To evaluate the effects of two different mandibular advancement devices (MADs) on craniofacial characteristics and upper airway dimensions of Chinese adult patients with obstructive sleep apnea ...(OSA).
Forty-five patients with OSA were recruited as part of a prospective randomized crossover trial for treatment with two different MADs. Lateral cephalograms were taken, and the Epworth Sleepiness Scale and the Sleep Apnea Quality of Life Index were completed at baseline.
The Apnea-Hypoxia Index was highly significantly reduced with the monoblock (P < .001) and significantly reduced with the twin block (P < .01). The monoblock demonstrated a superior result than the twin block (P < .05). A significant reduction was found in the distances between the hyoid bone to retrognathia (monoblock, P < .01; twin block, P < .001) as well as the distance between the hyoid bone and mandibular plane angle (P < .001). Furthermore, soft palate length increased significantly (P < .05) with both MADs. However, the changes did not differ in favor of either MAD.
Monoblock was the better MAD to improve OSA severity. No difference could be found in changes of subjective OSA indicators. Significant but similar cephalometric changes were observed, indicating both MADs alter the position of the surrounding musculature and improve upper airway patency. Therefore, the different design features of the MADs suggest an impact on some OSA indicators.
The Hedgehog signalling pathway plays a fundamental role in orchestrating normal craniofacial development in vertebrates. In particular, Sonic hedgehog (Shh) is produced in three key domains during ...the early formation of the head; neuroectoderm of the ventral forebrain, facial ectoderm and the pharyngeal endoderm; with signal transduction evident in both ectodermal and mesenchymal tissue compartments. Shh signalling from the prechordal plate and ventral midline of the diencephalon is required for appropriate division of the eyefield and forebrain, with mutation in a number of pathway components associated with Holoprosencephaly, a clinically heterogeneous developmental defect characterized by a failure of the early forebrain vesicle to divide into distinct halves. In addition, signalling from the pharyngeal endoderm and facial ectoderm plays an essential role during development of the face, influencing cranial neural crest cells that migrate into the early facial processes. In recent years, the complexity of Shh signalling has been highlighted by the identification of multiple novel proteins that are involved in regulating both the release and reception of this protein. Here, we review the contributions of Shh signalling during early craniofacial development, focusing on Hedgehog receptor function and describing the consequences of disruption for inherited anomalies of this region in both mouse models and human populations.
•Shh signalling is essential for normal craniofacial development in vertebrates.•Early signalling is from ventral neuroectoderm, facial ectoderm, pharyngeal endoderm.•We review the Shh pathway and focus on receptor function in craniofacial development.
Objectives:
To determine patient and parent/guardian motivation, expectation and understanding of orthodontic treatment.
Design:
A self-completion questionnaire survey of new patients referred for ...orthodontic assessment.
Setting:
Specialist practices in Surrey and Berkshire (United Kingdom).
Participants:
A total of 500 questionnaires were issued (250 were issued to patients and 250 to parents).
Methods:
The survey was based on a self-completed questionnaire which was issued at the assessment appointment. Both questionnaires were adapted and extended from originally validated questionnaires previously used in a hospital setting. Patients and parents were asked to complete separate anonymous questionnaires. The patient questionnaire consisted of 24 closed-ended questions divided into three domains: motivation; understanding; and expectation of orthodontic treatment. The parent questionnaire consisted of 13 questions covering the same three domains
Results:
The response rate for the patient and parent questionnaires was 95% and 91%, respectively. Forty-seven percent of the patients were aged 11–13 years. In 77% of cases, the referral was initiated by their dentist. Only 3% of patients thought there was nothing wrong with their teeth. There was a poor understanding of what a retainer is and for how long patients are expected to use it.
Conclusions:
Referral for orthodontic treatment was initiated by the patients’ general dental practitioner in the majority of the cases. The anticipation of improved dental appearance was a prime motivating factor. Participants had realistic expectations and there was a good acceptance of appliances and dental extractions for orthodontic treatment. Nevertheless, both patients and parents/guardians were less well informed on the nature and duration of orthodontic retention.
Holoprosencephaly (HPE) is a clinically heterogeneous developmental anomaly affecting the CNS and face, in which the embryonic forebrain fails to divide into distinct halves. Numerous genetic loci ...and environmental factors are implicated in HPE, but mutation in the sonic hedgehog (Shh) gene is an established cause in both humans and mice. Vax (ventral anterior homeobox) genes are a family of homeobox-containing genes which have been identified in mice, humans, Xenopus, chicken and zebrafish. They are transcription factors which are induced by Shh and ventralize the forebrain. In humans, it has been shown that a VAX1 mutation is associated with microphthalmia, agenesis of the corpus callosum, and orofacial clefting. Skeletal and histological analysis of Vax1-/- mice revealed a series of craniofacial defects predominently affecting the neurocranial and facial midlines as well as the visual and olfactory systems. These included anomalies of the ventral forebrain, a single maxillary incisor, premaxillary hypoplasia, cleft palate and the presence of an ectopic second pituitary gland. During early facial development, Vax1 was expressed in the developing ventral forebrain and facial structures in adjacent and partially overlapping areas of expression to Shh and in a broadly reciprocal manner to its' transcriptional target Ptch1. In the absence of Vax1 function, there was an overall reduction in the size of craniofacial regions, in particular of the developing forebrain. Moreover, mutant mice did have a midline cavity originating from the embryonic forebrain and extending through the nasal cavity to expand this region and prevent approximation of the palatal shelves. This was combined with a decrease in cellular proliferation in this region and reduced Shh signaling activity. This phenotypic and molecular analysis was strongly indicative of the role of Vax1 downstream of Shh during craniofacial development. Vax1-/- mice also demonstrate lobar HPE. Shh expression was reduced in both Gas1-/- and Vax1-/- mice, both modifiers of HPE. The craniofacial phenotype of Gas1 ;Vax1 compound mutant mice displayed a more severe defect of the facial midline thus demonstrating the combinatorial role of modifying genes in the wide spectrum of phenotypic variablility in Shh mediated HPE.
Holoprosencephaly (HPE) is a clinically heterogeneous developmental anomaly affecting the CNS and face, in which the embryonic forebrain fails to divide into distinct halves. Numerous genetic loci ...and environmental factors are implicated in HPE, but mutation in the sonic hedgehog (Shh) gene is an established cause in both humans and mice. Vax (ventral anterior homeobox) genes are a family of homeobox-containing genes which have been identified in mice, humans, Xenopus, chicken and zebrafish. They are transcription factors which are induced by Shh and ventralize the forebrain. In humans, it has been shown that a VAX1 mutation is associated with microphthalmia, agenesis of the corpus callosum, and orofacial clefting. Skeletal and histological analysis of Vax1-/- mice revealed a series of craniofacial defects predominently affecting the neurocranial and facial midlines as well as the visual and olfactory systems. These included anomalies of the ventral forebrain, a single maxillary incisor, premaxillary hypoplasia, cleft palate and the presence of an ectopic second pituitary gland. During early facial development, Vax1 was expressed in the developing ventral forebrain and facial structures in adjacent and partially overlapping areas of expression to Shh and in a broadly reciprocal manner to its' transcriptional target Ptch1. In the absence of Vax1 function, there was an overall reduction in the size of craniofacial regions, in particular of the developing forebrain. Moreover, mutant mice did have a midline cavity originating from the embryonic forebrain and extending through the nasal cavity to expand this region and prevent approximation of the palatal shelves. This was combined with a decrease in cellular proliferation in this region and reduced Shh signaling activity. This phenotypic and molecular analysis was strongly indicative of the role of Vax1 downstream of Shh during craniofacial development. Vax1-/- mice also demonstrate lobar HPE. Shh expression was reduced in both Gas1-/- and Vax1-/- mice, both modifiers of HPE. The craniofacial phenotype of Gas1 ;Vax1 compound mutant mice displayed a more severe defect of the facial midline thus demonstrating the combinatorial role of modifying genes in the wide spectrum of phenotypic variablility in Shh mediated HPE.
The association between chronic pain and depression is widely recognized, the comorbidity of which leads to a heavier disease burden, increased disability and poor treatment response. This study ...examined nociceptive responding to mechanical and thermal stimuli prior to and following L5‐L6 spinal nerve ligation (SNL), a model of neuropathic pain, in the olfactory bulbectomized (OB) rat model of depression. Associated changes in the expression of genes encoding for markers of glial activation and cytokines were subsequently examined in the amygdala, a key brain region for the modulation of emotion and pain. The OB rats exhibited mechanical and cold allodynia, but not heat hyperalgesia, when compared with sham‐operated counterparts. Spinal nerve ligation induced characteristic mechanical and cold allodynia in the ipsilateral hindpaw of both sham and OB rats. The OB rats exhibited a reduced latency and number of responses to an innocuous cold stimulus following SNL, an effect positively correlated with interleukin (IL)‐6 and IL‐10 mRNA expression in the amygdala, respectively. Spinal nerve ligation reduced IL‐6 and increased IL‐10 expression in the amygdala of sham rats. The expression of CD11b (cluster of differentiation molecule 11b) and GFAP (glial fibrillary acidic protein), indicative of microglial and astrocyte activation, and IL‐1β in the amygdala was enhanced in OB animals when compared with sham counterparts, an effect not observed following SNL. This study shows that neuropathic pain‐related responding to an innocuous cold stimulus is altered in an animal model of depression, effects accompanied by changes in the expression of neuroinflammatory genes in the amygdala.
Nociceptive responding to an innocuous cold stimulus following spinal nerve ligation is altered in the olfactory bulbectomized rat model of depression, effects accompanied by changes in the expression of neuroinflammatory genes in the amygdala.
MET is a receptor tyrosine kinase (RTK) that plays important roles in carcinogenesis. Despite being frequently overexpressed in cancer, clinical responses to targeting this receptor have been ...limited. Recently novel splicing mutations involving the loss of exon 14 (called METex14 skipping) have emerged as potential biomarkers to predict for responsiveness to targeted therapies with Met inhibitors in non-small cell lung cancer (NSCLC). Currently, the diverse genomic alterations responsible for METex14 skipping pose a challenge for routine clinical diagnostic testing. In this report, we examine three different methodologies to detect METex14 and assess their potential utility for use as a diagnostic assay for both the identification of METex14 and intra-tumoural distribution in NSCLC.
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