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Background and Aim: Breathing exercise is an exercise intended to promote effective and healthy breathing and breathing control. Virtual reality (VR) is defined as a computer-generated simulation, such as a set of images and sounds that represent a real place or situation that can be interacted within a seemingly real or physical way by a person using special electronic equipment. Breathing exercises with VR have shown benefits over conventional diaphragmatic breathing exercises in normal individuals in many new studies. We propose the use of a novel VR-based approach as a respiratory biofeedback to improve breathing patterns in chronic obstructive pulmonary disease (COPD) patients, decrease their work of breathing, and improve breathing control. Materials and Methods: In a randomized controlled study involving 72 COPD patients divided into two groups of 36 in each, the control and experimental groups performed a short 5 min breathing exercise for 6 consecutive days. In experimental group patients performed breathing exercise with VR goggles while in controls they performed without VR goggles. Results: Both the control and experimental groups showed improved changes in vitals and better quality of life, but not statistically as significant when compared to each other. Conclusion: Future studies need to address the long-term effects and stability of the results with a larger sample size, compare the approach with the existing treatments, and make the required smaller changes to the program for better outcomes.

Silent hypoxemia, or "happy hypoxia," is a puzzling phenomenon in which patients who have contracted COVID-19 exhibit very low oxygen saturation ( SaO 2 < 80%) but do not experience discomfort in breathing. The mechanism by which this blunted response to hypoxia occurs is unknown. We have previously shown that a computational model of the respiratory neural network (Diekman et al. in J Neurophysiol 118(4):2194–2215, 2017) can be used to test hypotheses focused on changes in chemosensory inputs to the central pattern generator (CPG). We hypothesize that altered chemosensory function at the level of the carotid bodies and/or the nucleus tractus solitarii are responsible for the blunted response to hypoxia. Here, we use our model to explore this hypothesis by altering the properties of the gain function representing oxygen sensing inputs to the CPG. We then vary other parameters in the model and show that oxygen carrying capacity is the most salient factor for producing silent hypoxemia. We call for clinicians to measure hematocrit as a clinical index of altered physiology in response to COVID-19 infection. [ABSTRACT FROM AUTHOR]

Background and Aim: Breathing exercise is an exercise intended to promote effective and healthy breathing and breathing control. Virtual reality (VR) is defined as a computer-generated simulation, such as a set of images and sounds that represent a real place or situation that can be interacted within a seemingly real or physical way by a person using special electronic equipment. Breathing exercises with VR have shown benefits over conventional diaphragmatic breathing exercises in normal individuals in many new studies. We propose the use of a novel VR-based approach as a respiratory biofeedback to improve breathing patterns in chronic obstructive pulmonary disease (COPD) patients, decrease their work of breathing, and improve breathing control. Materials and Methods: In a randomized controlled study involving 72 COPD patients divided into two groups of 36 in each, the control and experimental groups performed a short 5 min breathing exercise for 6 consecutive days. In experimental group patients performed breathing exercise with VR goggles while in controls they performed without VR goggles. Results: Both the control and experimental groups showed improved changes in vitals and better quality of life, but not statistically as significant when compared to each other. Conclusion: Future studies need to address the long-term effects and stability of the results with a larger sample size, compare the approach with the existing treatments, and make the required smaller changes to the program for better outcomes. [ABSTRACT FROM AUTHOR]

Purpose: Growing evidence suggests that respiratory frequency (fR) is a marker of physical effort and a variable sensitive to changes in exercise tolerance. The comparison between arm+leg cycling (Arm+leg) and leg cycling (Leg) has the potential to further test this notion because a greater exercise tolerance is expected in the Arm+leg modality. We systematically compared Arm+leg vs. Leg using different performance tests. Methods: Twelve males underwent six performance tests in separate, randomized visits. Three tests were performed in each of the two exercise modalities, i.e. an incremental test and two time-to-exhaustion (TTE) tests performed at 90% or 75% of the peak power output reached in the Leg incremental test (PPOLeg). Exercise tolerance, perceived exertion, and cardiorespiratory variables were recorded during all the tests. Results: A greater exercise tolerance (p < 0.001) was found for Arm+leg in the incremental test (337 ± 32W vs. 292 ± 28 W), in the TTE test at 90% of PPOLeg (638 ± 154 s vs. 307 ± 67 s), and in the TTE test at 75% of PPOLeg (1,675 ± 525 s vs. 880 ± 363 s). Unlike ...O2 and heart rate, both fR and minute ventilation were lower (p < 0.003) at isotime in all the Arm+leg tests vs. Leg tests. Furthermore, a lower perceived exertion was observed in the Arm+leg tests, especially during the TTE tests (p < 0.001). Conclusion: Minute ventilation, fR and perceived exertion are sensitive to the improvements in exercise tolerance observed when comparing Arm+leg vs. Leg, unlike ...O2 and heart rate. [ABSTRACT FROM AUTHOR]

In 1998, I was asked by the American Physiological Society to review a book written by Dr. Michael de Burgh Daly, Peripheral Arterial Chemoreceptors and Respiratory-Cardiovascular Integration. Inspired by this work, I came to appreciate how researchers in the later stages of their careers and who provide a detailed review of their experimental approach might effectively contribute to science, especially to the benefit of young scientists (Yu J. The Physiologist 41: 231, 1998.). This article is written in that vein. Over several decades of intensive investigation of cardiopulmonary reflexes, focused on the sensory receptors, my colleagues and I advanced a novel multiple-sensor theory (MST) to explain the role of the vagal mechanosensory system. Described here is our research journey through various stages of developing MST and the process of how the problem was identified, approached, and tackled. MST redefines conventional mechanosensor doctrines and is supported by new studies that clarify a century of research data. It entails reinterpretation of many established findings. Hopefully, this article will benefit young scientists, such as graduate and postdoctoral students in the cardiopulmonary sensory research field. [ABSTRACT FROM AUTHOR]

Background: Respiratory motion presents a challenge in radiotherapy of thoracic and upper abdominal tumors. Techniques to account for respiratory motion include tracking. Using magnetic resonance imaging (MRI) guided radiotherapy systems, tumors can be tracked continuously. Using conventional linear accelerators, tracking of lung tumors is possible by determining tumor motion on kilo voltage (kV) imaging. But tracking of abdominal tumors with kV imaging is hampered by limited contrast. Therefore, surrogates for the tumor are used. One of the possible surrogates is the diaphragm. However, there is no universal method for establishing the error when using a surrogate and there are particular challenges in establishing such errors during free breathing (FB). Prolonged breath‐holding might address these challenges. Purpose: The aim of this study was to quantify the error when using the right hemidiaphragm top (RHT) as surrogate for abdominal organ motion during prolonged breath‐holds (PBH) for possible application in radiation treatments. Methods: Fifteen healthy volunteers were trained to perform PBHs in two subsequent MRI sessions (PBH‐MRI1 and PBH‐MRI2). From each MRI acquisition, we selected seven images (dynamics) to determine organ displacement during PBH by using deformable image registration (DIR). On the first dynamic, the RHT, right and left hemidiaphragm, liver, spleen and right and left kidney were segmented. We used the deformation vector fields (DVF), generated by DIR, to determine the displacement of each organ between two dynamics in inferior‐superior (IS), anterior‐posterior (AP), left‐right (LR) direction and we calculated the 3D vector magnitude (|d|). The displacements of the RHT, both hemidiaphragms and the abdominal organs were compared using a linear fit to determine the correlation (R2 of the fit) and the displacement ratio (DR, slope of the fit) between displacements of the RHT and each organ. We quantified the median difference between the DRs of PBH‐MRI1 and PBH‐MRI2 for each organ. Additionally, we estimated organ displacement in the second PBH by applying the DR from the first PBH to the displacement of the RHT measured during the second PBH. We compared the estimated organ displacement to the measured organ displacement during the second PBH. The difference between the two values was defined as the estimation error of using the RHT as a surrogate and assuming a constant DR over MRI sessions. Results: The linear relationships were confirmed by the high R2 values of the linear fit between the displacements of the RHT and the abdominal organs (R2 > 0.96) in the IS and AP direction and |d|, and high to moderate correlations in the LR direction (0.93 > R2 > 0.64). The median DR difference between PBH‐MRI1 and PBH‐MRI2 varied between 0.13 and 0.31 for all organs. The median estimation error of the RHT as a surrogate varied between 0.4 and 0.8 mm/min for all organs. Conclusion: The RHT could serve as an accurate surrogate for abdominal organ motion during radiation treatments, for example, in tracking, provided the error of the RHT as motion surrogate is taken into account in the margins. Trial registration: The study was registered in the Netherlands Trial Register (NL7603). [ABSTRACT FROM AUTHOR]

Purpose: Growing evidence suggests that respiratory frequency (fR) is a marker of physical effort and a variable sensitive to changes in exercise tolerance. The comparison between arm+leg cycling (Arm+leg) and leg cycling (Leg) has the potential to further test this notion because a greater exercise tolerance is expected in the Arm+leg modality. We systematically compared Arm+leg vs. Leg using different performance tests.Methods: Twelve males underwent six performance tests in separate, randomized visits. Three tests were performed in each of the two exercise modalities, i.e. an incremental test and two time-to-exhaustion (TTE) tests performed at 90% or 75% of the peak power output reached in the Leg incremental test (PPOLeg). Exercise tolerance, perceived exertion, and cardiorespiratory variables were recorded during all the tests.Results: A greater exercise tolerance (p < 0.001) was found for Arm+leg in the incremental test (337 ± 32 W vs. 292 ± 28 W), in the TTE test at 90% of PPOLeg (638 ± 154 s vs. 307 ± 67 s), and in the TTE test at 75% of PPOLeg (1,675 ± 525 s vs. 880 ± 363 s). Unlike V˙O2 and heart rate, both fR and minute ventilation were lower (p < 0.003) at isotime in all the Arm+leg tests vs. Leg tests. Furthermore, a lower perceived exertion was observed in the Arm+leg tests, especially during the TTE tests (p < 0.001).Conclusion: Minute ventilation, fR and perceived exertion are sensitive to the improvements in exercise tolerance observed when comparing Arm+leg vs. Leg, unlike V˙O2 and heart rate.

Introduction: Chronic obstructive pulmonary disease (COPD) is a high disease burden and negatively impacts the bio-psycho-social well-being of patients, such as anxiety, depression, and shortness of breath. Anxiety and depression can increase morbidity and worsen the condition and health status of the patient. This systematic review aimed to analyze the effect of walking exercises with breathing control on the degree of shortness of breath, anxiety, and depression in COPD patients. Methods: The data sources were taken from EBSCO, PubMed, and ProQuest using related keywords. Articles were selected using the preferred reporting items for systematic reviews and meta-analyses (PRISMA) diagram method. Results: Ten articles in this systematic review obtained three intervention categories: 1) intervention combined walking exercises with breathing control can be performed 30 minutes per session 2-3 times a week; 2) walking exercise intervention is performed thrice a week for 30-45 minutes per session; 3) breathing control exercise intervention is performed 10-30 minutes with a duration of 2 times a day in the morning and night or can be performed three times a week. Those three intervention categories significantly reduced the degree of shortness of breath, anxiety, and depression in COPD patients. Conclusion: Findings from this systematic review suggest that walking exercise intervention in COPD patients can help reduce the degree of shortness of breath, anxiety, and depression.

The rhythmicity of breath is vital for normal physiology. Even so, breathing is enriched with multifunctionality. External signals constantly change breathing, stopping it when under water or deepening it during exertion. Internal cues utilize breath to express emotions such as sighs of frustration and yawns of boredom. Breathing harmonizes with other actions that use our mouth and throat, including speech, chewing, and swallowing. In addition, our perception of breathing intensity can dictate how we feel, such as during the slow breathing of calming meditation and anxiety-inducing hyperventilation. Heartbeat originates from a peripheral pacemaker in the heart, but the automation of breathing arises from neural clusters within the brainstem, enabling interaction with other brain areas and thus multifunctionality. Here, we document how the recent transformation of cellular and molecular tools has contributed to our appreciation of the diversity of neuronal types in the breathing control circuit and how they confer the multifunctionality of breathing. [ABSTRACT FROM AUTHOR]

The lack of a testable model explaining how ventilation is regulated in different exercise conditions has been repeatedly acknowledged in the field of exercise physiology. Yet, this issue contrasts with the abundance of insightful findings produced over the last century and calls for the adoption of new integrative perspectives. In this review, we provide a methodological approach supporting the importance of producing a set of evidence by evaluating different studies together—especially those conducted in 'real' exercise conditions—instead of single studies separately. We show how the collective assessment of findings from three domains and three levels of observation support the development of a simple model of ventilatory control which proves to be effective in different exercise protocols, populations and experimental interventions. The main feature of the model is the differential control of respiratory frequency (fR) and tidal volume (VT); fR is primarily modulated by central command (especially during high-intensity exercise) and muscle afferent feedback (especially during moderate exercise) whereas VT by metabolic inputs. Furthermore, VT appears to be fine-tuned based on fR levels to match alveolar ventilation with metabolic requirements in different intensity domains, and even at a breath-by-breath level. This model reconciles the classical neuro-humoral theory with apparently contrasting findings by leveraging on the emerging control properties of the behavioural (i.e. fR) and metabolic (i.e. VT) components of minute ventilation. The integrative approach presented is expected to help in the design and interpretation of future studies on the control of fR and VT during exercise. [ABSTRACT FROM AUTHOR]

Abstract Background Due to respiratory motion, accurate radiotherapy delivery to thoracic and abdominal tumors is challenging. We aimed to quantify the ability of mechanical ventilation to reduce respiratory motion, by measuring diaphragm motion magnitudes in the same volunteers during free breathing (FB), mechanically regularized breathing (RB) at 22 breaths per minute (brpm), variation in mean diaphragm position across multiple deep inspiration breath-holds (DIBH) and diaphragm drift during single prolonged breath-holds (PBH) in two MRI sessions. Methods In two sessions, MRIs were acquired from fifteen healthy volunteers who were trained to be mechanically ventilated non-invasively We measured diaphragm motion amplitudes during FB and RB, the inter-quartile range (IQR) of the variation in average diaphragm position from one measurement over five consecutive DIBHs, and diaphragm cranial drift velocities during single PBHs from inhalation (PIBH) and exhalation (PEBH) breath-holds. Results RB significantly reduced the respiratory motion amplitude by 39%, from median (range) 20.9 (10.6–41.9) mm during FB to 12.8 (6.2–23.8) mm. The median IQR for variation in average diaphragm position over multiple DIBHs was 4.2 (1.0–23.6) mm. During single PIBHs with a median duration of 7.1 (2.0–11.1) minutes, the median diaphragm cranial drift velocity was 3.0 (0.4–6.5) mm/minute. For PEBH, the median duration was 5.8 (1.8–10.2) minutes with 4.4 (1.8–15.1) mm/minute diaphragm drift velocity. Conclusions Regularized breathing at a frequency of 22 brpm resulted in significantly smaller diaphragm motion amplitudes compared to free breathing. This would enable smaller treatment volumes in radiotherapy. Furthermore, prolonged breath-holding from inhalation and exhalation with median durations of six to seven minutes are feasible. Trial registration Medical Ethics Committee protocol NL.64693.018.18.

• 6-OHDA Parkinson's disease (PD) animal model causes significant respiratory deficits. • Apocynin prevents oxidative stress (OS) in respiratory nuclei in the 6-OHDA model. • Apocynin-mediated OS inhibition reduces respiratory neurodegeneration in the 6-OHDA model. • Apocynin inhibits OS, which prevents breathing impairment in the 6-OHDA PD model. • A new perspective to improve breathing and the quality of life of PD patients is provided. Parkinson's Disease (PD) is a neurogenerative disorder characterized by the death of dopaminergic neurons in the Substantia Nigra pars compacta (SNpc), leading to motor, cognitive, learning, and respiratory dysfunctions. New evidence revealed that breathing impairment in PD mainly results from oxidative stress (OS) that initiates apoptotic signaling in respiratory neurons. Here, we investigated the role of OS inhibition using apocynin (non-specific NADPH oxidase inhibitor) in a 6-OHDA PD animal model in the neural control of breathing. The PD model was confirmed with a 70% reduction in TH-expressing neurons within the SNpc. After 20 and 40 days of PD induction, no differences were observed in superoxide anion levels in any respiratory nuclei. At 30 days after PD induction, 6-OHDA animals presented OS that was prevented in all respiratory nuclei by adding apocynin to the drinking water for 10 days. Forty days after PD animal model induction, impaired motor and breathing function, reduced Phox2b and NK1 receptors-expressing neurons in the medullary respiratory areas; decreased latency to fall in the rotarod motor test; and attenuated respiratory frequency and minute ventilation parameters at rest and under hypercapnia conditions were observed. After 20 days of apocynin treatment, neurodegeneration of respiratory nuclei and breathing dysfunction in 6-OHDA animals were prevented. Thus, OS contributes to respiratory neuron death, consequently leading to breathing dysfunction in the 6-OHDA PD animal model. Furthermore, these results present a new perspective for preventing the onset and progression of PD-related respiratory impairments. [ABSTRACT FROM AUTHOR]

Background: Heart rate variability (HRV) is the change in time intervals between heart beats, reflecting the autonomic nervous system's ability to adapt to psychological and physiological demands. Slow breathing enhances parasympathetic activity, increasing HRV. Pranayama , a yoga breathing technique, affords the conscious regulation of respiration frequency. This study aimed to characterize HRV, blood pressure and peripheral oxygen saturation of basic yoga breathing slow techniques with regular yoga practitioners. Methods: In total, 45 yoga practitioners were included in the study (including 7 males, mean age of 54.04 ± 11.97 years) with varying levels of yoga experience (minimum 3 months, maximum 37 years). Participants performed three breathing conditions: baseline (control) and two yoga techniques (abdominal ( adham ) and complete ( mahat )) breathing, each for 10 min in the supine position (i.e., savasana ). For each condition, respiratory frequency, heart rate (HR), blood pressure and peripheral oxygen levels were collected. Results: The findings revealed that both abdominal and complete yoga breathing techniques promoted a decrease in respiratory frequency ( p < 0.001, r = 0.61; p < 0.001, r = 0.61, respectively), and an increase in peripheral oxygen saturation ( p < 0.001, r = 0.50; p < 0.001, r = 0.46, respectively), along with blood pressure decreases in all mean values, and a significant decrease in systolic pressure, considering all conditions ( p = 0.034, W = 0.08). There were significant increases in standard deviation of HR during abdominal and complete yoga breathing techniques compared with the baseline ( p = 0.003, r = 0.31; p < 0.001, r = 0.47, respectively), indicating enhanced parasympathetic activity. Moreover, the complete breathing technique exhibited the greatest variability in HRV measures, with several significant differences compared with abdominal breathing (standard deviation of HR, p < 0.001, r = 0.42; SD2, standard deviation of points perpendicular to the Poincaré parallel line, p < 0.003, r = 0.31; SD1/SD2, p < 0.003, r = 0.31), suggesting a more profound impact on autonomic modulation. Conclusions: simple, inexpensive and non-intrusive abdominal and complete yoga breathing techniques can effectively and momentarily enhance HRV and oxygen saturation in adults, mature adults and the elderly.

Background: Severe pain during the first stage of labour can harm both the mother and fetus. Previous studies have shown that severe pain in childbirth can cause discomfort, stress, risk of depressive disorders, decreased intestinal motility and prolonged labour for the mother. For the fetus, it can cause hypoxia, metabolic acidosis, cognitive and emotional disorders and even death. Therefore, better management of labour pain during the first stage is needed. Aim: This study aimed to assess the effect of sensory stimulation to reduce pain in the first stage of labour. Methods: Garuda portal, the Perpustakaan Nasional Republik Indonesia e-resource, the Cochrane Central Register of Controlled Trials and Pubmed were used to search for literature. The inclusion criteria were original randomised controlled trials published in English, in 2014–2020, with a minimum sample size of 30 where the study outcome was rated on a pain scale. Results: Ten randomised controlled trials were included. The primary interventions using sensory stimulation to reduce pain during the first stage of labour were aromatherapy, music therapy, breathing control, focusing, and virtual reality. Conclusions: Sensory stimulation by aromatherapy, music therapy, breathing control, focusing and virtual reality are effective in reducing pain in the first stage of labour. [ABSTRACT FROM AUTHOR]

Highly trained aerobic athletes progressively use most of their breathing reserve with increased exercise intensity during whole-body exercise. Additionally, females typically present proportionally smaller lungs than males. Therefore, sex, exercise intensity, and breathing reserve use likely influence the volume and time in which respiratory parameters vary between consecutive breaths during whole-body exercise. However, breath-by-breath variability has been scarcely investigated during exercise. Accordingly, we sought to investigate breath-by-breath pulmonary ventilation (V̇ E), tidal volume (V T), and respiratory frequency (f R) variability during a maximal treadmill incremental exercise test in 17 females and 18 males highly trained professional endurance runners. The breath-by-breath variability was analyzed by root mean square of successive differences (RMSSD) within 1-minute windows. Females had lower absolute and percent predicted forced expiratory volume in one second (FEV 1) and forced vital capacity (FVC) than males, as well as lower height-adjusted absolute FVC than males. V̇ E and V T reserve use were similar between the sexes at peak exercise. While RMSSDV̇ E and RMSSD f R did not change over exercise (P > 0.05), RMSSDV T progressively decreased (P < 0.001). RMSSDV T was negatively correlated with V T reserve use only in males. Females showed lower RMSSDV̇ E than males during the entire exercise test (P < 0.001). At iso-V̇ E reserve use, between-sex differences in RMSSDV̇ E persisted (P = 0.003). Our findings indicate that exercise intensity decreases V T variability in professional runners, which is linked to V T reserve use in males but not females. Additionally, the female sex lowers V̇ E variability regardless of exercise intensity and V̇ E reserve use. • Breath-by-breath V̇ E , V T , and f R variability are barely studied during exercise. • Over incremental exercise, V T variability reduces, V̇ E and f R variability remain constant. • V T reserve use modulates V T variability in males but not females. • Females have lower V̇ E variability over incremental exercise than males. • The between-sex difference in V̇ E variability persists at iso-V̇ E reserve use. [ABSTRACT FROM AUTHOR]

Background: Due to respiratory motion, accurate radiotherapy delivery to thoracic and abdominal tumors is challenging. We aimed to quantify the ability of mechanical ventilation to reduce respiratory motion, by measuring diaphragm motion magnitudes in the same volunteers during free breathing (FB), mechanically regularized breathing (RB) at 22 breaths per minute (brpm), variation in mean diaphragm position across multiple deep inspiration breath-holds (DIBH) and diaphragm drift during single prolonged breath-holds (PBH) in two MRI sessions. Methods: In two sessions, MRIs were acquired from fifteen healthy volunteers who were trained to be mechanically ventilated non-invasively We measured diaphragm motion amplitudes during FB and RB, the inter-quartile range (IQR) of the variation in average diaphragm position from one measurement over five consecutive DIBHs, and diaphragm cranial drift velocities during single PBHs from inhalation (PIBH) and exhalation (PEBH) breath-holds. Results: RB significantly reduced the respiratory motion amplitude by 39%, from median (range) 20.9 (10.6–41.9) mm during FB to 12.8 (6.2–23.8) mm. The median IQR for variation in average diaphragm position over multiple DIBHs was 4.2 (1.0–23.6) mm. During single PIBHs with a median duration of 7.1 (2.0–11.1) minutes, the median diaphragm cranial drift velocity was 3.0 (0.4–6.5) mm/minute. For PEBH, the median duration was 5.8 (1.8–10.2) minutes with 4.4 (1.8–15.1) mm/minute diaphragm drift velocity. Conclusions: Regularized breathing at a frequency of 22 brpm resulted in significantly smaller diaphragm motion amplitudes compared to free breathing. This would enable smaller treatment volumes in radiotherapy. Furthermore, prolonged breath-holding from inhalation and exhalation with median durations of six to seven minutes are feasible. Trial registration: Medical Ethics Committee protocol NL.64693.018.18. [ABSTRACT FROM AUTHOR]

Stereotactic ablative radiotherapy (SABR) aims to deliver high doses of radiation to kill cancer cells and shrink tumors in less than or equal to 6 fractions. However, organ motion during treatment is a challenging issue for this kind of technique. We develop a control system via Bluetooth technology to simulate and correct body motion during SABR. Methods: Radiation doses were analyzed, and the radiation damage protection capability was checked by external beam therapy 3 (EBT3) films irradiated by a linear accelerator. A wireless signal test was also performed. A validation was performed with 8 previously treated patient respiratory pattern records and 8 healthy volunteers. Results: The homemade simulation system consisted of 2 linear actuators, one movable stage with a maximal moving distance of 6.5 cm × 12.5 cm × 5 cm to simulate the respiratory pattern of 8 patients precisely with a median error of 0.36 mm and a maximal motion difference of 1.17 mm, and 3.17 and chipset transited signals to display them as a waveform. From the test with 8 volunteers, the chip could detect deep respiratory movement up to 3 cm. The effect of the chip on a radiation dose of 400 monitor units (MUs) by 6 MV photons and 200 MUs by 10 MV photons showed high penetration rates of 98.8% and 98.6%, respectively. Conclusions: We invented a tubeless and wireless respiratory gating detection chip. The chip has minimal interference with the treatment angles, good noise immunity and the capability to easily penetrate a variety of materials. The simulation system consisting of linear actuators also successfully simulates the respiratory pattern of real patients. [ABSTRACT FROM AUTHOR]

Background: Sudden infant death syndrome (SIDS) is a tragic incident which remains a mystery even after post-mortem investigation and thorough researches.Methods: This comprehensive review is based on the genes reported in the molecular autopsy studies conducted on SIDS so far. A total of 20 original studies and 7 case reports were identified and included in this analysis. The genes identified in children or adults were not included. Most of the genes reported in these studies belonged to cardiac channel and cardiomyopathy. Cardiac channel genes in SIDS were scrutinized for further analysis.Results: After screening and removing the duplicates, 42 unique genes were extracted. When the location of these genes was assessed, it was observed that most of these belonged to Chromosomes 11, 1 and 3 in sequential manner. The pathway analysis shows that these genes are involved in the regulation of heart rate, action potential, cardiac muscle cell contraction and heart contraction. The protein-protein interaction network was also very big and highly interactive. SCN5A, CAV3, ALG10B, AKAP9 and many more were mainly found in these cases and were regulated by many transcription factors such as MYOG C2C1 and CBX3 HCT11. Micro RNA, “hsa-miR-133a-3p” was found to be prevalent in the targeted genes.Conclusions: Molecular and computational approaches are a step forward toward exploration of these sad demises. It is so far a new arena but seems promising to dig out the genetic cause of SIDS in the years to come.

New Findings: This article reviews a unique direct injection technique that complements the more conventional right atrial injection and aerosol delivery methods to study sensory and reflex effects of the lung sensors. Used in combination with other methods, this technique should contribute to the pulmonary sensory research. The lungs house sensory receptors (sensors) that mediate a variety of sensory and reflex responses to mechanical or chemical changes. These reflexes are mainly carried through pulmonary sympathetic and vagal afferent pathways. The chemosensors in the lung periphery are especially important in pulmonary diseases and their reflex responses have traditionally been studied either by aerosol delivery, which also activates receptors in the central airways, or by right atrial injection, which also activates receptors lying outside the lung. Thus, these techniques may confound the interpretation of sensory function. Our laboratory has developed a direct injection technique to deliver agents into the lung parenchyma, which complements the conventional techniques with some important advantages. This article reviews the technique. [ABSTRACT FROM AUTHOR]

In this short review, we provide an overview of developmental disorders causing autonomic nervous system dysregulation. We briefly discuss perinatal conditions that adversely impact developmental outcomes including apnea of prematurity, sudden infant death syndrome, and Rett syndrome. We provide a brief clinical description, an overview of known or hypothesized mechanisms for the disorder, and current standard of practice for treatment of each condition. Additionally, we consider preventative measures and complications of these disorders to provide further insight into the pathogenesis of specific autonomic dysregulation in neonates. The goal of this short review is to provide an updated understanding of the impact of autonomic dysregulation on development of brainstem circuits and to briefly highlight promising future treatment options and controversies. [ABSTRACT FROM AUTHOR]

This study investigated the respiratory activity in adult Wistar rats across different behavioral seizure severity induced by pentylenetetrazole (PTZ). Animals underwent surgery for electrodes implantation, allowing simultaneous EEG and diaphragm EMG (DIA EMG) recordings and the respiratory frequency and DIA EMG amplitude were measured. Seizures were acutely induced through PTZ injection and classified based on a pre-established score, with absence-like seizures (spike wave discharge (SWD) events on EEG) representing the lowest score. The respiratory activity was grouped into the different seizure severities. During absence-like and myoclonic jerk seizures, the breathing frequency decreased significantly (∼50% decrease) compared to pre- and post-ictal periods. Pronounced changes occurred with more severe seizures (clonic and tonic) with periods of apnea, especially during tonic seizures. Apnea duration was significantly higher in tonic compared to clonic seizures. Notably, during PTZ-induced tonic seizures the apnea events were marked by tonic DIA EMG contraction (tonic-phase apnea). In the majority of animals (5 out of 7) this was a fatal event in which the seizure-induced respiratory arrest preceded the asystole. In conclusion, we provide an assessment of the respiratory activity in the PTZ-induced acute seizures and showed that breathing dysfunction is more pronounced in seizures with higher severity. • This study assessed the respiratory activity in rats with varied seizure severities; • EEG and diaphragm EMG were recorded simultaneously; • PTZ-induced acute seizures revealed significant breathing alterations; • Breathing dysfunction is more pronounced in seizures with higher severity. • Tonic seizures exhibited tonic-phase apnea, leading to fatal respiratory arrest. [ABSTRACT FROM AUTHOR]

We have investigated the potential acute desensitizing role of the β arrestin 2 (β-arr2) pathway on the ventilatory depression produced by levels of fentanyl ranging from analgesic to life-threatening (0.1 to 60 mg/kg ip) in control and β-arr2-deficient nonsedated mice. Fentanyl at doses of 0.1, 0.5, and 1 mg/kg ip-corresponding to the doses previously used to study the role of β-arr2 pathway-decreased ventilation, but along the V̇e/V̇co2 relationship established in baseline conditions. This reduction in ventilation was therefore indistinguishable from the decrease in breathing during the periods of spontaneous immobility. Above 1.5 mg/kg, however, ventilation was depressed out of proportion of the changes in metabolic rate, suggesting a specific depression of the drive to breathe. The ventilatory responses were similar between the two groups. At high doses of fentanyl (60 mg/kg ip) 1 out of 20 control mice died by apnea versus 8 out of 20 β-arr2-deficient mice (P = 0.008). In the surviving mice, ventilation was however identical in both groups. The ventilatory effects of fentanyl in β-arr2-deficient mice, reported in the literature, are primarily mediated by the "indirect" effects of sedation/hypometabolism on breathing control. There was an excess mortality at very high doses of fentanyl in the β-arr2-deficient mice, mechanisms of which are still open to question, as the capacity of maintaining a rhythmic, although profoundly depressed, breathing activity remains similar in all of the surviving control and β-arr2-deficient mice. NEW & NOTEWORTHY When life-threatening doses of fentanyl are used in mice, the β-arrestin 2 pathway appears to play a critical role in the recovery from opioid overdose. This observation calls into question the use of G protein-biased μ-opioid receptor agonists, as a strategy for safer opioid analgesic drugs. [ABSTRACT FROM AUTHOR]

Key points: Parkinson's disease (PD) is associated with respiratory dysfunction. In the 6‐OHDA rat model of PD this is seen as a reduction in respiratory frequency and minute ventilation during normoxia and hypercapnia stimulus.Respiratory dysfunction is caused by neuronal death of medullary respiratory nuclei in the 6‐OHDA model of PD.Oxidative stress can be considered a strong candidate for neurodegeneration via miR‐34c downregulation and pro‐apoptotic signalling in respiratory neurons, preceding the functional impairment observed in the 6‐OHDA model of PD. Parkinson's disease (PD) is a neurodegenerative disease caused by dopaminergic neuron death in the substantia nigra (SN). New evidence has revealed that this neurodegeneration is the result of complex interactions between genetic abnormalities, environmental toxins, mitochondrial dysfunction and disruption of the blood–brain barrier (BBB) in the SN. In addition to classic symptoms, PD patients also exhibit respiratory failure. Here, we investigated whether oxidative stress was associated with neurodegeneration in a respiratory group (RG) of 6‐OHDA‐treated rats, which act as a model of PD. We analysed how oxidative stress affected apoptotic signalling in the RG 30 days after 6‐OHDA treatment, shortly before commencement of breathing impairment (40 days). After 30 days, a dihydroethidium assay showed increased oxidative stress in the RG, anti‐apoptotic signalling, as shown by an increase in p‐Akt and BcL‐2 and a decrease in Bax in the caudal aspect of the nucleus of the solitary tract (cNTS), and a decrease in p‐p38 and Bax levels in the retrotrapezoid nucleus (RTN); pro‐apoptotic signalling was indicated by a decrease in p‐Akt and BcL‐2 and an increase in Bax in the rostral ventral respiratory group (rVRG) and pre‐Botzinger complex (preBotC). miR‐34c, a known oxidative stress protector, was downregulated in 6‐OHDA animals in the RC. After 40 days of 6‐OHDA, the NTS, rVRG, preBotC and RTN exhibited reduced NeuN immunoreactivity, no BBB disruption and an increase in thiobarbituric acid reactivity. We conclude that in the 6‐OHDA model of PD, oxidative stress contributes to neurodegeneration in medullary respiratory neurons. Key points: Parkinson's disease (PD) is associated with respiratory dysfunction. In the 6‐OHDA rat model of PD this is seen as a reduction in respiratory frequency and minute ventilation during normoxia and hypercapnia stimulus.Respiratory dysfunction is caused by neuronal death of medullary respiratory nuclei in the 6‐OHDA model of PD.Oxidative stress can be considered a strong candidate for neurodegeneration via miR‐34c downregulation and pro‐apoptotic signalling in respiratory neurons, preceding the functional impairment observed in the 6‐OHDA model of PD. [ABSTRACT FROM AUTHOR]

Key points: Expiratory muscles (abdominal and thoracic) can be recruited when respiratory drive increases under conditions of increased respiratory demand such as hypercapnia. Studying hypercapnia‐induced active expiration in unanaesthetized rats importantly contributes to the understanding of how the control system is integrated in vivo in freely moving animals. In unanaesthetized rats, hypercapnia‐induced active expiration was not always recruited either in wakefulness or in sleep, suggesting that additional factors influence the recruitment of active expiration. The pattern of abdominal muscle recruitment varied in a state‐dependent manner with active expiration being more predominant in the sleep state than in quiet wakefulness. Pulmonary ventilation was enhanced in periods with active expiration compared to periods without it. Abstract: Expiration is passive at rest but becomes active through recruitment of abdominal muscles under increased respiratory drive. Hypercapnia‐induced active expiration has not been well explored in unanaesthetized rats. We hypothesized that (i) CO2‐evoked active expiration is recruited in a state‐dependent manner, i.e. differently in sleep or wakefulness, and (ii) recruitment of active expiration enhances ventilation, hence having an important functional role in meeting metabolic demand. To test these hypotheses, Wistar rats (280–330 g) were implanted with electrodes for EEG and electromyography EMG of the neck, diaphragm (DIA) and abdominal (ABD) muscles. Active expiratory events were considered as rhythmic ABDEMG activity interposed to DIAEMG. Animals were exposed to room air followed by hypercapnia (7% CO2) with EEG, EMG and ventilation ( V ̇ E) recorded throughout the experimental protocol. No active expiration was observed during room air exposure. During hypercapnia, CO2‐evoked active expiration was predominantly recruited during non‐rapid eye movement sleep. Its increased occurrence during sleep was evidenced by the decreased DIA‐to‐ADB ratio (1:1 ratio means that each DIA event is followed by an ABD event, indicating a high occurrence of ABD activity). Moreover, V ̇ E was also enhanced (P < 0.05) in periods with active expiration. V ̇ E had a positive correlation (P < 0.05) with the peak amplitude of ABDEMG activity. The data demonstrate strongly that hypercapnia‐induced active expiration increases during sleep and provides an important functional role to support V ̇ E in conditions of increased respiratory demand. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of "breathing control" on sonographic diaphragmatic excursion. Method: A prospective, randomized, assessor-blinded study design involving 20 physiotherapy students; ten with knowledge of the breathing control technique (Group BC) and ten without (Group CON). All participants were asked to perform a Chester step test. Group BC performed BC, while Group CON adopted their own breathing pattern during recovery after the step test. Respiratory rate and sonographic parameters of the diaphragm including diaphragmatic excursion, speed of diaphragmatic contraction (slope of contraction), and inspiratory time were recorded before and after the step test. Results: All baseline data were similar for both groups except age. Respiratory rate at 1 min post-step test was higher in Group CON (24.6±4.9 bpm) compared to Group BC (15.6 ± 3.8 bpm) (p < 0.001). Post-step test sonographic evaluation demonstrated an increase in diaphragmatic excursion with a significant time and group interaction (F(4,72) = 5.499, p = 0.005). Post hoc analysis revealed that the diaphragmatic excursion was significantly higher in Group BC compared to Group CON at first, second and third minute post-step test. Time and group interactions were not significant in inspiration time (F(4,72) = 2.459, p = 0.082) nor the slope of contraction (F(4,72) = 0.655, p = 0.582)]. Conclusion: Post-exercise diaphragmatic excursion was higher in participants applying BC. Non-invasive ultrasonography is able to promote objective evaluation of the relationship between breathing techniques and diaphragmatic function. [ABSTRACT FROM AUTHOR]

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Highlights: [•] In contrast to PSV, NAVA preserves carbon dioxide homeostasis, [•] Thus, overassistance during NAVA could be obtained without hypocapnia induction, [•] Finally identifying the optimal NAVA level remains a challenge. [Copyright &y& Elsevier]