Breathing Rhythm Research Articles

Evaluation of the effects of dexamethasone in modulating breathing pattern decomplexification in rats with 2-chloroethyl ethyl sulfide-induced lung injury

"Background and Objectives: Sulfur mustard is a functional alkylating chemical warfare agent that gives rise to appalling lung injury. In people with pulmonary diseases, including asthma, the complication of respirational dynamics is reduced. However, the complexity of breathing patterns in lung injury caused by chemical agents is not clear. In the current study, the outcome of 2-chloroethyl ethyl sulfide (CEES), and mustard analogue, upon breathing pattern of rats without or with treatment were reviewed. Methods: The interbeat interval (IBI) and respiratory volume (RV) data have been acquired from spontaneous respiration rats with lung injury by CEES using a whole-body plethysmograph. We calculated mean and coefficient of variation, alpha exponent derived from detrended fluctuation analysis (DFA), and sample entropy of IBI and RV. Finding: Entropy examination of respiratory variation displayed reduced inconsistency (less complication) in the breathing pattern of this rat model of lung injury. The mustard analogue also led to increased lung inflammation in damaged rats. However, treatment by NAC and dexamethasone had a compelling impact on the complication of the breathing rhythm and lung inflammation of rats with lung injury. Conclusion: Our findings show that inflammation could be the possible origin of respiratory dynamics shifting apart from the normal variation in CEES-induced lung injury"

The DIBH (Deep Inspiration Breath-Hold) Monitoring Development Using Ultrasonic and IR Sensors with a Microcontroller

<h3>Purpose/Objective(s)</h3> We devised and developed a motion tracking system by using an ultrasonic (HC-SRO4) and an IR (Infrared- VL6180X Time of Flight) distance sensor and detector interfacing with a microcontroller and the 3D printed devices such as a detector assembly and supporting holders. The purpose of this study was to demonstrate the functionality and performance of our system. <h3>Materials/Methods</h3> The first step of this project was to check the functionality of a detector of DIBH motion interfacing a microcontroller. This was tested on an RPM (Real-Time Positioning Management) phantom to check a breathing motion. Ultrasonic and IR sensors were utilized on the Arduino microcontroller. Based upon the phantom tests with customized programming in Arduino, we tried to devise this on CT scan in terms of real patient scan's situation using a body phantom to mimic DIBH pattern. From a several trials, we recognized to need a detector holder which was mounted perpendicularly on between the xiphoid and umbilicus with 6-degree variables in longitudinal, lateral, vertical, rotational, pitching and rolling motion. The versatility allowed for compensation of various patient body habitus and adaptation in the clinical setup. The plastic devices for this project were created on 3D printer and programming. The sensors were mounted on approximately 100mm to receive the directed echo signals and prevent any unwanted signals from scattering or recoiling from other parts such as detection edges and supporting holders. <h3>Results</h3> The acquired results (n=20) demonstrated the entire process of the DIBH visualization project with a real-time breathing tracking and recording the breathing pattern. The patient's breathing between inhale and exhale was detected on amplitude change with time. In case of s, we observed that big fluctuations before the stable plateau of holding breathing on the DIBH were due to the mismatched echo signals in terms of irregular breathing patterns from patients and scattered signals outside of detector. There were also noisy patterns due to the sensor resolution of 3mm. We noticed the signal detection was angular dependent between the fixed sensor and moving surface from patient breathing. We used a focusing cup to reduce the angular dependency, but there was not much of improvement. In order to resolve the difficulties of ultrasonic sensor, we have utilized an IR sensor with the same setup of the ultrasonic and evaluated that it has compensated the signal detection with ±20 degrees of angular variation during the DIBH and the maximum clinical range of 450mm. The ratio of amplitude on DIBH to free breathing has increased to 1.7 times. <h3>Conclusion</h3> Comparing with the ultrasonic sensor, the IR sensor DIBH system demonstrated of breathing rhythm without big fluctuations and reduced a battle with noise. For various irregular breathings, it showed comparable RPM breathing motion, adequate breathing amplitude, clinically acceptable DIBH pattern to check chest and abdominal motion.

The role of reciprocity in dynamic interpersonal coordination of physiological rhythms

A central question in social cognition research is how people coordinate their bodily rhythms, and how important reciprocity of interaction is for interpersonal coordination. Previous research has primarily focused on interpersonal action coordination, which has been shown to be facilitated by mechanisms of prediction and mutual adaption. Recent research is beginning to show that people also coordinate their physiological rhythms (i.e., respiration, heart rhythms) when they engage in natural forms of social interaction, such as conversation, choir singing, and rituals. However, the mechanisms underlying interpersonal physiological synchronization remain obscure, and could provide insight into the dynamic mechanisms that underlie continuous and regulatory, rather than instrumental, joint actions. Using real-time biofeedback, we investigated whether people synchronize their respiration rhythms by forming a joint dynamical system through reciprocity of interaction, or by producing more predictable respiration rhythms. Our results show that people are more in-phase synchronized but less phase-locked when interacting bidirectionally versus unidirectionally (online), but there is no difference in synchronization during reciprocal interaction and when adapting unidirectionally (offline) to recordings of respiration signals that emerged during the reciprocal interaction. Moreover, the strength of synchronization is driven by the predictability of the respiration rhythms that emerge in the bidirectional interaction – specifically, the slowing of breathing rhythms and stability of breathing frequencies – rather than the online mutual adaptation itself. These results suggest that coordination is facilitated by the emergence of predictable breathing patterns, rather than reciprocity itself.

µ-Opioid Receptor Activation Reduces Glutamate Release in the PreBötzinger Complex in Organotypic Slice Cultures.

The inspiratory rhythm generator, located in the brainstem preBötzinger complex (preBötC), is dependent on glutamatergic signaling and is affected profoundly by opioids. Here, we used organotypic slice cultures of the newborn mouse brainstem of either sex in combination with genetically encoded sensors for Ca2+, glutamate, and GABA to visualize Ca2+, glutamatergic and GABAergic signaling during spontaneous rhythm and in the presence of DAMGO. During spontaneous rhythm, the glutamate sensor SF-iGluSnFR.A184S revealed punctate synapse-like fluorescent signals along dendrites and somas in the preBötC with decay times that were prolonged by the glutamate uptake blocker (TFB-TBOA). The GABA sensor iGABASnFR showed a more diffuse fluorescent signal during spontaneous rhythm. Rhythmic Ca2+- and glutamate transients had an inverse relationship between the spontaneous burst frequency and the burst amplitude of the Ca2+ and glutamate signals. A similar inverse relationship was observed when bath applied DAMGO reduced spontaneous burst frequency and increased the burst amplitude of Ca2+, glutamate, and GABA transient signals. However, a hypoxic challenge reduced both burst frequency and Ca2+ transient amplitude. Using a cocktail that blocked glutamatergic, GABAergic, and glycinergic transmission to indirectly measure the release of glutamate/GABA in response to an electrical stimulus, we found that DAMGO reduces the release of glutamate in the preBötC but has no effect on GABA release. This suggest that the opioid mediated slowing of respiratory rhythm involves presynaptic reduction of glutamate release, which would impact the ability of the network to engage in recurrent excitation, and may result in the opioid-induced slowing of inspiratory rhythm.SIGNIFICANCE STATEMENT Opioids slow down breathing rhythm by affecting neurons in the preBötzinger complex (preBötC) and other brainstem regions. Here, we used cultured slices of the preBötC to better understand this effect by optically recording Ca2+, glutamate, and GABA transients during preBötC activity. Spontaneous rhythm showed an inverse relationship between burst frequency and burst amplitude in the Ca2+ and glutamate signals. Application of the opioid DAMGO slowed the rhythm, with a concomitant increase in Ca2+, glutamate, and GABA signals. When rhythm was blocked pharmacologically, DAMGO reduced the presynaptic release of glutamate, but not GABA. These data suggest the mechanism of action of opioids involves presynaptic reduction of glutamate release, which may play an important role in the opioid-induced slowing of inspiratory rhythm.

Heart Rate Variability Biofeedback for Substance Use Disorder: Health Policy Implications

Substance use disorder (SUD) exacts massive individual and public health burdens, in part because of its relapsing nature. First-line SUD treatments aim to strengthen affective and cognitive control to help individuals override impulses to use alcohol and other drugs, yet automatic physiological processes compromised by SUD interact with affective states and the environment, compromising effortful cognitive control and undermining attempts to avoid substance use. While existing first-line SUD treatments may indirectly help offset these vulnerabilities, none target them. Heart rate variability biofeedback (HRVB) involves rhythmic breathing that directly targets these deficits, complementing first-line SUD treatments. HRVB has evolved from a clinic-based treatment to an ambulatory intervention utilizing wearable biosensors and smartphone applications with capacity for just-in-time support of affective and behavioral self-regulation. There is evidence supporting the efficacy of HRVB for SUD, but more research is needed to fully assess HRVB's potential to support SUD recovery and inform policy.

Classifier for the functional state of the respiratory system via descriptors determined by using multimodal technology

Currently, intelligent systems built on a multimodal basis are used to study the functional state of living objects. Its essence lies in the fact that a decision is made through several independent information channels with the subsequent aggregation of these decisions. The method of forming descriptors for classifiers of the functional state of the respiratory system includes the study of the spectral range of the respiratory rhythm and the construction of the wavelet plane of the monitoring electrocardiosignal overlapping this range. Then, variations in the breathing rhythm are determined along the corresponding lines of the wavelet plane. Its analysis makes it possible to select slow waves corresponding to the breathing rhythm and systemic waves of the second order. Analysis of the spectral characteristics of these waves makes it possible to form a space of informative features for classifiers of the functional state of the respiratory system. To construct classifiers of the functional state of the respiratory system, hierarchical classifiers were used. As an example, we took a group of patients with pneumonia with a well-defined diagnosis (radiography, X-ray tomography, laboratory data) and a group of volunteers without pulmonary pathology. The diagnostic sensitivity of the obtained classifier was 76% specificity with a diagnostic specificity of 82%, which is comparable to the results of X-ray studies. It is shown that the corresponding lines of the wavelet planes are correlated with the respiratory system and, using their Fourier analysis, descriptors can be obtained for training neural network classifiers of the functional state of the respiratory system.

Closed-Loop Adaptive Neurostimulation Technologies in Cognitive Rehabilitation of High-Tech Specialists.

The study involved specialists who applied to the clinic with complaints of occupational pain syndromes and work stress. For the treatment of pain syndromes, analgesic electrical nerve stimulation was used with the parameters automatically modulated by feedback signals from the subject's breathing rhythm. To correct stress-induced states, musical stimulation was used, automatically modulated by feedback signals from the narrow-band rhythmic components of the electroencephalogram (EEG) of the subject - alpha EEG oscillators. Treatment procedures without feedback from rhythmic processes were used as а control. In the control sessions without the feedback from human rhythmic processes, no significant effects of stimulation were noted. With electrical stimulation controlled by the patient's breathing (experiment 1), the most significant changes were observed in subjective pain scores, which dropped by half. A significant increase was noted in the power of the EEG alpha rhythm, respiration amplitude, and subjective ratings of well-being and mood. With music stimulation automatically modulated by the rhythmic components of the patient's EEG (experiment 2), there was a significant increase in the power of the EEG alpha rhythm, as well as a decrease in the level of emotional disadaptation and stress. The data obtained clearly indicate that the developed and tested technologies of adaptive neurostimulation can be used for the timely correction of the functional state and cognitive rehabilitation of high-tech specialists by effectively eliminating the risks of their functional reliability caused by occupational pain and stress.

Improving physiological stability of very preterm babies: a preliminary randomised controlled trial

Background Preterm babies born below 32 weeks gestational age are placed in incubators, and therefore deprived of exposure to maternal heartbeat sounds and breathing rhythms. This article explored the use of a unique soft-robotics device that replicates these via a mattress in the incubator. Aims This study aimed to obtain data on mothers' experiences in the NHS COSYBABY study in relation to using the device and learn what, if any, value this device has to parents in the neonatal unit. Methods The study used qualitative focus groups conducted by patient and public involvement leads and interviews with parents. Framework analysis was used to analyse the data. Results Resulting themes were willingness to try anything, supporting mothers, scepticism and searching for causality, limitations of the device and beyond the intervention. Conclusions The device provides socioemotional benefits to mothers of neonatal babies, although the health benefits to their baby are uncertain.

Manifestations of forced efforts of elderly men with different breathing regimes

The analysis of the existing therapeutic and prophylactic systems of respiration is carried out, the influence of different respiratory regimes on the dynamics of force manifestations of male muscles taking into account age is investigated. Recommendations for strength exercises with observance of certain breathing rhythms of elderly men have been made.&#x0D; The aim of the study was to determine the peculiarities of the manifestation of strength abilities of older men with different respiratory regimes.&#x0D; In the course of the research the following tasks were solved: analysis of modern respiratory systems; study of the influence of different respiratory regimes on the dynamics of force manifestations of the muscles of the hand and abdominal press of elderly men; comparative assessment and determination of the influence of different respiratory regimes on the power manifestations of men aged 60+.&#x0D; Methods – before the start of the main study, the men of the experimental group mastered the method of breathing regimes (personally during strength exercises), with the men of the control group breathing practices were not performed.&#x0D; As a result of researches the optimum modes of breath for display are defined: wrist dynamometry, dynamics of display of force of abdominal muscles. Prospects for further development are seen in a more in-depth definition of the ability to perform strength exercises in different breathing modes to increase the physical performance of the elderly.

The impact of the mountain factor on the students» cardiorespiratory system

The work is devoted to studying the influence of mountain hypoxia on the state of the students» cardiovascular and respiratory systems. The results of our research indicate that under conditions of hypoxia, the activity of the respiratory system in students significantly increases while the activity of the cardiovascular system slightly decreases. Thus, the cardiac rate at an altitude of 1,600 m was 72.8 beats per minute for female students and 71.0 for males, with 76.2 and 74.8 beats respectively at 170 m. In the midlands, the value of systolic pressure fell to 113.6 mmHg in girls and 110.8 in young men, with the plain indicators at 117.6 and 114.6. The rhythm of breathing in conditions of oxygen deficiency in the surrounding air does not change. The level of respiratory volume in female students at an altitude of 600 and 1600 m was 0.62 l (P &lt;0.05) and 0.68 (P &lt;0.02), with 0.46 at 170 m. In the midlands, the inspiratory reserve volume in girls was 1.93 l (P &lt;0.02), and in the plains it was 1.74. The VC level at the maximum height was 3.92 l (P &lt;0.05) in female students and 4.42 l in male, and at a height of 170 m — 3.46 and 4.06 l, respectively.

Primary Breathing Survey Emergency with Oxygen Need Optimization and Nurse Caring on Covid-19 Patients in IGD UKI RSU Jakarta: Case Study

Emergency in Covid-19 is a respiratory tract infection caused by a new type of coronavirus (SARS-CoV-2) so that it can cause a decrease in oxygen levels in patients with saturation &lt;95% Objective: To carry out emergency nursing care for19 patients Covid-. 19 with the measures in Primary Survey and Secondary Survey order to increase oxygen saturation &gt;95%, reduce shortness of breath, regular breathing rhythm with a frequency of 20x/minute, symmetrical chest movements, and no chest muscle retraction Methods: The method of case study results uses a descriptive approach with a process approach. nursing care, independent action by monitoring the frequency of breath and oxygen saturation as well as giving the semi-fowler position, collaborative action by giving high concentration oxygen Non-Rebreathing Mask 10 liters/minute. Results: The patient's shortness of breath has been reduced with oxygen saturation increasing 99%, chest movement is symmetrical, irregular breathing rhythm 24x/minute is still partially resolved and the patient does not appear restless after being given high concentrations of oxygen. Conclusion: It takes speed and attitude caring towards patients to overcome anxiety and empathy, especially being a good listener by always providing support so that patients are always motivated to recover and providing independent action and the right collaboration of health workers so that the handling of Covid-19 can be resolved

Epidural electrical stimulation of the cervical spinal cord opposes opioid-induced respiratory depression.

Opioid overdose suppresses brainstem respiratory circuits, causes apnoea and may result in death. Epidural electrical stimulation (EES) at the cervical spinal cord facilitated motor activity in rodents and humans, and we hypothesized that EES of the cervical spinal cord could antagonize opioid-induced respiratory depression in humans. Eighteen patients requiring surgical access to the dorsal surface of the spinal cord between C2 and C7 received EES or sham stimulation for up to 90s at 5 or 30Hz during complete (OFF-State) or partial suppression (ON-State) of respiration induced by remifentanil. During the ON-State, 30Hz EES at C4 and 5Hz EES at C3/4 increased tidal volume and decreased the end-tidal carbon dioxide level compared to pre-stimulation control levels. EES of 5Hz at C5 and C7 increased respiratory frequency compared to pre-stimulation control levels. In the OFF-State, 30Hz cervical EES at C3/4 terminated apnoea and induced rhythmic breathing. In cadaveric tissue obtained from a brain bank, more neurons expressed both the neurokinin 1 receptor (NK1R) and somatostatin (SST) in the cervical spinal levels responsive to EES (C3/4, C6 and C7) compared to a region non-responsive to EES (C2). Thus, the capacity of cervical EES to oppose opioid depression of respiration may be mediated by NK1R+/SST+ neurons in the dorsal cervical spinal cord. This study provides proof of principle that cervical EES may provide a novel therapeutic approach to augment respiratory activity when the neural function of the central respiratory circuits is compromised by opioids or other pathological conditions. KEY POINTS: Epidural electrical stimulation (EES) using an implanted spinal cord stimulator (SCS) is an FDA-approved method to manage chronic pain. We tested the hypothesis that cervical EES facilitates respiration during administration of opioids in 18 human subjects who were treated with low-dose remifentanil that suppressed respiration (ON-State) or high-dose remifentanil that completely inhibited breathing (OFF-State) during the course of cervical surgery. Dorsal cervical EES of the spinal cord augmented the respiratory tidal volume or increased the respiratory frequency, and the response to EES varied as a function of the stimulation frequency (5 or 30Hz) and the cervical level stimulated (C2-C7). Short, continuous cervical EES restored a cyclic breathing pattern (eupnoea) in the OFF-State, suggesting that cervical EES reversed the opioid-induced respiratory depression. These findings add to our understanding of respiratory pattern modulation and suggest a novel mechanism to oppose the respiratory depression caused by opioids.

A Poem by Heart

A Poem by Heart

Maternal opioids decrease mu‐opioid receptor expression in the neonatal preBötzinger Complex

An understudied population in the opioid crisis are infants exposed to in utero opioids experiencing severe respiratory deficits. Our recent work demonstrated maternal opioids destabilized neonatal breathing, increased apneas, and blunted opioid‐induced respiratory frequency depression; however, the mechanism(s) underlying these neonatal breathing deficits remains unclear. We hypothesized deficits in neonatal breathing after maternal opioids are due to downregulation of mu‐opioid receptors on key cell types (e.g. neurons and astrocytes), essential for respiratory rhythm generation and modulation in the preBötzinger Complex. While opioid receptor expression is downregulated in the whole brain after maternal opioids, it remains unclear if opioid receptor expression changes in the preBötzinger Complex after in utero opioids to induce neonatal breathing deficits. To assess the typical developmental changes in opioid receptors in the preBötzinger Complex, mu‐opioid receptor expression was first assessed using immunohistochemistry and confocal microscopy on neonatal neurons and astrocytes in the preBötzinger Complex at three ages: the day of birth (postnatal day 0, P0) when neonates must begin robust rhythmic breathing, an early neonatal age (postnatal day 4, P4), and during a critical developmental window (postnatal day 11, P11). At all ages, mu‐opioid receptors were expressed on both neurons and astrocytes in the preBötzinger Complex; however, mu‐opioid receptor expression decreased from P0 (n=6) to P4 (n=6) and was lowest at P11 (n=6). Preliminary data after maternal opioids suggest mu‐opioid receptor expression was lower in preBötzinger Complexes at P0 (n=2) and P4 (n=2), but returned to control levels by P11 (n=2). These results are further supported by in vitro brainstem‐spinal cord recordings of the cervical rootlets (C4) from neonates after maternal opioids, demonstrating decreased opioid sensitivity of isolated respiratory control circuitry after maternal opioids (n=2). Results from these studies will contribute to our understanding of the mechanisms contributing to impaired neonatal breathing after maternal opioids and may lead to better treatments for infants suffering breathing deficits after maternal opioids.

Breathing rhythm stability is higher after intravenous injection of codeine relative to fentanyl in cats

Codeine is one of the opioids of abuse that is available by prescription, and fentanyl is the leading opioid drug of abuse. Both codeine and fentanyl are µ‐opioid agonists that are strong respiratory depressants. However, unlike fentanyl, codeine also binds to nicotinic receptors. We hypothesized that influence of these drugs on the stability of breathing would differ due to the relative non‐specificity of codeine. Ten anesthetized, spontaneously breathing adult cats were tracheotomized, and EMG activity was recorded from inspiratory muscles. Dose responses to codeine (n=5, 0.1 – 10 mg/kg, i.v.) or fentanyl (n=5, 0.1 – 10 ng/kg, i.v.) were performed in separate groups of animals. Total breathing cycle time (Ttot) was measured for 30 breaths at each dose. Measurements of Ttot were taken more than 5 minutes following administration of the drugs. Poincaré plots were constructed for Ttot, where an ellipse was fit to the data (Ɵ=45°). The ratio (SD1/SD2) was computed at each dose, where SD1 was the length the ellipse perpendicular to the line of identity, and SD2 was the length along the line of identity. SD1 is associated with short‐term variability and SD2 with long‐term variability of the data. The dose response relationships showed similar increases in Ttot from vehicle to the highest dose between codeine and fentanyl (codeine: 2.4 ± 0.2 s to 4.4 ± 1.0 s; fentanyl: 2.5 ± 0.4 s to 5.4 ± 0.5 s). Transient apnea (&lt; 60 s) was commonly observed immediately following doses of codeine that were larger than 1 mg/kg, but was not observed after any dose of fentanyl. SD1/SD2 differed between the two drugs, where SD1/SD2 did not change across doses for codeine, and SD1/SD2 decreased significantly in a dose‐dependent manner from 0.3 ng/kg (0.77 ± 0.10) to the 3 ng/kg dose (0.32 ± 0.7) for fentanyl. The shift in the SD1/SD2 ratio after fentanyl was driven more by changes in SD2 (81% compared to vehicle) rather than SD1 (‐17% compared to vehicle). We conclude that codeine induces relatively similar changes of short and long‐term variability of Ttot, whereas fentanyl preferentially reduces long‐term variability of Ttot. Alterations in long‐term variability are more consistent with a potential for network reconfiguration rather than the respiratory network correcting for breath‐to‐breath requirements. Our data suggest that a Poincaré plot may be a sensitive metric of the disruption of respiratory control dynamics for the µ‐receptor selective fentanyl relative to the µ‐opioid agonist/nicotinic ligand codeine.

Opto‐ and Chemogenetic Dissection of Ictal Apnea Neural Circuitry

Sudden Unexpected Death in Epilepsy (SUDEP) is defined as the sudden, unexpected and unexplained death of a person with epilepsy and accounts for between 8 and 17% of epilepsy‐related deaths, rising to 50% for patients with refractory epilepsy. In a mouse model of SUDEP, we have recently shown that death is due to seizure‐induced respiratory arrest. In addition, apnea is initiated during the tonic phase and tonic respiratory muscle contraction is a possible mechanism of apnea. In the present study, we explore 1) whether tonic activity of the inspiratory rhythm generator in the brainstem and/or 2) upper motor neuron activity in the motor cortex drives ictal apnea.We recorded video, electrocorticogram (ECoG), electrocardiogram (ECG), and breathing via whole body plethysmography in adult mice carrying the human SCN8A encephalopathy mutation p.Asn1768Asp (N1768D; “D/+ mice”) during audiogenic seizures. This mutation was identified from a patient that died from SUDEP and D/+ mice have severe convulsive seizures with apnea and many suffer seizure‐induced death.To test the hypothesis that tonic activity from the inspiratory oscillator results in apnea, we implanted fiberoptic ferrules bilaterally into the Bötzinger Complex (BötC) of mice that express Channelrhodopsin2 (ChR2) under the vesicular GABA transporter (VGAT; “VGAT‐ChR2” mice) that were crossed with D/+ mice (Fig. 1A &amp; B). The goal of the experiment is to photostimulate BötC during ictal apnea to inhibit tonic inspiratory activity and produce expiration (Fig. 1C). Seizures were evoked using a 15 kHz pure tone, as we have done before (Fig. 1D). Trains of light pulses (50 ms pulses, 5 mW of 473 nm light) were evoked repetitively during ictal apnea (Fig. 1E &amp; F). However, this did not recover normal breathing rhythm and apnea duration was no different for any photostimulation paradigm versus control (p = 0.7892, F = 0.1747, One‐Way ANOVA; Fig. 1G). Although breathing was not affected during seizures, the effects on baseline breathing were substantial; for example, inspiration was inhibited for a full 10 second photostimulation train (Fig. 1H).To test the necessity of ictal activity from upper motor neurons in the motor cortex are required for generating ictal apnea, we expressed iDREADD receptors in cortical excitatory neurons of D/+ mice and injected CNO i.p. prior to inducing seizures with a 15 kHz pure tone (Fig. 2A). Under control conditions, seizures presented with the usual tonic phase apnea and spike wave discharges (SWDs) in the motor cortex (Fig. 2B). CNO was able to robustly inhibit the SWDs, but the tonic phase and apnea were not affected (Figs. 2C‐E). The effect of 3 mg/kg CNO on ECoG power was significantly greater than the effect on apnea (p = 0.0059, paired t‐test).In sum, we found that the core inspiratory oscillator circuitry in the brainstem is likely bypassed to create tonic inspiratory activity. Furthermore, inhibition of cortical upper motor neurons has no effect on apnea. Thus, our interpretation is that other pools of upper motor neurons must drive the tonic inspiratory activity and apnea.

Putting the theory into 'burstlet theory' with a biophysical model of burstlets and bursts in the respiratory preBötzinger complex.

Inspiratory breathing rhythms arise from synchronized neuronal activity in a bilaterally distributed brainstem structure known as the preBötzinger complex (preBötC). In in vitro slice preparations containing the preBötC, extracellular potassium must be elevated above physiological levels (to 7-9 mM) to observe regular rhythmic respiratory motor output in the hypoglossal nerve to which the preBötC projects. Reexamination of how extracellular K+ affects preBötC neuronal activity has revealed that low-amplitude oscillations persist at physiological levels. These oscillatory events are subthreshold from the standpoint of transmission to motor output and are dubbed burstlets. Burstlets arise from synchronized neural activity in a rhythmogenic neuronal subpopulation within the preBötC that in some instances may fail to recruit the larger network events, or bursts, required to generate motor output. The fraction of subthreshold preBötC oscillatory events (burstlet fraction) decreases sigmoidally with increasing extracellular potassium. These observations underlie the burstlet theory of respiratory rhythm generation. Experimental and computational studies have suggested that recruitment of the non-rhythmogenic component of the preBötC population requires intracellular Ca2+ dynamics and activation of a calcium-activated nonselective cationic current. In this computational study, we show how intracellular calcium dynamics driven by synaptically triggered Ca2+ influx as well as Ca2+ release/uptake by the endoplasmic reticulum in conjunction with a calcium-activated nonselective cationic current can reproduce and offer an explanation for many of the key properties associated with the burstlet theory of respiratory rhythm generation. Altogether, our modeling work provides a mechanistic basis that can unify a wide range of experimental findings on rhythm generation and motor output recruitment in the preBötC.

INFLUENCE OF RESPIRATORY SYSTEM PROTECTION ON THE TREATMENT OF PATIENTS WITH CRANIOCEREBRAL TRAUMA

Introduction. Craniocerebral trauma (CCT) results in disorders of pharyngeal reflex, deglutition, breathing rhythm and frequency. All the mentioned conditions cause the development of respiratory complications. Whereas they become independent factors of negative therapeutic consequences in such category of patients.&#x0D; Aim of a paper. The research aims at evaluating protection/treatment possibilities of the respiratory system concerning the course of craniocerebral trauma in injured patients.&#x0D; Materials and methods. We examined 237 patients with CCT who underwent urgent surgical interventions in the form of a decompressive cranial trepanation and the removal of both subdural and epidural hematomata. All patients required prolonged mechanical ventilation of the lungs. The patients were retrospectively divided into two groups, namely: the first group (132 patients) – the patients with tracheostomy on the 5th-6th days of admission to the clinics of anesthesiology and intensive care; the second group (105 patients) – the patients with tracheostomy on the 1st-2nd days of hospitalization. Patients of both groups were not differentiated by gender, the severity of CCT and general condition. In addition to general clinical and biochemical blood markers, culturing of the secretion in the tracheostomy tube (at the moment of tracheostomy and further every 3-4 days), blood and urine were performed in all patients. Simultaneously we controlled the leucocyte count in the peripheral blood, number of immature forms, levels of CRP and procalcitonin. The evaluation of a neurological status of patients was carried out by the Glasgow and Richmond Agitation-Sedation Scale (RASS). The severity of CCT was visualized with the help of CT.&#x0D; Research results. Even at the moment of tracheostomy the frequency of colonization of tracheobronchial tree was significantly higher in the first group of patients compared to the second one. Such tendency was monitored in further stages as well. The phenomena of tracheobronchitis and pneumonia were detected more frequently in the group of patients with tracheostomy on the 5th-6th days of postoperative period in contrast to the patients with tracheostomy on the 1st-2nd days of postoperative period. Microorganisms of Enterobacteriaceae with the extended spectrum of ß-lactamase and non-fermenting Gram-negative bacteria were detected more frequently in the first group.&#x0D; Conclusion. Early tracheostomy in patients with CCT results in both the decrease in the frequency of positive culturing of secretions from the tracheobronchial tree and the reduction in a detection frequency of nosocomial pneumonia.

Characteristics and outcomes of hospitalized adults with COVID-19 in Nepal: a multicenter, prospective cohort study.

There is limited data on clinical course and outcomes of hospitalized adults with COVID-19 in Nepal. Thus, it is imperative to characterize the features of this disease in the domestic context. We identified all adult patients with laboratory-confirmed COVID-19 admitted to five different hospitals in Nepal from June 15 to July 15, 2020. We collected epidemiological, socio-cultural and clinicopathologic data, and stratified the patients based on their symptom status. The study included 220 patients with an overall median age of 31.5 (25-37) years, and 181 (82.3%) were males. 159 (72.3%) were asymptomatic, and 163 (74.1%) were imported cases. Of 217 patients with the available data, 110 (50.7%) reported their annual household income less than 2000 US dollars, and 122 (56.2%) practiced Pranayama (yogic rhythmic breathing techniques) regularly. Eight patients (3.6%) required supplemental oxygen and two patients (0.9%) died. None of the patients who practiced Pranayama regularly required supplemental oxygen. Compared to asymptomatic patients, symptomatic patients had greater proportion of females (31.1% vs. 12.6%, p = 0.001), imported cases (85.2% vs. 69.8%, p = 0.02), illiterates (26.8% vs. 12.1%, p = 0.01), alcohol users (43.3% vs. 24.5%, p = 0.01), and had higher platelet count (253×109/L vs. 185×109/L, p = 0.02). Most cases were imported, asymptomatic young males, with very few deaths. Pranayama practice was associated with protection against severe COVID-19, but more data is needed to substantiate this. The association of platelets count with symptom status in the Nepalese population needs further exploration.

Technical Note: Validation of the effectiveness of electric stunning for euthanasia of mature swine (Sus scrofa domesticus).

Electrocution and the use of a penetrating captive bolt gun (PCBG) are both acceptable methods of euthanasia for market weight swine. Research has demonstrated that a PCBG is effective in both growing and mature swine. Given limited to no published research base on electrocution in mature swine, the objectives of the present study were to evaluate the efficacy of a two-stage (head only followed by head to heart, 10s contact for each) mobile electric stunner (E-STUN, Hubert HAAS TBG 96N) and to assess euthanasia outcomes when comparing E-STUN with the frontal placement of a heavy-duty PCBG (Jarvis, In-line Cylinder Style) when applied to heavy-weight (>200kg) mature boars and sows. Effectiveness of the E-STUN and PCBG was evaluated first in unconscious anesthetized mature swine (n = 7 boars and sows per treatment; average weight 282±48kg, n = 28) to reduce the risk of failure in a conscious animal and then in conscious mature swine (n = 3 boars and sows per treatment; average weight 282±63kg, n = 12). Data from both stages were combined for analyses. Treatment efficacy was defined as any pig that achieved cardiac and respiratory arrest within 10min after treatment application. A three-point traumatic brain injury score (0 = normal; 1 = some abnormalities; and 2 = grossly abnormal, unrecognizable) was used to evaluate six neuroanatomical structures (cerebral cortex, cerebellum, hypothalamus, thalamus, pons, and brain stem), and the presence of intracranial hemorrhage was also noted. All animals were immediately rendered insensible with E-STUN and PCBG, and no difference was noted between treatments for the detection of corneal reflex following treatment application (P = 0.11). Rhythmic breathing was absent following the administration of either E-STUN or PCBG. When evaluating the time to last heartbeat, there was a significant interaction between sex and treatment. Boars euthanized via E-STUN had a 346.8-s decrease in time to last heartbeat compared with boars euthanized via PCBG (P < 0.001), and females euthanized via E-STUN had a 479.3-s decrease in time to last heartbeat compared with females euthanized via PCBG (P < 0.001). Intracranial hemorrhage was common for both methods, and visible disruption of neural tissue was evident due to the physical nature of the PCBG. This study demonstrated that a mobile E-STUN system is as effective as a heavy-duty PCBG in inducing insensibility and death and shows promise as an alternative method for euthanizing mature pigs on-farm.