Respiratory State Research Articles

A Non-canonical Function of BMAL1 Metabolically Limits Obesity-Promoted Triple-Negative Breast Cancer.

SummaryThe epidemiological association between disrupted circadian rhythms and metabolic diseases is implicated in increased risk of human breast cancer and poor therapeutic outcomes. To define a metabolic phenotype and the underlying molecular mechanism, we applied chronic insulin treatment (CIT) to an in vitro model of triple-negative breast cancer to directly address how BMAL1, a key circadian transcription factor, regulates cancer cell respiration and governs tumor progression. At the cellular level, BMAL1 suppresses the flexibility of mitochondrial substrate usage and the pyruvate-dependent mitochondrial respiration induced by CIT. We established an animal model of diet-induced obesity/hyperinsulinemia and observed that BMAL1 functions as a tumor suppressor in obese, but not lean, mice. Downregulation of BMAL1 is associated with higher risk of metastasis in human breast tumors. In summary, loss of BMAL1 in tumors confers advantages to cancer cells in both intrinsic mitochondrial metabolism and extrinsic inflammatory tumor microenvironment during pre-diabetic obesity/hyperinsulinemia.

Rapid Prediction of Respiratory Motion Based on Bidirectional Gated Recurrent Unit Network

In chest and abdomen robotic radiosurgery, due to the motion delay of the robotic manipulator, the tumor position tracking process has a period of delay. This delay ultimately affects the accuracy of radiosurgery treatment. To address the influence of the delay in robotic radiosurgery, a Long-and-Short-Term Memory (LSTM) network as a deep Recurrent Neural Network (RNN) has been applied in a prediction network model for respiratory motion tracking in recent years. However, patients' respiratory state may change in the process of treatment, which may influence the accuracy of prediction. Therefore, it is necessary to update the prediction network through additional data, such as the actual position of the tumor obtained by X-ray imaging. However, the LSTM network has a long update time, and it may not be able to complete the prediction model update in a cycle of X-ray acquisition. To solve this problem, a fast prediction model based on Bidirectional Gated Recurrent Unit (Bi-GRU), is proposed in this paper. This method can reduce the average updating time of the network model by 30%.

An investigation into the impact of deleting one copy of the glutaredoxin-2 gene on diet-induced weight gain and the bioenergetics of muscle mitochondria in female mice fed a high fat diet

ABSTRACT Our group recently documented that male mice containing a deletion for one copy of the glutaredoxin-2 (Grx2) gene were completely protected from developing diet-induced obesity (DIO). Objectives: Here, we conducted a similar investigation but with female littermates. Results: In comparison to our recent publication using male mice, exposure of WT and GRX2+/- female mice to a HFD from 3-to-10 weeks of age did not induce any changes in body mass, circulating blood glucose, food intake, hepatic glycogen levels, or abdominal fat pad mass. Examination of the bioenergetics of muscle mitochondria revealed no changes in the rate of superoxide (O2 ●−)/hydrogen peroxide (H2O2) or O2 consumption under different states of respiration or alterations in lipid peroxidation adduct levels regardless of mouse strain or diet. Additionally, we measured the bioenergetics of mitochondria isolated from liver tissue and found that partial loss of GRX2 augmented respiration but did not alter ROS production. Discussion: Overall, our findings demonstrate there are sex differences in the protection of female GRX2+/- mice from DIO, fat accretion, intrahepatic lipid accumulation, and the bioenergetics of mitochondria from muscle and liver tissue.

Mechanical Ventilation Monitoring: Development of a Network Data Acquisition System

Mechanical ventilator (MV) is a vital life support machine for respiratory failure patients in Intensive Care Unit (ICU). Critical and beneficial information on patient’s breathing pattern can be obtained from the ventilator for research studies in a form of ventilator waveform data (VWD). However, imperfect data collection system and lack of Electronic Health Record system integration has deterred the study of VWD to improve patient’s treatment. Furthermore, data acquisition of VWD is not easily accessible and cost-prohibitive to deploy. Therefore, current studies are limited to small samples of breathing cycle, despite continuously changing patient’s respiratory state during the day. Hence, this proposed system allows constant monitoring of patient’s ventilation data and real-time VWD visualization on mobile devices. This system consists of a data acquisition device (DAQ) to acquire VWD and a mobile web application to display patient’s breathing condition in real time. In addition, the collected VWD data are stored securely in network attached storage and onto cloud storage to prevent data loss. This framework has been successfully tested with MV attached with test lung. This proposed system can potentially expedite research studies by providing a better data collection and management specifically in the clinical environment.

Surgical management of complicated sporadic pulmonary arterio venous malformation

The onset of a spontaneous hemothorax may represent a life threatening emergency. Several etiologies may be involved, mainly vascular abnormalities. Pulmonary Arteriovenous Malformation (PAVM) is a rare etiology, and it is often associated with Hereditary Hemorrhagic Telangiectasia (HHT). We report the case of a young women who was presented to the emergency department with left basal chest pain and mild dyspnea. Hemodynamic and respiratory states were maintained. Vesicular murmuring was abolished on the left side. The chest roentgenogram showed a left pleural effusion with mild deviation of the mediastinum to the opposite side. Thoracocentesis found a serohematic liquid. While the patient was undergoing exploration by computed chest tomography, she represented a cardio respiratory arrest. Resuscitation was successful after few minutes. The chest CT showed a PAVM located on the upper lobe that was very enhanced after injection of the contrast product, with a feeding artery coming from the pulmonary artery. The patient underwent an emergent left upper lobectomy thorough a posterolateral thoracotomy. The PAVM was peripheral, large with a diameter of 5 cm, and ruptured on the pleural cavity. Elective controlling the hemorrhage was very difficult, so a total hilar clamping was done with a Satinsky clamp. The postoperative course was complicated with pulmonary embolism managed by anticoagulation treatment. The definitive histological management concluded to a PAVM. Retrospectively, there was no personal or familial sign of HHT, neither any anomaly of blood hemostasis. Isolated PAVM is a rare cause of spontaneous hemothorax. Rapid worsening of an initially maintained state makes the situation more critical. Rapid control of a massive bleeding is mandatory to better explore and plan surgical resection. For stable patient, endovascular treatment may represent an effective option.

Solunum Sıkıntısı Bulunan 1250 Gram Üzeri Preterm Bebeklerde Profilaktik Kafein Kullanımının Yararları

INTRODUCTION: Prophylactic caffeine therapy, reduces the frequency of apnea in premature babies. Moreover, its effect has been well established in reducing the intermittent hypoxemia, and the need for additional ventilator support of infants with a birthweight of <1.250 g. The aim of this study is to determine the effects of prophylactic caffeine use on neonatal outcomes in preterm babies with a birthweight of >1.250 g and respiratory distress. METHODS: Sixty-eight infants with birthweight of 1.250 to 2.000 g with respiratory distress and born at 32-34 GA and intubated with the indication of respiratory distress who also needed nasal ventilation for at least 48 hours were included in this prospective randomized controlled study, starting from birth one group received prophylactic caffeine citrate at loading dose of 20 mg/kg, and maintenance dose of 5 mg/kg in addition to respiratory support, long term neurological and developmental outcomes were recorded with Bayley-II. RESULTS: There was no difference in weight or gestational age at birth between the groups. Also, the groups were smilar in respiratory states. The caffeine group, was associated with a significant reduction in intubation requirement within the first 72 hr and shorter duration of mechanical and nasal ventilation, while there was no difference between the groups in total duration of oxygen therapy, and frequency of apneic episodes (respectively p=0.03, p=0.00, p=0.02, p>0.05). Any differences were not detected in terms of prematurity morbidities (p>0.05). Any significant intergroup differences were not detected as for PDA, NEC, IVC, laser-requiring ROP, and BPD (p>0.05). While the study was continuing regarding long-term neurodevelopmental outcomes Bayley neurodevelopmental tests were applied to 15 infants in the caffeine and 18 infants in the caffeine group at 12. and 18. months, and test results were csimilar in both groups (p>0.05). DISCUSSION AND CONCLUSION: The prophylactic use of caffeine in older preterm babies with respiratory distress, have short term benefits as lesser requirement for ntubation within the first 72 hours and decreased duration of ventilatory support without any advers side effects. Therefore if symptoms of respiratory distress are seen in preterm babies with a birthweight of >1.250 g, then initiation of prophylactic treatment may be considered. Larger scale randomized kontrollü studies are needed regarding this issue.

Donor brain stem death and cardiac transplantation causes mitochondrial dyscoupling and oxidative stress

Introduction: Mitochondria are essential for adequate cardiovascular function and are important in the generation of reactive oxygen species (ROS). However, mitochondrial function and ROS post donor brain stem death (BD) and heart transplantation HTx is poorly understood and may contribute to donor heart dysfunction (DHD) and post HTx graft failure (GF). Objectives∖Aims: To examine mitochondrial function and ROS production in hearts both after 24hrs of BSD and post HTx. Methods: Donor sheep underwent BD (BD n=13) or sham instrumentation (SH, n=8) and monitored for 24hrs followed by heart procurement or cold static storage. Orthotopic HTx followed, in 7∖13 BD (BD-Tx) and 4/8 SH donors (SH-Tx). Mitochondrial respirometry was assessed using the Oroboros Oxygraph using carbohydrate (CHO) or fatty acid (FAO) substrates for both ventricles. O2 flux control ratios (FCR) were calculated in LEAK (no ADP) and Complex- I (CI) & II (CII) OXPHOS (with ADP) respiration states. Tissue levels of 3-nitrotyrosine and glutathione:reduced glutathione (GSH:GSSG) ratio were assessed using plate based assays. Results: BD caused a significant increase in LEAK RV proton slip. Both ventricles showed a trend toward higher O2 consumption at CI (known driver of ROS) and a significant decrease in CII respiration for both substrates. Post HTx showed mitochondrial dyscoupling evidenced by a trend toward higher CI O2 consumption, significantly higher RV proton slip, and depressed LV and RV CII respiration. For the LV, GSH:GSSG ratios were significantly lower for BD, BD-Tx and SH-Tx. For the RV, GSH:GSSG ratios were non-significantly depressed post BD both pre and post Tx. Conclusions: We have shown that donor BD and Tx caused significant mitochondrial dyscoupling and higher oxidative stress. Mitochondrial function, particularly CI ROS production may then contribute to DHD and consequently post-HTx GF. Therapeutically targeting mitochondrial ROS could improve patient prognosis.

P1477 Features of structural and functional parameters of the right and left heart and their relationship with the spirometry parameters in patients with CHF of ischemic genesis with COPD

Abstract Purpose Сomparative analysis of structural and functional parameters of the heart, the state of external respiration in patients with CHF II-III FC of ischemic genesis in the absence and in combination with moderate to severe COPD. Material and methods The study included patients aged 65.6 ± 3.9 years with LVEF ≤ 45% (according to Simpson). The first group consisted of 87 patients with CHF of ischemic genesis, and the second group - 385 patients with CHF of ischemic genesis and coexisted COPD. All patients were evaluated for clinical condition, TTE, the study of respiratory function with bronchodilation test. Results Patients of both groups were comparable by sex, age, FC CHF (NYHA). In patients with COPD, linear and volumetric LV parameters exceeded the normal values and were significantly higher than in CHF patients without COPD. LVIMM, LV sphericity index were significantly higher in the group of patients with COPD, which is associated with more pronounced remodeling of the left heart. Correlation analysis showed direct moderate and reliable relationships between the RVIDd (internal end-diastolic diameter) and MPAP (r = 0.68, p < 0.01), RVIDd and LVSV (stroke volume) and FEV1 (r = 0.38, p < 0.05), FEV1 and LVMMI (r = 0.33, p < 0.05), FVC and LVMMI (r = 0.34, p < 0.05), LVEF and FEV1 (r = 0.44, p < 0.05) and VC (lung vital capacity) (r = 0.36, p < 0.05). Negative correlations were found between low-level FEV1 and RVIDd (r=-0.29, p < 0.05), FEV1 and SatO2 (r = 0.28, p < 0.05), and a strong degree between MPAP and FEV1 (r=-0.55, p < 0.05), moderate between MPAP and FEF75 (r=-0.57, p < 0.05). In patients with COPD more pronounced significant increases in RVIDd, MPAP, RA dimension were noted. In patients of this group (n = 385), the IVRT and time of deceleration during the early diastolic filling (DTE) of RV increased more significantly. RV diastolic dysfunction in patients with CHF with COPD may be due to slower relaxation of the right ventricular hypertrophy and an increase in afterload (evidenced by the relationship between the velocity of early diastolic filling (E) of the RV and the thickness of the anterior wall of the RV; the velocity of late filling (A) of the RV and MPAP (r= 0.3, p < 0.05)). Conclusion In patients with CHF of ischemic genesis with COPD, a more pronounced remodeling of the left and right parts of the heart was noted, reliable interrelationships of respiratory function indicators and structural and functional parameters of both the left and right ventricles of the heart were revealed.

The Role of Exhaled Nitric Oxide Fraction in Sarcoidosis Patients

Nitric oxide is a molecule that has important roles in various biological processes such as apoptosis, angiogenesis and endothelial permeability and therefore its disorder plays a role in the pathogenesis of various disorders. We aimed to investigate fractional exhaled nitric oxide values in sarcoidosis, a multi-systemic non-caseified granulomatous disease that commonly affects all organs, especially the pulmonary system. A total of 107 individuals, including 54 sarcoidosis patients and 53 healthy controls were included in this study. Data were analyzed retrospectively. Gender, age, body mass index, exhaled nitric oxide fraction values, respiratory function parameters, diagnostic methods and additional disease states were recorded. Exhaled nitric oxide fraction values in sarcoidosis patients and the control group were measured using Bedfont NObreath (UK) device, respiratory function parameters were measured using ZAN GPI.3.00 (Germany) device and the results were recorded. Sarcoidosis patients were graded as stage 0, 1, 2, 3, 4 according to chest x-ray findings. Exhaled nitric oxide fraction values detected in sarcoidosis patients and fractional exhaled nitric oxide values detected in the control group were compared. The sensitivity and specificity of exhaled nitric oxide fraction values in sarcoidosis were investigated. The relationship between respiratory function parameters and exhaled nitric oxide fraction values was examined. There was a significant difference between the exhaled nitric oxide fraction values detected in sarcoidosis patients and the exhaled nitric oxide fraction values detected in the control group and the specificity and sensitivity of the exhaled nitric oxide fraction value was found to be high in patients with and sarcoidosis. There was no relationship between respiratory function parameters and exhaled nitric oxide fraction values. Exhaled nitric oxide fraction values, which have been studied in very few studies in sarcoidosis patients, may be a biomarker that can be used in the evaluation of pulmonary parenchymal involvement of sarcoidosis.

Referral patterns to continence physiotherapy services for patients with chronic respiratory conditions

Chronic respiratory conditions are a widely recognised risk factor for urinary incontinence and current chronic respiratory condition management guidelines state that patients should be screened fo...

Формирование профессионально-прикладной физической культуры личности студентов (на примере специалистов библиотечного дела)

We analyze the most frequently encountered problems in the field of occupational hazards of library workers. Negative consequences of influence of professional work in the library is the nervous system overvoltage appearance, leading to internal emotional exhaustion and “emotional burnout” syndrome; the development of physical inactivity, leading to irregular functioning of the musculoskeletal and cardiovascular systems of workers; fatigue occurrence and vision loss in the process for a personal computer. In addition, the main activity of the librarian is carried out in paper and book dust negative impact conditions, the presence of pathogenic bacteria and fungi in the microflora, non-compliance of microclimate parameters in the premises of libraries with the required standards. A serious risk to which librarians are exposed in their workplaces is associated with the respiratory diseases development, which may be allergic in nature (bronchial asthma) or airborne transmission (tuberculosis, influenza viruses). The results of lung capacity testing, breathe retention time on inhalation and exhalation of female students of 1–2 courses of the Culture and Arts Faculty of Derzhavin Tambov State University allow us to reveal a picture of the respiratory system functional state, exposed to significant risk in the professional activity process of the library sphere employee. Knowledge and skills system formation related to occupational safety, health, library workers certain diseases prevention should be laid in the period of study at the university, including physical education.

Postobstructive pulmonary edema: A fatal complication in suicidal near-hanging

Postobstructive pulmonary edema is a life-threatening complication that occurs after the removal of severe upper airway obstruction. Development of postobstructive pulmonary edema has been described after several cases of upper airway obstruction. However, postobstructive pulmonary edema developing after non-lethal hanging has not been reported widely in the literature. Herein, we describe a fatal case of postobstructive pulmonary edema in a 10-year-old girl, which was brought to the hospital with history of attempted suicide by hanging. At presentation, the girl was breathing laboriously. The oxygen saturation was of 82% and pulmonary auscultation revealed bilateral and diffuse crepitations. The chest computed tomographic scan showed bilateral diffuse infiltrates consistent with pulmonary edema. After 3 days of hospitalization, the respiratory state of the girl worsened leading to death despite intensive care. An autopsy was conducted and confirmed the diffuse pulmonary edema. Hence, this case confirms that delayed death in near hanging may occur. Pulmonary edema which develops subsequently in such patients is an uncommon mechanism of death that physicians should consider in emergency room.

Exploiting tumor position differences between deep inspiration and expiration in lung stereotactic body radiation therapy planning

Purpose: We demonstrate proof of principle that normal tissue doses can be greatly reduced in lung stereotactic body radiation therapy (SBRT) for mobile tumors, if the delivered dose is split between opposite respiratory states. Methods: Patients that underwent 5 fraction lung SBRT at our institution and had deep inspiration breath hold (DIBH) and free breathing 4D computed tomography scans were included. Volumetric modulated arc therapy plans were generated on both respiratory phases and a third composite plan was generated delivering half the dose using the DIBH plan and the other half using the expiratory phase plan for each fraction. Computed tomography scans for the composite plan were fused based on ribs adjacent to the tumor to evaluate the dose volume histogram of critical structures. Results: Four patients with 4 total tumors had requisite planning scans available. Tumor size was between 0.7 to 2.9 cm and tumor movement 1.4 to 2.9 cm. Median reduction in the chest wall (CW) V30Gy for the composite plan was 74.6% (range 33.7 to 100%), 76.9% (range 32.9 to 100%), and 89.3% (range 69.5 to 100%) compared to the DIBH, expiration phase, and free breathing plans, respectively. Median reduction in CW maximum dose for the composite plan was 23.3% (range 0.27% to 46.4%), 23.5% (range 3.2 to 48.2%), and 23.4% (range 0.27% to 48.4%) compared to the DIBH, expiration phase, and free breathing plans, respectively. Greater reduction in CW maximum dose was observed when patients had no overlap in planning target volumes between DIBH and expiration phases (median reduction 43.9% for no overlap vs 2.7% with overlap). Between all plans, lung V20Gy absolute differences were within 1.3%. For 2 of 4 patients, the composite plan met constraints for 3 fraction SBRT, while standard plans did not. Conclusions: We conclude that composite DIBH-expiration SBRT planning has the potential to improve organ at risk sparing.

In vitro comparison of hydroxocobalamin (B12a) and the mitochondrial directed therapy by a succinate prodrug in a cellular model of cyanide poisoning

The objective of this study was to compare the use of hydroxocobalamin (B12a) and a succinate prodrug to evaluate for improvement in mitochondrial function in an in vitro model of cyanide poisoning. Peripheral blood mononuclear cells (PBMC) and human aortic smooth muscle cells (HASMC) incubated with 50 mM of sodium cyanide (CN) for five minutes serving as the CN group compared to controls. We investigated the following: (1) Mitochondrial respiration; (2) Superoxide and mitochondrial membrane potential with microscopy; (3) Citrate synthase protein expression. All experiments were performed with a cell concentration of 2−3 × 106 cells/ml for both PBMC and HASMC. There were four conditions: (1) Control (no exposure); (2) Cyanide (exposure only); (3) B12a (cyanide exposure followed by B12a treatment); (4) NV118 (cyanide followed by NV118 treatment). In this study the key findings include: (1) Improvement in key mitochondrial respiratory states with the succinate prodrug (NV118) but not B12a; (2) Attenuation of superoxide production with treatment of NV118 but not with B12a treatment; (3) The changes in respiration were not secondary to increased mitochondrial content as measured by citrate synthase; (4) The use of easily accessible human blood cells showed similar mitochondrial response to both cyanide and treatment to HASMC. The use of a succinate prodrug to circumvent partial CIV inhibition by cyanide with clear reversal of cellular respiration and superoxide production that was not attributed to changes in mitochondrial content not seen by the use of B12a.

Gill filament permeabilization: A novel approach to assess mitochondrial function in sheepshead minnows (Cyprinodon variegatus) following anthraquinone exposure

Anthracene is a highly toxic polycyclic aromatic hydrocarbon (PAH), and its toxicity is increased 8-fold after compounding exposure to UV radiation. Exposure to either the parent or photo-modified compound has been shown to cause increases in reactive oxygen species (ROS) production and lipid peroxidation. Since the majority of ROS production occurs within mitochondria, we investigated simultaneous mitochondrial respiration and ROS production in the gills of sheepshead minnows (Cyprinodon variegatus) acutely (48 h) exposed to anthraquinone (40 μg l−1). Anthraquinone exposure caused a 25% increase in oxidative phosphorylation with electrons donated to Complex I (OXPHOSCI) and a 33% increase in Leak respiration with oligomycin (Leak-OmyCI). ROS production was slightly increased (33.3%) in Leak state with oligomyocin respiring on Complex I substrates (Leak-OmyCI) after anthraquinone exposure, but this value remained unchanged in all other respiratory states. When ROS production was normalized to mitochondrial oxygen consumption, we found that ROS production was decreased in all respiratory states, but most noticeably in the Leak state. We speculate that differences in the antioxidant defense system may have played a role in decreased ROS production. Overall, in this paper we present a novel technique to measure mitochondrial function in the gill filaments of teleost fish exposed to xenobiotic molecules, and we show anthraquinone exposure alters aspects of oxidative phosphorylation and ROS production.

Bioenergetic consequences from xenotopic expression of a tunicate AOX in mouse mitochondria: Switch from RET and ROS to FET

Electron transfer from all respiratory chain dehydrogenases of the electron transport chain (ETC) converges at the level of the quinone (Q) pool. The Q redox state is thus a function of electron input (reduction) and output (oxidation) and closely reflects the mitochondrial respiratory state. Disruption of electron flux at the level of the cytochrome bc1 complex (cIII) or cytochrome c oxidase (cIV) shifts the Q redox poise to a more reduced state which is generally sensed as respiratory stress. To cope with respiratory stress, many species, but not insects and vertebrates, express alternative oxidase (AOX) which acts as an electron sink for reduced Q and by-passes cIII and cIV. Here, we used Ciona intestinalis AOX xenotopically expressed in mouse mitochondria to study how respiratory states impact the Q poise and how AOX may be used to restore respiration. Particularly interesting is our finding that electron input through succinate dehydrogenase (cII), but not NADH:ubiquinone oxidoreductase (cI), reduces the Q pool almost entirely (>90%) irrespective of the respiratory state. AOX enhances the forward electron transport (FET) from cII thereby decreasing reverse electron transport (RET) and ROS specifically when non-phosphorylating. AOX is not engaged with cI substrates, however, unless a respiratory inhibitor is added. This sheds new light on Q poise signaling, the biological role of cII which enigmatically is the only ETC complex absent from respiratory supercomplexes but yet participates in the tricarboxylic acid (TCA) cycle. Finally, we delineate potential risks and benefits arising from therapeutic AOX transfer.

Powerhouses in the cold: mitochondrial function during thermal acclimation in montane mayflies.

Mitochondria provide the vast majority of cellular energy available to eukaryotes. Therefore, adjustments in mitochondrial function through genetic changes in mitochondrial or nuclear-encoded genes might underlie environmental adaptation. Environmentally induced plasticity in mitochondrial function is also common, especially in response to thermal acclimation in aquatic systems. Here, we examined mitochondrial function in mayfly larvae (Baetis and Drunella spp.) from high and low elevation mountain streams during thermal acclimation to ecologically relevant temperatures. A multi-substrate titration protocol was used to evaluate different respiratory states in isolated mitochondria, along with cytochrome oxidase and citrate synthase activities. In general, maximal mitochondrial respiratory capacity and oxidative phosphorylation coupling efficiency decreased during acclimation to higher temperatures, suggesting montane insects may be especially vulnerable to rapid climate change. Consistent with predictions of the climate variability hypothesis, mitochondria from Baetis collected at a low elevation site with highly variable daily and seasonal temperatures exhibited greater thermal tolerance than Baetis from a high elevation site with comparatively stable temperatures. However, mitochondrial phenotypes were more resilient than whole-organism phenotypes in the face of thermal stress. These results highlight the complex relationships between mitochondrial and organismal genotypes, phenotypes and environmental adaptation. This article is part of the theme issue 'Linking the mitochondrial genotype to phenotype: a complex endeavour'.

Pathological consequences of the unfolded protein response and downstream protein disulphide isomerases in pulmonary viral infection and disease.

Protein folding within the endoplasmic reticulum (ER) exists in a delicate balance; perturbations of this balance can overload the folding capacity of the ER and disruptions of ER homoeostasis is implicated in numerous diseases. The unfolded protein response (UPR), a complex adaptive stress response, attempts to restore normal proteostasis, in part, through the up-regulation of various foldases and chaperone proteins including redox-active protein disulphide isomerases (PDIs). There are currently over 20 members of the PDI family each consisting of varying numbers of thioredoxin-like domains which, generally, assist in oxidative folding and disulphide bond rearrangement of peptides. While there is a large amount of redundancy in client proteins of the various PDIs, the size of the family would indicate more nuanced roles for the individual PDIs. However, the role of individual PDIs in disease pathogenesis remains uncertain. The following review briefly discusses recent findings of ER stress, the UPR and the role of individual PDIs in various respiratory disease states.

The role of temperature as a driver of metabolic flexibility in the Red-billed Leiothrix (Leiothrix lutea)

BackgroundThe thermoregulatory ability of animals is strongly influenced by the temperature of their environment. Acclimation to cold requires a range of physiological and morphological adjustments. In this study, we tested the hypothesis that a small passerine, the Red-billed Leiothrix (Leiothrix lutea), can maintain homeothermy in cold conditions by adjusting the physiology and biochemistry of its tissue and organs and return to its former physiological and biochemical state when moved to a warm temperature.MethodsPhenotypic variation in thermogenic activity of the Red-billed Leiothrixs (Leiothrix lutea) was investigated under warm (35 °C), normal (25 °C) or cold (15 °C) ambient temperature conditions. Oxygen consumption was measured using an open-circuit respirometry system. Mitochondrial state-4 respiration and cytochrome-c oxidase (COX) activity in liver, kidney heart and pectoral muscle were measured with a Clark electrode.ResultsBirds acclimated to an ambient temperature of 15 °C for 4 weeks significantly increased their basal metabolic rate (BMR) compared to a control group kept at 25 °C. Birds acclimated to 35 °C decreased their BMR, gross energy intake (GEI) and digestible energy intake (DEI). Furthermore, birds acclimated to 15 °C increased state-4 respiration in their pectoral muscles and cytochrome-c oxidase (COX) activity in their liver and pectoral muscle, compared to the 25 °C control group. Birds acclimated to 35 °C also displayed lower state-4 respiration and COX activity in the liver, heart and pectoral muscles, compared to those kept at 25 °C. There was a positive correlation between BMR and state-4 respiration, and between BMR and COX activity, in all of the above organs except the liver and heart.ConclusionsOur study illustrates that the morphological, physiological, and enzymatic changes are associated with temperature acclimation in the Red-billed Leiothrix, and supports the notion that the primary means by which small birds meet the energetic challenges of cold conditions is through metabolic adjustments.

Obstructive sleep apnea screening by heart rate variability-based apnea/normal respiration discriminant model

Objective: Obstructive sleep apnea (OSA) is a common sleep disorder; however, most patients are undiagnosed and untreated because it is difficult for patients themselves to notice OSA in daily living. Polysomnography (PSG), which is the gold standard test for sleep disorder diagnosis, cannot be performed in many hospitals. This fact motivates us to develop a simple system for screening OSA at home. Approach: The autonomic nervous system changes during apnea, and such changes affect heart rate variability (HRV). This work develops a new apnea screening method based on HRV analysis and machine learning technologies. An apnea/normal respiration (A/N) discriminant model is built for respiration condition estimation for every heart rate measurement, and an apnea/sleep ratio is introduced for final diagnosis. A random forest is adopted for the A/N discriminant model construction, which is trained with the PhysioNet apnea-ECG database. Main results: The screening performance of the proposed method was evaluated by applying it to clinical PSG data. Sensitivity and specificity achieved 76% and 92%, respectively, which are comparable to existing portable sleep monitoring devices used in sleep laboratories. Significance: Since the proposed OSA screening method can be used more easily than existing devices, it will contribute to OSA treatment.