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Study objectives Sleep is associated with a reduction in ventilation and an increase in upper airway resistance (UAR) in patients with obstructive sleep apnea (OSA). However, there is no consensus on the standard for assessment of UAR and therefore it is important to develop a method to reliably assess UAR in patients with OSA. The purpose of the present study is to determine whether the ratio of neural respiratory drive (NRD) to flow can be used to assess changes in UAR in OSA during sleep. Methods A total of 24 patients (21 men) with OSA and 10 normal subjects (6 males) were studied. The UAR was assessed by the ratio of NRD to flow, which measured by esophageal pressure (Poes), diaphragm electromyography (EMGdi) and superficial diaphragm electromyography (SEMGdi) in various stages including wakefulness, N2 sleep, N2 sleep with snoring, hypopneas, the in the “preapnea” states in OSA versus wakefulness, sleeponset, N2 sleep, N3 sleep in normal subjects. All subjects underwent overnight full polysomnography using standard techniques. Results Our study indicate that UAR was progressively higher from wakefulness to N2 sleep, N2 sleep with snoring, hypopneas, and the in the “preapnea” states in patients with OSA and had obvious difference in statistical significance (p Conclusions It is feasible to use the ratio of neural respiratory drive to flow to assess UAR in patients with OSA during sleep.

Background Although recent evidence suggests that OSA treatment may cause weight gain, the long-term effects of CPAP on weight are not well established. Methods This study was a post hoc analysis of the Sleep Apnea Cardiovascular Endpoints (SAVE) study, a multicenter, randomized trial of CPAP plus standard care vs standard care alone in adults with a history of cardiac or cerebrovascular events and moderate to severe OSA. Participants with weight, BMI, and neck and waist circumferences measured at baseline and during follow-up were included. Linear mixed models were used to examine sex-specific temporal differences, and a sensitivity analysis compared high CPAP adherers (≥ 4 h per night) with propensity-matched control participants. Results A total of 2,483 adults (1,248 in the CPAP group and 1,235 in the control group) were included (mean 6.1 ± 1.5 measures of weight available). After a mean follow-up of 3.78 years, there was no difference in weight change between the CPAP and control groups, for male subjects (mean [95% CI] between-group difference, 0.07 kg [–0.40 to 0.54]; P = .773) or female subjects (mean [95% CI] between-group difference, –0.14 kg [–0.37 to 0.09]; P = .233). Similarly, there were no significant differences in BMI or other anthropometric measures. Although male participants who used CPAP ≥ 4 h per night gained slightly more weight than matched male control subjects without CPAP (mean difference, 0.38 kg [95% CI, 0.04 to 0.73]; P = .031), there were no between-group differences in other anthropometric variables, nor were there any differences between female high CPAP adherers and matched control subjects. Conclusions Long-term CPAP use in patients with comorbid OSA and cardiovascular disease does not result in clinically significant weight change. Trial Registry ClinicalTrials.gov; No.: NCT00738179 ; URL: www.clinicaltrials.gov .

Background: Obstructive sleep apnoea (OSA) is a common comorbidity in patients with cardiovascular (CV) disease. We aimed to identify specific OSA clinical phenotypes relating to risks of serious CV events and response to continuous positive airway pressure (CPAP) treatment. Methods: Post-hoc analyses of the Sleep Apnea Cardiovascular Endpoints (SAVE) study in participants with moderate-to-severe OSA and coronary artery disease (CAD) and/or cerebrovascular disease (CeVD) randomised to CPAP plus usual care or usual care alone. Latent class analysis (LCA) was used to identify OSA clinical phenotypes among 2649 (out of 2687 total) patients with complete data on 19 patient-centered variables, supported by Bayesian information criteria and clinical interpretability. Cox regression models were used to evaluate risks of composite cardiac and stroke outcome events in phenotype groups. Preferential response to CPAP treatment was evaluated using interaction terms as well as the Chi-square test. Findings: LCA identified four OSA clinical phenotypes: CAD alone and with diabetes mellitus (CAD+DM), and CeVD alone and with DM (CeVD+DM), in 39%, 15%, 37% and 9% of participants, respectively. The rates of composite CV events were the highest in CAD+DM phenotype (HR 2.08, 95% CI 1.57–2.76) and for stroke were highest in CeVD+DM phenotype (HR 6.84, 95% CI 3.77–12.42). Adherence to CPAP treatment (nil or

Background In COPD, functional status is improved by pulmonary rehabilitation (PR) but requires specific facilities. Tai Chi, which combines psychological treatment and physical exercise and requires no special equipment, is widely practiced in China and is becoming increasingly popular in the rest of the world. We hypothesized that Tai Chi is equivalent (ie, difference less than ±4 St. George's Respiratory Questionnaire [SGRQ] points) to PR. Methods A total of 120 patients (mean FEV 1 , 1.11 ± 0.42 L; 43.6% predicted) bronchodilator-naive patients were studied. Two weeks after starting indacaterol 150 μg once daily, they randomly received either standard PR thrice weekly or group Tai Chi five times weekly, for 12 weeks. The primary end point was change in SGRQ prior to and following the exercise intervention; measurements were also made 12 weeks after the end of the intervention. Results The between-group difference for SGRQ at the end of the exercise interventions was –0.48 (95% CI PR vs Tai Chi, –3.6 to 2.6; P = .76), excluding a difference exceeding the minimal clinically important difference. Twelve weeks later, the between-group difference for SGRQ was 4.5 (95% CI, 1.9 to 7.0; P 1 was observed. Conclusions Tai Chi is equivalent to PR for improving SGRQ in COPD. Twelve weeks after exercise cessation, a clinically significant difference in SGRQ emerged favoring Tai Chi. Tai Chi is an appropriate substitute for PR. Trial Registry ClinicalTrials.gov; No.: NCT02665130; URL: www.clinicaltrials.gov.

A fall of ≥ 20 % in forced expiratory volume in the first second (FEV1) with a cumulative dose of histamine ≤ 7.8 μmol is considered to indicate bronchial hyperactivity, but no method exists for patients who cannot perform spirometry properly. Here we hypothesized that increases in respiratory central output measured by chest wall electromyography of the diaphragm (EMGdi-c) expressed as a function of tidal volume (EMGdi-c/VT) would have discriminative power to detect a 'positive' challenge test.In a physiological study EMGdi was recorded from esophageal electrode (EMGdi-e) in 16 asthma patients and 16 healthy subjects during a histamine challenge test. In a second study, EMGdi from chest wall surface electrodes (EMGdi-c) was measured during a histamine challenge in 44 asthma patients and 51 healthy subjects. VT was recorded from a digital flowmeter during both studies.With histamine challenge test the change in EMGdi-e/VT in patients with asthma was significantly higher than that in healthy subjects (104.2 % ± 48.6 % vs 0.03 % ± 17.1 %, p0.001). Similarly there was a significant difference in the change of EMGdi-c/VT between patients with asthma and healthy subjects (90.5 % ± 75.5 % vs 2.4 % ± 21.7 %, p0.001). At the optimal cut-off point (29 % increase in EMGdi-c/VT), the area under the ROC curve (AUC) for detection of a positive test was 0.91 (p0.001) with sensitivity 86 % and specificity 92 %.We conclude that EMGdi-c/VT may be used as an alternative for the assessment of bronchial hypersensitivity and airway reversibility to differentiate patients with asthma from healthy subjects.

Ascending thoracic aortic aneurysms (ATAAs) are focal dilatations in the aorta that are prone to rupture or dissection. To accurately evaluate the rupture risk, one must know the local mechanical conditions at the rupture site and understand how rupture is triggered in a layered fibrous media. A challenge facing experimental studies of ATAA rupture is that the ATAA tissue is highly heterogeneous; experimental protocols that operate under the premise of tissue homogeneity will have difficulty delineating the location conditions. In this work, we employed a previously established pointwise identification method to characterize wall stress, strain, and property distributions to a sub-millimeter resolution. Based on the acquired field data, we obtained the local mechanical properties at the rupture site in nine ATAA tissue samples. The rupture stress, ultimate strain, energy density, and the toughness of the tested samples were also reported. Our results show that the direction of the rupture is aligned with the direction of maximum stiffness, indicating that higher stiffness is not always related to higher strength. It was also found that the rupture generally occurs at a location of highest stored energy. As a higher stiffness and higher strain energy indicate a larger recruitment of collagen fibers in the tissue at the location and along the direction of rupture, the recruitment of collagen fibers in the deformation of the tissue is probably essential in ATAA rupture.A major challenge in the experimental study of aneurysm properties is that the tissues are heterogeneous. When the specimens are not reasonably homogeneous, traditional tests that work under the premise of tissue homogeneity cannot reliably delineate the local conditions at the rupture site. In this work, we investigated the local characteristics of rupture of human ascending aortic aneurysm tissue. We identified the stress, strain, and elastic properties to a submillimeter resolution. Based on the field values, we determined the local conditions - elastic properties, direction of maximum stiffness, stress, strain, energy consumption - at the rupture site. It was found that the tissues consistently cleave in the direction of the maximum stiffness, and generally occurs at the location of highest energy. Since a higher stiffness and higher strain energy indicate a larger recruitment of collagen fibers in the tissue at the location and along the direction of rupture, the work suggests that the recruitment of collagen fibers in the deformation of the tissue is probably essential in aneurysm rupture.

Wall stress in a curved membrane depends on the surface geometry and applied load, not the constitutive law of the wall material (static determinacy). This remarkable property suggests that the membrane stress can be determined without knowing of the material property. Being able to determine the wall stress without material knowledge is practically significant in numerous applications, particularly in in vivo biomedical stress analysis wherein patient-specific tissue properties are extremely difficult to obtain. In this article, we present two non-traditional methods that utilize the static determinacy to compute the membrane stress. A common theme is to start with a deformed configuration and use artificial material models. In one of these approaches, the equilibrium problem is formulated as an inverse elastostatic problem whereby the stress is determined by way of finding a (fictitious) reference configuration. The other approach utilizes the standard forward analysis, but in a penalty setting using artificially stiff material models. A continuum sensitivity analysis is implemented to quantitatively assess the influence of material parameters. These developments open new pathways of membrane analysis enabling stress prediction without using realistic material parameters. Numerical examples are provided to demonstrate and compare these two methods.

Clostridium thermocellum, a thermophilic anaerobe, has the unusual capacity to convert cellulosic biomass into ethanol and hydrogen. In this work, the cell wall proteome of C. thermocellum was investigated. The proteins in the cell wall fraction of C. thermocellum prepared by the boiling SDS method were released by mutanolysin digestion and resolved on two-dimensional (2D) gel. One hundred and thirty-two proteins were identified by mass spectrometry, among which the extracellular solute-binding protein (CbpB/cthe_1020), enolase, glyceraldehyde-3-phosphate dehydrogenase and translation elongation factor EF-Tu were detected as highly abundant proteins. Besides the known surface localized proteins, including FtsZ, MinD, GroEL, DnaK, many enzymes involved in bioenergetics, such as alcohol dehydrogenases and hydrogenases were also detected. By glycan stain and MS analysis of glycopeptides, we identified CbpB as a glycoprotein, which is the second glycoprotein from C. thermocellum characterized. The fact that CbpB was highly abundant in the cell wall region and glycosylated, reflects its importance in substrate assimilation. Our results indicate cell wall proteins constitute a significant portion of cellular proteins and may play important physiological roles (i.e. bioenergetics) in this bacterium. The insights described are relevant for the development of C. thermocellum as a biofuel producer.

The texture effect of AZ31 Mg alloy on its corrosion resistance in simulated body fluid (SBF) at 37 °C was examined by hydrogen evolution method, polarization curve and electrochemical impedance spectrum. It was found that at the early immersion time, the sample with c-axis of most grains normal to the exposed surface exhibited much higher corrosion resistance than the sample consisting mainly of ( 10 1 ¯ 0 ) and ( 11 2 ¯ 0 ) oriented grains. But after about 46 h of immersion, the corrosion rate of both samples was largely reduced, less than 0.011 ml/cm2/h due to the deposition of a film on surfaces. The profound texture effect on the corrosion resistance in SBF opened a new window to control the corrosion property of Mg alloys for biomedical applications.

Background The therapeutic value of transcutaneous electrical stimulation of the genioglossus muscle in patients with obstructive sleep apnea (OSA) to reduce sleep-disordered breathing is unclear. Methods Contraction of the genioglossus muscles during transcutaneous stimulation was investigated using ultrasonography in 11 healthy subjects (seven men, mean [SD] age 30 [6] years; BMI, 24.2 [3.5] kg/m 2 ). Esophageal and gastric pressures were measured with balloon catheters, and transesophageal diaphragm electromyogram (EMGdi) was recorded during polysomnography in 11 patients with OSA (eight men, aged 51 [16] years; BMI, 42.0 [9.7] kg/m 2 ) while transcutaneous electrical stimulation of the genioglossus was applied in non-rapid eye movement sleep (stage N2). Results Ultrasonography measurements showed a significant increase in tongue diameter during stimulation (sagittal: 10.0% [2.8%]; coronal: 9.4 % [3.7%]). The measurements were reproducible and repeatable. In patients with OSA, snoring decreased during stimulation ( P P = .001); the respiratory disturbance index (RDI) fell from 28.1 (26.3) to 10.2 (10.2) events per hour during stimulation ( P = .002), returning to 26.6 (26.0) events per hour after stimulation was stopped. Transdiaphragmatic pressure swing decreased from 24.1 (13.5) cm H 2 O to 19.7 (7.1) cm H 2 O ( P = .022), increasing to 24.2 (10.8) cm H 2 O afterward, and EMGdi fell from 23.8% max (12.6% max) to 15.7% max (6.4% max) ( P Conclusions Continuous transcutaneous electrical stimulation of the genioglossus contracts the genioglossus muscle and reduces ventilatory load and neural respiratory drive in patients with OSA.

An efficient system is presented for pre-delignifying cereal straw in vitro using laccase produced by Pycnoporus sanguineus H275. Under our experimental conditions, over 97% of the klason lignin was removed from 1 g wheat straw lignocellulose, without loss of Somogyi carbohydrate (reducing sugar). Microscopic observation of birefringence changes further indicated that the structure of the cellulose building blocks (microfibrils) of wheat straw scattered after pre-degradation, compared with the tightly arranged microfibrils in untreated control straw. The P . sanguineus H275-laccase-encoding gene was then cloned and successfully expressed in Pichia pastoris X-33, with a production of 3000 U/L after 6 days of cultivation. The identity of the expressed laccase was further confirmed by using MALDI-TOF-MS/MS. Homology modeling revealed that the native H275-laccase, predicted with five possible N -glycosylation sites, has extra cupredoxine domains and three common Cu-oxidase domains. Both kinetic characterization on the substrate ABTS and pre-delignification investigation on wheat straw lignocellulose showed that the activity of the recombinant laccase was nearly the same as that of the native laccase.

Background Distinguishing central sleep apnea from obstructive sleep apnea can be clinically important because different types of apnea may require different treatment approaches. Academically, this distinction is important for investigating the pathological mechanism of different types of sleep apnea. Conventional polysomnography with recording of chest and abdominal movement may overestimate the frequency of CSA, leading to inappropriate treatment of sleep-disordered breathing. We hypothesized that diaphragm electromyogram (EMGdi) could be a useful technique to assess neural respiratory drive and respiratory effort and, therefore, to distinguish accurately CSA from OSA. Methods A multipair esophageal electrode catheter mounted with a balloon was used to record the EMGdi and esophageal pressure (Pes) during overnight PSG. Nineteen patients were included in the study, 12 of whom had previously been identified as having central apnea-hypopnea on a diagnostic PSG undertaken for symptoms that suggest OSA and 7 of whom were known to have heart failure. Results A good relationship was found between the swing of Pes and the root mean (± SD) square of the EMGdi during OSA events (0.89 ± 0.10). About one third of CSA events diagnosed by uncalibrated respiratory inductance plethysmography could not be confirmed by Pes or EMGdi. No difference was found in the number of CSAs diagnosed by Pes (1,319) vs EMGdi (1,293; p > 0.01). Conclusions We conclude that both Pes and EMGdi measurements are useful in accurately differentiating central from obstructive respiratory events. Conventional PSG with recording of chest and abdominal movement overestimates the frequency of CSA events.

A novel strategy for design of haptens that were used to produce catalytic antibodies was developed and three monoclonal antibodies, 3G5, 2F3, and 5C9, were generated using this strategy. These monoclonal antibodies were converted into selenium-containing abzymes by chemically modifying the hydroxyl group of serines followed by sodium hydrogen selenide displacement. These selenium-containing abzymes exhibited remarkable glutathione peroxidase activity, which surpasses the activity of some native glutathione peroxidases. The activities of the selenium-containing abzymes Se-3G5, Se-2F3, and Se-5C9 which catalyzed reduction of hydroperoxides by glutathione were 2.23, 4.20, and 3.79 times that of rabbit liver glutathione peroxidase, respectively. Detailed steady-state kinetics study on Se-2F3 was carried out and the value of k(cat)/K(m) (H(2)O(2)) was found to be 2.11 x 10(7) M(-1) min(-1) which was supposed to be one of the highest among the known catalytic antibodies. The data of association constants and glutathione peroxidase activities of these catalytic antibodies and the steady-state kinetics of Se-2F3 showed that the method might be a remarkably efficient one for generating catalytic antibodies with glutathione peroxidase activity.

Background Breathlessness is an important cause of exercise limitation and reduced quality of life for patients with chronic obstructive pulmonary disease (COPD). One of the challenges of breathlessness management in COPD is the lack of physiological markers that reliably correlate with patients' symptoms. The aim of this study was to test the hypothesis that neural respiratory drive (NRD), measured with diaphragm electromyogram (EMGdi) activity, is closely related to breathlessness in COPD. We also investigated whether neuroventilatory uncoupling, which is the dissociation of ventilation from NRD as a consequence of abnormal pulmonary mechanics, contributes to breathlessness intensity over an awareness of levels of NRD alone. Methods EMGdi and ventilation were measured continuously during exhaustive incremental cycle and treadmill exercise in 12 patients with COPD (mean FEV 1 38·7% predicted [SD 14·5]). EMGdi was expressed as a percentage of maximum (EMGdi%max), and relative to tidal volume expressed as a percentage of predicted vital capacity (EMGdi%max/VT%VCpred) to measure neuroventilatory uncoupling. Breathlessness (modified Borg scale) was recorded at baseline, at the end of each minute of exercise, and at completion of exercise. Linear regression analysis was used to determine the associations between breathlessness, EMGdi%max, neuroventilatory uncoupling, and ventilation. Findings EMGdi%max was closely related to breathlessness in both cycle ( r =0·98, p=0·0001) and treadmill exercise ( r =0·94, p=0·005), this association being at least as strong as that between neuroventilatory uncoupling and breathlessness (cycle r =0·94, p=0·005; treadmill r =0·91, p=0·01). The association between breathlessness and ventilation was poor when expansion of tidal volume became restricted, whereas the association between EMGdi%max and breathlessness remained close. Interpretation EMGdi%max is closely related to the intensity of exertional breathlessness in COPD. These data suggest that breathlessness in COPD can be largely explained by an awareness of levels of NRD, rather than the association between NRD and achieved ventilation. EMGdi%max could provide a useful physiological biomarker for breathlessness, with advantages over mechanical and ventilatory indices in COPD and the many other diseases in which neuroventilatory uncoupling occurs. Funding UK Medical Research Council, British Council.