Sertindole, an Antipsychotic Drug, Curbs the STAT3/BCL-xL Axis to Elicit Human Bladder Cancer Cell Apoptosis In Vitro.

Bladder cancer is the leading urinary tract malignancy. Epidemiological evidence has linked lower cancer incidence in schizophrenia patients to long-term medication, highlighting the anticancer potential of antipsychotics. Sertindole is an atypical antipsychotic agent with reported anticancer action on breast and gastric cancers. Yet, sertindole's effect on bladder cancer remains unaddressed. We herein present the first evidence of sertindole's antiproliferative effect and mechanisms of action on human bladder cancer cells. Sertindole was cytotoxic against bladder cancer cells while less cytotoxic to normal urothelial cells. Apoptosis was a primary cause of sertindole's cytotoxicity, as the pan-caspase inhibitor z-VAD-fmk rescued cells from sertindole-induced killing. Mechanistically, sertindole inhibited the activation of signal transducer and activator of transcription 3 (STAT3), an oncogenic driver of bladder cancer, as sertindole lowered the levels of tyrosine 705-phosphorylated STAT3 along with that of STAT3's target gene BCL-xL. Notably, ectopic expression of the dominant-active STAT3 mutant impaired sertindole-induced apoptosis in addition to restoring BCL-xL expression. Moreover, bladder cancer cells overexpressing BCL-xL were refractory to sertindole's proapoptotic action, arguing that sertindole represses STAT3 to downregulate BCL-xL, culminating in the induction of apoptosis. Overall, the current study indicated sertindole exerts bladder cancer cytotoxicity by provoking apoptosis through targeted inhibition of the antiapoptotic STAT3/BCL-xL signaling axis. These findings implicate the potential to repurpose sertindole as a therapeutic strategy for bladder cancer.

Omega-3 fatty acids and blood-based biomarkers in Alzheimer's disease and mild cognitive impairment: A randomized placebo-controlled trial.

BACKGROUND: Increased serum levels of pro-inflammatory biomarkers are consistently associated with cognitive decline. The omega-3 unsaturated fatty acids (n-3 PUFAs) had been linked to slowing cognitive decline due to their potential anti-inflammatory effects. To our knowledge, the different regiments of pure DHA, pure EPA, and their combination on various associated symptoms of dementia, including a mild form of cognitive impairment (MCI) and Alzheimer's disease (AD), have never been studied. METHODS: This multisite, randomized, double-blind, placebo-controlled trial was conducted at two veteran's retirement centers and one medical center in central Taiwan between 2013 and 2015. 163 MCI or AD patients were randomly assigned to placebo (n = 40), docosahexaenoic acid (DHA, 0.7 g/day, n = 41), eicosapentaenoic acid (EPA, 1.6 g/day, n = 40), or EPA (0.8 g/day) + DHA (0.35 g/day) (n = 42) group for 24 months. The results were measured as the cognitive and functional abilities, biochemical, and inflammatory cytokines profiles. Chi-square tests, two-sample t-test, ANOVA, and linear mixedeffects models were conducted with p < 0.05. RESULTS: 131 (80%) participants had completed the trial with all cognitive, functional, and mood status assessments. The statistically significant difference between the placebo and treatment groups was not determined, concerning the changes in cognitive, functional, and mood status scores, the biochemical profiles, and inflammatory cytokines levels. However, EPA was found to reduce the C-C motif ligands 4 (CCL4) level (p < 0.001). Additionally, EPA could reduce the constructional praxis (p < 0.05) and spoken language ability scores (p < 0.01), and DHA also reduced the spoken language ability score (p < 0.05). CONCLUSION: Overall, n-3 PUFAs supplements did not reduce cognitive, functional, and depressive symptom outcomes, but spoken language ability and constructional praxis subitems of ADAS-cog. These findings show that attention to clinical heterogeneity in dementia is crucial when studying nutrients interventions, such as n-3 PUFAs. In addition, with small effect size CCL4 is a better indicator than other inflammatory cytokines for EPA treatment response.

Associations between daily steps and cognitive function among inpatients with schizophrenia.

BACKGROUND: Walking is the fundamental component of taking steps and is the main form of physical activity among individuals with schizophrenia; it also offers a range of health benefits. This study aimed to examine the associations between daily steps and cognitive function and further explored how many steps were related to better cognitive function among inpatients with schizophrenia. METHODS: Inpatients with schizophrenia were recruited from long-stay psychiatric wards across two hospitals (n=199 at site 1 and n=195 at site 2). Daily steps were collected with an accelerometer for 7 days. Four cognitive domains (attention, processing speed, reaction time, and motor speed) were tested at site 1, and two cognitive domains (attention and processing speed) were tested at site 2. The associations of daily steps and levels of steps/day with cognitive function were tested using multivariable linear regressions separated by site. Covariates included demographic variables, weight status, metabolic parameters, and clinical state. RESULTS: Participants took an average of 7445 (±3442) steps/day. More steps were related to better attention, processing speed, reaction time, and motor speed after multivariable adjustments. Compared with participants taking <5000 steps/day, those taking ≥5000 steps/day showed significantly better processing speed. Participants taking ≥7500 steps/day were associated with better attention, better reaction time, and better motor speed than those taking <5000 steps/day. CONCLUSION: Daily steps are associated with better cognitive function among inpatients with schizophrenia. The optimal benefit for cognitive function among this clinical population is achieving 7500 steps/day or more.

Increased risk of pulmonary and extrapulmonary tuberculosis infection in patients with polycystic kidney disease: a nationwide population-based study with propensity score-matching analysis.

BACKGROUND: Polycystic kidney disease (PKD) is a common renal disorder affecting approximately 1 in 1000 live births. Tuberculosis (TB) is an infectious disease worldwide. This study investigated the risk of TB infection in patients with PKD. METHODS: A nationwide population-based cohort study was performed using Taiwan's National Health Insurance Research Database. We used patients' hospitalization files for the entire analysis during 2000-2012. As per diagnosis, we divided patients into PKD and non-PKD cohorts and the major outcome was TB infection. RESULTS: A total of 13,540 participants with 6770 patients in each cohort were enrolled. The PKD cohort had a higher risk of TB infection than did the non-PKD cohort after adjusting for age, sex, and comorbidities (adjusted hazard ratio (aHR) = 1.91, 95% confidence interval [CI] = 1.51-2.43). When classifying by sites of pulmonary TB (PTB) and extrapulmonary TB (EPTB), the PKD cohort demonstrated a significantly higher risk of EPTB (aHR = 2.44, 95% CI = 1.46-4.08) as well as a risk of PTB (aHR = 1.69, 95% CI = 1.29-2.22). When stratified by the presence or absence of a comorbidity, high TB infection risk was noted in the PKD patients without any comorbidity (HR = 2.69, 95% CI = 1.69-4.30). CONCLUSIONS: Taken together, our findings suggest that PKD is associated with a 1.91-fold increased risk of TB infection. Medical professionls should maintain a high index of suspicion in daily practice for patients with PKD, particularly those with EPTB infection.

Low-Intensity Pulsed Ultrasound Attenuates LPS-Induced Neuroinflammation and Memory Impairment by Modulation of TLR4/NF-κB Signaling and CREB/BDNF Expression.

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

Effects of kidney function, serum albumin and hemoglobin on dementia severity in the oldest old people with newly diagnosed Alzheimer's disease in a residential aged care facility: a cross-sectional study.

BACKGROUND: Chronic kidney disease (CKD), low serum albumin, and anemia are known risk factors for cognitive decline in older people. We investigated the association between kidney function and cognitive impairment severity in oldest-old people with a diagnosis of Alzheimer's disease (AD). METHODS: A cross-sectional study of patients aged 80 years and older was conducted at a veterans' home in Taiwan between 2012 and 2016. Their estimated glomerular filtration rate (eGFR) was determined using the Modification of Diet in Renal Diseases (MDRD) equation. Cognitive function was evaluated with the Mini-Mental State Examination (MMSE) and Clinical Dementia Rating (CDR). RESULTS: A total of 84 patients (age mean ± SD, 86.6 ± 3.9 years) had MMSE scores of 10.1 ± 6.7, and CDR scores of 1.6 ± 0.7. The average eGFR was 61.7 ± 21.5 mL/min/1.73m2. The mean hemoglobin concentration was 12.7 ± 1.7 g/dl, and the mean albumin concentration was 4.5 ± 4.8 g/dl. Multivariate regression analyses showed that scores of CDR were significantly correlated with eGFR after adjustment for potential confounders. The scores of MMSE were significantly correlated with serum albumin and hemoglobin after adjustment for potential confounders. CONCLUSIONS: We found dementia severity was significantly associated with kidney function, serum albumin, and hemoglobin in the oldest-old with AD. We recommend that oldest-old people with a diagnosis of AD be evaluated to determine kidney function, as well as nutritional and hematological status. Further study is needed to establish whether prevention of CKD deterioration, and correction of malnutrition and anemia may help to slow cognitive decline in oldest-old people with dementia.

Predictors of Mortality in the Oldest Old Patients with Newly Diagnosed Alzheimer Disease in a Residential Aged Care Facility.

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

Comparative Effectiveness of Varenicline and Nicotine Replacement Therapy for Smoking Cessation in Older and Younger Smokers: A Prospective Cohort in Taiwan.

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

Randomization and resilience of brain functional networks as systems-level endophenotypes of schizophrenia.

Schizophrenia is increasingly conceived as a disorder of brain network organization or dysconnectivity syndrome. Functional MRI (fMRI) networks in schizophrenia have been characterized by abnormally random topology. We tested the hypothesis that network randomization is an endophenotype of schizophrenia and therefore evident also in nonpsychotic relatives of patients. Head movement-corrected, resting-state fMRI data were acquired from 25 patients with schizophrenia, 25 first-degree relatives of patients, and 29 healthy volunteers. Graphs were used to model functional connectivity as a set of edges between regional nodes. We estimated the topological efficiency, clustering, degree distribution, resilience, and connection distance (in millimeters) of each functional network. The schizophrenic group demonstrated significant randomization of global network metrics (reduced clustering, greater efficiency), a shift in the degree distribution to a more homogeneous form (fewer hubs), a shift in the distance distribution (proportionally more long-distance edges), and greater resilience to targeted attack on network hubs. The networks of the relatives also demonstrated abnormal randomization and resilience compared with healthy volunteers, but they were typically less topologically abnormal than the patients' networks and did not have abnormal connection distances. We conclude that schizophrenia is associated with replicable and convergent evidence for functional network randomization, and a similar topological profile was evident also in nonpsychotic relatives, suggesting that this is a systems-level endophenotype or marker of familial risk. We speculate that the greater resilience of brain networks may confer some fitness advantages on nonpsychotic relatives that could explain persistence of this endophenotype in the population.

Predictors of smoking reduction outcomes in a sample of 287 patients with schizophrenia spectrum disorders.

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

Secondary mania due to AIDS and cryptococcal meningitis in a 78-year-old patient.

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

Hydroxychloroquine reduces risk of incident diabetes mellitus in lupus patients in a dose-dependent manner: a population-based cohort study.

OBJECTIVE: SLE is associated with increased risk of diabetes mellitus. Treatment for SLE requires high-dose glucocorticoids that may worsen glucose homoeostasis. HCQ can reduce diabetes risk in RA. This study aimed to investigate the association of HCQ use and diabetes mellitus risk in SLE patients. METHODS: This nationwide, population-based cohort study was conducted using the Taiwan National Health Insurance Research Database. In the period 2001-10, 8628 newly diagnosed SLE patients were identified after excluding those with a previous diagnosis of RA, psoriasis or diabetes mellitus. Incidence of diabetes mellitus was identified as a new diagnostic code using a diabetes mellitus-specific medication. RESULTS: Two hundred and twenty-one newly diagnosed diabetes mellitus patients were identified among SLE patients (6795 had taken HCQ and 1833 had never taken HCQ), with an average follow-up period of 5.6 years. Compared with patients without HCQ treatment, the hazard ratio (HR) of diabetes mellitus in patients taking HCQ at a cumulative dose ≥129 g was reduced [HR 0.26 (95% CI 0.18, 0.37), P < 0.001]. Daily glucocorticoid ≥10 mg prednisolone-equivalent dose was associated with increased risk of developing diabetes mellitus [HR 2.47 (95% CI 1.44, 4.23), P = 0.001], which was minimized by concomitant HCQ use at a cumulative dose ≥129 g. CONCLUSION: In SLE patients, the use of HCQ is associated with reduced risk of incident diabetes mellitus in a dose-dependent manner. High-dose glucocorticoids increase the risk of diabetes, which can be decreased by concomitant HCQ use.

A reduced risk of stroke with lithium exposure in bipolar disorder: a population-based retrospective cohort study.

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

Onset age affects mortality and renal outcome of female systemic lupus erythematosus patients: a nationwide population-based study in Taiwan.

OBJECTIVE: The objective of this study was to investigate the impact of disease onset age on mortality and renal survival in female SLE patients. METHODS: This nationwide, population-based, retrospective cohort study used data from the National Health Insurance Research Database of Taiwan. Female patients newly diagnosed with SLE from 2001 to 2004 were identified as the study cohort. A non-SLE group was matched for age, sex and initial diagnosis date (index date) as the comparison cohort. Co-morbidities, mortality rates and end-stage renal disease (ESRD) incidences were compared among SLE patients of different onset age. Hazard ratios with a 95% CI were determined by the Cox proportional hazard model to quantify the mortality rates and ESRD incidences. Juvenile-onset, adult-onset and late-onset SLE patients were categorized according to disease onset age: <18, 18-50 and >50 years old. RESULTS: In total, 513 juvenile-onset, 3076 adult-onset and 764 late-onset SLE patients were identified. Compared with non-SLE controls, the hazard ratios of mortality were 6.49 (95% CI 3.73, 11.32, P < 0.001) for juvenile-onset, 1.75 (95% CI 1.47, 2.08, P < 0.001) for adult-onset and 3.44 (95% CI 2.76, 4.28, P < 0.001) for late-onset SLE patients. The hazard ratios of incident ESRD were 20.28 (95% CI 12.79, 32.15, P < 0.001) for adult-onset lupus patients and 1.99 (95% CI 1.36, 2.93, P < 0.001) for late-onset patients. CONCLUSION: Female patients with late-onset SLE carried a higher risk of mortality than those with adult-onset disease in the presence of co-morbidities. Juvenile-onset SLE patients were at greatest risk of mortality, which is probably due to disease severity.

Season of birth in obsessive-compulsive disorder.

BACKGROUND: Effects of season of birth (SOB) have been documented in numerous neuropsychiatric disorders. To date, few studies have evaluated this issue in obsessive-compulsive disorder (OCD). The aim of this study was to investigate the birth seasonality in OCD. METHODS: This study was based on Taiwan National Health Insurance Research Database. Data for the birth-year period 1956-1991 were extracted for analysis (273,837 males and 292,207 females). The International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM), code 300.3 was used as the diagnosis of OCD. Birth seasonality was compared between the OCD patients (519 males and 528 females) and the general population. RESULTS: The birth distributions across the 12 months were significantly different between the OCD patients and the general population (P-value for the Walter & Elwood's test = .04). A significant decrease of births from March to July and an excess from August to November in OCD patients as compared to the general population was noted (the relative risk of these months vs. the rest months of the year: 0.85 (95% CI 0.74-0.96) and 1.19 (95% CI 1.05-1.36). Effects of SOB in OCD were present in males (P-value for the Walter & Elwood's test = .03) but not in females. CONCLUSION: The findings support an effect of SOB in people with OCD, especially for men.

Germinal center kinase-like kinase overexpression in T cells as a novel biomarker in rheumatoid arthritis.

OBJECTIVE: Germinal center kinase-like kinase (GLK; also called MAPKKKK-3) activates protein kinase Cθ (PKCθ) during T cell activation and controls autoimmunity in lupus patients. Intracellular kinases are involved in the pathogenesis of rheumatoid arthritis (RA). We undertook this study to determine the role of GLK in RA. METHODS: The severity of collagen-induced arthritis (CIA) was studied in GLK-deficient mice. Expression levels of GLK from RA patients were determined by Western blotting, flow cytometry, real-time polymerase chain reaction, and immunohistochemical staining. Localization of GLK in T cells was identified by confocal microscopy. RA disease activity was assessed using the Disease Activity Score in 28 joints. RESULTS: GLK-deficient mice displayed impaired CIA development and decreased inflammatory cytokine levels. Local T cell infiltration and collagen restimulation responses were impaired by GLK deficiency. RA patients showed significantly higher GLK protein and messenger RNA levels in peripheral blood T cells than did healthy controls. GLK-overexpressing T cells in synovial fluid and synovial tissue samples from RA patients were increased compared with those from osteoarthritis patients. Confocal microscopy and flow cytometry showed that GLK colocalized and coexisted with phosphorylated PKCθ in T cells from RA patients. Frequencies of GLK-expressing T cells were significantly correlated with RA disease activity. CONCLUSION: GLK overexpression in T cells contributes to the pathogenesis of RA, indicating that GLK is a novel biomarker for autoimmune disease severity and a potential therapeutic target for RA.

Asthma in patients with attention-deficit/hyperactivity disorder: a nationwide population-based study.

BACKGROUND: Asthma symptoms can interrupt daily activities, disturb sleep, and increase the risk of a child having an attention deficit or irritability, which also are symptoms of attention-deficit/hyperactivity disorder (ADHD). Previous studies have shown conflicting results regarding the association between ADHD and asthma. This study investigates the possible correlation between asthma and ADHD. METHODS: We retrieved data on 221,068 pediatric patients from Taiwan's National Health Insurance Research Database in 2005, and calculated the prevalence and risk factors of allergic diseases among ADHD patients. RESULTS: The prevalence of asthma in the ADHD group, compared with the control group, was 4.3 fold higher in the age 12 to 17 subgroup (95% CI, 1.71 to 10.6), 1.5-fold higher in males (95% CI, 1.05 to 2.03), and 1.6-fold higher for children living in urban areas (95% CI, 1.12 to 2.28). Multivariate logistic regression models showed the odds ratio of asthma for children with ADHD was 1.43 (95% CI, 1.05 to 1.95) as compared with children without ADHD. CONCLUSIONS: Pediatric ADHD was associated positively with asthma, but the underlying mechanisms require further clarification.

Prevalence of gastroesophageal reflux disease in major depressive disorder: a population-based study.

BACKGROUND: Gastroesophageal reflux disease (GERD) is a common physical disease among psychiatric patients. OBJECTIVE: We conducted this study to investigate the prevalence and risk of GERD in patients with major depressive disorder (MDD) in Taiwan. METHODS: We conducted a cross-sectional study using the National Health Insurance Research Database in Taiwan. The study subjects included 4790 patients with MDD and 728,749 people in the general population during 2005. Distributions of GERD as well as age, gender, income, region of residence, and medical comorbidities, such as diabetes mellitus, hypertension, renal disease, hyperlipidemia, and ischemic heart disease, in the 2 groups were examined by χ(2)-tests. Multivariate logistic regression models were used to analyze the associations between MDD and GERD. RESULTS: The 1-year prevalence rates of GERD in patients with MDD and the general population were 3.75% and 1.05%, respectively. The prevalence rate of GERD was significantly higher in patients with MDD in all age, sex, insurance amount, region, and urbanicity subgroups (all p < 0.001). The multivariate logistic regression analysis showed that patients with MDD were significantly associated with an increased rate for GERD ([Odds Ratio] = 3.16; 95% Confidence Interval = 2.71-3.68; p < 0.001). CONCLUSION: The prevalence of GERD was significantly higher in patients with MDD. In clinical practice, psychiatrists should pay attention to the possibility of GERD symptoms, such as heartburn, regurgitation, or dysphagia, and should consider consulting Gastroenterology specialists when clinically indicated.

The association of selective serotonin reuptake inhibitors use and stroke in geriatric population.

OBJECTIVES: Selective serotonin reuptake inhibitor (SSRI) exposure has controversial results in increasing the stroke risk. With the risk of stroke increased with age, the safety of SSRI use among older adults attracts much concern. METHODS: We analyzed 28,145 subjects older than 65 years from a subset of a 9-year cohort database from the National Health Insurance Research Database, Taiwan. RESULTS: The survival analysis showed a greater probability of stroke in subjects with SSRI exposure after adjusting other covariates. Compared with other variables, SSRI exposure had the strongest effect (hazard ratio: 2.66, 95% confidence interval: 2.21-3.20). The risk was independent to depression-related stroke risk. CONCLUSIONS: The use of SSRIs independently increases the risk of stroke among older patients. SSRIs are still practically safe to most users, providing precautionary measures are taken.