Search

Invariant natural killer T cell (iNKT) cells produce large amounts of cytokines in response to α-Galactosylceramide (α-GalCer) stimulation. An analog containing two phenyl rings on the acyl chain, C34, was previously found to be more Th1-biased than α-GalCer and triggered greater anticancer activities against breast cancer, melanoma and lung cancer in mice. Since liver is enriched in iNKT cells, we investigated anticancer efficacy of C34 on neuroblastoma with hepatic metastasis. C34 induced Th1-biased cytokine secretions in the liver, significantly suppressed neuroblastoma growth/metastasis and prolonged mouse survival. The anti-tumor efficacy might be attributed to greater expansions of hepatic NKT, NK, CD4 + T, and CD8 + T cells as well as reduction of the number of SSC lo Gr1 int CD11b + subset of myeloid-derived suppressor cells (MDSCs) in the liver of tumor-bearing mice, as compared to DMSO control group. C34 also upregulated expression of CD1d and CD11c, especially in the SSC lo Gr1 int CD11b + subset of MDSCs, which might be killed by C34-activated NKT cells, attributing to their reduced number. In addition, C34 also induced expansion of CD4 + T, CD8 + T, and NK cells, which might eliminate neuroblastoma cells. These immune-modulating effects of C34 might act in concert in the local milieu of liver to suppress the tumor growth. Further analysis of database of neuroblastoma revealed that patients with high CD11c expression in the monocytic MDSCs in the tumor had longer survival, suggesting the potential clinical application of C34 for treatment of neuroblastoma., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objective: Exposure to ambient PM 2.5 and its bound metals poses a risk to health and disease, via, in part, oxidative stress response. A variety of oxidative stress markers have been used as markers of response, but their relevance to environmental exposure remains to be established. We evaluated, longitudinally, a battery of oxidative stress markers and their relationship with the exposure of PM 2.5 and its bound metals in a panel of healthy participants., Material and Methods: Levels of residence- and personal-based ambient air PM 2.5 and its bound metals, as well as of lung function parameters, were assessed in a total of 58 questionnaire-administered healthy never smoker participants (male, 39.7%). Levels of urinary oxidative stress markers, including Nε-(hexanoyl)-lysine (HEL; an early lipid peroxidation product), 4-hydroxynonenal (4-HNE), N7-methylguanine (N7-meG), and 8-hydroxy-2-deoxyguanosine (8-OHdG), plasma antioxidants [superoxide dismutase (SOD) and glutathione peroxidase (GPx), and urinary metals were measured by ELISA, LC-MS, and ICP-MS, respectively. The results of three repeated measurements at two-month intervals were analyzed using the Generalized Estimating Equation (GEE)., Results: After adjusting for confounders, residence- and personal-based PM 2.5 levels were positively associated with HEL (β = 0.22 and 0.18) and N7-meG (β = 0.39 and 0.13). Significant correlations were observed between personal air PM 2.5 -Pb and urinary Pb with HEL (β = 0.08 and 0.26). While FVC, FEV 1 , FEV 1 /FVC, MMF, and PEFR predicted% were normal, a negative interaction (pollutant*time, P < 0.05) was noted for PM 2.5 -V, Mn, Co, Ni, Zn, As, and Pb. Additionally, a negative interaction was found for N7-meG (β = -21.35, -18.77, -23.86) and SOD (β = -26.56, -26.18, -16.48) with FEV 1 , FVC, and PEFR predicted%, respectively., Conclusion: These findings emphasize potential links between environmental exposure, internal dose, and health effects, thereby offering valuable markers for future research on metal exposure, oxidative stress, and health outcomes., Competing Interests: Declaration of competing interest All authors declare no conflict of interest in relation to this work., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Competing Interests: Competing interests: None declared.

This longitudinal cohort study investigated the associations of air pollutant exposures, including CO, NO, NO 2 , NO x , O 3 , PM 10 , PM 2.5 , and SO 2 , with long-term kidney function changes in patients with chronic kidney disease (CKD). We enrolled 447 CKD patients who took part in a universal hospital pre-ESRD care program during 2011-2015. The daily average air pollutant exposures and temperature were estimated for each patient, with different levels of air pollutant concentrations defined by 5-knot and restricted cubic spline function. Predicted annual estimated glomerular filtration (eGFR) slope values by one mixed model were considered as the study outcome. The average age of the study population was 77.1 ± 12.6 years, and the median annual eGFR decreased by 2.1 ml/min/1.73 m 2 per year from 30 ml/min/1.73 m 2 at baseline during a mean follow-up time of 3.4 years. The univariable and multivariable analyses revealed no significant linear and non-linear associations between 5-knot air pollutant concentrations and annual eGFR slope. In addition, the visualized spline effect plots show insignificant variation patterns in annual eGFR slope values with increased air pollutant concentrations. These results encourage more extensive studies to clarify the causal relationships and mechanisms of long-term specific air pollutant exposures and longitudinal kidney function change, especially in CKD populations., (© 2023. The Author(s).)

Background: Archery exercise exerts a rehabilitative effect on patients with paraplegia and might potentially serve as complementary physiotherapy for patients with Parkinson's disease., Objective: This study aimed to examine the rehabilitative effects of an archery intervention., Methods: A randomized controlled trial of a 12-week intervention was performed in patients with idiopathic Parkinson's disease. Thirty-one of the 39 eligible patients recruited from a medical center in Taiwan participated in the trial, of whom 16 were in the experimental group practicing archery exercises and 15 were in the control group at the beginning; twenty-nine completed the whole process. The Purdue pegboard test (PPT), the Unified Parkinson's Disease Rating Scale I to III (UPDRS I to III), physical fitness test, and timed up and go test (TUG) were used to assess the intervention effects of archery exercise., Results: Compared to the control group, the outcome differences between the posthoc and baseline tests in PPT, UPDRS I to III, lower extremity muscular strength, and TUG in the experimental group (between-group difference in difference's mean: 2.07, 1.59, 1.36, -2.25, -3.81, -9.10, 3.57, and -1.51, respectively) did show positive changes and their effect sizes examined from Mann-Whitney U tests ( η : 0.631, 0.544, 0.555, 0.372, 0.411, 0.470, 0.601, and 0.381, respectively; Ps < 0.05) were medium to large, indicating that the archery intervention exerted promising effects on improving hand flexibility and finger dexterity, activity functions in motor movement, lower extremity muscular strength, and gait and balance ability., Conclusions: Traditional archery exercise was suggested to have a rehabilitative effect for mild to moderate Parkinson's disease and could be a form of physiotherapy. Nevertheless, studies with larger sample sizes and extended intervention periods are needed to ascertain the long-term effects of archery exercise., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Chiu-Ying Chen et al.)

To compare the treatment efficacies of high-intensity focused ultrasound (HIFU), HIFU combined with gonadotrophin-releasing hormone agonist (GnRH-a), and HIFU combined with GnRH-a and levonorgestrel-releasing intrauterine system (LNG-IUS) for adenomyosis. We conducted a literature search in SCIENCE DIRECT, COCHRANE LIBRARY, WILLEY ONLINE LIBRARY, PUBMED, and TAYLOR FRANCIS. A total of 471 articles identified, 12 were included in a systematic review, and 11 of them deemed quantitively eligible included in the meta-analysis. The efficacies of the three treatment regimens were assessed using the dysmenorrhea and menstrual scores at 3, 6, 12, 24 months. Of the three regimens, HIFU combined with GnRH-a and LNG-IUS provides the best outcome. On dysmenorrhea score at 6 months there was significantly different higher heterogeneity with P < 0.00001 (I 2  = 100% WMD 21.44 [6.34, 36.53]) with statistical significance P = 0.005. At 12 months there was significantly different higher heterogeneity P < 0.00001 (I 2  = 100% WMD 23.47 [6.00, 40.94]) with statistically significant P < 0.008. At 24 months there was significantly different higher heterogeneity P < 0.0005 (I 2  = 92% WMD 6.05 [4.81, 7.30]) with statistical significance P < 0.00001. HIFU combined with GnRH-a and LNG-IUS on menstrual score at 3 months was significantly different higher heterogeneity with P < 0.00001 (I 2  = 100% WMD 56.23 [16.01, 96.45]) with statistical significance P = 0.006. At 6 months there was significantly different higher heterogeneity P < 0.00001 (I 2  = 99% WMD 93.86 [64.15, 123.57]) with statistical significance P < 0.00001. At 12 months there was significantly different higher heterogeneity P < 0.00001 (I 2  = 99% WMD 97.13 [67.81, 126.46]) with statistical significance P < 0.00001 compared to treatments with only HIFU and HIFU combined with GnRH-a. HIFU combined with GnRH-a and LNG-IUS treatment is more effective than only HIFU monotherapy and HIFU combined with GnRH-a., Competing Interests: Declaration of competing interest We have no conflicts of interest to disclose., (Copyright © 2023. Published by Elsevier B.V.)

Background: This study aimed to investigate the risk of stroke incidence in patients with periodontitis., Methods: Data on patients diagnosed with periodontitis were collected from Taiwan's National Health Insurance Research Database and were matched (1:1) with patients without periodontitis between 2001 and 2010. A multivariable Cox survival model was used to predict stroke between patients with and without periodontitis, and the possibility of confounders. Hazard ratios (HRs) with 95% confidence intervals (CIs) were used to explore the risk of stroke in the case and control groups. Diseases found during the follow-up period were analyzed to determine possible effects on the study. A total of 282 560 periodontitis and nonperiodontitis patients were enrolled, with most subjects aged 40 to 59 years., Results: The overall cumulative incidence of stroke was 2.14 times higher in periodontitis than in nonperiodontitis, and the highest HR was in the more than 80 years age group (HR = 9.30; 95% CI, 7.06-12.26). The multivariate Cox model indicated that the adjusted HR (aHR) between the case and control was 2.03 (95% CI, 1.99-2.08), and a higher aHR was associated with hypertension. Atherosclerosis, atrial fibrillation, obesity, kidney disease, anxiety, and gout discovered during follow-up also showed a potential risk of stroke in patients with periodontitis., Conclusion: Therefore, this study suggests a high risk of stroke in patients with periodontitis., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2022, the Chinese Medical Association.)

Influenza, also known as "flu", is an infectious disease caused by influenza viruses. Three types of influenza virus, A, B, and C, are able to infect humans. In most people, influenza causes mild symptoms, but it can also induce severe complications and death. Annual influenza vaccines are currently the main intervention used to minimize mortality and morbidity. However, vaccination frequently fails to provide adequate protection, especially in the elderly. Traditional flu vaccine targets hemagglutinin to prevent virus infection, but the constant mutation of hemagglutinin means that it is a challenge to develop vaccines quickly enough to keep up with mutations. Thus, other methods of curbing influenza incidence would be welcomed, especially for vulnerable populations. Although influenza viruses primarily infect the respiratory tract, influenza virus infection also induces intestinal dysbiosis. Through gut microbiota-derived secreted products and the circulating immune cells, gut microbiota can affect pulmonary immunity. The crosstalk between the respiratory tract and gut microbiota, termed the "gut-lung axis", is observed in the regulation of immune responses against influenza virus infection or inflammation-induced lung damage, indicating the possibility of using probiotics to prevent influenza virus infection or alleviate respiratory symptoms. In this review, we summarize the current findings on the antiviral functions of particular probiotics and/or combinations and discuss the antiviral mechanisms and immunomodulatory activities of probiotics in vitro , in mice, and in humans. Clinical studies show probiotic supplements can provide health benefits, not only to the elderly or children with compromised immune systems, but also to young- and middle-aged adults., Competing Interests: The authors declare no conflict of interest to report this work., (© 2022 Center for Food and Biomolecules, National Taiwan University. Production and hosting by Elsevier Taiwan LLC.)

Nephrotoxicity is a major adverse reaction of cisplatin-based chemotherapy. Organic cation transporter 2 (OCT2) which is located on the basement membrane of human proximal renal tubules is responsible for the renal accumulation of cisplatin and its nephrotoxicity. This study aimed to investigate the protective effect of PPIs to CP-induced nephrotoxicity. Three kinds of PPIs including lansoprazole, omeprazole and rabeprazole (Rab) were co-administrated with CP to mice. In addition, OCT2-overexpressed HEK293, HK-2 and A549 cells were co-incubated with CP and PPIs. The results showed that PPIs can attenuate CP-induced increase of CRE, BUN and histological damage of kidney. Among the three PPIs, Rab was found with a superior protective effect. It significantly reduced the accumulation of CP in OCT2-overexpressed HEK293 cells and in the renal cortex tissues of mice, but not in HK-2 cells. Moreover, Rab reduced the expression levels of cleaved-caspase-3, RIPK1, RIPK3, MLKL and p-MLKL and the apoptosis rate of renal tubular cells induced by CP in vivo, but not in HK-2 cells. However, Rab increased the viability of CP-treated cells in a concentration-dependent manner and attenuated CP-induced apoptosis and necroptosis in OCT2 over-expressed HEK293 cells. Finally, we demonstrated that Rab have no influence on the antitumor effect of CP. In conclusion, Rab attenuate CP-induced nephrotoxicity mainly through inhibiting OCT2-mediated CP uptake, without interfering with its anti-tumor property of inducing apoptosis and necroptosis., Competing Interests: Conflicts of interest We warrant that the final manuscript has been read by all co-authors and that the article is original, not under consideration to submit to any other journals. It has never been previously published. None of the authors has any conflict of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Fatal vehicle crashes (FVCs) are among the leading causes of death worldwide. Professional drivers often drive under dangerous conditions; however, knowledge of the risk factors for FVCs among professional drivers remain scant. We investigated whether professional drivers have a higher risk of FVCs than non-professional drivers and sought to clarify potential risk factors for FVCs among professional drivers. We analyzed nationwide incidence rates of FVCs as preliminary data. Furthermore, by using these data, we created a 1:4 professionals/non-professionals preliminary study to compare with the risk factors between professional and non-professional drivers. In Taiwan, the average crude incidence rate of FVCs for 2003-2016 among professional drivers was 1.09 per 1,000 person-years; professional drivers had a higher percentage of FVCs than non-professional drivers among all motor vehicle crashes. In the 14-year preliminary study with frequency-matched non-professional drivers, the risk of FVCs among professional drivers was significantly associated with a previous history of involvement in motor vehicle crashes (adjustment odds ratio [OR] = 2.157; 95% confidence interval [CI], 1.896-2.453), previous history of benzodiazepine use (adjustment OR = 1.385; 95% CI, 1.215-1.579), and speeding (adjustment OR = 1.009; 95% CI, 1.006-1.013). The findings have value to policymakers seeking to curtail FVCs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tsai, Yang, Ho, Wu, Guo, Chen and Chuang.)

Gliomatosis peritonei (GP), almost exclusively linked to mature or immature ovarian teratoma, is a very rare disease. To the best of our knowledge, reports on the complete clinical course and imaging features of ovarian mature teratoma with GP are extremely rare. We present a case of ovarian mature teratoma with GP in a 9-year-old girl admitted to the emergency department for a 2-month history of a large abdominal mass found accidentally. Carcinoembryonic antigen and cancer antigen 125 levels were elevated. CT scans suggested a large mass with mild enhancement, and an immature teratoma derived from the left ovary with ascites was diagnosed by ultrasound. Subsequently, left ovarian tumor resection and omentectomy were performed, and a solid cystic mass accompanied by massive ascites and numerous white to grayish nodules was identified on the left ovary. The pathology results revealed a mature teratoma with GP. The patient had good postoperative recovery, and her serum tumor marker levels decreased to normal at the 3-month follow-up., (© 2021 Wiley Periodicals LLC.)

The information on the outpatient expenditure of patients with oromaxillofacial cancer is minimal. This study aimed to compare the average annual expenditure on dental treatment for these patients 5 years before and 5 years after oromaxillofacial cancer diagnosis. In this study, 7731 patients who received oromaxillofacial cancer diagnosis in 2005 were selected from the Registry of Catastrophic Illness Database as the case-cohort. In the control cohort, 38,655 people without cancer were selected from the National Health Insurance Research Database, with the case-control ratio being 1:5. All participants were observed for 5 years before diagnosis and 5 years after diagnosis. The conditional logistic regression model was used to determine the odds ratios of annual expenditures incurred by participants in the case-cohort. The measurement results indicated that in the oromaxillofacial cancer cohort, the average annual dental expenditure levels at 1, 2, 3, 4, and 5 years after diagnosis were US $97.34, US $77.23, US $109.65, US $128.43, and US $128.03 and those at these years before diagnosis were US $37.52, US $32.10, US $31.86, US $29.14, and US $29.35, respectively. In conclusion, the average annual expenditure on the dental treatment of oromaxillofacial cancer patients after five years of diagnosis was increased compared to five years before diagnosis.

Triple-negative breast cancer (TNBC) is defined based on the absence of estrogen, progesterone, and human epidermal growth factor receptor 2 receptors. Currently, chemotherapy is the major therapeutic approach for TNBC patients; however, poor prognosis after a standard chemotherapy regimen is still commonplace due to drug resistance. Abnormal tumor metabolism and infiltrated immune or stromal cells in the tumor microenvironment (TME) may orchestrate mammary tumor growth and metastasis or give rise to new subsets of cancer cells resistant to drug treatment. The immunosuppressive mechanisms established in the TME make cancer cell clones invulnerable to immune recognition and killing, and turn immune cells into tumor-supporting cells, hence allowing cancer growth and dissemination. Phytochemicals with the potential to change the tumor metabolism or reprogram the TME may provide opportunities to suppress cancer metastasis and/or overcome chemoresistance. Furthermore, phytochemical intervention that reprograms the TME away from favoring immunoevasion and instead towards immunosurveillance may prevent TNBC metastasis and help improve the efficacy of combination therapies as phyto-adjuvants to combat drug-resistant TNBC. In this review, we summarize current findings on selected bioactive plant-derived natural products in preclinical mouse models and/or clinical trials with focus on their immunomodulatory mechanisms in the TME and their roles in regulating tumor metabolism for TNBC prevention or therapy.

Background: As studies on ethnic disparities in metabolic syndrome and its risk factors in Taiwan are still rare, the aims of this study were: (1) to detect the differences in the rates of metabolic syndrome, obesity and health behaviors between two ethnic groups (indigenous Tsou and nonindigenous Han) living in the same area and with similar age and sex distributions; (2) to examine whether ethnicity per se plays a significant role in the occurrence of metabolic syndrome, while taking other risk factors including sociodemographic characteristics, obesity and health behaviors into consideration., Methods: This is a cross-sectional study using data from a community survey conducted in Chiayi County in southwestern Taiwan. A frequency matching strategy by age and sex with a ratio of 1 (Tsou) to 3 (Han) was applied to select a comparable sample between both ethnic groups (667 Tsou and 2001 Han) from among the survey participants. Furthermore, participants with cardiometabolic diseases diagnosed before the surveyed day were excluded to avoid confounding any associated risk factors for developing metabolic syndrome (MS). A final analytic sample of 1482 remained. The used information included sociodemographic characteristics, medical histories, health behaviors, and the concentrations of triglycerides, cholesterol, and glucose., Results: Indigenous Tsou had significantly higher rates of metabolic syndromes, obesity and unhealthy behaviors than their Han counterparts (MS: 54.0% vs. 29.1%, obesity: 54.0% vs. 23.2%, drinking alcohol: 17.5% vs. 13.6%, and higher intake of fried food: 6.4% vs. 4.4%), even though they were similar in age and sex distributions. The significant risk factors for subsequently developing MS included being indigenous Tsou (adjusted POR = 2.62, P < 0.001), older, single, and obese. Stratified analyses on the risk factors for developing MS by health behaviors and by obese problems also indicated increased risks of being indigenous Tsou., Conclusions: There existed ethnic differences in the rates of metabolic syndrome, obesity, and health behaviors. Ethnicity per se did play a significant role in developing MS; in particular indigenous Tsou people had increased risks, suggesting possible biological reasons rooted in their origins that need further exploration. In addition, unhealthy behaviors may potentially have an indirect effect on developing MS via their effect on obesity., (© 2021. The Author(s).)

Methadone maintenance treatment (MMT) can alleviate opioid dependence. However, MMT possibly increases the risk of motor vehicle collisions. The current study investigated preliminary estimation of motor vehicle collision incidence rates. Furthermore, in this population-based retrospective cohort study with frequency-matched controls, opiate adults receiving MMT (cases) and those not receiving MMT (controls) were identified at a 1:2 ratio by linking data from several nationwide administrative registry databases. From 2009 to 2016, the crude incidence rate of motor vehicle collisions was the lowest in the general adult population, followed by that in opiate adults, and it was the highest in adults receiving MMT. The incidence rates of motor vehicle collisions were significantly higher in opiate users receiving MMT than in those not receiving MMT. Kaplan-Meier curves of the incidence of motor vehicle collisions differed significantly between groups, with a significant increased risk during the first 90 days of follow-up. In conclusion, drivers receiving MMT have higher motor vehicle collision risk than those not receiving MMT in opiate users, and it is worthy of noticing road safety in such drivers, particularly during the first 90 days of MMT., Competing Interests: YY, PH, TW, PW, CL, JT, YG, HC No competing interests declared, (© 2021, Yang et al.)

In-situ chemical oxidation (ISCO) can remove pollutants efficiently. However, the most important key to successfully conducting ISCO on site is to place the oxidant in close contact with the contaminant. Therefore, monitoring tools that provide for enhanced tracking of the injectate offer considerable benefit to guide subsequent ISCO injections. In this study, we applied the MagnetoMetric Resistivity (MMR) method to survey the distribution of an injected oxidant. A pilot test was conducted on a 10 m × 10 m site, and the sodium persulfate injection involved four pulse injections from one injection well. A magnetic field survey coupled with conventional monitoring was performed before the initial injection and after each pulse injection. The results of this study showed that groundwater samples from six observation wells and seven direct-push EC loggings did not provide sufficient data to quantify the distribution and flow behavior of the injected oxidant. However, the magnetic field survey visually showed the dynamic distribution of the injected oxidant, and the flow pathways and flow behavior were assessed accordingly. Although the flow behavior of injected solution was changeable in the aquifer, but the magnetic field survey combined with the monitoring of the well samples helped to explain the abnormal changes in the electrical conductivity of the observation wells and supports the use of the magnetic field survey technology as a method of monitoring ISCO injections., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: The association between asthma and benign prostatic hyperplasia (BPH) has rarely been explored. We investigated whether male asthmatic patients had an increased risk of BPH by conducting this retrospective nationwide population-based study., Methods: We utilized data derived from the National Health Insurance Research Database (NHIRD) in Taiwan. A total of 9778 male patients aged >40 years who were newly diagnosed with asthma between 2000 and 2006 were included in the asthma group. Male enrollees without asthma were selected as the non-asthma group from the same database. Both the groups were followed up until the end of 2013. We performed Cox proportional hazard regression analysis to estimate the risk of BPH and transurethral resection of the prostate (TURP) in the male patients with asthma compared with that in those without asthma., Results: The risk of BPH and TURP in the asthma group was 1.40-fold (95% confidence interval [CI] = 1.30-1.42) and 1.30-fold (95% CI= 1.31-1.50) higher than that in the non-asthma group, respectively, after adjusting for comorbidities, relevant medications and number of annual outpatient visits., Conclusions: The male patients with asthma were found to have a higher risk of BPH than did those without asthma.

Immune dysfunction is implicated in the etiology of bipolar disorder. The single-nucleotide polymorphism rs17026688 in the gene encoding glutamate decarboxylase-like protein 1 (GADL1) has been found to be associated with lithium response in Han Chinese patients with bipolar I disorder (BDI). However, whether patients with GADL1 polymorphisms have different immunophenotypes is unknown. To address this issue, differences in the immune profiles based on analysis of peripheral blood mononuclear cells (PBMCs) were compared among BDI patients and healthy controls who lack or carry the T allele of rs17026688. BDI patients had significantly higher percentages of total T cells, CD4 + T cells, activated B cells, and monocytes than healthy controls, suggesting that immunologic imbalance might be involved in BDI development or progression. Treatment of BDI patients-derived PBMCs with lithium in vitro increased the percentage of CD14 + monocytes and dendritic cells, suggesting that lithium plays an immunomodulatory role in CD14 + monocytes and dendritic cells. Among BDI patients, non-T carriers had a significantly higher percentage of CD11b + /CD33 lo /HLA-DR - myeloid-derived suppressor cells than T carriers. Moreover, only T carriers exhibited differential sensitivity to lithium therapeutic use with respect to the percentage of myeloid cells. These findings suggest that rs17026688 polymorphisms in GADL1 are associated with immune dysfunction in BDI patients.

Potassium channel tetramerization domain containing 12 (KCTD12), the auxiliary GABA B receptor subunit, is identified as a susceptibility gene for bipolar I (BPI) disorder in the Han Chinese population. Moreover, the single-nucleotide polymorphism (SNP) rs17026688 in glutamate decarboxylase-like protein 1 (GADL1) is shown to be associated with lithium response in Han Chinese BPI patients. In this study, we demonstrated for the first time the relationship among lithium, GADL1, and KCTD12. In circulating CD11b + macrophage cells, BPI patients showed a significantly higher percentage of KCTD12 expression than healthy controls. Among BPI patients, carriers of the 'T' allele (i.e., CT or TT) at site rs17026688 were found to secrete lower amounts of GADL1 but higher amounts of GABA b receptor 2 (GABBR2) in the plasma. In human SH-SY5Y neuroblastoma cells, lithium treatment increased the percentage of KCTD12 expression. Through inhibition of glycogen synthase kinase-3 (GSK-3), lithium induced cyclic AMP-response element binding protein (CREB)-mediated KCTD12 promoter activation. On the other hand, GADL1 overexpression enhanced GSK-3 activation and inhibited KCTD12 expression. We found that lithium induced, whereas GADL1 inhibited, KCTD12 expression. These findings suggested that KCTD12 may be an important gene with respect to neuron excitability and lithium response in BPI patients. Therefore, targeting GSK-3 activity and/or KCTD12 expression may constitute a possible therapeutic strategy for treating patients with BPI disorder.

Background: Two main job stress models-the Demand-Control-Support (DC) model and the Effort-Reward Imbalance (ERI) model have been used to assess the impact of psychosocial work-related factors for cardiovascular disease (CVD). Limited evidence elaborates the independent and combined effects on CVD events, especially for professional drivers. This study assesses the independent and combined effects of DC and ERI models on an 8-year risk of CVD among professional drivers., Methods: The Taiwan Bus Driver Cohort Study recruited 1650 professional drivers from a large bus company in 2005. The subjects were interviewed in person and completed the two job stress questionnaires. Researchers found 94 new cases of CVD (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM]: 390-459) from 2006 to 2012. A Cox proportional hazards model was performed to estimate the hazard ratio (HR) for CVD events., Results: Occupational drivers with high overcommitment scores (thresholds of 15) had an elevated risk for CVD (HR = 1.71; 95% CI = 1.04, 2.82). Regarding target disease, overcommitment had an increased risk for CVD (not including hypertensive disease) (HR = 1.27; 95% CI = 1.05, 1.54) and ischemic heart disease (HR = 1.32; 95% CI = 1.05-1.65)., Conclusion: Overcommitment, which is associated with job stress, appears to be associated with CVD risk in professional drivers.

The purpose of this study was to describe the current evidence found through a patent search about robotics used to assist nurses in providing care. The authors used a modified seven-step strategy of searching patents according to the US Patent and Trademark Office guidelines. The nursing robotic search was performed in four databases including the US Patent and Trademark Office issued patent database, the US Patent and Trademark Office published patent application database, the European Patent Office database, and Relecura. Keywords reflecting the scope of the term "robot" were defined for the purposes of this specific search. This broad search yielded large numbers of patents germane to nursing care. These results were narrowed using keywords and the Cooperative Patent Classification schemes to determine relevance, ensure rigor, and capture the most relevant results. This review of patents suggests robots for nursing care are proliferating. The opportunity for robotics in nursing is emerging in industry. Although nursing will likely benefit from robotics, we must determine the appropriate place to include robots in nursing care delivery.

Background: The global prevalence of type 2 diabetes continues to increase in both developed and developing countries. Environmental exposure to mercury may be an important and modifiable risk factor for type 2 diabetes. However, the epidemiological results are controversial., Objectives: This study aimed to examine the association between blood mercury levels and prevalence of type 2 diabetes., Methods: A total of 646 adult participants were selected from the National Nutrition and Health Survey in Taiwan (NAHSIT) 2005-2008. The participants were interviewed using structured questionnaires to record data on basic demographics, socioeconomic status, lifestyle, medical history, and 24-h dietary recall. Specimens of blood and urine were collected at the health examination. Type 2 diabetes was defined as a fasting blood glucose level ≥ 126 mg/dL or intake of hypoglycemic medications. The mercury concentration in red blood cells (RBC-Hg) was quantified by cold vapor atomic absorption spectrometry., Results: Participants with type 2 diabetes had a significantly higher RBC-Hg than those without type 2 diabetes. A significant association between the RBC-Hg and prevalence of type 2 diabetes was observed [odds ratio (OR): 1.64; 95% confidence intervals: 1.14-2.35] after potential confounders were well considered, including age, sex, body mass index (BMI), hypertension, total cholesterol, saltwater fish consumption, geographical strata, seasonality and hemoglobin (Hb) level., Conclusion: Our findings showed that elevated RBC-Hg is significantly associated with type 2 diabetes prevalence. Future research, particularly for longitudinal cohort studies with suitable specimens, needs to be performed to verify our findings., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Lithium has been used for maintenance treatment of bipolar disorder, but drug response varies among patients. Single-nucleotide polymorphisms in glutamate decarboxylase-like protein 1 (GADL1) are found to be associated with lithium response in Han Chinese bipolar patients. In this study, we assessed GADL1 function using a neuroblastoma cell line that stably overexpressed GADL1. Genes encoding factors involved in cell migration, such as FN1, ITGA2, ITGAV and CCL2, were downregulated in GADL1-overexpressing cells. GADL1 overexpression indeed suppressed cell migration. Cell migration speed and perimeter length exhibited similar trends, both of which were decreased under GADL1 overexpression or lithium treatment but increased upon stimulation with CCL2. Secreted GADL1 or its enzyme product, taurine, in the conditioned medium might exert only mild effects on the observed changes. Compared with SH-SY5Y cells, GADL1-overexpressing cells were much more sensitive to CCL2 treatment but less sensitive to lithium, indicating that the level of GADL1 expression can affect cell sensitivity to lithium or  CCL2 treatment. Together, these results suggest that cell migration and related morphological changes might provide good indicators of the sensitivity toward lithium treatment, and the GADL1 stable overexpression cell line might serve as a useful platform to screen novel therapeutics for bipolar disorder.

Introduction. Previous studies have examined the association between specific mental disorders, particularly mood and anxiety disorders, and substance-related disorders; but the temporal link between them remains unclear. This study aimed to examine whether individuals with specific mental disorders, including affective psychoses, neurotic disorders, schizophrenia, personality disorders, and adjustment reaction, have higher risks for subsequently developing substance-related disorders compared to those without. Methods. A large-scale study with longitudinal data was conducted using the Taiwan National Health Insurance Research Database (NHIRD) consisting of 2,000,118 patients' medical records from 2000 to 2009. A total of 124,423 people diagnosed with selected mental disorders and the same number of people without the diagnoses of the selected disorders were identified between January 1, 2001, and December 31, 2006, and followed up for the diagnoses of substance-related disorders till the end of 2009. We estimated the risk for subsequently developing substance-related disorders among patients with the selected mental disorders compared to those without by using Cox proportional hazard models. The cumulative incidence of substance-related disorders was calculated using the Kaplan-Meier method. Results. The risk for developing substance-related disorders in patients with selected mental disorders is about 5 times (HR=5.09, 95% CI: 4.74-5.48) higher than those without after adjusting for potential confounding variables. From the multivariate analyses of subsamples stratified by age, sex, and urban and income levels, we found all adjusted hazard ratios were significantly higher than 1.0, ranging from 2.12 (95% CI: 1.72-2.62) to 14.55 (95% CI: 7.89-26.83). For children and adolescents aged 10-19 years, those with specific mental disorders had 14.55-fold higher risk for developing substance-related disorders in later life compared to their counterparts. Furthermore, patients with personality disorders had the highest risk (HR=25.05). Conclusions. The earlier onset of the selected mental disorders is a potential risk for developing substance-related disorders in later life, particularly for personality disorders. Health professionals should pay more attention to this at-risk population, especially to adolescents with mental disorders.

Adipose tissue (AT) inflammation is crucial to the development of obesity-associated insulin resistance. Our aim was to investigate the contribution of cyclooxygenase-2 (COX-2)/macrophage migration inhibitory factor (MIF)-mediated cross-talk between hypertrophic adipocytes and macrophages to the etiology of AT inflammation and the involvement of CD74 using human SGBS adipocytes, THP-1 macrophages and mice fed a high-fat (HF) diet. The MIF and CD74 mRNA levels in the adipocytes and stromal vascular cells (SVCs) of white fat were highly correlated with body weight (BW), homeostatic model assessment for insulin resistance (HOMA-IR), and adipose macrophage marker expression levels, especially those in SVCs. COX-2 inhibition suppressed the elevation of MIF production in HF white adipocytes as well as palmitate and hypoxic-treated SGBS adipocytes. Treatment of adipocytes transfected with shCOX-2 and siMIF or subjected to MIF depletion in the medium reversed the pro-inflammatory responses in co-incubated THP-1 cells. Inhibition of NF-κB activation reversed the COX2-dependent MIF secretion from treated adipocytes. The targetted inhibition of macrophage CD74 prevented M1 macrophage polarization in the above co-culture model. The COX-2-dependent increases in CD74 gene expression and MIF release in M1-polarized macrophages facilitated the expression of COX-2 and MIF in co-cultured SGBS adipocytes. CD74 shRNA intravenous injection suppressed HF-induced AT M1 macrophage polarization and inflammation as well as insulin resistance in mice. The present study suggested that COX-2-mediated MIF secretion through NF-κB activation from hypertrophic and hypoxic adipocytes as well as M1 macrophages might substantially contribute to the phenotypic switch of AT macrophages through CD74 in obesity. Inhibition of CD74 could attenuate AT inflammation and insulin resistance in the development of HF diet-induced obesity., (© 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

Background: It is unclear whether inhaled corticosteroids (ICS) have chemopreventive effect on lung cancer (LC) development in humans. We investigated the association between the ICS use in asthma patients and the risk of LC., Methods: We conducted a nationwide, population-based retrospective cohort study using the National Health Insurance database. We identified 4210 asthmatics who were initially free of LC and regularly used ICS between 2001 and 2005 and 37,228 asthmatics without regular ICS use. Patients with documented history of tobacco use were excluded from the analyses. Asthmatics were categorized into a mild and a severe asthma group. Each patient was tracked until the end of 2010 to identify incident cases of LC. Cox proportional hazards models were used to evaluate the effect of ICS on the risk of LC, further stratifying by asthma severity and comorbidities., Results: During follow-up, we identified 747 incident cases of LC diagnosed in the asthma cohort. Compared with severe asthmatics without regular ICS use, the risk of LC for those with mild asthma with regular ICS use was lower (adjusted hazard ratio = 0.42, 95% confidence interval = 0.31-0.56, P < 0.0001). The risk of LC was calculated among the following rankings of risk severe asthma without regular ICS use, low severity without regular ICS, high severity with regular ICS, and low severity with regular ICS group showed a decreasing trend of LC incidence ( P = 0.041). Analyses stratified by comorbidities revealed that the protective effect of ICS was assessed with better precision and more pronounced in those with renal diseases, stroke, and hyperlipidemia., Conclusions: For patients with asthma, regular ICS use might have a protective effect against LC. Further studies are required to assess this potential association from both immunohistopathological and clinical aspects., Competing Interests: There are no conflicts of interest.

An increased understanding is needed of the physiological effects and plausible biological mechanisms that link PM 2.5 (particulate matter with an aerodynamic diameter below 2.5μm) exposure to mortality and morbidities such as atherosclerosis and respiratory disease. PM 2.5 causes carcinogenic health effects. Biomonitoring in humans has suggested that 8-oxo-7, 8-dihydro-2-deoxyguanosine (8-oxodG) and N7-methylguanine (N7-MeG) are correlated with oxidative and methylated DNA damage. Thus, it is meaningful to explore the mechanisms of mutagenesis and carcinogenesis associated with oxidative and methylated DNA damage by simultaneously measuring these two markers. We recruited 72 participants from 2 areas (residential and commercial as well as residential and industrial) in the greater Taipei metropolitan area at baseline. Personal samplers were used to collect 24-hour PM 2.5 -integrated samples. All participants completed an interview, and blood and urine samples were collected the next morning. All collection procedures were repeated twice after a two-month follow-up period. Urinary 8-oxodG and N7-MeG were assayed as biomarkers of oxidative and methylated DNA damage, respectively. Plasma superoxide dismutase (SOD) and glutathione peroxidase-1 (GPX-1) were measured as biomarkers of antioxidants. Urinary 1-hydroxypyrene (1-OHP) was used as a biomarker of exposure to polycyclic aromatic hydrocarbons (PAHs). The mean PM 2.5 level was 37.3μg/m 3 at baseline. PM 2.5 concentrations were higher during winter than during spring and summer. After adjusting for confounds through a generalized estimating equation (GEE) analysis, N7-MeG was significantly increased by 8.1% (β=0.034, 95% CIs=0.001-0.068) per 10μg/m 3 increment in PM 2.5 . 8-oxodG levels were positively correlated with N7-MeG according to both cross-sectional and longitudinal analyses, and 1-OHP was significantly associated with increasing 8-oxodG and N7-MeG concentrations. Exposure to PM 2.5 increases methylated DNA damage. The mean level of urinary N7-MeG was 1000-fold higher than that of 8-oxodG., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Evidence regarding the association between asthma and endometriosis is limited and inconsistent. The goal of the study was to investigate whether women diagnosed as having asthma were at a greater risk of endometriosis than age-matched unaffected women., Methods: We conducted a nationwide population-based retrospective study by using data retrieved from the Taiwan National Health Insurance Research Database during the period of 2000-2005 with follow-up through 2013. The current analysis included 7337 women aged 12-50 years with newly diagnosed asthma and using asthma-related medications and 29,348 age-matched women without asthma. A Cox proportional hazards regression model was used to estimate the risks of endometriosis in women with asthma as compared with those without asthma., Results: The overall risk of endometriosis in the asthma group was 1.50-fold higher (95% confidence interval = 1.33-1.70) than that in the nonasthma group. A stratified analysis by age further revealed that patients with asthma were associated with a higher risk of endometriosis in age groups of 21-50 years., Conclusion: Compared with women without asthma, women with asthma of reproductive age are at a higher risk of endometriosis. Additional studies are warranted to elucidate the mechanism(s) underlying the association between asthma and a higher risk of endometriosis., (Copyright © 2017. Published by Elsevier Ltd.)

Environmental factors contribute significantly to the pathogenesis of chronic kidney disease. However, these factors, and particularly the toxic effects of heavy metals, have not been completely evaluated. Chromium is a widespread industrial contaminant that has been linked to nephrotoxicity in animal and occupational population studies. Nevertheless, its role in population renal health and its potential interactions with other nephrotoxic metals, such as lead and cadmium, remain unknown. We assessed the association between exposure to chromium, lead, and cadmium with renal function using estimated glomerular filtration rate (eGFR) in an analysis of 360 Taiwanese adults aged 19-84 years from the National Nutrition and Health Survey in Taiwan (2005-2008). Doubling of urinary chromium or lead decreased the eGFR by -5.99 mL/min/1.73 m 2 (95% confidence interval -9.70, -2.27) and -6.61 (-9.71, -3.51), respectively, after adjusting for age, sex, body mass index, hypertension, diabetes, cigarette smoking, sodium intake, education, urinary volume, and other metals. For those in the highest tertile of cadmium exposure, the eGFR decreased by -12.68 mL/min/1.73 m 2 (95% confidence interval -20.44, -4.93) and -11.22 mL/min/1.73 m 2 (-17.01, -5.44), as urinary chromium or lead levels doubled, respectively. Thus, there is a significant and independent association between chromium exposure and decreased renal function. Furthermore, co-exposure to chromium with lead and cadmium is potentially associated with additional decline in the glomerular filtration rate in Taiwanese adults., (Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background: Previous studies revealed that chronic exposure to air pollution can significantly increase the risk of the development of Parkinson's disease (PD), but this relationship is inconclusive as large-scale prospective studies are limited and the results are inconsistent. Therefore, the purpose of this study was to ascertain the adverse health effects of air pollution exposure in a nationwide population using a longitudinal approach., Materials and Methods: We conducted a nested case-control study using the National Health Insurance Research Dataset (NHIRD), which consisted of 1,000,000 beneficiaries in the National Health Insurance Program (NHI) in the year 2000 and their medical records from 1995 to 2013 and using public data on air pollution concentrations from monitoring stations across Taiwan released from the Environmental Protection Administration to identify people with ages ≥ 40 years living in areas with monitoring stations during 1995-1999 as study subjects. Then, we excluded subjects with PD, dementia, stroke and diabetes diagnosed before Jan. 1, 2000 and obtained 54,524 subjects to follow until Dec. 31, 2013. In this observational period, 1060 newly diagnosed PD cases were identified. 4240 controls were randomly selected from those without PD using a matching strategy for age, sex, the year of PD diagnosis and the year of entering the NHI program at a ratio of 1:4. Ten elements of air pollution were examined, and multiple logistic regression models were used to measure their risks in subsequent PD development., Results: The incidence of PD in adults aged ≥ 40 years was 1.9%, and the median duration for disease onset was 8.45 years. None of the chemical compounds (SO2, O3, CO, NOx, NO, NO2, THC, CH4, or NMHC) significantly affected the incidence of PD except for particulate matter. PM10 exposure showed significant effects on the likelihood of PD development (T3 level: > 65μg/m3 versus T1 level: ≤ 54μg/m3; OR = 1.35, 95% CI = 1.12-1.62, 0.001 ≤ P < 0.01). In addition, comorbid conditions such as dementia (ORs = 3.53-3.93, Ps < 0.001), stroke (ORs = 2.99-3.01, Ps < 0.001), depression (ORs = 2.51-2.64, Ps < 0.001), head injury (ORs = 1.24-1.29, 0.001 ≤ Ps < 0.01 or 0.01 ≤ Ps < 0.05), sleep disorder (OR = 1.23-1.26, 0.001 ≤ Ps < 0.01), and hypertension (ORs = 1.18-1.19, 0.01 ≤ Ps < 0.05) also significantly increased the risk for PD development., Conclusions: Although PM10 plays a significant role in PD development, the associated chemical/metal compounds that are capable of inducing adverse biological mechanisms still warrant further exploration. Because of a link between comorbid conditions and PM exposure, research on the causal relationship between long-term exposure to PM and the development of PD should be considered with caution because other possible modifiers or mediators, comorbid diseases in particular, may be involved.

Objective: Chronic obstructive pulmonary disease (COPD) and benign prostatic hyperplasia (BPH) are common disorders in ageing male populations. Nevertheless, the relationship between the two diseases has rarely been explored. The objective of this study was to examine whether patients with COPD are at an increased risk of BPH., Design: Retrospective nationwide cohort study., Setting: Data retrieved from the Taiwan National Health Insurance Research Database., Participants: Overall, 19 959 male patients aged 40 years and over with newly diagnosed COPD between 2000 and 2006 were included as the COPD group, and 19 959 sex-matched and age-matched enrollees without COPD were included as the non-COPD group. Both groups were followed-up until the end of 2011., Outcome Measures: A Cox proportional hazards regression model was used to compute the risk of BPH in patients with COPD compared with enrollees without COPD., Results: The overall incidence rate of BPH was 1.53 times higher in the COPD group than that in the non-COPD group (44.7 vs 25.7 per 1000 person-years, 95% CI 1.46 to 1.60) after adjusting for covariates. An additional stratified analysis revealed that this increased risk of BPH in patients with COPD remained significantly higher than that in enrollees without COPD in all men aged 40 years and over., Conclusion: After adjustment for covariates, male patients with COPD were found to be at a higher risk of BPH. We suggest that clinicians should be cautious about the increased risk of BPH in male patients with COPD., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Purpose: Studies on the association between continuous positive airway pressure (CPAP) treatment and liver diseases such as non-alcoholic fatty liver disease (NAFLD) and cirrhosis in patients with obstructive sleep apnea/hypopnea syndrome (OSAHS) are limited. To the best of our knowledge, none exists that makes use of a national database in an Asian population. This study aims to evaluate the effects of CPAP treatment on patients with these two disorders in a retrospective, population-based study in Taiwan., Methods: Using the Taiwan National Health Insurance claims database, this study collected the data of OSAHS patients diagnosed between 2000 and 2008 and divided them into CPAP treatment and non-CPAP treatment groups. All subjects were followed up until 2010. Liver disease incidence and risk were calculated., Results: The CPAP group had a lower cumulative incidence rate of developing liver disease than the non-CPAP group within the observation periods (p < 0.001). After adjusting for age, gender, urbanization level, and comorbidities, the CPAP treatment group showed a lower risk of developing liver disease compared with the non-CPAP treatment group (sub-aHR of 0.66 (95% CI 0.55-0.80), p < 0.001)., Conclusions: Our observations suggest that CPAP treatment may play an important role to delay the progression of liver disease in OSAHS patients and decreases the incidence of liver disease among OSAHS patients. Thus, CPAP therapy may be a feasible way to decrease the risk of liver disease among patients with OSAHS.

Objectives: We assessed environmental tobacco smoke (ETS) and examined its association with pregnancy discomforts., Methods: We used structured questionnaires to interview a convenience sample of 139 pregnant women (8-20 weeks of gestation) recruited from 2 hospitals in central Taiwan., Results: We found that 84% of the participants experienced ETS exposure in their households, workplaces, and/or public areas. Bivariate analyses showed the severity of pregnancy discomforts in the participants exposed to a high level of ETS was higher than that in those exposed to a low level of ETS. We found the discomfort symptoms of thirst, heartburn, lower abdominal pain, frequent urination, and depression to be significantly associated with ETS exposure. There also was a dose-response relationship between ETS exposure and discomfort. In addition, the presence of at least 4 out of those 5 symptoms served as a signal for raising women's self-awareness to avoid ETS hazards., Conclusion: Our study provides empirical evidence of an adverse relationship between ETS exposure and early pregnancy discomforts. The exposure to ETS in pregnant women remains high, and health education programs targeting this population should enhance their self-awareness to the discomforts related to ETS exposure and prompt them to adopt prevention strategies.

Background: In order to support health service organizations in arranging a system for prevention of road traffic collisions (RTC), it is important to study the usefulness of sleep assessment tools. A cohort study was used to evaluate the effectiveness of subjective and objective sleep assessment tools to assess for the 6-year risk of both first RTC event only and recurrent RTC events., Methods: The Taiwan Bus Driver Cohort Study (TBDCS) recruited 1650 professional drivers from a large bus company in Taiwan in 2005. The subjects were interviewed in person, completed the sleep assessment questionnaires and had an overnight pulse oximeter survey. Moreover, this cohort of drivers was linked to the National Traffic Accident Database (NTAD) and researchers found 139 new RTC events from 2005 to 2010. Primary outcomes were traffic collisions from NTAD, nocturnal oxygen desaturation index (ODI) from pulse oximeter, Pittsburg sleeping quality score, Epworth daytime sleepiness score, Snore Outcomes Survey score and working patterns from questionnaires. A Cox proportional hazards model and an extended Cox regression model for repeated events were performed to estimate the hazard ratio for RTC., Results: The RTC drivers had increased ODI4 levels (5.77 ± 4.72 vs 4.99 ± 6.68 events/h; P  = 0.008) and ODI3 levels (8.68 ± 6.79 vs 7.42 ± 7.94 events/h; P  = 0.007) in comparison with non-RTC drivers. These results were consistent regardless of whether ODI was evaluated as a continuous or a categorical variable. ODI4 and ODI3 levels increased the 6-year RTC risks among professional drivers even after adjusting for age, education, history of cardiovascular disease, caffeine intake, sleeping pills used, bus driving experience and shift modes. Moreover, there was an increased trend for ODI between the stratification of the number of RTCs in comparison with the non-RTC group. In the extended Cox regression models for repeated RTC events with the Anderson and Gill intensity model and Prentice-Williams-Petersen model, measurement of ODI increased hazards of the subsequent RTC events., Conclusion: This study showed that an increase in the 6-year risk of RTC was associated with objective measurement of ODI for a sign of sleep-disordered breathing (SDB), but was not associated with self-reported sleeping quality or daytime sleepiness. Therefore, the overnight pulse oximeter is an effective sleep assessment tool for assessing the risk of RTC. Further research should be conducted regarding measures to prevent against SDB among professional drivers., (© The Author 2016; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association)

Glycosphingolipids (GSLs) bearing the α-galactosyl headgroup and the acyl chain terminated with a phenyl derivative were found to be more potent than α-galactosyl ceramide (αGalCer) to stimulate both murine and human invariant natural killer T (iNKT) cells and to induce an antibody isotope switch to IgG. In this study, we replaced the galactosyl group with glucose (αGlc) and its fluoro-analogs and found that phenyl GSLs with αGlc (C34-Glc) and its fluoro-analog 6F-C34-Glc were stronger than those with αGal in stimulating human iNKT cells but weaker in mice. Their activities have a strong correlation with the binding avidities of the ternary interaction between the iNKT-cell receptor (iNKTCR) and CD1d-GSL complex. It was the iNKTCR rather than CD1d that dictated the species-specific responses. C34-Glc was further used as an adjuvant for a SSEA4-crm-197 vaccine, and after immunization in mice, the vaccine was highly effective against Lewis lung carcinoma.

Background: Professional drivers' work under conditions predisposes them for development of sleep-disordered breathing (SDB) and cardiovascular disease (CVD). However, the effect of SDB on CVD risk among professional drivers has never been investigated. A cohort study was used to evaluate the effectiveness of overnight pulse oximeter as a sleep apnea screening tool to assess the 8-year risk of CVD events., Methods: The Taiwan Bus Driver Cohort Study (TBDCS) recruited 1014 professional drivers in Taiwan since 2005. The subjects completed questionnaire interview and overnight pulse oximeter survey. This cohort was linked to the National Health Insurance Research Dataset (NHIRD). Researchers found 192 CVD cases from 2005 to 2012. Cox proportional hazards model was performed to estimate the hazard ratio for CVD. The statistical analysis was performed using SAS software in 2015., Results: ODI4 and ODI3 levels increased the 8-year CVD risk, even adjusting for CVD risk factors (HR: 1.36, 95% CI: 1.05 to 1.78; p=0.022, and HR: 1.40, 95% CI: 1.03 to 1.90; p=0.033). ODI4 and ODI3 thresholds of 6.5 and 10events/h revealed differences of CVD risks (HR: 1.72, 95% CI: 1.00 to 2.95; p=0.048, and HR: 1.76, 95% CI: 1.03 to 3.03; p=0.041). Moreover, the ODI levels had an increased risk for hypertensive disease (not including essential hypertension)., Conclusions: This study concludes that ODI for a sign of SDB is an independent predictor of elevated risk of CVD. Further research should be conducted regarding measures to prevent against SDB in order to reduce CVD risk in professional drivers., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Lead accumulates in adult bones for many decades; previous studies have shown lead's detrimental effects on osteoblast and osteoclast activity in association with bone remodeling. Osteoporosis is a disease of the bones resulting in low bone mass that induces fragile bones and hence susceptibility of fracture. We estimated the association between urinary lead (U-Pb) levels and bone health in adults participating in the third Nutrition and Health Survey in Taiwan (NAHSIT) from 2005 to 2008. A total of 398 participants were divided into normal (T-score>-1), osteopenic (T-score between -1 and -2.5), or osteoporotic (T-score<-2.5) groups according to the results of bone mineral density (BMD) measurements. Heavy metals were measured in urine specimens using inductively coupled plasma-mass spectrometry. In the multivariable logistic regression analysis, age (OR=1.08; 95% CI=1.05-1.10), former smokers (OR=2.95; 95% CI=1.22-7.11) and higher U-Pb levels than upper tertile (OR=2.30; 95% CI=1.19-4.48) were associated with osteopenia/osteoporosis. Furthermore, age (OR=1.06; 95% CI=1.02-1.10) and higher U-Pb levels (OR=2.81; 95% CI=1.13-6.97) were significantly associated with osteopenia and osteoporosis in women. These results suggest that adults, particularly in women, with higher U-Pb levels may have increased odds of osteopenia and osteoporosis.

Purpose: Despite links between maternal and child health status, evidence on the association between gum infection in pregnant mothers and childhood allergies is scarce. We aim to evaluate the risk of developing allergy in children born to periodontal mothers in a nationwide study., Methods: We conducted a 9-year population-based, retrospective cohort study using Taiwan's National Health Insurance database. A study cohort of 42,217 newborns born to mothers with periodontal disease during pregnancy was identified in 2001 and matched with 42,334 babies born to mothers without any infection (control) by mother's age at delivery and baby sex. With a follow-up period from 2001 to 2010, we observed the incidence of allergic rhinitis (AR), allergic conjunctivitis (AC), and eczema in these children. Cox proportional hazards regression models were performed with premature deaths as competing risk for the estimation of allergic disease risks., Results: Nine-year cumulative incidences were the highest among children born to periodontal mothers; they reached 46.8%, 24.2%, and 40.4% (vs. 39.5%, 18.3% and 34.8% in control) for AR, AC, and eczema, respectively. Our results showed moderately increased risks for the allergies in children born to periodontal mothers relative to their matched non-inflammatory control (adjusted HRs: 1.17, 95% CI: 1.15-1.20; 1.27, 1.24-1.31; 1.14, 1.12-1.17, respectively). Because the impact of food consumption and living environment cannot be considered using insurance data, we attempted to control it by adjusting for parental income and mother's residential area., Conclusions: Overall cumulative incidence and risks of children born to periodontal mothers for AR, AC, and eczema are significantly higher than those born to non-inflammatory mothers. Gum infection in women during pregnancy is an independent risk factor for allergic diseases in children, thus its intergenerational consequences should be considered in gestational care.

Traditional Chinese medicine (TCM) formulates treatment according to body constitution (BC) differentiation. Different constitutions have specific metabolic characteristics and different susceptibility to certain diseases. This study aimed to assess the Yang-Xu constitution using a body constitution questionnaire (BCQ) and clinical blood variables. A BCQ was employed to assess the clinical manifestation of Yang-Xu. The logistic regression model was conducted to explore the relationship between BC scores and biomarkers. Leave-one-out cross-validation (LOOCV) and K-fold cross-validation were performed to evaluate the accuracy of a predictive model in practice. Decision trees (DTs) were conducted to determine the possible relationships between blood biomarkers and BC scores. According to the BCQ analysis, 49% participants without any BC were classified as healthy subjects. Among them, 130 samples were selected for further analysis and divided into two groups. One group comprised healthy subjects without any BC (68%), while subjects of the other group, named as the sub-healthy group, had three BCs (32%). Six biomarkers, CRE, TSH, HB, MONO, RBC, and LH, were found to have the greatest impact on BCQ outcomes in Yang-Xu subjects. This study indicated significant biochemical differences in Yang-Xu subjects, which may provide a connection between blood variables and the Yang-Xu BC.

Background: It is unclear whether obstructive sleep apnea (OSA) is independently associated with increased levels of the acute-phase reactant C-reactive protein (CRP). The purpose of this study was to evaluate the relationship between OSA and high-sensitivity CRP (hs-CRP) levels according to the presence or absence of metabolic syndrome (MetS)., Methods: This study recruited 245 male bus drivers from one transportation company in Taiwan. Each participant was evaluated by a polysomnography (PSG) test, blood lipids examination, and hs-CRP. Severity of OSA was categorized according to the apnea-hypopnea index (AHI)., Results: Subjects were categorized into severe OSA group (n = 44; 17.9 %), moderate and mild OSA group (n = 117; 47.8 %), and non-OSA group (n = 84; 34.3 %). AHI had a significant association with hs-CRP (β = 0.125, p = 0.009) adjusting for age, smoking, drinking, and MetS status. Hs-CRP was elevated with severe OSA (β = 0.533, p = 0.005) even adjusting for BMI and MetS. Moreover, there was an independent effect for adjusted odds ratios (AORs) between the stratification of the severity for OSA and MetS., Conclusion: Elevated hs-CRP level is associated with severe OSA, independent of known confounders. The effect of OSA in CRP is independent of MetS was identified.

Peripheral neuropathy and inflammatory reactions of the central nervous system may accompany rheumatoid arthritis (RA). Inflammatory processes play a critical role in epilepsy. Therefore, we conducted this study to determine the risk of epilepsy in patients with RA.The RA cohort comprised patients ages 20 years and older who were newly diagnosed with RA between 2000 and 2011, with data obtained from the Registry of Catastrophic Illnesses Patient Database. Patients without RA were frequency matched with an RA cohort at a 1:1 ratio according to age, sex, and year of RA diagnosis.The overall crude hazard ratio (HR) for epilepsy was 1.27-fold higher in the RA cohort compared with that in the controls. After adjustment for age, sex, comorbidities, and medications, the patients with RA were associated with an increased risk of epilepsy compared with those without RA (adjusted HR [aHR] = 1.52, 95% confidence interval [CI] = 1.12-2.07). Compared with the RA patients with ≤ 560 days of nonsteroidal anti-inflammatory drug (NSAID) use, the RA patients with 1181 to 2145 and >2145 days of NSAID use had a significantly lower risk of epilepsy (aHR = 0.35, 95% CI = 0.24-0.52 and aHR = 0.15, 95% CI = 0.09-0.24, respectively).This study provides compelling evidence of an increased risk of epilepsy in patients with RA. The period of NSAID treatment is negatively associated with the risk of epilepsy in RA patients.

Background: Developmental status at birth and subsequent obesity have been implicated in the development of childhood atopic dermatitis (AD) and allergic rhinitis (AR)., Methods: The current study analysed the cohort data of 74 688 junior high school students from a national retrospective birth cohort study in Taiwan. A random 10% sample was selected from singleton livebirths with complete data on the analytical variables of interest. Atopic disorders, including AD and AR, were assessed by questionnaires (International Study of Asthma and Allergies in Childhood). Logistic regression analyses were applied with adjustments for related risk factors., Results: Among subjects mainly 13-15 years of age, the estimated prevalence was 7.6% for AD and 22.4% for AR. While the role of fetal growth in allergic disorders was less evident, the risk of developing AD and AR were both influenced by a combination of fetal growth status and adolescent body mass index (BMI). Compared with those with normal fetal growth and school-aged BMI, the risk of developing AD increased 64% among adolescents with both restricted fetal growth and high BMI (odds ratio 1.64, 95% confidence interval 1.37, 1.97). The risk for this combination was higher than that for either restricted fetal growth or high BMI alone. Nevertheless, the overall interaction between BMI and fetal growth status on atopic disorders did not reach statistical significance., Conclusions: Excessive weight gain could be an important risk factor related to developing atopic dermatitis and allergic rhinitis during adolescence, especially among infants born small for gestational age., (© 2015 John Wiley & Sons Ltd.)

Background: Recent findings from clinical trials have indicated inconsistent associations between angiotensin II receptor blockers and the risk of cancer incidence. Furthermore, the relationship between antihypertensive drugs and prostate cancer in hypertensive patients remains unclear., Methods: From Taiwan's national health insurance database, we identified 80,299 patients diagnosed with hypertension in 2001 and matched with 321,916 subjects without hypertension by age, income, urbanization level, and index day. A total of 684 hypertensive patients without antihypertensive drug use (drug non-user subcohort) were also matched (1:4) with 2736 patients on antihypertensive medication (drug subcohort) using the same criteria. Each subject in the two study groups was followed up for a maximum of nine years, during which death was considered a competing event when performing the stratified Fine and Gray regression hazards model for the estimation of prostate cancer risk for the cohorts. Uptake of antihypertensive prescription was considered a time-dependent variable., Results: Our findings indicate that patients with hypertension are at significantly increased risk for prostate cancer incidence when compared to their matched non-hypertensive counterparts (sHR=6.80, 95% CI=1.97-23.44, p=0.0024). Among hypertensive patients, those with long term antihypertensive drug use are not at elevated risk of developing prostate cancer relative to non-users of antihypertensive drugs (1-5 year vs. non-user sHR=0.99, 95% CI=0.32-3.05; >5 year vs. non-user sHR=0.88, 95% CI=0.34-2.26)., Conclusions: Hypertension is considered a risk factor for prostate cancer. However, long term uptake of antihypertensive medication in male hypertensive patients should not be a concern for the development of prostate cancer., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Geniposide as the major active component of Gardenia jasminoides Ellis has neuroprotective activity. This study elucidated the potential antidepressant-like effect of geniposide and its related mechanisms using a depression rat model induced by 3 consecutive weeks of chronic unpredictable mild stress (CUMS). Sucrose preference test, open field test (OFT) and forced swimming test (FST) were applied to evaluate the antidepressant effect of geniposide. Adrenocorticotropic hormone (ACTH) and corticosterone (CORT) serum levels, adrenal gland index and hypothalamic corticotrophin-releasing hormone (CRH) mRNA expression were measured to assess the activity of hypothalamus-pituitary-adrenal (HPA) axis. Hypothalamic glucocorticoid receptor α (GRα) mRNA expression and GRα protein expression in hypothalamic paraventricular nucleus (PVN) were also determined by real-time PCR and immunohistochemistry, respectively. We found that geniposide (25, 50, 100mg/kg) treatment reversed the CUMS-induced behavioral abnormalities, as suggested by increased sucrose intake, improved crossing and rearing behavior in OFT, shortened immobility and prolonged swimming time in FST. Additionally, geniposide treatment normalized the CUMS-induced hyperactivity of HPA axis, as evidenced by reduced CORT serum level, adrenal gland index and hypothalamic CRH mRNA expression, with no significant effect on ACTH serum level. Moreover, geniposide treatment upregulated the hypothalamic GRα mRNA level and GRα protein expression in PVN, suggesting geniposide could recover the impaired GRα negative feedback on CRH expression and HPA axis. These aforementioned therapeutic effects of geniposide were essentially similar to fluoxetine. Our results indicated that geniposide possessed potent antidepressant-like properties that may be mediated by its effects on the HPA axis., (Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.)

Background: The association between obstructive sleep apnea (OSA) and the risk of liver disease is unclear. Moreover, population-based studies on the risk of liver disease among people with OSA have not yet been conducted. This study aimed to investigate the risk of subsequent development of liver disease among people with OSA., Methods: Using Taiwan National Health Insurance claims data, this study collected subjects from a cohort of 17,374 people with OSA who were diagnosed between 2000 and 2008. A control group of 69,496 people was selected from the same database and matched by age, gender, urbanization, income, and date of initial admission. All subjects were followed up until 2010. Liver disease incidence and risk were calculated., Results: The overall risk of liver disease among people with OSA was significantly higher than in the control group (aHR = 5.52, p <0.001). Non-alcoholic fatty liver disease, cirrhosis, and hepatitis C had significant aHRs of 5.29, 7.50, and 7.19 (all at p <0.001), respectively. In contrast, hepatitis B had the smallest aHR of 3.71., Conclusions: The risk of liver disease was more than five times higher among people with OSA compared with the control group; this was particularly for cirrhosis and hepatitis C. Liver disease is thus a very important health issue among people with OSA., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Purpose: Long-term follow-up studies of asbestos-related cancer in shipbreaking workers are lacking. This study examines the relationship between cancer incidence and asbestos exposure among former Taiwan shipbreaking workers., Methods: A total of 4,427 shipbreaking workers and 22,135 population-based matched controls were successfully followed in this study. The study cohort was linked to the Taiwan Cancer Registry for new cancer cases. The adjusted hazard ratio (aHR) for cancer was calculated for the shipbreaking workers with Total Exposure Potential Scores (TEP) for asbestos., Results: Follow-up generated 109,932 person-years, with 940 deaths and 436 cancer cases, among 4,427 shipbreaking workers from 1985 to 2008. The high asbestos exposure group also had a statistically significant increase in the risk of overall cancer (aHR= 1.71; 95% CI: 1.42-2.05), esophagus cancer (aHR= 2.31; 95% CI: 1.00-5.41), liver and intrahepatic bile duct cancer (aHR= 1.60; 95% CI: 1.08-2.36), and trachea, bronchus, and lung cancer (aHR= 3.08; 95% CI: 1.80-5.25). Mesothelioma cases were found in the high asbestos exposure group. Moreover, overall cancer, esophagus cancer, and trachea, bronchus, and lung cancer were seen in a dose-dependent relationship with asbestos exposure., Conclusions: This study presented the elevated trend of asbestos exposure with cancer incidence for overall cancer, esophagus cancer, and trachea, bronchus, and lung cancer among shipbreaking workers. Those workers previously exposed to asbestos should receive persistent monitoring in order to early detect adverse health outcomes.

There are limited population-based studies on the progress of oseltamivir therapy for influenza infection.Using insurance claims data of 2005, 2009, and 2010, the authors established an "in-time" cohort and a "lag-time" cohort representing influenza patients taking the medicine within and not within 1 week to examine the treatment progress. Incident outpatient visit, emergency care and hospitalization, and fatality were compared between the 2 cohorts in the first week and the second week of follow-up periods, after the oseltamivir therapy.A total of 112,492 subjects diagnosed with influenza on oseltamivir therapy in 2005, 2009, and 2010 were identified. The multivariate logistic regression analysis showed that the in-time treatment was superior to the lag-time treatment with less repeat outpatient visits, hospitalizations, and fatality. The overall corresponding in-time treatment to lag-time treatment odds ratios (OR) were 0.50, 0.54, and 0.71 (all P value < 0.05), respectively. The in-time to lag-time ORs of all events were 0.50 in 2009 and 0.54 in 2010.Our study demonstrates that the in-time oseltamivir therapy leads to significantly better treatment outcomes. Oseltamivir should be administered as early as the onset of influenza symptoms appears.