Respiratory Control Research Articles

Evaluation of the spatial distribution of aerosols produced by various respiratory activities

This study investigated the dispersion and evaporation characteristics of droplets and droplet nuclei emitted during human respiratory activities. A specially designed wind tunnel was filled with purified air, wherein selected subjects performed various respiratory activities with their heads positioned inside. An optical particle sizer was used to collect particles with sizes of 0.3–10 μm at 63 points in front of the mouth. The dilution factors were analyzed to investigate the impact of combining the exhaled airflow with ambient air on droplet evaporation. At a distance of 0.01 m from the mouth opening, the volume concentration of the particles was the highest during breathing, followed by coughing and speaking. The volumetric concentration of particles decreased with an increase in the distance from the inlet for all activities. The spatial volume concentration distribution of particles showed that coughing tended to disperse the particles in the forward direction, whereas speaking tended to disperse them laterally. Utilizing these findings in CFD analysis can provide in-depth insights into dispersion and evaporation dynamics. This can contribute significantly to the development of preventive measures through the implementation of proactive HVAC systems to effectively remove infectious particles and control the spread of infectious diseases. Future studies should explore a wider range of particle sizes and advanced sampling techniques for a clear understanding of respiratory particle dynamics and infection control strategies.

Development of Respiratory Infection Prevention and Control Self-Efficacy Scale for Adults.

This study aimed to develop a scale for respiratory infection prevention and control self-efficacy (R-PACS) to measure self-efficacy in the prevention and control of the spread of respiratory infections among adults and to confirm the applicability of the developed scale by testing its validity and reliability. This methodological study was conducted in two phases. During the first phase, the R-PACS scale was developed after conducting a thorough literature review, content validity, and a pilot test. In the second phase, its validity and reliability were verified against 210 university students in Korea. The criterion validity of the developed R-PACS scale was tested using the correlation with resilience scale. Item analysis, explanatory factor analysis, and convergent and discriminant validity analyses were conducted in order to verify construct validity. Furthermore, Cronbach's α was used to verify internal consistency reliability. The final version of the R-PACS scale comprises 4 factors and 16 items rated on a 5-point Likert scale. Higher scores are interpreted as higher levels of self-efficacy in the prevention and control of respiratory infection. The R-PACS scale exhibited good content validity, construct validity, criterion validity, and reliability. The correlation coefficient of the four factors was ≥.4, confirming the validity of item convergence; meanwhile, the Cronbach's α coefficient for the final 16 items of the developed scale was 0.923, verifying reliability. This scale consists of four factors: "environmental management", "contact restrictions", "general infection prevention and control", and "early detection". The applicability of the R-PACS scale exhibited acceptable validity and reliability. This scale can be utilized to assess and evaluate the degree of self-efficacy in the prevention and control of respiratory infections among adults. Data obtained using this scale can be utilized for preparing health behavior change and health promotion programs, and practical policies for preventing respiratory infections.

Mitochondrial dysfunction precedes hippocampal IL-1β transcription and cognitive impairments after low-dose lipopolysaccharide injection in aged mice

Acute cognitive impairments termed delirium often occur after inflammatory insults in elderly patients. While previous preclinical studies suggest mitochondria as a target for reducing neuroinflammation and cognitive impairments after LPS injection, fewer studies have evaluated the effects of a low-grade systemic inflammation in the aged brain. Thus, to identify the significance of mitochondrial dysfunction after a clinically relevant systemic inflammatory stimulus, we injected old-aged mice (18–20 months) with low-dose lipopolysaccharide (LPS, 0.04 mg/kg). LPS injection reduced mitochondrial respiration in the hippocampus 24 h after injection (respiratory control ratio [RCR], state3u/state4o; control = 2.82 ± 0.19, LPS = 2.57 ± 0.08). However, gene expression of the pro-inflammatory cytokine IL-1β was increased (RT-PCR, control = 1.00 ± 0.30; LPS = 2.01 ± 0.67) at a more delayed time point, 48 h after LPS injection. Such changes were associated with cognitive impairments in the Barnes maze and fear chamber tests. Notably, young mice were unaffected by low-dose LPS, suggesting that mitochondrial dysfunction precedes neuroinflammation and cognitive decline in elderly patients following a low-grade systemic insult. Our findings highlight mitochondria as a potential therapeutic target for reducing delirium in elderly patients.

Cardiac mitochondrial metabolism during pregnancy and the postpartum period.

The goal of the present study was to characterize changes in mitochondrial respiration in the maternal heart during pregnancy and after birth. Timed pregnancy studies were performed in 12-wk-old female FVB/NJ mice, and cardiac mitochondria were isolated from the following groups of mice: nonpregnant (NP), midpregnancy (MP), late pregnancy (LP), and 1-wk postbirth (PB). Similar to our previous studies, we observed increased heart size during all stages of pregnancy (e.g., MP and LP) and postbirth (e.g., PB) compared with NP mice. Differential cardiac gene and protein expression analyses revealed changes in several mitochondrial transcripts at LP and PB, including several mitochondrial complex subunits and members of the Slc family, important for mitochondrial substrate transport. Respirometry revealed that pyruvate- and glutamate-supported state 3 respiration was significantly higher in PB vs. LP mitochondria, with respiratory control ratio (RCR) values higher in PB mitochondria. In addition, we found that PB mitochondria respired more avidly when given 3-hydroxybutyrate (3-OHB) than mitochondria from NP, MP, and LP hearts, with no differences in RCR. These increases in respiration in PB hearts occurred independent of changes in mitochondrial yield but were associated with higher abundance of 3-hydroxybutyrate dehydrogenase 1. Collectively, these findings suggest that, after birth, maternal cardiac mitochondria have an increased capacity to use 3-OHB, pyruvate, and glutamate as energy sources; however, increases in mitochondrial efficiency in the postpartum heart appear limited to carbohydrate and amino acid metabolism.NEW & NOTEWORTHY Few studies have detailed the physiological adaptations that occur in the maternal heart. We and others have shown that pregnancy-induced cardiac growth is associated with significant changes in cardiac metabolism. Here, we examined mitochondrial respiration and substrate preference in isolated mitochondria from the maternal heart. We show that following birth, cardiac mitochondria are "primed" to respire on carbohydrate, amino acid, and ketone bodies. However, heightened respiratory efficiency is observed only with carbohydrate and amino acid sources. These results suggest that significant changes in mitochondrial respiration occur in the maternal heart in the postpartum period.

In vivo chronic exposure to inorganic mercury worsens hypercholesterolemia, oxidative stress and atherosclerosis in the LDL receptor knockout mice

Heavy metal exposure leads to multiple system dysfunctions. The mechanisms are likely multifactorial and involve inflammation and oxidative stress. The aim of this study was to evaluate markers and risk factors for atherosclerosis in the LDL receptor knockout mouse model chronically exposed to inorganic mercury (Hg) in the drinking water. Results revealed that Hg exposed mice present increased plasma levels of cholesterol, without alterations in glucose. As a major source and target of oxidants, we evaluated mitochondrial function. We found that liver mitochondria from Hg treated mice show worse respiratory control, lower oxidative phosphorylation efficiency and increased H2O2 release. In addition, Hg induced mitochondrial membrane permeability transition. Erythrocytes from Hg treated mice showed a 50% reduction in their ability to take up oxygen, lower levels of reduced glutathione (GSH) and of antioxidant enzymes (SOD, catalase and GPx). The Hg treatment disturbed immune system cells counting and function. While lymphocytes were reduced, monocytes, eosinophils and neutrophils were increased. Peritoneal macrophages from Hg treated mice showed increased phagocytic activity. Hg exposed mice tissues present metal impregnation and parenchymal architecture alterations. In agreement, increased systemic markers of liver and kidney dysfunction were observed. Plasma, liver and kidney oxidative damage indicators (MDA and carbonyl) were increased while GSH and thiol groups were diminished by Hg exposure. Importantly, atherosclerotic lesion size in the aorta root of Hg exposed mice were larger than in controls. In conclusion, in vivo chronic exposure to Hg worsens the hypercholesterolemia, impairs mitochondrial bioenergetics and redox function, alters immune cells profile and function, causes several tissues oxidative damage and accelerates atherosclerosis development.

Sex-specific colonic mitochondrial dysfunction in the indomethacin-induced rat model of inflammatory bowel disease.

Introduction: Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract and encompasses Crohn's Disease and Ulcerative Colitis. Women appear to have more severe and recurring symptoms of IBD compared to men, most likely due to hormonal fluctuations. Studies have shown that mitochondrial dysfunction plays a role in the development of inflammation and there is evidence of colon mitochondrial alterations in IBD models and patients. In this study we have identified the presence of sex-specific colon mitochondrial dysfunction in a rat model of IBD. Methods: Eight-week-old male and female rats were treated with indomethacin to induce IBD and mitoTEMPO was administered daily either after or before induction of IBD and until euthanasia. Colons were collected for histology and mitochondrial experiments. Intact mitochondrial respiration, reactive oxygen species (mtROS), the activities of the individual electron transport complexes and the activities of the antioxidant enzymes were measured to assess mitochondrial function. Results: IBD male rats showed a decrease in citrate synthase activity, cardiolipin levels, catalase activity and an increase in mtROS production. IBD females show a decrease in intact colon mitochondrial respiration, colon mitochondria respiratory control ratio (RCR), complex I activity, complex IV activity, and an increase in mtROS. Interestingly, control females showed a significantly higher rate of complex I and II-driven intact mitochondrial respiration, MCFA oxidation, complex II activity, complex III activity, and complex IV activity compared to control males. The use of a mitochondrial-targeted therapy, mitoTEMPO, improved the disease and colon mitochondrial function in female IBD rats. However, in the males there was no observed improvement, likely due to the decrease in catalase activity. Conclusion: Our study provides a better understanding of the role mitochondria in the development of IBD and highlights sex differences in colon mitochondrial function. It also opens an avenue for the development of strategies to re-establish normal mitochondrial function that could provide more options for preventive and therapeutic interventions for IBD.

Cardiorespiratory Effects of Yogic Versus Slow Breathing in Individuals with a Spinal Cord Injury: An Exploratory Cohort Study.

Background: An intricate physiological and pathophysiological connection exists between the heart and lungs, which is especially important in individuals with spinal cord injury (SCI). While an exercise intervention may seem the best approach to leverage this relationship, the prior work has shown that, despite numerous health benefits, regular exercise training does not improve cardiorespiratory control in individuals with SCI. Breath training presents an alternative intervention that is uniquely accessible, with yogic breathing directly engaging linked fluctuations in respiration and cardiovascular control. In addition, there is evidence across a range of populations that regular yogic breathing reduces cardiovascular disease risk. It is possible that the chronic decrease in breathing frequency associated with regular yogic breathing, rather than the specific yogic breathing techniques themselves, is the primary contributor to the observed risk reduction. Methods: Therefore, in 12 individuals with traumatic SCI from C4 to T8, the authors compared Unpaced and conventional 0.083 Hz (Slow) paced breathing with various yogic breathing techniques including: (1) inspiratory-expiratory breath holds (i.e., Kumbhaka or "Box Breathing"), (2) extended exhalation (1:2 duty cycle), and (3) expiratory resistance via throat constriction (i.e., Ujjayi). Beat-to-beat heart rate and blood pressure were measured as well as end-tidal CO2 and O2 saturation were measured. Statistical analysis was performed using a one-way repeated-measures analysis of variance with post hoc pairwise t tests corrected for multiple comparisons. Results: As expected, all slow breathing patterns markedly increased respiratory sinus arrhythmia (RSA) compared with Unpaced in all (n = 12) individuals. More importantly, Ujjayi breathing appeared to improve ventilatory efficiency over Unpaced breathing in individuals with SCI by increasing O2 saturation (97.6% vs. 96.1%; p = 0.042) and tended to decrease end-tidal CO2 (32 mmHg vs. 35 mmHg; p = 0.08). While other slow breathing patterns demonstrated similar effects, only Ujjayi improved RSA while increasing heart rate and improving ventilatory efficiency. Conclusions: Hence, slow breathing per se can result in important cardiorespiratory changes, but the yogic breathing practice of Ujjayi, with glottic throat resistance, may hold the greatest promise for improving cardiorespiratory control in individuals with SCI (CTR ID No. NCT05480618).

Recurrence of CCHS-associated PHOX2B Poly-Alanine expansion variant due to paternal mosaicism

BackgroundPaired-like Homeobox 2B (PHOX2B) is considered the causative gene of Congenital Central Hypoventilation Syndrome (CCHS), a dominant genetic disorder characterized by impaired central respiratory control and subsequent hypoventilation during sleep. MethodsHerein, we present a family with recurrent severe CCHS. The potential causative genetic variant was confirmed through Whole-Exome Sequencing (WES), Sanger sequencing, and droplet digital PCR (ddPCR). Furthermore, prenatal diagnosis was performed on the proband's mother at 20 weeks of her fourth pregnancy upon request. ResultsThe proband and her brother were both carriers of the PHOX2B polyalanine expansion variant: c.744_758dupCGCGGCAGCGGCGGCGGCGGC. Sanger sequencing revealed that the proband's father had a small variant peak in the gene position, implying potential somatic mosaicism. In addition, ddPCR results showed that the proband's father had germline mosaicism, with a mosaicism proportion of 14.3%. Notably, the detect p.(Ala241[26]) variant was not detected in the fetus. ConclusionsThese findings have important implications for improving genetic counseling of CCHS families as they suggest that even parents without CCHS symptoms may have somatic chimerism, necessitating careful genetic counseling and consideration of prenatal testing for subsequent pregnancies.

Effect of Expiratory Muscle Strength Training on the Performance of Professional Male Trumpet Players.

Many trumpet players use breathing training devices in addition to their daily practice routine. Playing a brass instrument requires, besides many other skills, a controlled air stream to generate the necessary air pressures. On the trumpet, high intraoral pressures are needed, especially during high and loud notes. Therefore, it is not uncommon in trumpet pedagogy to teach that the use of breathing training devices enhances physical strength so that the required pressures can be produced with less effort. However, to date, no systematic assessment of the use of breathing training devices among trumpet players exists and their effect on playing performance is still unclear. In this a pre-post, within-subject repeated measure study, we investigated the influence of a 5-week expiratory muscle strength training (EMST) upon trumpet performance. Twenty-four male professional trumpet players were allocated to either a control or intervention group. The intervention group (n =13) trained with an EMST device against a set resistance of 55% of their maximum expiratory pressure (MEP) for 5 weeks on 5 days per week. The control group (n =11) did no intervention. All participants underwent the same measures (MEP and rate of perceived exertion [RPE]) and played the same tasks (maximum long note, maximum high note, maximum dynamics and phrasing in high register) prior to and after the 5 weeks. After EMST, MEP increased significantly (13%, p = 0.049) in the intervention group, whereas no significant change was found in the control group. Performance parameters did not change in either of the groups, also after EMST. Despite the increase in MEP, we found no evidence that EMST has an influence on trumpet performance. We conclude that EMST seems unnecessary for the enhancement of trumpet playing, at least in a population of male professionals who already demonstrate excellent respiratory condition and control.

Pathophysiology of Respiratory Failure in Neuromuscular Diseases

Based on a recent review by Krohn et al, the respiratory center and its regulatory mechanisms are described. Although the respiratory control centers in the medulla and pons ensure rhythmic respiration, maintaining and regulating respiration involves a complex network of peripheral chemoreceptors, vagal nerves, and central chemoreceptors. This review discusses the pathophysiology of respiratory disorders in neuromuscular diseases and evaluation and treatment methods based on the anatomy of the respiratory network.

Mitochondrial function and reactive oxygen species production during human sperm capacitation: Unraveling key players.

Sperm capacitation is a critical process for male fertility. It involves a series of biochemical and physiological changes that occur in the female reproductive tract, rendering the sperm competent for successful fertilization. The precise mechanisms and, specifically, the role of mitochondria, in sperm capacitation remain incompletely understood. Previously, we revealed that in mouse sperm mitochondrial activity (e.g., oxygen consumption, membrane potential, ATP/ADP exchange, and mitochondrial Ca2+ ) increases during capacitation. Herein, we studied mitochondrial function by high-resolution respirometry (HRR) and reactive oxygen species production in capacitated (CAP) and non-capacitated (NC) human spermatozoa. We found that in capacitated sperm from normozoospermic donors, the respiratory control ratio increased by 36%, accompanied by a double oxygen consumption rate (OCR) in the presence of antimycin A. Extracellular hydrogen peroxide (H2 O2 ) detection was three times higher in CAP than in NC sperm cells. To confirm that H2 O2 production depends on mitochondrial superoxide ( ) formation, we evaluated mitochondrial aconitase (ACO2) amount, activity, and role in the metabolic flux from the sperm tricarboxylic acid cycle. We estimated that CAP cells produce, on average by individual, (59 ± 22)% more in the steady-state compared to NC cells. Finally, we analyzed two targets of oxidative stress: lipid peroxidation by western blot against 4-hydroxynonenal and succinate dehydrogenase (SDH) activity by HRR. We did not observe modifications in lipoperoxidation nor the activity of SDH, suggesting that during capacitation, the increase in mitochondrial H2 O2 production does not damage sperm and it is necessary for the normal CAP process.

Apnea behavior in early- and late-stage mouse models of Parkinson's disease: Cineradiographic analysis of spontaneous breathing, acute stress, and swallowing

This study aimed to evaluate the timing and frequency of spontaneous apneas during breathing and swallowing by using cineradiography on mouse models of early/initial or late/advanced Parkinson’s disease (PD). C57BL/6 J mice received either 6-OHDA or vehicle injections into their right striatum, followed by respiratory movement recordings during spontaneous breathing and swallowing, and a stress challenge, two weeks later. Experimental group animals showed a significantly lower respiratory rate (158.66 ± 32.88 breaths/minute in late PD, 173.16 ± 25.19 in early PD versus 185.27 ± 25.36 in controls; p<0.001) and a significantly higher frequency of apneas (median 1 apnea/minute in both groups versus 0 in controls; p<0.001). Other changes included reduced food intake and the absence of swallow apneas in experimental mice. 6-OHDA-induced nigrostriatal degeneration in mice disrupted respiratory control, swallowing, stress responsiveness, and feeding behaviors, potentially hindering airway protection and elevating the risk of aspiration.

Warming-induced “plastic floors” improve hypoxia vulnerability, not aerobic scope, in red drum (Sciaenops ocellatus)

Ocean warming is a prevailing threat to marine ectotherms. Recently the “plastic floors, concrete ceilings” hypothesis was proposed, which suggests that a warmed fish will acclimate to higher temperatures by reducing standard metabolic rate (SMR) while keeping maximum metabolic rate (MMR) stable, therefore improving aerobic scope (AS). Here we evaluated this hypothesis on red drum (Sciaenops ocellatus) while incorporating measures of hypoxia vulnerability (critical oxygen threshold; Pcrit) and mitochondrial performance. Fish were subjected to a 12-week acclimation to 20 °C or 28 °C. Respirometry was performed every 4 weeks to obtain metabolic rate and Pcrit; mitochondrial respirometry was performed on liver and heart samples at the end of the acclimation. 28 °C fish had a significantly higher SMR, MMR, and Pcrit than 20 °C controls at time 0, but SMR declined by 36.2 % over the 12-week acclimation. No change in SMR was observed in the control treatment. Contrary to expectations, SMR suppression did not improve AS relative to time 0 owing to a progressive decline in MMR over acclimation time. Pcrit decreased by 27.2 % in the warm-acclimated fishes, which resulted in temperature treatments having statistically similar values by 12-weeks. No differences in mitochondrial traits were observed in the heart – despite a Δ8 °C assay temperature – while liver respiratory and coupling control ratios were significantly improved, suggesting that mitochondrial plasticity may contribute to the reduced SMR with warming. Overall, this work suggests that warming induced metabolic suppression offsets the deleterious consequences of high oxygen demand on hypoxia vulnerability, and in so doing greatly expands the theoretical range of metabolically available habitats for red drum.

Acute effects of the 4-4-8 breathing technique on arterial stiffness in healthy young men.

Increased arterial stiffness is a risk factor for cardiovascular disease. Slow, deep breathing decreases blood pressure related to arterial stiffness. The objective of the present study was to determine the acute effects of a single session of slow breathing on arterial stiffness, blood pressure, and cardiac autonomic function. Fifteen healthy men (20 ± 0 years) were administered (a) a slow breathing condition (12 consecutive breaths of 4 s of inhalation, 4 s of pause, and 8 s of exhalation through the nose, approximately 5 min per breath) and (b) a control, two-condition crossover design. Carotid-femoral artery pulse wave velocity (cfPWV), brachial-ankle PWV (baPWV), brachial blood pressure, high frequency (HF) and low frequency (LF) were measured at baseline, 30 min, 60 min and 24 h after respiratory control. Brachial-ankle PWV and brachial systolic pressure on the 4-4-8 breathing trial decreased after 30 min of respiratory control compared to baseline (p < 0.05), but did not change on the CON trial. Carotid-femoral PWV on both trials was unchanged; HF on the 4-4-8 breathing trial increased (p < 0.05) and LF decreased (p < 0.05) after 30 min of respiratory control compared to baseline, but was unchanged on the CON trial. These results suggest that slow breathing techniques may be effective in modulating autonomic function and improving arterial stiffness in healthy young adults.

Abstract WP308: TGFBR2 Knockdown Improves Cognitive Function and Breathing in AD Mice

Introduction: Respiratory disorders, including sleep apnea, are an independent risk factor for the development of cognitive dysfunction and dementia. Disordered breathing occurs frequently in patients with AD (Alzheimer’s Disease). Disruption of the brainstem breathing centers, including the Retro-trapezoid nucleus (RTN), leads to breathing disorders. Our previous work showed that upregulation of Transforming Growth Factor Beta Receptor 2 (TGFBR2) signaling in the RTN leads to respiratory dysfunction in mice. The present study investigated if inhibiting TGFBR2 selectively in the RTN region could improve breathing and cognitive function in AD mice. Methods: We used 20 WT and 20 TG2576 mice (15 months old). Mice were randomly assigned into two sub-groups; treatment with a shTGFBR2 vector (knockdown) or vector control with scrambled shRNA. After baseline behavior and breathing testing, lentiviral stereotaxic injections of vehicle and shTGFBR2 were done directly into the RTN. After 6 weeks, behavior and breathing testing was performed, and then brain tissues were collected for histological analysis. All the data are presented as Mean±SEM. Results: Tg2576 mice had significantly higher number of apnea (7.91±0.95) than WT mice (4.10±0.85) with a p -value of 0.0079. When injected with shTGFBR2 into the RTN, Tg2576 had improved recognition of a novel object (69.24%±5.75) as compared to the Tg2576 vehicle-treated group (51.02%±4.88) in the NORT ( p =0.0213). They also showed a significant improvement in the latency to escape (64.94±15.56) compared to the Tg2576 vehicle-treated group (136.4±20.90) in the Barnes maze ( p =0.0109). The number of apneas was also significantly reduced in TG2675 mice treated with shTGFBR2 in the RTN (3.33±0.69), when compared to the Tg2576 vehicle-treated group (8.22±1.30) with a p -value of 0.0029. Conclusions: Our study revealed that the knockdown of TGFBR2 in the RTN, a brainstem nucleus involved in respiratory control, improved both the cognitive and breathing phenotypes in AD-model mice. Our work suggests that improving respiratory control and reducing apnea in AD may be a potential treatment for the disease. This is especially relevant as new treatments for central apnea, such as phrenic nerve stimulation, are available.

Successful transition from intravenous to inhalation anesthesia for respiratory management of coronavirus disease pneumonia: A case report.

In patients with coronavirus disease pneumonia, strong spontaneous breathing increases pulmonary vascular permeability and induces self-inflicted lung injury, prolonging the intensive care unit stay and worsening prognosis. Therefore, spontaneous respiration must be strictly controlled. A 48-year-old man was admitted for respiratory management of severe coronavirus disease pneumonia. Despite immediate ventilatory management, ventilatory failure and air leak syndrome developed, necessitating venovenous extracorporeal membrane oxygenation, intravenous sedation, and muscle relaxation. Over time, the patient's inspiratory effort worsened and the requirement for transvenous anesthesia increased. Therefore, management was switched to inhalation anesthesia after discontinuation of all transvenous anesthetics, maintaining morphine-only analgesia. Subsequent management enabled effective control of spontaneous respiration, allowing eventual discontinuation of inhalation anesthesia, venovenous extracorporeal membrane oxygenation, and ventilation. Management of spontaneous respiration in coronavirus disease pneumonia can be complicated by resistance to transvenous anesthesia; however, the use of an inhaled anesthetic may present a valuable alternative.

Etonogestrel promotes respiratory recovery in an invivo rat model of central chemoreflex impairment.

The central CO2 chemoreflex is a vital component of respiratory control networks, providing excitatory drive during resting conditions and challenges to blood gas homeostasis. The retrotrapezoid nucleus is a crucial hub for CO2 chemosensitivity; its ablation or inhibition attenuates CO2 chemoreflexes and diminishes restful breathing. Similar phenotypes characterize certain hypoventilation syndromes, suggesting underlying retrotrapezoid nucleus impairment in these disorders. Progesterone stimulates restful breathing and CO2 chemoreflexes. However, its mechanisms and sites of actions remain unknown and the experimental use of synthetic progestins in patients and animal models have been met with mixed respiratory outcomes. We investigated whether acute or chronic administration of the progestinic drug, etonogestrel, could rescue respiratory chemoreflexes following selective lesion of the retrotrapezoid nucleus with saporin toxin. Adult female Sprague Dawley rats were grouped based on lesion size determined by the number of surviving chemosensitive neurons, and ventilatory responses were measured by whole body plethysmography. Ventilatory responses to hypercapnia (but not hypoxia) were compromised in a lesion-dependent manner. Chronic etonogestrel treatment improved CO2 chemosensitivity selectively in rats with moderate lesion, suggesting that a residual number of chemosensitive neurons are required for etonogestrel-induced CO2 chemoreflex recovery. This study provides new evidence for the use of progestins as respiratory stimulants under conditions of central hypoventilation and provides a new testable model for assessing the mechanism of action of progestins in the respiratory network.

Does acute exposure to thimerosal, an organic mercury compound, affect the mitochondrial function of an infant model?

BackgroundThimerosal (TM) is a toxic, organometallic mercury compound (which releases ethyl-mercury-containing compounds in aqueous solutions) used as a preservative in vaccines. Mitochondria are organelle which are highly vulnerable to many chemical compounds, including mercury (Hg) and its derivatives. MethodWistar rats (at 21 days of age) were used to model a child’s TM exposure following childhood vaccination, divided in two groups: TM exposed (20 μg/kg/day) and unexposed controls (saline solution), both for 24 h. Atomic Fluorescence Spectrometry was used to quantify the amounts of mercury in tissues. The electron transport chain (ETC) from isolated mitochondria was evaluated using an oxygen electrode. The mitochondrial membrane potential and H2O2 production were analyzed using selective fluorescence probes. The activity of some enzymes (SOD, CAT, GPx, and AChE) and secondary markers of oxidative stress (GSH, GSSG, total free thiol) were also examined in tissues. ResultsHg accumulation in the brain and liver was higher in exposed animals when compared to the control. Liver-isolated mitochondria showed that TM improved respiratory control by 23%; however, states 3 and 4 of the ETC presented a decrease of 16% and 37%, respectively. Furthermore, brain-isolated mitochondria presented an improvement of 61% in respiratory control. Brain enzyme activities were significantly impacted in TM-exposed rats compared to unexposed rats as follows: decreases in SOD (32%) and AChE (42%) and increases in GPx (79%) and CAT (100%). GPx enzyme activity in the liver was significantly increased (37%). Among secondary oxidative stress markers, the brain’s total reduced thiol (SH) concentration was significantly increased (41%). ConclusionAcute TM treatment exposure in a Wistar rat model mimicking TM exposure in an infant following childhood vaccination significantly damaged brain bioenergetic pathways. This study supports the ability of TM exposure to preferentially damage the nervous system.

Insights into estrogen impact in oral health & microbiome in COVID-19

BackgroundCOVID-19 emerged in late 2019 and has occasioned more than 765 millions cumulative cases and 6.9 millions of deaths globally. Notably, around 70% of patients with severe COVID-19 are men. Therefore, it is to be presumed that women have a hormonal protector factor in inflammation and ACE2 expression. On the other hand, oral health status, and local microbiome can be key factors to respiratory viral infections control. Nevertheless, it has been poorly investigated. In our study 20 premenopausal, 18 postmenopausal and 22 men with COVID-19 were included. Oral health status, viral load, lingual ACE2 expression, as well as microbiome, estrogens and cytokines in saliva were analyzed.ResultsOur results showed a lower expression of ACE2 in tongue cells of postmenopausal compared with premenopausal (p = 0.05), and a strong negative correlation between saliva estrogen and viral load (r = -0.76; p = 0.001). Respect to IFN-γ (p = 0.05), IL-1β, TNF-α, IL-18, and IL-23 levels were increased in postmenopausal. Oral microbiome signature of premenopausal was characterized by Prevotella melaninogenica (Log2 = 26.68; p = 1.34e-10), Haemophilus (Log2 = 23.99; p = 2.96e-9), and Alloprevotella (Log2 = 7.92; p = 0.0001). On the other hand, Leptotrichia (Log2 = -18.74; p = 0.001), Tanerella (Log2 = -17.08; p = 0.004), and Clostridiales (Log2 = -2.88; p = 0.04) represented the poor oral health group compared with the adequate group which was enriched with the commensal microorganism Neisseria perflava (Log2 = 26.70; p = 1.74e-7). Furthermore, the high viral load group was characterized by Prevotella nanceiensis (Log2 = 19.60; p = 6.06e-8), Prevotella melaninogenica (Log2 = 21.45; p = 9.59e-6), Alloprevotella (Log2 = 23.50; p = 2.70e-7) and bacteria from the red complex Porphyromonas endodentalis (Log2 = 21.97; p = 1.38e-7).ConclusionsPostmenopausal and men have a poor oral health status which could be related to a detrimental progression of COVID-19 also linked to a lower expression of ACE2, lower saliva estrogen levels and oral dysbiosis. Nevertheless, functional studies are required for a deeper knowledge.

Effects of Inspiratory Muscles Training on the Development of Respiratory Function in University Students: A Case Study of Guangzhou Sport University

Background and Aim: The objective of this research was to develop Inspiratory Muscle Training for Respiratory Function in University Students. Materials and Methods: This research was experimental research. From the initial 48 third-year college students recruited at Guangzhou Sport University, we excluded 8 students who also participated in other sports programs or had school absences due to personal reasons, leaving the remaining 40 students as experimental subjects. They had just learned Four kinds of swimming in their second year of college and began the early stages of formal swimming training. Using the simple randomization method, 40 male college students were divided into two groups, one experimental group and one control group with 20 students in each group. The experimental group participated in the swimming training three times a week and designed the respiratory control training. The control group participated in swimming training three times a week, and the whole training time was 6 weeks. The specific approach is as follows: before the grouping, the 50-meter freestyle test was conducted, ranked according to the swimming result from the highest to the highest, and the balance was allocated to the experimental group and the control group. This study investigated the effects of inspiratory muscle training on respiratory function in college swimmers from four aspects: (1) VC (vital capacity), (2) MIP (maximum inspiratory pressure), (3) MIF (maximum inspiratory flow), and (4) MIC (maximum inspiratory capacity). In this research, T-test and ANOVA were used to compare and analyze the data. The statistical significance level was 0.05. Result: After 6 weeks of continuous inspiratory muscle training in swimmers, regarding the index of vital capacity (VC), there was no significant change in the control group. However, there was a significant increase in the experimental group (p=0.01); regarding the three indicators of maximum inspiratory pressure (MIP), maximum inspiratory flow (MIF), and maximum inspiratory capacity (MIC): both the experimental group and the control group showed an improvement, but the experimental group showed a greater improvement, and the enhancement appeared earlier. Conclusion: Inspiratory muscle training is beneficial to the development of respiratory function in university students.