Risk of Periodontitis in Patients with Gastroesophageal Reflux Disease: A Nationwide Retrospective Cohort Study.

Background: Gastroesophageal reflux disease (GERD) is the most common digestive clinical problem worldwide that affects approximately 20% of the adult populations in Western countries. Poor oral hygiene has been reported to be associated with GERD as an atypical clinical complication. However, evidence showing the relationship between GERD and the risk of periodontitis is less clear. The present study aimed to use a retrospective cohort study design to further clarify the association between GERD and the subsequent risk of periodontitis. Methods: The risk of periodontitis in patients with GERD was investigated by analyzing epidemiological data from the Taiwan National Health Insurance Research Database from 2008 to 2018. We selected 20,125 participants with a minimum age of 40 years in the GERD group and 1:1 propensity-matched these with non-GERD individuals by sex, age, and comorbidities. The incidence of periodontitis was determined at the end of 2018. A Cox proportional hazards regression model was used to evaluate the risk of periodontitis in patients with GERD. Results: The overall incidence rate of the periodontitis risk was 1.38-fold higher (30.0 vs. 21.7/1000 person years, adjusted hazard ratio (aHR) = 1.36, 95% confidence interval (CI) = 1.28−1.45) in patients with GERD than in those without GERD. After stratified analyses for sex, age, and comorbidity, patients with GERD had a higher risk of periodontitis for age (aHR = 1.31, 95% CI = 1.20−1.42 for 40−54 years and aHR = 1.42, 95% CI =1.28−1.57 for 55−69 years), sex (aHR = 1.40, 95% CI = 1.28−1.54 for men and aHR = 1.33, 95% CI = 1.23−1.45 for women), and presence (aHR = 1.36, 95% CI = 1.27−1.45) and absence (aHR = 1.40, 95% CI = 1.21−1.62) of comorbidity than those without GERD. Among the GERD cohort, the risk for periodontitis was increased with an increasing number of emergency room visits (≥ 1 vs. <1, aHR = 5.19, 95% CI = 2.16−12.5). Conclusions: Our results revealed that patients with GERD have a higher risk of periodontitis development than those without GERD. Clinicians should pay more attention to identifying and managing periodontitis in patients with GERD.

The impact of multidisciplinary pre-dialysis care on the outcomes of incident peritoneal dialysis patients.

BACKGROUND: This study aims to evaluate the impact of multidisciplinary pre-dialysis care (MDPC) on the risks of peritonitis, technique failure and mortality in peritoneal dialysis (PD) patients. METHODS: Incident end-stage kidney disease patients who received peritoneal dialysis (PD) for more than 90 days were recruited in this study from 1 January 1, 2007 to December 31, 2018. Patients were classified into two groups, the MDPC group and the control group, that received the usual care by nephrologists. Risks of the first episode of peritonitis, technique failure and mortality were compared between the two groups. RESULTS: There were 126 patients under the usual care and 546 patients under the MDPC. Patients in the MDPC group initiated dialysis earlier than those in the non-MDPC group. There was no significant difference between these two groups in time to the first episode of peritonitis. Compared to the non-MDPC group, the MDPC group was at similar risks of technique failure (adjusted HR = 0.85, 95% CI = 0.64-1.15) and mortality (adjusted HR = 0.66, 95% CI = 0.42-1.02). Among patients with diabetes, the risk of mortality was significantly reduced in the MDPC group with an adjusted HR of 0.45 (95% CI = 0.25-0.80). CONCLUSIONS: There was no significant difference in time to develop the first episode of peritonitis, and risks of technique failure and mortality between these two groups. Diabetic PD patients under MDPC had a lower risk of mortality than those under the usual care.

Periodontitis and Subsequent Risk of Cataract: Results From Real-World Practice.

BACKGROUND: Periodontitis can lead to systemic inflammation and oxidative stress, contributing to the development of various diseases. Periodontitis could also be associated with several ocular diseases. METHODS: We conducted a retrospective population-based cohort study using the National Health Insurance Research Database of Taiwan to evaluate the risk of cataract in people with and without periodontitis. We established a periodontitis cohort and a non-periodontitis cohort, which included 359,254 individuals between 2000 and 2012. Age, gender, and enrolled year were matched. All participants were monitored until the end of 2013. Cox proportional hazard models were applied to estimate hazard ratios (HRs) and confidence intervals (CIs). RESULTS: Patients with periodontitis had a significantly higher risk to develop cataract than those without periodontitis [10.7 vs. 7.91 per 1,000 person-years, crude HR = 1.35 (95% CI = 1.32-1.39), and adjusted HR = 1.33 (95% CI = 1.30-1.36)]. The significant levels remained the same after stratifying by age, gender, presence of comorbidity, and use of corticosteroid. In addition, we found that diabetes mellitus and hyperlipidemia had a synergistic effect in the interaction of periodontitis and cataract development. CONCLUSION: Patients with periodontitis have a higher risk of cataract development than those without periodontitis. Such patients may request frequent ocular health check-up. Further studies should be performed to confirm the association and to understand the mechanisms.

Calycosin Alleviates Paraquat-Induced Neurodegeneration by Improving Mitochondrial Functions and Regulating Autophagy in a Drosophila Model of Parkinson's Disease.

Parkinson's disease (PD) is the second most common age-related neurodegenerative disorder with limited clinical treatments. The occurrence of PD includes both genetic and environmental toxins, such as the pesticides paraquat (PQ), as major contributors to PD pathology in both invertebrate and mammalian models. Calycosin, an isoflavone phytoestrogen, has multiple pharmacological properties, including neuroprotective activity. However, the paucity of information regarding the neuroprotective potential of calycosin on PQ-induced neurodegeneration led us to explore whether calycosin can mitigate PD-like phenotypes and the underlying molecular mechanisms. We used a PQ-induced PD model in Drosophila as a cost-effective in vivo screening platform to investigate the neuroprotective efficacy of natural compounds on PD. We reported that calycosin shows a protective role in preventing dopaminergic (DA) neuronal cell death in PQ-exposed Canton S flies. Calycosin-fed PQ-exposed flies exhibit significant resistance against PQ-induced mortality and locomotor deficits in terms of reduced oxidative stress, loss of DA neurons, the depletion of dopamine content, and phosphorylated JNK-caspase-3 levels. Additionally, mechanistic studies show that calycosin administration improves PQ-induced mitochondrial dysfunction and stimulates mitophagy and general autophagy with reduced pS6K and p4EBP1 levels, suggestive of a maintained energy balance between anabolic and catabolic processes, resulting in the inhibition of neuronal cell death. Collectively, this study substantiates the protective effect of calycosin against PQ-induced neurodegeneration by improving DA neurons' survival and reducing apoptosis, likely via autophagy induction, and it is implicated as a novel therapeutic application against toxin-induced PD pathogenesis.

Incisor liability and its effects among East Asian children.

BACKGROUND/PURPOSE: Incisor liability is the discrepancy in the sum of the mesiodistal crown width between the primary and permanent incisors. Incisor liability affects the integrity and eruption of the permanent incisors during the transition from the primary to permanent dentition. This study investigated the incisor liability in the primary dentition of Taiwanese children. METHODS: The digital periapical films of 203 upper arches of 105 boys and 98 girls and 195 lower arches of 119 boys and 76 girls aged between 3 and 6 years were selected in this retrospective study. The mesiodistal crown widths of the primary and permanent incisors were measured using the medical imaging software for both arches. Differences in incisor liability values were statistically analyzed. RESULTS: The mean ± standard deviation of the incisor liability values were 8.32 ± 1.88 and 6.91 ± 1.13 mm for the upper and lower arches, respectively, in all children. The incisor liability was closely related with the total crown widths of the permanent incisors for upper and lower arches. The incisor liability values were higher among boys than girls for the upper but not lower arch. CONCLUSION: Incisor liability differs depending on ethnicity. In Taiwanese children, incisor liability was closely related with the crown widths of the permanent incisors. The incisor liability values of boys were higher than those of girls in the upper arch but not the lower arch.

Higher Risk of Gastric Helicobacter pylori Infection in Patients with Periodontitis: A Nationwide Population-Based Retrospective Cohort Study in Taiwan.

Periodontitis is the most prevalent chronic inflammatory oral disease that is characterized by tooth loss and is commonly associated with several systemic inflammatory diseases. Some epidemiological studies suggest that those suffering from periodontitis might be at a greater risk of developing gastric Helicobacter pylori (Hp) infection; however, evidence that showing the association between periodontitis and the risk of gastric Hp infection is less clear. We conducted a large-scale, population-based study in Taiwan with a 13-year follow-up period to evaluate the risk of gastric Hp in a periodontitis patient cohort. To conduct this study, we used epidemiological data from the Taiwanese Longitudinal National Health Insurance Research Database (NHIRD) from 2000 to 2013. We selected 134,474 participants (64,868 males and 69,606 females with a minimum age of 20 years), with and without periodontitis, and matched patient cohort groups for age, sex, index year, and co-morbidities. The Cox proportional hazards regression model was used to examine the risk of gastric Hp infection in patients with periodontitis. Patients with periodontitis exhibited a higher risk of developing gastric Hp infection compared to those individuals/groups without periodontitis (1.35 vs. 0.87 per 1000 person-years, adjusted the hazards ratio (aHR 1.52), and 95% confidence intervals (CIs) 1.38-1.67, p < 0.001). The risk of gastric Hp infection persisted even after stratifying by age (aHR = 1.96 (1.79-2.13) for 50-64 years and 1.70 (1.49-1.94) for ≥65 years), gender (aHR = 1.20 (1.11-1.29) for men), and presence of comorbidities of hypertension (aHR = 1.24 (1.11-1.38)), hyperlipidemia (aHR = 1.28 (1.14-1.42)), COPD (aHR = 1.45 (1.31-1.61)), CLD (aHR = 1.62 (1.47-1.77)) and CKD (aHR = 1.44 (1.04-1.99)). Overall, our findings showed that periodontitis patients have a greater risk for gastric Hp than individuals without periodontitis. Clinicians should perform regular good oral hygiene practices, along with newer treatments, for patients with periodontitis, especially those at higher risk of gastric Hp infection.

Easy to Read Health Education Material Improves Oral Health Literacy of Older Adults in Rural Community-Based Care Centers: A Quasi-Experimental Study.

Health education increases older adults' health knowledge and affects their health outcomes. Older adults have physical changes with aging, such as blurred vision and cognitive decline. Therefore, health education materials must be legible in their case. This study, following the "easy (EZ) to read" concept, designed oral health education material and tested the learning effectiveness of older adults in rural community-based care centers in central Taiwan. Three of the communities were provided EZ to read health education material (n = 72), while three were given general text material (n = 57) as the control group. We collected pre-test and post-test scores using the Mandarin version of the oral health literacy adult questionnaire (MOHL-AQ). The demographic background of the EZ to read and general text groups showed no significant difference (p > 0.05). Analysis of covariance (ANCOVA) showed that the EZ to read material significantly improved total scores of oral health literacy (p < 0.001). The chi-square test showed a significant improvement in oral health literacy levels (p < 0.001). We suggest applying EZ to read concepts to widen the field of older adult education and to reduce illegibility-induced health knowledge disparities.

Effects of Gender and Age in Mandibular Leeway Space for Taiwanese Children.

PURPOSE: Leeway space is clinically crucial in pediatric dentistry because it is utilized to resolve tooth crowding and allow the first molars to drift mesially to establish a Class I molar relationship in the later stages of mixed dentition. This study investigated leeway space in the mixed dentition of Taiwanese children of different sexes and ages. MATERIALS AND METHODS: The digital panoramic dental films of 182 lower arches of 119 boys and 63 girls aged 5-10 years were analyzed in this retrospective study. The mesiodistal crown widths of the primary canines and first and second molars and the permanent canines and first and second premolars were measured using medical imaging software. Differences in leeway space were statistically analyzed. RESULTS: The average leeway space was 1.29 ± 1.48 mm on each side of the lower arch. The leeway space of children aged 5-6 years was significantly greater than that of children aged 7-8 years. No gender difference in crown width was discovered, except with regard to the primary first molar. Although no gender difference in leeway space was observed, permanent teeth affected leeway space more for girls than for boys. CONCLUSION: In Taiwanese children, although leeway space does not differ by sex, age affects leeway space. However, permanent tooth size has an influence on the leeway space of girls.

In Vitro Assessment of the Cell Metabolic Activity, Cytotoxicity, Cell Attachment, and Inflammatory Reaction of Human Oral Fibroblasts on Polyetheretherketone (PEEK) Implant-Abutment.

The purpose of this research is to compare the cytotoxicity of polyetheretherketone (PEEK) and polyetherketoneketone (PEKK) with conventional dental implant-abutment materials, namely titanium alloy (Ti-6Al-4V) and yttria-stabilized tetragonal zirconia polycrystal (Y-TZP), to evaluate the cell metabolic activity, cytotoxicity, and inflammation potential of human oral fibroblasts (HOF) on these materials. Disk-shaped specimens were designed and prepared via a dental computer-aided manufacturing technology system. Surface topography, roughness, and free energy were investigated by atomic force microscope and contact angle analyzer; cell metabolic activity and cytotoxicity by MTT assay; and morphological changes by scanning electron microscopy (SEM). The effect of pro-inflammatory gene expression was evaluated by RT-qPCR. The obtained data were analyzed with one-way analysis of variance and post-hoc Tukey's honest significant difference tests. PEEK and PEKK exhibited higher submicron surface roughness (0.04 µm) and hydrophobicity (>80°) than the control. Although the cell activity of PEEK was lower than that of Ti-6Al-4V and Y-TZP for the first 24 h (p < 0.05), after 48 h there was no difference (p > 0.05). According to the cell cytotoxicity and the pro-inflammatory cytokine gene expression assays, there was no difference between the materials (p > 0.05). SEM observations indicated that HOF adhered poorly to PEKK but properly to Ti-6Al-4V, Y-TZP, and PEEK. PEEK and PEKK show comparable epithelial biological responses to Ti-6Al-4V and Y-TZP as implant-abutment materials. Between the two polymeric materials, the PEEK surface, where the HOF showed better cell metabolic activity and cytotoxicity, was a more promising implant-abutment material.

Exosomal tumor necrosis factor-α from hepatocellular cancer cells (Huh-7) promote osteoclast differentiation.

Bone is the common extra-hepatic site for cancer metastasis. Hepatic cancer is associated with a higher incidence of pathological fracture. However, this important regulatory mechanism remains unexplored. Thus, exosome-mediated cell-cell communication between hepatocellular cancer and bone might be key to osteolytic bone destruction. Huh-7 exosomes were characterized for size and exosome marker expressions (CD63, Alix). Exosome mediated osteoclast differentiation in the RAW 264.7 cells was monitored from day 1 to 6 and multinucleated osteoclast formation and bone resorption activity were analyzed. The osteoclastogenic factor expressions in the exosomes and osteoclast differentiation markers such as tumor necrosis factor receptor 6 (TRAF6), nuclear factor κB (NF-κB), nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), and cathepsin K (CTSK) were analyzed using western blot. Exosomes released by liver cancer cells (Huh-7) promoted osteoclast differentiation in RAW 264.7 cells. Analysis of osteoclastogenic factors in the exosomes showed that exosomes were specifically enriched with tumor necrosis factor α (TNF-α). Huh-7 exosomes promoted osteoclast differentiation by significantly increasing the number of TRAP-positive multi nucleated osteoclasts and resorption pits. Importantly, exosomes upregulated osteoclast markers TRAF6, NF-κB, and CTSK expressions. Further, neutralizing exosomal TNF-α reverted exosome-mediated osteoclast differentiation in RAW 264.7 cells. Collectively, our findings show that cellular communication of exosomal TNF-α from hepatocellular cancer cells (Huh-7) regulates osteoclast differentiation through NF-κB/CTSK/TRAP expressions. Thus, exosomal TNF-α might act as an important therapeutic target to prevent hepatocellular cancer mediated pathological bone disease.

Human antigen R regulates hypoxia-induced mitophagy in renal tubular cells through PARKIN/BNIP3L expressions.

Mitochondrial dysfunction contributes to the pathophysiology of acute kidney injury (AKI). Mitophagy selectively degrades damaged mitochondria and thereby regulates cellular homeostasis. RNA-binding proteins (RBPs) regulate RNA processing at multiple levels and thereby control cellular function. In this study, we aimed to understand the role of human antigen R (HuR) in hypoxia-induced mitophagy process in the renal tubular cells. Mitophagy marker expressions (PARKIN, p-PARKIN, PINK1, BNIP3L, BNIP3, LC3) were determined by western blot analysis. Immunofluorescence studies were performed to analyze mitophagosome, mitolysosome, co-localization of p-PARKIN/TOMM20 and BNIP3L/TOMM20. HuR-mediated regulation of PARKIN/BNIP3L expressions was determined by RNA-immunoprecipitation analysis and RNA stability experiments. Hypoxia induced mitochondrial dysfunction by increased ROS, decline in membrane potential and activated mitophagy through up-regulated PARKIN, PINK1, BNIP3 and BNIP3L expressions. HuR knockdown studies revealed that HuR regulates hypoxia-induced mitophagosome and mitolysosome formation. HuR was significantly bound to PARKIN and BNIP3L mRNA under hypoxia and thereby up-regulated their expressions through mRNA stability. Altogether, our data highlight the importance of HuR in mitophagy regulation through up-regulating PARKIN/BNIP3L expressions in renal tubular cells.

Periodontitis and the subsequent risk of glaucoma: results from the real-world practice.

Periodontitis is a multifactorial inflammatory disease that can cause tooth loss and contribute to systemic inflammation. It is suggested that periodontitis may be associated with the development of glaucoma. Based on data from Taiwan's National Health Insurance Research Database, a retrospective cohort study was conducted to investigate the risk of developing glaucoma in patients with periodontitis. The periodontitis cohort consisted of newly diagnosed adult patients (n = 194,090, minimum age = 20 years) between 2000 and 2012. The comparison group included age-, gender-, and diagnosis date-matched people without periodontitis (n = 194,090, minimum age = 20 years). Incident glaucoma was monitored until the end of 2013. Hazard ratios (HRs) with confidence intervals (CIs) were established based on the Cox proportional hazard models. The risk of developing glaucoma was higher in patients with periodontitis than those without periodontitis (31.2 vs. 23.3 patients per 10,000 person-years, with an adjusted HR of 1.26 [95% CI 1.21-1.32]). A high risk was evident even after stratifying by age (adjusted HRs = 1.34 [1.26-1.44] for ages 20-49, 1.24 [1.13-1.36] for ages ≥ 65, and 1.20 [1.12-1.29] for ages 50-64 years), sex (adjusted HRs = 1.33 [1.24-1.41] and 1.21 [1.14-1.28] for men and women, respectively), presence of comorbidity (adjusted HRs = 1.38 [1.29-1.47] and 1.18 [1.12-1.25] for without and with comorbidity, respectively), and corticosteroid use (adjusted HRs = 1.27 [1.21-1.33] and 1.21 [1.08-1.35] for without and with corticosteroid use, respectively). Specifically, patients with periodontitis exhibited a significantly high risk of primary open-angle glaucoma (adjusted HR = 1.31 [1.21-1.32]) but not for primary closed-angle glaucoma (adjusted HR = 1.05 [0.94-1.17]). People with periodontitis are at a greater risk of glaucoma than individuals without periodontitis. Ocular health should be emphasized for such patients, and the underlying mechanisms need further investigation.

The functional interplay of lncRNA EGOT and HuR regulates hypoxia-induced autophagy in renal tubular cells.

Autophagy, an important cellular homeostatic mechanism regulates cell survival under stress and protects against acute kidney injury. However, the role of long noncoding RNA (lncRNA) in autophagy regulation in renal tubular cells (HK-2) is unclear. The study was aimed to understand the importance of lncRNA in hypoxia-induced autophagy in HK-2 cells. LncRNA eosinophil granule ontogeny transcript (EGOT) was identified as autophagy-associated lncRNA under hypoxia. The lncRNA EGOT expression was significantly downregulated in renal tubular cells during hypoxia-induced autophagy. Gain- and loss-of-EGOT functional studies revealed that EGOT overexpression reduced autophagy by downregulation of ATG7, ATG16L1, LC3II expressions and LC 3 puncta while EGOT knockdown reversed the suppression of autophagy. Importantly, RNA-binding protein, (ELAVL1)/Hu antigen R (HuR) binds and stabilizes the EGOT expression under normoxia and ATG7/16L1 expressions under hypoxia. Furthermore, HuR mediated stabilization of ATG7/16L1 expressions under hypoxia causes a decline in EGOT levels and thereby promotes autophagy. Altogether, the study first reveals the functional interplay of lncRNA EGOT and HuR on the posttranscriptional regulation of the ATG7/16L1 expressions. Thus, the HuR/EGOT/ATG7/16L1 axis is crucial for hypoxia-induced autophagy in renal tubular cells.

RISK OF AGE-RELATED MACULAR DEGENERATION IN PATIENTS WITH PERIODONTITIS: A Nationwide Population-Based Cohort Study.

PURPOSE: Periodontitis is an inflammatory disease that results in loss of connective tissue and bone support. Evidence shows a possible relationship between periodontitis and age-related macular degeneration (AMD). METHODS: This population-based cohort study was conducted using data from the National Health Insurance Research Database in Taiwan, with a 13-year follow-up, to investigate the risk of AMD in patients with periodontitis. The periodontitis cohort included patients with newly diagnosed periodontitis between 2000 and 2012. The nonperiodontitis cohort was frequency-matched with the periodontitis cohort by age and sex, with a sample size of 41,661 in each cohort. RESULTS: Patients with periodontitis had an increased risk of developing AMD compared with individuals without periodontitis (5.95 vs. 3.41 per 1,000 person-years, adjusted hazard ratio = 1.58 [95% confidence interval, 1.46-1.70]). The risk of developing AMD remained significant after stratification by age (adjusted hazard ratio = 1.48 [1.34-1.64] for age <65 years and 1.76 [1.57-1.97] for age ≥65 years), sex (adjusted hazard ratio = 1.40 [1.26-1.55] for women and 1.82 [1.63-2.04] for men), and presence of comorbidity (adjusted hazard ratio = 1.52 [1.40-1.66] for with comorbidity and 1.92 [1.63-2.26] for without comorbidity). In addition, patients with periodontitis showed an increased incidence for both nonexudative type AMD (5.43 vs. 3.13 per 1,000 person-years) and exudative type AMD (0.52 vs. 0.28 per 1,000 person-years). CONCLUSION: People with periodontitis could be at a greater risk of developing AMD than those without periodontitis. However, we need more evidence to support this association.

The Joint Effect of Interleukin-12B rs3212227 Genotype and Behavioral Factors on Oral Cancer Risk in Taiwanese.

BACKGROUND/AIM: Oral cancer is of the highest incidence worldwide in Taiwan, and a better marker for personalized therapeutic strategies such as immunotherapies is urgently needed. Interleukin-12 (IL12) is a cytokine that has been reported to exhibit potent tumoricidal effects, however, its genotypic contribution to oral cancer is still largely unknown. The current study aimed at investigating whether IL12B rs3212227 genotype is associated with oral cancer in Taiwan. MATERIALS AND METHODS: Genotypic characteristics of IL12B rs3212227 were determined among 958 oral cancer cases and age- and gender-matched individuals via typical polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. RESULTS: The AA, AC and CC genotypes of IL12B rs3212227 were 38.2, 38.9 and 22.9% in the case group and 36.2, 41.5 and 22.3% in the control group (p=0.5189), respectively. CONCLUSION: IL12B rs3212227 genotype was associated with oral cancer risk only in betel quid chewers.

Association of Caspase-8 Genotypes With Oral Cancer Risk in Taiwan.

BACKGROUND/AIM: Recently, mounting evidence has shown that caspase-8 (CASP8) rs3834129 (-652, 6N insertion/deletion) polymorphism may serve as a genetic biomarker for personal risk of various cancer types. The contribution of CASP8 rs3834129 polymorphism has been investigated in several oral cancer populations, but not in Taiwan. This study investigated the role of CASP8 rs3834129 polymorphism on oral risk in Taiwan. MATERIALS AND METHODS: CASP8 rs3834129 polymorphic genotypes were determined and their associations with oral cancer risk were investigated among 788 patients with oral cancer and 956 age- and gender-matched healthy controls via polymerase chain reaction-restrictive fragment length polymorphism (PCR-RFLP) methodology. In addition, the interaction of CASP8 rs3834129 genotype with personal behavior and clinicopathological features were also examined. RESULTS: The frequencies of II, ID and DD genotypes for CASP8 rs3834129 were 57.5, 36.5 and 6.0% in the patient group and 54.0, 39.0 and 7.0% in the healthy control group, respectively (p for trend=0.3052), genotypes were not significantly differentially distributed between the two groups. The comparisons in allelic frequency distribution also supported the findings that the D variant allele may not serve as a determinant of risk for oral cancer. There was no interaction of CASP8 rs3834129 genotype with age, gender, smoking, alcohol or betel quid consumption in regard to oral cancer risk. CONCLUSION: Our results indicate that the caspase-8 genotype does not appear to play a direct role in personal susceptibility to oral cancer in Taiwan.

Effects of mineral trioxide aggregate and bioceramics on macrophage differentiation and polarization in vitro.

BACKGROUND/PURPOSE: Mineral trioxide aggregate (Pro-Root MTA, PR-MTA) and bioceramics (iRoot® SP Injectable Root Canal Sealer, iR-BC) are used for making apical plugs used in apexification, repairing root perforations during root canal therapy, and treating internal root resorption. The purpose of the present in vitro study was to compare the biological effects of PR-MTA- and iR-BC-based dental sealers in the mouse macrophage cell line RAW 264.7. METHODS: Cytotoxicity and cell proliferation were analyzed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and cell hemocytometer, respectively. Protein expression of biomarkers of cell proliferation, autophagy, and osteoclast differentiation was determined by western blotting. Pro-inflammatory gene expression was examined using quantitative reverse transcription-PCR. RESULTS: PR-MTA induced cytotoxicity in RAW 264.7 cells in a dose-dependent manner, and iR-BC was more cytotoxic than PR-MTA. Low-dose and short-term treatments of both PR-MTA and iR-BC induced RAW 264.7 cell proliferation. PR-MTA induced autophagy, whereas iR-BC did not. Neither PR-MTA nor iR-BC induced osteoclastogenesis. Pro-inflammatory genes were activated by both materials. However, the expression of inducible nitric oxide synthase (iNOS) mRNA was upregulated by iR-BC treatment, but not by PR-MTA treatment. CONCLUSION: Overall, dental PR-MTA and iR-BC induced pro-inflammatory genes but did not induce osteoclastogenesis in macrophages. PR-MTA and iR-BC induced M2 and M1 polarization, respectively, of RAW 264.7 cells.

The association between Type 1 diabetes mellitus and periodontal diseases.

BACKGROUND/PURPOSE: Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease affecting oral health. Evidence shows possible association between T1DM and periodontal diseases (PDs). We conducted a nationwide population-based study in Taiwan, with a 14-year follow-up to investigate the risk of PDs in T1DM patients. METHODS: We used data from the National Health Insurance Research Database in Taiwan. The T1DM cohort was identified with newly diagnosed T1DM from 1998 to 2011. The non-T1DM cohort was frequency matched with the T1DM cohort. Participants comprised 4248 patients in the T1DM cohort and 16992 persons in the non-T1DM cohort. RESULTS: The T1DM patients showed an increased risk of PDs compared to non-T1DM individuals [adjusted hazard ratio (aHR) = 1.45]. T1DM patients who visited the emergency room more than twice per year had a higher aHR of 13.0 for developing PDs. The aHR for PDs was 13.2 in the T1DM patients who had been hospitalized more than twice per year. CONCLUSION: T1DM patients are at higher risk of developing PDs than non-T1DM individuals. Our results further showed that the number of T1DM interventions; that is, annual emergency visits and hospitalizations were associated with increased the risk of developing PDs.

Sequential risk of depression in children born prematurely: A nationwide population- based analysis.

BACKGROUND: Whether children born prematurely are at a high risk of depression is still unknown. The present study examined the risk of depression in children who were born prematurely, by analyzing a national cohort in Taiwan. METHODS: All premature births between January 1, 2000, and December 31, 2010, by using the Taiwan National Health Insurance Research Database. A total of 21,478 preterm children and 85,903 full-term children were enrolled in this study. Sex, level of urbanization of residential area, and parental occupation were considered. We included participants who received a diagnosis of depression in more than two clinical visits or were hospitalized due to depression. RESULTS: Preterm children had a 2.75-fold higher risk of depression than full-term children (95% confidence interval [CI] = 1.58-4.79, p < 0.001). Sex was not likely to be associated with depression in this study (p = 0.95). The lowest level of urbanization significantly contributed to the risk of depression in preterm children (adjusted hazard ratio = 6.8, 95% CI = 1.63-28.46, p < 0.01). Regarding parental occupation, preterm children whose parents had blue-collar and other occupations had a 3.4- and 6.06-fold higher risk of depression, respectively, compared with other children (blue-collar occupations: 95% CI = 1.04-11.15, p < 0.05; other occupations: 95% CI = 1.71-21.49, p < 0.01). CONCLUSIONS: Preterm children had a 2.7-fold higher risk of depression than children born full-term. Early identification, timely psychiatric care, intervention strategies, and support for their families may reduce the complications of mental illness in preterm children.