. A Fourier transform optical system was adopted to expand the viewing angle. The results of experiments were that the calculation time of our method was over 6 times faster than that of the conventional method. Furthermore, the degradation in CGH animation quality was found to be sufficiently small.

An evolutionary medicine approach to understanding factors that contribute to chronic obstructive pulmonary disease.

Although many studies have been published on the causes and mechanisms of chronic obstructive pulmonary disease (COPD), the reason for the existence of COPD and the reasons why COPD develops in humans have hardly been studied. Evolutionary medical approaches are required to explain not only the proximate factors, such as the causes and mechanisms of a disease, but the ultimate (evolutionary) factors as well, such as why the disease is present and why the disease develops in humans. According to the concepts of evolutionary medicine, disease susceptibility is acquired as a result of natural selection during the evolutionary process of traits linked to the genes involved in disease susceptibility. In this paper, we discuss the following six reasons why COPD develops in humans based on current evolutionary medical theories: (1) evolutionary constraints; (2) mismatch between environmental changes and evolution; (3) co-evolution with pathogenic microorganisms; (4) life history trade-off; (5) defenses and their costs, and (6) reproductive success at the expense of health. Our perspective pursues evolutionary answers to the fundamental question, 'Why are humans susceptible to this common disease, COPD, despite their long evolutionary history?' We believe that the perspectives offered by evolutionary medicine are essential for researchers to better understand the significance of their work.

Computer Simulation and Field Experiment for Downlink Multiuser MIMO in Mobile WiMAX System.

The transmission performance for a downlink mobile WiMAX system with multiuser multiple-input multiple-output (MU-MIMO) systems in a computer simulation and field experiment is described. In computer simulation, a MU-MIMO transmission system can be realized by using the block diagonalization (BD) algorithm, and each user can receive signals without any signal interference from other users. The bit error rate (BER) performance and channel capacity in accordance with modulation schemes and the number of streams were simulated in a spatially correlated multipath fading environment. Furthermore, we propose a method for evaluating the transmission performance for this downlink mobile WiMAX system in this environment by using the computer simulation. In the field experiment, the received power and downlink throughput in the UDP layer were measured on an experimental mobile WiMAX system developed in Azumino City in Japan. In comparison with the simulated and experimented results, the measured maximum throughput performance in the downlink had almost the same performance as the simulated throughput. It was confirmed that the experimental mobile WiMAX system for MU-MIMO transmission successfully increased the total channel capacity of the system.

Promotion of adipogenesis by an EP2 receptor agonist via stimulation of angiogenesis in pulmonary emphysema.

Body weight loss is a common manifestation in patients with chronic obstructive pulmonary disease (COPD), particularly those with severe emphysema. Adipose angiogenesis is a key mediator of adipogenesis and use of pro-angiogenic agents may serve as a therapeutic option for lean COPD patients. Since angiogenesis is stimulated by PGE2, we examined whether ONO-AE1-259, a selective E-prostanoid (EP) 2 receptor agonist, might promote adipose angiogenesis and adipogenesis in a murine model of elastase-induced pulmonary emphysema (EIE mice). Mice were intratracheally instilled with elastase or saline, followed after 4 weeks by intraperitoneal administration of ONO-AE1-259 for 4 weeks. The subcutaneous adipose tissue (SAT) weight decreased in the EIE mice, whereas in the EIE mice treated with ONO-AE1-259, the SAT weight was largely restored, which was associated with significant increases in SAT adipogenesis, angiogenesis, and VEGF protein production. In contrast, ONO-AE1-259 administration induced no alteration in the weight of the visceral adipose tissue. These results suggest that in EIE mice, ONO-AE1-259 stimulated adipose angiogenesis possibly via VEGF production, and thence, adipogenesis. Our data pave the way for the development of therapeutic interventions for weight loss in emphysema patients, e.g., use of pro-angiogenic agents targeting the adipose tissue vascular component.

Systemic effects of acute cigarette smoke exposure in mice.

CONTEXT: Cigarette smoke (CS) causes both pulmonary and extrapulmonary disorders. OBJECTIVE: To determine the pulmonary and extrapulmonary effects of acute CS exposure in regard to inflammation, oxidative stress and DNA damage. MATERIALS AND METHODS: Mice were exposed to CS for 10 days and then their lungs, heart, liver, pancreas, kidneys, gastrocnemius muscle and subcutaneous (inguinal and flank) and visceral (retroperitoneum and periuterus) adipose tissues were excised. Bronchoalveolar lavage fluid samples were obtained for differential cell analysis. Inflammatory cell infiltration of the tissues was assessed by immunohistochemistry for Mac-3(+) cells, F4/80(+) cells and CD45(+) cells. Oxidative stress was determined by immunohistochemistry for thymidine glycol (a marker of DNA peroxidation) and 4-hydroxy hexenal (a marker of lipid peroxidation), by enzyme-linked immunosorbent assay for protein carbonyls (a marker of protein peroxidation) and by measurements of enzyme activities of glutathione peroxidase, superoxide dismutase and catalase. DNA double-strand breaks were assessed by immunohistochemistry for γH2AX. RESULTS: CS exposure-induced inflammatory cell infiltration, oxidative stress and DNA damage in the lung. Neither inflammatory cell infiltration nor DNA damage was observed in any extrapulmonary organs. However, oxidative stress was increased in the heart and inguinal adipose tissue. DISCUSSIONS: Induction of inflammatory cell infiltration and DNA damage by acute CS exposure was confined to the lung. However, an increased oxidative burden occurred in the heart and some adipose tissue, as well as in the lung. CONCLUSIONS: Although extrapulmonary effects of CS are relatively modest compared with the pulmonary effects, some extrapulmonary organs are vulnerable to CS-induced oxidative stress.

Variational Bayes inference for hidden Markov diagnostic classification models.

Diagnostic classification models (DCMs) can be used to track the cognitive learning states of students across multiple time points or over repeated measurements. This study developed an effective variational Bayes (VB) inference method for hidden Markov longitudinal general DCMs. The simulations performed in this study verified the validity of the proposed algorithm for satisfactorily recovering true parameters. Simulation and applied data analyses were conducted to compare the proposed VB method to Markov chain Monte Carlo (MCMC) sampling. The results revealed that the parameter estimates provided by the VB method were consistent with the MCMC method with the additional benefit of a faster estimation time. The comparative simulation also indicated differences between the two methods in terms of posterior standard deviation and coverage of 95% credible intervals. Thus, with limited computational resources and time, the proposed VB method can output estimations comparable to that of MCMC.

Characteristics and Clinical Assessment of Elbow Pain in Youth Baseball Players.

Elbow injuries related to the throwing motion in baseball during the growth period present difficulties for early detection and may cause serious future disabilities. This study aimed to comprehensively determine the characteristics and clinical assessment of elbow pain in youth baseball players. Two hundred and sixteen young baseball players underwent elbow medical examination. Basic information and physical examination, clinical assessment, and ultrasonography results were examined. Univariate analyses were statistically performed between the pain-free (98 participants) and elbow pain (118 participants) groups. The mean age was 11.6 years, and ultrasonographic abnormalities were found on the medial side of the elbow in 37.5%. In total, 118 (54.6%) participants experienced elbow pain, with 64.4% of them complaining of elbow pain on the medial side. Players with multiple positions (≥2 positions) had a significantly higher prevalence of elbow pain. Height, weight, length of baseball experience, and positive rates of horizontal flexion and moving valgus stress tests were higher in the elbow pain group than in the pain-free group. The risk factors and clinical assessment for elbow pain are useful for the prevention and early detection of throwing elbow injuries in youth baseball players.

The danger signal plus DNA damage two-hit hypothesis for chronic inflammation in COPD.

Inflammation in chronic obstructive pulmonary disease (COPD) is thought to originate from the activation of innate immunity by a danger signal (first hit), although this mechanism does not readily explain why the inflammation becomes chronic. Here, we propose a two-hit hypothesis explaining why inflammation becomes chronic in patients with COPD. A more severe degree of inflammation exists in the lungs of patients who develop COPD than in the lungs of healthy smokers, and the large amounts of reactive oxygen species and reactive nitrogen species released from inflammatory cells are likely to induce DNA double-strand breaks (second hit) in the airways and pulmonary alveolar cells, causing apoptosis and cell senescence. The DNA damage response and senescence-associated secretory phenotype (SASP) are also likely to be activated, resulting in the production of pro-inflammatory cytokines. These pro-inflammatory cytokines further stimulate inflammatory cell infiltration, intensifying cell senescence and SASP through a positive-feedback mechanism. This vicious cycle, characterised by mutually reinforcing inflammation and DNA damage, may cause the inflammation in COPD patients to become chronic. Our hypothesis helps explain why COPD tends to occur in the elderly, why the inflammation worsens progressively, why inflammation continues even after smoking cessation, and why COPD is associated with lung cancer.

Realistic expression for full-parallax computer-generated holograms with the ray-tracing method.

This paper presents a calculation method of computer-generated holograms that involves removing the hidden surface and provides realistic rendering. The method was based on the ray-tracing method that simulates rays traveling paths. Rays are cast from every elementary hologram into virtual objects and then the traveling paths of the rays are determined. Since the method is considering intersection with objects, absorption, reflection, and refraction, the method is capable of rendering realistic images. Multiple reflections and refraction are expressed by casting additional rays into the reflection direction and the transmission direction and calculating the length of the light path. To express the quality of materials, the Phong reflection model and Cook-Torrance reflection model were used. Results of optical reconstructions show that the hidden surface removal was conducted. Moreover, the texture of material appeared as well as other effects by the proposed method.

Computer-generated holograms using multiview images captured by a small number of sparsely arranged cameras.

Computer-generated holograms (CGHs) using multiview images (MVIs) are holograms generated with multiple ordinary cameras. This process typically requires a huge number of cameras arranged at high density. In this paper, we propose a method to improve CGH using MVIs that obtains the MVIs by using voxel models rather than cameras. In the proposed method the voxel model is generated using the shape-from-silhouette (SFS) technique. We perform SFS using a small number of cameras arranged sparsely to create voxel models of objects and then generate the required number of images from these models by volume rendering. This enables us to generate CGHs using MVIs with just a small number of sparsely arranged cameras. Moreover, the proposed method arrange CGHs using MVIs at arbitrary positions.

Precalculation method using spherical basic object light for computer-generated hologram.

Precalculation methods for computer-generated holograms provide fast calculation by transforming precalculated object light in accordance with the subject shape in the spatial domain. In this paper, a novel method is proposed that uses precalculated object light recorded on a spherical surface, which makes the data size half that of the conventional method. Moreover, representations of the transforms by homogeneous coordinates on the spherical surface are discussed. These representations allow common operations of transforms and solve the calculation complexity that conventional precalculation methods have. The effectiveness of the proposed method was confirmed by optical image-reconstruction experiments successfully.

Interaction of BMI and respiratory status in obstructive sleep apnea, a cross-sectional COPD study.

This cross-sectional study of 136 patients with chronic obstructive pulmonary disease (COPD) investigated the mechanism underlying overlap syndrome, defined as coexisting COPD and obstructive sleep apnea (OSA). OSA was defined as a respiratory event index (REI) ≥ 5 events/h, determined using type-3 portable monitors. The mean REI was 12.8 events/h. Most participants (60.1%) had mild OSA (REI: 5-15 events/h). The REI was positively correlated with forced expiratory volume in one second (%FEV1) (r = 0.33, p < 0.001), body mass index (BMI) (r = 0.24, p = 0.005), and fat-free mass index (r = 0.31, p = 0.005), and negatively correlated with residual volume divided by total lung capacity (r = -0.27, p = 0.003). Receiver-operating characteristic curve analysis revealed an optimal BMI cutoff of 21.96 kg/m2 for predicting moderate/severe OSA. A BMI ≥ 21.96 kg/m2 was associated with OSA among participants with %FEV1 ≥ 50%, but not those with %FEV1 < 50%. This study revealed an interaction between airflow limitation and hyperinflation, nutritional status, and OSA.

Direct Estimation of Diagnostic Classification Model Attribute Mastery Profiles via a Collapsed Gibbs Sampling Algorithm.

This paper proposes a novel collapsed Gibbs sampling algorithm that marginalizes model parameters and directly samples latent attribute mastery patterns in diagnostic classification models. This estimation method makes it possible to avoid boundary problems in the estimation of model item parameters by eliminating the need to estimate such parameters. A simulation study showed the collapsed Gibbs sampling algorithm can accurately recover the true attribute mastery status in various conditions. A second simulation showed the collapsed Gibbs sampling algorithm was computationally more efficient than another MCMC sampling algorithm, implemented by JAGS. In an analysis of real data, the collapsed Gibbs sampling algorithm indicated good classification agreement with results from a previous study.

Reconsidering the structure of the questionnaire for eudaimonic well-being using wide age-range Japanese adult sample: An exploratory analysis.

BACKGROUND: An increasing amount of research is now highlighting the importance of approaching issues of happiness through eudaimonic well-being. However, the literature does not conclusively show a full understanding of the construct of eudaimonic well-being, as previous studies primarily focused on younger samples from Western countries and only a few studies have attempted to explore its psychological construct through exploratory approaches. Therefore, we conducted a survey among a wide range of age groups in Japan to capture the psychological construct of eudaimonic well-being, through an exploratory analytic approach using Questionnaire for Eudaimonic Wellbeing (QEWB). METHODS: A total of 1126 Japanese participants (580 females, 546 males) were included for analysis. Participants were divided into three age groups according to their age, including 10s to 20s (18-29 years), 30s to 40s (30-49 years) and 50s to 60s (50-69 years). After narrowing down the total number of factors by exploratory structural equation modeling (ESEM), we conducted an ESEM and bifactor ESEM with oblique goemin and oblique bi-geomin rotations for choosing and assessing the final model based on the rotated results and its interpretability. RESULTS: The results of a parallel analysis and goodness-of-fit indices obtained by ESEM indicated that the QEWB consisted of three or more factors. Both a three-to-six factor and bifactor ESEM with oblique goemin rotation showed that three-factor structure for the 30s to 40s and 50s to 60s and four-factor structure for the 10s to 20s should be chosen, respectively. "Deep and Meaningful Engagement," a factor only relevant to the 10s to 20s may be an expanded version of what original paper called the Intense Involvement in Activities, with more emphasis on the enthusiastic attitude one has towards activities. CONCLUSIONS: The structure of eudaimonic well-being may differ across cultures and ages, thus requiring further investigation in the field.

Calculation method for computer-generated holograms considering various reflectance distributions based on microfacets with various surface roughnesses.

Computer-generated holograms are generated by three-dimensional technology, and they can be used to reconstruct natural and virtual objects by simulating light waves based on holography. This research was an improvement on previous work that took into consideration reflectance distributions from the various roughnesses of objects. The previous work generated roughness by using a simple model, so that only simple roughness was generated. The proposed method generated more complex roughness than that in the previous work, and the influence of roughness on the reflectance distributions was investigated. Computer simulations, which were compared with the reflectance distributions from the various roughnesses, were carried out. Moreover, computational and optical reconstructions were carried out as examples of reconstructions. As a result of the experiments, we confirmed that the various roughnesses actually influenced the reflectance distributions.