SubSol-HIe is an AMPK-dependent hypoxia-responsive subnucleus of the nucleus tractus solitarius that coordinates the hypoxic ventilatory response and protects against apnoea in mice.

Functional magnetic resonance imaging (fMRI) suggests that the hypoxic ventilatory response is facilitated by the AMP-activated protein kinase (AMPK), not at the carotid bodies, but within a subnucleus (Bregma -7.5 to -7.1 mm) of the nucleus tractus solitarius that exhibits right-sided bilateral asymmetry. Here, we map this subnucleus using cFos expression as a surrogate for neuronal activation and mice in which the genes encoding the AMPK-α1 (Prkaa1) and AMPK-α2 (Prkaa2) catalytic subunits were deleted in catecholaminergic cells by Cre expression via the tyrosine hydroxylase promoter. Comparative analysis of brainstem sections, relative to controls, revealed that AMPK-α1/α2 deletion inhibited, with right-sided bilateral asymmetry, cFos expression in and thus activation of a neuronal cluster that partially spanned three interconnected anatomical nuclei adjacent to the area postrema: SolDL (Bregma -7.44 mm to -7.48 mm), SolDM (Bregma -7.44 mm to -7.48 mm) and SubP (Bregma -7.48 mm to -7.56 mm). This approximates the volume identified by fMRI. Moreover, these nuclei are known to be in receipt of carotid body afferent inputs, and catecholaminergic neurons of SubP and SolDL innervate aspects of the ventrolateral medulla responsible for respiratory rhythmogenesis. Accordingly, AMPK-α1/α2 deletion attenuated hypoxia-evoked increases in minute ventilation (normalised to metabolism), reductions in expiration time, and increases sigh frequency, but increased apnoea frequency during hypoxia. The metabolic response to hypoxia in AMPK-α1/α2 knockout mice and the brainstem and spinal cord catecholamine levels were equivalent to controls. We conclude that within the brainstem an AMPK-dependent, hypoxia-responsive subnucleus partially spans SubP, SolDM and SolDL, namely SubSol-HIe, and is critical to coordination of active expiration, the hypoxic ventilatory response and defence against apnoea.

Percent duration of heart rate acceleration within the respiratory cycle: a novel approach to assess heart rate asymmetry.

Accelerations and decelerations of heart rate are nonsymmetrical in the magnitude and number of beat-to-beat changes. The asymmetric features of heart rate variability are related to respiratory durations. To explore the link between respiration and heart rate asymmetry (HRA), we evaluated 14 seated, healthy young adults who breathed with nine combinations of inspiration duration (TI) and expiration duration (TE), chosen respectively from 2, 4, and 6 s. A 5-min R-R interval (RRI) time series was obtained from each study period to construct an averaged pattern waveform relative to the respiratory cycle. We observed that the time interval between inspiration onset and RRI minimum progressively lengthened as TI and TE increased. The time interval between expiration onset and RRI maximum also lengthened when TE increased but shortened when TI increased. Consequently, TI and TE had different effects on the acceleration time (AT; from RRI maximum to RRI minimum) and deceleration time (DT; from RRI minimum to RRI maximum). The percentage of AT within the respiratory cycle showed a strong correlation with traditional Guzik's (r = 0.862, P < 0.001) and Porta's (r = 0.878, P < 0.001) indexes of HRA assessed in a Poincaré plot analysis. These findings suggest that, in addition to considering the magnitude and number of beat-to-beat changes, HRA can also be assessed based on another aspect: the duration of consecutive changes. The stepwise link between the duration of heart rate change and respiratory duration provides insight into the mechanisms connecting respiration to HRA.NEW & NOTEWORTHY In healthy adults who regulated their breathing across nine combinations of inspiration and expiration durations, we used averaged pattern waveform technique to quantify the durations of heart rate acceleration and deceleration within the respiratory cycle. The percent duration of acceleration showed a strong correlation with traditional heart rate asymmetry indexes, which evaluate the magnitude and number of beat-to-beat changes. This new approach opens a window to explore the asymmetric features of heart rate variability.

Different effects of inspiratory duration and expiratory duration on heart rate deceleration capacity and heart rate asymmetry.

PURPOSE: Low values of heart rate deceleration capacity (DC) and heart rate asymmetry (HRA) are associated with cardiovascular risks. Slow respiration has been proven to enhance the magnitudes of these indexes, but individual inspiratory (TI) and expiratory (TE) durations were not controlled in most studies. This study aims to examine whether the effects of TI and TE on these indexes would be the same and, if not, how to adjust TI and TE to maximize the effect of slow respiration. METHODS: We evaluated 14 seated healthy young adults who randomly controlled their breathing to nine combinations of TI and TE, each chosen respectively from 2, 4, and 6 s. A 5-min R-R interval time series was obtained from each study period for further analysis. RESULTS: The magnitude of DC increased when TI or TE increased, while that of acceleration capacity (AC) remained almost unchanged by TI. We further defined a new index as 100 × DC2/(DC2 + AC2) and found it to be correlated with conventional Guzik's (r = 0.94) and Porta's (r = 0.99) indexes of HRA during different combinations of TI and TE. Increasing TI and increasing TE both enhanced the magnitudes of HRA indexes, with TI taking effect when ≤ 4 s, and TE taking effect when > 4 s. DC and HRA indexes were maximized with a TI of 4 s and a TE of 6 s. CONCLUSION: We suggest that a TI of 3-4 s with a TE of 7-6 s is an appropriate standard for slow respiration.

Implementation and Evaluation of Standardized Drug Expiration Processes Across Non-automated Areas.

Objective: The study aimed to enhance medication management efficiency by introducing a systematic approach to redistributing medications to high-utilization zones, thereby mitigating the volume and expenses associated with non-returnable expired medications. Methods: This quality improvement initiative encompassed 2 key phases. Initially, a standardized workflow for managing expiring medications was implemented across 2 satellite pharmacy areas. Subsequently, the impact of these interventions was assessed by comparing pre-implementation and post-implementation data on the quantity and monetary value of expired medications. Baseline data were derived from expired medication records spanning January 1, 2022, to December 31, 2022. The new workflow was established in December 2022, and post-implementation data were collected from January 1, 2023, to March 31, 2023. The process rollout involved devising workflow protocols, creating supportive documentation, and delivering training to pharmacy personnel. Data collection encompassed medication identifiers, stock locations, date medications were received, expiration dates, along with wholesale acquisition cost for each item. Descriptive statistical methods were employed for analysis. Results: Comparative analysis of pre-implementation and post-implementation data revealed substantial reductions in the annual estimated quantity of expired medications (284 fewer items, representing a 13.6% decrease) and corresponding wholesale acquisition costs ($5075 USD reduction, translating to a 19.7% decrease) within the satellite areas during the study period. Moreover, a comparison of post-implementation quarter one data with the corresponding data from the previous year highlighted even more significant reductions in the quantity of expired medications (203 fewer items, reflecting a 31.1% decrease) and associated wholesale acquisition costs ($2548 USD reduction, signifying a 33.0% decrease) within the satellite areas. Conclusions: This study underscores the potential advantages of employing a standardized process to proactively reallocate medications prior to their expiration, thereby enabling their utilization in other hospital sections. Future endeavors could concentrate on the wider implementation of similar workflows throughout different hospital locations and the broader enterprise.

Maternal high-fat diet changes breathing pattern and causes excessive sympathetic discharge in juvenile offspring rat.

Early life over-nutrition, as experienced in maternal obesity, is a risk factor for developing cardiorespiratory and metabolic diseases. Here we investigated the effects of high-fat diet (HFD) consumption on the breathing pattern and sympathetic discharge to blood vessels in juvenile offspring from dams fed with HFD (O-HFD). Adult female Holtzman rats were given a standard diet (SD) or HFD from 6 wk before gestation to weaning. At weaning (P21), the male offspring from SD dams (O-SD) and O-HFD received SD until the experimental day (P28-P45). Nerve recordings performed in decerebrated in situ preparations demonstrated that O-HFD animals presented abdominal expiratory hyperactivity under resting conditions and higher vasoconstrictor sympathetic activity levels. The latter was associated with blunted respiratory-related oscillations in sympathetic activity, especially in control animals. When exposed to elevated hypercapnia or hypoxia levels, the O-HFD animals mounted similar ventilatory and respiratory motor responses as the control animals. Hypercapnia and hypoxia exposure also increased sympathetic activity in both groups but did not reinstate the respiratory-sympathetic coupling in the O-HFD rats. In freely behaving conditions, O-HFD animals exhibited higher resting pulmonary ventilation and larger variability of arterial pressure levels than the O-SD animals due to augmented sympathetic modulation of blood vessel diameter. Maternal obesity modified the functioning of cardiorespiratory systems in offspring at a young age, inducing active expiration and sympathetic overactivity under resting conditions. These observations represent new evidence about pregnancy-related complications that lead to the development of respiratory distress and hypertension in children of obese mothers.NEW & NOTEWORTHY Maternal obesity is a risk factor for developing cardiorespiratory and metabolic diseases. This study highlights the changes on the breathing pattern and sympathetic discharge to blood vessels in juvenile offspring from dams fed with HFD. Maternal obesity modified the functioning of cardiorespiratory systems in offspring, inducing active expiration and sympathetic overactivity. These observations represent new evidence about pregnancy-related complications that lead to the development of respiratory distress and hypertension in children of obese mothers.

The Effect of the Drug Life Cycle Price on Cost-Effectiveness: Case Studies Using Real-World Pricing Data.

OBJECTIVES: Cost-effectiveness analyses (CEAs) generally assume constant drug prices throughout the model time horizon, yet it is known that prices are not constant, often with price decreases near loss of exclusivity (LOE). This study explores the impact of using dynamic drug-specific prices on the incremental cost-effectiveness ratio (ICER) using selected reproduced case studies. METHODS: Case studies were selected following explicit criteria to reflect a variety of drug characteristics. For each drug, a published CEA model was identified, replicated, and modified with dynamic real-world pricing data, to compare ICERs based on constant drug prices with estimates obtained when including drug life cycle pricing. The impact of dynamic real-world pricing-inclusive LOE-was analyzed using a single patient cohort and multiple cohorts over time. RESULTS: Fluvastatin, alendronic acid + colecalciferol combination therapy, letrozole and clopidogrel were selected as case studies. Inclusion of real-world pricing data compared with applying constant prices reduced the ICER in a single-cohort setting up to 43%. In the multicohort analyses, further reductions of the ICERs were observed of up to 113%. The ICERs were sensitive to the period of drug usage relative to the models' time horizons, the relative proportions of drug costs in the overall treatment costs, and timing of LOE compared with the cost year of the original analysis. CONCLUSIONS: Assuming dynamic drug prices may lead to more representative ICER estimates. Future CEAs for drugs could account for predicted and disaggregated life cycle price developments based on retrospective data.

Can you breathe yourself to a better pelvic floor? A systematic review.

INTRODUCTION: Some authors suggest that breathing exercises should be recommended instead of or in combination with pelvic floor muscle training (PFMT) to prevent and treat urinary incontinence (UI) and pelvic organ prolapse (POP). AIMS: The primary aim of the present study was to investigate the evidence for breathing as an intervention alone or in addition to PFM contraction in treatment of UI and POP. MATERIALS & METHODS: This systematic review included short-term experimental studies and randomize controlled trials (RCTs) indexed on PubMed, EMBASE, and PEDro database. A form was used to extract data that was analyzed qualitatively due to the heterogeneity in interventions and outcome measures of the included studies. The individual methodological quality of RCTs was analyzed using the PEDro scale. RESULTS: A total of 18 studies were included, 374 participants from short-term experimental studies and 765 from nine RCTs. PEDro score varied from 4 to 8. Activation of the PFM during expiration was significantly less than during a PFM contraction. In general, the RCTs showed that training the PFM is significantly more effective to improve PFM variables and UI and POP than breathing exercises, and that adding breathing exercises to PFMT have no additional effect. CONCLUSION: This systematic review indicates that the evidence for incorporating breathing exercise in clinical practice in addition to or instead of PFMT is scant or non-existing, both based on short-term experimental studies and small RCTs.

Technical note: estimating longer drug shelf-life with reliability plotting.

A graphical plot of drug stability-study data can be extrapolated to estimate the drug's percent degradation and therefore its shelf-life beyond the time period of the study. However, after a statistical confidence limit is applied, that shelf-life estimate is significantly reduced. Such a reduction can be minimized by transforming the data so that it plots as close as possible to linearity, a process that is called reliability plotting. Reliability plotting seems to have been rarely if ever used on drug stability data, despite its being mentioned in relevant guidance documents and its ability to justify longer shelf-life at no additional cost. For example, an 18-month stability study resulted in a 19-month shelf-life using standard extrapolation methods but resulted in a 23 month shelf-life using reliability plotting.

Effects and safety of hypertonic saline combined with airway clearance in non-hospitalized children with recurrent wheezing.

Background: The International Study of Wheezing in Infants defines recurrent wheezing as the presence of three or more medically documented episodes of wheezing within one year. To date, there is no evidence on the use of hypertonic saline (HS) combined with airway clearance techniques (ACT) for children with recurrent wheezing treated in an outpatient setting. Therefore, this is the first study to explore the use of such interventions in infants with recurrent wheezing. Objectives: To evaluate the effects and safety of a three-month protocol including HS and ACT for non-hospitalized infants with recurrent wheezing. Methods: Randomized, double-blind, controlled trial, including outpatient infants with recurrent wheezing. Children were randomized to either 3% HS or 0.9% saline groups and were treated with bronchodilator and nebulized with the respective solutions before ACT. The primary outcome was the Wang score. Secondary outcomes included the number of hospitalizations and respiratory crisis, need for rescue medication, and school absences. All variables were measured during the three previous months from inclusion and during intervention period. The study protocol was registered at ClinicalTrials.gov (NCT04331496) on March, 31, 2020. Results: Forty children were included. Regarding immediate effects, significant differences (p<0.001) were found for time, but not for group or interaction (group × time), in all outcome variables (increase in SpO2, decrease in heart and respiratory rate, wheezing episodes, retraction, and Wang score). Comparing the previous three months with the study period, there were significant differences in both groups for the severity of crisis (p<0.001) and medication steps (p=0.002). Conclusion: A three-month protocol including HS and ACT for outpatient infants with recurrent wheezing was safe and reduced morbidity. No differences were found between the use of HS and 0.9% saline.

Expiratory activity during sleep in children.

Sleep irregularities and respiratory events (apnea, O2 desaturation or a combination thereof) are often present in the infant population. While inspiration is the main active process in the act of breathing, expiration is generally thought to occur passively. Although commonly considered as quiet during sleep, expiratory abdominal muscles have been proposed to be recruited to promote ventilation, facilitate gas exchange, and reduce the work of breathing during conditions of increased respiratory drive, exercise, or airway obstruction. In this study, we investigated the occurrence of expiratory abdominal muscle activity in polysomnographic studies of subjects (aged 0-2 years) suspected of sleep disordered breathing. Our results indicate that abdominal muscle activation occurs during sleep, most frequently during non-rapid eye movement and rapid-eye movement states compared to slow-wave sleep. Furthermore, abdominal muscle activity was present during regular breathing or associated with respiratory events (apneas or O2 desaturation). In the latter case, abdominal muscle recruitment more frequently followed the onset of respiratory events and terminated with recovery from blood O2 desaturation events. We conclude that expiratory abdominal muscle activity contributes to the pattern of respiratory muscle recruitment during sleep in infants and given its temporal relationship with respiratory events, we propose that its recruitment could facilitate proper ventilation by counteracting airway resistance and O2 desaturation in infancy across different stages of sleep.

Time constant to determine PEEP levels in mechanically ventilated COVID-19 ARDS: a feasibility study.

BACKGROUND: We hypothesized that the measured expiratory time constant (TauE) could be a bedside parameter for the evaluation of positive end-expiratory pressure (PEEP) settings in mechanically ventilated COVID-19 patients during pressure-controlled ventilation (PCV). METHODS: A prospective study was conducted including consecutively admitted adults (n = 16) with COVID-19-related ARDS requiring mechanical ventilation. A PEEP titration using PCV with a fixed driving pressure of 14 cmH2O was performed and TauE recorded at each PEEP level (0 to 18 cmH2O) in prone (n = 29) or supine (n = 24) positions. The PEEP setting with the highest TauE (TauEMAX) was considered to represent the best tradeoff between recruitment and overdistention. RESULTS: Two groups of patterns were observed in the TauE plots: recruitable (R) (75%) and nonrecruitable (NR) (25%). In the R group, the optimal PEEP and PEEP ranges were 8 ± 3 cmH2O and 6-10 cmH2O for the prone position and 9 ± 3 cmH2O and 7-12 cmH2O for the supine position. In the NR group, the optimal PEEP and PEEP ranges were 4 ± 4 cmH2O and 1-8 cmH2O for the prone position and 5 ± 3 cmH2O and 1-7 cmH2O for the supine position, respectively. The R group showed significantly higher optimal PEEP (p < 0.004) and PEEP ranges (p < 0.001) than the NR group. Forty-five percent of measurements resulted in the most optimal PEEP being significantly different between the positions (p < 0.01). Moderate positive correlation has been found between TauE vs CRS at all PEEP levels (r2 = 0.43, p < 0.001). CONCLUSIONS: TauE may be a novel method to assess PEEP levels. There was wide variation in patient responses to PEEP, which indicates the need for personalized evaluation.

Compacted Area with Effective Links (CAEL) for Data Dissemination in VANETs.

Vehicular ad hoc network (VANET) is a specialized form of wireless network that is solely intended for collaboration between vehicles. Several studies have shown that standard routing protocols cannot be implemented in VANETs because of their unique characteristics such as their significant count of vehicles on the network and the rapid evolution of the network's design. Because VANET communication links are broken very frequently, it is necessary to address the routing consistency of these highly dynamic networks. The transmission of VANET data may result in a substantial amount of overhead in the routing process; thus, it is vital to address the issue of overhead to enhance the overall network performance. The proposed protocol named compacted area with effective links (CAEL) is designed to focus on decreasing overhead to achieve an enhancement in PDR performance inside the network. The communication between selected nodes that have been judged to be dependable in terms of geographical location and appropriate existing links between vehicles is focused on achieving this goal. With the inclusion of the reliability factor, it is possible to complete the important step of removing extraneous nodes, with the selection of the trustworthy nodes being made based on the link expiration time during the whole routing procedure. When compared to our previously published protocols, i.e., Dynamic Trilateral Enrollment (DyTE) and Reliable Group of Vehicles (RGoV), the results of the simulations demonstrate that CAEL has achieved an overall improvement in the performance of the network.

System for Storage, Dispensing, and Tracking Expiration of Electrocardiography Electrodes.

Electrocardiography electrodes have expiration dates that are foreshortened once the manufacturer's packaging is opened. A system is described for storing and dispensing these perishable electrodes while tracking their new expiration date for safety and regulatory purposes.

Nonlinear Statistical Analysis of Normal and Pathological Infant Cry Signals in Cepstrum Domain by Multifractal Wavelet Leaders.

Multifractal behavior in the cepstrum representation of healthy and unhealthy infant cry signals is examined by means of wavelet leaders and compared using the Student t-test. The empirical results show that both expiration and inspiration signals exhibit clear evidence of multifractal properties under healthy and unhealthy conditions. In addition, expiration and inspiration signals exhibit more complexity under healthy conditions than under unhealthy conditions. Furthermore, distributions of multifractal characteristics are different across healthy and unhealthy conditions. Hence, this study improves the understanding of infant crying by providing a complete description of its intrinsic dynamics to better evaluate its health status.

Differential Contribution of the Retrotrapezoid Nucleus and C1 Neurons to Active Expiration and Arousal in Rats.

Collectively, the retrotrapezoid nucleus (RTN) and adjacent C1 neurons regulate breathing, circulation and the state of vigilance, but previous methods to manipulate the activity of these neurons have been insufficiently selective to parse out their relative roles. We hypothesize that RTN and C1 neurons regulate distinct aspects of breathing (e.g., frequency, amplitude, active expiration, sighing) and differ in their ability to produce arousal from sleep. Here we use optogenetics and a combination of viral vectors in adult male and female Th-Cre rats to transduce selectively RTN (Phox2b+/Nmb+) or C1 neurons (Phox2b+/Th+) with Channelrhodopsin-2. RTN photostimulation modestly increased the probability of arousal. RTN stimulation robustly increased breathing frequency and amplitude; it also triggered strong active expiration but not sighs. Consistent with these responses, RTN innervates the entire pontomedullary respiratory network, including expiratory premotor neurons in the caudal ventral respiratory group, but RTN has very limited projections to brainstem regions that regulate arousal (locus ceruleus, CGRP+ parabrachial neurons). C1 neuron stimulation produced robust arousals and similar increases in breathing frequency and amplitude compared with RTN stimulation, but sighs were elicited and active expiration was absent. Unlike RTN, C1 neurons innervate the locus ceruleus, CGRP+ processes within the parabrachial complex, and lack projections to caudal ventral respiratory group. In sum, stimulating C1 or RTN activates breathing robustly, but only RTN neuron stimulation produces active expiration, consistent with their role as central respiratory chemoreceptors. Conversely, C1 stimulation strongly stimulates ascending arousal systems and sighs, consistent with their postulated role in acute stress responses.SIGNIFICANCE STATEMENT The C1 neurons and the retrotrapezoid nucleus (RTN) reside in the rostral ventrolateral medulla. Both regulate breathing and the cardiovascular system but in ways that are unclear because of technical limitations (anesthesia, nonselective neuronal actuators). Using optogenetics in unanesthetized rats, we found that selective stimulation of either RTN or C1 neurons activates breathing. However, only RTN triggers active expiration, presumably because RTN, unlike C1, has direct excitatory projections to abdominal premotor neurons. The arousal potential of the C1 neurons is far greater than that of the RTN, however, consistent with C1's projections to brainstem wake-promoting structures. In short, C1 neurons orchestrate cardiorespiratory and arousal responses to somatic stresses, whereas RTN selectively controls lung ventilation and arterial Pco2 stability.

Inhibitory mechanisms control active expiration by limiting parafacial expiratory drive.

Activity of parafacial neurons that control active expiration is heavily dependent on tonic and CO2/H+-dependent excitatory and inhibitory inputs from yet poorly defined sources. Contrary to the idea that CO2/H+ disinhibits parafacial expiratory neurons, the recent work of J. D. Silva et al. (Silva JD, Oliveira LM, Souza FC, Moreira TS, Takakura AC. J Neurophysiol 123: 1933-1943, 2020) suggests that GABAergic raphe neurons preferentially limit expiratory activity during high CO2. Here, I discuss these findings and propose a model where GABAergic raphe neurons function as CO2/H+-dependent breaks on expiratory drive.

Extending the post-thaw viability of cryoprecipitate.

BACKGROUND: Cryoprecipitate has a short post-thaw expiry time of 6 h. The aim of this study was to assess the stability and function of cryoprecipitate components (FVIII, fibrinogen, vWF, and FXIII) and cryoprecipitate sterility up to 120 h post-thawing when stored at two temperatures (2-6°C and room temperature [20-24°C]). METHODS AND MATERIALS: Twenty batches (110 individual units) of time-expired, thawed cryoprecipitate were collected. Units were sampled at the 6-h expiration mark and then stored at 2-6°C or room temperature (RT). They were resampled every 24 h for 120 h. One unit from each batch was sent for sterility testing at 120 h. Samples had FVIII (one stage and chromogenic), fibrinogen, FXIII, vWFag, and vWF:RCo assays performed in batches. Rotational thromboelastometry (ROTEM) was also performed. RESULTS: FVIII levels declined significantly at 120 h post-thawing at both RT and 2-6°C, but still met international standards for FVIII content. Fibrinogen, vWF antigen, and FXIII levels reduced minimally over 120 h and always met international standard requirements when stored at either temperature. ROTEM analysis demonstrated that fibrinogen function was not compromised at 120 h post-thawing under both storage conditions. vWF:RCo levels declined significantly over 120 h at both storage temperatures. No bacterial contamination was detected in 20 units of cryoprecipitate following storage for 120 h post-thawing. CONCLUSION: These results demonstrate that extension of the storage time of thawed cryoprecipitate to 120 h, stored at either 2-6°C or RT, is feasible while still maintaining required FVIII, fibrinogen, and vWFag levels. Storage at 2-6°C has the advantage of reduced risk of potential bacterial contamination.

Changes in the autonomic and respiratory patterns in mice submitted to short-term sustained hypoxia.

NEW FINDINGS: What is the central question of this study? Do mice submitted to sustained hypoxia present autonomic and respiratory changes similarly to rats? What is the main finding and its importance? Arterial pressure in the normal range, reduced baseline heart rate and tachypnoea were observed in behaving sustained hypoxia mice. Recordings in the in situ preparation of mice submitted to sustained hypoxia show an increase in cervical vagus nerve activity and a simultaneous reduction in thoracic sympathetic nerve activity correlated with changes in the respiratory cycle. Therefore, mice are an important model for studies on the modulation of sympathetic activity to the cardiovascular system and the vagus innervation of the upper airways due to changes in the respiratory network induced by sustained hypoxia. ABSTRACT: Short-term sustained hypoxia (SH) in rats induces sympathetic overactivity and hypertension due to changes in sympathetic-respiratory coupling. However, there are no consistent data about the effect of SH on mice due to the different protocols of hypoxia and difficulties associated with the handling of these rodents under different experimental conditions. In situ recordings of autonomic and respiratory nerves in SH mice have not been performed yet. Herein, we evaluated the effects of SH ( FiO2  = 0.1 for 24 h) on baseline mean arterial pressure (MAP), heart rate (HR), respiratory frequency (fR ) and responses to chemoreflex activation in behaving SH mice. A characterization of changes in cervical vagus (cVN), thoracic sympathetic (tSN), phrenic (PN) and abdominal (AbN) nerves in SH mice using the in situ working heart-brainstem preparation was also performed. SH mice presented normal MAP, significant reduction in baseline HR, increase in baseline fR , as well as increase in the magnitude of bradycardic response to chemoreflex activation. In in situ preparations, SH mice presented a reduction in PN discharge frequency, and increases in the time of expiration and incidence of late-expiratory bursts in AbN activity. Nerve recordings also indicated a significant increase in cVN activity and a significant reduction in tSN activity during expiration in SH mice. These findings make SH mice an important experimental model for better understanding how changes in the respiratory network may impact on the modulation of vagal control to the upper airways, as well as in the sympathetic activity to the cardiovascular system.

An assessment of techniques and practices used to elevate intra-abdominal pressure when assessing pelvic floor dysfunction.

AIMS: To determine terminology and methods for raising intra-abdominal pressure (IAP) currently used by clinicians to assess pelvic floor dysfunction (PFD) and to measure the effect of these maneuvers on IAP. METHODS: Three-hundred questionnaires were distributed at two scientific meetings in the United Kingdom to determine methods clinicians used to raise IAP and their perceptions of these methods. Twenty healthy volunteers were also recruited to measure the effect of two methods of raising IAP: Valsalva maneuver (VM) and bear down maneuver (BDM). IAP pressure was measured with rectal catheters connected to pressure sensors. The IAP was measured during each maneuver in both standing and supine positions. RESULTS: Maneuvers used in practice were cough (79%), BDM (60%), and VM (38%). 44% of clinicians felt patients found it difficult to raise their IAP. There was uncertainty among clinicians as to which method was the most effective in raising IAP and whether the different methods produced the same rise in IAP. On testing IAP in 20 healthy volunteers, median (interquartile range) IAP generated during BDM; 101 (59.1) cmH2 O was significantly higher than that generated during VM; 80.3 (43.6) cmH2 O (p < .0001). CONCLUSION: Clinicians varied widely in the maneuvers they used to raise patients' IAP to test for PFD and there was uncertainty about the maneuvers' effect on IAP. In healthy volunteers, BDM produced significantly higher IAP than VM. We recommend standardization of terminology and techniques used to raise IAP when assessing PFD, to ensure consistency of diagnosis and assessment of treatment outcomes.

Variability in expiratory trajectory angles during consonant production by one human subject and from a physical mouth model: Application to respiratory droplet emission.

The COVID-19 pandemic has highlighted the need to improve understanding of droplet transport during expiratory emissions. While historical emphasis has been placed on violent events such as coughing and sneezing, the recognition of asymptomatic and presymptomatic spread has identified the need to consider other modalities, such as speaking. Accurate prediction of infection risk produced by speaking requires knowledge of both the droplet size distributions that are produced, as well as the expiratory flow fields that transport the droplets into the surroundings. This work demonstrates that the expiratory flow field produced by consonant productions is highly unsteady, exhibiting extremely broad inter- and intra-consonant variability, with mean ejection angles varying from ≈+30° to -30°. Furthermore, implementation of a physical mouth model to quantify the expiratory flow fields for fricative pronunciation of [f] and [θ] demonstrates that flow velocities at the lips are higher than previously predicted, reaching 20-30 m/s, and that the resultant trajectories are unstable. Because both large and small droplet transport are directly influenced by the magnitude and trajectory of the expirated air stream, these findings indicate that prior investigations of the flow dynamics during speech have largely underestimated the fluid penetration distances that can be achieved for particular consonant utterances.