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Objectives: The association between tinnitus and anxiety disorder remains debated. We used a retrospective cohort study to investigate the relationship between anxiety disorder and tinnitus, aiming to decipher possible risk factors for tinnitus in patients with anxiety disorder., Method: Data on a total of 7,525 patients with anxiety disorder and 15,050 patients without (comparison cohort) were extracted from the Longitudinal Health Insurance Database 2005 in Taiwan. The Kaplan-Meier estimator with the log rank test and the Cox proportional-hazard regression model were used to compare the incidence of tinnitus in both groups and to identify risk factors that predicted tinnitus., Results: After adjusting for related covariates, the hazard ratio for the development of tinnitus during the follow-up period was 3.54 (95% confidence interval: 3.11-4.02, P < .001) for anxiety disorder cohort relative to comparison cohort. Age ≧ 60 years, female sex, hypertension, and hyperlipidemia were statistically significant predictive risk factors of tinnitus in patients with anxiety disorder., Conclusion: A significant increase in the lifetime incidence of tinnitus was exhibited in patients with anxiety disorder. Elderly subjects, female sex, hypertension, and hyperlipidemia were risk factors. Clinicians should be alert to the possibility of tinnitus in subjects with anxiety disorder., (Copyright © 2020 Hou, Yang, Tsai, Shen and Lan.)

Discovering drug candidates for the modulation of metastasis is of great importance in inhibiting oral cancer malignancy. Although most pomegranate extract applications aim at the antiproliferation of cancer cells, its antimetastatic effects remain unclear, especially for oral cancer cells. The aim of this study is to evaluate the change of two main metastasis characters, migration and invasion of oral cancer cells. Further, we want to explore the molecular mechanisms of action of pomegranate extract (POMx) at low cytotoxic concentration. We found that POMx ranged from 0 to 50 μg/mL showing low cytotoxicity to oral cancer cells. In the case of oral cancer HSC-3 and Ca9-22 cells, POMx inhibits wound healing migration, transwell migration, and matrix gel invasion. Mechanistically, POMx downregulates matrix metalloproteinase (MMP)-2 and MMP-9 activities and expressions as well as epithelial-mesenchymal transition (EMT) signaling. POMx upregulates extracellular signal-regulated kinases 1/2 (ERK1/2), but not c-Jun N-terminal kinase (JNK) and p38 expression. Addition of ERK1/2 inhibitor (PD98059) significantly recovered the POMx-suppressed transwell migration and MMP-2/-9 activities in HSC-3 cells. Taken together, these findings suggest to further test low cytotoxic concentrations of POMx as a potential antimetastatic therapy against oral cancer cells., (© 2020 Wiley Periodicals, Inc.)

The aim of this study was to compare the accuracy of implant placement by using the conventional freehand method, the surgical guide alone, the dental navigation system alone, and the dental navigation system with a surgical guide. The participants were aged 20 years or older and were requiring dental implant surgery according to an assessment made by a dentist between July 2014 and December 2017. A total of 128 dental implants were inserted, 32 dental implants in each group, and participants with similar or identical age (i.e., 20-50 years or 50 years or above) and missing tooth locations were paired for comparison. Accuracy was measured by overlaying the real position in the postoperative Cone Beam Computerized Tomography (CBCT) on the virtual presurgical placement of the implant in a CBCT image. Using the dental navigation system with a surgical guide could help dentists to position implants more accurately. Total, longitudinal, and angular error deviation were significantly different ( p < 0.0001). The same level of accuracy could be obtained for the different jaws and tooth positions. The one-way analysis of variance (ANOVA) showed that the total, longitudinal, and angular errors differed significantly ( p < 0.0001). A comparison of the four dental implant surgical methods indicated that the combination of a dental implant navigation system and a surgical guide kit achieved the highest accuracy in terms of the different tooth positions and jaws.

This study aimed to conduct a stress analysis of four types of cervical finish lines in posterior all-ceramic crowns on the primary roots of molar teeth. Four different types of finish lines (shoulder 0.5 mm, feather-edged, chamfer 0.6 mm, and mini chamfer 0.4 mm) and two all-ceramic crown materials (zirconia and lithium disilicate) were used to construct eight finite element primary tooth models with full-coverage crowns. A load of 200 N was applied at two different loading angles (0° and 15°) so as to mimic children's masticatory force and occlusal tendency. The maximum stress distribution from the three-dimensional finite element models was determined, and the main effect of each factor (loading type, material, and finish line types) was evaluated in terms of the stress values for all of the models. The results indicated that the loading type (90.25%) was the main factor influencing the maximum stress value of the primary root, and that the feather-edged margin showed the highest stress value ( p = 0.002). In conclusion, shoulder and chamfer types of finish lines with a 0.4-0.6 mm thickness are recommended for deciduous tooth preparation, according to the biomechanical analysis., Competing Interests: The authors declare no conflict of interest.

Background: The intrinsic motivation behind the "need to complete" is more influential than external incentives. We introduced a novel progress-bar tool to motivate the completion of programs designed to treat stimulant and cannabis use disorders. We further examined the effectiveness of the progress bar's scoring approach in forecasting consistently negative urine tests. Methods: This study's participants included 568 patients with stimulant, amphetamine-type, and cannabis use disorders who were undergoing 12-month mandatory treatment programs at Taichung Veterans General Hospital in Taiwan. Patients were given scores of 1, -1, or 0 depending on whether they received negative, positive, or missing urinalysis reports, respectively. The autonomic progress bar generated weekly score totals. At the group level, score i donated scores from all patients for a given week (i denoted the week). Score i was standardized to adjusted score i . We then conducted Autoregressive Integrated Moving Average (ARIMA) Model of time-series analyses for the adjusted score i . Results: A total of 312 patients maintained treatment progress over the 12-month program. The autonomic score calculator totaled the shared achievements of these patients. The coefficients of the lag variables for mean (p), lag variables for residual error term (q), and number of orders for ensuring stationary (d) were estimated at p = 3, d = 4, and q = 7 for the first half of the treatment program, and were estimated at p = 2, d = 2, and q = 3 for the second half. Both models were stationary and tested as fit for prediction (p < 0.05). Sharply raised adjusted scores were predicted during the high-demand treatment phase. Discussion: This study's novel progress-bar tool effectively motivated treatment completion. It was also effective in forecasting continually negative urine tests. The tool's free open-source code makes it easy to implement among many substance-treatment services., (Copyright © 2020 Chen, Teng, Chen, Lan and Liu.)

Objective: This observational study on adult Taiwanese cadavers focused mainly on the intersection of buccal branches of the facial nerve with Stensen's duct, using the emergence of Stensen's duct as the reference landmark., Materials and Methods: Thirty-five cadaveric hemifaces were included in our research. Samples with facial defects due to tumor, trauma, or surgery were all excluded. Buccal branches of the facial nerve were identified according to the Gray's Anatomy 40th edition definition. The distance was measured from the intersection to the emergence of Stensen's duct, running from the anterior border of the parotid gland., Results: In the 35 hemifaces, the number of buccal branch/Stensen's duct intersections ranged from 1 to 5 (average 2.49 ± 1.15). Two-point intersections accounted for 37% (13 hemifaces) of the sample, forming the largest group. Samples of facial nerve buccal branches were divided into four types: Type 1, with two buccal branches, accounted for 37.15% (13/35); Type 2, with three buccal branches, made up 48.59% (17/35) of our samples - the biggest group (Type 2-a was the most frequent pattern among our samples, with two superior buccal branches and one inferior buccal branch, accounting for 34.31% of our samples); Type 3, with four buccal branches, accounted for only 5.7%. Three cases of double Stensen's duct were classified as Type 4, though this is supposed to be a very rare anatomical variation. With Type 2a, the most frequent pattern among our specimens, the distance from the emergence of the Stensen's duct to the emergence point of the first superior buccal branch along the anterior border of the parotid gland was 9.58 ± 5.68 mm. The distance from the emergence point to the emergence of the inferior buccal branch along the anterior border of the parotid gland was 11.03 ± 5.38 mm. The distance (D1) from Stensen's duct to the emergence of the first superiorly located buccal branch of the group Type 2-a was statistically different from the distance (D1) of the other groups (p = 0.02). No direct anastomoses or communicating fibers between upper and lower buccal branches were noted in 11 hemifaces (31%)., Conclusion: The distribution of buccal branches was described using the emergence of Stensen's duct as a reference landmark. According to our observations, the relationship between the buccal branches and Stensen's duct was much more complicated than described in previous studies. This was the first study to investigate the complete distribution of buccal branches of the facial nerve emerging from the anterior of the parotid gland, and their relative locations and branching numbers., (Copyright © 2018. Published by Elsevier Ltd.)

Background: This study evaluated the operating performance of an implant navigation system used by dental students and dentists of prosthodontic background with varying levels of experience. A surgical navigation system and optical tracking system were used, and dentists' accuracies were evaluated in terms of differences between the positions of actually drilled holes and those of the holes planned using software before surgeries., Methods: The study participants were 5 dental students or dentists who had studied in the same university and hospital but had different experience levels regarding implants. All participants were trained in operating the AqNavi system in the beginning of the study. Subsequently, using 5 pairs of dental models, each participant drilled 5 implant holes at 6 partially edentulous positions (11, 17, 26, 31, 36, and 47). In total, each participant conducted 30 drilling tests., Results: In total, 150 tests among 5 dentists at 6 tooth positions (11, 17, 26, 31, 36, and 47) were conducted. Although a comparison of the tests revealed significant differences in the longitudinal error (P < .0001) and angular error (P = .0011), no significant difference was observed in the total error among the dentists., Conclusions: A relatively long operating time was associated with relatively little implant experience. Through the dental navigation system, dental students can be introduced to dental implant surgery earlier than what was possible in the past. The results demonstrated that the operational accuracy of the dental implant navigation system is not restricted by participants' implant experience levels. The implant navigation system assists the dentist in the ability to accurately insert the dental implant into the correct position without being affected by his/her own experience of implant surgery.

Mild traumatic brain injury (mTBI) is a common cause of brain damage with a high incidence of multiple mTBIs found among athletes and soldiers. The purpose of this study is to examine the diurnal behavioral changes after multiple mTBIs. Adult mice were anesthetized; mTBI was conducted by dropping a 30-g weight to the right temporal skull once (mTBI1) or three times (mTBI3) over 3-week. Open-field motor behavior was recorded for 3 days after the last mTBI. In the first 4-hour exploratory phase, mTBI1 or mTBI3 equally reduced locomotor activity. A significant reduction of locomotor activity was found in the dark cycle between 4-72 hour in mTBI1 or mTBI3 mice; higher motor activity was seen after mTBI3 compared to mTBI1. In the light cycle, mTBI3 mice demonstrated an earlier immobilization followed by hyperactivity. The response to light change significantly correlated with the number of impacts. The IBA1 and BAX protein levels were equally increased in the lesioned cortex after mTBI1 and mTBI3. mTBI3 selectively upregulated the expression of circadian clock gene Per1 in hypothalamus and hippocampus as well as iNOS expression in the lesioned side cortex. Our data suggest multiple mTBIs alter diurnal locomotor activity and response to the change of light, which may involve Per1 expression in the lesioned brain.

Orbital fractures pose specific challenge in its surgical management. One of the greatest challenges is to obtain satisfactory reconstruction by correct positioning of orbital implant. Intraoperative computed tomography (CT) scan may facilitate this procedure. The aim of this study was to describe the early use of intraoperative CT in orbital fractures repair in our center. The authors assessed the revision types and rates that have occurred with this technique. With the use of pre-surgical planning, optical intraoperative navigation, and intraoperative CT, the impact of intraoperative CT on the management of 5 cases involving a total number of 14 orbital wall fractures were described. There were 6 pure orbital blowout wall fractures reconstructed, involving both medial and inferior wall of the orbit fracturing the transition zone and 8 impure orbital wall fractures in orbitozygomaticomaxillary complex fracture. 4 patients underwent primary and 1 had delayed orbital reconstruction. Intraoperative CT resulted in intraoperative orbital implant revision, following final navigation planning position, in 40% (2/5) of patients or 14% (2/14) of the fractures. In revised cases, both implant repositioning was conducted at posterior ledge of orbit. Intraoperative CT confirmed true to original reconstruction of medial wall, inferior wall and transition zone of the orbit. Two selected cases were illustrated. In conclusion, intraoperative CT allows real-time assessment of fracture reduction and immediate orbital implant revision, especially at posterior ledge. As a result, no postoperative imaging was indicated in any of the patients. Long-term follow-ups for orbital fracture patients managed with intraoperative CT is suggested.

The small GTPase KRAS, which is frequently mutated in human cancers, must be localized to the plasma membrane (PM) for biological activity. We recently showed that the KRAS C-terminal membrane anchor exhibits exquisite lipid-binding specificity for select species of phosphatidylserine (PtdSer). We, therefore, investigated whether reducing PM PtdSer content is sufficient to abrogate KRAS oncogenesis. Oxysterol-related binding proteins ORP5 and ORP8 exchange PtdSer synthesized in the ER for phosphatidyl-4-phosphate synthesized in the PM. We show that depletion of ORP5 or ORP8 reduced PM PtdSer levels, resulting in extensive mislocalization of KRAS from the PM. Concordantly, ORP5 or ORP8 depletion significantly reduced proliferation and anchorage-independent growth of multiple KRAS-dependent cancer cell lines, and attenuated KRAS signaling in vivo. Similarly, functionally inhibiting ORP5 and ORP8 by inhibiting PI4KIIIα-mediated synthesis of phosphatidyl-4-phosphate at the PM selectively inhibited the growth of KRAS-dependent cancer cell lines over normal cells. Inhibiting KRAS function through regulating PM lipid PtdSer content may represent a viable strategy for KRAS-driven cancers., (© 2019 Kattan et al.)

Objective: To identify the risk factors of perioperative complications after radical gastrectomy for gastric cancer. Methods: A retrospective case-control study was performed. Case inclusion criteria: (1) patients undergoing radical gastrectomy (D2); (2) primary gastric cancer without distant organ metastasis confirmed by postoperative pathology; (3) no neoadjuvant chemotherapy before surgery. Patients with peritoneal tumor dissemination found during operation, undergoing palliative operation due to distant metastasis, and undergoing combined organ resection and those without complete clinicopathological data were excluded. According to the above criteria, 426 patients with gastric cancer at our department from January 2015 to June 2017 were included in this study. Of 426 patients, 285 were male and 141 were female with a mean age of (55.4±9.7) years. According to the "Japan Clinical Cancer Research Group (JCOG) classification criteria for postoperative complications of gastric cancer", patients with grade II and higher complications were classified as complication group, and patients with no complication or grade I complication were classified as non-complication group. Baseline data were compared between two groups. Associations of perioperative complication with gender, age, body mass index, preoperative routine laboratory test, American Society of Anesthesiologists (ASA) classification, activities of daily living (ADL) assessment, past medical history as well as preoperative conditions (hypertension and/or diabetes), surgical resection procedure, incision type, operation time, intraoperative blood loss/body mass ratio were examined. Univariate analysis was performed using χ(2) test and the Wilcoxon rank sum test to screen the statistically significant variables associated with perioperative complications. The significant variables were included in multivariate logistic regression analysis to identify risk factors of perioperative complication. Results: Grade II or higher complications after surgery were developed in 97 patients (22.8%), which included anastomotic leakage in 18 cases (4.2%), postoperative bleeding in 9 cases (2.1%), abdominal abscess in 5 cases (1.2%), intestinal obstruction in 5 cases (1.2%), pancreatic leakage in 1 case (0.2%), and other adverse events in 59 cases (13.8%). Univariate analysis suggested that the gender, age, ADL, incision type, intraoperative blood loss/body mass ratio, and operation time were associated with perioperative complication (all P <0.05). Multivariate analysis revealed that elder age (OR=1.033, 95% CI:1.013-1.053, P =0.013), incision type of laparotomy (OR=2.091, 95% CI:1.247-3.508, P =0.004), longer operation time (OR=1.004, 95% CI:1.001-1.007, P =0.001) and higher ratio of intraoperative blood loss/body mass (OR=1.100, 95% CI: 1.039-1.163, P =0.031) were risk factors for postoperative complications. Conclusion: Attention should be paid to those cases with elder age, laparotomy incision, longer operation time and higher ratio of intraoperative blood loss/body mass, and perioperative management after gastrectomy should be improved.

Introduction: Alzheimer's disease is associated with a higher mortality rate after the diagnosis. We hypothesized that patients with Alzheimer's disease who received antidementia drugs may have a lower mortality rate than those without such treatment., Methods: Patients with newly diagnosed Alzheimer's disease aged ⩾65 years during 2001-2006 were identified in the National Health Institute Research Database, Taiwan. We included patients with Alzheimer's disease who received antidementia drugs as the exposure group (ADD group), and compared them with a non-exposure group who did not receive any antidementia drugs (non-ADD group) matched for age at the index date, gender and Charlson Comorbidity Index score before the index date. All-cause mortality rates and Charlson Comorbidity Index scores at one and two years after the index date were compared between the ADD and non-ADD groups., Results: There were 529 patients in non-ADD group and 529 in the ADD group. The mortality rate was significantly lower in the ADD group compared with the non-ADD group (42% versus 58.6%; p <0.0001)., Conclusion: Our results suggest that antidementia drugs may have a protective effect against mortality in patients with Alzheimer's disease.

The aim of this study is to determine the minimum required thickness of a monolithic zirconia crown in the mandibular posterior area for patients with bruxism. Forty-nine full zirconia crowns, with seven different occlusal thicknesses of 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, and 1.0 mm, were made by using a computer-aided design/computer-aided manufacturing system (CAD/CAM). Seven crowns in each group were subjected to cyclic loading at 800 N and 5 Hz in a servohydraulic testing machine until fracture or completion of 100,000 cycles. Seven finite element models comprising seven different occlusal thicknesses of 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, and 1.0 mm were simulated using three different loads of vertical 800 N, oblique 10 degrees 800 N, and vertical 800 N + x N torque (x = 10, 50, and 100). The results of cyclic loading tests showed that the fracture resistance of the crown was positively associated with thickness. Specimen breakage differed significantly according to the different thicknesses of the prostheses ( p < 0.01). Lowest von Mises stress values were determined for prostheses with a minimal thickness of 1.0 mm in different loading directions and with different forces. Zirconia specimens of 1.0 mm thickness had the lowest stress values and high fracture resistance and under 800 N of loading.

The fat mass and obesity-associated ( FTO ) gene is a significant genetic contributor to polygenic obesity. We investigated whether physical activity (PA) modulates the effect of FTO rs3751812 on body mass index (BMI) among Taiwanese adults. Analytic samples included 10,853 Taiwan biobank participants. Association of the single-nucleotide polymorphism (SNP) with BMI was assessed using linear regression models. Physical activity was defined as any kind of exercise lasting 30 min each session, at least three times a week. Participants with heterozygous (TG) and homozygous (TT) genotypes had higher BMI compared to those with wild-type (GG) genotypes. The β value was 0.381( p < 0.0001) for TG individuals and 0.684 ( p = 0.0204) for TT individuals. There was a significant dose-response effect among carriers of different risk alleles ( p trend <0.0001). Active individuals had lower BMI than their inactive counterparts (β = -0.389, p < 0.0001). Among the active individuals, significant associations were found only with the TG genotype (β = 0.360, p = 0.0032). Inactive individuals with TG and TT genotypes had increased levels of BMI compared to those with GG genotypes: Their β values were 0.381 ( p = 0.0021) and 0.950 ( p = 0.0188), respectively. There was an interaction between the three genotypes, physical inactivity, and BMI ( p trend  = 0.0002). Our data indicated that increased BMI owing to genetic susceptibility by FTO rs3751812 may be reduced by physical activity.

The purpose of this study was to investigate the restorative role of low-intensity pulsed ultrasound (LIPUS) against lipopolysaccharide (LPS)-induced neuroinflammation and memory impairments in a simulation of Alzheimer's disease. Mice subjected to LPS administration (250 μg/kg, i.p.) were treated with LIPUS daily for 7 days. The levels of brain-derived neurotrophic factor (BDNF) and inflammatory markers were estimated in brain tissue using western blot. After LIPUS treatment, the neuroprotective effects of LIPUS in mice were assessed by behavioral tests. LPS plus LIPUS-treated mice exhibited a significant increase in the average time spent in the target quadrant compared to the LPS-treated group. Compared with the LPS-treated group, LPS plus LIPUS-treated mice revealed a preference for the novel object. LIPUS treatment significantly attenuated LPS-induced increases in the expression of amyloid-beta (Aβ) and amyloid precursor protein (APP) in the hippocampus region of LPS-treated mice. Furthermore, LIPUS significantly reduced the protein levels of TNF-α, IL-1β, and IL-6 in the mice brain induced by LPS. LIPUS treatment induces neuroprotection by inhibiting the LPS-induced activation of TLR4/NF-κB inflammatory signaling and by enhancing the associated CREB/BDNF expression in LPS-treated mice. Our data showed that LIPUS attenuated LPS-induced memory impairment as well as amyloidogenesis via the suppression of neuroinflammatory activity and BDNF decline., (© The Author(s) 2018. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: Intelligent decision support systems (IDSS) have been applied to tasks of disease management. Deep neural networks (DNNs) are artificial intelligent techniques to achieve high modeling power. The application of DNNs to large-scale data for estimating stroke risk needs to be assessed and validated. This study aims to apply a DNN for deriving a stroke predictive model using a big electronic health record database., Methods and Results: The Taiwan National Health Insurance Research Database was used to conduct a retrospective population-based study. The database was divided into one development dataset for model training (~70% of total patients for training and ~10% for parameter tuning) and two testing datasets (each ~10%). A total of 11,192,916 claim records from 840,487 patients were used. The primary outcome was defined as any ischemic stroke in inpatient records within 3 years after study enrollment. The DNN was evaluated using the area under the receiver operating characteristic curve (AUC or c-statistic). The development dataset included 672,214 patients (a total of 8,952,000 records) of whom 2,060 patients had stroke events. The mean age of the population was 35.5±20.2 years, with 48.5% men. The model achieved AUC values of 0.920 (95% confidence interval [CI], 0.908-0.932) in testing dataset 1 and 0.925 (95% CI, 0.914-0.937) in testing dataset 2. Under a high sensitivity operating point, the sensitivity and specificity were 92.5% and 79.8% for testing dataset 1; 91.8% and 79.9% for testing dataset 2. Under a high specificity operating point, the sensitivity and specificity were 80.3% and 87.5% for testing dataset 1; 83.7% and 87.5% for testing dataset 2. The DNN model maintained high predictability 5 years after being developed. The model achieved similar performance to other clinical risk assessment scores., Conclusions: Using a DNN algorithm on this large electronic health record database is capable of obtaining a high performing model for assessment of ischemic stroke risk. Further research is needed to determine whether such a DNN-based IDSS could lead to an improvement in clinical practice., Competing Interests: The authors have declared that no competing interests exist.

Background: To investigate boosting effects on treatment stabilization in the mandatory treatment modality for patients of amphetamine-type stimulant use disorder., Methods: This is a retrospective follow-up study over a period from January 2013 to December 2018. We analyzed 425 patients of amphetamine-type stimulant use disorder under mandating treatments. Treatment stabilization for a given patient was defined once 4 negative urinalysis had been observed. We developed a dynamic monitoring model of boosting effects informed by the available data, specifically the number of negative urine samples required to reach stabilization, the sum of urinalyses done at the time when the given number of negative urine samples had been observed and who the patient was. To represent the simulated population, a Monte Carlo method was used to generate p-values from 1000 experiments conducted on a computer., Results: In the observed samples, the probability of 4 negative results in urinalysis from 4 outpatient visits was 75.5%. In comparison, the probability for achieving 4th negative results in urinalysis over 4 visits from negative binominal distribution was 57.3%, and from the computer simulation, 49.8%. The observed samples had significantly higher probability of achieving 4 negative results in urinalysis over 4 outpatient visits (p < 0.001)., Conclusions: The mandatory treatment modality boosted treatment stabilization for patients of amphetamine-type stimulant use disorder. The major benefit of using the monitoring model is the ability to monitor boosting effects of stabilization. Results supported the effectiveness of this mandatory treatment modality and can be implemented in deferred-prosecution based treatment modality., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: The effectiveness of varenicline compared with nicotine replacement therapy (NRT) in achieving smoking cessation in older smokers has not been investigated. This study prospectively compared the effectiveness of varenicline relative to NRT in smokers aged 25-54 years and separately in smokers aged 55 years or older., Methods: Among 13 397 smokers participating in the Smoking Cessation Program in Taiwan, 2012-2015, 6336 (19.2%, aged ≥55) received varenicline and 7061 received NRT patch or gum (23.2%, aged ≥55). Participants self-reported smoking behaviors by phone interview after 6 months. Logistic regression models estimated odds ratios (ORs) and 95% confidence intervals (CIs) for 7-day, 1-month, and 6-month point-prevalence abstinence. Age-specific models adjusted for sex, education, marital status, smoke-years, nicotine dependence, medical institution, clinic visit number, and duration of medication received., Results: Among smokers aged 25-54 years, varenicline users had a greater point-prevalence abstinence than NRT users (e.g., 7-day point-prevalence: 34.0% vs. 23.5%), with adjusted OR ranging from 1.23 (CI: 1.09-1.39; 6-month point-prevalence) to 1.37 (CI: 1.24-1.50; 1-month point-prevalence). Among smokers aged 55 years or older, point-prevalence was similar for varenicline and NRT users (e.g., 7-day point-prevalence: 32.3% vs. 33.1%), and ORs did not suggest that varenicline has greater effectiveness than NRT. Sex and level of nicotine dependence did not modify the age-specific effectiveness of varenicline relative to NRT., Conclusions: Varenicline did not offer greater effectiveness in achieving abstinence than NRT for smokers 55 years or older, whereas it was more effective than NRT in smokers aged 25-54 years. These findings highlighted the need for age-specific approaches for effective tobacco control., Implications: In this prospective investigation of a national cohort, older smokers (aged ≥55 years) who received varenicline did not have a greater point-prevalence abstinence after 6 months compared with those who used NRT patch or gum. Younger smokers (aged 25-54 years) who received varenicline had a greater likelihood of abstinence than NRT users. Sex and nicotine dependence did not modify the age-specific effectiveness of varenicline relative to NRT patch or gum. Age-appropriate approaches for effective tobacco control are needed.

Background: In Taiwan, the causes of death and related factors in the oldest old people with Alzheimer disease (AD) are not well characterized. We investigated the factors associated with mortality in the oldest old patients with newly diagnosed AD admitted to a long-stay residential facility., Methods: We performed a prospective study of newly diagnosed AD patients at a veterans' home between 2012 and 2016. At admission, all eligible participants received a comprehensive geriatric assessment, including demographic variables, lifestyle habits, cognitive evaluations, medical conditions (comorbidities, Age-Adjusted Charlson Comorbidity Index score, and polypharmacy), nutritional status evaluated by the Mini Nutritional Assessment-Short Form and body mass index (BMI), and global functional status. A Cox proportional hazards model was used to evaluate the predictive values of clinical parameters for all-cause mortality., Results: The cohort comprised 84 newly diagnosed AD patients (mean age 86.6 ± 3.9 years) with a mean follow-up period of 2.1 ± 1.2 years. The overall median survival was 3.5 years from the time of AD diagnosis (95% confidence interval, 3.1-3.9 years). BMI was significantly lower in the deceased group than in the alive group (20.7 ± 2.9 vs. 22.6 ± 3.4, p = 0.023). Logistic regression demonstrated that the clinical parameters significantly associated with mortality were high global comorbidity, low nutritional status (malnutrition and underweight), and impaired physical function at the time of AD diagnosis., Conclusion: Comorbidity burden, nutritional status, and physical functional status at the time of dementia diagnosis are important contributors to poor outcome in the oldest old. Efforts to control concurrent chronic disorders, nutritional interventions, and physical independency as a long-term care strategy for dementia may provide survival benefit., (© 2019 S. Karger AG, Basel.)

Objective: The purpose of this study was to identify the association between antipsychotics and mortality in Alzheimer's disease patients., Methods: Using the Taiwan National Health Insurance Research Database, 735 newly diagnosed Alzheimer's disease patients aged over 65 years and receiving antipsychotic treatments, and 735 age, sex, physical comorbidity, and entry year with propensity scores, matched control subjects were enrolled and followed for a 10-year period until the end of 2011. Multivariate Cox proportional hazards regression models were used for analysis., Results: The mortality rate was 56% in Alzheimer's disease patients treated with antipsychotics, and 65% in Alzheimer's disease patients not treated with antipsychotics during an average of 5.2 years of follow-up. The use of antipsychotics, typical antipsychotics, and atypical antipsychotics was found to be associated with lower mortality (adjusted hazard ratio=0.66, 95% confidence interval 0.58-0.75; 0.69, 0.60-0.79; 0.56, 0.44-0.71, respectively, all p<0.001). In addition, Alzheimer's disease patients with higher cumulative dose and longer duration of exposure to antipsychotics showed a significantly reduced risk of mortality. Other variables associated with higher risk of mortality included age (adjusted hazard ratio=1.08, 95% confidence interval 1.07-1.09, p<0.001), male gender (1.27, 1.11-1.45, p<0.001), diabetes mellitus (1.30, 1.10-1.54, p<0.01), congestive heart failure (1.54, 1.11-2.12, p<0.01), and stroke (1.23, 1.05-1.44, p<0.01)., Conclusion: The use of antipsychotics was found to be associated with lower mortality in Alzheimer's disease patients. Moreover, dose and duration response effects were also identified.

The purpose of this study was to assess the long-term treatment efficacy of low-intensity pulsed ultrasound (LIPUS) on functional outcomes, brain edema, and the possible involvement of reactions in mice following traumatic brain injury (TBI). Mice subjected to controlled cortical impact injury received LIPUS treatment daily for a period of 4 weeks. The effects of LIPUS on edema were detected by MR imaging in the mouse brain at 148 days following TBI. Long-term functional outcomes of LIPUS stimulation were evaluated by behavioral analyses. One-way or two-way analysis of variance and Student's t test were used for statistical analyses, with a significant level of .05. Up to post-injury day 148, treatment with LIPUS significantly improved functional outcomes (all p < 0.05). LIPUS also significantly attenuated brain edema and neuronal death at day 148 after TBI (all p < 0.05). Furthermore, LIPUS reduced MMP9 activity, neutrophil infiltration, and microglial activation at day 1 or day 4 following TBI (all p < 0.05). Meanwhile, LIPUS increased the Bcl-2/Bax ratio and enhanced the phosphorylation of Bad and FOXO-1 at day 1 or day 4 following TBI (all p < 0.05). Almost 5 months of follow-up showed that the treatment efficacy of post-injury LIPUS stimulation on reduced brain edema and improved functional outcomes persisted over time after TBI. The neuroprotective effects of LIPUS are associated with a reduction of early inflammatory events and inhibition of apoptotic progression.

Pulmonary arterial hypertension (PAH) is a chronic progressive disease which leads to elevated pulmonary arterial pressure and right heart failure. 3,7-Bis(2-hydroxyethyl)icaritin (ICT), an icariin derivatives, was reported to have potent inhibitory activity on phosphodiesterase type 5 (PDE5) which plays a crucial role in the pathogenesis of PAH. The present study was designed to investigate the effects of ICT on monocrotaline (MCT)-induced PAH rat model and reveal the underlying mechanism. MCT-induced PAH rat models were established with intragastric administration of ICT (10, 20, 40 mg/kg/d), Icariin (ICA) (40 mg/kg/d) and Sildenafil (25 mg/kg/d). The mean pulmonary arterial pressure (mPAP) and right ventricle hypertrophy index (RVHI) were measured. Pulmonary artery remodeling was assessed by H&E staining. Blood and lung tissue were collected to evaluate the level of endothelin 1 (ET-1), nitric oxide (NO), and cyclic guanosine monophosphate (cGMP). The expressions endothelial nitric oxide synthase (eNOS) and PDE5A in lung tissues were determined by Western blot analysis. The results showed that ICT reduced RVHI and mPAP, and reversed lung vascular remodeling in rats with MCT-induced PAH. ICT also reversed MCT-induced ET-1 elevation, NO and cGMP reduction in serum or lung tissue. Moreover, ICT administration significantly induced eNOS activation and PDE5A inhibition. ICT with lower dose had better effects than ICA. In summary, ICT is more effective in preventing MCT-induced PAH in rats via NO/cGMP activation compared with ICA. These findings demonstrate a novel mechanism of the action of ICT that may have value in prevention of PAH., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Cardiovascular diseases (CVDs) have been recognized as first killer of human health. The underlying mechanisms of CVDs are extremely complicated and not fully revealed, leading to a challenge for CVDs treatment in modern medicine. Traditional Chinese medicine (TCM) characterized by multiple compounds and targets has shown its marked effects on CVDs therapy. However, system-level understanding of the molecular mechanisms is still ambiguous. In this study, a system pharmacology approach was developed to reveal the underlying molecular mechanisms of a clinically effective herb formula (Wen-Dan Decoction) in treating CVDs. 127 potential active compounds and their corresponding 283 direct targets were identified in Wen-Dan Decoction. The networks among active compounds, targets, and diseases were built to reveal the pharmacological mechanisms of Wen-Dan Decoction. A "CVDs pathway" consisted of several regulatory modules participating in therapeutic effects of Wen-Dan Decoction in CVDs. All the data demonstrates that Wen-Dan Decoction has multiscale beneficial activity in CVDs treatment, which provides a new way for uncovering the molecular mechanisms and new evidence for clinical application of Wen-Dan Decoction in cardiovascular disease.

Background: The aim of this study was to investigate whether use of mood stabilizers (MS) is associated with an increased risk of cataract development., Methods: We conducted a nested case-control study using National Health Insurance Research Database in Taiwan. A total of 14,288 patients with bipolar disorder (BD) and schizophrenia were included; 7651 in the cataract group and 6637 in the control group. Based on overall cumulative period of MS (lithium, carbamazepine, valproate, and lamotrigine) treatment, we categorized into following groups: no use, and duration < 1 year, 1 to 2 years, and > 2 years. Conditional logistic regression analysis was used to explore the association between use of MS and risk of cataract development., Results: The risks for cataract development were significantly higher in patients using lithium alone and lithium combined with other MS for more than 2 years (adjusted odd ratio [AOR] = 1.39; 95% CI = 1.01-1.92, p = 0.043 and AOR = 1.44; 95% CI = 1.13-1.85, p = 0.003, respectively) than in non-users. Furthermore, the risks of cataract development increased in those treated with valproic acid combined with other MS (AOR = 1.26; 95% CI = 1.02-1.57, p = 0.035). Finally, no increased risks of cataract development were found in carbamazepine and lamotrigine users., Conclusions: We found increased risks of cataract development in long-term users of lithium, lithium combined with other MS and valproic acid combined with other MS for more than two years among patients with BD and schizophrenia., (Copyright © 2017 Elsevier B.V. All rights reserved.)

No study has investigated the effect of learning curves on the accuracy of dental implant navigation systems. This study evaluated the accuracy of the dental implant navigation system and established the learning curve according to operation site and operating time. Each dental model was used for drilling 3 missing tooth positions, and a patient tracking module was created. The same dentist performed the drilling test for 5 sets of dental models. CT back scanning was performed on the dental models. Customized implants based on the drilled holes were inserted. The relative error between the preoperative planning and actual implant was calculated. Using the dental navigation system could help dentists position implants more accurately. Increasing the frequency with which a dentist used the navigation system resulted in shorter operations. Longitudinal and angular deviation were significantly (P < 0.0001 and P = 0.0164). We found that the same level of accuracy could be obtained for the maxilla and mandible implants. The Student's t test demonstrated that the longitudinal error, but not the total or angular error, differed significantly (P = 0.0012). The learning curve for the dental implant navigation system exhibited a learning plateau after 5 tests. The current system exhibited similar accuracy for both maxillary and mandibular dental implants in different dental locations. The one-way ANOVA revealed that the total, longitudinal, and angular errors differed significantly (P < 0.0001, P < 0.0001 and P = 0.0153). In addition, it possesses high potential for future use in dental implant surgery and its learning curve can serve as a reference for dentists., (Copyright © 2017. Published by Elsevier Taiwan.)

Cleidocranial dysplasia (CCD) is an autosomal-dominant malformation syndrome affecting bones and teeth. The most common skeletal and dental abnormalities in affected individuals are hypoplastic/aplastic clavicles, open fontanelles, short stature, retention of primary teeth, delayed eruption of permanent teeth, supernumerary teeth, and multiple impacted teeth. Treatment of CCD requires a multidisciplinary approach that may include dental corrections, orthognathic surgery and cranioplasty along with management of any complications of CCD. Early diagnosis of this condition enables application of the treatment strategy that provides the best quality of life to such patients. Notably, Runx2 gene mutations have been identified in CCD patients. Therefore, further elucidation of the molecular mechanism of supernumerary teeth formation related to Runx2 mutations may improve understanding of dental development in CCD. The insights into CCD pathogenesis may assist in the development of new treatments for CCD.

Hyperhomocystinemia (HHcy) is known as an independent risk factor for cardiovascular disease. Our previous study showed that ginsenoside Rb1, the major active constituent of ginseng, prevents homocysteine (Hcy)-induced endothelial damage. However, the role of ginsenoside Rb1 in Hcy-induced dysfunction in endothelial progenitor cells (EPCs) remains unknown. In the study, we found that ginsenoside Rb1 reversed the Hcy-induced impairment of adhesive and migratory ability in EPCs which were significantly abolished by CXCR4 antagonist AMD3100 and VEGFR2 inhibitor SU5416. Ginsenoside Rb1 significantly reversed Hcy-induced SDF-1 reduction in the supernatant and in the serum. Ginsenoside Rb1 reversed downregulation of SDF-1 and VEGFR2 protein expression, inhibition of p38MAPK phosphorylation induced by Hcy. Re-endothelialization in balloon-injured carotid arteries significantly increased with EPCs transplant, and was even better with Rb1 treatment. This effect was significantly abolished by AMD3100. AMD3100 also decreased the number of CM-DiI labeled EPCs in injured arteries. Here we show for the first time that Rb1 prevents Hcy-induced EPC dysfunction via VEGF/p38MAPK and SDF-1/CXCR4 activation. These findings demonstrate a novel mechanism of the action of Rb1 that may have value in prevention of HHcy associated cardiovascular disease.

Objective: Exposure to selective serotonin reuptake inhibitors (SSRIs) has been shown to increase the risk of stroke. In this study, we investigated age and time effects on the risk of first onset stroke in SSRI-exposed (SSRIEXP) adult subjects., Methods: We analyzed an 8-year cohort from the National Health Insurance Research Database, Taiwan. Patients were defined as SSRIEXP subjects if they received SSRI prescriptions for at least 2 consecutive months during January 1, 2001, to December 31, 2007. Otherwise, they were categorized as SSRI-nonexposed (SSRINONE) subjects. Stroke diagnosis was made according to ICD-9 codes 430-432 (hemorrhagic stroke) and 433-437 (ischemic stroke)., Results: Kaplan-Meier survival analysis showed a greater probability of first onset stroke in SSRIEXP than SSRINONE subjects (P < .001). The higher incidence rates in SSRIEXP subjects persisted to the 3 year time point. Ischemic/hemorrhagic stroke cumulative incidence ratios were also higher during the first 3 years in SSRIEXP subjects. Analysis of adjusted hazard ratios indicated that younger SSRIEXP subjects were more likely to experience stroke, with a slight increase of risk in subjects older than 65 years. Stratified analysis of ischemic stroke and hemorrhagic stroke resulted in a similar hazard ratio trend., Conclusions: Use of SSRIs independently increases the risk of stroke across age strata. The risk is higher in younger adult subjects, and the stroke is more likely to be ischemic than hemorrhagic. The underlying mechanisms of stroke may be related to cerebral microbleeding or an overcorrection of hemostasis function., (© Copyright 2017 Physicians Postgraduate Press, Inc.)

Background: Students may adopt various approaches to academic learning. Occupational therapy students' approaches to study and the impact of cultural context have not been formally investigated to date., Aim: To examine the approaches to study adopted by undergraduate occupational therapy students from four different cultural settings., Method: 712 undergraduate occupational therapy students (n = 376 from Australia, n = 109 from Hong Kong, n = 160 from Norway and n = 67 from Singapore) completed the Approaches and Study Skills Inventory for Students (ASSIST). A one-way analysis of variance (ANOVA) was conducted to compare the ASSIST subscales for the students from the four countries., Results: Post-hoc comparisons using the Tukey HSD test indicated that the mean scores for the strategic approach were significantly different between Australia and the other three countries. The mean scores for the surface approach were significantly different between Australia and Hong Kong, and Hong Kong and Norway. There were no significant differences between the deep approach to studying between Australia, Norway, Singapore and Hong Kong., Conclusion & Implications: Culture and educational context do appear to impact the approaches to study adopted by undergraduate occupational therapy students. Academic and practice educators need to be cognizant of what approaches to studying the students they work with adopt.

Background: Previous studies demonstrated increased risk of cataract development among users of selective serotonin reuptake inhibitors (SSRIs). However, it remains unknown whether this risk also prevails with the use of other types of antidepressants. The aim of this study was to investigate whether use of antidepressants is associated with an increased risk of cataract development. Moreover, the relationship between binding affinities of serotonin transporter (SERT) of antidepressant and the risk of cataracts is examined., Methods: We conducted a nested case-control study using National Health Insurance Research Database in Taiwan. A total of 14,288 patients were included; 7651 in the cataract group and 6637 in the control group. Antidepressant exposure was categorized by type, duration of use, and binding affinities of SERT. The association between antidepressant exposure and cataract development was assessed using conditional logistic regression analysis., Results: The adjusted odds ratios (AORs) for developing cataracts among continuous users of SSRIs, serotonin norepinephrine reuptake inhibitors (SNRIs), and other antidepressants were 1.26 (95% confidence interval (CI): 1.12-1.41, p<0.001), 1.21 (95% CI: 1.02-1.43, p=0.027), and 1.18 (95% CI: 1.04-1.34, p=0.009) respectively. Specifically, continuous uses of fluoxetine (AOR: 1.21; 95% CI: 1.01-1.46, p=0.042), fluvoxamine (AOR: 1.47; 95% CI: 1.01-2.12, p=0.043), venlafaxine (AOR: 1.44; 95% CI: 1.19-1.74, p<0.001) significantly increased the risk of cataract development. Moreover, continuous users of antidepressants with intermediate SERT binding affinities (AOR: 1.68; 95% CI: 1.10-2.56, p=0.017) were significantly associated with increased risks of cataract development., Limitations: Several confounding factors such as obesity, multiple drug users, family history of cataracts, substance use, and environmental factors (such as sunlight or radiation exposure) were acquired., Conclusions: We found increased risk of cataract development in patients continuously using antidepressants. Regular ocular evaluations in these patients are warranted., (Copyright © 2017. Published by Elsevier B.V.)

To investigate the milling properties of different yttria-tetragonal zirconia polycrystalline (Y-TZP) block materials by applying a dental computer numerical control (CNC) milling center. Low temperature sintering zirconia block denoted by KMUZ (experimental) with two commercial zirconia blocks for T block made in Taiwan and a G block made in Germany were compared for the milling properties. Seventy-two specimens were milled using the same CNC milling center, and properties were evaluated by measuring the weight loss (g), milling time (s), margin integrity (%) and broken diameter (μm). The crystalline phases contents were identified by X-ray diffraction and the microstructures of the sintering specimens were observed by scanning electron microscopy and transmission electron microscopy. The mean milling time of G and KMUZ were significantly shorter than T (P<0.05). The KMUZ samples exhibited the least weight loss among the three kinds of blocks (P<0.05). The percentages of marginal integrity after milling were high in G and KMUZ but low in T (P<0.05). The mean broken diameters were from 90μm to 120μm. The phase transformation of t-ZrO 2 (KMUZ: 7.4%, G: 5.9%, T: 3.2%) to m-ZrO 2 when facing the milling pressure in ZrO 2 blocks was observed by XRD. The result of TEM microstructure of KMUZ revealed that Y and Si were soluble in grain boundaries. The results show that the milling properties of KMUZ were better than one commercial T and near the G. The hindered grain growth, as a result of the Y 3+ content in the grain boundaries, also plays a role in promoting the abnormal grain growth of 3Y-TZP., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The neurology of male sexuality has been poorly studied owing to difficulties in studying brain circuitry in humans. Dopamine (DA) is essential for both physiological and behavioural responses, including the regulation of sexuality. Previous studies have revealed that alterations in DA synthesis in dopaminergic neurons can induce male-male courtship behaviour, while increasing DA levels in the protocerebral posteriolateral dopaminergic cluster neuron 2ab (PPL2ab) may enhance the intensity of male courtship sustainment in Drosophila. Here we report that changes in the ability of the PPL2ab in the central nervous system (CNS) to produce DA strongly impact male-male courtship in D. melanogaster. Intriguingly, the DA-synthesizing abilities of these neurons appear to affect both the courting activities displayed by male flies and the sex appeal of male flies for other male flies. Moreover, the observed male-male courtship is triggered primarily by target motion, yet chemical cues can replace visual input under dark conditions. This is interesting evidence that courtship responses in male individuals are controlled by PPL2ab neurons in the CNS. Our study provides insight for subsequent studies focusing on sexual circuit modulation by PPL2ab neurons.

Background: No previous study has focused on the association between use of antipsychotic drugs and the development of cataracts in patients with bipolar disorder (BD); hence, we aimed to examine this association in the present study., Methods: We conducted a retrospective nested case-control study using data from the National Health Insurance Database of Taiwan between 2000 and 2011. A total of 3292 BD patients, 1684 with cataracts and 1608 controls matched for age, sex, and index date, were included. Antipsychotic drug exposure was categorized by type of drug and duration of use. A conditional logistic regression analysis was used to analyze the association., Results: Among BD patients, we found significantly reduced odds ratio (OR) of cataract development among past (adjusted OR (AOR), 0.74; 95% confidence interval (CI), 0.62-0.89; p=0.001) and continuous users (AOR, 0.71; 95% CI, 0.59-0.85; p<0.001) of atypical antipsychotics. No association was found between the odds of cataract development and typical antipsychotics. Besides, concomitant use of antidepressants (AOR, 1.23; 95% CI, 1.06-1.43; p=0.007) and mood stabilizers (AOR, 1.23; 95% CI, 1.06-1.42; p=0.007) were associated with increased odds of cataract development., Limitations: Some important contributors to cataract development such as family history of cataract, smoking and alcohol exposure could not be measured from the claims data and this may confound the results., Conclusions: Reduced odds of cataract were found in patients with BD taking atypical antipsychotics. However, given that BD patients often have risk factors for developing cataract, regular ocular evaluations are recommended for those treated with antipsychotics drugs., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Many studies have investigated whether a type of antipsychotics or type of adjuvant is associated with smoking reduction in patients with schizophrenia. However, there has been no study exploring a comprehensive range of factors related to smoking reduction in schizophrenia patients. We analyzed a dataset of 287 smoking patients with schizophrenia who participated in an 8-week open-label study with high- (n = 90) or low-dose nicotine dermal patches (n = 132) or bupropion (n = 65). A logistic regression model and a linear mixed model were used to explore factors associated with the outcomes of smoking cessation and reduction, i.e., the number of cigarettes smoked and the level of nicotine dependence. The total cessation rate was 6.3 % (18/287). There were no significant predictors of cessation. The time effect of reduction was significant during the program (p = 0.001). Type of antipsychotics (p = 0.018), readiness to quit (p = 0.014), baseline number of cigarettes smoked per day (p = 0.001), and nicotine dependence level (p = 0.001) were significantly associated with smoking reduction. Patients on first-generation antipsychotics (n = 129) or clozapine (n = 70) reduced their smoking more than those on non-clozapine second-generation antipsychotics (n = 74). Patients in the preparation stage (n = 97) or in the contemplation (n = 70) reduced their smoking more than those in the precontemplation stage (n = 120). The mechanisms of tobacco addiction need to be better understood for further development of effective cessation programs in patients with schizophrenia.

Objective: Current evidence for the association between use of lithium and risk of dementia is mixed. The objective of this study was to assess the risk of Alzheimer's disease associated with use of lithium., Methods: A population-based, nested case-control study was conducted using data from the National Health Insurance Research Database in 2002 covering 24.5 million beneficiaries of the Taiwan National Health Insurance Program from January 1, 1997, to December 31, 2009. A total of 2,548,625 older people were included in the study cohort. We analyzed 63,347 cases of Alzheimer's disease (ICD-9-CM codes 290.0-290.3, and 331.0) and 2 controls per case matched by age, sex, and index date (the date of the first AD claim). Conditional logistic regression was performed, adjusting for health care utilization, use of other common mood stabilizers (valproic acid and carbamazepine), hypothyroidism, type 2 diabetes, hypertension, hyperlipidemia, chronic kidney disease, epilepsy, schizophrenia, and bipolar disorder., Results: We identified 63,347 cases with Alzheimer's disease and 126,694 controls. The adjusted odds ratio (aOR) of Alzheimer's disease risk with lithium use was 1.79 (95% confidence interval [CI], 1.34-2.38) in the general population. However, when we restricted the analyses to patients with bipolar disorder to minimize potential confounding by indication, lithium was not associated with Alzheimer's disease risk (aOR = 1.36; 95% CI, 0.89-2.09), and there were no apparent trends of greater risk with increasing duration or dose., Conclusions: These findings do not support an increased or decreased risk of lithium use with Alzheimer's disease when taking into account potential confounding by indication. Further investigations of the effect of lithium with dementia need to consider the influence of confounding by indication., (© Copyright 2016 Physicians Postgraduate Press, Inc.)

Despite an increasing number of reports on the associations between chronic occupational stress and structural and functional changes of the brain, the underlying neural correlates of perceived occupational stress is still not clear. Perceived stress reflects the extents to which situations are appraised as stressful at a given point in one's life. Using near-infrared spectroscopy, we investigated the associations between perceived occupational stress and cortical activity over the bilateral frontotemporal regions during a verbal fluency test. Sixty-eight participants (17 men, 51 women), 20-62 years of age were recruited. Perceived occupational stress was measured using the Chinese version of Job Content Questionnaire, and the Chinese version of the Copenhagen Burnout Inventory. We found statistically significant negative associations between occupational burnout and brain cortical activity over the fronto-polar and dorsolateral prefrontal cortex during the VFT (r = -0.343 to -0.464). In conclusion, our research demonstrated a possible neural basis of perceived occupational stress that are distributed across the prefrontal cortex.

Objectives: The new International Association of Diabetes and Pregnancy Study Groups (IADPSG) recommendations for diagnosis of gestational diabetes mellitus (GDM) are generating discussion regarding their universal adoption. Our centre is currently using stricter GDM diagnostic criteria than those proposed by the IADPSG. Evaluation of complication rates and their predictors in our cohort may provide insight for the care of this high-risk population. Therefore, we determined complication rates and identified antepartum maternal predictors of adverse outcomes in our cohort with mild GDM., Methods: A retrospective cohort study was performed between 2005 and 2011. It included women with and without GDM, which was diagnosed if fasting plasma glucose levels were 5.0 or above or 2-hour post 75 gram oral glucose tolerance test (OGTT) were 7.8 mmol/L or higher., Results: A total of 3712 women, with and without diabetes, were included. Rates of macrosomia and pre-eclampsia were significantly higher in the group with GDM but were lower than the rates usually reported. Macrosomia, the need for insulin therapy or caesarean section and postpartum glucose intolerance predictors included prepregnancy body mass index, excessive gestational weight gain and OGTT screening results, although no specific threshold was found., Conclusions: This study provides insight into GDM-related complications rates and the benefits of intervention in a large cohort of women with levels of hyperglycemia lower than those currently recommended for diagnosis of GDM. These findings suggest a continuous association between adverse outcomes and maternal hyperglycemia and highlight the important role of maternal risk factors other than glycemic results in the development of pregnancy-related complications. Milder forms of hyperglycemia that would not be identified by IADPSG guidelines may benefit from treatment., (Copyright © 2016 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.)

Background: Previous research has suggested a link between antidepressants use and the development of cerebrovascular events, but there has never been any study investigating the risk of stroke in obsessive-compulsive disorder (OCD) patients treated with a selective serotonin reuptake inhibitor (SSRI)., Methods: A retrospective observational cohort study was conducted using data from the National Health Insurance Database of Taiwan between the year of 2001 and 2009. A total of 527 OCD patients with 412 subjects in the SSRI use group and 115 in the non SSRI use group were included. Multivariable Cox proportional-hazards models were used to explore the associations between SSRI use and the occurrence of stroke, controlling for age, gender, concomitant medications, and comorbid medical illnesses., Results: A total of nineteen OCD patients were diagnosed with new onset of stroke during the follow-up period including six cases in the SSRI group and thirteen in the non SSRI use group. SSRI use was demonstrated to be associated with a decreased risk of stroke (hazard ratio [HR] = 0.30; 95% confidence interval [CI] = 0.10-0.86, P = 0.02). The increase in age-related risk of strokes was 2.55 per decade (HR = 2.55; 95% CI = 1.74-3.75, P<0.001). Alternatively, sex, concomitant use of aspirin and non-steroidal anti-inflammatory drugs, and comorbidities with angina pectoris, diabetes mellitus, hypertension, and hyperlipidemia were not found to be associated with an increased risk for stroke in OCD patients., Conclusions: Our study showed that SSRI use was associated with decreased risk of stroke in OCD patients. Further investigation into the possible biological mechanisms underlying the relationship between stroke and SSRI use in OCD patients is warranted., Competing Interests: All authors declared no conflicts of interest regarding this study.

Objective: Previous research has suggested a link between typical antipsychotic use and the development of cataracts, but the association between atypical antipsychotics and cataracts remains unclear in schizophrenia (SZ)., Methods: A retrospective nested case-control study was conducted using data from the National Health Insurance Database of Taiwan between the year of 2000 and 2011. A total of 2144 SZ patients with cataracts and 2222 controls matched for age, sex, and index date were included. Antipsychotic exposure was categorized by type and duration, and the association between antipsychotic exposure and cataract development was assessed using a conditional logistic regression analysis., Results: We found that the severity of physical comorbidities, concurrent antidepressant use, and comorbidity with glaucoma or other retinal disorders were associated with an increased risk for cataract development. Alternatively, we did not find significant associations between continuous use of clozapine, risperidone, paliperidone, ziprasidone, olanzapine, quetiapine, amisulpride, zotepine or aripiprazole and risk of cataract development in SZ patients., Conclusions: We did not detect any association between atypical antipsychotic use and risk of cataract development in SZ patients. Future studies with longitudinal ocular evaluations in patients using atypical antipsychotics are warranted to confirm our findings., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: The suicide rate is high among bipolar disorder (BD) patients. Previous studies have focused on the anti-suicidal effect of long-term treatment with mood stabilizers but less on the immediate preventive effects of interventions. The aim of the study was to evaluate the short-term and immediate anti-suicidal effects of mood stabilizers on recent-onset BD patients., Methods: The National Health Insurance Database (NHID) of Taiwan was used to perform a nationwide cohort observation study of suicide behaviors in bipolar disorder. All the recent-onset BD patients (ICD-9-CM code 296 except 296.2 and 296.3) diagnosed between 2000-2005 were collected (n=5091) and followed through 2009. The primary endpoint was the presence of a suicide code or the end of observation; exposure to mood stabilizers in the final month of observation was the independent variable., Results: The hazard ratios (HRs) of suicide-related events, completed suicide, and all-cause mortality were significantly lower for those treated with lithium, divalproex, or carbamazepine compared with no use in the last month (HRs of suicide-related events were 0.10, 0.14 and 0.10, respectively, and all-cause mortality HRs were 0.03; P<0.0001); there was no significant difference in HR between the mood stabilizers., Limitations: The NIHD does not provide information on the severity, mood status, or treatment adherence of BD patients. Neither substance-related disorder nor personality disorder were included in the analysis. We focused on the effect of the final prescription time period, not the long-term protective effect., Conclusions: The immediate recent use of any mood stabilizer significantly lowers the rate of death, suicide, or suicidal behavior in BD., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Many studies discuss factors related to the decision-making capacity to consent to clinical research (DMC) of patients with schizophrenia. However, these studies rarely approached willingness to participate and the association between psychopharmacological properties (e.g., antipsychotic-induced side effects) and DMC. This study aimed to explore factors related to DMC and willingness to participate in patients with schizophrenia. All 139 patients with schizophrenia were assessed with the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR) and other measures. A linear regression model was used to find the predictors of MacCAT-CR scores. A logistic regression model was used for exploring the predictors of willingness to participate. Patients with more severe negative symptoms performed poorly in DMC outcomes. In addition, females, those with fewer years of education and reduced cognitive function are more likely to experience difficulties in decision-making. Forty-three subjects (30.4%) chose to participate. Patients with higher level of positive symptoms, longer length of stay, higher burden of anticholinergics and users of atypical antipsychotics were more likely to participate in a clinical study which aimed to "enhance cognition". These finding suggest that research investigators should consider many variables for patients who require more intensive screening for impaired DMC., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

We report a 78-year-old man without past psychiatric history who experienced his first manic episode successfully treated with quetiapine and lorazepam, but was ultimately found to have AIDS and Cryptococcus neoformans meningitis. Our presented case highlights the importance of comprehensive differential diagnoses to rule out secondary causes of psychiatric symptoms presenting for the first time in elderly patients., (© 2015 The Authors. Psychogeriatrics © 2015 Japanese Psychogeriatric Society.)

Statement of Problem: The use of monolithic zirconia crowns in implant prostheses is increasing, especially when the interdental space is insufficient. However, fractures have been reported in clinical practice., Purpose: The purpose of this study was to determine the minimal thickness of a complete zirconia crown used for an implant prosthesis in the posterior dental region., Material and Methods: Fifty complete zirconia crowns were produced using a computer-aided design/computer-aided manufacturing technique. In each group, 5 crowns of varying thicknesses (0.4, 0.5, 0.6, 0.7, and 0.8 mm) were subjected to cycles of vertical and 10-degree oblique compressive loading at 5 Hz and 300 N in a servohydraulic testing machine. Five finite element models comprising 5 different occlusal thicknesses (0.4, 0.5, 0.6, 0.7, and 0.8 mm) were simulated at 2 loading angles (0 and 10 degrees) and 3 loading forces (300, 500, and 800 N). Data were statistically analyzed, and fracture patterns were observed with a scanning electron microscope., Results: Cyclic loading tests revealed that the fracture resistance of the specimens was positively associated with prosthesis thickness (P<.01). Low von Mises stress values were obtained for prostheses with a minimal thickness of 0.7 mm under varying loading directions and forces., Conclusions: Zirconia prostheses with a minimal thickness of 0.7 mm had a high fracture resistance and the lowest stress values. Therefore, dentists and laboratory technicians should carefully choose the optimum thickness of zirconia prostheses., (Copyright © 2016 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

Background: Sleep disorders, especially chronic insomnia, have become major health problem worldwide and, as a result, the use of hypnotics is steadily increasing. However, few studies with a large sample size and long-term observation have been conducted to investigate the relationship between specific hypnotics and mortality., Methods: We conducted this retrospective cohort study using data from the National Health Insurance Research Database in Taiwan. Information from claims data including basic characteristics, the use of hypnotics, and survival from 2000 to 2009 for 1,320,322 individuals were included. The use of hypnotics was divided into groups using the defined daily dose and the cumulative length of use. Hazard ratios (HRs) were calculated from a Cox proportional hazards model, with two different matching techniques to examine the associations., Results: Compared to the non-users, both users of benzodiazepines (HR = 1.81; 95% confidence interval [CI] = 1.78-1.85) and mixed users (HR = 1.44; 95% CI = 1.42-1.47) had a higher risk of death, whereas the users of other non-benzodiazepines users showed no differences. Zolpidem users (HR = 0.73; 95% CI = 0.71-0.75) exhibited a lower risk of mortality in the adjusted models. This pattern remained similar in both matching techniques. Secondary analysis indicated that zolpidem users had a reduced risk of major cause-specific mortality except cancer, and that this protective effect was dose-responsive, with those using for more than 1 year having the lowest risk., Conclusions: The effects of different types of hypnotics on mortality were diverse in this large cohort with long-term follow-up based on representative claims data in Taiwan. The use of zolpidem was associated with a reduced risk of mortality.

In this prospective study, we investigated the effects of antidepressant therapy on total antioxidant capacity and free radical levels in patients with major depressive disorder (MDD). We recruited thirty-five first-episode patients who met the criteria of the Fourth Edition of Diagnostic and Statistical Manual of Mental Disorders of MDD and 35 age- and sex-matched healthy controls. Superoxide and hydroxyl radicals were measured to investigate oxidative status and the total radical-trapping antioxidant parameter (TRAP) assay was performed to evaluate antioxidant capacity in healthy controls and in patients before and after receiving a 12-week regimen of sertraline. The severity of depression was evaluated using the 17-item Hamilton Depression Rating Scale (HDRS). Before treatment, the mean HDRS score in patients with MDD was 26.11±4.93. Of the 35 patients with MDD, 19 (54.29%) completed the 12-week treatment regimen and all achieved remission. Patients with MDD had significantly lower TRAP baseline values than healthy controls. After adjusting for age, sex, occupation, education and marital status, we found that HDRS score was negatively correlated with TRAP value and level of superoxide radicals. After treatment, the MDD group demonstrated significantly higher TRAP values and significantly lower levels of superoxide and hydroxyl radicals. In conclusion, MDD patients are accompanied by lowered antioxidant capacity than healthy individuals. Antidepressant treatment for 12 weeks results in increased antioxidant capacity and a decrease in circulating free radicals., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

A longer duration of untreated psychosis (DUP) has been associated with poor clinical outcomes in patients with schizophrenia (SZ); however, it remains unclear whether this is due to neurotoxic effects of psychosis. The purpose of this study was to use near-infrared spectroscopy (NIRS) to investigate the influence of DUP on brain function using two verbal fluency tests (VFTs) in patients with first-episode SZ (FES). A total of 28 FES patients and 29 healthy controls (HC) underwent NIRS during VFTs. Group comparisons of cortical activity were made using two-tailed t-tests and the false discovery rate method. We then examined the associations between DUP and hemodynamic changes in each channel to identify any effects of DUP on brain cortical activity. During the letter VFT, the HC group exhibited significantly greater cortical activations over bilateral frontotemporal regions compared to FES patients. However, this distinction was not observed while performing a category version of the VFT. In addition, no associations between DUP and brain cortical activity were observed in the FES group during either VFT. In conclusion, we did not find an association between DUP and frontotemporal cortical activities. This might be because neurodevelopmental disturbances result in neurocognitive deficits long before psychotic symptoms onset.

Objectives: The risk of stroke is increased in patients with bipolar disorder. Lithium exhibits neuroprotective effects but the association between lithium use and the risk of stroke is unknown., Methods: A population-based retrospective cohort study was conducted by utilizing the National Health Insurance Research Database in Taiwan. Subjects who had first been diagnosed with bipolar disorder between 2001 and 2006 were identified. A propensity score (PS) for receiving lithium was calculated with variables of age, gender, and comorbidities. The patients with bipolar disorder receiving lithium within the period from diagnosis through to December 2011 were designated as the lithium group (n = 635). A 1:2 ratio was used to select PS-matched subjects with bipolar disorder without lithium use (n = 1,250). Multivariate Cox proportional hazards regression models were used to explore the association, rather than causal inference, of lithium exposure and the risk of stroke., Results: Of the 1,885 subjects, 86 (4.6%) experienced stroke, including 2.8% of the lithium group and 5.4% of the non-lithium group. Lithium use was associated with a significantly reduced risk of stroke [hazard ratio (HR) = 0.39, 95% confidence interval (CI): 0.22-0.68]. Reduced risks of stroke were also associated with the highest cumulative lithium dose [≥720 defined daily dose (DDD), HR = 0.25, 95% CI: 0.10-0.59], the longest cumulative exposure period (≥720 days, HR = 0.20, 95% CI: 0.06-0.64), and the highest exposure rate (≥2 DDD/day, HR = 0.39, 95% CI: 0.21-0.70)., Conclusions: Lithium use was significantly related to a reduced risk of stroke in patients with bipolar disorder., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)