Respiratory State Research Articles

Skeletal Muscle Mitochondrial Capacity Is Similar In Ambulatory And Non-ambulatory Children With Cerebral Palsy

PURPOSE: Cerebral palsy (CP) is the most common childhood movement dysfunction secondary to a brain injury around birth. These children can be classified as ambulatory or non-ambulatory based on their functional abilities. Importantly, they expend significantly increased energy expenditure during movement. Muscle mitochondria, specifically the electron transport system are responsible for oxidative capacity, energy production and are associated with functional capacity. Unfortunately, mitochondrial oxidative capacity in children with CP and its association with different functional levels is not known. We measured maximum mitochondrial respiration rates directly from biopsies in children with CP, compared across ambulatory levels. METHODS: Twenty children (6-16 years, 10 M/6F, Ambulatory-12), undergoing surgery participated in this study. Twenty-nine biopsies were obtained from adductors, vastus lateralis, gastrocnemius. Carbohydrate and fatty acid respirometry substrate-uncoupler-inhibitor titration (SUIT) protocols were performed on permeabilized muscle fiber bundles. In addition, muscle homogenate was used to measure citrate synthase activity as a marker of mitochondrial content. Ambulatory capacity was measured using 6-minute walk tests (n=7), muscle strength, and gait velocity (n=15) during routine therapy visits. RESULTS: Surprisingly, maximal mitochondrial phosphorylation capacity was similar across between functionally ambulatory and non-ambulatory children (77.1± 23.9 vs. 84.9± 24.0 pmol O2/s/mg). This was uncorrelated with mitochondrial content (p>0.1), as measured by citrate synthase. Mitochondria in children with CP still preferentially used carbohydrates over fatty acids based on state-3 respiration. Functionally ambulatory children showed positive associations between mitochondrial function and ambulatory capacity measures (r2 values for gait velocity=0.50, 6-meter walk test=0.33, p< 0.05). CONCLUSIONS: Mitochondrial function are typically associated with activity level. Surprisingly, functionally ambulatory children with CP did not have greater mitochondrial function compared to non-ambulatory children and might even be lower. Importantly, within ambulatory children walking capacity was related to maximal mitochondrial function.

Swimming And Respiratory System: Impact Of Exercise On Pro-oxidants Production And Lung Function

The respiratory redox state of swimmers can be affected by the increase of minute ventilation (VE) during exercise and/or by chronic exposure to chlorine used to sanitize the water of swimming pools. However, in indoor-pools, the high-humidity and warm-water temperature are recognized as respiratory protecting factors. The exhaled breath condensate (EBC) is a non-invasive method used to assess the pro-oxidants species (EBC) is a non-invasive method used to assess the pH and pro-oxidants species (nitrite [NO2-], hydrogen peroxide [H2O2]), while spirometry the lung function (FEV1, FEV1/FVC, FEF25-75% ). PURPOSE: To assess the impact of a high-intensity and prolonged-time exercise on the production of [H2O2]EBC, [NO2-]EBC, pHEBC and lung function in swimmers. METHODS: Longitudinal quasi-experimental study. 18 competitive swimmers (8 female) (22±2 years; 53.1±3.5 mL·kg-1·min-1 VO2-máx.) completed 3.500-m of swim in indoor pool treated by chlorine (intensity of 80.2±3.1% of HRmax.) with no exposure to respiratory irritants by 5-days previous to tests. The spirometry test and EBC collection were done at rest, 20-minutes and 24-hours post-exercise and were analyzed using one-way RM-ANOVA test by the GraphPad-Prism software (v.6.0). The p-value<0.05 was considered for differences. RESULTS: The [H2O2]EBC (0.35±0.15 vs 0.28±0.12 vs 0.20±0.10 (umol·L-1 )) and [NO2-]EBC (1.79±0.21 vs 1.37±0.15 vs 1.03±0.16 (umol·L-1 )) decreased significantly at 24-hr post-exercise. The pHEBC (p=0.23 and 0.32) and FEV1, FEV1/FVC, FEF25-75% do not changed significantly between stages. CONCLUSION: A acute high-intensity and prolonged-time swimming session decreased the pro-oxidants production with no changes in lung function in swimmers exposed chronically to exercise and respiratory irritants. More studies are necessary to identify and isolate the plausible factors involucrated in the formation of respiratory pro-oxidants during exercise in athletes chronically exposed to respiratory irritants.

Respiration Monitoring: From Molecular Reconstruction of Mesoscopic Functional Conductive Silk Fibrous Materials to Remote Respiration Monitoring (Small 26/2020)

In article number 2000203, Xiang Yang Liu and co-workers meso-reconstruct silkworm silk fibrous materials based on carbon nanotubes which give rise to conductive silk fibers, for the fabrication of silk flexible electronics. They have humidity dependent conductivity and can be developed into biocompatible electronic humidity sensors. The combination with cloud computation and big data leads to remote monitoring and diagnosis of respiration and other physiological conditions.

High-fat Diet Induces Nr4a3-dependent Decrease In Respiratory Capacity Of Mouse Soleus Muscle

The Nuclear Hormone Receptor 4A family of genes have been observed to play a role in proper metabolic function in various tissues, including skeletal muscle. PURPOSE: To analyze the effect of the Nr4a3 gene on respiratory capacity of mitochondria in skeletal muscle of mice on a normal or high fat diet. METHODS: Nr4a3-/- and WT mice were fed a normal chow (NC) or high fat diet (HF) for at least 20 weeks. After euthanasia, soleus muscle was harvested and wet weight was measured. Muscle fibers were teased apart and permeabilized with saponin in preparation for respirometry. Mitochondrial respiration was evaluated using an Oroboros Oxygraph Respirometer. Respiratory capacity comparisons were made with a two-way ANOVA and Tukey multiple comparison test. RESULTS: Oxygen consumption is reported as pmol/(s*mg wet tissue) and statistics are represented as mean ± SEM. In the WT male mice there was a decrease in coupled complex I supported respiration in HF vs. NC diet (25.9 ± 7.3 vs. 64.5 ± 5.0, p=0.004). In the HF WT group there was also a decrease in coupled complex I and II supported respiration (57.2 ± 13.4 vs. 102.5 ± 7.0, p=0.0005) and uncoupled respiration (61.4 ± 15.0 vs. 107.8 ± 7.1, p=0.0004) compared to NC WT. In female mice there was also a decrease between HF WT and NC WT in complex I (28.2 ± 3.7 vs. 57.4 ± 5.7, p=0.0005) and complex I and II (78.2 ± 6.1 vs. 108.8 ± 6.7, p=0.0003) supported respiration as well as in uncoupled respiration (87.1 ± 7.1 vs. 119.4 ± 8.9, p=0.0001). However, there was no significant difference between the WT NC mice and either of the Nr4a3-/- groups. Coupled complex I, complex I and II and uncoupled respiration states in both Nr4a3-/- groups were not significantly different from WT. CONCLUSIONS: The Nr4a3 gene plays a role in mitochondrial function in mouse skeletal muscle. Feeding mice a high fat diet impairs proper mitochondrial function in muscle when compared to a normal chow diet. The decrease in respiration from the HF diet is dependent upon the function of the Nr4a3 gene, as no decrease was observed in Nr4a3-/- mice. A limitation of this study is that this effect could be due to the lack of Nr4a3 in the skeletal muscle, or a secondary effect of lacking the gene in other parts of the body.

Mitochondrial physiology varies with parity and body mass in the laboratory mouse (Mus musculus).

The life-history patterns that animals display are a product of their ability to maximize reproductive performance while concurrently balancing numerous metabolic demands. For example, the energetic costs of reproduction may reduce an animal's ability to support self-maintenance and longevity. In this work, we evaluated the impact of parity on mitochondrial physiology in laboratory mice. The theory of mitohormesis suggests that modest exposure to reactive oxygen species can improve performance, while high levels of exposure are damaging. Following this theory, we hypothesized that females that experienced one bout of reproduction (primiparous) would display improved mitochondrial capacity and reduced oxidative damage relative to non-reproductive (nulliparous) mice, while females that had four reproductive events (multiparous) would have lower mitochondrial performance and greater oxidative damage than both nulliparous and primiparous females. We observed that multiple reproductive events enhanced the mitochondrial respiratory capacity of liver mitochondria in females with high body mass. Four-bout females showed a positive relationship between body mass and mitochondrial capacity. In contrast, non-reproductive females showed a negative relationship between body mass and mitochondrial capacity and primiparous females had a slope that did not differ from zero. Other measured variables, too, were highly dependent on body mass, suggesting that a female's body condition has strong impacts on mitochondrial physiology. We also evaluated the relationship between how much females allocated to reproduction (cumulative mass of all young weaned) and mitochondrial function and oxidative stress in the multiparous females. We found that females that allocated more to reproduction had lower basal respiration (state 4), lower mitochondrial density, and higher protein oxidation in liver mitochondria than females that allocated less. These results suggest that, at least through their first four reproductive events, female laboratory mice may experience bioenergetic benefits from reproduction but only those females that allocated the most to reproduction appear to experience a potential cost of reproduction.

4263 The cardioprotective effects of ramipril during the course of experimental hypercholesterolemia in rabbits

4263 The cardioprotective effects of ramipril during the course of experimental hypercholesterolemia in rabbits

Wearable respiratory strain monitoring system based on textile-based capacitive strain sensor

Respiratory state analysis based on respiratory strain monitoring plays an increasingly important role in the assessment of the continuous dynamic physiological state of the human body. The proposed respiratory strain monitoring system uses the STM32F411 single-chip microcomputer as the main control chip, combined with the FDC2214 capacitor-to-digital converter, collects the capacitance value of the flexible cloth-based capacitive strain sensor through the IIC method, and sends the collected result to the upper computer for processing and analysis through Bluetooth. The device collects the respiratory strain signal of the chest in three motion states: stationary, walking, and running. Through data acquisition and algorithm processing, it can clearly display the waveform of respiratory strain, and the extraction accuracy of the respiratory rate is ±1rpm. The experimental results show that the system has good stability and accuracy, strong anti-interference ability, and can meet the requirements of continuous dynamic high-precision respiratory rate monitoring.

From Molecular Reconstruction of Mesoscopic Functional Conductive Silk Fibrous Materials to Remote Respiration Monitoring.

Turning insulating silk fibroin materials into conductive ones turns out to be the essential step toward achieving active silk flexible electronics. This work aims to acquire electrically conductive biocompatible fibers of regenerated Bombyx mori silk fibroin (SF) materials based on carbon nanotubes (CNTs) templated nucleation reconstruction of silk fibroin networks. The electronical conductivity of the reconstructed mesoscopic functional fibers can be tuned by the density of the incorporated CNTs. It follows that the hybrid fibers experience an abrupt increase in conductivity when exceeding the percolation threshold of CNTs >35 wt%, which leads to the highest conductivity of 638.9 S m-1 among organic-carbon-based hybrid fibers, and 8 times higher than the best available materials of the similar types. In addition, the silk-CNT mesoscopic hybrid materials achieve some new functionalities, i.e., humidity-responsive conductivity, which is attributed to the coupling of the humidity inducing cyclic contraction of SFs and the conductivity of CNTs. The silk-CNT materials, as a type of biocompatible electronic functional fibrous material for pressure and electric response humidity sensing, are further fabricated into a smart facial mask to implement respiration condition monitoring for remote diagnosis and medication.

Bacterial Community Interactions During Chronic Respiratory Disease.

Chronic respiratory diseases including chronic rhinosinusitis, otitis media, asthma, cystic fibrosis, non-CF bronchiectasis, and chronic obstructive pulmonary disease are a major public health burden. Patients suffering from chronic respiratory disease are prone to persistent, debilitating respiratory infections due to the decreased ability to clear pathogens from the respiratory tract. Such infections often develop into chronic, life-long complications that are difficult to treat with antibiotics due to the formation of recalcitrant biofilms. The microbial communities present in the upper and lower respiratory tracts change as these respiratory diseases progress, often becoming less diverse and dysbiotic, correlating with worsening patient morbidity. Those with chronic respiratory disease are commonly infected with a shared group of respiratory pathogens including Haemophilus influenzae, Streptococcus pneumoniae, Staphylococcus aureus, Pseudomonas aeruginosa, and Moraxella catarrhalis, among others. In order to understand the microbial landscape of the respiratory tract during chronic disease, we review the known inter-species interactions among these organisms and other common respiratory flora. We consider both the balance between cooperative and competitive interactions in relation to microbial community structure. By reviewing the major causes of chronic respiratory disease, we identify common features across disease states and signals that might contribute to community shifts. As microbiome shifts have been associated with respiratory disease progression, worsening morbidity, and increased mortality, these underlying community interactions likely have an impact on respiratory disease state.

Continuous Normobaric Hypoxia Improved Cardiac Bioenergetics after Ischemia/Reperfusion: Role of Opioid Receptors.

We analyzed the role of opioid receptors in the conditioning effect of continuous normobaric hypoxia on bioenergetics of the heart subjected to ischemia/reperfusion injury. Male Wistar rats were adapted to a 21-day continuous normobaric hypoxia (12% pO2). Then, the hearts were isolated and subjected to 45-min total ischemia followed by 30-min reperfusion. Damage to the myocardium was assessed by activity of creatine phosphokinase in the perfusate. Experiments on isolated mitochondria showed that ischemia/reperfusion injury decreased the respiration rate in state 3 (V3), the ratio of added ADP and oxygen consumption in respiration state 3 (ADP/O ratio), the mitochondrial potential across the inner membrane (Δψ), and Ca2+ binding capacity of mitochondria. In addition, ischemia/reperfusion injury decreased myocardial ATP. Preventive continuous normobaric hypoxia pronouncedly moderated these adverse effects of reperfusion. It was found that its protective effects were related to activation of cardiac μ- and δ2-opioid receptors.

Antineoplastic activity of a novel ruthenium complex against human hepatocellular carcinoma (HepG2) and human cervical adenocarcinoma (HeLa) cells

Novel metal complexes have received much attention recently because of their potential anticancer activity. Notably, ruthenium-based complexes have emerged as good alternatives to the currently used platinum-based drugs for cancer therapy, with less toxicity and fewer side effects. The beneficial properties of Ru, which make it a highly promising therapeutic agent, include its variable oxidative states, low toxicity, and high selectivity for cancer cells. The present study evaluated the cytotoxic effects of a ruthenium complex, namely cis-[Ru(1,10-phenanthroline)2(imidazole)2]2+ (RuC), on human hepatocellular carcinoma (HepG2) and human cervical adenocarcinoma (HeLa) cells and analyzed metabolic parameters. RuC reduced HepG2 and HeLa cell viability at all tested concentrations (10, 50, and 100 nmol/L) at 48 h of incubation, based on the MTT, Crystal violet, and neutral red assays. The proliferation capacity of HepG2 cells did not recover, whereas HeLa cell proliferation partially recovered after RuC treatment. RuC also inhibited all states of cell respiration and increased the levels of the metabolites pyruvate and lactate in both cell lines. The cytotoxicity of RuC was higher than cisplatin (positive control) in both lineages. These results indicate that RuC affects metabolic functions that are related to the energy provision and viability of HepG2 and HeLa cells and is a promising candidate for further investigations that utilize models of human cervical adenocarcinoma and mainly hepatocellular carcinoma.

All-in-One Wearable Self-Powered Respiratory Sensor Enabled By Contact Electrification

Introduction Human respiration is rich in physiological and pathological information as biomarker for health assessment and illness prediction. Respiratory diagnosis method carries various advantages, such as continuity, non-invasiveness, comfort and user-friendly [6]. Typically, ammonia (NH3) in exhaled breath can be served as biomarker for some diseases like end-stage renal disease (ESRD), ulcers caused by Helicobacter pylori or bacterial in oral cavity [12-15]. NH3 concentration in healthy people’ exhaled breath is about 0.425-1.8 ppm (mean 0.96 ppm), while the one in ESRD patients’ breathing ranges from 0.82 to14.7 ppm (mean 4.88 ppm) [12].Even though various traditional sensors have been applied to monitor human physiological information like heartbeat or respiration, some limitations, such as bulky structure, poor portability and requirement of external power sources remarkably restricted their widespread application in smart mobile medical electronics [16]. Therefore, a self-powered ammonia sensor that can harvest energy from human body is desperately needed. In addition, it is underexplored but will be a novel and superior solution if a wearable sensor that could simultaneously chemically detect the inhalation and measure the breath rate for respiration analysis without a power supply. Device fabrication The as-developed triboelectric self-powered respiration sensor (TSRS) is composed of Ce-doped ZnO, Polydimethylsiloxane (PDMS), Au foils and PET films, as revealed in Fig. 1a. Ce-doped ZnO plays dual roles of gas sensing material and triboelectrification layer (Fig. 1b). PDMS functions as the triboelectric layer and Au foils were coated on the back of both triboelectric layers as electrodes. To improve the flexibility and air tightness, the whole device was packed with soft silica gel films. The patterned PDMS film exhibits good transparency and flexibility, as shown in Fig. 1c and 1d. Figure 1e sketches the fabrication flow of the TSRS. Driven by the continuous expansion and contraction of the chest during respiration (Fig. 1g), the deformation of TSRS inflated can be converted into electric signals and human exhaled gas can flow into the TSRS through a soft tube with the breathing process, enabling the real-time spontaneous monitoring of both respiratory behaviors and exhaled gas. Method To explore the sensing behavior of as-prepared TSRS toward NH3 from 0.1 to 10 ppm, including the trace level region (region Ⅰ, 0.1 to 1 ppm) and micro level region (region Ⅱ, 2 to 10 ppm), the NH3-sensing response-concentration fitting curves are plotted in Fig. 2a for five samples. It is found that without moisture atmosphere, the TSRS exhibits an opposite sensing behavior and the response declines with increasing ammonia concentration in both region Ⅰ (Fig. 2e) and region Ⅱ (Fig. 2f). A steeper slope is observed under humid NH3 atmosphere in comparison with the dry NH3 atmosphere, indicating that the existence of water molecular will raise the sensing performance. As a consequence, the moisture-resistant feature of the as-developed TSRS favours NH3 detection in human exhaled gas. Figure 2g elucidates dynamic response profile of TSRS when exposed to 0.01 ppm NH3 with 97.5%RH, which indicates that the TSRS is sensitive to NH3 as low as 0.01 ppm and the response time is nearly 155 s. Results and Conclusions Attached on the human chest, the as-prepared TSRS delivers a stable output voltage signal within 5 min normal breathing (Fig. 3a). The wearable sensor can be applied to distinguish different types of breathing behaviors and human respiratory states after physical exercise. Figure 3b presents the real-time output recording of diverse breathing behaviors, including normal breathing, deep breathing, shallow breathing and rapid breathing. Human respiration rate and depth can be clearly recognized in terms of frequency and amplitude of the output voltage signals. The deep breathing pattern has a bigger peak-to-peak amplitude and wider interval than normal breathing pattern due to the larger and slower change in chest circumference. In addition, the physiological process of human body after exercise can also be accurately reflected by breathing intensity and frequence. The breathing amplitude after 100 squats is more intense than that after 50 squats, as displayed in Fig. 3c. Meanwhile, the injection of exhaled NH3 gas into the TSRS apparently enlarges the amplitude of the output voltage (Fig. 3d), revealing the capability of simultaneously detecting breathing behaviors and exhaled gases.

Impact of temporal resolution and motion correction for dynamic contrast-enhanced MRI of the liver using an accelerated golden-angle radial sequence

This paper presents a prospective study evaluating the impact on image quality and quantitative dynamic contrast-enhanced (DCE)-MRI perfusion parameters when varying the number of respiratory motion states when using an eXtra-Dimensional Golden-Angle Radial Sparse Parallel (XD-GRASP) MRI sequence. DCE acquisition was performed using a 3D stack-of-stars gradient-echo golden-angle radial acquisition in free-breathing with 100 spokes per motion state and temporal resolution of 6 s/volume, and using a non-rigid motion compensation to align different motion states. Parametric analysis was conducted using a dual-input single-compartment model. Nonparametric analysis was performed on the time-intensity curves. A total of 22 hepatocellular carcinomas (size: 11–52 mm) were evaluated. XD-GRASP reconstructed with increasing number of spokes for each motion state increased the signal-to-noise ratio (SNR) (p < 0.05) but decreased temporal resolution (0.04 volume/s vs 0.17 volume/s for one motion state) (p < 0.05). A visual scoring by an experienced radiologist show no change between increasing number of motion states with same number of spokes using the Likert score. The normalized maximum intensity time ratio, peak enhancement ratio and tumor arterial fraction increased with decreasing number of motion states (p < 0.05) while the transfer constant from the portal venous plasma to the surrounding tissue significantly decreased (p < 0.05). These same perfusion parameters show a significant difference in case of tumor displacement more than 1 cm (p < 0.05) whereas in the opposite case there was no significant variation. While a higher number of motion states and higher number of spokes improves SNR, the resulting lower temporal resolution can influence quantitative parameters that capture rapid signal changes. Finally, fewer displacement compensation is advantageous with lower number of motion state due to the higher temporal resolution. XD-GRASP can be used to perform quantitative perfusion measures in the liver, but the number of motion states may significantly alter some quantitative parameters.

Energy metabolism and oxidative status of rat liver mitochondria in conditions of experimentally induced hyperthyroidism

The aim of the present work was to investigate the energy metabolism and antioxidant status of rat liver mitochondria using a model of hyperthyroidism. In experimental animals, the level of triiodothyronine and thyroxine was increased 3- and 4-fold, respectively, in comparison with that in the control group, indicating the development of hyperthyroidism in these animals. Oxygen consumption was found to be higher in rats with experimentally induced hyperthyroidism (from 20 to 60% depending on the experimental scheme used), with a slight decrease in the efficiency of oxidative phosphorylation and respiratory state ratio. It was shown for the first time that the level the respiratory complexes of the electron transport chain in hyperthyroid rats increased; however, the quantity of complexes III and V changed unreliably. The assay of respiratory chain enzymes revealed that the activities of complexes I, II, and citrate synthase increased, whereas the activities complexes II + III, III, IV decreased in liver mitochondria of the experimental animals. Alterations in the oxidative state in liver mitochondria were found: a 60% increase in the hydrogen peroxide production rate and a 45% increase in lipid peroxidation. The activities of superoxide dismutase and catalase in the liver of experimental rats were higher than in the control. At the same time, the activity of glutathione peroxidase did not change. The data obtained indicate that the known activation of metabolism and changes in the oxidative status in thyrotoxicosis are associated with variations in the respiratory chain functioning and the antioxidant enzymes of mitochondria.

Progressive Alterations of Mitochondrial Function in the Kidney and Heart During the Development of Salt‐Induced Hypertension

IntroductionHypertension is a multi‐factorial disease and a leading cause of morbidity and mortality globally. Nearly half of these individuals are sensitive to dietary salt intake with the kidney and oxidative stress playing a key role in this disease leading to eventual failure of both the kidney and heart. Although oxidative stress and mitochondrial dysfunction in the kidney and heart have been studied in various models of hypertension, progressive alterations of mitochondrial function and development of oxidative stress in these two organs have not been studies in parallel during the development of hypertension. The goal of the present study was to investigate progressive alterations in mitochondrial energy metabolism in both the kidney and heart concurrently in the Dahl salt‐sensitive (SS) rats during the development of hypertension when rats were switched from a 0.4% NaCl (LS) to a 4% NaCl (HS) diet.MethodMitochondria were isolated from the ventricles of the heart and outer medulla (OM) and cortex of the kidney of SS rats fed a LS diet since weaning and studied at days 3, 7, 14 &amp; 21 of a HS diet feeding. Oxygen consumption rates (OCR) were measured in mitochondria energized with pyruvate + malate as substrates for 3 different respiratory states using an Oroboros Oxygraph‐2k respirometer. This includes a) leak state (energized mitochondria in the absence of ADP), b) ADP‐stimulated state, and c) uncoupled state (energized mitochondria in the presence of an uncoupler FCCP).ResultsA biphasic pattern of ADP‐stimulated OCR with progressive uncoupling was observed in both the kidney (OM &amp; cortex) and heart mitochondria. In kidney, mitochondrial efficiency for ATP synthesis was increased in the early phase of hypertension (3 &amp; 7 days) but was severely compromised in the established phase of hypertension (14 &amp; 21 days). Cardiac mitochondria also showed a similar pattern, however the reduced mitochondrial efficiency for ATP synthesis occurred at a later time, specifically at day 21. This decreased mitochondrial efficiency was hypothesized to be associated with higher levels of uncoupling, ROS production, and oxidative stress in both organs due to mitochondrial ROS‐cellular ROS crosstalk. To test this, experiments were performed in SS rats with double knock out (DKO) of the Nox family of NADPH oxidases: Nox4 and p67phox cytosolic subunit of Nox2 (SSp67phox−/−/Nox4−/−) and determined the role of mitochondrial ROS in stimulating cellular ROS production, particularly by membrane Noxs, and vice versa. Specifically, the DKO SS rats were fed a HS diet and isolated mitochondrial OCR was studied at days 7 and 14. DKO SS rats fed a HS diet showed no significant differences in mitochondrial OCR as compared to the control group (LS diet) in the kidney (OM &amp; cortex) and heart.ConclusionOur data suggest that a HS diet in SS rats results initially in increased efficiency of renal cortical and medullary mitochondrial energy production during the 1st week of a HS diet followed by an enhanced ROS production with mitochondrial uncoupling and reduced efficiency of ATP production by the 3rd week. Similar changes occurred in the heart but 1–2 weeks following the changes observed in the kidney.Support or Funding InformationP01‐GM066730, P01‐HL116264

Methylmalonic Acid Compromises Energy Metabolism and Decreases the Expression of Neuronal Differentiation Genes in SH‐SY5Y Human Neuroblastoma Cells

Methylmalonic acidemia is an organic acidemia caused by deficient activity of L‐methylmalonyl‐CoA mutase or its cofactor cyanocobalamin and it is biochemically characterized by an accumulation of methylmalonic acid (MMA) in tissue and body fluids of patients. The main clinical manifestations of this disease are neurological and symptoms during metabolic decompensation commonly appear in newborns. Considering that the mechanisms underlying neurological alterations of this disorder are not fully understood, this study aimed to investigate the toxic effects of MMA in a neuroblastoma cell line presenting neuronal features. Undifferentiated and retinoic acid (RA)‐differentiated human neuroblastoma SH‐SY5Y cells were exposed to MMA (1–10mM) for 24 or 48 hours and cell viability, glucose consumption and mitochondrial metabolic function were analyzed. Additionally, the expression of some molecular markers of neuronal differentiation was also quantified after co‐exposition with 10 μM RA and 1 mM of MMA for 3 and 7 days.MMA significantly reduced cell viability after 48‐hour period exposition in undifferentiated and RA differentiated SH‐SY5Y cells. It was also observed an increase in glucose consumption in cells exposed to MMA. Regarding oxygen consumption, there was an increase in respiratory parameters in RA differentiated SH‐SY5Y cells when compared to undifferentiated cells. MMA significantly reduced basal, ATP‐linked and maximal respiration, as well as the reserve respiratory capacity of cells after 48‐hour exposition in both undifferentiated and RA differentiated SH‐SY5Y cells. Regarding the effects of MMA in the neuronal differentiation process, it was observed that co‐exposition to RA and MMA significantly decreased the expression of enolase 2 (ENO2) and synaptophysin (SYP) genes after 7 days of exposition.In summary, MMA cell viability and oxygen consumption in SH‐SY5Y neuronal cells, suggesting that this organic acid compromises cell respiration, at resting and reserve capacity states, which might influence the cell capacity to meet energetic demands. In addition, glucose uptake was increased after exposition to MMA, corroborating that aerobic metabolism is compromised. The expression of mature neuronal genes was also reduced, suggesting that MMA possibly compromises neuronal differentiation, which can be involved in symptoms presented by affected patients during brain development. Finally, our findings suggest that these effects could be involved in the pathophysiology of neurological dysfunction of this disease.Support or Funding InformationThis study was supported by grants from FAPESP (2015/25541‐0), CAPES and UFABC.

Experimental oxygen concentration influences rates of mitochondrial hydrogen peroxide release from cardiac and skeletal muscle preparations.

Mitochondria utilize the majority of oxygen (O2) consumed by aerobic organisms as the final electron acceptor for oxidative phosphorylation (OXPHOS) but also to generate reactive oxygen species (mtROS) that participate in cell signaling, physiological hormesis, and disease pathogenesis. Simultaneous monitoring of mtROS production and oxygen consumption (Jo2) from tissue mitochondrial preparations is an attractive investigative approach, but it introduces dynamic changes in media O2 concentration ([O2]) that can confound experimental results and interpretation. We utilized high-resolution fluorespirometry to evaluate Jo2 and hydrogen peroxide release (Jh2o2) from isolated mitochondria (Mt), permeabilized fibers (Pf), and tissue homogenates (Hm) prepared from murine heart and skeletal muscle across a range of experimental [O2]s typically encountered during respirometry protocols (400-50 µM). Results demonstrate notable variations in Jh2o2 across tissues and sample preparations during nonphosphorylating (LEAK) and OXPHOS-linked respiration states at 250 µM [O2] but a linear decline in Jh2o2 of 5-15% per 50-µM decrease in chamber [O2] in all samples. Jo2 was generally stable in Mt and Hm across [O2]s above 50 µM but tended to decline below 250 µM in Pf, leading to wide variations in assayed rates of Jh2o2/O2 across chamber [O2]s and sample preparations. Development of chemical background fluorescence from the H2O2 probe (Amplex Red) was also O2 sensitive, emphasizing relevant calibration considerations. This study highlights the importance of monitoring and reporting the chamber [O2] at which Jo2 and Jh2o2 are recorded during fluorespirometry experiments and provides a basis for selecting sample preparations for studies addressing the role of mtROS in physiology and disease.

Criteria lor determining the severity of respiratory failure of patients suffering bilateral vocal fold paralysis

Topicality: Despite of the large number of research works concerning respiratory failure of patients suffering bilateral vocal fold paralysis, there are no objective systematized data of clinical and instrumental studies characterizing this verity of ventilation obstructive insufficiency of external respiration and their interpretation, taking into account the aerodynamic condition pathophysiology in vocal fold mobility presence or absence. Purpose: Definition of the criteria for the severity of respiratory failure of patients suffering bilateral vocal fold paralysis, based on a study of external respiration state according to the spirometry. Materials and methods: 106 patients suffering bilateral vocal fold paralysis took part in thes study. They were divided into two groups. 55 patients suffering bilateral vocal fold paralysis entered the first group while 51 patients suffering bilateral vocal fold paralysis who received surgery treatment, namely endoscopic unilateral chordoarytenoidotomy. As a control group, 15 practically healthy people, having not any disturbances of vocal apparatus or respiratory system, were examined. All the patients underwent a standard respiratory quality survey (SGRQ survey), laryngeal endoscopy (Storz, Germany), spirometric studies of external respiratory function (Vitalograph Pneumotrac, Germany). Results: In order to search for criteria that would allow a more accurate assessment of the patient's external respiration, as well as maximally approximate objective and subjective assessment, we made subdivision of the first group patients, suffering bilateral vocal fold paralyses, into two subgroups: subgroup 1a and subgroup 1b. Subgroup 1a included the patients suffering bilateral vocal fold paralysis whose value indicator of the subjective overall assessment according to SGRQ data was up to 70 points (n=29). While subgroup 1b included the patients whose indicator was more than 70 points (n=26). According to spirometry data, all the patients showed signs of obstructive ventilation of respiratory failure expressed in varying degrees, namely, a significant decrease in speed indicators FEV1, PEF and PIF compared with the control group (p&lt;0,01). The most significant was a decrease in peak inspiration volume tricrate PIF, the value of which in patients suffering bilateral vocal cords fold paralysis was less than 50% of the standard nominative values. The lowest values of PIF indicator (22,14±1,41%) were determined in subgroup 1b. 61,54% of patients’ this subgroup, who clinically had the most pronounced indicators of respiratory failure, also revealed a decrease in peak expiration volume tricrate PEF (31,36±2,31%) less than 40%. PEF and PIF indicators of patients in subgroup 1b had a significant difference from PEF and PIF indicators in subgroup 1a (PEF – 45,92±4,40%, PIF – 34,08±1,60%) and group 2 (PEF – 53,22±2,48%, PIF – 37,78±2,35%) (p&lt;0,01). Besides, the patients in subgroup 1b showed a significant decrease in VC and FVC indicators as compared to group 2 and subgroup 1a (p&lt;0,01, p&gt;0,05). Conclusions: Speaking about patients suffering bilateral vocal cords fold paralysis, their most informative criterion for determining these verity of the obstructive variant of ventilation respiratory failure, as well as of the effectiveness of the treatment used, is PEF indicator and, especially, PIF indicator. Indicators of PIF (22,14±1,41%) and PEF (31,36±2,31%), differing for more than 80% and 60 % from normative indicators, are considered to be critical. They prove of severe respiratory failure.

Research Program: Modeling of Motor Abilities Development and Teaching of Schoolchildren

The purpose of this study was to find methodological approaches to the development of a research program in modeling the process of teaching physical exercises, motor abilities development and pedagogical control in schoolchildren’s physical education.&#x0D; Materials and methods. The total number of schoolchildren involved in the experiment was: 6-10 years old – 465 (240 boys and 225 girls); 11-13 years old – 430 schoolchildren (205 boys and 225 girls); 14-16 years old – 221 schoolchildren (122 boys and 99 girls). To achieve the purpose set, the following research methods were used: modeling, systems approach, methods of theoretical analysis and generalization; pedagogical testing, methods of recording the respiratory system state, observation and pedagogical experiment; methods of mathematical analysis (logistic and asymptotic functions); mathematical methods of planning multifactorial experiments. Factor, discriminant, and regression analyses were performed.&#x0D; Results. The research program of modeling schoolchildren’s physical education includes the development of factor, discriminant, and regression models to obtain new information for planning and managing the processes of teaching physical exercises, motor abilities development, and pedagogical control in schoolchildren’s physical education.&#x0D; Conclusions. Modeling is an effective tool for studying the regularities of motor training and for developing physical education programs for children and adolescents. In the program of modeling schoolchildren’s physical education, initial data, study object, research methods must meet the following conditions: parametrical description (formulation of tasks, consideration of physical components, analysis of coefficients); initial data (information potential, reliability, accuracy, quantity); methods (similarity, accuracy, implementation time, coincidence with control criteria).

Characterization of Artifact Signals in Neck Photoplethysmography.

The neck is a very attractive measurement location for multimodal physiological monitoring, since it offers the possibility of extracting clinically relevant parameters, which cannot be obtained from other body locations, such as lung volumes. It is for this reason that obtaining PPG from the neck would be of interest. PPG signals, however, are very susceptible to artifacts which greatly compromise their quality. But the extent of this is going to depend on, the nature of the artifacts and the strength of the sensed signal, both of which are location dependent. This paper presents for the first time the characterization of artifacts affecting neck PPG signals. Neck PPG data was recorded from 19 participants, who performed ten different activities to deliberately introduce common artifacts. 41 PPG features were extracted and statistically analyzed to investigate which ones showed the greatest ability to differentiate normal PPG from each artifact. A customized minimum Redundancy Maximum Relevance (mRMR) feature selection approach was implemented, to select the top 10 features. Artifacts caused by Swallowing, Yawning and Coughing exhibited larger Spectral Entropy, Average Power and smaller Spectral Kurtosis, than normal PPG. Head movement artifacts, also demonstrated highly disordered and noisy frequency spectra, and were characterized by having larger and irregular time domain features. In addition, the analysis showed that different respiratory states that could be of clinical interests, such as presence of apneas, were also distinguishable from sources of interference. These findings are important for the development of PPG denoising algorithms and subsequent obtention of biomarkers of interest, or alternatively for applications where the events of interest are the artifacts themselves.