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Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease that results in death within 2–5 years of diagnosis. Respiratory failure is the most common cause of death in ALS. Mutations in the transactive response DNA binding protein 43 (TDP-43) encoded by the TARDBP gene are associated with abnormal cellular aggregates in neurons of patients with both familial and sporadic ALS. The role of these abnormal aggregates on breathing is unclear. Since respiratory failure is a major cause of death in ALS, we sought to determine the role of TDP-43 mutations on the respiratory motor unit in the Prp-hTDP43A315T mouse model – a model that expresses human TDP-43 containing the A315T mutation. We assessed breathing using whole-body plethysmography, and investigated neuropathology in hypoglossal and phrenic respiratory motor units. Postmortem studies included quantification of hypoglossal and putative phrenic motor neurons, activated microglia and astrocytes in respiratory control centers, and assessment of hypoglossal and phrenic nerves of TDP43A315T mice. The male TDP43A315T mice display an early onset of rapid progression of disease, and premature death (less than 15 weeks) compared to control mice and compared to female TDP43A315T mice who die between 20 and 35 weeks of age. The TDP43A315T mice have progressive and profound breathing deficits at baseline and during a respiratory challenge. Histologically, hypoglossal and putative phrenic motor neurons of TDP43A315T mice are decreased and have increased microglial and astrocyte activation, indicating pronounced neurodegeneration and neuroinflammation. Further, there is axonopathy and demyelination in the hypoglossal and phrenic nerve of TDP43A315T mice. Thus, the TDP-43A315T mice have significant respiratory pathology and neuropathology, which makes them a useful translatable model for the study of novel therapies on breathing in ALS. [ABSTRACT FROM AUTHOR]

There is evidence that astrocytes modulate synaptic transmission in the nucleus tractus solitarius (NTS) interacting with glutamatergic and purinergic mechanisms. Here, using in situ working heart-brainstem preparations, we evaluated the involvement of astrocyte and glutamatergic/purinergic neurotransmission in the processing of autonomic and respiratory pathways in the NTS of control and rats exposed to sustained hypoxia (SH). Baseline autonomic and respiratory activities and the responses to chemoreflex activation (KCN) were evaluated before and after microinjections of fluorocitrate (FCt, an astrocyte metabolic inhibitor), kynurenic acid, and pyridoxalphosphate-6-azophenyl-2′,4′-disulfonate (PPADS) (nonselective antagonists of glutamatergic and purinergic receptors) into the rostral aspect of the caudal commissural NTS. FCt had no effects on the baseline parameters evaluated but reduced the bradycardic response to chemoreflex activation in SH rats. FCt combined with kynurenic acid and PPADS in control rats reduced the baseline duration of expiration, which was attenuated after SH. FCt produced a large increase in PN frequency discharge in control rats, which was reduced after SH, indicating a reduction in the astrocyte modulation after SH. The data show that 1) the bradycardic component of the peripheral chemoreflex is reduced in SH rats after astrocytes inhibition, 2) the inhibition of astrocytes in the presence of double antagonists in the NTS affects the modulation of baseline duration of expiration in control but not in SH rats, and 3) the autonomic and respiratory responses to chemoreflex activation are mediated by glutamatergic and purinergic receptors in the rostral aspect of the caudal commissural NTS. NEW & NOTEWORTHY: Our findings indicate that the neurotransmission of autonomic and respiratory components of the peripheral chemoreflex in the nucleus tractus solitarius (NTS) is mediated by glutamatergic and purinergic mechanisms and reveal a selective involvement of NTS astrocytes in controlling the chemoreflex parasympathetic response in rats exposed to sustained hypoxia (SH) and the baseline duration of expiration mainly in control rats, indicating a selective role for astrocytes modulation in the NTS of control and SH rats. [ABSTRACT FROM AUTHOR]

Development of the respiratory system can be affected by the use of drugs during pregnancy, as the prenatal phase is highly sensitive to pharmacological interventions, resulting in long-term consequences. The deleterious effects of external cannabinoids during gestation may be related to negative interference in central nervous system formation, cardiorespiratory system function, and behavioral disorders. Nevertheless, the impact of external cannabinoids on cardiorespiratory network development, chemosensitivity, and its future consequences in adulthood is still unclear. We evaluated the effects of prenatal exposure to a synthetic cannabinoid (WIN 55,212-2, 0.5 mg·kg−1·day−1) on the cardiorespiratory control and panic-like behavior of male and female rats in adulthood. Exogenous cannabinoid exposure during pregnancy resulted in a sex-dependent difference in breathing control. Specifically, males showed increased chemosensitivity to CO2 and O2, whereas females exhibited decreased sensitivity. Altered cardiovascular control was evident, with prenatally treated males and females being more susceptible to hypertension and tachycardia under adverse environmental conditions. Moreover, WIN-treated males exhibited higher fragmentation of sleep episodes, whereas females displayed anxiolytic and panicolytic behavioral responses to CO2. However, no changes were observed in the mechanical component of the respiratory system, and there were no neuroanatomical alterations, such as changes in the expression of CB1 receptors in the brainstem or in the quantification of catecholaminergic and serotonergic neurons. These findings highlight that external interference in cannabinoid signaling during fetal development causes sex-specific, long-lasting effects for the cardiorespiratory system and behavioral responses in adulthood. NEW & NOTEWORTHY: The surge in recreational cannabis use and cannabinoid-based medication prescription among pregnant women has been notable in recent years, fueled by the misconception that natural products are inherently safe. Significant gaps persist regarding the potential risks of maternal consumption of cannabinoids and the long-term effects on the cardiorespiratory system of their offspring, which may be determined by sex. Accordingly, this research aims to diminish this lack of information and raise a note of caution. [ABSTRACT FROM AUTHOR]

Obstructive Sleep Apnea (OSA) is a disorder characterized by repeated upper airway collapse during sleep, leading to apneas and/or hypopneas, with associated symptoms like intermittent hypoxia and sleep fragmentation. One of the agents contributing to OSA occurrence and development seems to be serotonin (5-HT). Currently, the research focuses on establishing and interlinking OSA pathogenesis and the severity of the disease on the molecular neurotransmitter omnipresent in the human body—serotonin, its pathway, products, receptors, drugs affecting the levels of serotonin, or genetic predisposition. The 5-HT system is associated with numerous physiological processes such as digestion, circulation, sleep, respiration, and muscle tone—all of which are considered factors promoting and influencing the course of OSA because of correlations with comorbid conditions. Comorbidities include obesity, physiological and behavioral disorders as well as cardiovascular diseases. Additionally, both serotonin imbalance and OSA are connected with psychiatric comorbidities, such as depression, anxiety, or cognitive dysfunction. Pharmacological agents that target 5-HT receptors have shown varying degrees of efficacy in reducing the Apnea-Hypopnea Index and improving OSA symptoms. The potential role of the 5-HT signaling pathway in modulating OSA provides a promising avenue for new therapeutic interventions that could accompany the primary treatment of OSA—continuous positive airway pressure. Thus, this review aims to elucidate the complex role of 5-HT and its regulatory mechanisms in OSA pathophysiology, evaluating its potential as a therapeutic target. We also summarize the relationship between 5-HT signaling and various physiological functions, as well as its correlations with comorbid conditions. [ABSTRACT FROM AUTHOR]

Our understanding of human brain function can be greatly aided by studying analogous brain structures in other organisms. One brain structure with neurochemical and anatomical homology throughout vertebrate species is the locus coeruleus (LC), a small collection of norepinephrine (NE)-containing neurons in the brainstem that project throughout the central nervous system. The LC is involved in nearly every aspect of brain function, including arousal and learning, which has been extensively examined in rats and nonhuman primates using single-unit recordings. Recent work has expanded into putative LC single-unit electrophysiological recordings in a nonmodel species, the zebra finch. Given the importance of correctly identifying analogous structures as research efforts expand to other vertebrates, we suggest adoption of consensus anatomical and electrophysiological guidelines for identifying LC neurons across species when evaluating brainstem single-unit spiking or calcium imaging. Such consensus criteria will allow for confident cross-species understanding of the roles of the LC in brain function and behavior. [ABSTRACT FROM AUTHOR]

µ-Opioid receptors (MORs) are responsible for mediating both the analgesic and respiratory effects of opioid drugs. By binding to MORs in brainstem regions involved in controlling breathing, opioids produce respiratory depressive effects characterized by slow and shallow breathing, with potential cardiorespiratory arrest and death during overdose. To better understand the mechanisms underlying opioid-induced respiratory depression, thorough knowledge of the regions and cellular subpopulations that may be vulnerable to modulation by opioid drugs is needed. Using in situ hybridization, we determined the distribution and coexpression of Oprm1 (gene encoding MORs) mRNA with glutamatergic (Vglut2) and neurokinin-1 receptor (Tacr1) mRNA in medullary and pontine regions involved in breathing control and modulation. We found that >50% of cells expressed Oprm1 mRNA in the preBötzinger complex (preBötC), nucleus tractus solitarius (NTS), nucleus ambiguus (NA), postinspiratory complex (PiCo), locus coeruleus (LC), Kölliker-Fuse nucleus (KF), and the lateral and medial parabrachial nuclei (LBPN and MPBN, respectively). Among Tacr1 mRNA-expressing cells, >50% coexpressed Oprm1 mRNA in the preBötC, NTS, NA, Bötzinger complex (BötC), PiCo, LC, raphe magnus nucleus, KF, LPBN, and MPBN, whereas among Vglut2 mRNA-expressing cells, >50% coexpressed Oprm1 mRNA in the preBötC, NTS, NA, BötC, PiCo, LC, KF, LPBN, and MPBN. Taken together, our study provides a comprehensive map of the distribution and coexpression of Oprm1, Tacr1, and Vglut2 mRNA in brainstem regions that control and modulate breathing and identifies Tacr1 and Vglut2 mRNA-expressing cells as subpopulations with potential vulnerability to modulation by opioid drugs. NEW & NOTEWORTHY: Opioid drugs can cause serious respiratory side-effects by binding to µ-opioid receptors (MORs) in brainstem regions that control breathing. To better understand the regions and their cellular subpopulations that may be vulnerable to modulation by opioids, we provide a comprehensive map of Oprm1 (gene encoding MORs) mRNA expression throughout brainstem regions that control and modulate breathing. Notably, we identify glutamatergic and neurokinin-1 receptor-expressing cells as potentially vulnerable to modulation by opioid drugs and worthy of further investigation using targeted approaches. [ABSTRACT FROM AUTHOR]

Hypoxia, especially the chronic type, leads to disruptive results in the brain that may contribute to the pathogenesis of some neurodegenerative diseases such as Alzheimer's disease (AD). The ventrolateral medulla (VLM) contains clusters of interneurons, such as the pre-Bötzinger complex (preBötC), that generate the main respiratory rhythm drive. We hypothesized that exposing animals to chronic sustained hypoxia (CSH) might develop tauopathy in the brainstem, consequently changing the rhythmic manifestations of respiratory neurons. In this study, old (20–22 months) and young (2–3 months) male rats were subjected to CSH (10 ± 0.5% O2) for ten consecutive days. Western blotting and immunofluorescence (IF) staining were used to evaluate phosphorylated tau. Mitochondrial membrane potential (MMP or ∆ψm) and reactive oxygen species (ROS) production were measured to assess mitochondrial function. In vivo diaphragm's electromyography (dEMG) and local field potential (LFP) recordings from preBötC were employed to assess the respiratory factors and rhythmic representation of preBötC, respectively. Findings showed that ROS production increased significantly in hypoxic groups, associated with a significant decline in ∆ψm. In addition, tau phosphorylation elevated in the brainstem of hypoxic groups. On the other hand, the power of rhythms declined significantly in the preBötC of hypoxic rats, parallel with changes in the respiratory rate, total respiration time, and expiration time. Moreover, there was a positive and statistically significant correlation between LFP rhythm's power and inspiration time. Our data showed that besides CSH, aging also contributed to mitochondrial dysfunction, tau hyperphosphorylation, LFP rhythms' power decline, and changes in respiratory factors. [ABSTRACT FROM AUTHOR]

In Parkinson's disease (PD), along with typical motor dysfunction, abnormal breathing is present; the cause of which is not well understood. The study aimed to analyze the effects of stimulation of the serotonergic system with 5-HT1A and 5-HT2A agonists in a model of PD induced by injection of 6-hydroxydopamine (6-OHDA). To model PD, bilateral injection of 6-OHDA into both striata was performed in male Wistar rats. Respiratory disturbances in response to 7% hypercapnia (CO2 in O2) in the plethysmographic chamber before and after stimulation of the serotonergic system and the incidence of apnea were studied in awake rats 5 weeks after 6-OHDA or vehicle injection. Administration of 6-OHDA reduced the concentration of serotonin (5-HT), dopamine (DA) and norepinephrine (NA) in the striatum and the level of 5-HT in the brainstem of treated rats, which have been associated with decreased basal ventilation, impaired respiratory response to 7% CO2 and increased incidence of apnea compared to Sham-operated rats. Intraperitoneal (i.p.) injection of the 5-HT1AR agonist 8-OH-DPAT and 5-HT2AR agonist NBOH-2C-CN increased breathing during normocapnia and hypercapnia in both groups of rats. However, it restored reactivity to hypercapnia in 6-OHDA group to the level present in Sham rats. Another 5-HT2AR agonist TCB-2 was only effective in increasing normocapnic ventilation in 6-OHDA rats. Both the serotonergic agonists 8-OH-DPAT and NBOH-2C-CN had stronger stimulatory effects on respiration in PD rats, compensating for deficits in basal ventilation and hypercapnic respiration. We conclude that serotonergic stimulation may have a positive effect on respiratory impairments that occur in PD. [ABSTRACT FROM AUTHOR]

Opioids are well-known to cause respiratory depression, but despite clinical evidence of dysphagia, the effects of opioids on swallow excitability and motor pattern are unknown. We tested the effects of the clinically relevant opioid buprenorphine on pharyngeal swallow and respiratory drive in male and female rats. We also evaluated the utility of 5-HT1A agonists (8-OH-DPAT and buspirone) to improve swallowing and breathing following buprenorphine administration. Experiments were performed on 44 freely breathing Sprague-Dawley rats anesthetized with sodium pentobarbital. Bipolar fine wire electrodes were inserted into the mylohyoid, thyroarytenoid, posterior cricoarytenoid, thyropharyngeus, and diaphragm muscles to measure electromyographic (EMG) activity of swallowing and breathing. We evaluated the hypotheses that swallowing varies by stimulus, opioids depress swallowing and breathing, and that 5-HT1A agonists improve these depressions. Our results largely confirmed the following hypotheses: 1) swallow-related EMG activity was larger during swallows elicited by esophageal distension plus oral water infusion than by either stimulus alone. 2) Buprenorphine depressed swallow in both sexes, but females were more susceptible to total swallow suppression. 3) Female animals were also more vulnerable to opioid-induced respiratory depression. 4) 8-OH-DPAT rescued breathing following buprenorphine-induced respiratory arrest, and pretreatment with the partial 5-HT1A agonist buspirone prevented buprenorphine-induced respiratory arrest in female animals. 5) 8-OH-DPAT enhanced mylohyoid and thyropharyngeus EMG amplitude during swallow but did not restore excitability of the swallow pattern generator following total suppression by buprenorphine. Our results highlight sex-specific and behavior-specific effects of buprenorphine and provide preclinical evidence of a 5HT1A agonist for the treatment of respiratory depression and dysphagia. NEW & NOTEWORTHY: This is the first study, to our knowledge, to evaluate sex-specific effects of opioid administration on pharyngeal swallow. We expand on a small but growing number of studies that report a lower threshold for opioid-induced respiratory depression in females compared with males, and we are the first to produce this effect with the partial μ-opioid-receptor agonist buprenorphine. This is the first demonstration, to our knowledge, that activation of 5-HT1A receptors can improve swallow and breathing outcomes following systemic buprenorphine administration. [ABSTRACT FROM AUTHOR]

Crocodylomorphs constitute a clade of archosaurs that have thrived since the Mesozoic until today and have survived numerous major biological crises. Contrary to historic belief, their semiaquatic extant representatives (crocodylians) are not living fossils, and, during their evolutionary history, crocodylomorphs have evolved to live in a variety of environments. This review aims to summarize the non-semiaquatic adaptations (i.e., either terrestrial or fully aquatic) of different groups from different periods, highlighting how exactly those different lifestyles are inferred for those animals, with regard to their geographic and temporal distribution and phylogenetic relationships. The ancestral condition for Crocodylomorpha seems to have been a terrestrial lifestyle, linked with several morphological adaptations such as an altirostral skull, long limbs allowing a fully erect posture and a specialized dentition for diets based on land. However, some members of this clade, such as thalattosuchians and dyrosaurids display adaptations for an opposite, aquatic lifestyle, interestingly inferred from the same type of morphological observations. Finally, new techniques for inferring the paleobiology of those extinct animals have been put forward in the last decade, appearing as a complementary approach to traditional morphological descriptions and comparisons. Such is the case of paleoneuroanatomical (CT scan data), histological, and geochemical studies., (© 2024 American Association for Anatomy.)

Exercise preserves neuromuscular function in aging through unknown mechanisms. Skeletal muscle fibroblasts (FIB) and stem cells (MuSC) are abundant in skeletal muscle and reside close to neuromuscular junctions, but their relative roles in motor neuron maintenance remain undescribed. Using direct cocultures of embryonic rat motor neurons with either human MuSC or FIB, RNA sequencing revealed profound differential regulation of the motor neuron transcriptome, with FIB generally favoring neuron growth and cell migration and MuSC favoring production of ribosomes and translational machinery. Conditioned medium from FIB was superior to MuSC in preserving motor neurons and increasing their maturity. Lastly, we established the importance of donor age and exercise status and found an age-related distortion of motor neuron and muscle cell interaction that was fully mitigated by lifelong physical activity. In conclusion, we show that human muscle FIB and MuSC synergistically stimulate the growth and viability of motor neurons, which is further amplified by regular exercise., (© 2024 The Author(s). Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Background: The treatment of diverse diseases using plant-derived products is actively encouraged. In the past few years, cannabidiol (CBD) has emerged as a potent cannabis-derived drug capable of managing various debilitating neurological infections, diseases, and their associated complications. CBD has demonstrated anti-inflammatory and curative effects in neuropathological conditions, and it exhibits therapeutic, apoptotic, anxiolytic, and neuroprotective properties. However, more information on the reactions and ability of CBD to alleviate brain-related disorders and the neuroinflammation that accompanies them is needed. Main body: This narrative review deliberates on the therapeutic and remedial prospects of CBD with an emphasis on neurological and neuropsychiatric disorders. An extensive literature search followed several scoping searches on available online databases such as PubMed, Web of Science, and Scopus with the main keywords: CBD, pro-inflammatory cytokines, and cannabinoids. After a purposive screening of the retrieved papers, 170 (41%) of the articles (published in English) aligned with the objective of this study and retained for inclusion. Conclusion: CBD is an antagonist against pro-inflammatory cytokines and the cytokine storm associated with neurological infections/disorders. CBD regulates adenosine/oxidative stress and aids the downregulation of TNF-α, restoration of BDNF mRNA expression, and recovery of serotonin levels. Thus, CBD is involved in immune suppression and anti-inflammation. Understanding the metabolites associated with response to CBD is imperative to understand the phenotype. We propose that metabolomics will be the next scientific frontier that will reveal novel information on CBD's therapeutic tendencies in neurological/neuropsychiatric disorders. [ABSTRACT FROM AUTHOR]

Cervical spinal cord injury impacts ventilatory and non-ventilatory functions of the diaphragm muscle (DIAm) and contributes to clinical morbidity and mortality in the afflicted population. Periodically, integrated brainstem neural circuit activity drives the DIAm to generate a markedly augmented effort or sigh--which plays an important role in preventing atelectasis and thus maintaining lung function. Across species, the general pattern of DIAm efforts during a normal sigh is variable in amplitude and the extent of post-sigh "apnea" (i.e., the post- sigh interbreath interval). This post-sigh inter-breath interval acts as a respiratory reset, following the interruption of regular respiratory rhythm by sigh. We examined the impact of upper cervical (C2) spinal cord hemisection (C2SH) on the transdiaphragmatic pressure (Pdi) generated during sighs and the post-sigh respiratory reset in rats. Sighs were identified in Pdi traces by their characteristic biphasic pattern. We found that C2SH results in a reduction of Pdi during both eupnea and sighs, and a decrease in the immediate post-sigh breath interval. These results are consistent with partial removal of descending excitatory synaptic inputs to phrenic motor neurons that results from C2SH. Following cervical spinal cord injury, a reduction in the amplitude of Pdi during sighs may compromise the maintenance of normal lung function. [ABSTRACT FROM AUTHOR]

Simple Summary: Area A5 in the brain stem plays a crucial role in controlling our body's automatic responses, especially stress, heart function and survival mechanisms. This area is re-sponsible for activating the sympathetic nervous system, which is essential for responding to stress and regulating our cardiovascular system. By understanding how the A5 area works, we can better understand how our body maintains balance and responds to changes both internally and ex-ternally. In this overview, the details of Area A5, including its structure, chemical make-up and effects on our nervous system and cardiopulmonary operations, are further explained, highlight-ing its importance to the harmony of our body systems. Area A5 is a noradrenergic cell group in the brain stem characterised by its important role in triggering sympathetic activity, exerting a profound influence on the sympathetic outflow, which is instrumental in the modulation of cardiovascular functions, stress responses and various other physiological processes that are crucial for adaptation and survival mechanisms. Understanding the role of area A5, therefore, not only provides insights into the basic functioning of the sympathetic nervous system but also sheds light on the neuronal basis of a number of autonomic responses. In this review, we look deeper into the specifics of area A5, exploring its anatomical connections, its neurochemical properties and the mechanisms by which it influences sympathetic nervous system activity and cardiorespiratory regulation and, thus, contributes to the overall dynamics of the autonomic function in regulating body homeostasis. [ABSTRACT FROM AUTHOR]

Histone deacetylase 6 (HDAC6) is a class II histone deacetylase that is predominantly localized in the cytoplasm of cells. HDAC6 associates with microtubules and regulates acetylation of tubulin and other proteins. The possibility that HDAC6 participates in hypoxic signaling is supported by evidence that 1) hypoxic gas challenges cause microtubule depolymerization, 2) expression of hypoxia inducible factor alpha (HIF-1α) is regulated by microtubule alterations in response to hypoxia, and 3) inhibition of HDAC6 prevents HIF-1α expression and protects tissue from hypoxic/ischemic insults. The aim of this study was to address whether the absence of HDAC6 alters ventilatory responses during and/or after hypoxic gas challenge (10% O2, 90% N2 for 15 min) in adult male wildtype (WT) C57BL/6 mice and HDAC6 knock-out (KO) mice. Key findings were that 1) baseline values for frequency of breathing, tidal volume, inspiratory and expiratory times, and end expiratory pause were different between knock-out mice and wildtype mice, 2) ventilatory responses during hypoxic challenge were more robust in KO mice than WT mice for recorded parameters including, frequency of breathing, minute ventilation, inspiratory and expiratory durations, peak inspiratory and expiratory flows, and inspiratory and expiratory drives, and 3) responses upon return to room-air were markedly different in KO compared to WT mice for frequency of breathing, minute ventilation, inspiratory and expiratory durations, end expiratory pause (but not end inspiratory pause), peak inspiratory and expiratory flows, and inspiratory and expiratory drives. These data suggest that HDAC6 may have a fundamentally important role in regulating the hypoxic ventilatory response in mice. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a neurodegenerative brain disease that is the most common cause of dementia among the elderly. In addition to dementia, which is the loss of cognitive function, including thinking, remembering, and reasoning, and behavioral abilities, AD patients also experience respiratory disturbances. The most common respiratory problems observed in AD patients are pneumonia, shortness of breath, respiratory muscle weakness, and obstructive sleep apnea (OSA). The latter is considered an outcome of Alzheimer's disease and is suggested to be a causative factor. While this narrative review addresses the bidirectional relationship between obstructive sleep apnea and Alzheimer's disease and reports on existing studies describing the most common respiratory disorders found in patients with Alzheimer's disease, its main purpose is to review all currently available studies using animal models of Alzheimer's disease to study respiratory impairments. These studies on animal models of AD are few in number but are crucial for establishing mechanisms, causation, implementing potential therapies for respiratory disorders, and ultimately applying these findings to clinical practice. This review summarizes what is already known in the context of research on respiratory disorders in animal models, while pointing out directions for future research. [ABSTRACT FROM AUTHOR]

Copyright of Canadian Journal of Psychiatry is the property of Sage Publications Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Serotonin or 5-hydroxytryptamine (5-HT) is a ubiquitous neuro-modulator–transmitter that acts in the central nervous system, playing a major role in the control of breathing and other physiological functions. The midbrain, pons, and medulla regions contain several serotonergic nuclei with distinct physiological roles, including regulating the hypercapnic ventilatory response, upper airway patency, and sleep–wake states. Obesity is a major risk factor in the development of sleep-disordered breathing (SDB), such as obstructive sleep apnea (OSA), recurrent closure of the upper airway during sleep, and obesity hypoventilation syndrome (OHS), a condition characterized by daytime hypercapnia and hypoventilation during sleep. Approximately 936 million adults have OSA, and 32 million have OHS worldwide. 5-HT acts on 5-HT receptor subtypes that modulate neural control of breathing and upper airway patency. This article reviews the role of 5-HT in SDB and the current advances in 5-HT-targeted treatments for SDB. [ABSTRACT FROM AUTHOR]

Increased ventilator use during the COVID-19 pandemic resurrected persistent questions regarding mechanical ventilation including the difference between physiological and artificial breathing induced by ventilators (i.e., positive- versus negative-pressure ventilation, PPV vs NPV). To address this controversy, we compare murine specimens subjected to PPV and NPV in ex vivo quasi-static loading and quantify pulmonary mechanics via measures of quasi-static and dynamic compliances, transpulmonary pressure, and energetics when varying inflation frequency and volume. Each investigated mechanical parameter yields instance(s) of significant variability between ventilation modes. Most notably, inflation compliance, percent relaxation, and peak pressure are found to be consistently dependent on the ventilation mode. Maximum inflation volume and frequency note varied dependencies contingent on the ventilation mode. Contradictory to limited previous clinical investigations of oxygenation and end-inspiratory measures, the mechanics-focused comprehensive findings presented here indicate lung properties are dependent on loading mode, and importantly, these dependencies differ between smaller versus larger mammalian species despite identical custom-designed PPV/NPV ventilator usage. Results indicate that past contradictory findings regarding ventilation mode comparisons in the field may be linked to the chosen animal model. Understanding the differing fundamental mechanics between PPV and NPV may provide insights for improving ventilation strategies and design to prevent associated lung injuries. [ABSTRACT FROM AUTHOR]

Background: The utilization of titanium dioxide nanoparticles (TIO2NPs) has experienced a significant surge in recent decades, and these particles are now commonly found in various everyday consumer products. Due to their small size, TIO2NPs can penetrate biological barriers and elicit adverse interactions with biological tissues. Notably, exposure of pregnant females to TIO2NPs during the perinatal period has been shown to disrupt the growth of offspring. Furthermore, this exposure induces epigenetic modifications in the DNA of newborns, suggesting the possibility of multigenerational effects. Thus, perinatal exposure to TIO2NPs may induce immediate metabolic impairments in neonates, which could be transmitted to subsequent generations in the long term. Results: In this study, we utilized perinatal exposure of female mice to TIO2NPs through voluntary food intake and observed impaired metabolism in newborn male and female F1 offspring. The exposed newborn mice exhibited reduced body weight gain and a slower breathing rate compared to non-exposed animals. Additionally, a higher proportion of exposed F1 newborns experienced apneas. Similar observations were made when the exposure was limited to the postnatal period, highlighting lactation as a critical period for the adverse effects of TIO2NPs on postnatal metabolism. Importantly, the breathing deficits induced by TIO2NPs were transmitted from F1 females to the subsequent F2 generation. Moreover, re-exposure of adult F1 females to TIO2NPs exacerbated the breathing deficits in newborn F2 males. Conclusions: Our findings demonstrate that perinatal exposure to TIO2NPs disrupts postnatal body weight gain and respiration in the offspring, and these deficits are transmissible to future generations. [ABSTRACT FROM AUTHOR]

Manuel de Falla's (1876-1946) oeuvre was already discussed in terms of national Spanish music and specific Spanish values during the composer's lifetime. Following de Falla's death, some of his compositions, most notably the ballet El Amor brujo (1915), which refers to the culture of Gitanos and the phenomenon of flamenco, began to function as emblematically Spanish works, i.e. representative of contemporary Spanish music. As a result of the cultural diplomacy implemented by the Francoist government, flamenco was endorsed internationally as a hallmark of Spanishness. Works referring to flamenco, such as de Falla's El Amor brujo, were thus also intensively promoted: numerous film productions referring to flamenco alluding to de Falla's ballet in the plot and in the musical layer, significantly contributed to the international success of this work. [ABSTRACT FROM AUTHOR]

Copyright of Gestion et Management Public is the property of Association Internationale de Recherche en Management Public (AIRMAP) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Internal circadian phase assessment is increasingly acknowledged as a critical clinical tool for the diagnosis, monitoring, and treatment of circadian rhythm sleep-wake disorders and for investigating circadian timing in other medical disorders. The widespread use of in-laboratory circadian phase assessments in routine practice has been limited, most likely because circadian phase assessment is not required by formal diagnostic nosologies, and is not generally covered by insurance. At-home assessment of salivary dim light melatonin onset (DLMO, a validated circadian phase marker) is an increasingly accepted approach to assess circadian phase. This approach may help meet the increased demand for assessments and has the advantages of lower cost and greater patient convenience. We reviewed the literature describing at-home salivary DLMO assessment methods and identified factors deemed to be important to successful implementation. Here, we provide specific protocol recommendations for conducting at-home salivary DLMO assessments to facilitate a standardized approach for clinical and research purposes. Key factors include control of lighting, sampling rate, and timing, and measures of patient compliance. We include findings from implementation of an optimization algorithm to determine the most efficient number and timing of samples in patients with Delayed Sleep-Wake Phase Disorder. We also provide recommendations for assay methods and interpretation. Providing definitive criteria for each factor, along with detailed instructions for protocol implementation, will enable more widespread adoption of at-home circadian phase assessments as a standardized clinical diagnostic, monitoring, and treatment tool., (© 2024 The Author(s). Journal of Pineal Research published by John Wiley & Sons Ltd.)