Anatomy and mechanisms of vocal production in harvest mice.

Characterizing mechanisms of vocal production provides important insight into the ecology of acoustic divergence. In this study, we characterized production mechanisms of two types of vocalizations emitted by western harvest mice (Reithrodontomys megalotis), a species uniquely positioned to inform trait evolution because it is a sister taxon to peromyscines (Peromyscus and Onychomys spp.), which use vocal fold vibrations to produce long-distance calls, but more ecologically and acoustically similar to baiomyines (Baiomys and Scotinomys spp.), which employ a whistle mechanism. We found that long-distance calls (∼10 kHz) were produced by airflow-induced vocal fold vibrations, whereas high-frequency quavers used in close-distance social interactions (∼80 kHz) were generated by a whistle mechanism. Both production mechanisms were facilitated by a characteristic laryngeal morphology. Our findings indicate that the use of vocal fold vibrations for long-distance communication is widespread in reithrodontomyines (Onychomys, Peromyscus, Reithrodontomys spp.) despite overlap in frequency content that characterizes baiomyine whistled vocalizations. The results illustrate how different production mechanisms shape acoustic variation in rodents and contribute to ecologically relevant communication distances.

Breathing a low-density gas reduces respiratory muscle force development and marginally improves exercise performance in master athletes.

INTRODUCTION: We tested the hypothesis that breathing heliox, to attenuate the mechanical constraints accompanying the decline in pulmonary function with aging, improves exercise performance. METHODS: Fourteen endurance-trained older men (67.9 ± 5.9 year, [Formula: see text]O2max: 50.8 ± 5.8 ml/kg/min; 151% predicted) completed two cycling 5-km time trials while breathing room air (i.e., 21% O2-79% N2) or heliox (i.e., 21% O2-79% He). Maximal flow-volume curves (MFVC) were determined pre-exercise to characterize expiratory flow limitation (EFL, % tidal volume intersecting the MFVC). Respiratory muscle force development was indirectly determined as the product of the time integral of inspiratory and expiratory mouth pressure (∫Pmouth) and breathing frequency. Maximal inspiratory and expiratory pressure maneuvers were performed pre-exercise and post-exercise to estimate respiratory muscle fatigue. RESULTS: Exercise performance time improved (527.6 ± 38 vs. 531.3 ± 36.9 s; P = 0.017), and respiratory muscle force development decreased during inspiration (- 22.8 ± 11.6%, P < 0.001) and expiration (- 10.8 ± 11.4%, P = 0.003) with heliox compared with room air. EFL tended to be lower with heliox (22 ± 23 vs. 30 ± 23% tidal volume; P = 0.054). Minute ventilation normalized to CO2 production ([Formula: see text]E/[Formula: see text]CO2) increased with heliox (28.6 ± 2.7 vs. 25.1 ± 1.8; P < 0.001). A reduction in MIP and MEP was observed post-exercise vs. pre-exercise but was not different between conditions. CONCLUSIONS: Breathing heliox has a limited effect on performance during a 5-km time trial in master athletes despite a reduction in respiratory muscle force development.

Heliox Protects SH-SY5Y Cells from Oxygen-Glucose Deprivation/Reperfusion-Induced Ferroptosis.

BACKGROUND: Heliox shows protective effects against acute focal ischemia-reperfusion injury in the brain. However, further research is needed to unveil the intricate molecular mechanisms involved. Determining how heliox affects ferroptosis caused by oxygen-glucose deprivation/reoxygenation (OGD/R) in SH-SY5Y cells as well as the underlying mechanism was the goal of the current work. METHODS: With the use of 2',7'-Dichlorodihydrofluorescein diacetate (DCFH-DA), JC-1, and methyl thiazolyl tetrazolium, we assessed the survival, reactive oxygen species (ROS), and mitochondrial membrane potential in SH-SY5Y cells after they had been exposed to OGD/R and heliox. The expression of molecules associated with ferroptosis and the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway was analyzed using quantitative polymerase chain reaction (PCR) and immunoblotting, while malondialdehyde (MDA), oxidized glutathione disulfide (GSSG), ferrous ion (Fe2+), and reduced glutathione (GSH) levels were evaluated using biochemical kits. RESULTS: OGD/R treatment reduced the GSH to GSSG ratio; the potential of the mitochondrial membrane; the expression of the proteins GSH, SLC7A11, and glutathione peroxidase 4 (GPX4); and the ability of SH-SY5Y cells to survive. In contrast, OGD/R treatment increased the expression of cyclooxygenase-2 (COX2), ACSL4, and ferritin heavy chain 1 (FTH1) proteins, the production of MDA and GSSG, and the levels of ROS and Fe2+. However, heliox effectively mitigated all these OGD/R-induced effects. Furthermore, in OGD/R-treated SH-SY5Y cells, heliox administration stimulated the PI3K/AKT pathway while suppressing the nuclear factor-κB (NF-κB) pathway. When MK-2206, an AKT inhibitor, was applied concurrently to the cells, these outcomes were reversed. CONCLUSIONS: Heliox prevents OGD/R from causing ferroptosis in SH-SY5Y cells by activating the PI3K/AKT pathway. This suggests a promising therapeutic potential for heliox use in the management of ischemia/reperfusion injury.

Mechanisms of sound production in deer mice (Peromyscus spp.).

Rodent diversification is associated with a large diversity of species-specific social vocalizations generated by two distinct laryngeal sound production mechanisms: whistling and airflow-induced vocal fold vibration. Understanding the relative importance of each modality to context-dependent acoustic interactions requires comparative analyses among closely related species. In this study, we used light gas experiments, acoustic analyses and laryngeal morphometrics to identify the distribution of the two mechanisms among six species of deer mice (Peromyscus spp.). We found that high frequency vocalizations (simple and complex sweeps) produced in close-distance contexts were generated by a whistle mechanism. In contrast, lower frequency sustained vocalizations (SVs) used in longer distance communication were produced by airflow-induced vocal fold vibrations. Pup isolation calls, which resemble adult SVs, were also produced by airflow-induced vocal fold vibrations. Nonlinear phenomena (NLP) were common in adult SVs and pup isolation calls, suggesting irregular vocal fold vibration characteristics. Both vocal production mechanisms were facilitated by a characteristic laryngeal morphology, including a two-layered vocal fold lamina propria, small vocal membrane-like extensions on the free edge of the vocal fold, and a singular ventral laryngeal air pocket known as the ventral pouch. The size and composition of vocal folds (rather than total laryngeal size) appears to contribute to species-specific acoustic properties. Our findings suggest that dual modes of sound production are more widespread among rodents than previously appreciated. Additionally, the common occurrence of NLP highlights the nonlinearity of the vocal apparatus, whereby small changes in anatomy or physiology trigger large changes in behavior. Finally, consistency in mechanisms of sound production used by neonates and adults underscores the importance of considering vocal ontogeny in the diversification of species-specific acoustic signals.

Heliox for Pediatric Critical Asthma: A Multicenter, Retrospective, Registry-Based Descriptive Study.

BACKGROUND: In cases of critical asthma (CA), heliox may be applied as an adjunctive rescue therapy to avoid invasive mechanical ventilation (MV), improve deposition of aerosolized medications, and enhance laminar airflow through obstructed airways. Using the Pediatric Health Information System (PHIS) registry, we evaluate heliox prescribing and explored for differences in MV rates and hospital length of stay (LOS) among children with and without heliox exposure. METHODS: We performed a retrospective cohort study using PHIS data from 42 pediatric intensive care units among children 5-17 years of age admitted for CA from 2010 through 2019. Primary outcomes were heliox prescribing rates and trends. Secondary outcomes were invasive MV rates and LOS assessed in a subgroup of children receiving ≥ 1 adjunctive intervention(s). RESULTS: Of the 19,780 studied, heliox was prescribed in 12.5% and linearly declined from 16.1% in 2010 to 5.6% in 2019. The overall MV rate was 12.8% and was lower in subjects receiving heliox alone (4.9%) compared to heliox plus alternative adjunctive therapies [31.2%] or children receiving non-heliox adjunctive therapies [22.1%], P < .01). Accounting for MV, no difference in LOS was observed. In exploratory adjusted models, MV free hospitalization was associated with heliox-only exposure (OR: 0.33, 95% CI: 0.17-0.63, P < .01) and exposure to multiple adjunctive therapies was associated with MV (OR: 2.48, 95% CI: 1.56-3.94, P < .01). CONCLUSIONS: In this multicenter retrospective study from 42 children's hospitals, heliox prescribing for CA declined over the last decade. Subjects receiving multiple adjunctive therapies more commonly required invasive MV perhaps indicating a greater severity of illness. At this time, prospective trials needed to identify the role of heliox for pediatric CA.

[Chronic respiratory failure correction in cicatricial laryngeal and tracheal stenosis using helium-oxygen mixture]. / Korrektsiya khronicheskoi dykhatel'noi nedostatochnosti pri rubtsovykh stenozakh gortani i sheinogo otdela trakhei s ispol'zovaniem gelii-kislorodnoi smesi.

The article provides a review of the literature on the development of chronic respiratory failure in patients with chronic cicatricial stenosis of the larynx and cervical trachea. The authors provide data on the etiology, pathogenetic features of the course of cicatricial stenosis of the larynx and trachea, the reasons for the development of chronic respiratory failure, the effect of hypoxemia on general metabolic processes in the body and on regeneration processes, as well as on methods of their correction and improvement of the postoperative period. The methods of respiratory impact on chronic respiratory failure in these patients are considered, based on the experience of a number of researchers and technical advances in recent years.

The effects of heliox non-saturation diving on the cardiovascular system and cognitive functions.

The purpose of this study was to investigate the effects of a single bout of heliox non-saturation diving on the cardiovascular system and cognitive function. Ten recreational scuba divers (10 males, ∼35 years old) participated in this study. These subjects made two pool dives within a one-week interval, alternating gases with compressed air (21% O2, 79% N2) and with heliox (21% O2 and 79% He). The depth was to 26 meters over a 20-minute duration. The results showed that heliox diving significantly increased blood O2 saturation by 1.15% and significantly decreased blood lactate levels by ∼57% when compared with air diving (P ≺ 0.05). However, there were no significant differences in resting heart rate, systolic or diastolic pressure, core body blood pressure, and pulse wave velocity between the heliox and air dives. The Stroop test showed that the heliox dive significantly increased cognitive function compared with the air dive in both the simple test (Offtime) and interference test (Ontime) (P ≺ 0.05). It was concluded that the heliox dive increases blood O2 saturation and decreases blood lactate concentration when compared with air dives. These conditions are likely to help divers reduce hypoxia in the water, reduce the risk of loss of consciousness, reduce fatigue and allow them to dive for longer. Heliox diving may also help judgment and risk coping skills in the water due to the improvement of cognitive ability as compared to air breathing dives.

Manipulation of mechanical ventilatory constraint during moderate intensity exercise does not influence dyspnoea in healthy older men and women.

KEY POINTS: The perceived intensity of exertional breathlessness (i.e. dyspnoea) is higher in older women than in older men, possibly as a result of sex-differences in respiratory system morphology. During exercise at a given absolute intensity or minute ventilation, older women have a greater degree of mechanical ventilatory constraint (i.e. work of breathing and expiratory flow limitation) than their male counterparts, which may lead to a greater perceived intensity of dyspnoea. Using a single-blind randomized study design, we experimentally manipulated the magnitude of mechanical ventilatory constraint during moderate-intensity exercise at ventilatory threshold in healthy older men and women. We found that changes in the magnitude of mechanical ventilatory constraint within the physiological range had no effect on dyspnoea in healthy older adults. When older men and women perform moderate intensity exercise, mechanical ventilatory constraint does not contribute significantly to the sensation of dyspnoea. ABSTRACT: We aimed to determine the effect of manipulating mechanical ventilatory constraint during submaximal exercise on dyspnoea in older men and women. Eighteen healthy subjects (aged 60-80 years; nine men and nine women) completed two days of testing. On day 1, subjects were assessed for pulmonary function and performed a maximal incremental cycle exercise test. On day 2, subjects performed three 6-min bouts of cycling at ventilatory threshold, in a single-blind randomized manner, while breathing: (i) normoxic helium-oxygen (HEL) to reduce the work of breathing (Wb ) and alleviate expiratory flow limitation (EFL); (ii) through an inspiratory resistance (RES) of ∼5 cmH2 O L-1  s-1 to increase Wb ; and (iii) ambient air as a control (CON). Oesophageal pressure, diaphragm electromyography, and sensory responses (category-ratio 10 Borg scale) were monitored throughout exercise. During the HEL condition, there was a significant decrease in Wb (men: -21 ± 6%, women: -17 ± 10%) relative to CON (both P < 0.01). Moreover, if EFL was present during CON (four men and five women), it was alleviated during HEL. Conversely, during the RES condition, Wb (men: 42 ± 19%, women: 50 ± 16%) significantly increased relative to CON (both P < 0.01). There was no main effect of sex on Wb (P = 0.59). Across conditions, women reported significantly higher dyspnoea intensity than men (2.9 ± 0.9 vs. 1.9 ± 0.8 Borg scale units, P < 0.05). Despite significant differences in the degree of mechanical ventilatory constraint between conditions, the intensity of dyspnoea was unaffected, independent of sex (P = 0.46). When older men and women perform moderate intensity exercise, mechanical ventilatory constraint does not contribute significantly to the sensation of dyspnoea.

A proof-of-concept trial of HELIOX with different fractions of helium in a human study modeling upper airway obstruction.

BACKGROUND: Helium in oxygen (HELIOX) can relieve airway obstruction and lower the work of breathing because it increases the threshold at which turbulent gas flow is induced. Less turbulent and more laminar flow lowers the work of breathing. According to guidelines, the fraction of Helium in HELIOX should be maximized (e.g. to 79%). Here, we investigate whether HELIOX with less than 60% of Helium is able to relieve the sensation of dyspnea in healthy volunteers. METHODS: 44 volunteers underwent resistive loading breathing different gases (medical air and HELIOX with a fraction of 25%, 50% or 75% helium in oxygen) in a double-blinded crossover design. Subjects rated their degree of dyspnea (primary outcome parameter) and the variability of noninvasively measured systolic blood pressure was assessed. RESULTS: Dyspnea was significantly reduced by HELIOX-containing mixtures with a fraction of helium of 25% or more. Similarly, blood pressure variability was reduced significantly even with helium 25% during respiratory loading with the higher load, whereas with the smaller load an effect could only be obtained with the highest helium fraction of 75%. CONCLUSION: In this clinical trial, HELIOX with less than 60% of helium in oxygen decreased the sensation of dyspnea and blood pressure variability, a surrogate parameter for airway obstruction. Therefore, higher oxygen fractions might be applied without losing the helium-related benefits for the treatment of upper airway obstruction. TRIAL REGISTRATION: Registration with clinical trials (NCT00788788) and EMA (EudraCT number: 2006-005289-37).

Respiration of thermogenic inflorescences of skunk cabbage Symplocarpus renifolius in heliox.

The respiration rate of the thermogenic inflorescences of Japanese skunk cabbage Symplocarpus renifolius can reach 300 nmol s-1 g-1 , which is sufficient to raise spadix temperature (Ts ) up to 15 °C above ambient air temperature (Ta ). Respiration rate is inversely related to Ta , such that the Ts achieves a degree of independence from Ta , an effect known as temperature regulation. Here, we measure oxygen consumption rate (Mo2 ) in air (21% O2 in mainly N2 ) and in heliox (21% O2 in He) to investigate the diffusive conductance of the network of gas-filled spaces and the thermoregulatory response. When Ts was clamped at 15 °C, the temperature that produces maximal Mo2 in this species, exposure to high diffusivity heliox increased mean Mo2 significantly from 137 ± 17 to 202 ± 43 nmol s-1 g-1 FW, indicating that respiration in air is normally limited by diffusion in the gas phase and some mitochondria are unsaturated. When Ta was clamped at 15 °C and Ts was allowed to vary, exposure to heliox reduced Ts 1 °C and increased Mo2 significantly from 116 ± 10 to 137 ± 19 nmol s-1 g-1 , indicating that enhanced heat loss by conduction and convection can elicit the thermoregulatory response.