Corrigendum: Virtual reality in managing dental pain and anxiety: a comprehensive review.

[This corrects the article DOI: 10.3389/fmed.2023.1285142.].

Virtual reality in managing dental pain and anxiety: a comprehensive review.

Objectives: This study aimed to identify, analyze, and summarize the clinical efficacy of virtual reality (VR) distraction therapy for oral treatment in different hospital settings in contrast to medical interventions that induce anxiety and pain. Furthermore, this review aimed to determine the implications for research and clinical practice of VR distraction therapy. Data: This review investigated the clinical efficacy of VR in the oral treatment of procedural pain or anxiety. Quality assessment of the included studies was conducted. A narrative synthesis of the collected data was performed. Sources: Literature studies from six electronic databases were searched for a comprehensive review, namely, the Cochrane Oral Health's Trials Register, Cochrane Central Register of Controlled Trials (Central), MEDLINE (PubMed), EMBASE, Scopus, and Web of Science. Study selection: One thousand five hundred twenty-two patients aged between 0 and 60 years who used VR during dental treatment were included in this review. Among these studies, 8 and 14 studies comprised adult and pediatric patients. Conclusion: Overall, the reviewed studies underscore the efficacy of VR to mitigate pain and anxiety in the context of dental treatment. VR is an innovative pain and anxiety management approach that facilitates dental treatment patients to immerse themselves in a virtual world while using distractions to reduce pain and anxiety. Clinical significance: VR is an effective and novel non-pharmacological method of behavioral management that contributes to improving medication safety for dental patients. VR as a distractive approach can reduce the fear associated with medical interventions and prevent severe pain sensitivity, anxiety, and medical avoidance among adults and children.

Efficacy of high-flow nasal oxygenation compared with laryngeal mask airway in children undergoing ambulatory oral surgery under deep sedation: A randomized controlled non-inferiority trial.

Background: High-flow nasal oxygenation (HFNO) has been suggested as an alternative oxygenation method during procedural sedation. This randomized, non-inferiority trial evaluated the safety and efficacy of HFNO compared with laryngeal mask airway (LMA) in pediatric ambulatory oral surgery under deep sedation. Methods: In total, 120 children aged 2-7 years (weight: 10-30 kg) were equally assigned into two groups, namely, HFNO with propofol total intravenous anesthesia infusion (HFNO-IV) or LMA with propofol total intravenous anesthesia infusion (LMA-IV). The primary objective was to monitor carbon dioxide (CO2) accumulation during perioperative surgery. Secondary objectives included monitoring transcutaneous oxygen saturation, grade exposure to the surgical field, perioperative adverse events, or other events. The predefined non-inferiority margin was 7 mmHg. During the COVID-19 pandemic, a novel WeChat applet was implemented to gather follow-up data after discharge. Results: Non-inferiority could be declared for HFNO relative to LMA (mean difference in transcutaneous CO2 (TcCO2) = -1.4 mmHg, 95% CI: -2.9, 0.1 mmHg; P > 0.05). The pre-surgical TcCO2 of the HFNO-IV group (45.4 ± 4.5 mmHg) was similar to that of the LMA-IV group (44.0 ± 3.5 mmHg), within the clinically acceptable normal range. All the children maintained SpO2 levels of >97%. The surgical field exposure score of the HFNO group was significantly better than that of the LMA group. There was no significant difference between the two groups regarding risk or adverse events. Conclusion: HFNO was not inferior to LMA for maintaining oxygenation and ventilation in patients undergoing pediatric ambulatory oral surgery under deep sedation under strict isolation from the oral cavity to the upper airway.

The design, development and usability testing of a smartphone-based mobile system for management of children's oral health.

The aim of the study was to design and develop a mobile system for better management of children's oral health by using the internet technology. This study was followed in a three-step approach. (1) Design stage: participatory design (including patients, dentists and computer scientists) was taken in order to adapt the system to the clinical practice of dentistry; (2) Development stage: dentists and computer scientists were involved in this stage to develop the system by using internet technology; (3) Usability testing stage: the quality (MARS), usability (SUS) and satisfaction of the system were assessed by children's caregivers. The system contains patient-side app, doctor-side app and Web side program for manager. Children and their caregivers could acquire many useful services through the app, such as oral healthcare education, brushing management, dietary record, online consultation, online appointment, feedback of adverse events. The overall value of SUS was 67.75. The final quality mean score was 3.44 ± 0.95, with the highest mean score of functionality. The majority of caregivers were satisfied with the system. They expressed the system could improve the current medical services and their oral health literacy.

Application of virtual reality on non-drug behavioral management of short-term dental procedure in children.

BACKGROUND: Due to the inherent characteristics of immersion, imagination, and interactivity in virtual reality (VR), it might be suitable for non-drug behavior management of children in dental clinics. The purpose of this trial was to measure the role of VR distraction on behavior management in short-term dental procedures in children. METHODS: A randomized clinical trial design was carried out on 120 children aged between 4 and 8 years to identify the comparative efficacy of VR and tell-show-do (TSD) to improve behavioral management during dental procedures. The primary outcomes were evaluated anxiety, pain, and compliance scores in perioperative children. The levels of operative anxiety and pain were assessed using the Children's Fear Survey Schedule-Dental Subscale (CFSS-DS) and Wong Baker FACES Pain Rating Scale (WBFS), respectively. The Frankl Behavior Rating Scale (FBRS) was tested before and during dental procedures. The length of the dental procedure was compared between both groups after treatment. RESULTS: The average anxiety and behavioral scores of the VR group significantly reduced compared with the control. The decreased anxiety score for the VR group and control group were 8 (7, 11) and 5 (5, 7), p < 0.05. The compliance scores of the control group during treatment were 3 (2, 3), and the same in the VR intervention were 3 (3, 4), p = 0.02. A significant reduction in pain was observed when using VR distraction (p < 0.05). Comparing the length of the dental procedure, the VR group (19.0 2 ± 5.32 min) had a shorter treatment time than the control group (27.80 ± 10.40 min). CONCLUSION: The use of VR significantly reduced the anxiety and pain of children and the length of the dental procedure and improved the compliance of children that underwent short-term dental procedures without an adverse reaction. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000029802 . Registered on February 14, 2020.

Deacetylation of Ku70 by SIRT6 attenuates Bax-mediated apoptosis in hepatocellular carcinoma.

SIRT6 is a class III histone deacetylase that has been implicated in HCC development. We previously reported that SIRT6 potentiated apoptosis evasion in hepatocellular carcinoma by inhibiting both Bax expression and mitochondrial translocalization. However, the mechanism underlying SIRT6-mediated inhibition of Bax mitochondrial localization remains elusive. In this study, we found that although SIRT6 had no effect on the expression level of Ku70, SIRT6 could interact with Ku70 and deacetylate it. The increased acetylation of Ku70 in SIRT6-depleted cells disrupt its interaction with Bax, which finally resulted in Bax mitochondrial translocalization. Furthermore, lysine K542 on Ku70 was the target for deacetylation by SIRT6. Ku70K542Q mutation abolished suppression of association between Ku70 and Bax and caused redistribution of Bax to the cytosol in SIRT6-depleted cells. Finally, Ku70K542Q mutation could reversed the inhibition of growth and apoptosis promotion mediated by SIRT6 silencing. Together, our findings revealed SIRT6 could block the mitochondrial translocation of Bax and decrease the apoptotic ratio of HCC cells by deacetylation of Ku70. SIRT6 may serve as a promising target for developing targeted therapies for HCC in the future.

SIRT6 Overexpression Potentiates Apoptosis Evasion in Hepatocellular Carcinoma via BCL2-Associated X Protein-Dependent Apoptotic Pathway.

PURPOSE: To characterize the functional role of SIRT6 in hepatocellular carcinoma (HCC). EXPERIMENTAL DESIGN: The expression of SIRT6 in 60 paired paraffin-embedded HCC tissues and adjacent nontumoral liver tissues was examined by immunohistochemistry. The expression of SIRT6 in 101 paired frozen HCC tissues and adjacent nontumoral liver tissues was analyzed by Western blotting analysis and qPCR. The biologic consequences of overexpression and knockdown of SIRT6 in HCC cell lines were studied in vitro and in vivo RESULTS: SIRT6 expression was frequently upregulated in clinical HCC samples, and its expression was highly associated with tumor grade (P = 0.02), tumor size (P = 0.02), vascular invasion (P = 0.004), and shorter survival (P = 0.024). Depletion of SIRT6 from multiple liver cancer cell lines inhibited their growth and induced apoptosis in vitro At the molecular level, we observed that the activation of the BCL2-associated X protein (Bax) signaling pathway, a major pathway that determines cancer cell apoptosis, is regulated by SIRT6 via its deacetylase activity. SIRT6 was recruited to the promoter of Bax, where it deacetylated histone 3 lysine 9 and suppressed its promoter activity. Binding of transcription factors (p53 and E2F-1) to Bax promoter was also generally increased in SIRT6-depleted cells. In mouse xenografts, SIRT6 suppression inhibited tumor growth and induced apoptosis. Finally, there is a negative correlation between SIRT6 and Bax mRNA expressions in human HCC samples. CONCLUSIONS: SIRT6 is an important protumorigenic factor in liver carcinogenesis. Thus, the therapeutic targeting of SIRT6 may offer options for HCC treatment. Clin Cancer Res; 22(13); 3372-82. ©2016 AACR.

The SIRT1 inhibitor, nicotinamide, inhibits hepatitis B virus replication in vitro and in vivo.

We previously reported that SIRT1, an NAD(+)-dependent deacetylase belonging to the class III histone deacetylases, enhances hepatitis virus B (HBV) replication by targeting the transcription factor AP-1. However, the potential antiviral effects of nicotinamide, a SIRT1 inhibitor, have not yet been explored. In this study, we show that nicotinamide exhibits potent anti-HBV activity with little cytotoxicity. Nicotinamide suppressed both HBV DNA replicative intermediates and 3.5-kb mRNA expression. Moreover, nicotinamide treatment also suppressed core protein expression and the secretion of the hepatitis B surface antigen (HBsAg) and the hepatitis B e antigen (HBeAg) in HBV-expressing cell models. Importantly, nicotinamide treatment suppressed serum HBV DNA, HBsAg and HBeAg levels and liver HBV DNA in HBV-transgenic mice. Furthermore, using a dual-luciferase reporter assay, it was found that nicotinamide exhibited a marked inhibitory effect on the HBV core, SpI, SpII and X promoters, accompanied by decreased expression of the transcription factors AP-1, C/EBPα and PPARα. Therefore, nicotinamide suppresses HBV replication in vitro and in vivo by diminishing HBV promoter activity. This study highlights the potential application of nicotinamide in HBV therapy.

Cyclin D2 plays a regulatory role in HBV replication.

Hepatitis B virus (HBV) infection is the leading cause of liver diseases. However, the molecular mechanisms of HBV infection and carcinogenesis have not been fully elucidated. In this study, we found that cyclin D2 was upregualted in HBV-expressing cells and liver tissues of HBV-transgenic mice. Gene silencing of cyclin D2 inhibited HBV DNA replicative intermediates, 3.5 kb mRNA, core protein level, as well as the secretions of HBsAg and HBeAg. On the contrary, overexpression of cyclin D2 promoted HBV replication. Furthermore, cyclin D2 regulated HBV replication by enhancing the activity of HBV core and Sp1 promoters by targeting transcription factor CREB2. Silencing of CREB2 abolished enhancement of HBV replication induced by cyclin D2. Together, our study has uncovered a positive role of cyclin D2 in HBV replication. It is conceivable that therapeutic application of cyclin D2 inhibitor in HBV infection therapy.

Sirtuin 1 regulates hepatitis B virus transcription and replication by targeting transcription factor AP-1.

Chronic hepatitis B virus (HBV) infection is a major risk factor for liver cirrhosis and hepatocellular carcinoma. Nevertheless, the molecular mechanism of HBV replication remains elusive. SIRT1 is a class III histone deacetylase that is a structure component of the HBV cccDNA minichromosome. In this study, we found by using microarray-based gene expression profiling analysis that SIRT1 was upregulated in HBV-expressing cells. Gene silencing of SIRT1 significantly inhibited HBV DNA replicative intermediates, 3.5-kb mRNA, and core protein levels. In contrast, the overexpression of SIRT1 augmented HBV replication. Furthermore, SIRT1 enhanced the activity of HBV core promoter by targeting transcription factor AP-1. The c-Jun subunit of AP-1 was bound to the HBV core promoter region, as demonstrated by using a chromatin immunoprecipitation assay. Mutation of AP-1 binding site or knockdown of AP-1 abolished the effect of SIRT1 on HBV replication. Finally, SIRT1 inhibitor sirtinol also suppressed the HBV DNA replicative intermediate, as well as 3.5-kb mRNA. Our study identified a novel host factor, SIRT1, which may facilitate HBV replication in hepatocytes. These data suggest a rationale for the use of SIRT1 inhibitor in the treatment of HBV infection.