Prevalence and Risk Factors for Obstructive Sleep Apnea Syndrome Among Children and Adolescents with Cleft lip and Palate: A Survey Study in Hong Kong.

OBJECTIVE: To investigate the prevalence of obstructive sleep apnea syndrome (OSAS) risk and related risk factors among children and adolescents of Hong Kong with cleft lip and/or palate (CL/P). DESIGN: Retrospective survey study adopting three questionnaires, obstructive sleep apnea-18 (OSA-18), pediatric sleep questionnaire-22 (PSQ-22), and modified Epworth Sleepiness Scale (ESS). SETTINGS: Multicenter study in two public hospitals. PATIENTS: A total of 351 Chinese children and adolescents with non-syndromic CL/P (6-18-year-old, 57% males) visited between September 2017 and November 2019, with primary palatal repair surgery done before 3-year-old. MAIN OUTCOME MEASURE: Positive OSAS risk was determined based on cut-off ≥60 for OSA-18, ≥8 for PSQ-22, and >8 for ESS. Age, sex, overweight presence, cleft type, embryonic secondary palate involvement, palatal repair surgery, palatal revision surgery, and orthodontic treatment were analyzed as possible risk factors. RESULTS: A total of 9.5% of patients had positive OSAS risk based on OSA-18, 13.6% based on PSQ-22, and 13.2% according to ESS. A higher prevalence of patients with positive OSAS risk was of younger age (OSA-18, p = .034), had cleft involving embryonic secondary palate (PSQ-22, p = .009), and history of fixed orthodontic treatment (ESS, p = .002). The regression model identified only involvement of embryonic secondary palate as a risk factor (PSQ-22, odds ratio = 3.7, p = .015). CONCLUSIONS: OSAS risk among children and adolescents of Hong Kong with CL/P was 9.5% to 13.6%. Patients at higher risk were those with cleft involving embryonic secondary palate. OSAS risk assessment may be influenced by different aspects of the disease spectrum, and a multimodal approach should be considered for such assessment.

A review of laser applications in orthodontics.

Laser technique now is widely applied in orthodontic treatment and proved to have many benefits. Soft tissue lasers can be used to perform gingivectomy, frenectomy and surgical exposure of tooth with less bleeding and swelling, improved precision, reduced pain and less wound contraction. Other laser applications include enamel etching and bonding and bracket debonding. Lower level lasers have the potential effects of pain control and accelerating tooth movement. Clinicians must be aware of the safety issues and risks associated with laser and receive proper training before the laser treatment is started.

Effect of different advancement positions on the maximum retrusive force of the mandible.

INTRODUCTION: Functional appliances lead, in different degrees, to loss of anchorage in the lower arch. By anchoring them to the mandibular bone, any dental side effects may be avoided and the skeletal effect enhanced. Stability of bone-borne fixation would be affected by forces created by the pull of the masticatory muscles. We aimed to identify mean maximum forces produced by mandibular retrusive muscles, at different degrees of advancement. SUBJECTS AND METHODS: Eighteen healthy adult volunteers participated in the study. Maximum retrusive force was measured using a splint/load cell system. Readings of the maximum forces of retrusion were taken from five mandibular positions: unstrained retruded position, and 4, 5, 6, and 7 mm anterior to the unstrained position. Data were presented as means ± SD and anova was performed to examine statistical significant differences between means of the maximum retrusion force. RESULTS: Mean maximum retrusion force ranged between 63.3 and 198.2 newtons at the unstrained and 7 mm positions, respectively. It increased as the distance of advancement increased, being statistically significantly (p < 0.05) less at unstrained position compared with all advancement distances, 4 mm of advancement than 6 and 7 mm advancement, 5 mm of advancement than at 7 mm advancement. CONCLUSION: Magnitude of the forces exerted by muscles during voluntary maximum retrusion movement from different advancement positions increased proportionately as the retrusion distance increased up to 7 mm. Such range of high forces might be important to consider when designing a bone-borne functional appliance.

Association of CD247 with systemic lupus erythematosus in Asian populations.

OBJECTIVE: Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease with complex genetic inheritance. CD247 (CD3Z, TCRZ) plays a vital role in antigen recognition and signal transduction in antigen-specific immune responses, and is known to be involved in SLE pathogenesis. Weak disease association was reported for genetic variants in this gene in Caucasian studies for SLE, Crohn's disease and systemic sclerosis, but its role as a genetic risk factor was never firmly established. METHODS: In this study, using a collection of 612 SLE patients and 2193 controls of Chinese ethnicity living in Hong Kong in a genome-wide study, single nucleotide polymorphisms (SNPs) in and around CD247 were identified as being associated with SLE. The two most significant SNPs in this locus were selected for further replication using TaqMan genotyping assay in 3339 Asian patients from Hong Kong, Mainland China, and Thailand, as well as 4737 ethnically and geographically matched controls. RESULTS: The association of CD247 with SLE in Asian populations was confirmed (rs704853: odds ratio [OR] = 0. 81, p = 2.47 × 10(-7); rs858543: OR = 1.10, p = 0.0048). Patient-only analysis suggested that rs704853 is also linked to oral ulcers, hematologic disorders and anti-double-stranded DNA (dsDNA) antibody production. CONCLUSION: A significant association between variants in CD247 and SLE was demonstrated in Asian populations. Understanding the involvement of CD247 in SLE may shed new light on disease mechanisms and development of new treatment paradigms.

Two missense variants in UHRF1BP1 are independently associated with systemic lupus erythematosus in Hong Kong Chinese.

UHRF1BP1 encodes a highly conserved protein with unknown function. Previously, a coding variant in this gene was found to be associated with systemic lupus erythematosus (SLE) in populations of European ancestry (rs11755393, R454Q, P=2.22 x 10⁻8, odds ratio=1.17). In this study, by a combination of genome-wide study and replication involving a total of 1230 patients and 3144 controls, we confirmed the association of this coding variant to SLE in Hong Kong Chinese. We also identified another coding variant in this gene that independently contributes to SLE susceptibility (rs13205210, M1098T, P=4.44 x 10⁻9, odds ratio=1.49). Cross-population confirmation establishes the involvement of this locus in SLE and indicates that distinct alleles are contributing to disease susceptibility.

Resveratrol inhibits periodontal pathogens in vitro.

The gram-negative anaerobic bacteria A. actinomycetemcomitans (Aa) and P. gingivalis (Pg) are key components in the aetiology of periodontal disease, and associated hard-tissue destruction. Resveratrol is a phytoalexin, produced naturally by several plants when under attack by bacterial or fungal pathogens. It is found in many foods including mulberries, peanuts and the skin of labrusca and muscadine grapes. The objective of this study was to evaluate the effect of resveratrol on the in vitro growth of periodontal pathogens Aa and Pg. For comparison, resveratrol's effect on a variety of other oral microorganisms was also evaluated. Resveratrol demonstrates a poor solubility in water, thus different concentrations of resveratrol in the solvent dimethyl sulphoxide (DMSO) were added to calibrated suspensions of Aa and Pg. As a control, a parallel series of dilutions containing the vehicle DMSO alone was made to measure the effect of the solvent. Minimum inhibitory concentrations of the periodontal pathogens were calculated. All suspensions were incubated for 1, 3, 6 and 24 h in an anaerobic chamber at 37 °C. At each time interval, selected dilutions from each culture broth were plated on blood agar plates. Colonies appearing on blood agar plates were visually counted at 3 days for Aa, and at 5 days for Pg. The periodontal bacteria showed a significant decrease (p < 0.05) in viable counts after 1 h, whilst no colony forming units could be observed after 24 h. The results suggest that resveratrol possesses significant antimicrobial properties on periodontal pathogens in vitro.

Genes, genetics, and Class III malocclusion.

To present current views that are pertinent to the investigation of the genetic etiology of Class III malocclusion. Class III malocclusion is thought to be a polygenic disorder that results from an interaction between susceptibility genes and environmental factors. However, research on family pedigrees has indicated that Class III malocclusion might also be a monogenic dominant phenotype. Recent studies have reported that genes that encode specific growth factors or other signaling molecules are involved in condylar growth under mechanical strain. These genes, which include Indian hedgehog homolog (IHH), parathyroid-hormone like hormone (PTHLH), insulin-like growth factor-1 (IGF-1), and vascular endothelial growth factor (VEGF), and variations in their levels of expression play an important role in the etiology of Class III malocclusion. In addition, genome-wide scans have revealed chromosomal loci that are associated with Class III malocclusion. It is likely that chromosomal loci 1p36, 12q23, and 12q13 harbor genes that confer susceptibility to Class III malocclusion. In a case-control association study, we identified erythrocyte membrane protein band 4.1 (EPB41) to be a new positional candidate gene that might be involved in susceptibility to mandibular prognathism. Most of the earlier studies on the genetic etiology of Class III malocclusion have focused on the patterns of inheritance of this phenotype. Recent investigations have focused on understanding the genetic variables that affect Class III malocclusion and might provide new approaches to uncovering the genetic etiology of this phenotype.

Effects of vascular endothelial growth factor (VEGF) on MC3T3-E1.

UNLABELLED: Osteogenesis and angiogenesis are closely correlated. Vascular endothelial growth factor (VEGF) is believed to play a critical role in skeletal development. OBJECTIVE: To investigate whether VEGF has direct effects on bone cells activities and to better understand how VEGF promotes bone remodeling. MATERIALS AND METHODS: MC3T3-E1 cell line was cultured with and without VEGF in vitro. The cells in both control and test groups were collected at different culture time points of 24, 48 and 72 h. Real-time polymerase chain reaction (qPCR) was carried out to quantify the mRNA expression of VEGF receptor (VEGFR2), alkaline phosphatase (ALP) and osteocalcin (OCN), osteoprotegerin (OPG) and receptor activator of nuclear factor kappa ß ligand (RANKL). RESULTS: The expression of VEGFR2 significantly increased by 53% at 24 h and remained increased by 8% at 72 h compared to control (p < 0.05). ALP showed an early increase by 73% at 24 h (p < 0.001), but dropped by 14 and 41% at 48 and 72 h, respectively (p < 0.05). OCN was down-regulated by 41% at 24 h but then up-regulated by 149% at 72 h (p < 0.001). The expression of OPG significantly decreased by 7% at 24 h (p < 0.001) while dramatically increased by 133% at 72 h (p < 0.001). RANKL remained unchanged at all three time points (p > 0.05). CONCLUSION: VEGF promotes bone remodeling by direct effects on osteoblastic cells via regulating gene expression of ALP, OCN, and OPG through VEGFR2 signaling pathway.

Effect of Buguzhi (Psoralea corylifolia fruit) extract on bone formation.

The objective of the study is to compare the amount of new bone produced by Buguzhi (Psoralea corylifolia fruit) extract in collagen matrix to that produced and collagen matrix in vivo. Eighteen bone defects, 5 mm by 10 mm, were created in the parietal bone of 9 New Zealand white rabbits. Six defects were grafted with Buguzhi extract mixed with collagen matrix. Six defects were grafted with collagen matrix alone (positive control) and 6 were left empty (negative control). Animals were sacrificed on day 14 and the defects were dissected and prepared for histological assessment. Quantitative analysis of new bone formation and bone cells was made on 100 sections (50 sections for each group) using image analysis. A total of 275% more new bone was present in defects grafted with Buguzhi extract in collagen matrix than those grafted with collagen matrix. No bone was formed in the negative control group. The amount of bone cells was also significantly greater in the Buguzhi group than in the positive control group. To conclude, Buguzhi extract in collagen matrix has the effect of increasing new bone formation locally in vivo. Buguzhi extract in collagen matrix can be used as a bone graft material.

Inhibitory effect of quercetin on periodontal pathogens in vitro.

Actinobacillus actinomycetemcomitans (Aa) and Porphyromonas gingivalis (Pg) are bacteria strongly associated with early onset, progressive and refractory periodontal disease and associated alveolar bone loss. Quercetin is a flavonoid found in many foods including apples, onions and tea. The aim of this study was to evaluate the effect of quercetin on in vitro growth of periodontal pathogens Aa and Pg. For comparison, quercetin's effect on several oral microbes was also evaluated. Different concentrations of quercetin solution were added to calibrated suspensions of Aa and Pg. All suspensions were incubated for 1, 3, 6, and 24 h in an anaerobic chamber at 37 degrees C. At each time point, selected dilutions from each culture broth were plated on blood agar plates. Colonies appearing on blood agar plates were visually counted on 3 days for Aa and 5 days for Pg. Minimum inhibitory concentrations of both periodontal pathogens were also determined. Both periodontal bacteria showed a significant decrease (p < 0.05) in viable counts after 1 h. No colony forming units of Pg could be observed after 24 h. The results suggest that quercetin possesses significant antimicrobial properties on periodontal pathogens in vitro.

Population differences in SLE susceptibility genes: STAT4 and BLK, but not PXK, are associated with systemic lupus erythematosus in Hong Kong Chinese.

In this study, we compared the association of several newly discovered susceptibility genes for systemic lupus erythematosus (SLE) between populations of European origin and two Asian populations. Using 910 SLE patients and 1440 healthy controls from Chinese living in Hong Kong, and 278 SLE patients and 383 controls in Thailand, we studied association of STAT4, BLK and PXK with the disease. Our data confirmed association of STAT4 (rs7574865, odds ratio (OR) =1.71, P=3.55 x 10(-23)) and BLK (rs13277113, OR=0.77, P=1.34 x 10(-5)) with SLE. It was showed that rs7574865 of STAT4 is also linked to hematologic disorders and potentially some other subphenotypes of the disease. More than one genetic variant in STAT4 were found to be associated with the disease independently in our populations (rs7601754, OR=0.59, P=1.39 x 10(-9), and P=0.00034 when controlling the effect of rs7574865). With the same set of samples, however, our study did not detect any significant disease association for PXK, a risk factor for populations of European origin (rs6445975, joint P=0.36, OR=1.06, 95% confidence interval: 0.93-1.21). Our study indicates that some of the susceptibility genes for this disease may be population specific.

Association of BANK1 and TNFSF4 with systemic lupus erythematosus in Hong Kong Chinese.

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease with complex genetic inheritance. Recently, single nucleotide polymorphisms (SNPs) in BANK1 and TNFSF4 have been shown to be associated with SLE in Caucasian populations, but it is not known whether they are also involved in the disease in other ethnic groups. Recent data from our genome-wide association study (GWAS) for 314 SLE cases and 920 controls collected in Hong Kong identified SNPs in and around BANK1 and TNFSF4 to be associated with SLE risk. On the basis of the results of the reported studies and our GWAS, SNPs were selected for further genotyping in 949 SLE patients (overlapping with the 314 cases in our GWAS) and non-overlapping 1042 healthy controls. We confirmed the associations of BANK1 and TNFSF4 with SLE in Chinese (BANK1, rs3733197, odds ratio (OR)=0.84, P=0.021; BANK1, rs17266594, OR=0.61, P=4.67 x 10(-9); TNFSF4, rs844648, OR=1.22, P=2.47 x 10(-3); TNFSF4, rs2205960, OR=1.30, P=2.41 x 10(-4)). Another SNP located in intron 1 of BANK1, rs4522865, was separately replicated by Sequenom in 360 cases and 360 controls and was also confirmed to be associated with SLE (OR=0.725, P=2.93 x 10(-3)). Logistic regression analysis showed that rs3733197 (A383T in ankyrin domain) and rs17266594 (a branch point-site SNP) from BANK1 had independent contributions towards the disease association (P=0.037 and 6.63 x 10(-8), respectively). In TNFSF4, rs2205960 was associated with SLE independently from the effect of rs844648 (P=6.26 x 10(-3)), but not vice versa (P=0.55). These findings suggest that multiple independent genetic variants may be present within the gene locus, which exert their effects on SLE pathogenesis through different mechanisms.

Prognostically distinct clinical patterns of systemic lupus erythematosus identified by cluster analysis.

The objective of this study was to evaluate the patterns of clinical manifestations and their mortality in a large cohort of Chinese patients with systemic lupus erythematosus. The cumulative clinical manifestations of a large group of Chinese systemic lupus erythematosus patients who fulfilled at least four American College of Rheumatology criteria for systemic lupus erythematosus were studied. Patients were divided into distinct groups by using the K-mean cluster analysis. Clinical features, prevalence of proliferative lupus nephritis (World Health Organization class III, IV), autoantibody profile, and treatment data were compared and the standardized mortality ratios were calculated for each cluster of patients. There were 1082 patients included in the study (mean age at systemic lupus erythematosus diagnosis 30.5 years; mean systemic lupus erythematosus duration 10.3 years). Three distinct groups of patients were identified. Cluster 1 (n = 347) was characterized predominantly by mucocutaneous manifestations (malar rash, discoid rash, photosensitivity, oral ulcer) and arthritis but having the lowest prevalence of serositis, hematologic manifestations (hemolytic anemia, leukopenia, and thrombocytopenia), and proliferative lupus nephritis. Patients in cluster 2 (n = 409) had mainly renal and hematological manifestations but having the lowest prevalence of mucocutaneous manifestations. Pulmonary and gastrointestinal manifestations were significantly more frequent in cluster 2 than the other clusters. Cluster 3 patients (n = 326) had the most heterogeneous features. Besides having a high prevalence of mucocutaneous manifestations, serositis and hematologic manifestations, renal involvement, and proliferative lupus nephritis was also most prevalent among the three clusters. Patients in cluster 2 had a much higher standardized mortality ratio [standardized mortality ratio 7.23 (6.7-7.7), p < 0.001] than those in cluster 3 [standardized mortality ratio 1.27 (1.1-1.5), p = 0.005] and cluster 1 [standardized mortality ratio 0.95 (0.5-1.7), p = 0.86]. In conclusion, patients with systemic lupus erythematosus could be clustered into prognostically distinct patterns of clinical manifestations.

The inhibitory effects of naringin on the growth of periodontal pathogens in vitro.

Naringin is a flavonoid that is commonly found in grapefruits. The objective of this study was to evaluate the effects of naringin on the growth of periodontal pathogens such as A. actinomycetemcomitans and P. gingivalis in vitro. For comparison, the effects of naringin on several oral microbes were also studied. Different concentrations of naringin solution were added to calibrated suspensions of A. actinomycetemcomitans and P. gingivalis. All the suspensions were incubated for 3, 6 and 24 h in an anaerobic chamber at 37 degrees C. At each time point, selected dilutions from each culture broth were plated on blood agar plates. Colonies recovered on blood agar were visually counted on days 3 and 5, respectively. A. actinomycetemcomitans showed a significant decrease (p < 0.05) in viable counts after 3 h when naringin was added at baseline. P. gingivalis also showed a marked growth reduction in the presence of naringin, and no colony forming units could be observed after 24 h. Naringin also had an inhibitory effect against all bacteria and yeasts tested. The results suggest that naringin possesses significant antimicrobial properties on periodontal pathogens in vitro. It also has an inhibitory effect on some common oral microorganisms in low concentrations.

Tooth dimensions of Southern Chinese.

Teeth in casts of a random sample from the Hong Kong Oral Health Survey of 12-year-old children (n=459; 295 boys and 164 girls) were measured in the mesiodistal, buccolingual, and clinical crown height dimensions. Sexual dimorphism was evident in all tooth types in nearly all tooth dimensions, with the exception of the mesiodistal dimension of mandibular central incisors. The Chinese male tooth dimensions were larger than in females in nearly all characters. The measurements were compared with other human groups. Results showed that the Southern Chinese had larger tooth dimensions than the Japanese and than the White Americans. Hence it is important to have data concerning a relevant human group for purposes of clinical diagnosis and planning of treatment. These data may also be useful in forensic dentistry.

ZNF750 is a lineage-specific tumour suppressor in squamous cell carcinoma.

ZNF750 controls epithelial homeostasis by regulating epidermal-differentiation genes, a role underscored by its pathogenic mutations in esophageal squamous cell cancers (SCCs). However, the precise role of ZNF750 in SCC cell biology remains unclear. In this study, we report that ZNF750 is exclusively deleted, mutated and underexpressed in human SCCs, and low ZNF750 expression is associated with poor survival. Restoration of wildtype, but not mutant ZNF750 protein uniquely inhibited the malignant phenotypes of SCC cells both in vitro and in vivo. Notably, ZNF750 promoted the expression of a long non-coding RNA (TINCR), which mediated both cancer-inhibition and differentiation-induction effects of ZNF750. In addition, ZNF750 potently suppressed cell migration by directly inhibiting the transactivation of LAMC2. Together, our findings characterize ZNF750 as a crucial SCC-specific suppressor and uncover its novel anticancer-associated functions.

Factors regulating condylar cartilage growth under repeated load application.

Mechanical loading can influence the biological behavior of the bone-associated cells leading to adaptive changes in skeletal mass and architecture. SOX9 and PTHrP genes are known to regulate chondrocyte differentiation and delay maturation, ultimately control the endochondral bone formation. To investigate the effects of repeated mechanical loading on bone, 280 Sprague-Dawley rats were used in this experiment. The animals were randomly allocated into experimental and control groups. Repeated mechanical loading was applied through a bite-jumping device in the experimental group. The experimental animals were sacrificed on 10 different time points together with the matched control. Total RNA was extracted from the mandibular condylar cartilage for PTHrP and SOX9 genes quantification using real-time RTPCR. Results showed that PTHrP expression was increased and reached a peak level on the seventh day after mechanical loading was given. Repeated mechanical loading triggered a significant increase of PTHrP expression leading to another peak increment. The expression of SOX9 was highly correlated with the PTHrP expression, and its pattern of expression was similar to that of PTHrP after repeated mechanical loading. In conclusions, repeated mechanical loading on the condyle triggers the expression of PTHrP and SOX9, which in turn promotes condylar cartilage growth.

Effect of naringin on bone cells.

Statin, a HMG-CoA reductase inhibitor, was shown to increase BMP-2 gene expression for bone formation, by blocking the mevalonate pathway in cholesterol production. We investigated the effect of naringin, a flavonoid available commonly in citrus fruits, which was also a HMG-CoA reductase inhibitor, in UMR 106 osteoblastic cell line in vitro. The control group consisted of cells cultured without any intervention for different time intervals (24 h, 48 h, and 72 h), whereas the experimental (naringin) group consisted of cells cultured with naringin of different concentrations (0.001 micromol/L, 0.01 micromol/L, and 0.1 micromol/L) for the same time intervals of the control. Colorimetric Tetrazolium (MTT) assay, total protein content assay, and alkaline phosphatase activity were used to measure the cellular activities. Results for the naringin group showed an increase in MTT assay compared with the control and the effect was dose dependent. At high concentration (0.1 micromol), the increases ranged from 60% to 80%. In the total protein content assay, naringin also showed an increase compared with control and the effect was also dose dependent. At high concentration (0.1 micromol), the increases ranged from 9% to 20%. In the alkaline phosphatase activity assay, naringin at high concentration (0.1 micromol) significantly increased the activity up to 20%. In conclusion, naringin significantly increased bone cell activities in vitro. This is the first study specifically attempted to investigate the effect of naringin on bone cell activities. Besides statin, this provided another example of mevalonate pathway blockage in the cholesterol production pathway by HMG-CoA reductase inhibition will increase the bone cell activities.