A vagal-brainstem interoceptive circuit for cough-like defensive behaviors in mice.

Coughing is a respiratory behavior that plays a crucial role in protecting the respiratory system. Here we show that the nucleus of the solitary tract (NTS) in mice contains heterogenous neuronal populations that differentially control breathing. Within these subtypes, activation of tachykinin 1 (Tac1)-expressing neurons triggers specific respiratory behaviors that, as revealed by our detailed characterization, are cough-like behaviors. Chemogenetic silencing or genetic ablation of Tac1 neurons inhibits cough-like behaviors induced by tussive challenges. These Tac1 neurons receive synaptic inputs from the bronchopulmonary chemosensory and mechanosensory neurons in the vagal ganglion and coordinate medullary regions to control distinct aspects of cough-like defensive behaviors. We propose that these Tac1 neurons in the NTS are a key component of the airway-vagal-brain neural circuit that controls cough-like defensive behaviors in mice and that they coordinate the downstream modular circuits to elicit the sequential motor pattern of forceful expiratory responses.

Intradental mechano-nociceptors serve as sentinels that prevent tooth damage.

Pain is the anticipated output of the trigeminal sensory neurons that innervate the tooth's vital interior 1,2 ; however, the contribution of intradental neurons to healthy tooth sensation has yet to be defined. Here, we employ in vivo Ca 2+ imaging to identify and define a population of myelinated high-threshold mechanoreceptors (intradental HTMRs) that detect superficial structural damage of the tooth and initiate jaw opening to protect teeth from damage. Intradental HTMRs remain inactive when direct forces are applied to the intact tooth but become responsive to forces when the structural integrity of the tooth is compromised, and the dentin or pulp is exposed. Their terminals collectively innervate the inner dentin through overlapping receptive fields, allowing them to monitor the superficial structures of the tooth. Indeed, intradental HTMRs detect superficial enamel damage and encode its degree, and their responses persist in the absence of either PIEZO2 or Na v 1.8 3,4 . Optogenetic activation of intradental HTMRs triggers a rapid, jaw opening reflex via contraction of the digastric muscle. Taken together, our data indicate that intradental HTMRs serve as sentinels that guard against mechanical threats to the tooth, and their activation results in physical tooth separation to minimize irreversible structural damage. Our work provides a new perspective on the role of intradental neurons as protective rather than exclusively pain-inducing and illustrates additional diversity in the functions of interoreceptors.

Association between developmental defects of enamel and early childhood caries in children under 6 years old: A systematic review and meta-analysis.

Early childhood caries (ECC) are an oral health problem worldwide in children under 6 years of age. This disease of rapid development has a multifactorial etiology, and one of the possible risk factors is developmental defects of enamel (DDE), such as hypoplasia and opacities. The aim of this systematic review was to evaluate the association between DDE and ECC in children under 6 years of age. An electronic search was conducted until March 2022 using Medline (PubMed), Scopus, Science-Direct, LILACS, Web of Science, Cochrane Library, EBSCO-Host, EMBASE, and Google Scholar and complemented with a manual search, with no restrictions on language or date of publication. Longitudinal studies of children under 6 years of age with primary dentition were included. A total of 1158 studies were found, of which 651 records were reviewed by title and abstract, and 24 articles were selected for full-text evaluation. Finally, nine studies that met the selection criteria were included in the qualitative synthesis. Study quality and certainty were assessed using the Newcastle-Ottawa scale and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool. Three cohort studies of good quality were included in the meta-analysis. A risk associated with DDE (RR = 1.94; 95% CI: 1.52-2.49) and a risk associated with enamel hypoplasia (RR = 5.45; 95% CI: 1.84-16.14) were found. The results for diffuse opacity (RR = 1.21; 95% CI: 0.18-8.15) and demarcated opacity (RR = 1.26; 95% CI: 0.43-3.65) were not significant. GRADE analysis presented low and very low certainty of evidence. It was concluded that there is an association between DDE and ECC. However, the results should be interpreted with caution because of the limitations of the study. The protocol for this study has been registered in PROSPERO under identification number CRD42021238919.

Antiviral effect of mouthwashes against SARS-COV-2: A systematic review.

OBJECTIVE: This systematic review aimed to evaluate the antiviral effect of mouthwashes against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). MATERIAL AND METHODS: An electronic search was performed on PubMed, Scopus, Web of Science, Cochrane Library, LILACS, ProQuest, and Google Scholar, and was complemented by a manual search. Both clinical and in vitro studies that focused on the antiviral effect of mouthwashes against SARS-CoV-2 were included. Risk of bias assessment was performed only on the clinical studies using the RoB-2 and ROBINS-I tools. RESULTS: A total of 907 records were found; after initial selection by title and abstract, 33 full-text articles were selected to be evaluated for eligibility. Finally, a total of 27 studies were included for the qualitative synthesis, including 16 in vitro studies and 11 clinical trials. Antiviral effects were evaluated separately for the in vitro and clinical studies. In vitro studies included mouthwashes containing hydrogen peroxide, chlorhexidine digluconate, povidone-iodine, essential oils, cetylpyridinium chloride, and other compounds; in vivo studies included mouthwashes containing hydrogen peroxide, chlorhexidine digluconate, povidone-iodine, cetylpyridinium chloride, essential oils, chlorine dioxide, ß-cyclodextrin-citrox, and sorbitol with xylitol. Povidone-iodine, cetylpyridinium chloride, and essential oils were effective in vitro, while hydrogen peroxide, chlorhexidine digluconate, povidone-iodine, cetylpyridinium chloride, ß-cyclodextrin-citrox, and sorbitol with xylitol were effective in vivo. Unclear or high risk of bias was found for almost all clinical studies, and only one study presented with a low risk of bias. No further quantitative analysis was performed. CONCLUSION: Although povidone-iodine, cetylpyridinium chloride, and essential oils may be an alternative to reduce the viral load in vitro and in vivo, more studies are needed to determine the real antiviral effect of these different mouthwashes against SARS-CoV-2.This work was not funded. The protocol was registered in PROSPERO (identification number: CRD42021236134).

Temporospatial regulation of intraflagellar transport is required for the endochondral ossification in mice.

Ciliogenic components, such as the family of intraflagellar transport (IFT) proteins, are recognized to play key roles in endochondral ossification, a critical process to form most bones. However, the unique functions and roles of each IFT during endochondral ossification remain unclear. Here, we show that IFT20 is required for endochondral ossification in mice. Utilizing osteo-chondrocyte lineage-specific Cre mice (Prx1-Cre and Col2-Cre), we deleted Ift20 to examine its function. Although chondrocyte-specific Ift20 deletion with Col2-Cre mice did not cause any overt skeletal defects, mesoderm-specific Ift20 deletion using Prx1-Cre (Ift20:Prx1-Cre) mice resulted in shortened limb outgrowth. Primary cilia were absent on chondrocytes of Ift20:Prx1-Cre mice, and ciliary-mediated Hedgehog signaling was attenuated in Ift20:Prx1-Cre mice. Interestingly, loss of Ift20 also increased Fgf18 expression in the perichondrium that sustained Sox9 expression, thus preventing endochondral ossification. Inhibition of enhanced phospho-ERK1/2 activation partially rescued defective chondrogenesis in Ift20 mutant cells, supporting an important role for FGF signaling. Our findings demonstrate that IFT20 is a critical regulator of temporospatial FGF signaling that is required for endochondral ossification.

Factores de riesgo de caries en niños pre escolares de la Amazonía peruana

Objetivo: Investigar la influencia de los factores sociodemográficos y las características atribuidas al huésped, sustrato y microorganismos en el riesgo de caries de infancia temprana en niños de 2 a 5 años de una comunidad rural de la Amazonía peruana. Material y métodos: Estudio transversal en 155 niños de 2 a 5 años del distrito de Pichanaki. Se realizó un examen clínico, y cuestionario. Para el análisis de riesgo, se realizaron modelos de regresión logística univariados y multivariados, corregidos mediante el método de Holm-Bonferroni y un bootstrapping con 10000 ciclos de muestreo. Resultados: La prevalencia de caries fue del 83.3%. Los factores asociados a caries dental fueron los antecedentes de infecciones del tracto urinario durante el embarazo (p = 0.005), una higiene bucal pobre (p = 0.001), el compartir cubiertos con su cuidador principal (p = 0.018), y tener hermanos mayores con caries (p = 0.025). El análisis univariado mostró que las infecciones urinarias durante el embarazo, la mala higiene bucal, compartir cubiertos y tener hermanos mayores con caries aumentaron el riesgo de caries. El modelo multivariado mostró que solo la mala higiene bucal (OR: 1.99, 95% CI: 1.34 ­ 2.96, p = 0.001) y la infección urinaria (OR: 2.98, 95% CI: 1.13 ­ 7.81, p = 0.027) se asociaron a un mayor riesgo de caries dental. Conclusión: Las infecciones urinarias durante el embarazo y una higiene bucal inadecuada son factores fuertemente predisponentes para la caries de infancia temprana en niños de 2 a 5 años de una comunidad rural de la Amazonía peruana.

Estudio de la longitud y diámetro radicular de incisivos laterales primarios utilizando la tomografía computarizada cone beam: un estudio in vitro

Objetivo: Determinar la longitud y el diámetro radicular de los incisivos laterales superiores deciduos a través de la Tomografía Computarizada Cone Beam. Metodología: Estudio descriptivo y transversal. Se recolectaron 20 incisivos deciduos laterales superiores recién extraídos o avulsionados de la clínica odontológica de la Universidad Nacional Mayor de San Marcos, en el año 2016. Los dientes fueron escaneados utilizando la Tomografía Cone Beam, se empleó el equipo OP300 Maxio, Orthopantomograph ®. Las imágenes resultantes fueron analizadas en el software de análisis de imagen ONDEMAND3DDENTAL. Se midió el eje axial, la longitud de la corona, raíz y la longitud total de la pieza dentaria. Para el análisis estadístico se utilizó el software Stata v14 (Stata Corporation College Station, Texas), previo al análisis los datos obtenidos fueron sometidos a la prueba de normalidad de Shapiro-Wilk, cumpliendo con esto, se usaron las pruebas paramétricas ANOVA y T de Student. Resultados: El 100% de los incisivos laterales superiores deciduos presentó un único canal radicular. La longitud promedio de la corona y de la raíz fue de 3.8mm y 11,86mm respectivamente. El diámetro medio del canal radicular según profundidad fue de 1.11 mm a nivel cervical, de 0.94 mm a nivel medio y de 0.74 mm a nivel apical, estos mostraron diferencias estadísticamente significativas (p<0.05).Conclusiones: La longitud promedio de los incisivos laterales superiores deciduos fue de 15,68mm y el diámetro radicular disminuyo de cervical a apical.

Unilateral nasal obstruction affects motor representation development within the face primary motor cortex in growing rats.

Postnatal growth is influenced by genetic and environmental factors. Nasal obstruction during growth alters the electromyographic activity of orofacial muscles. The facial primary motor area represents muscles of the tongue and jaw, which are essential in regulating orofacial motor functions, including chewing and jaw opening. This study aimed to evaluate the effect of chronic unilateral nasal obstruction during growth on the motor representations within the face primary motor cortex (M1). Seventy-two 6-day-old male Wistar rats were randomly divided into control (n = 36) and experimental (n = 36) groups. Rats in the experimental group underwent unilateral nasal obstruction after cauterization of the external nostril at 8 days of age. Intracortical microstimulation (ICMS) mapping was performed when the rats were 5, 7, 9, and 11 wk old in control and experimental groups (n = 9 per group per time point). Repeated-measures multivariate ANOVA was used for intergroup and intragroup statistical comparisons. In the control and experimental groups, the total number of positive ICMS sites for the genioglossus and anterior digastric muscles was significantly higher at 5, 7, and 9 wk, but there was no significant difference between 9 and 11 wk of age. Moreover, the total number of positive ICMS sites was significantly smaller in the experimental group than in the control at each age. It is possible that nasal obstruction induced the initial changes in orofacial motor behavior in response to the altered respiratory pattern, which eventually contributed to face-M1 neuroplasticity.NEW & NOTEWORTHY Unilateral nasal obstruction in rats during growth periods induced changes in arterial oxygen saturation (SpO2) and altered development of the motor representation within the face primary cortex. Unilateral nasal obstruction occurring during growth periods may greatly affect not only respiratory function but also craniofacial function in rats. Nasal obstruction should be treated as soon as possible to avoid adverse effects on normal growth, development, and physiological functions.

Unilateral Nasal Obstruction during Later Growth Periods Affects Craniofacial Muscles in Rats.

Nasal obstruction can occur at different life stages. In early stages of life the respiratory system is still under development, maturing during the growth period. Previous studies have shown that nasal obstruction in neonatal rats alters craniofacial function. However, little is known about the effects of nasal obstruction that develops during later growth periods. The aim of this study was to investigate the effects of nasal obstruction during later periods of growth on the functional characteristics of the jaw-opening reflex (JOR) and tongue-protruding muscles. In total, 102 6-day-old male Wistar rats were randomized into either a control or experimental group (both n = 51). In order to determine the appropriate timing of nasal obstruction, the saturation of arterial oxygen (SpO2) was monitored at 8 days, and at 3, 5, 7, 9, and 11 weeks in the control group. Rats in the experimental group underwent unilateral nasal obstruction at the age of 5 weeks. The SpO2 was monitored at 7, 9, and 11 weeks in the experimental group. The electromyographic responses of JOR and the contractile properties of the tongue-protruding muscles were recorded at 7, 9, and 11 weeks. In the control group, SpO2 decreased until 5 weeks of age, and remained relatively stable until 11 weeks of age. The SpO2 was significantly lower in the experimental group than in the control. In the experimental group, JOR changes included a longer latency and smaller peak-to-peak amplitude, while changes in the contractile properties of the tongue-protruding muscles included larger twitch and tetanic forces, and a longer half-decay time. These results suggest that nasal obstruction during later growth periods may affect craniofacial function.

Effect of unilateral nasal obstruction on tongue protrusion forces in growing rats.

Mouth breathing caused by nasal obstruction affects the normal growth and development of craniofacial structures, including changes in the orofacial muscles. Tongue muscles play an important role in patency of the pharyngeal airway, and changes in the breathing pattern may influence tongue function. The purpose of this study was to evaluate the effect of unilateral nasal obstruction during growth on contractile properties of the tongue-protruding muscles. Sixty 6-day-old male Wistar albino rats were divided randomly into control (n = 30) and experimental (n = 30) groups. Rats in the experimental group underwent a unilateral nasal obstruction after cauterization of the external nostril at the age of 8 days, and muscle contractile characteristics were measured at 5, 7, and 9 wk of age. The specific parameters measured were twitch force, contraction time, half-decay time, tetanic force, and fatigue index. Repeated-measures multivariate analysis of variance was used for intergroup and intragroup statistical comparisons. Twitch contraction force and half-decay time were significantly increased in the experimental group at all ages. Tetanic forces at 60 and 80 Hz were significantly higher in the experimental group at all ages. The fatigue index was decreased significantly in the experimental group at the age of 5 wk. These results suggest that early unilateral nasal obstruction may increase the contraction force of the tongue-protruding muscles and prolong the duration of muscle contraction, which may influence the shape and development of the craniofacial complex.