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Background Women with endometriosis (EM) have increased vulnerability to certain psychiatric disorders, including depression and anxiety, as well as bipolar disorder (BD). This study investigates the risk of BD development in EM patients. Also, the impact of EM treatment on the risk of developing BD is examined. Methods A total of 17,832 EM patients and 17,832 non-EM controls matched by age, index year, and Charlson Comorbidity Index (CCI) score were included between 2000–2012 and followed to the end of 2013. Participants newly diagnosed as BD by board-certified psychiatrist were defined as incidents. Cox regression analysis was used to calculate the hazard ratio (HR) with 95% confidence interval (CI) of the BD incidence rate between two studied groups. Results EM patients were associated with an increased risk of BD development compared with non-EM controls after adjusting for age, CCI score, and different treatment options (1.04 versus 0.56 per 1,000 person-years, HR: 2.34, 95% CI: 1.75–3.12). Also, there was no significant difference in the risk estimate between different hormonal or surgical treatment groups, suggesting a limited impact of EM treatment on the risk of BD development. Limitations This study deals with the duration of hormonal treatment, whether operated or not, which reduces the chances of showing the effect of individual EM treatment on the risk of BD development. Conclusion This study shows that EM patients are associated with an increased risk of BD development. Further studies would be needed to elucidate the mechanism linking the EM and BD.

Objectives Narcolepsy symptoms, such as excessive daytime sleepiness or cataplexy, can pose a risk to safety. Stimulants or antidepressants have been used to treat these symptoms. The study investigated the risk of bone fractures in narcolepsy patients. Also, the exposure pattern of stimulants and antidepressants to the risk of bone fractures was examined. Methods In all, 493 narcolepsy patients and 490 controls matched by gender, age, index year, and comorbidity severity were enrolled between 1998 and 2012, then followed until the end of 2013 using Taiwan's National Health Insurance Research Database. During the follow-up period, participants who developed bone fractures were identified. Cox regression analysis was used to calculate the hazard ratio (HR) with 95% confidence interval (CI) for the incidence rates of bone fractures between narcolepsy patients and unaffected controls. Results Narcolepsy patients had a significantly increased risk of bone fractures compared with unaffected controls (19.6 versus 12.3 per 1000 person-years, HR: 1.74, 95% CI: 1.29–2.35). In addition, the use of stimulants in narcolepsy patients showed lower incidence rates of bone fractures compared to non-users (incidence rates were 14.2, 11.9, and 20.0 per 1000 person-years, respectively, among frequent users, infrequent users, and non-users), but the risk estimate was not statistically significant. The evidence for associations between antidepressant use in narcolepsy patients and bone fractures was contradictory. Conclusion This study highlights the need to pay attention to the risk of bone fractures in narcolepsy patients, and the importance of adequate stimulants use might reduce the risk of bone fractures.

Patients with schizophrenia (SCZ) have a higher prevalence of known risk factors for obstructive sleep apnea (OSA). This study aims to determine if SCZ patients are at increased risk of incident OSA. A total of 5092 newly diagnosed SCZ patients and 5092 non-SCZ controls matched by gender, age, and index year were included between 2000 and 2012 and followed to 2013. Participants newly diagnosed with OSA were defined as incidents. Cox regression analysis was used to calculate the hazard ratio (HR) with 95% confidence intervals (CI) of the OSA incidence rate between the two groups studied. SCZ patients were at increased risk of OSA compared to non-SCZ controls after adjusting for gender, age, comorbidities, and duration of antipsychotic use (2.12 versus 1.01 per 1000 person-years, HR: 1.97, 95% CI: 1.36–2.85). Also, this study confirmed the existence of some known risk factors for OSA, including male gender (HR 1.65, 95% CI 1.14–2.37), obesity (HR 2.62, 95% CI 1.19–5.80), hypertension (HR 1.61, 95% CI 1.06–2.47), hyperlipidemia (HR 1.55, 95% CI 1.04–2.38), diabetes (HR 1.53, 95% CI 1.01–2.38), and antipsychotic use (duration

To investigate whether patients with polycystic ovary syndrome (PCOS) are at increased risk for incident schizophrenia and whether PCOS treatment (clomiphene, cyproterone, or metformin) affects the incidence of schizophrenia.An overall of 7146 PCOS patients and 28,580 non-PCOS controls matched by age, index year, and Charlson Comorbidity Index (CCI) score were included between 2000 and 2012 and followed up until 2013 using a validated nationally representative sample from Taiwan. Participants newly diagnosed as schizophrenia were defined as incidents. Cox regression analysis was used to calculate the hazard ratio (HR) with a 95% confidence interval (CI) of the schizophrenia incidence rate between the two studied groups.PCOS patients were at increased risk of incident schizophrenia compared to non-PCOS controls after adjusting for age, CCI score, comorbidities, and different treatment options (0.49 versus 0.09 per 1000 person-years, HR: 6.93, 95% CI: 3.25-14.7). After adjusting for above-mentioned covariates, metformin treatment had a protective effect against the incident schizophrenia compared to non-users (HR: 0.16, 95% CI: 0.06-0.41). Also, treatment with clomiphene and cyproterone had only a limited impact on the incident schizophrenia.This study shows PCOS patients are at increased risk of incident schizophrenia, and the metformin treatment has a protective effect against incident schizophrenia.

Background The study investigated the risk of newly developed bipolar disorder (BD) in patients with polycystic ovary syndrome (PCOS) and examined the relationship between PCOS treatment (hormone therapy (clomiphene or cyproterone) or metformin) and risk of BD development. Methods In all, 7175 PCOS patients and 28,697 non-PCOS controls matched by age, index year, and Charlson Comorbidity Index (CCI) score were included between 2000 and 2012, then followed until the end of 2013. Participants newly diagnosed as BD by board-certified psychiatrists were defined as incidents. Cox regression analysis was used to calculate the hazard ratio (HR) with 95% confidence interval (CI) of the BD incidence rate between two studied groups. Results PCOS patients had a significantly increased risk of developing BD compared to unaffected controls after adjusting for age, CCI score, and different treatment options (1.05 vs. 0.12 per 1,000 person-years, HR: 8.29, 95% CI: 4.65–14.7). Also, the use of metformin in PCOS patients showed a significantly reduced risk of developing BD compared to non-users after adjusting for the above-mentioned variables (HR: 0.36, 95% CI: 0.16–0.81). Although hormone therapy in PCOS patients showed a lower incidence rate of BD development compared to non-users, the risk estimate was not statistically significant (HR: 0.68, 95% CI: 0.35–1.32). Limitations This study didn't assess the PCOS severity, which reduced the chances of showing the effects of PCOS severity on BD development. Conclusion This study shows PCOS patients have an increased risk of developing BD, and the use of metformin may reduce its risk.

Narcolepsy is a rare brain disorder characterized by excessive daytime sleepiness (EDS), cataplexy, hypnagogic hallucinations, and sleep paralysis. Stimulants have been used to relieve the symptoms of EDS. Narcolepsy symptoms may pose a risk to burn injury. The study aimed to investigate the risk of burn injury in narcolepsy patients and to examine the relationship between the use of stimulants and the risk of burn injury. In all, 507 narcolepsy patients and 504 controls matched by gender, age, index year, and Charlson Comorbidity Index (CCI) score were enrolled between 1998 and 2012, then followed until the end of 2013 using Taiwan’s National Health Insurance Research Database. During the follow-up period, participants who developed burn injury were identified. Cox regression analysis was used to calculate the hazard ratio (HR) with 95% confidence interval (CI) of the burn incidence rate between narcolepsy patients and unaffected controls. Narcolepsy patients had a significantly increased risk of burn injury compared to unaffected controls (5.37 versus 2.69 per 1,000 person-years, HR: 2.04, 95% CI: 1.13–3.67) after adjusting for gender, age, CCI score, urbanization degree, and duration of stimulants use. Also, the use of stimulants in narcolepsy patients was associated with a lower incidence rate of developing burn injury, but the risk estimate was not statistically significant after adjusting for the above-mentioned variables. This study shows narcolepsy patients have an increased risk of burn injury and the use of stimulants may reduce the burn incidence rate, providing a reference for developing prevention interventions.

Objectives Studies have suggested a possible autoimmune contribution in a subset of patients with schizophrenia. The purpose of this study was to determine if a history of autoimmune diseases (AD) is associated with an increased risk of later onset of schizophrenia. Methods Taiwan's National Health Insurance Research Database was used to identify a total of 64,817 AD patients and an equal number of age-matched control patients. The incidence rates of schizophrenia with a maximum follow-up period of 10 years between patients with and without AD were compared using a Cox proportional hazard model to estimate the hazard ratio (HR) and 95% confidence interval (95% CI). Results The main finding was the discovery of a higher incidence of subsequent schizophrenia in patients with AD (HR: 1.72, 95% CI: 1.23–2.4) after adjustment for other demographic characteristics. Specifically, the risk of schizophrenia was observed to be a significant increase in systemic lupus erythematosus (3.73, 2.07–6.72), rheumatoid arthritis (2.89, 1.97–4.23), dermatomyositis (5.85, 1.32–25.94) and autoimmune vasculitis (2.44, 1.17–5.06). Also, this study revealed some potential risk factors for developing schizophrenia, including younger age (less than or equal to 50 years) and some comorbidities (hypertension, chronic obstructive pulmonary disease, and alcohol use disorder). Conversely, this study found that steroid use was a potential protective factor for the development of schizophrenia. Conclusions This study found that AD were associated with an increased risk of developing schizophrenia, suggesting that the abnormal autoimmune process was associated with an increase in the expression of psychiatric disturbances.

Background: Abnormalities in the immune system of endometriosis has been demonstrated and may reflect the chronic inflammatory response or the autoimmune reaction to the presence of ectopic endometrial tissue. Rheumatoid arthritis (RA) is a chronic inflammatory joint disease of an autoimmune nature. The study aimed to investigate the risk of incident RA in patients with endometriosis. Materials and Methods: A total of 17,913 patients with endometriosis and 17,913 unaffected controls matched by age, index year, and Charlson Comorbidity Index (CCI) score were enrolled between 2000 and 2012. Patients were followed until the end of 2013 using Taiwan's National Health Insurance Research Database, at which time participants who developed RA were identified. Cox regression analysis was used to calculate the hazard ratio (HR) with a 95% confidence interval (CI) of RA incidence rate between patients with endometriosis and unaffected controls. Results: Patients with endometriosis were associated with an increased risk of incident RA compared with unaffected controls after adjusting for age, CCI score, and hormonal and surgical treatments (3.56 vs. 1.30 per 10,000 person-years, HR: 3.71, 95% CI: 2.91-5.73). Among these adjusted variables, hormonal and surgical treatments were treated as time-dependent covariates. Stratification analyses also revealed similar risk associations linking endometriosis to subsequent RA in all stratified age and CCI score subgroups (adjusted HR all >1, although not all were significant) Conclusions: Patients with endometriosis was associated with an increased risk of incident RA. Additional prospective studies that take into account genetic vulnerability and environmental exposures are warranted to confirm this relationship.

Hyperthyroidism contributes to many other disease conditions, including neurodegenerative diseases. Parkinson’s disease (PD) is one of the most common neurodegenerative diseases. The purpose of this study was to investigate the risk of PD in patients with hyperthyroidism. A total of 8788 patients with hyperthyroidism and 8788 controls (without hyperthyroidism) matched by age, gender, index year, and Charlson Comorbidity Index (CCI) score were enrolled between 2000 and 2012. Patients were then followed until the end of 2013 using Taiwan’s National Health Insurance Research Database, at which time participants who developed PD were identified. Cox regression analysis was used to calculate the hazard ratio (HR) with a 95% CI of PD incidence rate between patients with hyperthyroidism and unaffected controls. Patients with hyperthyroidism had a significantly increased risk of PD compared with unaffected controls (1.21 vs 0.45 per 1000 person-years, HR: 2.69, 95% CI: 1.08–6.66) after adjusting for age, gender, CCI score, comorbidities, and antithyroid therapy. Hyperthyroidism and PD may share common manifestations. After excluding the first year of observation, a similar result is obtained (HR: 2.57, 95% CI: 1.61–4.01). Also, this study found that older age (HR: 3.74–8.53), more comorbidities (HR: 1.58–1.63), and specific comorbidities (brain injury (HR: 1.57) and cerebrovascular disease (HR: 3.44)) were associated with an increased risk of developing PD. Patients with hyperthyroidism have an increased risk of developing PD. Additional prospective clinical studies are warranted to examine the relationship between hyperthyroidism and PD and determine if there is an intervention that could reduce PD risk.

Objective Previous case reports have linked Graves' disease to incident systemic lupus erythematosus (SLE). It has also been reported that antithyroid drugs used to treat Graves' disease can induce SLE development. The purpose of this study was to investigate the risk of SLE in patients with Graves' disease. Methods A total of 8779 patients with Graves' disease and 8779 controls (without Graves' disease) matched by age, gender, index year, and Charlson Comorbidity Index (CCI) score were enrolled between 2000-2012. Patients were then followed until the end of 2013 using Taiwan's National Health Insurance Research Database, at which time participants who developed SLE were identified. Cox regression analysis was used to calculate the hazard ratio (HR) with a 95% confidence interval (CI) of SLE incidence rate between patients with Graves' disease and unaffected controls. Results Patients with Graves' disease had a significantly increased risk of SLE than unaffected controls (8.81 vs 2.83 per 10 000 person-years, HR: 5.45, 95% CI: 1.74-17.0) after adjusting for antithyroid therapies (antithyroid drugs, radioactive iodine ablation, and surgery). Diagnostic bias may be present as patients with Graves' disease may seek more help from healthcare providers. After excluding the first 0.5 and 1 year of observation period, similar results were obtained (excluding 0.5 year - HR: 4.30, 95% CI: 2.78-8.57; excluding 1 year - HR: 4.63, 95% CI: 2.33-7.79). Conclusion This study shows that Graves' disease is associated with an increased risk of incident SLE. Further studies on the underlying pathogenesis linking Graves' disease and SLE are warranted.

Introduction Continuous positive airway pressure (CPAP) is the main treatment for obstructive sleep apnea (OSA). To date, the link between CPAP usage and incident stroke has been inconsistent. Objective This nationwide population study is designed to examine the effect of CPAP on stroke incidence in OSA patients. Methods Using Taiwan's National Health Insurance Research Database (NHIRD), this study collected data from 4275 OSA patients diagnosed between 2000 and 2011 and divided them into two groups according to whether they received CPAP treatment. After matching baseline demographics and comorbidities, both cohorts contained 959 OSA patients and were followed to a newly diagnosed stroke or until the end of 2013. Cox regression analysis was performed to examine the incidence of stroke between patients with OSA receiving CPAP or no CPAP treatment. Results CPAP treatment for OSA patients predicted a lower incidence rate (3.41 vs 5.43 per 1000 person-years) and tended to protect against the development of stroke (hazard ratio (HR): 0.68, 95% confidence interval (95% CI): 0.38-1.23) compared to those without CPAP treatment, but the estimate was not statistically significant. Similar results were also observed by dividing stroke into ischemic (2.65 vs 4.30 per 1000 person-years; HR: 0.67, 95% CI: 0.35-1.31) or hemorrhagic origin (0.76 vs 1.12 per 1000 person-years; HR: 0.67, 95% CI: 0.19-2.40). Conclusions It is possible that treatment with CPAP might be beneficial for protection against stroke, but this conclusion should be interpreted with caution. Future studies with satisfactory CPAP quality and duration are needed to validate this observation.

The etiology of endometriosis is mostly under-explored, but abnormalities in the immune system leading to an autoimmune reaction have been suggested. The systemic lupus erythematosus (SLE) is one of the most common autoimmune diseases. The purpose of this study was to investigate the risk of SLE in patients with endometriosis. A total of 17,779 patients with endometriosis and 17,779 controls (without endometriosis) matched by age, index year, and Charlson Comorbidity Index (CCI) score were enrolled between 2000 and 2012. Patients were then followed until the end of 2013 using Taiwan’s National Health Insurance Research Database, at which time participants who developed SLE were identified. Cox regression analysis was used to calculate the hazard ratio (HR) with a 95% confidence interval (CI) of SLE incidence rate between patients with endometriosis and unaffected controls. After adjusting for age, CCI score, and different treatment options, patients with endometriosis were at increased risk of SLE compared to unaffected controls (0.85 versus 0.57 per 1000 person-years, HR 1.86, 95% CI 1.36–2.53). Also, higher baseline CCI scores (CCI score 1–2 and ≥ 3 vs. 0—HR 2.33–4.98) were at increased risk of SLE. During follow-up, hormonal treatment for endometriosis could reduce the risk of SLE (short-term and long-term vs. non-use HR 0.48–0.62), while surgical treatment appeared to have a limited impact on the risk of SLE. Patients with endometriosis were at increased risk of SLE, and adequate hormonal treatment could reduce the risk of SLE, providing a reference for developing prevention interventions.

Hypothyroidism has been implicated in many other disease conditions, including neurodegenerative diseases. Parkinson's disease (PD) is one of the most common neurodegenerative diseases. The purpose of this study was to investigate the risk of PD in patients with hypothyroidism.A total of 4725 patients with hypothyroidism and 4725 controls (without hypothyroidism) matched by age, gender, index year, and Charlson Comorbidity Index (CCI) score were enrolled between 2000 and 2012. Patients were then followed until the end of 2013 using Taiwan's National Health Insurance Research Database, at which time participants who developed PD were identified. Cox regression analysis was used to calculate the hazard ratio (HR) with a 95% confidence interval (CI) of PD incidence rate between patients with hypothyroidism and unaffected controls.Patients with hypothyroidism had a significantly increased risk of PD compared with unaffected controls (2.00 versus 1.10 per 1,000 person-years, HR: 1.77, 95% CI: 1.13-2.76) after adjusting for age, gender, CCI score, physical comorbidities (brain injury, cerebrovascular disease, hypertension, dyslipidemia, and diabetes mellitus), and duration of levothyroxine use. Also, older age (≥50 vs.50 - HR:14.83), higher CCI score (CCI score 1-2≥3 vs. 0 - HR: 1.66-1.74), and specific comorbidities (brain injury (HR: 1.78) and cerebrovascular disease (HR: 2.46)) significantly increased the risk of PD after adjusting for the variables mentioned above.Patients with hypothyroidism have an increased risk of developing PD. Other prospective studies that take into account genetic vulnerability and environmental exposures are warranted to confirm their relationship.

Pinostrobin, a flavonoid phytochemical found in variety of plants, has been demonstrated to possess numerous bioactivities such as antioxidant, anti-inflammatory, anticancer, and neuroprotective properties. The aim of this study was to investigate the hypocholesterolemic effect of pinostrobin on the regulation of the gene expression of PCSK9 and its underlying mechanisms in hepatic cells. We found that pinostrobin (20 and 40 μM) significantly inhibited the PCSK9 promoter activity from 1.00 ± 0.16 (fold) to 0.85 ± 0.06 and 0.54 ± 0.05, respectively, as well as the suppression of PCSK9 mRNA expression from 1.00 ± 0.11 (fold) to 0.81 ± 0.07 and 0.58 ± 0.07, respectively, in HepG2 cells. Pinostrobin significantly reduced the mature form of the PCSK9 protein, inhibited the catalytic activity of PCSK9, and increased the protein level of LDLR and the LDL uptake activity in HepG2 cells. We further demonstrated that pinostrobin markedly increased the level of nuclear forkhead box O3a (FoxO3a) protein, enhanced FoxO3a/PCSK9 promoter complexes formation, and attenuated the promoter binding capacity of nuclear HNF-1α. The knockdown of FoxO3a in HepG2 cells by small interference RNA (siRNA) abolished the pinostrobin-mediated PCSK9 reduction. Finally, we demonstrated that pinostrobin attenuated simvastatin-induced PCSK9 overexpression in HepG2 cells. Our current findings reveal that pinostrobin is a PCSK9 inhibitor and down-regulates the PCSK9 gene expression through the up-regulation of the FoxO3a level in hepatic cells. Pinostrobin with potential PCSK9 inhibitory activity may serve as a novel agent for cholesterol regulation and lipid management.

Background Studies suggested autoimmunity plays a role in the etiology of bipolar disorder (BD). This study aimed to investigate the association between systemic autoimmune diseases (SADs) and the subsequent development of BD, and examine the potential risk factors for developing BD. Methods Patients with SADs were identified in the Taiwan National Health Insurance Program (NHIP). A comparison cohort was created by matching patients without SADs with age. The SADs cohort consisted of 65,498 while the comparison cohort consisted of 261,992 patients. The incidence of BD was evaluated in both cohorts. Results The major finding was the discovery of a higher incidence of subsequent BD among patients with SADs (adjusted hazard ratio: 1.98). Specifically, the risk of BD was observed to be significant increase in systemic lupus erythematosus, rheumatoid arthritis, autoimmune vasculitis, Sicca syndrome and Crohn's disease. Furthermore, our study revealed some potential risk factors for developing BD including female, younger age and patients who lived in eastern Taiwan. Also, some comorbidities including dyslipidemia, chronic obstructive pulmonary disease, diabetes mellitus, asthma, cerebrovascular disease, alcohol used disorder, liver cirrhosis, and malignancies were potential risk factors for incident BD. Limitations The diagnosis of SADs was based on the catastrophic illness certificate defined by Taiwanese NHIP. Thus, not every form of SADs was explored for subsequent developing BD. Conclusion This study confirms that SADs are associated with higher incidence of BD, suggesting that abnormal autoimmune process is associated with increased expression of psychiatric disturbances.

Xanthohumol, a prenylated flavonoid found in hops (Humulus lupulus L.), exhibits multiple biological activities such as antiatherosclerosis and hypolipidemic activities. In this study, we aim to investigate the hypocholesterolemic effects and molecular mechanisms of xanthohumol in hepatic cells. We found that xanthohumol (10 and 20 μM) increased the amount of cell-surface low-density lipoprotein receptor (LDLR) from 100.0 ± 2.1% to 115.0 ± 1.3% and 135.2 ± 2.7%, and enhanced the LDL uptake activity from 100.0 ± 0.9% to 139.1 ± 13.2% in HepG2 cells (p0.01). The mRNA levels of LDLR, HMGCR, and PCSK9 were not altered. Xanthohumol (20 μM) reduced the expression of inducible degrader of the LDL receptor (Mylip/Idol) mRNA and protein by approximately 45% (p0.01), which was reported to be associated with increases of LDLR level. We demonstrated that xanthohumol suppressed hepatic Mylip/Idol expression via counteracting liver X receptor (LXR) activation. The molecular docking results predicted that xanthohumol has a high binding affinity to interact with the LXRα ligand-binding domain, which may result in attenuation of LXRα-induced Mylip/Idol expression. Finally, we demonstrated that the Mylip/Idol expression and LDLR activity were synergistically changed by a combination of xanthohumol and simvastatin treatment. Our findings indicated that xanthohumol may regulate the LXR-Mylip/Idol axis to modulate hepatic LDLR abundance and activity.

Among the applications of the internet and cloud computing, online social network (OSN) is a very popular service. Since a lot of personal information is stored on the OSN platform, privacy protection on such an application has become a critical issue. Apart from this, OSN platforms need advertisement revenue to enable continued operations. However, if the users encrypt their messages, then OSN providers cannot generate accurate advertisement to users. Thus, how to achieve both privacy preserving and accurate advertisement is a worth-discussing issue. Unfortunately, none of the works on OSNs can achieve both privacy preserving and accurate advertisement simultaneously. In view of this, we propose the first multireceiver predicate encryption scheme for OSN platforms. Not only does the proposed scheme protects the users’ privacy but it achieves customized advertisement as well. Compared with other predicate encryptions deployed in OSN platforms, the proposed scheme gains much shorter ciphertext. The semantic security and attribute hiding of the proposed scheme are proved under the standard model.

Background Suboptimal management of diabetes can lead to a hyperglycemic crisis episode (HCE), which could be further enhanced in the presence of bipolar disorder (BD) and the prescription of antipsychotics. This study aims to investigate the risk of HCE in diabetic patients with BD. Additionally, the duration of antipsychotic prescription on HCE risk is examined. Methods Using the Taiwan National Health Insurance Research Database, 6099 diabetic patients with BD and 24,378 diabetic patients without BD matched by gender, age, index year, and Charlson Comorbidity Index score were enrolled between 1999 and 2010 and followed to the end of 2013. Participants who developed HCE during the follow-up period were identified. Cox regression analysis was used to calculate the hazard ratio (HR) with 95% confidence interval (CI) of the HCE incidence rate between two groups studied. Results Diabetic patients with BD were associated with an increased risk of HCE compared with unaffected controls after adjusted for baseline demographics and duration of antipsychotic prescription (3.84 versus 2.71 per 1,000 person-years, HR: 1.41, 95% CI: 1.15–1.71). Also, this study revealed that male gender, more comorbidities, and a longer duration of antipsychotic prescription were potential risk factors for developing HCE. Limitations This study only deals with data on the duration of antipsychotic prescription, without showing the effects of different antipsychotics on HCE risk. Conclusion This study highlights the need to pay attention to the risk of HCE in diabetic patients with BD and the importance of careful prescription of antipsychotics to reduce the HCE incident.

Aims This study aims to investigate the risk of hyperglycemic crisis episode (HCE) in diabetic patients with depression and to examine the relationship between the duration of antidepressants use and the risk of HCE. Methods In all, 26,746 diabetic patients with depression and 106,853 controls (without depression) matched by gender, age, index year, and Charlson Comorbidity Index (CCI) score were included between 1999 and 2010, then followed until the end of 2013. During the follow-up period, participants who developed HCE were identified. Cox regression analysis was used to calculate the hazard ratio (HR) with 95% confidence interval (CI) of the HCE incidence rate between the two groups studied. Results Diabetic patients with depression had a significantly increased risk of HCE compared to unaffected controls after adjusted for gender, age, CCI score, and duration of antidepressants use (2.87 versus 2.50 per 1000 person-years, HR: 1.78, 95% CI: 1.56–2.03). Also, long-term use of antidepressants in diabetic patients with depression showed a significantly reduced risk of HCE compared to non-users after adjusting for the above-mentioned variables (HR: 0.44, 95% CI: 0.35–0.55). Conclusions This study shows diabetic patients with depression have an increased risk of HCE, and the use of antidepressants may reduce its risk.

Introduction Violent motor tics or severe self-harm behaviors have been reported in patients with Tourette's syndrome (TS) and leading to traumatic brain injury (TBI). The study aimed to determine the risk of TBI in TS patients, the effects associated with concurrent psychiatric disorders (attention-deficit/hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), or depressive disorder), and the effects of medication treatment (antipsychotics, antidepressants, or clonidine) on the risk of TBI. Methods Using the National Health Insurance Research Database of Taiwan, 2261 TS patients and 20349 non-TS controls matched by gender and age were enrolled between 2000 and 2012, and followed until the end of 2013. Participants who developed TBI during the follow-up period were identified. Cox regression analysis was performed to examine the risk of TBI between TS patients and non-TS controls. Results TS patients were associated with an increased risk of TBI compared to non-TS controls (hazard ratio (HR): 1.59, 95% confidence interval (95% CI): 1.37–1.85). Also, this study revealed TS patients with ADHD, OCD, or depressive disorder predicted a higher TBI incidence rate than those who did not, but the estimate was not statistically significant. Moreover, this study found that TS patients with frequent use of antipsychotics were associated with a lower risk of TBI than infrequent users (HR: 0.76, 95% CI: 0.57–0.99). Conclusions This study highlights the need to pay more attention to the risk of TBI in TS patients, and the importance of adequate antipsychotic medication may reduce the risk of TBI.

BackgroundSeveral features of borderline personality disorder (BPD) are likely to be associated with sexual health problems, such as unstable attachment, unstable sexual identity and sexual impulsivity. Since the issue of sex is not openly discussed in Taiwanese society, sexual health needs, including screening and prevention of sexually transmitted infections (STI), are often neglected in this population.ObjectiveThe study aims to determine whether BPD is associated with an increased risk of subsequent STI in Taiwan.MethodsOverall 669 patients with BPD and 2676 controls matched by gender and age were enrolled between 2000 and 2012 and followed until the end of 2013 using Taiwan’s National Health Insurance Research Database. During the follow-up period, participants who developed STI (human immunodeficiency virus, syphilis, genital warts, gonorrhoea, chlamydia and trichomoniasis) were identified. Cox regression analysis was used to calculate the hazard ratio (HR) with 95% confidence interval (CI) of the STI incidence rate between patients with BPD and unaffected controls.ResultsPatients with BPD were predisposed to developing STI (HR: 4.17, 95% CI 1.62 to 10.8) after adjusting for demographic data and psychiatric comorbidities. The stratification analysis revealed a similar risk trend with BPD and subsequent STI in each gender and age group and was significant in the subgroups of male (HR: 11.3, 95% CI 2.97 to 42.7) and those aged 18–34 years (HR: 4.85, 95% CI 1.71 to 13.7). Also, the comorbidity stratification analysis revealed that, when the effect of comorbidities was excluded, patients with pure BPD significantly exhibited the risk association for subsequent STI after adjusting for all variables (HR: 4.24, 95% CI 1.25 to 14.4).ConclusionGiven the greater potential of BPD to be associated with an increased risk of STI, there should be direct implications for the development of targeted prevention interventions in Taiwan’s mental health clinics.

Since many studies have shown a reduction in the incidence of rheumatoid arthritis (RA) in patients with schizophrenia (SCZ), little effort has been devoted to studying this link in the Asian population. Moreover, the relationship between these two disorders could be bidirectional, but the influence of RA on the SCZ incidence is unclear. The study aims to determine whether there is a bidirectional association between RA and SCZ in an Asian population. We analyzed a 10-year population- based longitudinal cohort using the National Health Insurance Research Database of Taiwan. In the first analysis, we included a total of 58,847 SCZ patients and 235,382 non-SCZ controls, and in the second analysis, a total of 30,487 RA patients and 121,833 non-RA controls, both matched by gender, age, and index date. Cox regression analyses were performed to examine the risk of RA incidence in the first analysis and the risk of SCZ incidence in the second analysis. The main finding of this study was the discovery of a lower incidence of RA in patients with SCZ (hazard ratio (HR): 0.48, 95% confidence interval (95% CI): 0.31–0.77) after adjustment for baseline demographics and comorbidities. Additionally, the presence of RA predicted a reduced incidence rate for SCZ, but the estimate was not statistically significant (HR: 0.77, 95% CI: 0.44–1.37). The study found a unidirectional association between RA and SCZ. However, RA has an age of onset later than RA, and the protective effect of RA on SCZ incidence would be biased due to the limited number of cases.

Background Previous studies have suggested that sexually transmitted infections (STI) tend to increase in patients with bipolar disorder during a manic or hypomanic episode. However, in the long-term course of this disease, it is unclear whether patients with bipolar disorder have a higher risk of incident STI. Methods Using the National Health Insurance Research Database of Taiwan, 3721 patients with bipolar disorder and 14,884 controls without bipolar disorder matched by gender and age were enrolled between 2000 and 2010 and followed up until the end of 2013. Participants who developed any STI (human immunodeficiency virus [HIV], syphilis, genital warts, gonorrhea, chlamydial infection, and trichomoniasis) during the follow-up period were identified. Cox regression analysis was performed to examine the risk of STI between patients with bipolar disorder and comparative controls. Results Patients with bipolar disorder were prone to develop STI (hazard ratio [HR], 1.67, 95% confidence interval [95% CI], 1.27-2.18) especially for HIV (HR, 3.59; 95% CI, 1.16-11.08) and syphilis (HR, 2.26; 95% CI, 1.06-4.85). In addition, this study found that the incidence of STI was higher among women than men (HR, 1.83; 95% CI, 1.41-2.39). Conclusions This study shows that bipolar disorder is associated with an increased risk of developing STI, which has direct implications for the development of targeted prevention interventions or regular sexual health screening in mental health clinics to reduce the disproportionate burden of HIV and other STI in patients with bipolar disorder.

Objectives In Taiwan, there has been a growing emphasis on physical health screening, health education and improving access to treatment in patients with schizophrenia (SCZ). However, sexual health needs, including screening and prevention of sexually transmitted infections (STI), are neglected in this population. The study aimed to investigate the association between SCZ and the subsequent incident STI and to examine potential risk factors. Methods Using the National Health Insurance Research Database of Taiwan, 58,948 SCZ patients and 235,784 controls matched by gender and age were enrolled between 2000 and 2010 and followed until the end of 2011. Participants who developed any STI (HIV, syphilis, genital warts, gonorrhea, chlamydial infection, and trichomoniasis) during the follow-up period were identified. Cox regression analysis was performed to examine the risk of STI between SCZ patients and controls. Results SCZ patients were predisposed to developing STI (hazard ratio (HR): 1.11, 95% confidence interval (95% CI): 1.01–1.21) that could be caused by syphilis (HR: 2.58, 95% CI: 2.14–3.10) or possibly HIV (Crude HR: 1.39, 95% CI: 1.04–1.86; adjusted HR: 1.11, 95% CI: 0.81–1.52). Additionally, this study found that female, young adults, low-income, living in less urbanized areas, and comorbid substance abuse were potential risk factors for developing STI. Conclusion This study shows that SCZ is associated with an increased risk of developing STI, which has direct implications for the development of targeted prevention interventions or regular sexual health screening in mental health clinics to reduce the disproportionate burden of HIV and other STI in SCZ patients.

Studies suggested autoimmunity plays a role in the etiology of obsessive–compulsive disorder (OCD). The purpose of this study was to determine if a history of systemic autoimmune diseases (SADs) is associated with an increased risk of subsequent onset of OCD. Patients with or without SADs were identified in the Taiwan National Health Insurance Program. The SADs cohort consisted of 63,165, while the comparison cohort consisted of 315,825 patients. The incidence rates of OCD with a maximum follow-up period of 10 years between patients with and without SADs were compared using a Cox proportional hazard model to estimate the hazard ratio (HR) and 95% confidence interval (95% CI). The major finding was the discovery of a higher incidence of subsequent OCD among patients with SADs (HR: 1.85; 95% CI 1.41–2.43) after adjusted for other demographic characteristics. Specifically, the risk of OCD was observed to be significant increase in systemic lupus erythematosus (1.65, 1.07–2.54) dermatomyositis (3.25, 1.04–10.17), and Sjogren’s syndrome (2.38, 1.53–3.72). Also, this study revealed some potential risk factors for developing OCD, including younger age (less than or equal to 50-year-old) and some comorbidities (alcohol use disorder, liver cirrhosis, and malignancies). Conversely, this study found that steroid use was a potential protective factor for the development of OCD. This study confirms that SADs are associated with higher incidence of OCD, suggesting that abnormal autoimmune process is associated with increased expression of psychiatric disturbances.

Heat shock protein 27 (HSP27) is a molecular chaperone adapting to stresses and sustaining physiological functions. Neuronal or ubiquitous overexpression of HSP27 which is located in nucleus can enhance stress resistance and extend lifespan in Drosophila. However, whether the nuclear localization of HSP27 is required for enhanced stress response and longevity remains unknown. Here we report that nuclear localization of HSP27 plays an important role in starvation response and longevity upon overexpression in Drosophila. Site-directed mutagenesis of three arginine residues responsible for HSP27 nuclear localization to glycines excludes mutant HSP27 in nucleus and instead accumulates in cytoplasm. While overexpressing wild-type HSP27 confers starvation resistance, overexpression of the mutant HSP27 fails to retain the enhanced starvation tolerance in the transgenic flies. Overexpressing the mutant HSP27 in neurons or ubiquitously loses the ability to extend lifespan in Drosophila. Together, the results shed a light on the importance of nuclear localization of HSP27 in modulating starvation response and longevity in Drosophila. The further identification of nuclear HSP27 interacting proteins accountable for starvation adaptation and longevity will be next to pursue.

Objectives Schizophrenia is a highly inheritable disorder, but many aspects of its etiology and pathophysiology remain poorly understood. Recently, in the Han Chinese population, a SNP rs1635 located within the exon of the NKAPL gene (encoding NFKB activating protein-like) achieved genome-wide significance in schizophrenia. Methods In order to find the causal variants of the NKAPL gene in schizophrenia, we searched for genetic variants in the promoter region, and exons (including both UTR ends) using direct sequencing in a sample of patients with schizophrenia (n = 515) and non-psychotic controls (n = 456), all Han Chinese from Taiwan, and conducted an association and rudimentary functional study. Results We identified 5 common SNPs (defined as minor allele frequency (MAF) > 0.01) in the NKAPL gene. In a case–control association analysis, the minor allele (A) of rs1635 was significantly more common among patients than controls (P = 0.0003, OR = 1.41, 95% CI = 1.17–1.71). A haplotype analysis of the 5 common SNPs indicated a risk haplotype (rs12000C–rs1635A–rs9461446C–rs3734564G–rs1679709G) associated with schizophrenia (P = 2.77e-005, OR = 1.53, 95% CI = 1.25–1.87). In addition, we identified 4 patient-specific rare SNPs (MAF A, c.213G > A, c.752C > T (rs370337122), and c.844G > A (rs147161729)) within the NKAPL gene. In silico analysis demonstrated their functional impact on the protein; however, there was also 1 control-specific rare SNP (c.119G > A) detected within the NKAPL gene, indicating that the clinical relevance of these putatively pathological rare SNPs is not straightforward. Conclusions This study suggested that rs1635 in the NKAPL gene appeared to play a role in conferring susceptibility to schizophrenia. In addition, some rare SNPs in the NKAPL gene with possibly damaging effects may be important in our patients. Our study provides genetic clues to indicate the involvement of NKAPL in schizophrenia.

Objectives Synaptophysin (SYP) has been shown to be critical for regulating neurotransmitter release and synaptic plasticity, a process thought to be disrupted in schizophrenia. In addition, abnormal SYP expression in different brain regions has been linked to this disorder in postmortem brain studies. We investigated the involvement of the SYP gene in the susceptibility to schizophrenia. Methods We searched for genetic variants in the promoter region, all exons, and both UTR ends of the SYP gene using direct sequencing in a sample of patients with schizophrenia (n = 586) and non-psychotic controls (n = 576), both being Han Chinese from Taiwan, and conducted an association and functional study. Results We identified 2 common SNPs (c.*4+271A>G and c.*4+565T>C) in the SYP gene. SNP and haplotype-based analyses displayed no associations with schizophrenia. In addition, we identified 6 rare variants in 7 out of 586 patients, including 1 variant (g.-511T>C) located at the promoter region, 1 synonymous (A104A) and 2 missense variants (G293A and A324T) located at the exonic regions, and 2 variants (c.*31G>A and c.*1001G>T) located at the 3′UTR. No rare variants were found in the control subjects. The results of the reporter gene assay demonstrated the influence of g.-511T>C and c.*1001G>T on the regulatory function of the SYP gene, while that the influence of c.*31G>A may be tolerated. In silico analysis demonstrated the functional relevance of other rare variants. Conclusion Our study lends support to the hypothesis of multiple rare mutations in schizophrenia, and provides genetic clues that indicate the involvement of SYP in this disorder.

In earlier reports, growth-associated protein 43 (GAP-43) has been shown to be critical for initial establishment or reorganization of synaptic connections, a process thought to be disrupted in schizophrenia. Additionally, abnormal GAP-43 expression in different brain regions has been linked to this disorder in postmortem brain studies. In this study, we investigated the involvement of the gene encoding GAP-43 in the susceptibility to schizophrenia.We searched for genetic variants in the promoter region and 3 exons (including both UTR ends) of the GAP-43 gene using direct sequencing in a sample of patients with schizophrenia (n=586) and non-psychotic controls (n=576), both being Han Chinese from Taiwan, and conducted an association and functional study.We identified 11 common polymorphisms in the GAP-43 gene. SNP and haplotype-based analyses displayed no associations with schizophrenia. Additionally, we identified 4 rare variants in 5 out of 586 patients, including 1 variant located at the promoter region (c.-258-4722GT) and 1 synonymous (V110V) and 2 missense (G150R and P188L) variants located at exon 2. No rare variants were found in the control subjects. The results of the reporter gene assay demonstrated that the regulatory activity of construct containing c.-258-4722T was significantly lower as compared to the wild type construct (c.-258-4722G; p0.001). In silico analysis also demonstrated the functional relevance of other rare variants.Our study lends support to the hypothesis of multiple rare mutations in schizophrenia, and it provides genetic clues that indicate the involvement of GAP-43 in this disorder.

The payment schemes used in mergers and acquisitions (M&As) have attracted attention from finance and management scholars. Although prior finance studies examined variations in the cash-plus-stock ...

Luteolin, a flavonoid nutraceutical abundant in vegetables and fruits, exhibits a wide range of bioactive properties, including antioxidant, anti-inflammatory and anti-cancer activities. Pituitary tumor-transforming gene 1 (PTTG1), an oncoprotein that regulates cell proliferation, is highly expressed in several types of cancer cells including leukemia. In this study, we aim to investigate the anti-cancer effects of luteolin on cells with differential PTTG1 expression and their underlying mechanisms in human myeloid leukemia cells. Methyl thiazolyl tetrazolium (MTT) assay data showed that luteolin (25–100 μM) significantly reduced cell viability in THP-1, HL-60 and K562 cells but did not affect normal peripheral blood mononuclear cells (PBMCs). Flow cytometric analysis and Western blot data demonstrated that luteolin induced a stronger apoptosis on undifferentiated myeloid leukemia cells with higher PTTG1 protein levels than on 12-myristate 13-acetate (PMA)- or all-trans-retinoic acid (ATRA)-differentiated cells with lower PTTG1 expression. Furthermore, PTTG1 knockdown by shRNA in leukemia cells suppressed cell proliferation, arrested cell-cycle progression and impaired the effectiveness of luteolin on cell-cycle regulation. Moreover, PTTG1-knockdown cells with luteolin exposure presented a reduction of the apoptotic proteins and maintained higher levels of the anti-apoptotic proteins such as Mcl-1, Bcl-2 and p21, which exhibited greater resistance to apoptosis. Finally, microarray analysis showed that 20 genes associated with cell proliferation, such as CXCL10, VEGFA, TNF, TP63 and FGFR1, were dramatically down-regulated in PTTG1-knockdown cells. Our current findings clearly demonstrate that luteolin-triggered leukemic cell apoptosis is modulated by the differential expression of the PTTG1. PTTG1 oncoprotein overexpression may modulate cell proliferation-related regulators and enhance the response of myeloid leukemia cells to luteolin. Luteolin is beneficial for the treatment of cancer cells with highly expressed PTTG1 oncoprotein.

Aripiprazole acts as a partial agonist at dopamine D2 and D3 and serotonin 1A receptors and as an antagonist at serotonin 2A receptors (HTR2A). Since aripiprazole acts as an antagonist at HTR2A, genetic variants of HTR2A may be important in explaining variability in response to aripiprazole. This study investigated whether the efficacy of aripiprazole can be predicted by functional HTR2A A-1438G/T102C polymorphisms (rs63311/rs6313) as modified by clinical factors in Han Chinese hospitalized patients with acutely exacerbated schizophrenia. After hospitalization, the patients (n = 128) were given a 4-week course of aripiprazole. Patients were genotyped for HTR2A A-1438G/T102C polymorphisms via the restriction fragment length polymorphism method. Clinical factors such as gender, age, duration of illness, education level, diagnostic subtype, and medication dosage were noted as well. The researchers measured psychopathology biweekly, using the Positive and Negative Syndrome Scale (PANSS). A mixed model regression approach (SAS Proc MIXED) was used to analyze the effects of genetic and clinical factors on PANSS performance after aripiprazole treatment. We found that the GG/CC genotype group of HTR2A A-1438G/T102C polymorphisms predicts poor aripiprazole response specifically for negative symptoms. In addition, the clinical factors, including dosage of aripiprazole, age, duration of illness, and diagnostic subtype, were found to influence PANSS performance after aripiprazole treatment. The data suggest HTR2A A-1438G/T102C polymorphisms may predict negative symptoms performance upon aripiprazole treatment in schizophrenic patients as modified by clinical factors.

Objectives Aripiprazole, a novel antipsychotic agent, acts as a partial agonist at dopamine D2 receptors (DRD2). We investigate whether its efficacy is predictable by DRD2/ANKK1 gene polymorphisms and clinical factors in Han Chinese hospitalized patients with acutely exacerbated schizophrenia. Method After hospitalization, the patients (n = 128) were given aripiprazole for up to 4 weeks. They were genotyped for four functional DRD2/ANKK1 polymorphisms: −141 Ins/Del, Ser311Cys, C957T, and TaqIA. Clinical factors such as gender, age, illness duration, education level, diagnostic subtype, and medication dosage were also recorded. Psychopathology was measured biweekly with the positive and negative syndrome scale (PANSS). The effects of genetic and clinical factors on PANSS performance upon aripiprazole treatment were analyzed by a mixed modeling approach (SAS Proc MIXED). Results Compared to the patients with TaqI A2/A2 genotype, A1 carriers are associated with superior therapeutic response on positive symptoms after 4-week aripiprazole treatment. Regarding the C957T polymorphism, patients with C/C genotype were associated with poor aripiprazole response for excitement symptoms when compared with T/T patients. The other two polymorphisms, −141 Ins/Del, and Ser311Cys, have no significant effects on PANSS performance. The clinical factors including medication dosage, illness duration, and diagnostic subtype could influence PANSS performance upon aripiprazole treatment. Conclusion This study suggests that DRD2/ANKK1 gene variations and some clinical factors may predict individual response to aripiprazole.

The study explores development of the concept of death among 204 Chinese children and adolescents and analyzes the relationships between death concept development and background variables. A coding manual for content analysis of death constructs adapted from R. A. Neimeyer et al. (1983) was used to classify each construct in the paragraphs written by participants regarding their views of death. The 6 categories most frequently identified were Internal Causality, Negative Emotion State, External Causality, Nonexistence, Negative Body State, and Existence. Death-related experiences did not significantly influence concepts regarding death, while significant differences emerged as a function of grade, gender, religion, and family death discussion for several death constructs. Compared with earlier American samples, Chinese children and adolescents identified less with choice and purposeful death constructs and were less likely to view death in terms of personal choice and morals or in terms of psychological or natural meaning. Whether the differences were due to cultural, methodological or age factors deserves further study. Finally, this study concludes with some recommendations for the future study of death constructs.

Prion diseases are induced by pathologically misfolded prion protein (PrPSc), which recruit normal sialoglycoprotein PrPCby a template-directed process. In this study, we investigated the expression of PrPCin a rat model of cerebral ischemia to more fully understand its physiological role. Immunohistochemical analysis demonstrated that PrPC-immunoreactive cells increased significantly in the penumbra of ischemic rat brain compared with the untreated brain. Western blot analysis showed that PrPCprotein expression increased in ischemic brain tissue in a time-dependent manner. In addition, PrPCprotein expression was seen to colocalize with neuron, glial, and vascular endothelial cells in the penumbric region of the ischemic brain. Overexpression of PrPCby injection of rAd (replication-defective recombinant adenoviral)-PGK (phosphoglycerate kinase)-PrPC-Flag into ischemic rat brain improved neurological behavior and reduced the volume of cerebral infarction, which is supportive of a role for PrPCin the neuroprotective adaptive cellular response to ischemic lesions. Concomitant upregulation of PrPCand activated extracellular signal-regulated kinase (ERK1/2) under hypoxia–reoxygenation in primary cortical cultures was shown to be dependent on ERK1/2 phosphorylation. During hypoxia–reoxygenation, mouse neuroblastoma cell line N18 cells transfected with luciferase rat PrPCpromoter reporter constructs, containing the heat shock element (HSE), expressed higher luciferase activities (3- to 10-fold) than those cells transfected with constructs not containing HSE. We propose that HSTF-1 (hypoxia-activated transcription factor), phosphorylated by ERK1/2, may in turn interact with HSE in the promoter of PrPCresulting in gene expression of the prion gene. In summary, we conclude that upregulation of PrPCexpression after cerebral ischemia and hypoxia exerts a neuroprotective effect on injured neural tissue. This study suggests that PrPChas physiological relevance to cerebral ischemic injury and could be useful as a therapeutic target for the treatment of cerebral ischemia.

Background Autophagy and molecular chaperones both regulate protein homeostasis and maintain important physiological functions. Atg7 (autophagy-related gene 7) and Hsp27 (heat shock protein 27) are involved in the regulation of neurodegeneration and aging. However, the genetic connection between Atg7 and Hsp27 is not known. Methods The appearances of the fly eyes from the different genetic interactions with or without polyglutamine toxicity were examined by light microscopy and scanning electronic microscopy. Immunofluorescence was used to check the effect of Atg7 and Hsp27 knockdown on the formation of autophagosomes. The lifespan of altered expression of Hsp27 or Atg7 and that of the combination of the two different gene expression were measured. Results We used the Drosophila eye as a model system to examine the epistatic relationship between Hsp27 and Atg7. We found that both genes are involved in normal eye development, and that overexpression of Atg7 could eliminate the need for Hsp27 but Hsp27 could not rescue Atg7 deficient phenotypes. Using a polyglutamine toxicity assay (41Q) to model neurodegeneration, we showed that both Atg7 and Hsp27 can suppress weak, toxic effect by 41Q, and that overexpression of Atg7 improves the worsened mosaic eyes by the knockdown of Hsp27 under 41Q. We also showed that overexpression of Atg7 extends lifespan and the knockdown of Atg7 or Hsp27 by RNAi reduces lifespan. RNAi-knockdown of Atg7 expression can block the extended lifespan phenotype by Hsp27 overexpression, and overexpression of Atg7 can extend lifespan even under Hsp27 knockdown by RNAi. Conclusions We propose that Atg7 acts downstream of Hsp27 in the regulation of eye morphology, polyglutamine toxicity, and lifespan in Drosophila.

In recent years, the identification of several new dystonia genes has provided important insights into the nature of this clinically and genetically heterogeneous disorder. Currently, about twenty different forms of monogenic dystonia are distinguished genetically and have been designated DYT 1–13; DYT 14, which has been redefined as DYT 5; and DYT 15–21 (Ozelius et al., 2011; Wider et al., 2008). Among these DYTs, ten genes have been identified using linkage analysis in families: DYT 1, 3, 5/14, 6, 8, 11, 12, 16, and 18 (See Table 1 and Figure 1) (Ozelius et al., 2011).

Objectives Schizophrenia is a highly heritable disorder, but many aspects of its etiology and pathophysiology remain poorly understood. Recently, a SNP rs12807809 located upstream of the neurogranin (NRGN) gene achieved genome-wide significance in this disorder. Methods In order to find the causal variants of NRGN gene in schizophrenia, we searched for genetic variants in the promoter region and all the exons (including both UTR ends and rs12807809) using direct sequencing in a sample of patients with schizophrenia (n = 346) and non-psychotic controls (n = 345), both being Han Chinese from Taiwan, and conducted an association and functional study. Results We identified 7 common polymorphisms in the NRGN gene. SNP and haplotype-based analyses displayed no associations with schizophrenia. Additionally, we identified 5 rare variants in 6 out of 346 patients, including 3 rare variants located at the promoter region (g.-620A>G, g.-578C>G, and g.-344G>A) and 2 rare variants located at 5′ UTR (c.-74C>G, and c.-41G>A). No rare variants were found in the control subjects. The results of the reporter gene assay demonstrated that the regulatory activity of construct containing g.-620G, g.-578G, g.-344A, c.-74G, and c.-41A was significantly lower as compared to the wild type construct (P In silico analysis also demonstrated their influences on the regulatory function of NRGN gene. Conclusions Our study lends support to the hypothesis of multiple rare mutations in schizophrenia, and provides genetic clues that indicate the involvement of NRGN in this disorder.

Inhalants encompass a wide range of pharmacologically diverse substances that readily vaporize. They are widely available and frequently misused. The type, frequency, and method of inhalant abuse vary widely in relation to the age of the abuser, the geographic region, and availability. Inhalant abuse causes psychosocial as well as organic morbidity. The chief organic morbidity is dementia and cerebellar dysfunction. Death due to inhalant abuse can occur by several mechanisms, including asphyxia, suffocation, risky behaviors, aspiration, and sudden sniffing death syndrome. The Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision provides two categories of inhalant-related disorders. The first category is inhalant use disorders (inhalant abuse and dependence), which are characterized by a maladaptive pattern of inhalant use. The second category is inhalant-induced disorders (intoxication delirium, persisting dementia, psychotic disorder, anxiety disorder, and mood disorder), which result from the toxic effects of inhalants. This chapter reviews important aspects of inhalant addiction and makes several recommendations involving prevention and education strategies to address this problem.

This study administered an open-ended questionnaire about death and the Multidimensional Fear of Death Scale (MFODS) to explore the relationships between personal constructs about death and fears of death among Taiwanese adolescents. The sample included 329 adolescents in junior and senior high school grades 7 to 12. A coding manual was used to conduct content analysis of death constructs in paragraphs about death written by respondents, and the MFODS was used to measure fear of death. The results revealed that concepts and fears about death differed significantly according to grade, gender, religion, death-related experiences, and death-related discussions in the family. Constructs regarding negative emotional states, as well as low levels of attachment, emerged as significant predictors of the seven MFODS subscales. Generalization of these results to other populations merits further investigation.

Aripiprazole, a novel antipsychotic agent, has a unique pharmacological action (partial agonist) on the dopamine neurotransmission system. Aripiprazole has high affinity for dopamine D2 and D3 receptors (DRD2 and DRD3). We investigated whether the efficacy of aripiprazole can be predicted by a functional DRD3 gene polymorphism Ser9Gly (rs6280) as modified by clinical factors in Han Chinese hospitalized patients with acutely exacerbated schizophrenia. After hospitalization, the patients (n=128) were given aripiprazole for up to four weeks. Patients were genotyped for DRD3 Ser9Gly polymorphism by Restriction Fragment Length Polymorphism (RFLP) method. Clinical factors such as gender, age, duration of illness, education level, diagnostic subtype and medication dosage were recorded. Psychopathology was measured biweekly with the Positive and Negative Syndrome Scale (PANSS). The effects of genetic and clinical factors on PANSS performance after aripiprazole treatment were analyzed by a mixed model regression approach (SAS Proc MIXED). We found that, although the Ser carriers have numerically larger score reductions when compared with non-carriers in almost all PANSS dimensions, the difference of their effects are statically not significant. However, the clinical factors, including dosage of aripiprazole, age, duration of illness, and diagnostic subtype could influence PANSS performance after aripiprazole treatment. This study suggests that DRD3 Ser9Gly polymorphism may not contribute significantly to inter-individual differences in therapeutic efficacy of aripiprazole, but some clinical factors may predict treatment efficacy.