Nasopharyngeal lymphatic plexus is a hub for cerebrospinal fluid drainage.

Cerebrospinal fluid (CSF) in the subarachnoid space around the brain has long been known to drain through the lymphatics to cervical lymph nodes1-17, but the connections and regulation have been challenging to identify. Here, using fluorescent CSF tracers in Prox1-GFP lymphatic reporter mice18, we found that the nasopharyngeal lymphatic plexus is a major hub for CSF outflow to deep cervical lymph nodes. This plexus had unusual valves and short lymphangions but no smooth-muscle coverage, whereas downstream deep cervical lymphatics had typical semilunar valves, long lymphangions and smooth muscle coverage that transported CSF to the deep cervical lymph nodes. α-Adrenergic and nitric oxide signalling in the smooth muscle cells regulated CSF drainage through the transport properties of deep cervical lymphatics. During ageing, the nasopharyngeal lymphatic plexus atrophied, but deep cervical lymphatics were not similarly altered, and CSF outflow could still be increased by adrenergic or nitric oxide signalling. Single-cell analysis of gene expression in lymphatic endothelial cells of the nasopharyngeal plexus of aged mice revealed increased type I interferon signalling and other inflammatory cytokines. The importance of evidence for the nasopharyngeal lymphatic plexus functioning as a CSF outflow hub is highlighted by its regression during ageing. Yet, the ageing-resistant pharmacological activation of deep cervical lymphatic transport towards lymph nodes can still increase CSF outflow, offering an approach for augmenting CSF clearance in age-related neurological conditions in which greater efflux would be beneficial.

Reliability of maximal respiratory nasal pressure tests in healthy young adults.

INTRODUCTION: Sniff nasal inspiratory (SNIP) and expiratory pressure (SNEP) may complement the assessment of respiratory muscle strength. Thus, specifying their reliability is relevant to improving the clinical consistency of both tests. OBJECTIVE: To assess the reliability of SNIP and SNEP in healthy young adults. METHODS: This cross-sectional study included self-reported healthy aged 18 to 29 years. SNIP was performed using a plug to occlude one nostril, while SNEP was conducted using a facemask. Participants performed 20 SNIP and SNEP maneuvers with 30-second intervals in between. The intraclass correlation coefficient (ICC), standard error of measurement (SEM), and minimum detectable change (MDC) assessed the reliability of SNIP and SNEP. Analyses were conducted between the highest peak pressure and the first reproducible maneuver in men and women. RESULTS: The total sample comprised 32 participants: 16 men and 16 women. The ICC, SEM, and MDC for SNIP maneuvers were 0.994 (95%CI 0.988 to 0.997), 1.820 cmH2O, and 5.043 cmH2O, respectively. For SNEP, these parameters were 0.950 (95%CI 0.897 to 0.976), 6.03 cmH2O, and 16.716 cmH2O. The SNIP and SNEP in men showed ICC of 0.992 (95%CI 0.977 to 0.997) and 0.877 (95%CI 0.648 to 0.957), SEM of 2.07 and 7.66 cmH2O, and MDC of 5.74 and 21.23 cmH2O. In women, SNIP and SNEP presented ICC of 0.992 (95%CI 0.977 to 0.997) and 0.957 (95%CI 0.878 to 0.985), SEM of 1.15 and 6.11 cmH2O, and MDC of 3.19 and 16.95 cmH2O. Also, 60% of the highest SNIPs occurred among the 11th and 20th maneuvers in men and women. In men, 55% of the highest SNEPs occurred among the 11th and 20th maneuvers; this value was 50% in women. CONCLUSION: SNIP and SNEP showed excellent reliability. The reliability of SNIP and SNEP in men was good and excellent, respectively, whereas both tests had excellent reliability in women. Also, women reached the highest peak pressure faster than men in both tests.

Odor modality is transmitted to cortical brain regions from the olfactory bulb.

Odor perception is the impetus for important animal behaviors with two predominate modes of processing: odors pass through the front of the nose (orthonasal) while inhaling and sniffing, or through the rear (retronasal) during exhalation and while eating. Despite the importance of olfaction for an animal's well-being and that ortho and retro naturally occur, it is unknown how the modality (ortho vs. retro) is even transmitted to cortical brain regions, which could significantly affect how odors are processed and perceived. Using multielectrode array recordings in tracheotomized anesthetized rats, which decouples ortho-retro modality from breathing, we show that mitral cells in rat olfactory bulb can reliably and directly transmit orthonasal versus retronasal modality with ethyl butyrate, a common food odor. Drug manipulations affecting synaptic inhibition via GABAA lead to worse decoding of ortho versus retro, independent of whether overall inhibition increases or decreases, suggesting that the olfactory bulb circuit may naturally favor encoding this important aspect of odors. Detailed data analysis paired with a firing rate model that captures population trends in spiking statistics shows how this circuit can encode odor modality. We have not only demonstrated that ortho/retro information is encoded to downstream brain regions but also used modeling to demonstrate a plausible mechanism for this encoding; due to synaptic adaptation, it is the slower time course of the retronasal stimulation that causes retronasal responses to be stronger and less sensitive to inhibitory drug manipulations than orthonasal responses.NEW & NOTEWORTHY Whether ortho (sniffing odors) versus retro (exhalation and eating) is encoded from the olfactory bulb to other brain areas is not completely known. Using multielectrode array recordings in anesthetized rats, we show that the olfactory bulb transmits this information downstream via spikes. Altering inhibition degrades ortho/retro information on average. We use theory and computation to explain our results, which should have implications on cortical processing considering that only food odors occur retronasally.

Dedicated odor-taste stimulation design for fMRI flavor studies.

BACKGROUND: Flavor is a mental representation that results from the brain's integration of at least odor and taste, and fMRI can highlight brain-related areas. However, delivering stimuli during fMRI can be challenging especially when administrating liquid stimuli in supine position. It remains unclear how and when odorants are released in the nose and how to improve odorant release. NEW METHOD: We used a proton transfer reaction mass spectrometer (PTR-MS) to monitor the in vivo release of odorants via the retronasal pathway during retronasal odor-taste stimulation in a supine position. We tested techniques to improve odorant release, including avoiding or delaying swallowing and velum open training (VOT). RESULTS: Odorant release was observed during retronasal stimulation, before swallowing, and in a supine position. VOT did not improve odorant release. Odorant release during stimulation had a latency more optimal for fitting with BOLD timing than after swallowing. COMPARISON WITH EXISTING METHOD(S): Previous in vivo measurements of odorant release under fMRI-like conditions showed that odorant release occurred only after swallowing. On the contrary, a second study found that aroma release could occur before swallowing, but participants were sitting. CONCLUSION: Our method shows optimal odorant release during the stimulation phase, meeting the criteria for high-quality brain imaging of flavor processing without swallowing-related motion artifacts. These findings provide an important advancement in understanding the mechanisms underlying flavor processing in the brain.

Effects of Nasalization on Vocal Tract Response Curve.

BACKGROUND: Earlier studies have shown that nasalization affects the radiated spectrum by modifying the vocal tract transfer function in a complex manner. METHODS: Here we study this phenomenon by measuring sine-sweep response of 3-D models of the vowels /u, a, ᴂ, i/, derived from volumetric MR imaging, coupled by means of tubes of different lengths and diameters to a 3-D model of a nasal tract. RESULTS: The coupling introduced a dip into the vocal tract transfer function. The dip frequency was close to the main resonance of the nasal tract, a result in agreement with the Fujimura & Lindqvist in vivo sweep tone measurements [Fujimura & Lindqvist, 1972]. With increasing size of the coupling tube the depth of the dip increased and the first formant peak either changed in frequency or was split by the dip. Only marginal effects were observed of the paranasal sinuses. For certain coupling tube sizes, the spectrum balance was changed, boosting the formant peaks in the 2 - 4 kHz range. CONCLUSION: A velopharyngeal opening introduces a dip in the transfer function at the main resonance of the nasal tract. Its depth increases with the area of the opening and its frequency rises in some vowels.

Clinical Observation of the Effect of Nasal Breathing on Nonanalgesic and Sedative Gastroscopy.

This study aimed to investigate the safety, tolerance, and comfort of the subjects in gastroscopy by observing and comparing the effect of gastroscopy under two different breathing modes: nasal breathing and nasal inspiration and oral expiration. A total of 60 subjects who underwent routine gastroscopy in the hospital from January 2021 to June 2021 were selected as the research subjects. According to the willingness of the subjects, they were divided into a nasal breathing group and a nasal inspiration and oral expiration group. The differences in vital signs, adverse reactions, and visual analog scale (VAS) scores were compared between the two groups. There were no significant differences in mean arterial pressure, heart rate, and blood oxygen saturation between the two groups before, during, and after the examination (P > 0.05). The nasal breathing group had fewer adverse reactions such as nausea, cough, belching, and restlessness than the nasal inspiration and oral expiration group, and the difference was statistically significant (P < 0.01). VAS score of the nasal breathing group was lower than that of the nasal inspiration and oral expiration group, and the difference was statistically significant (P < 0.01). Subjects are more tolerant to nasal breathing mode, which causes fewer adverse reactions, less pain, and more comfort and is more worthy to be popularized in primary hospitals.

Skin wrinkles and folds enable asymmetric stretch in the elephant trunk.

The elephant's trunk is multifunctional: It must be flexible to wrap around vegetation, but tough to knock down trees and resist attack. How can one appendage satisfy both constraints? In this combined experimental and theoretical study, we challenged African elephants to reach far-away objects with only horizontal extensions of their trunk. Surprisingly, the trunk does not extend uniformly, but instead exhibits a dorsal "joint" that stretches 15% more than the corresponding ventral section. Using material testing with the skin of a deceased elephant, we show that the asymmetry is due in part to patterns of the skin. The dorsal skin is folded and 15% more pliable than the wrinkled ventral skin. Skin folds protect the dorsal section and stretch to facilitate downward wrapping, the most common gripping style when picking up items. The elephant's skin is also sufficiently stiff to influence its mechanics: At the joint, the skin requires 13 times more energy to stretch than the corresponding length of muscle. The use of wrinkles and folds to modulate stiffness may provide a valuable concept for both biology and soft robotics.

Importance of the numerical schemes in the CFD of the human nose.

Computational fluid dynamics of the air flow in the human nasal cavities, starting from patient-specific Computer Tomography (CT) scans, is an important tool for diagnostics and surgery planning. However, a complete and systematic assessment of the influence of the main modelling assumptions is still lacking. In designing such simulations, choosing the discretization scheme, which is the main subject of the present work, is an often overlooked decision of primary importance. We use a comparison framework to quantify the effects of the major design choices. The reconstructed airways of a healthy, representative adult patient are used to set up a computational study where such effects are systematically measured. It is found that the choice of the numerical scheme is the most important aspect, although all varied parameters impact the solution noticeably. For a physiologically meaningful flow rate, changes of the global pressure drop up to more than 50% are observed; locally, velocity differences can become extremely significant. Our results call for an improved standard in the description of this type of numerical studies, where way too often the order of accuracy of the numerical scheme is not mentioned.

Uniqueness of inspiratory airflow patterns in a realistic rat nasal cavity.

In this study, we present a detailed flow analysis using an anatomically accurate rat nasal cavity model, in which the anatomy and physiology of the nasal airway was thoroughly examined. Special efforts were given to the swirling flow structures in the nasal vestibule (anterior section of the nose, lined by squamous epithelium), fractional flow patterns in the olfactory (posterior superior section of the rat nose, lined by olfactory epithelium), and a designated method to precisely quantify flow apportionment in the olfactory region was developed. Results revealed distinct inspiratory flow patterns in the anterior vestibule region, where the accelerated airflow undergoes two sharp turns as traveling through the tortuous airway, making a route in a shape of 8. Besides this, exceptionally large flow apportionment was observed at the interface of the olfactory recess, which can be as much as 15 times greater than that in the human nose. The thorough understanding of the airflow dynamics in the rat nasal cavity is necessary to avoid potential misinterpretation of rat-derived inhalation toxicity results. Research findings are expected to play a fundamental role in developing unbiased rat to human interspecies data extrapolation schemes.

Otogenic Pneumocephalus After Tegmen Bone Reconstruction: A Case Report.

Pneumocephalus is usually induced by trauma, infections, tumors of the skull base, and surgical interventions. Spontaneous pneumocephalus occurs due to a defect in the temporal bone with no obvious cause. Few cases have been reported with spontaneous otogenic pneumocephalus. However, delayed postoperative pneumocephalus is rarely reported in the literature. Here, we present a case of otogenic pneumocephalus through Eustachian tube (ET) preceded by nose blowing 10 days after surgical treatment of meningoencephalocele of the right middle ear (ME) cleft and reconstruction of tegmen and dural defects. Pneumocephalus was provoked by decreased intracranial pressure (ICP) secondary to placement of lumbar drain, which caused direct communication between unsutured dural defect and the defective posterior wall of external auditory canal skin. A revision surgery of combined transmastoid/middle cranial fossa approach was performed for intracranial decompression followed by appropriate closure by suturing the dura, obliterating the ET and ME.

Exhaled and nasal NO measurement: NO in your breath doesn't imply a negative attitude!

Measurement of exhaled nitric oxide (NO) and nasal nitric oxide commenced in the 1990s shortly after the scientific world learned about the endogenous production of NO and its multiple roles in physiologic and pathologic processes. Exhaled NO is an established approved clinical test in asthma that can cast light on eosinophilic airway inflammation and the response to anti-inflammatory medications e.g., inhaled corticosteroids. Nasal NO which is extremely low in primary ciliary dyskinesia is an established screening test for this condition. This review is a high-level practical guide for those wishing to use exhaled and nasal NO for research and clinical application.

The accuracy of tactile assessment of canine nose temperature to identify rectal hyperthermia and hypothermia in dogs presenting on an emergency basis.

The goals of this study were to evaluate whether touch can identify a warm nose as opposed to a cold nose, to examine the correlation between thermographically measured nose temperatures and rectal temperatures, and to calculate the accuracy of tactile assessment of nose temperature in detecting rectal hyperthermia and hypothermia in dogs. A total of 100 dogs presenting to an emergency room was prospectively enrolled. Tactile nose assessment was carried out on triage. Noses were subjectively categorized as warm, cold, or intermediate (neither warm nor cold). Thermographic nose temperatures were recorded using a thermal imaging camera. Tactile assessment categorized noses as warm, intermediate, or cold (P < 0.01). There was no correlation between thermographically measured nose temperature and rectal temperature (r = 0.02). Tactile assessment of noses as warm had a sensitivity of 29.4% and a specificity of 79.5% for detecting rectal hyperthermia; calculated test accuracy was 71%. Tactile assessment of noses as cold had a sensitivity of 54.5% and a specificity of 62.9%; calculated test accuracy was 62%. It was concluded that nose temperatures do not correlate with rectal temperatures. Tactile assessment of nose temperature is inaccurate for identifying rectal hyperthermia or hypothermia.

Les objectifs de cette étude étaient d'évaluer si le toucher peut identifier un nez chaud par opposition à un nez froid, d'examiner la corrélation entre les températures nasales mesurées thermographiquement et les températures rectales, et de calculer la précision de l'évaluation tactile de la température nasale dans la détection de l'hyperthermie et l'hypothermie rectale chez le chien. Un total de 100 chiens se présentant aux urgences a été enrôlé de manière prospective. Une évaluation tactile du nez a été réalisée lors du triage. Les nez ont été classés subjectivement comme chaud, froid ou intermédiaire (ni chaud ni froid). Les températures thermographiques du nez ont été enregistrées à l'aide d'une caméra thermique. L'évaluation tactile a classé les nez comme chauds, intermédiaires ou froids (P < 0,01). Il n'y avait pas de corrélation entre la température nasale mesurée par thermographie et la température rectale (r = 0,02). L'évaluation tactile des nez chauds avait une sensibilité de 29,4 % et une spécificité de 79,5 % pour détecter l'hyperthermie rectale; la précision calculée du test était de 71 %. L'évaluation tactile des nez froids avait une sensibilité de 54,5 % et une spécificité de 62,9 %; la précision calculée du test était de 62 %. Il a été conclu que les températures nasales ne sont pas corrélées avec les températures rectales. L'évaluation tactile de la température du nez est imprécise pour identifier l'hyperthermie ou l'hypothermie rectale.(Traduit par les auteurs).

Influence of Prebiotic Fructans on Retronasal Aroma from Elderly Individuals.

This study investigates for the first time the role of fructans with prebiotic effects (oligofructose and inulin) on retronasal aroma among elderly individuals. The impact of oligofructose (20% w/w) on retronasal aroma release was investigated using proton transfer reaction-mass spectrometry (PTR-MS) after 73 elderly individuals consumed aqueous solutions aromatized with five aroma compounds (pentan-2-one, nonan-2-one, hexan-2,3-dione, octanal and linalool). The influence of oligofructose and inulin (10% w/w) on the perceived intensity (n = 26) of two aroma descriptors (butter and floral) was also studied together with the possibility of a dumping effect on aroma evaluation due to the sweetness provided by the fructans. The results showed that the presence of oligofructose produced a significant reduction in retronasal aroma release, which could be generally explained by the physicochemical properties of aroma compounds. The presence of prebiotic fructans did not significantly affect the perceived intensity of butter and floral notes, although a dumping effect for the butter descriptor in the presence of oligofructose was observed. To conclude, these findings suggest that although fructans can exert an impact on retronasal aroma, they can be used at precise concentrations to increase the prebiotic fibre content of food products without affecting the aroma profile of foods.

The nasocardiac reflex during nasoendoscopy: A commonly overlooked risk.

PURPOSE: The nasocardiac reflex is known but not well researched. We aimed to ascertain the electrocardiographic features of the reflex and to chronologically map the heart rhythm dynamics during nasoendoscopy. We also intended to identify variables that could potentially affect the occurrence of this reflex. MATERIAL AND METHODS: A prospective, quasi-experimental physiological study. Selected healthy subjects were observed electrocardiographically for 60 s continuously in three equal phases of 20 s each - baseline phase, nasoendoscopic phase, and recovery phase (post-nasoendoscopy). Heart rate fluctuations were charted, followed by identification of a positive nasocardiac reflex group of subjects and a negative group. Analyses against multiple variables were done. RESULTS: A total of 53 subjects were analysed. Heart rate during the baseline phase was 81.0 ± 9.9, nasoendoscopic phase was 72.7 ± 10.1, and recovery phase was 75.2 ± 9.6. Sixteen subjects (30.2%) had a positive nasocardiac reflex, and they remained in sinus rhythm with no occurrences of skipped beats, atrioventricular blocks or asystoles. One subject (1.9%) developed temporary ectopic premature ventricular contractions after nasoendoscopy. No variables were found affecting the incidence of a nasocardiac reflex in our study. CONCLUSIONS: The pattern of heart rate dynamics was consistent as heart rates drop rapidly upon endoscope insertion and recover in some measure after its withdrawal. Although all our subjects remained asymptomatic, clinicians should not overlook the risks of a severe nasocardiac reflex when performing nasoendoscopy. We recommend that electrical cardiac monitoring be part of the management of vasovagal responses during in-office endonasal procedures.

Odor identification performance in children aged 3-6 years.

BACKGROUND: While valid and reliable olfactory tests have been developed for children aged >5 years, olfactory testing has not systematically been evaluated in younger children. The aim of this study was to evaluate the reliability and validity of the "U-Sniff" odor identification test in children aged 3-6 years. METHODS: We included 160 healthy children (age range 3-6 years) and 14 congenitally anosmic children. Participants were investigated in two identical sessions. The "U-Sniff" test was used to evaluate olfactory function. A picture identification test (PIT) and the Kasel-Concentration-Task (KKA) were administered to identify factors influencing odor identification performance. RESULTS: Age significantly influenced odor identification performance, with older children achieving higher scores. PIT and KKA scores correlated positively with odor identification scores. The "U-Sniff" test demonstrated a high test-retest reliability (r160 = 0.75, p < 0.001). It was possible to distinguish between healthy and anosmic children by means of "U-Sniff" scores starting at age 4 years with high sensitivity (79-93%) and specificity (88-95%). CONCLUSIONS: The "U-Sniff" test is feasible for children starting at age 3 years. In children aged ≥4 years, it is a reliable and valid method to distinguish between normal olfactory function and anosmia. IMPACT: Olfactory testing is reliable and valid starting at an age of 4 years. The study adds a systematic evaluation of olfactory testing in young children. Results of this study are especially interesting for clinicians in the diagnosis of olfactory dysfunction.

Network study of nasal transcriptome profiles reveals master regulator genes of asthma.

BACKGROUND: Nasal transcriptomics can provide an accessible window into asthma pathobiology. OBJECTIVE: Our goal was to move beyond gene signatures of asthma to identify master regulator genes that causally regulate genes associated with asthma phenotypes. METHODS: We recruited 156 children with severe persistent asthma and controls for nasal transcriptome profiling and applied network-based and probabilistic causal methods to identify severe asthma genes and their master regulators. We then took the same approach in an independent cohort of 190 adults with mild/moderate asthma and controls to identify mild/moderate asthma genes and their master regulators. Comparative analysis of the master regulator genes followed by validation testing in independent children with severe asthma (n = 21) and mild/moderate asthma (n = 154) was then performed. RESULTS: Nasal gene signatures for severe persistent asthma and for mild/moderate persistent asthma were identified; both were found to be enriched in coexpression network modules for ciliary function and inflammatory response. By applying probabilistic causal methods to these gene signatures and validation testing in independent cohorts, we identified (1) a master regulator gene common to asthma across severity and ages (FOXJ1); (2) master regulator genes of severe persistent asthma in children (LRRC23, TMEM231, CAPS, PTPRC, and FYB); and (3) master regulator genes of mild/moderate persistent asthma in children and adults (C1orf38 and FMNL1). The identified master regulators were statistically inferred to causally regulate the expression of downstream genes that modulate ciliary function and inflammatory response to influence asthma. CONCLUSION: The identified master regulator genes of asthma provide a novel path forward to further uncovering asthma mechanisms and therapy.

Computational modelling of nasal respiratory flow.

CFD has emerged as a promising diagnostic tool for clinical trials, with tremendous potential. However, for real clinical applications to be useful, overall statistical findings from large population samples (e.g., multiple cases and models) are needed. Fully resolved solutions are not a priority, but rather rapid solutions with fast turn-around times are desired. This leads to the issue of what are the minimum modelling criteria for achieving adequate accuracy in respiratory flows for large-scale clinical applications, with a view to rapid turnaround times. This study simulated a highly-resolved solution using the large eddy simulation (LES) method as a reference case for comparison with lower resolution models that included larger time steps and no turbulence modelling. Differences in solutions were quantified by pressure loss, flow resistance, unsteadiness, turbulence intensity, and hysteresis effects from multiple cycles. The results demonstrated that sufficient accuracy could be achieved with lower resolution models if the mean flow was considered. Furthermore, to achieve an established transient result unaffected by the initial start-up quiescent effects, the results need to be taken from at least the second respiration cycle. It was also found that the exhalation phase exhibited strong turbulence. The results are expected to provide guidance for future modelling efforts for clinical and engineering applications requiring large numbers of cases using simplified modelling approaches.

Nasal respiration is necessary for ketamine-dependent high frequency network oscillations and behavioral hyperactivity in rats.

Changes in oscillatory activity are widely reported after subanesthetic ketamine, however their mechanisms of generation are unclear. Here, we tested the hypothesis that nasal respiration underlies the emergence of high-frequency oscillations (130-180 Hz, HFO) and behavioral activation after ketamine in freely moving rats. We found ketamine 20 mg/kg provoked "fast" theta sniffing in rodents which correlated with increased locomotor activity and HFO power in the OB. Bursts of ketamine-dependent HFO were coupled to "fast" theta frequency sniffing. Theta coupling of HFO bursts were also found in the prefrontal cortex and ventral striatum which, although of smaller amplitude, were coherent with OB activity. Haloperidol 1 mg/kg pretreatment prevented ketamine-dependent increases in fast sniffing and instead HFO coupling to slower basal respiration. Consistent with ketamine-dependent HFO being driven by nasal respiration, unilateral naris blockade led to an ipsilateral reduction in ketamine-dependent HFO power compared to the control side. Bilateral nares blockade reduced ketamine-induced hyperactivity and HFO power and frequency. These findings suggest that nasal airflow entrains ketamine-dependent HFO in diverse brain regions, and that the OB plays an important role in the broadcast of this rhythm.