Interactions between Arousal State and CO Determine the Activity of Central Chemoreceptor Neurons That Drive Breathing.

The homeostatic regulation of pulmonary ventilation, and ultimately arterial PCO, depends on interactions between respiratory chemoreflexes and arousal state. The ventilatory response to CO is triggered by neurons in the retrotrapezoid nucleus (RTN) that function as sensors of central pH, which can be identified in adulthood by the expression of Phox2b and neuromedin B. Here, we examine the dynamic response of genetically defined RTN neurons to hypercapnia and arousal state in freely behaving adult male and female mice using the calcium indicator jGCaMP7 and fiber photometry.

Statistically Significant Associations Between HPV33, HPV35, and HPV56 With Anal HSIL in a Population of MSMLWH.

Objective: The aim of the study is to determine the prevalence of high-risk human papillomavirus (hrHPV) genotypes in men who have sex with other men and are living with HIV and the factors associated with anal high-grade squamous intraepithelial lesions (HSIL).

Methods: Anal swabs were collected for hrHPV genotyping from a cross-sectional group ( N = 163) of eligible men who have sex with other men and are living with HIV attending a high-resolution anoscopy clinic. Persistent hrHPV infections were studied in a longitudinal subset ( n = 37).

Molecular Organization of Autonomic, Respiratory, and Spinally-Projecting Neurons in the Mouse Ventrolateral Medulla.

The ventrolateral medulla (VLM) is a crucial region in the brain for visceral and somatic control, serving as a significant source of synaptic input to the spinal cord. Experimental studies have shown that gene expression in individual VLM neurons is predictive of their function. However, the molecular and cellular organization of the VLM has remained uncertain.

Dorsal motor vagal neurons can elicit bradycardia and reduce anxiety-like behavior.

Cardiovagal neurons (CVNs) innervate cardiac ganglia through the vagus nerve to control cardiac function. Although the cardioinhibitory role of CVNs in nucleus ambiguus (CVN) is well established, the nature and functionality of CVNs in dorsal motor nucleus of the vagus (CVN) is less clear. We therefore aimed to characterize CVN anatomically, physiologically, and functionally.

Loss-of-function of chemoreceptor neurons in the retrotrapezoid nucleus: What have we learned from it?

Central respiratory chemoreceptors are cells in the brain that regulate breathing in relation to arterial pH and PCO. Neurons located at the retrotrapezoid nucleus (RTN) have been hypothesized to be central chemoreceptors and/or to be part of the neural network that drives the central respiratory chemoreflex. The inhibition or ablation of RTN chemoreceptor neurons has offered important insights into the role of these cells on central respiratory chemoreception and the neural control of breathing over almost 60 years since the original identification of acid-sensitive properties of this ventral medullary site.

Molecular Disambiguation of Heart Rate Control by the Nucleus Ambiguus.

The nucleus ambiguus (nAmb) provides parasympathetic control of cardiorespiratory functions as well as motor control of the upper airways and striated esophagus. A subset of nAmb neurons innervates the heart through the vagus nerve to control cardiac function at rest and during key autonomic reflexes such as the mammalian diving reflex. These cardiovagal nAmb neurons may be molecularly and anatomically distinct, but how they differ from other nAmb neurons in the adult brain remains unclear.

Dorsal Motor Vagal Neurons Can Elicit Bradycardia and Reduce Anxiety-Like Behavior.

Cardiovagal neurons (CVNs) innervate cardiac ganglia through the vagus nerve to control cardiac function. Although the cardioinhibitory role of CVNs in nucleus ambiguus (CVN) is well established, the nature and functionality of CVNs in dorsal motor nucleus of the vagus (CVN) is less clear. We therefore aimed to characterize CVN anatomically, physiologically, and functionally.

Molecular cell types as functional units of the efferent vagus nerve.

The vagus nerve vitally connects the brain and body to coordinate digestive, cardiorespiratory, and immune functions. Its efferent neurons, which project their axons from the brainstem to the viscera, are thought to comprise "functional units" - neuron populations dedicated to the control of specific vagal reflexes or organ functions. Previous research indicates that these functional units differ from one another anatomically, neurochemically, and physiologically but have yet to define their identity in an experimentally tractable way.

The astrocytic Na -HCO cotransporter, NBCe1, is dispensable for respiratory chemosensitivity.

The interoceptive homeostatic mechanism that controls breathing, blood gases and acid-base balance in response to changes in CO /H is exquisitely sensitive, with convergent roles proposed for chemosensory brainstem neurons in the retrotrapezoid nucleus (RTN) and their supporting glial cells. For astrocytes, a central role for NBCe1, a Na -HCO cotransporter encoded by Slc4a4, has been envisaged in multiple mechanistic models (i.e.

Chemogenetic activation of noradrenergic A5 neurons increases blood pressure and visceral sympathetic activity in adult rats.

In mammals, the pontine noradrenergic system influences nearly every aspect of central nervous system function. A subpopulation of pontine noradrenergic neurons, called A5, are thought to be important in the cardiovascular response to physical stressors, yet their function is poorly defined. We hypothesized that activation of A5 neurons drives a sympathetically mediated increase in blood pressure (BP).

The arcuate nucleus: A site of synergism between Angiotensin II and leptin to increase sympathetic nerve activity and blood pressure in rats.

The action of leptin in brain to increase sympathetic nerve activity (SNA) and blood pressure depends upon functional Angiotensin II (AngII) type 1a receptors (AT1aR); however, the sites and mechanism of interaction are unknown. Here we identify one site, the hypothalamic arcuate nucleus (ArcN), since prior local blockade of AT1aR in the ArcN with losartan or candesartan in anesthetized male rats essentially eliminated the sympathoexcitatory and pressor responses to ArcN leptin nanoinjections. Unlike mice, in male and female rats, AT1aR and LepR rarely co-localized, suggesting that this interdependence occurs indirectly, via a local interneuron or network of neurons.

Genetic encoding of an esophageal motor circuit.

Motor control of the striated esophagus originates in the nucleus ambiguus (nAmb), a vagal motor nucleus that also contains upper airway motor neurons and parasympathetic preganglionic neurons for the heart and lungs. We disambiguate nAmb neurons based on their genome-wide expression profiles, efferent circuitry, and ability to control esophageal muscles. Our single-cell RNA sequencing analysis predicts three molecularly distinct nAmb neuron subtypes and annotates them by subtype-specific marker genes: Crhr2, Vipr2, and Adcyap1.

Adrenergic C1 neurons monitor arterial blood pressure and determine the sympathetic response to hemorrhage.

Hemorrhage initially triggers a rise in sympathetic nerve activity (SNA) that maintains blood pressure (BP); however, SNA is suppressed following severe blood loss causing hypotension. We hypothesized that adrenergic C1 neurons in the rostral ventrolateral medulla (C1) drive the increase in SNA during compensated hemorrhage, and a reduction in C1 contributes to hypotension during decompensated hemorrhage. Using fiber photometry, we demonstrate that C1 activity increases during compensated hemorrhage and falls at the onset of decompensated hemorrhage.

Nurse-led projects for people experiencing homelessness and other inclusion health groups: a realist evaluation.

Nursing service development or innovation projects, even small-scale ones, can be difficult to deliver and evaluate, due to a lack of resources and support. Results can also be difficult to disseminate, limiting transfer of learning. This paper presents findings from a realist evaluation of 10 small projects supported by the Queen's Nursing Institute Homeless and Inclusion Health Programme to deliver innovation in health care for people experiencing homelessness and other marginalised groups.

Respiratory alkalosis provokes spike-wave discharges in seizure-prone rats.

Hyperventilation reliably provokes seizures in patients diagnosed with absence epilepsy. Despite this predictable patient response, the mechanisms that enable hyperventilation to powerfully activate absence seizure-generating circuits remain entirely unknown. By utilizing gas exchange manipulations and optogenetics in the WAG/Rij rat, an established rodent model of absence epilepsy, we demonstrate that absence seizures are highly sensitive to arterial carbon dioxide, suggesting that seizure-generating circuits are sensitive to pH.

Chemoreceptor mechanisms regulating CO -induced arousal from sleep.

Arousal from sleep in response to CO is a life-preserving reflex that enhances ventilatory drive and facilitates behavioural adaptations to restore eupnoeic breathing. Recurrent activation of the CO -arousal reflex is associated with sleep disruption in obstructive sleep apnoea. In this review we examine the role of chemoreceptors in the carotid bodies, the retrotrapezoid nucleus and serotonergic neurons in the dorsal raphe in the CO -arousal reflex.

Vagus nerve stimulation activates two distinct neuroimmune circuits converging in the spleen to protect mice from kidney injury.

Acute kidney injury is highly prevalent and associated with high morbidity and mortality, and there are no approved drugs for its prevention and treatment. Vagus nerve stimulation (VNS) alleviates inflammatory diseases including kidney disease; however, neural circuits involved in VNS-induced tissue protection remain poorly understood. The vagus nerve, a heterogeneous group of neural fibers, innervates numerous organs.

Cross comparison of AmpFire HPV genotyping assay and Roche human papillomavirus (HPV) linear array for HPV genotyping of anal swab samples.

Although anal cancers represent just 0.5 % of all new cancer cases in U.S.

TRPM4 mediates a subthreshold membrane potential oscillation in respiratory chemoreceptor neurons that drives pacemaker firing and breathing.

Brainstem networks that control regular tidal breathing depend on excitatory drive, including from tonically active, CO/H-sensitive neurons of the retrotrapezoid nucleus (RTN). Here, we examine intrinsic ionic mechanisms underlying the metronomic firing activity characteristic of RTN neurons. In mouse brainstem slices, large-amplitude membrane potential oscillations are evident in synaptically isolated RTN neurons after blocking action potentials.

The Risk of Anal Carcinoma After Anogenital Warts in Adults Living With HIV.

Importance: In the US, incidence of and mortality due to anal carcinoma are rising faster than for most other cancers. Identifying populations who have a higher risk of developing anal cancers is critical to target preventive interventions.

Objective: To assess the risk of developing anal carcinoma in adults living with HIV who have a history of anogenital warts.