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.

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.

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.

Down-modulation of nucleoporin RanBP2/Nup358 impaired chromosomal alignment and induced mitotic catastrophe.

Chromosomal missegregation is a common feature of many human tumors. Recent studies have indicated a link between nucleoporin RanBP2/Nup358 and chromosomal segregation during mitosis; however, the molecular details have yet to be fully established. Observed through live cell imaging and flow cytometry, here we show that RNA interference-mediated knockdown of RanBP2 induced G2/M phase arrest, metaphase catastrophe and mitotic cell death. Furthermore, RanBP2 down-modulation disrupted importin/karyopherin ß1 as well as the expression and localization of the Ran GTPase activating protein 1. We found that N-terminal of RanBP2 interacted with the N-terminal of importin ß1. Moreover, at least a portion of RanBP2 partially localizes at the centrosome during mitosis. Notably, we also found that GTPase Ran is also involved in the regulation of RanBP2-importin ß1 interaction. Overall, our results suggest that mitotic arrest and the following cell death were caused by depletion of RanBP2. Our findings point to a crucial role for RanBP2 in proper mitotic progression and faithful chromosomal segregation.

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.

Minocycline inhibits D-amphetamine-elicited action potential bursts in a central snail neuron.

Minocycline is a second-generation tetracycline that has been reported to have powerful neuroprotective properties. In our previous studies, we found that d-amphetamine (AMPH) elicited action potential bursts in an identifiable RP4 neuron of the African snail, Achatina fulica Ferussac. This study sought to determine the effects of minocycline on the AMPH-elicited action potential pattern changes in the central snail neuron, using the two-electrode voltage clamping method. Extracellular application of AMPH at 300 µM elicited action potential bursts in the RP4 neuron. Minocycline dose-dependently (300-900 µM) inhibited the action potential bursts elicited by AMPH. The inhibitory effects of minocycline on AMPH-elicited action potential bursts were restored by forskolin (50 µM), an adenylate cyclase activator, and by dibutyryl cAMP (N(6),2'-O-Dibutyryladenosine 3',5'-cyclic monophosphate; 1mM), a membrane-permeable cAMP analog. Co-administration of forskolin (50 µM) plus tetraethylammonium chloride (TEA; 5mM) or co-administration of TEA (5mM) plus dibutyryl cAMP (1mM) also elicited action potential bursts, which were prevented and inhibited by minocycline. In addition, minocycline prevented and inhibited forskolin (100 µM)-elicited action potential bursts. Notably, TEA (50mM)-elicited action potential bursts in the RP4 neuron were not affected by minocycline. Minocycline did not affect steady-state outward currents of the RP4 neuron. However, minocycline did decrease the AMPH-elicited steady-state current changes. Similarly, minocycline decreased the effects of forskolin-elicited steady-state current changes. Pretreatment with H89 (N-[2-(p-Bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride; 10 µM), a protein kinase A inhibitor, inhibited AMPH-elicited action potential bursts and decreased AMPH-elicited steady-state current changes. These results suggest that the cAMP-protein kinase A signaling pathway and the steady-state current are involved in the inhibitory effects of minocycline upon AMPH-elicited action potential bursts.

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.

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.

3D CBCT McNamara's cephalometric analysis in an adult southern Chinese population.

Preliminary results were determined for a database on 3-dimensional (3D) cephalometrics using McNamara's analysis in an adult southern Chinese population based on cone-beam computerized tomography (CBCT). 3D dentoskeletal morphology was assessed from CBCTs from 80 (39 males; 41 females; 21-30 years) consecutive adult southern Chinese without gross craniofacial deformity or asymmetry, adopting 16 variables from McNamara's cephalometric method. For variables in relation to maxilla to cranial base, mandible to cranial base and dentition, there were no significant differences between males and females. For variables in relation to mandible to maxilla, 8 of 11 showed significant differences between males and females: Cd(L)-Gn (♂: 127.65 mm; ♀: 119.56 mm, P<0.01), Cd(R)-Gn (♂: 127.85 mm; ♀: 119.94 mm, P<0.01), Cd(L)-A (♂: 99.38 mm; ♀: 94.18 mm, P<0.01), Cd(R)-A (♂: 93.93 mm; ♀: 94.99 mm, P<0.01), MxMD-DF(L) (♂: 28.26 mm; ♀: 25.40 mm, P<0.05), MxMD-DF(R) (♂: 27.74 mm; ♀: 24.02 mm, P<0.05), ANS-Me (♂: 71.09 mm; ♀: 65.84 mm, P<0.01), and MD-P(L) (♂: 22.85°; ♀: 25.25°, P<0.05). The method errors did not exceed 0.5 mm for any variables. A preliminary CBCT cephalometric database of the population was created. The significant sexual differences in the 3D McNamara's analysis indicate that gender specific data should be made available. The sample size should be increased to create a more representative database.

In vivo production of mineralised tissue pieces for clinical use: a qualitative pilot study using human dental pulp cell.

Numerous previous studies have investigated the production of mineralised tissues by transplanting human dental pulp cells with calcium based scaffolds. The potential of alternative setups remains largely uninvestigated, therefore in this study, human dental pulp cells were encapsulated into non-calcium based biomaterial - self-assembling peptide nano-fibre hydrogel. The cell-gel constructs were cultured in full medium for 2 weeks. Then they were cultured in full medium supplemented with ß-glycerophosphate, dexamethasone and l-ascorbic acid for 2 more weeks. These cell-gel constructs and plain-gel constructs (with no cells) were transplanted subcutaneously into five nude mice. The gel constructs were retrieved 4 weeks after surgery. The plain-gel constructs were all completely resorbed with no new tissue formation. The cell-gel constructs were transformed into tissue pieces that were mineralised and contained blood capillaries. Immunohistochemistry analysis confirmed the expression of multiple bone markers (osteopontin, osteocalcin, osteonectin and parathyroid hormone receptor) in these tissue pieces. Computerised analysis of the contact radiographs gave the mean radio-opaque area percentage as 78% (N=5, P<0.001 compared with the 0% of the control). The results demonstrate good prospects for using human dental pulp cell plus self-assembling peptide nano-fibre hydrogel to produce mineralised tissue pieces for clinical use.

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.

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.

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.

Effect of bio-oss collagen and collagen matrix on bone formation.

OBJECTIVE: to compare the amount of new bone produced by Bio-Oss((R)) Collagen to that produced by collagen matrix in vivo. METHOD: eighteen bone defects, 5mm by 10mm were created in the parietal bone of 9 New Zealand White rabbits. 6 defects were grafted with Bio-Oss((R)) Collagen. 6 defects were grafted with collagen matrix alone (positive control) and 6 were left empty (negative control). Animals were killed on day 14 and the defects were dissected and prepared for histological assessment. Quantitative analysis of new bone formation was made on 100 sections (50 sections for each group) using image analysis. RESULTS: A total of 339% more new bone was present in defects grafted with Bio-Oss((R)) Collagen than those grafted with collagen matrix (positive control). No bone was formed in the negative control group. CONCLUSION: Bio-Oss((R)) Collagen has the effect of stimulating new bone formation locally compared with collagen matrix in vivo. Bio-Oss((R) )Collagen may be utilized as a bone graft material.

Antimicrobial activity of Chinese medicine herbs against common bacteria in oral biofilm. A pilot study.

Twenty traditional Chinese medicines (TCM) were evaluated for their antimicrobial activity against four common oral bacteria. TCMs were tested for sensitivity against Streptococcus mitis, Streptococcus sanguis, Streptococcus mutans and Porphyromonas gingivalis. Aliquots of suspension of each bacterial species were inoculated onto a horse blood agar plate with TCMs soaked separately on 6mm paper disks. The plates were incubated for 48h anaerobically and the mean diameters of growth inhibition of three different areas obtained. 0.2% (w/v) chlorhexidine was used as a positive control. Broth microdilution assay was used to determine minimum inhibitory concentration and minimum bactericidal concentration. Fructus armeniaca mume was effective against all four bacteria. Thirteen TCMs demonstrated antimicrobial activity against Porphyromonas gingivalis, including Cortex magnoliae officinalis, Cortex phellodendri, Flos caryophylli, Flos lonicerae japonicae, Fructus armeniaca mume, Fructus forsythiae suspensae, Herba cum radice violae yedoensitis, Herba menthae haplocalycis, Pericarpium granati, Radix et rhizoma rhei, Radix gentianae, Ramulus cinnamomi cassia and Rhizoma cimicifugae. Cortex phellodendri showed antimicrobial activity against Streptococcus mutans, while Radix et rhizoma rhei was effective against Streptococcus mitis and Streptococcus sanguis. Fructus armeniaca mume had inhibitory effects against Streptococcus mitis, Streptococcus sanguis, Streptococcus mutans and Porphyromonas gingivalis in vitro.

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.