Development of a tool for monitoring the jaw-opening pace and preliminary comparison the pace between young and old ages.

OBJECTIVES: Studies have demonstrated that high-speed jaw-opening exercises are effective in improving swallowing function. However, there has been no objective tool available for monitoring jaw-opening pace. This study aimed to develop an objective tool for monitoring and validating jaw-opening pace and compare it between young and old ages from different age groups. MATERIALS AND METHODS: A load cell plug-in jaw pad connected to an automatic recording and analysis system was used to record jaw-opening motions for offline analysis. We recruited 58 healthy volunteers from different age groups (20-39 y/o; 40-59y/o; 60-79y/o). During a 2-min recording session, each participant was instructed to fully open and close their jaw as quickly as possible while wearing a sensor. Bland-Altman plot, paired t-test and Pearson's correlation test were used to compare the number of jaw-opening motions between manual counting and automatic software analysis. The number of jaw-opening motions during the 2-min recording was compared between the three age groups. RESULTS: Automated analysis of jaw-opening pace was efficient and equally comparable with the traditional manual counting method across the three age groups. A declining trend in jaw-opening pace among the old age group was found but with no statistically significant difference. CONCLUSIONS: A jaw-opening motion monitoring tool with reliable automatic pace analysis software was validated in young and old ages. The jaw-opening pace demonstrated a tendency to decline with age. CLINICAL RELEVANCE: This monitoring tool can also be used to provide visual feedback during jaw-opening motion training in pace control.

MiR-630 Promotes Radioresistance by Induction of Anti-Apoptotic Effect via Nrf2-GPX2 Molecular Axis in Head-Neck Cancer.

Head and neck cancer (HNC) ranks among the top ten prevalent cancers worldwide. Radiotherapy stands as a pivotal treatment component for HNC; however, radioresistance in cancerous cells often leads to local recurrence, becoming a substantial factor in treatment failure. MicroRNAs (miRNAs) are compact, non-coding RNAs that regulate gene expression by targeting mRNAs to inhibit protein translation. Although several studies have indicated that the dysregulation of miRNAs is intricately linked with malignant transformation, understanding this molecular family's role in radioresistance remains limited. This study determined the role of miR-630 in regulating radiosensitivity in HNC. We discovered that miR-630 functions as an oncomiR, marked by its overexpression in HNC patients, correlating with a poorer prognosis. We further delineated the malignant function of miR-630 in HNC cells. While it had a minimal impact on cell growth, the miR-630 contributed to radioresistance in HNC cells. This result was supported by decreased cellular apoptosis and caspase enzyme activities. Moreover, miR-630 overexpression mitigated irradiation-induced DNA damage, evidenced by the reduced levels of the γ-H2AX histone protein, a marker for double-strand DNA breaks. Mechanistically, the overexpression of miR-630 decreased the cellular ROS levels and initiated Nrf2 transcriptional activity, resulting in the upregulation of the antioxidant enzyme GPX2. Thus, this study elucidates that miR-630 augments radioresistance by inducing an anti-apoptotic effect via the Nrf2-GPX2 molecular axis in HNC. The modulation of miR-630 may serve as a novel radiosensitizing target for HNC.

Lip and tongue strength associated with chewing patterns in aging population.

BACKGROUND: Improving chewing function of older adults increases the health-related quality of life. Few studies indicated the correlation between tongue, lip strength on masticatory performance in older people. The study aimed to investigate the association between lip, tongue strength on chewing pattern in aging population. METHODS: The older adults had independent daily intake without assistance were enrolled. They had intact dentition and no periodontitis. To estimate the number of chewing strokes and chewing time by consuming a cornstarch cookie were used to represent chewing pattern. Lip and tongue pressure were evaluated with an Iowa Oral Performance Instrument. Linear regression analysis was used to analyze the lip and tongue pressure associated with the chewing time and strokes. Spearman's correlation analysis was utilized to evaluate the associations among chewing time and chewing strokes or lip and tongue pressure. RESULTS: 35 women and 35 men with an average age of 73.2 years were investigated. Tongue pressure was significantly related to the chewing time and the number of chewing strokes (p = 0.01 and 0.03). There was a close association between chewing time and the number of chewing strokes (p < 0.0001). The correlation between lip and tongue pressure was significant (p < 0.0001). CONCLUSION: The tongue strength significantly related to chewing ability in aging population. Increasing the tongue strength greatly reduced the number of chewing strokes and chewing time. Good masticatory ability could increase the motor function of tongue; raising the tongue strength might be able to improve mastication in older adults.

Cbx7 promotes the generation of induced pluripotent stem cells.

The iPS cells were discovered in 2006. With their ability to differentiate into cells of all three germ layers, iPS cells have great potential for clinical applications. Oct4, Sox2, c-Myc, and Klf4 were identified as the most effective factors for generating iPS cells. Despite this, iPS cells manufactured with these factors would still be inefficient. As a member of the chromobox family, chromobox protein homolog 7 (Cbx7) binds to PRC1 and PRC2 to inhibit genes involved in differentiation. A decrease in the expression of Cbx7 is observed during embryonic stem cell differentiation. Currently, no report discusses the role of Cbx7 in the production of iPS cells. In this study, we hypothesized that Cbx7 could increase iPS cell generation. We confirmed that Cbx7 is highly expressed in pluripotent stem cells (including ES and iPS cells). In addition, transfecting Cbx7 into fibroblasts increased Oct4, Sox2, c-Myc, and Klf4 expression. Moreover, we describe a novel approach to producing iPS cells using Cbx7 in combination with Oct4, Sox2, c-Myc, and Klf4. In summary, we have demonstrated that Cbx7 enhances the reprogramming of iPS cells and characterized the stemness and pluripotency of iPS cells.

Surface Electromyography for Evaluating the Effect of Aging on the Coordination of Swallowing Muscles.

Swallowing function can deteriorate with age, leading to a risk of dysphagia. Swallowing evaluation by surface electromyography (sEMG) can be easily and extensively applied for an elderly population. This study evaluated the temporal events observed by sEMG to clarify how aging affects the coordination among the masticatory and suprahyoid muscles. We recruited elderly individuals (over 65 years old) who denied dysphagia. The sEMG activities of anterior temporalis, masseter, and suprahyoid muscles were recorded during 3, 15, and 30 ml water swallowing tests (WST). We calculated the time interval between anterior temporalis and suprahyoid peak activity (T-SH interval) and masseter and suprahyoid peak activity (M-SH interval) and analyzed their correlation with age. The subjects who could and could not swallow 30 ml of water in one gulp were further assigned into the one-gulp and piecemeal groups, respectively, for subgroup analysis. We recruited 101 subjects, among whom 75 (26 males and 49 females) were analyzed after excluding those with suspected dysphagia or low-quality sEMG recordings. Age was significantly correlated with the bilateral T-SH (left: r = 0.249, p = 0.031; right: r = 0.412, p < 0.01) and right M-SH (r = 0.242, p = 0.037) intervals in the 30 ml WST. The correlation between intervals and age were observed in both subgroups. sEMG can be used to investigate the effect of aging on the temporal coordination between masticatory and suprahyoid contraction. Further studies are needed to verify the validity of screening subclinical dysphagia in the elderly.

Ph-Positive B-Cell Acute Lymphoblastic Leukemia Occurring after Receipt of Bivalent SARS-CoV-2 mRNA Vaccine Booster: A Case Report.

The coronavirus disease 2019 (COVID-19) pandemic is a universal emergency public health issue. A large proportion of the world's population has had several spike antigen exposures to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and/or COVID-19 vaccinations in a relatively short-term period. Although sporadic hematopoietic adverse events after COVID-19 vaccine inoculation were reported, there is currently no sufficient evidence correlating anti-spike protein immune responses and hematopoietic adverse events of vaccinations. We reported the first case of Ph-positive B-cell acute lymphoblastic leukemia (ALL) occurring after a bivalent mRNA COVID-19 vaccine inoculation. The otherwise healthy 43-year-old female patient had a total of six spike antigen exposures in the past 1.5 years. Informative pre-vaccine tests and bone marrow study results were provided. Although the causal relationship between bivalent vaccinations and the subsequent development of Ph-positive B-cell ALL cannot be determined in the case report, we propose that anti-spike protein immune responses could be a trigger for leukemia. Clinicians must investigate the hematopoietic adverse events closely after COVID-19 vaccinations. Further pre-clinical studies to investigate the safety of bivalent mRNA COVID-19 vaccine are required.

Convergent angles of a tapered implant referred from the root profile of premolars.

Background/purpose: Limited studies have discussed the convergent profiles regarding tapered implants based on biological considerations. This study analyzed the convergent angles (CAs) of premolar roots and imitated a tapered implant according to the anatomy of tooth roots. Materials and methods: A total of 60 single-rooted premolars were explored by micro-computed tomography. Every individual root was divided into 10 segments corono-apically, and the roots' buccolingual (BL) and mesiodistal (MD) CAs were measured by sections. To mimic a dental implant, the irregular shape of examined root cross-sections was transformed into a circular shape with equal areas. A biomimetic dental implant (BDI) was reconstructed and its CAs were compared with those of the natural roots' BL and MD at the examined levels and overall estimation. Results: In general, the maxillary and mandibular premolars demonstrated comparable CA patterns. However, significantly different CA patterns of BL, MD, and BDI were developed for both the maxillary and mandibular roots at the examined levels. The BL's CAs were greater than those CAs measured from the BDI and MD aspects, particularly for the sections at the middle and apical thirds of the roots. For overall CAs, the BDI's CAs were comparable with the average CAs of the BL and MD for both premolar groups. Conclusion: Instead of a cylindrical configuration, the BDI prototype demonstrated a tapered model with a continuous slope. The average CA of BDI was 14°-24°, serving as a biological reference for future tapered implant design and research.

Tumor Suppressor miRNA-503 Inhibits Cell Invasion in Head and Neck Cancer through the Wnt Signaling Pathway via the WNT3A/MMP Molecular Axis.

Head and neck cancer (HNC) is the fifth most common cancer worldwide, and its incidence and death rates have been consistently high throughout the past decades. MicroRNAs (miRNAs) have recently gained significant attention because of their role in the regulation of a variety of biological processes via post-transcriptional silencing mechanisms. Previously, we determined a specific profile of miRNAs associated with HNC using a miRNA microarray analysis. Of the 23 miRNAs with highly altered expression in HNC cells, miR-503 was the most significantly downregulated miRNA. In this study, we confirmed that miR-503 acts as a tumor suppressor, as our results showed decreased levels of miR-503 in cancer cells and patients with HNC. We further characterized the role of miR-503 in the malignant functions of HNC. Although there was a minimal effect on cell growth, miR-503 was found to inhibit cellular invasion significantly. Algorithm-based studies identified multiple potential target genes and pathways associated with oncogenic mechanisms. The candidate target gene, WNT3A, was confirmed to be downregulated by miR-503 at both the mRNA and protein levels and validated by a reporter assay. Furthermore, miR-503 modulated multiple invasion-associated genes, including matrix metalloproteinases (MMPs), through the Wnt downstream signaling pathway. Overall, this study demonstrates that miR-503 suppresses HNC malignancy by inhibiting cell invasion through the Wnt signaling pathway via the WNT3A/MMP molecular axis. The modulation of miR-503 may be a novel therapeutic approach to intervene in cancer invasion.

The correlation between two occlusal analyzers for the measurement of bite force.

BACKGROUND: Occlusal force represents masticatory function. Using quantifiable occlusal indicators provides a more objective occlusal force evaluation. In the recent dental practice, digital methods such as the Dental Prescale II (DP2, GC Corp., Tokyo, Japan) and T-scan (T-Scan III v8; Tekscan Inc.) are commonly used in clinics to evaluate treatment outcomes. The T-scan provides the relative bite force (%) compared to the maximal bite force on individual teeth or the unilateral arch. The DP2 can quantify occlusal force, measured in newtons (N), on the half arch or the overall bite, but it is difficult to identify the bite force on an individual tooth. It is difficult to select a device that fulfils all the requirements to record occlusal force. This study aimed to investigate the association between the bite measured by the DPS2 and T-scan to determine whether the measured bite force is comparable through calculation. METHODS: A total of 80 healthy adults, including 41 women and 39 men with a mean age of 38.2, were requested to bite pressure sensitive film sheets ten minutes apart. Linear regression analysis was used to estimate the measured bite force by the DP2 and T-scan. RESULTS: There was a significant positive correlation between the occlusal force measured by the DP2 and T-scan (P < 0.01) when intercept was equal to zero as confounders were adjused. These results provided the comparability of the measured occlusal forces determined by the DP2 and T-scan. CONCLUSION: The estimated bite force determined by DP2 and T-Scan is convertible using the linear equation from this study to increase the value for clinical applications. The estimated bite force from the two quantifiable occlusal indicators are comparable. The two commercially available quantifiable occlusal indicators can be fully adapted to all clinical requirements according to this result.

The association between the severity of periodontitis and osteonecrosis of the jaw in patients with different cancer locations: a nationwide population-based study.

OBJECTIVES: To determine the relation between the severity of periodontitis and osteonecrosis of the jaw (ONJ) occurrence among different cancer locations and estimate the effect of dental care on ONJ prevention in cancer patients. MATERIALS AND METHODS: This population-based cross-sectional study was conducted through the Longitudinal Health Insurance Database, Taiwan. Patients with malignancies were collected and subdivided into groups according to their different cancer locations, the severity of periodontitis, and dental care. Multivariable logistic regression analysis was performed to assess the associations between ONJ and ONJ-related factors. RESULTS: A total of 8,234 ONJ patients and 32,912 control patients were investigated. Lip, oral cavity, and pharynx malignancies had the highest ONJ risk among all cancer locations (OR from 3.07 to 9.56, P < 0.01). There is a linear relationship between different severities of periodontitis and ONJ. Patients with radiotherapy and severe periodontitis had the highest ONJ risk (adjusted OR, 9.56; 95% CI, 5.34-17.1). Patients with good dental care had a lower ONJ risk. CONCLUSIONS: The periodontal condition and cancer location showed a significant impact on the risk of developing ONJ after adjusting for bisphosphonate use. Good dental care could decrease the risk of ONJ in cancer patients. The severity of periodontitis might be a target to predict the potency of ONJ. CLINICAL RELEVANCE: Dentists must be vigilant about the increased risk of ONJ in cancer patients with periodontitis, especially in the head and neck cancer population. Good dental care is advised for cancer patients with severe periodontitis.

The impact of dental therapy timelines and irradiation dosages on osteoradionecrosis in oral cancer patients: A population-based cohort study.

OBJECTIVES: This study aimed to investigate how different timelines of various dental therapies were related to osteoradionecrosis development under consideration of radiotherapy dosage in patients with oral cancer. MATERIALS AND METHODS: A total of 7,107 oral cancer patients were enrolled, including 88 osteoradionecrosis patients treated with low radiotherapy dosages (<60 Gy) or high radiotherapy dosages (≥60 Gy), from the Longitudinal Health Insurance Database for Catastrophic Illness Patients of Taiwan. Cox proportional hazard regression was used to compare the osteoradionecrosis risk of various dental treatment timelines under different irradiation dosages. RESULTS: In the oral cancer population with low irradiation dosages (<60 Gy), performing periodontal therapy combined with irradiation significantly raised the risk of osteoradionecrosis by 2.21-fold. Starting radiotherapy within three months after dental surgery greatly increased the risk of developing osteoradionecrosis by 1.87-fold. The oral cancer patients treated with high radiation doses (≥60 Gy) receiving dental surgery within one month prior to radiotherapy had a significantly raised osteoradionecrosis occurrence by 1.60-fold. While the dental surgery was performed during the radiotherapy course, the risk of osteoradionecrosis was greatly increased by 2.21-fold. CONCLUSION: For oral cancer patients, performing dental surgery within three months before radiotherapy might significantly induce osteoradionecrosis. Patients that were treated with high irradiation dosages (≥60 Gy) had a higher tendency to develop osteoradionecrosis if they received dental surgery during radiotherapy. Those who were treated with low radiation dosages (<60 Gy) and received periodontal therapy during radiotherapy might have an increased risk in developing osteoradionecrosis.

Calcitriol and enamel matrix derivative differentially regulated cemento-induction and mineralization in human periodontal ligament-derived cells.

BACKGROUND: Alveolar bone and cementum share many biological and developmental similarities. The mineralizing effect of calcitriol has been previously reported. Yet, its cemento-inductivity has not been confirmed. This study evaluated the potential cemento-inductivity effect of calcitriol and enamel matrix derivative (EMD) on human periodontal ligament-derived cells (hPDLCs). METHODS: The hPDLCs obtained from extracted third molars or premolars were cultured with calcitriol, or EMD. Cementogenic gene expression was examined using real-time quantitative reverse transcription polymerase chain reaction. Expression analysis also included cementoblast-specific markers, cementum protein 1 (CEMP1), cementum attachment protein (CAP), and recently reported cementoblast-enriched genes, secreted frizzled related protein 1 (SFRP1), and Dickkopf-related protein 1 (DKK1). Mineralization capacities were evaluated by alkaline phosphatase (ALP) activity, Alizarin Red, and Von Kossa staining followed by scanning electron microscope imaging and element mapping. RESULTS: Among tested conditions, 10 nM calcitriol enhanced most cementogenic gene expression, transforming growth factor-ß1, bone morphogenetic proteins (BMP-2 and BMP-4), core-binding factor subunit alpha-1/Runt-related transcription factor 2, Type I collagen, ALP, bone sialoprotein, osteopontin), osteocalcin, CEMP1, and CAP, and Wnt signaling negative modulators, SFRP1 and DKK1, along with highest ALP activity and mineralization formation in hPDLCs. However, only moderate CEMP1 protein was observed. In contrast, EMD stimulated stronger CEMP1 and CAP protein, but presented weaker mineralization capacity, hinting at the possibility that strong stimulation of mineralization might dominate cemetogenic specific factors and vice versa. CONCLUSIONS: Calcitriol demonstrated not only great osteoinductivity, but also the potential to induce cementogenic gene expression by initiating hPDLC differentiation and promoting mineralization. Compared with calcitriol, EMD promoted cemento-inductivity in hPDLCs at a later time point via highly expressed CEMP1 and CAP protein, but with less mineralization. Thus, calcitriol and EMD could provide differential enhancement of cemento-induction and mineralization, likely acting at various differentiation stages.

Systemic Investigation Identifying Salivary miR-196b as a Promising Biomarker for Early Detection of Head-Neck Cancer and Oral Precancer Lesions.

BACKGROUND: Liquid biopsy is a rapidly growing field, for it may provide a minimally invasive way to acquire pathological data for personalized medicine. This study developed a systemic strategy to discover an effective salivary biomarker for early detection of patients with head-neck squamous carcinoma (HNSC) and oral precancer lesion (OPC). METHODS: A total of 10 miRNAs were examined in parallel with multiple independent cohorts. These included a training set of salivary samples from HNSC patients, the TCGA-HNSC and GSE31277 cohorts to differentiate miRNAs between tumor and normal tissues, and groups of salivary samples from healthy individuals, patients with HNSC and OPC. RESULTS: The combined results from the salivary training set and the TCGA-HNSC cohort showed that four miRNAs (miR-148b, miR-155, miR-196b, and miR-31) consistently increased in HNSC patients. Further integration with the GSE31277 cohort, two miRNAs (miR-31 and miR-196b) maintained at high significances. Further assessment showed that salivary miR-196b was a prominent diagnostic biomarker, as it remarkably discriminated between healthy individuals and patients with HNSC (p < 0.0001, AUC = 0.767, OR = 5.64) or OPC (p < 0.0001, AUC = 0.979, OR = 459). CONCLUSION: Salivary miR-196b could be an excellent biomarker for diagnosing OPC and early detection of HNSC. This molecule may be used for early screening high-risk groups of HNSC.

Vertical dimension of occlusion related to mandibular movement during swallowing.

BACKGROUND: Increasing the vertical dimension of occlusion (VDO) is a common procedure in complicated prosthodontic treatment. The swallowing technique had been verified as a functional method to determine the VDO. The purpose of this study was to investigate the association between increasing VDO and mandibular movement during swallowing. METHODS: 26 females and 14 males were enrolled (age range: 21 to 30 year-old). Under different increased VDO (3, 5, and 8 mm), the mandibular trajectory during swallowing was measured by K7 Evaluation System (Myotronics®). When the subjects were instructed to salivary swallowing, the range of mandibular movement in vertical, anteroposterior and lateral directions were recorded. RESULTS: Increasing VDO significantly impacted the range of mandibular movement in lateral direction during swallowing (p < 0.0001, F value = 40.09). The average variance of the mandibular movement distance in lateral direction during swallowing raise 1.58 (p = 0.001); 3.59 (p = 0.0001) and 2.01 (p = 0.001) when th VDO was raised from 3 mm to 5 mm; from 3 mm to 8 mm and from 5 to 8 mm respectively. The range of mandibular movement was significantly correlated to the increasing VDO (p ≤ 0.05) under the analysis of the Post Hoc test. CONCLUSIONS: VDO was closely correlated to the trajectory of mandibular motion during swallowing. The increase in VDO could change the extent of mandibular trajectory during swallowing if the increase was more than 3 mm. The range of mandibular motion when swallowing had positive correlative tendency as the VDO was increased.

Bidirectional relationship between temporomandibular disorder and ankylosing spondylitis: a population-based cohort study.

OBJECTIVES: This study aimed to determine the relation between temporomandibular disorder (TMD) and ankylosing spondylitis (AS) bidirectionally and ascertain the important comorbidities for AS occurrence in TMD patients. MATERIALS AND METHODS: We conducted this population-based cohort study through Longitudinal Health Insurance Database, Taiwan. Study 1 investigated the risk of TMD in AS patients. Study 2 assessed the risk of AS in TMD patients. RESULTS: In total, 3204 AS patients and 12,816 age-matched and gender-matched comparisons were enrolled in study 1. The TMD incidence in the AS cohort was 2.88-fold higher when compared with the comparisons (1.54 vs. 0.53 per 10,000 person-years). After adjusting for age, gender, and comorbidity, the AS cohort had a 2.66-fold (95% CI = 1.79-3.97) increased risk of TMD occurrence (P < 0.0001). The second study recruited 4998 TMD patients and 19,991 age-matched and gender-matched comparisons. Both TMD and comparison cohorts showed similar AS risk (HR = 1.49, 95% CI = 0.91-2.43, P = 0.1108) in the adjusted model. Study 2 identified a 3.66-fold increased risk of AS occurrence in TMD patients with comorbidity, including parapsoriasis, rheumatoid arthritis, osteoporosis, Cushing's syndrome, and climacteric arthritis (P < 0.012). CONCLUSIONS: AS appears to significantly impact the occurrence of TMD. TMD might play a synergic role in AS development. CLINICAL RELEVANCE: Clinicians have to be vigilant about the increased risk of TMD in AS patients and take care of AS disease activity and prognosis. The symptoms and signs of TMD could be a predictor of AS in patients with the aforementioned comorbidities.

The impact of occluding pairs on the chewing patterns among the elderly.

OBJECTIVES: This study aims to investigate the impact of occluding pairs (OPs) on chewing strokes, chewing time, mealtime duration, and bite force in an aging population. METHODS: The 100 participants included 52 women and 48 men with average age of 71.2 years. The subjects were restricted to those who can eat what they wanted and had no temporomandibular joint disorder (TMD) and dysphagia history; their OPs were counted in the posterior occlusal support zone in accordance with the Eichner classification. Free habitual mastication of a cornstarch cookie was analyzed by recording the number of chewing strokes and the amount of time needed for complete mastication. Strokes were counted by considering the opening and closing mandibular movements. Mealtime was defined as the time spent to finish a lunchbox and accomplish swallowing. Bite force was estimated with a T-Scan III®. A linear regression analysis was used to evaluate the impact of the OPs on the chewing strokes, chewing time, mealtime duration, and bite force. RESULTS: In this study, 76% of the participants had 4 OPs and 12% participants had 3 OPs. Increasing the OPs significantly shortened the chewing time and mealtime duration (P = 0.02). The mealtime duration did not notably affect the chewing time (P = 0.237). There was significant association between OPs and bite force (P < 0.0001). CONCLUSIONS: In elderly, increasing OPs significantly raised the bite force and shortened the chewing time and strokes. More OPs might be the key to maintain good chewing function. CLINICAL SIGNIFICANCE: Among the elderly, increasing OPs significantly raised the bite force and shortened the chewing time and mealtime duration. To provide better chewing function, good oral hygiene is important to maintain as many OPs as possible; how to gain more OPs is essential concern in the prosthodontic treatment plan making.

The impact of timing and modalities of dental prophylaxis on the risk of 5-fluorouracil-related oral mucositis in patients with head and neck cancer: a nationwide population-based cohort study.

PURPOSE: This study investigated the impact of dental prophylaxis on 5-fluorouracil (5-FU)-related oral mucositis (OM) according to the head and neck cancer (HNC) locations and treatment times. METHODS: A total of 13,969 HNC participants, including 482 5-FU-related OM subjects and 13,487 comparisons were enrolled from the Longitudinal Health Insurance Database for Catastrophic Illness Patients of Taiwan between 2000 and 2008. All subjects were stratified into subgroups based on the times to perform chlorhexidine use, scaling, and fluoride application before 5-FU administration. The dental prophylaxis related to 5-FU-related OM was estimated by multiple logistic regression and represented with odds ratio (OR) and 95% confidence interval (CI). RESULTS: Fluoride gel application and scaling significantly impacted on OM development (p < 0.001), and the joint effect of fluoride gel and scaling induced 5-FU-related OM (OR = 3.46, 95% CI = 2.39-5.01). The risk of OM was raised 2.25-fold as scaling within 3 weeks before 5-FU-related chemotherapy (95% CI = 1.81-2.81), and a 3.22-fold increased risk of OM while fluoride gel was applied during 5-FU-related treatment (95% CI = 1.46-7.13). CONCLUSION: Dental prophylaxis significantly affected 5-FU-related OM in the HNC population. A short interval between dental scaling or fluoride application and 5-FU administration may be associated with higher prevalence of OM. Scaling simultaneously combined with chlorohexidine promoted 5-FU-related OM in specific HNC patients excluding the oral cancer and nasopharyngeal cancer population. Proper timing of the prophylactic dental treatments prior to 5-FU therapy could reduce the risk to develop 5-FU-related OM.

MicroRNA-155 inhibits dengue virus replication by inducing heme oxygenase-1-mediated antiviral interferon responses.

MicroRNAs (miRNAs) have been reported to directly alter the virus life cycle and virus-host interactions, and so are considered promising molecules for controlling virus infection. In the present study, we observed that miR-155 time-dependently downregulated upon dengue virus (DENV) infection. In contrast, exogenous overexpression of miR-155 appeared to limit viral replication in vitro, suggesting that the low levels of miR-155 would be beneficial for DENV replication. In vivo, overexpression of miR-155 protected ICR suckling mice from the life-threatening effects of DENV infection and reduced virus propagation. Further investigation revealed that the anti-DENV activity of miR-155 was due to target Bach1, resulting in the induction of the heme oxygenase-1 (HO-1)-mediated inhibition of DENV NS2B/NS3 protease activity, ultimately leading to induction of antiviral interferon responses, including interferon-induced protein kinase R (PKR), 2'-5'-oligoadenylate synthetase 1 (OAS1), OAS2, and OAS3 expression, against DENV replication. Collectively, our results provide a promising new strategy to manage DENV infection by modulation of miR-155 expression.

The association between dental therapy timelines and osteoradionecrosis: a nationwide population-based cohort study.

OBJECTIVES: The study aimed to investigate the timeline association with specific dental therapy and osteoradionecrosis (ORN) in oral cancer patients. MATERIALS AND METHODS: A total of 7394 oral cancer patients, including 198 ORN subjects, were retrieved from a Longitudinal Health Insurance Database for Catastrophic Illness Patients of Taiwan and were analyzed with the Cox proportional hazard regression to compare the ORN risk of individual dental treatments under different dental treatments. RESULTS: The initial dental treatment time significantly impacted on the risk of ORN in oral cancer patients (P<0.05). Pre-radiotherapy endodontic treatment and post-radiotherapy scaling or subgingival curettage increased ORN prevalence (hazard ratio [HR], 2.28 and 1.77, respectively). Endodontic treatment within 2 weeks to 1 month prior to radiotherapy increased the ORN risk by 5.83-fold. Dental scaling or subgingival curettage initialized from three to 6 months post-radiotherapy raised the ORN prevalence by 2.2-fold. Exodontia initialized within 2 weeks before radiotherapy (HR=1.49) or 1 to 3 months after radiotherapy (HR=2.63) greatly increased ORN prevalence. To perform oral surgery from 3 months pre-radiotherapy to 6 months after radiotherapy increased the 1.85-fold ORN risk. The chemotherapy combined oral surgery increased the ORN prevalence by 2.55-fold. CONCLUSIONS: Timing of dental treatment, including pre-radiotherapy endodontic treatment, post-radiotherapy scaling or subgingival curettage, and oral surgery or exodontia before and after radiotherapy, could closely relate to ORN development in oral cancer patients. CLINICAL RELEVANCE: Choosing right time to perform appropriate dental treatment could effectively reduce oral infection and ORN risk.