Psychological symptoms and salivary inflammatory biomarkers in patients with dentofacial deformities: a case-control study.

Individuals with dentofacial deformities often display a low quality of life (QoL) through biological mechanisms that remain unraveled. In this case-control study, the salivary levels of cytokines, glutamate, and kynurenine metabolites were assessed in patients undergoing orthognathic surgery (OS), while correlating these parameters with QoL and psychological symptoms. Thirty-six patients were enrolled in control (under orthodontic treatment) and test (undergoing OS) groups, matched by age and sex. The QoL was assessed through the World Health Organization Quality of Life BREF (WHOQOL-BREF) and the Orthognathic Quality of Life Questionnaire (OQLQ). The psychological symptoms were evaluated by the Satisfaction with Life Scale, the Rosenberg Self-Esteem Scale (RSES), and the Depression, Anxiety, and Stress Scale-21 (DASS-21). The salivary levels of IL-1ß, IL-6, IL-10, glutamate, and kynurenine metabolites were evaluated. The OQLQ demonstrated increased QoL scores in the test group, regarding social aspects, facial esthetics, and function domains, without significant differences in respect to the other surveys. These patients displayed higher IL-1ß and glutamate levels; conversely, the kynurenine metabolites were unaltered. The glutamate levels positively correlated with the OQLQ function scores. The data brings novel evidence about the psychobiological features of patients with dentofacial deformities, showing salivary variations of inflammatory biomarkers in these individuals.

Progressive Atrial Conduction Defects Associated With Bone Malformation Caused by a Connexin-45 Mutation.

BACKGROUND: Inherited cardiac conduction disease is a rare bradyarrhythmia associated with mutations in various genes that affect action potential propagation. It is often characterized by isolated conduction disturbance of the His-Purkinje system, but it is rarely described as a syndromic form. OBJECTIVES: The authors sought to identify the genetic defect in families with a novel bradyarrhythmia syndrome associated with bone malformation. METHODS: The authors genetically screened 15 European cases with genotype-negative de novo atrioventricular (AV) block and their parents by trio whole-exome sequencing, plus 31 Japanese cases with genotype-negative familial AV block or sick sinus syndrome by targeted exon sequencing of 457 susceptibility genes. Functional consequences of the mutation were evaluated using an in vitro cell expression system and in vivo knockout mice. RESULTS: The authors identified a connexin-45 (Cx45) mutation (p.R75H) in 2 unrelated families (a de novo French case and a 3-generation Japanese family) who presented with progressive AV block, which resulted in atrial standstill without ventricular conduction abnormalities. Affected individuals shared a common extracardiac phenotype: a brachyfacial pattern, finger deformity, and dental dysplasia. Mutant Cx45 expressed in Neuro-2a cells showed normal hemichannel assembly and plaque formation. However, Lucifer yellow dye transfer and gap junction conductance between cell pairs were severely impaired, which suggested that mutant Cx45 impedes gap junction communication in a dominant-negative manner. Tamoxifen-induced, cardiac-specific Cx45 knockout mice showed sinus node dysfunction and atrial arrhythmia, recapitulating the intra-atrial disturbance. CONCLUSIONS: Altogether, the authors showed that Cx45 mutant p.R75H is responsible for a novel disease entity of progressive atrial conduction system defects associated with craniofacial and dentodigital malformation.

Signalling molecules in jaw bones and gingival tissues of patients with Class II and Class III dentofacial deformities.

OBJECTIVES: To detect signalling molecule specificities in jaw bone growth zones in skeletal class II and class III patients and compare them to those of a control group. MATERIAL AND METHODS: Twenty skeletal Class II and 20 skeletal Class III patients who underwent orthognathic surgery treatment were in the study group and five skeletal Class I patients who had impacted third molars extracted were in the control group. During the orthognathic surgery, tissue samples were taken from the tuber maxillae, ramus mandibulae anterior and posterior part together with mucosa from the gingival transitory fold in the second molar region of the lower jaw. The samples were stained to detect TGF-ß, BMP2/4, FGFR1, VEGF, OC, OP and MMP2 expression. The distributions of these factors were assessed semiquantitatively. RESULTS: We observed significant expression of TGF-ß, BMP2/4, OC and OP in the bone tissue of the study group. FGFR1 expression was more pronounced only in mucosa. VEGF and MMP2 were found only in some tissue samples. More apoptotic cells were observed in the bone tissue and soft tissue of the control patients than in those of the skeletal Class II and Class III patients, in which apoptotic cell frequencies were relatively equal. CONCLUSION: From bone tissue in tuber maxillae region the greater TGF-ß and BMP2/4 expression is seen in Class III and control groups, comparing to Class II. In ramus mandibulae anterior part the expression of significant factors in bone tissue growth (TGF-ß un BMP2/4) is higher in the control group and Class II patients, while in ramus mandibulae posterior part higher expression of TGF-ß and BMP2/4 is in Class III patients, comparing to Class II, which indicates to a preserved growth potential in these jaw bone regions. More active bone extracellular matrix protein (osteocalcin and osteopontin) expression in tuber maxillae region both in class II and class III patient groups and different expression in ramus mandibulae anterior part, prove to the bone mineralization and metabolism activity changes, which, perhaps, characterize just these dentofacial deformations.