Mechanical power density, spontaneous breathing indexes, and prolonged weaning failure: a prospective cohort study.

A prospective observational study comparing mechanical power density (MP normalized to dynamic compliance) with traditional spontaneous breathing indexes (e.g., predicted body weight normalized tidal volume [VT/PBW], rapid shallow breathing index [RSBI], or the integrative weaning index [IWI]) for predicting prolonged weaning failure in 140 tracheotomized patients. We assessed the diagnostic accuracy of these indexes at the start and end of the weaning procedure using ROC curve analysis, expressed as the area under the receiver operating characteristic curve (AUROC). Weaning failure occurred in 41 out of 140 patients (29%), demonstrating significantly higher MP density (6156 cmH2O2/min [4402-7910] vs. 3004 cmH2O2/min [2153-3917], P < 0.01), lower spontaneous VT/PBW (5.8 mL*kg-1 [4.8-6.8] vs. 6.6 mL*kg-1 [5.7-7.9], P < 0.01) higher RSBI (68 min-1*L-1 [44-91] vs. 55 min-1*L-1 [41-76], P < 0.01) and lower IWI (41 L2/cmH2O*%*min*10-3 [25-72] vs. 71 L2/cmH2O*%*min*10-3 [50-106], P < 0.01) and at the end of weaning. MP density was more accurate at predicting weaning failures (AUROC 0.91 [95%CI 0.84-0.95]) than VT/PBW (0.67 [0.58-0.74]), RSBI (0.62 [0.53-0.70]), or IWI (0.73 [0.65-0.80]), and may help clinicians in identifying patients at high risk for long-term ventilator dependency.

Effects of linalool on respiratory neuron activity in the brainstem-spinal cord preparation from newborn rats.

Linalool and linalyl acetate are major components of lavender essential oil. These substances possess many biological activities, such as anti-inflammatory activity, analgesic and anxiolytic effects, and anticonvulsant properties, and they also induce modulation of neuronal activity in the autonomic nervous system. However, there are no reports of the direct effects of linalool on respiratory activity. In the present study, we analyzed the effects of linalool and linalyl acetate on central respiratory activity in the brainstem-spinal cord preparation isolated from newborn rats. Linalool dose-dependently decreased the rate of respiratory activity. This effect was reversed by bicuculline, suggesting that linalool enhanced inhibitory synaptic connections via GABAA receptors. In addition, linalool reduced the coefficient of variation of inspiratory burst intervals and thus could work to stabilize the respiratory rhythm. Linalyl acetate did not cause inhibitory effects as observed in linalool treatment. Linalool depressed burst activity of pre-inspiratory neurons in the medullary respiratory networks and increased the amplitude of inspiratory inhibitory postsynaptic potentials of pre-inspiratory neurons. We concluded that linalool caused inhibitory effects on respiratory rhythm generation mainly through activation of presynaptic GABAA receptors of pre-inspiratory neurons.

Millimeter-Wave Radar-Based Identity Recognition Algorithm Built on Multimodal Fusion.

Millimeter-wave radar-based identification technology has a wide range of applications in persistent identity verification, covering areas such as security production, healthcare, and personalized smart consumption systems. It has received extensive attention from the academic community due to its advantages of being non-invasive, environmentally insensitive and privacy-preserving. Existing identification algorithms mainly rely on a single signal, such as breathing or heartbeat. The reliability and accuracy of these algorithms are limited due to the high similarity of breathing patterns and the low signal-to-noise ratio of heartbeat signals. To address the above issues, this paper proposes an algorithm for multimodal fusion for identity recognition. This algorithm extracts and fuses features derived from phase signals, respiratory signals, and heartbeat signals for identity recognition purposes. The spatial features of signals with different modes are first extracted by the residual network (ResNet), after which these features are fused with a spatial-channel attention fusion module. On this basis, the temporal features are further extracted with a time series-based self-attention mechanism. Finally, the feature vectors of the user's vital sign modality are obtained to perform identity recognition. This method makes full use of the correlation and complementarity between different modal signals to improve the accuracy and reliability of identification. Simulation experiments show that the algorithm identity recognition proposed in this paper achieves an accuracy of 94.26% on a 20-subject self-test dataset, which is much higher than that of the traditional algorithm, which is about 85%.

mmWave-RM: A Respiration Monitoring and Pattern Classification System Based on mmWave Radar.

Breathing is one of the body's most basic functions and abnormal breathing can indicate underlying cardiopulmonary problems. Monitoring respiratory abnormalities can help with early detection and reduce the risk of cardiopulmonary diseases. In this study, a 77 GHz frequency-modulated continuous wave (FMCW) millimetre-wave (mmWave) radar was used to detect different types of respiratory signals from the human body in a non-contact manner for respiratory monitoring (RM). To solve the problem of noise interference in the daily environment on the recognition of different breathing patterns, the system utilised breathing signals captured by the millimetre-wave radar. Firstly, we filtered out most of the static noise using a signal superposition method and designed an elliptical filter to obtain a more accurate image of the breathing waveforms between 0.1 Hz and 0.5 Hz. Secondly, combined with the histogram of oriented gradient (HOG) feature extraction algorithm, K-nearest neighbours (KNN), convolutional neural network (CNN), and HOG support vector machine (G-SVM) were used to classify four breathing modes, namely, normal breathing, slow and deep breathing, quick breathing, and meningitic breathing. The overall accuracy reached up to 94.75%. Therefore, this study effectively supports daily medical monitoring.

Sensing, feeling and regulating: investigating the association of focal brain damage with voluntary respiratory and motor control.

Breathing is a complex, vital function that can be modulated to influence physical and mental well-being. However, the role of cortical and subcortical brain regions in voluntary control of human respiration is underexplored. Here we investigated the influence of damage to human frontal, temporal or limbic regions on the sensation and regulation of breathing patterns. Participants performed a respiratory regulation task across regular and irregular frequencies ranging from 6 to 60 breaths per minute (bpm), with a counterbalanced hand motor control task. Interoceptive and affective states induced by each condition were assessed via questionnaire, and autonomic signals were indexed via skin conductance. Participants with focal lesions to the bilateral frontal lobe, right insula/basal ganglia and left medial temporal lobe showed reduced performance relative to individually matched healthy comparisons during the breathing and motor tasks. They also reported significantly higher anxiety during the 60 bpm regular and irregular breathing trials, with anxiety correlating with difficulty in rapid breathing specifically within this group. This study demonstrates that damage to frontal, temporal or limbic regions is associated with abnormal voluntary respiratory and motor regulation and tachypnoea-related anxiety, highlighting the role of the forebrain in affective and motor responses during breathing. This article is part of the theme issue 'Sensing and feeling: an integrative approach to sensory processing and emotional experience'.

Respiratory and muscular effort during pre-slaughter stress affect Nile tilapia fillet quality.

Nile Tilapia (Oreochromis niloticus) management procedures are directly linked to the final quality of the product. The aim of this study was to evaluate the effect of pre-slaughter density and different stunning methods on biochemical, respiratory and muscle injury parameters associated with quality and sensory characteristics of Nile tilapia fillets. Fish with an average weight of 762±105 g were used, first collected called the control group. The experiment was conducted in a 2 × 2 factorial scheme, with two densities (50 and 300 kg of live weight m-3) and two stunning methods thus totaling four treatments, with 15 repetitions per treatment totaling 75 fish sampled. Blood gas analysis, evaluation of biochemical parameters, analysis of meat quality and sensory analysis were carried out. For blood gas, biochemical and enzymatic parameters, the highest values were obtained for the density of 300 kg m-3 and asphyxia method: partial pressures of CO2; glucose and lactate, the highest values presented were 268.98 and 11.33 mg dL-1 respectively. As well as enzymatic activities, Creatinine kinase (CPK); Creatinine kinase isoenzyme (CKMB) showed higher values (768.93 and 1078.98 mg dL-1 respectively) in the higher density and asphyxia method. Conversely, when evaluating the quality parameters, the highest values were observed for lower density and thermonarcosis. High depuration density (300 kg m-3), combined with the asphyxiation stunning method, promotes changes in respiratory dynamics and provides greater stress, less firm fillet texture and greater weight loss due to cooking, as well as changes in creatine kinase (CK) and its CK-MB isoenzyme, demonstrating greater muscle damage. On the other hand, the density of 50 kg m-3 during pre-slaughter, combined with the method of stunning by thermonarcosis, provide a longer period of permanence in pre rigor mortis, which will result in fillets with a better sensory profile.

Breathing-Swallowing discoordination after definitive chemoradiotherapy for head and neck cancers is associated with aspiration pneumonia.

PURPOSE: Swallowing dysfunction and the risk of aspiration pneumonia are frequent clinical problems in the treatment of head and neck squamous cell carcinomas (HNSCCs). Breathing-swallowing coordination is an important factor in evaluating the risk of aspiration pneumonia. To investigate breathing-swallowing discoordination after chemoradiotherapy (CRT), we monitored respiration and swallowing activity before and after CRT in patients with HNSCCs. METHODS: Non-invasive swallowing monitoring was prospectively performed in 25 patients with HNSCCs treated with CRT and grade 1 or lower radiation-induced dermatitis. Videoendoscopy, videofluoroscopy, Food Intake LEVEL Scale, and patient-reported swallowing difficulties were assessed. RESULTS: Of the 25 patients selected for this study, four dropped out due to radiation-induced dermatitis. The remaining 21 patients were analyzed using a monitoring system before and after CRT. For each of the 21 patients, 405 swallows were analyzed. Swallowing latency and pause duration after the CRT were significantly extended compared to those before the CRT. In the analysis of each swallowing pattern, swallowing immediately followed by inspiration (SW-I pattern), reflecting breathing-swallowing discoordination, was observed more frequently after CRT (p = 0.0001). In 11 patients, the SW-I pattern was observed more frequently compared to that before the CRT (p = 0.00139). One patient developed aspiration pneumonia at 12 and 23 months after the CRT. CONCLUSION: The results of this preliminary study indicate that breathing-swallowing discoordination tends to increase after CRT and could be involved in aspiration pneumonia. This non-invasive method may be useful for screening swallowing dysfunction and its potential risks.

Cardiorespiratory dynamics of type 2 diabetes mellitus: An extensive view of breathing and fitness challenges in a diabetes prevalent population.

BACKGROUND: Diabetes mellitus (DM) is well known for related micro and macrovascular complications. Uncontrolled hyperglycemia in diabetes mellitus leads to endothelial dysfunction, inflammation, microvascular impairment, myocardial dysfunction, and skeletal muscle changes which affect multiple organ systems. This study was designed to take an extensive view of cardiorespiratory dynamics in patients with type 2 DM. METHODS: One hundred healthy controls (HC) and 100 DM patients were enrolled. We measured and compared the breathing patterns (spirometry), VO2 max levels (heart rate ratio method) and self-reported fitness level (international fitness scale) of individuals with and without diabetes. Data was analyzed in SPSS v.22 and GraphPad Prism v8.0. RESULTS: We observed restrictive spirometry patterns (FVC <80%) in 22% of DM as compared to 2% in HC (p = 0.021). There was low mean VO2 max in DM as compared to HC(32.03 ± 5.36 vs 41.91 ± 7.98 ml/kg/min; p value <0.001). When evaluating physical fitness on self-reported IFiS scale, 90% of the HC report average, good, or very good fitness levels. In contrast, only 45% of the DM shared this pattern, with a 53% proportion perceiving their fitness as poor or very poor (p = <0.05). Restrictive respiratory pattern, low VO2 max and fitness level were significantly associated with HbA1c and long-standing DM. CONCLUSION: This study shows decreased pulmonary functions, decreased cardiorespiratory fitness (VO2 max) and IFiS scale variables in diabetic population as compared to healthy controls which are also associated with glycemic levels and long-standing DM. Screening for pulmonary functions can aid optimum management in this population.

The breath shape controls intonation of mouse vocalizations.

Intonation in speech is the control of vocal pitch to layer expressive meaning to communication, like increasing pitch to indicate a question. Also, stereotyped patterns of pitch are used to create distinct sounds with different denotations, like in tonal languages and, perhaps, the 10 sounds in the murine lexicon. A basic tone is created by exhalation through a constricted laryngeal voice box, and it is thought that more complex utterances are produced solely by dynamic changes in laryngeal tension. But perhaps, the shifting pitch also results from altering the swiftness of exhalation. Consistent with the latter model, we describe that intonation in most vocalization types follows deviations in exhalation that appear to be generated by the re-activation of the cardinal breathing muscle for inspiration. We also show that the brainstem vocalization central pattern generator, the iRO, can create this breath pattern. Consequently, ectopic activation of the iRO not only induces phonation, but also the pitch patterns that compose most of the vocalizations in the murine lexicon. These results reveal a novel brainstem mechanism for intonation.

Mapping responses to focal injections of bicuculline in the lateral parafacial region identifies core regions for maximal generation of active expiration.

The lateral parafacial area (pFL) is a crucial region involved in respiratory control, particularly in generating active expiration through an expiratory oscillatory network. Active expiration involves rhythmic abdominal (ABD) muscle contractions during late-expiration, increasing ventilation during elevated respiratory demands. The precise anatomical location of the expiratory oscillator within the ventral medulla's rostro-caudal axis is debated. While some studies point to the caudal tip of the facial nucleus (VIIc) as the oscillator's core, others suggest more rostral areas. Our study employed bicuculline (a γ-aminobutyric acid type A [GABA-A] receptor antagonist) injections at various pFL sites (-0.2 mm to +0.8 mm from VIIc) to investigate the impact of GABAergic disinhibition on respiration. These injections consistently elicited ABD recruitment, but the response strength varied along the rostro-caudal zone. Remarkably, the most robust and enduring changes in tidal volume, minute ventilation, and combined respiratory responses occurred at more rostral pFL locations (+0.6/+0.8 mm from VIIc). Multivariate analysis of the respiratory cycle further differentiated between locations, revealing the core site for active expiration generation with this experimental approach. Our study advances our understanding of neural mechanisms governing active expiration and emphasizes the significance of investigating the rostral pFL region.

Continuous Monitoring of Heart Rate Variability and Respiration for the Remote Diagnosis of Chronic Obstructive Pulmonary Disease: Prospective Observational Study.

BACKGROUND: Conventional daytime monitoring in a single day may be influenced by factors such as motion artifacts and emotions, and continuous monitoring of nighttime heart rate variability (HRV) and respiration to assist in chronic obstructive pulmonary disease (COPD) diagnosis has not been reported yet. OBJECTIVE: The aim of this study was to explore and compare the effects of continuously monitored HRV, heart rate (HR), and respiration during night sleep on the remote diagnosis of COPD. METHODS: We recruited patients with different severities of COPD and healthy controls between January 2021 and November 2022. Vital signs such as HRV, HR, and respiration were recorded using noncontact bed sensors from 10 PM to 8 AM of the following day, and the recordings of each patient lasted for at least 30 days. We obtained statistical means of HRV, HR, and respiration over time periods of 7, 14, and 30 days by continuous monitoring. Additionally, the effects that the statistical means of HRV, HR, and respiration had on COPD diagnosis were evaluated at different times of recordings. RESULTS: In this study, 146 individuals were enrolled: 37 patients with COPD in the case group and 109 participants in the control group. The median number of continuous night-sleep monitoring days per person was 56.5 (IQR 32.0-113.0) days. Using the features regarding the statistical means of HRV, HR, and respiration over 1, 7, 14, and 30 days, binary logistic regression classification of COPD yielded an accuracy, Youden index, and area under the receiver operating characteristic curve of 0.958, 0.904, and 0.989, respectively. The classification performance for COPD diagnosis was directionally proportional to the monitoring duration of vital signs at night. The importance of the features for diagnosis was determined by the statistical means of respiration, HRV, and HR, which followed the order of respiration > HRV > HR. Specifically, the statistical means of the duration of respiration rate faster than 21 times/min (RRF), high frequency band power of 0.15-0.40 Hz (HF), and respiration rate (RR) were identified as the top 3 most significant features for classification, corresponding to cutoff values of 0.1 minute, 1316.3 nU, and 16.3 times/min, respectively. CONCLUSIONS: Continuous monitoring of nocturnal vital signs has significant potential for the remote diagnosis of COPD. As the duration of night-sleep monitoring increased from 1 to 30 days, the statistical means of HRV, HR, and respiration showed a better reflection of an individual's health condition compared to monitoring the vital signs in a single day or night, and better was the classification performance for COPD diagnosis. Further, the statistical means of RRF, HF, and RR are crucial features for diagnosing COPD, demonstrating the importance of monitoring HRV and respiration during night sleep.

Drosophila immune cells transport oxygen through PPO2 protein phase transition.

Insect respiration has long been thought to be solely dependent on an elaborate tracheal system without assistance from the circulatory system or immune cells1,2. Here we describe that Drosophila crystal cells-myeloid-like immune cells called haemocytes-control respiration by oxygenating Prophenoloxidase 2 (PPO2) proteins. Crystal cells direct the movement of haemocytes between the trachea of the larval body wall and the circulation to collect oxygen. Aided by copper and a neutral pH, oxygen is trapped in the crystalline structures of PPO2 in crystal cells. Conversely, PPO2 crystals can be dissolved when carbonic anhydrase lowers the intracellular pH and then reassembled into crystals in cellulo by adhering to the trachea. Physiologically, larvae lacking crystal cells or PPO2, or those expressing a copper-binding mutant of PPO2, display hypoxic responses under normoxic conditions and are susceptible to hypoxia. These hypoxic phenotypes can be rescued by hyperoxia, expression of arthropod haemocyanin or prevention of larval burrowing activity to expose their respiratory organs. Thus, we propose that insect immune cells collaborate with the tracheal system to reserve and transport oxygen through the phase transition of PPO2 crystals, facilitating internal oxygen homeostasis in a process that is comparable to vertebrate respiration.

Relative Severity of Human Performance Decrements Recorded in Rapid vs. Gradual Decompression.

INTRODUCTION: Cabin decompression presents a threat in high-altitude-capable aircraft. A chamber study was performed to compare effects of rapid (RD) vs. gradual decompression and gauge impairment at altitude with and without hypoxia, as well as to assess recovery.METHODS: There were 12 participants who completed RD (1 s) and Gradual (3 min 12 s) ascents from 2743-7620 m (9000-25000 ft) altitude pressures while breathing air or 100% O2. Physiological indices included oxygen saturation (SPo2), heart rate (HR), respiration, end tidal O2 and CO2 partial pressures, and electroencephalography (EEG). Cognition was evaluated using SYNWIN, which combines memory, arithmetic, visual, and auditory tasks. The study incorporated ascent rate (RD, gradual), breathing gas (air, 100% O2) and epoch (ground-level, pre-breathe, ascent-altitude, recovery) as factors.RESULTS: Physiological effects in hypoxic "air" ascents included decreased SPo2 and end tidal O2 and CO2 partial pressures (hypocapnia), with elevated HR and minute ventilation (V˙E); SPo2 and HR effects were greater after RD (-7.3% lower and +10.0 bpm higher, respectively). HR and V˙E decreased during recovery. SYNWIN performance declined during ascent in air, with key metrics, including composite score, falling further (-75% vs. -50%) after RD. Broad cognitive impairment was not recorded on 100% O2, nor in recovery. EEG signals showed increased slow-wave activity during hypoxia.DISCUSSION: In hypoxic exposures, RD impaired performance more than gradual ascent. Hypobaria did not comprehensively impair performance without hypoxia. Lingering impairment was not observed during recovery, but HR and V˙E metrics suggested compensatory slowing following altitude stress. Participants' cognitive strategy shifted as hypoxia progressed, with efficiency giving way to "satisficing," redistributing effort to easier tasks.Beer J, Mojica AJ, Blacker KJ, Dart TS, Morse BG, Sherman PM. Relative severity of human performance decrements recorded in rapid vs. gradual decompression. Aerosp Med Hum Perform. 2024; 95(7):353-366.

Acid-sensing ion channel 1 in nucleus tractus solitarii neurons contributes to the enhanced CO2-stimulated cardiorespiratory effect in spontaneously hypertensive rats.

AIMS: Activation of central respiratory chemoreceptors provides excitatory drive to both respiratory and sympathetic outputs. The enhanced respiratory-sympathetic coupling contributes to the onset and development of hypertension. However, the specific central targets and molecular mechanisms involved in this process remain elusive. This study aimed to investigate the role of acid-sensing ion channel 1 (ASIC1) in nucleus tractus solitarii (NTS) neurons in CO2-stimulated cardiorespiratory effects in spontaneously hypertensive rats (SHRs). MAIN METHODS: Respiration and blood pressure of conscious rats were recorded by whole-body plethysmography and telemetry, respectively. Western blot was used to detect the expression difference of ASIC1 protein in NTS region between Wistar-Kyoto (WKY) rats and SHRs. Excitability of NTS neurons were assessed by extracellular recordings. KEY FINDINGS: Compared to WKY rats, the enhanced CO2-stimulated cardiopulmonary effect and up-regulation of ASIC1 in the NTS were already observed in 4-week-old prehypertensive SHRs. Furthermore, specific blockade of ASIC1 effectively attenuated the CO2-stimulated increase in firing rate of NTS neurons in anesthetized adult SHRs. Intracerebroventricular injections of the ASIC1a blocker PcTx1 or knockdown Asic1 in NTS neurons significantly reduced the heightened CO2-stimulated ventilatory response, and diminished the CO2-stimulated increase in arterial pressure and heart rate in adult SHRs. SIGNIFICANCE: These findings showed that dysregulated ASIC1 signaling in the NTS contribute to the exaggerated CO2-stimulated cardiorespiratory effects observed in SHRs.

Patient's airway monitoring during cardiopulmonary resuscitation using deep networks.

Cardiopulmonary resuscitation (CPR) is a crucial life-saving technique commonly administered to individuals experiencing cardiac arrest. Among the important aspects of CPR is ensuring the correct airway position of the patient, which is typically monitored by human tutors or supervisors. This study aims to utilize deep transfer learning for the detection of the patient's correct and incorrect airway position during cardiopulmonary resuscitation. To address the challenge of identifying the airway position, we curated a dataset consisting of 198 recorded video sequences, each lasting 6-8 s, showcasing both correct and incorrect airway positions during mouth-to-mouth breathing and breathing with an Ambu Bag. We employed six cutting-edge deep networks, namely DarkNet19, EfficientNetB0, GoogleNet, MobileNet-v2, ResNet50, and NasnetMobile. These networks were initially pre-trained on computer vision data and subsequently fine-tuned using the CPR dataset. The validation of the fine-tuned networks in detecting the patient's correct airway position during mouth-to-mouth breathing achieved impressive results, with the best sensitivity (98.8 %), specificity (100 %), and F-measure (97.2 %). Similarly, the detection of the patient's correct airway position during breathing with an Ambu Bag exhibited excellent performance, with the best sensitivity (100 %), specificity (99.8 %), and F-measure (99.7 %).

Performance of cone-beam computed tomography imaging during megavoltage beam irradiation under phase-gated conditions.

PURPOSE: Target positions should be acquired during beam delivery for accurate lung stereotactic body radiotherapy. We aimed to perform kilovoltage (kV) imaging during beam irradiation (intra-irradiation imaging) under phase-gated conditions and evaluate its performance. METHODS: Catphan 504 and QUASAR respiratory motion phantoms were used to evaluate image quality and target detectability, respectively. TrueBeam STx linac and the Developer Mode was used. The imaging parameters were 125 kVp and 1.2 mAs/projection. Flattened megavoltage (MV) X-ray beam energies 6, 10 and 15 MV and un-flattened beam energies 6 and 10 MV were used with field sizes of 5 × 5 and 15 × 15 cm2 and various frame rates for intra-irradiation imaging. In addition, using a QUASAR phantom, intra-irradiation imaging was performed during intensity-modulated plan delivery. The root-mean-square error (RMSE) of the CT-number for the inserted rods, image noise, visual assessment, and contrast-to-noise ratio (CNR) were evaluated. RESULTS: The RMSEs of intra-irradiation cone-beam computed tomography (CBCT) images under gated conditions were 50-230 Hounsfield Unit (HU) (static < 30 HU). The noise of the intra-irradiation CBCT images under gated conditions was 15-35 HU, whereas that of the standard CBCT images was 8.8-27.2 HU. Lower frame rates exhibited large RMSEs and noise; however, the iterative reconstruction algorithm (IR) was effective at improving these values. Approximately 7 fps with the IR showed an equivalent CNR of 15 fps without the IR. The target was visible on all the gated intra-irradiation CBCT images. CONCLUSION: Several image quality improvements are required; however, intra-irradiated CBCT images showed good visual target detection.

BREATHE DMD: boosting respiratory efficacy after therapeutic hypoxic episodes in Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a fatal genetic neuromuscular disorder, characterised by progressive decline in skeletal muscle function due to the secondary consequences of dystrophin deficiency. Weakness extends to the respiratory musculature, and cardiorespiratory failure is the leading cause of death in men with DMD. Intermittent hypoxia has emerged as a potential therapy to counteract ventilatory insufficiency by eliciting long-term facilitation of breathing. Mechanisms of sensory and motor facilitation of breathing have been well delineated in animal models. Various paradigms of intermittent hypoxia have been designed and implemented in human trials culminating in clinical trials in people with spinal cord injury and amyotrophic lateral sclerosis. Application of therapeutic intermittent hypoxia to DMD is considered together with discussion of the potential barriers to progression owing to the complexity of this devastating disease. Notwithstanding the considerable challenges and potential pitfalls of intermittent hypoxia-based therapies for DMD, we suggest it is incumbent on the research community to explore the potential benefits in pre-clinical models. Intermittent hypoxia paradigms should be implemented to explore the proclivity to express respiratory plasticity with the longer-term aim of preserving and potentiating ventilation in pre-clinical models and people with DMD.

Impact of setup and geometric uncertainties on the robustness of free-breathing photon radiotherapy of small lung tumors.

PURPOSE: Respiratory motion and patient setup error both contribute to the dosimetric uncertainty in radiotherapy of lung tumors. Managing these uncertainties for free-breathing treatments is usually done by margin-based approaches or robust optimization. However, breathing motion can be irregular and concerns have been raised for the robustness of the treatment plans. We have previously reported the dosimetric effects of the respiratory motion, without setup uncertainties, in lung tumor photon radiotherapy using free-breathing images. In this study, we include setup uncertainty. METHODS: Tumor positions from cine-CT images acquired in free-breathing were combined with per-fraction patient shifts to simulate treatment scenarios. A total of 14 patients with 300 tumor positions were used to evaluate treatment plans based on 4DCT. Four planning methods aiming at delivering 54 Gy as median tumor dose in three fractions were compared. The planning methods were denoted robust 4D (RB4), isodose to the PTV with a central higher dose (ISD), the ISD method normalized to the intended median tumor dose (IRN) and homogeneous fluence to the PTV (FLU). RESULTS: For all planning methods 95% of the intended dose was achieved with at least 90% probability with RB4 and FLU having equal CTV D50% values at this probability. FLU gave the most consistent results in terms of CTV D50% spread and dose homogeneity. CONCLUSIONS: Despite the simulated patient shifts and tumor motions being larger than observed in the 4DCTs the dosimetric impact was suggested to be small. RB4 or FLU are recommended for the planning of free-breathing treatments.

Prediction of fluid responsiveness in spontaneously breathing patients with hemodynamic stability: a prospective repeated-measures study.

Evaluating fluid responsiveness with dynamic parameters is recommended for fluid management. However, in hemodynamically stable patients who are breathing spontaneously, accurately measuring stroke volume variation via echocardiography and passive leg raising is challenging due to subtle SV changes. This study aimed to identify normal SV changes in healthy volunteers and evaluate the precision of hemodynamic parameters in screening mild hypovolemia in patients. This prospective, repeated-measures, cross-sectional study screened 269 subjects via echocardiography. Initially, 45 healthy volunteers underwent a fluid challenge test, the outcomes of which served as criteria to screen 215 ICU patients. Among these patients, 53 underwent additional fluid challenge testing. Hemodynamic parameters, including medians of maximum velocity time integrals (VTImaxs), peak velocity of VTImax (PV), internal jugular vein diameters (IJVD), and area (IJVA) were repeatedly measured first at a 60° upper body elevation (UBE), second in a supine position, third at UBE, fourth in a supine position, and lastly in a supine position after fluid loading. The hemodynamic responses to the position changes were compared between 83 fluid non-responders and 15 fluid responders. Fluid responsiveness was defined as fluid-induced medians' change of VTImaxs (fluid-induced median VTImax change) ≥ 10%. None of the healthy volunteers showed the mean value of repeatedly measured medians of VTImaxs ≥ 7%, following either UBE position (UBE-induced median VTImax change) or fluid loading (fluid-induced median VTImax change). UBE-induced median VTImax and PV changes were significantly correlated with fluid responsiveness (p < 0.001, AUC 0.959; p < 0.001, AUC 0.804). The significant correlations were demonstrated via multivariable analysis using binary logistic regression (p = 0.001, OR 90.1) and the correlation coefficient (R2 = 0.793) using linear regression analysis. UBE-induced median VTImax changes (≥ 11.8% and 7.98%) predicted fluid-induced median VTImax changes ≥ 10% and 7% (AUC 0.959 and 0.939). The collapsibility and variation of IJVD and IJVA showed no significant correlation. An increase in the mean value of medians of repeatedly measured VTImaxs transitioning from an UBE to a supine position, effectively screened mild hypovolemia and demonstrated a significant correlation with fluid responsiveness in spontaneously breathing patients maintaining hemodynamic stability.

Neural respiratory drive during maximal voluntary ventilation in individuals with hypertension: A case-control study.

Neural respiratory drive (NRD) is measured using a non-invasive recording of respiratory electromyographic signal. The parasternal intercostal muscle can assess the imbalance between the load and capacity of respiratory muscles and presents a similar pattern to diaphragmatic activity. We aimed to analyze the neural respiratory drive in seventeen individuals with hypertension during quite breathing and maximal voluntary ventilation (MVV) (103.9 ± 5.89 vs. 122.6 ± 5 l/min) in comparison with seventeen healthy subjects (46.5 ± 2.5 vs. 46.4 ± 2.4 years), respectively. The study protocol was composed of quite breathing during five minutes, maximum inspiratory pressure followed by maximal ventilatory ventilation (MVV) was recorded once for 15 seconds. Anthropometric measurements were collected, weight, height, waist, hip, and calf circumferences, waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), BMI, and conicity index (CI). Differences between groups were analyzed using the unpaired t-test or Mann-Whitney test to determine the difference between groups and moments. A significance level of 5% (p<0,05) was adopted for all statistical analyses. The group of individuals with hypertension presented higher values when compared to the healthy group for neural respiratory drive (EMGpara% 17.9±1.3 vs. 13.1±0.8, p = 0.0006) and neural respiratory drive index (NRDi (AU) 320±25 vs. 205.7±15,p = 0.0004) during quiet breathing and maximal ventilatory ventilation (EMGpara% 29.3±2.7 vs. 18.3±0.8, p = 0.000, NRDi (AU) 3140±259.4 vs. 1886±73.1,p<0.0001), respectively. In conclusion, individuals with hypertension presented higher NRD during quiet breathing and maximal ventilatory ventilation when compared to healthy individuals.