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Introduction : Diabetes mellitus (DM) is associated with worse surgical outcomes, and is a risk factor for bladder cancer and subsequent oncological outcomes. This study evaluated outcomes robot-assisted radical cystectomy (RARC) compared to open radical cystectomy (ORC) in patients with DM. Materials and Methods : Data of adults ≥ 18 years old with DM who underwent radical cystectomy were extracted from the United States National Inpatient Sample database 2005-2018. The outcomes were in-hospital mortality, prolonged length of stay (LOS), and postoperative complications. Results : Data of 2,765 patients were analyzed. Patients who received RARC had a significantly lower odds of prolonged LOS (adjusted odd ratio (aOR) = 0.56, 95% CI: 0.45, 0.71), unfavorable discharge (aOR = 0.74, 95% CI: 0.56, 0.97), urinary complications (aOR = 0.75, 95% CI: 0.57, 0.98) and wound and device-related complications (aOR = 0.59, 95% CI: 0.41, 0.86) than ORC. Of patients < 70 years old, RARC was significantly associated with decreased odds for urinary complications (aOR = 0.59, 95% CI: 0.41, 0.84) and wound and device-related complications (aOR = 0.55, 95% CI: 0.32, 0.94) compared to ORC. In patients with a Charlson Comorbidity Index score of 0-1, RARC was associated with a lower risk of urinary complications (aOR = 0.74, 95% CI: 0.56, 0.98) and wound and device-related complications (aOR = 0.63, 95% CI: 0.43, 0.93) compared to ORC. Conclusions : In patients with DM and bladder cancer, RARC appears to be associated with better short-term outcomes in terms of reduced risks of prolonged LOS, unfavorable discharge, urinary complications, and wound and device-related complications compared to ORC., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: This study investigated the use of ultrasound-guided extracorporeal shock wave lithotripsy (ESWL) to break stones in the genitourinary tract and prevent genitourinary injury. Our goals were to achieve accurate focusing and minimal X-ray exposure for the benefit of the patients., Methods: The LiteMed LM-9200 lithotripter with ultrasonography and fluoroscopy was used for two different procedures: autoaimed and autoperiodical. These procedures enabled dual focusing on stone localization and tracking., Results: Out of 108 patients who underwent autoperiodical procedures, 29 had no gross hematuria. Among the 335 patients who received autoaimed procedures, 194 had no gross hematuria. The average duration of X-ray exposure during autoperiodical and autoaimed procedures was 120 and 50 s, respectively., Conclusion: The ultrasound-guided ESWL with minimal X-ray exposure was found to be useful in treating genitourinary upper-tract urolithiasis in the autoaimed procedure. Patients who underwent the autoaimed procedure experienced less gross hematuria compared to those who underwent the autoperiodical procedure., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Neck hybrid schwannoma/neurofibromas are uncommon and classified as peripheral nerve sheath tumors (PNSTs). PNSTs develop from soft tissues, of which schwannoma, perineurioma, and neurofibroma are the most common. Hybrid PNSTs consist of more than 1 type of PNST, such as hybrid schwannoma/neurofibromas. The exact epidemiology and pathogenesis of these tumors are still largely unknown because of the limited studies on this topic. Such tumors can spread over the soft tissues, although most cases reported involve the subcutaneous layer or dermis. Some studies have suggested that hybrid schwannoma/neurofibromas may be associated with neurofibromatosis. We present a case of a 51-year-old female patient with a neck hybrid schwannoma/neurofibroma diagnosed by histopathology and immunohistochemistry. The patient was referred to the neurology department for neurofibromatosis screening, which reported negative results. After 12 months, the patient showed no evidence of tumor recurrence., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Chronic kidney disease (CKD) patients possess a higher risk for renal cell carcinoma (RCC) possibly because of related underlying inflammation and immune dysregulation. In the current population-based cohort study, we evaluate the effects of influenza vaccination on RCC among CKD patients., Methods: We analysed the vaccinated and unvaccinated CKD patients (≥55 years of age) identified from the Taiwan National Health Insurance Database. Propensity score matching was used to reduce the selection bias. Subgroup analyses based on comorbid conditions, dialysis status and vaccinated dosages were also conducted., Results: The incidence of RCC decreased significantly in the vaccinated compared with unvaccinated group {unadjusted hazard ratio [HR] 0.50 [95% confidence interval (CI) 0.31-0.81], P  < .01; adjusted HR 0.46 [95% CI 0.28-0.75], P  < .01}. Such protective effects of influenza vaccination were noted significantly among those ≥75 years of age [unadjusted HR 0.29 (95% CI 0.12-0.74), P  < .01; adjusted HR 0.22 (95% CI 0.08-0.58), P  < .01]. A reverse association was noted between the total number of vaccinations and RCC events in both unadjusted and adjusted models. The Kaplan-Meier estimates of the RCC events showed significantly higher free survival rates in the vaccinated as compared with the unvaccinated patients (logrank P  = .005)., Conclusion: This population-based cohort study found a significant inverse relationship between influenza vaccination and the risk of RCC in CKD patients and the protective effects were more prominent in patients >75 years of age. A possible relation exists between the total number of vaccinations and RCC events. Future randomized clinical and basic studies will be needed to prove these findings and underlying pathophysiological mechanisms., Competing Interests: The authors declare no conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

With the quickly growing population of patients receiving dialysis treatment in Taiwan in recent years, concerns about whether more incidence of inguinal hernia exists in dialysis patients are increasing. In Taiwan, peritoneal dialysis (PD) and hemodialysis (HD) are the 2 most common dialysis types. Therefore, the relationship between dialysis type and inguinal hernia occurrence needs to be evaluated and compared. Our retrospective cohort study included a study population total of 3891 patients diagnosed with end stage renal disease (ESRD) under the HD or PD procedure from 2001 to 2009 from the Longitudinal Health Insurance Database. Also, International Statistical Classification of Diseases and Related Health Problems 9th Revision codes were used to identify ESRD and hernia occurrence. Cox proportional-hazards regression model was applied to measure the risk factors to the hernia occurrence. During the follow-up periods of 3 years, the number of hernia occurrences was 44 (1.13%), 1 (0.03%), and 8 (0.21%) with inguinal, femoral, and ventral hernias, respectively. Only the dialysis type revealed significantly increased hernia risk because PD would increase hernia risk 7 times (adjusted hazard ratio [aHR] = 6.98, 95% CI = 3.59-13.25) than HD. If the patients received PD and shifted to HD later, the risk of hernia was 5 times (aHR = 4.98, 95% CI = 2.29-10.85) than patients with HD. Patients with ESRD receiving PD or PD-HD shift were risk factors of inguinal hernia occurrence. The results may help clinicians increase the alert of possible risk factors and complications at the beginning of dialysis treatment in patients with ESRD., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The coronavirus infection disease 2019 (COVID-19) pandemic is likely to put healthcare professionals across the world in an unprecedented situation. Methods: A total of 683 healthcare workers were recruited in this study. Short form - 12 items (SF-12), Societal Influences Survey Questionnaire (SISQ), and Disaster-Related Psychological Screening Test (DRPST) were used to survey participants. Multiple linear regression and structural equation model (SEM) were used to explore the possible factors to the societal influences and quality of life. Results: After multiple linear regression analysis, female, older, more education years, married, regular intake, and posttraumatic stress disorder (PTSD) frequency had positive association with SISQ. To physical component summary (PCS) of SF-12, chronic illness, sleep score, PTSD frequency, and social distance had negative association, and exercise habits had positive association. A mental component summary (MCS) value of SF-12, age, participate in social activities, and social information had positive association, and PTSD frequency, sleep score, social anxiety, and depression had negative association. Under SEM analysis, PTSD had positive influence on SISQ. Sleep score and MCS value had negative influences on SISQ. PTSD severity, older age, sleep score, smoking, and nursing staff had negative influences on PCS value. Young age, PTSD frequency, sleep score, and depression had negative influences on MCS value. Conclusion: Healthcare team members with severe PTSD symptoms suffered more societal influences. Relative to PTSD severity, PTSD frequency was more important to the quality of life. Members of older age who frequently participate in clubs, volunteers, or charity activities had better mental life quality., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kao, Hsu, Chou, Chou, Hsieh, Li, Lin, Wu, Chen and Huang.)

Naphthalimide derivatives have multiple biological activities, including antitumour and anti-inflammatory activities. We previously synthesized several naphthalimide derivatives; of them, compound 5 was found to exert the strongest inhibitory effect on human DNA topoisomerase II activity. However, the effects of naphthalimide derivatives on platelet activation have not yet been investigated. Therefore, the mechanism underlying the antiplatelet activity of compound 5 was determined in this study. The data revealed that compound 5 (5-10 μM) inhibited collagen- and convulxin- but not thrombin- or U46619-mediated platelet aggregation, suggesting that compound 5 is more sensitive to the inhibition of glycoprotein VI (GPVI) signalling. Indeed, compound 5 could inhibit the phosphorylation of signalling molecules downstream of GPVI, followed by the inhibition of calcium mobilization, granule release and GPIIb/IIIa activation. Moreover, compound 5 prevented pulmonary embolism and prolonged the occlusion time, but tended to prolong the bleeding time, indicating that it can prevent thrombus formation but may increase bleeding risk. This study is the first to demonstrate that the naphthalimide derivative compound 5 exerts antiplatelet and antithrombotic effects. Future studies should modify compound 5 to synthesize more potent and efficient antiplatelet agents while minimizing bleeding risk, which may offer a therapeutic potential for cardiovascular diseases., (© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Background: Despite its widespread use, the use of prostate-specific antigen (PSA) alone as a screening biomarker for prostate cancer (PCa) leads often to unwarranted prostate biopsy, over-diagnosis, and consequently, over-treatment, because of its limited specificity. There are reports that the apoptosis inhibitor of macrophage (AIM), secreted mainly by macrophages and epithelial cells, is upregulated during inflammation and facilitates immune recognition of cancerous cells by blocking human regulator of complement activation., Objective: These controversies around the PSA utility necessitate a reexamination of its use as a screening tool. More so, despite the suggested implication of AIM in anticancer immunosurveillance, there is a dearth of information on its role in therapy response, disease progression, and clinical outcomes of patients with PCa. These inform the present study to probe the nature and role of AIM/PSA signaling in anticancer immunity and prognosis in PCa., Methods: A combination of bioinformatics-aided statistical analyses, gene function annotation, and immune infiltrate analyses, coupled with tissue staining, and function assays, namely migration, invasion, and clonogenicity assays, we employed., Results: We demonstrated that AIM and PSA expression levels are inversely correlated in PCa clinical samples and cell lines, with AIM low PSA high defining PCa, compared to AIM high PSA low in normal samples. Concomitant aberrant PSA and significantly suppressed AIM expression levels positively correlated with high-grade disease and characterized by advanced stage prostate cancer, regardless of mutation status. We found that a high PSA/AIM ratio is associated with disease recurrence in patients with prostate cancer but is equivocal for overall survival. In addition, PSA-associated AIM suppression is implicated in the enhanced 'metastability' of PCa and a high AIM/PSA ratio is associated with strong castration-induced regression. CRISPR-mediated AIM knockout was associated with higher PSA expression while ectopic expression of AIM significantly attenuated the migration and invasive capability of PC3 and DU145 cells. Interestingly, compared to normal samples, we observed that AIM, biomarkers of T-cell activation and M1 phenotype markers are co-suppressed in PCa samples., Conclusion: Herein, we demonstrate that AIM/CD5L binds to PSA and that a high PSA/AIM ratio defines advanced stage PCa (regardless of mutation status), is implicated in enhanced metastability, and associated with disease recurrence, while a high AIM/PSA ratio is associated with strong castration-induced regression. More so, the ectopic expression of AIM significantly enhances the anticancer effect of Pembrolizumab and elicits an increased CD8+ T-cell count in AIM hi PSA lo PDL1+ PCa cases that are respondent to Pembrolizumab treatment.

Spatial orientation memory plays a crucial role in animal navigation. Recent studies of tethered Drosophila melanogaster (fruit fly) in a virtual reality setting showed that the head direction is encoded in the form of an activity bump, i.e., localized neural activity, in the torus-shaped ellipsoid body (EB). However, how this system is involved in orientation working memory is not well understood. We investigated this question using free moving flies ( D. melanogaster ) in a spatial orientation memory task by manipulating two EB subsystems, C and P circuits, which are hypothesized for stabilizing and updating the activity bump, respectively. To this end, we suppressed or activated two types of inhibitory ring neurons (EIP and P) which innervate EB, and we discovered that manipulating the two inhibitory neuron types produced distinct behavioral deficits, suggesting specific roles of the inhibitory neurons in coordinating the stabilization and updating functions of the EB circuits. We further elucidate the neural mechanisms underlying such control circuits using a connectome-constrained spiking neural network model., (Copyright © 2021 Han et al.)

The aims of the current study were to identify factors associated with sleep disturbance and Coronavirus disease-19 related psychological distress (CPD), and to develop a conceptual model to verify the mediating effect of CPD on the association between social impact and sleep disturbance. This study recruited patients with schizophrenia. Factors associated with the level of sleep disturbance and CPD were identified using univariate linear regression, and further selected into a stepwise multivariate linear regression model. Using structural equation modeling, a mediation model was developed to test the mediating effect of CPD on the association between social impact and sleep disturbance. After estimating with the stepwise and bootstrap regression, higher levels of CPD were associated with higher levels of social anxiety and subjects without a regular diet. Sleep disturbance was associated with a higher level of social anxiety, a history of psychological trauma, chronic disease, and those who did not smoke. The final model confirmed the mediating effects of CPD; whereas, the direct effect from social impact to sleep disturbance did not reach statistical significance. The current study manifests the crucial role of CPD on the association between social impact and sleep disturbance, and timely intervention for CPD is warranted., (© 2021. The Author(s).)

Background: The outbreak of coronavirus disease 2019 (COVID-19), like severe acute respiratory syndrome (SARS), provokes fear, anxiety and depression in the public, which further affects mental health issues. Taiwan has used their experience of the SARS epidemic for the management of foreseeable problems in COVID-19 endemic., Aim/objective: This review summarizes issues concerning mental health problems related to infectious diseases from current literatures., Results: In suspected cases under quarantine, confirmed cases in isolation and their families, health care professionals, and the general population and related effective strategies to reduce these mental health issues, such as helping to identify stressors and normalizing their impact at all levels of response as well as public information and communication messages by electronic devices. The importance of community resilience was also addressed. Psychological first aid, psychological debriefing, mental health intervention and psychoeducation were also discussed. Issues concerning cultures and religions are also emphasized in the management plans., Conclusion: Biological disaster like SARS and COVID-19 not only has strong impact on mental health in those being infected and their family, friends, and coworkers, but also affect wellbeing in general public. There are evidenced that clear and timely psychoeducation, psychological first aid and psychological debriefing could amileorate negative impact of disaster, thus might also be helpful amid COVID-19 pandemic.

The coronavirus disease 2019 (COVID-19) pandemic can have a negative impact on patients with mood disorders. The aim of this study is to explore the societal influence of COVID-19 and associated impacts on levels of depression, sleep disturbance, and subjective pain among patients with mood disorders. This cross-sectional study recruited inpatients with depression and bipolar disorder. Levels of depression, sleep disturbance, subjective pain, and related demographic variables were collected through self-reported questionnaires. Potential factors associated with levels of depression, sleep disturbance, and subjective pain were identified using univariate linear regression and further entered into a stepwise multivariate linear regression model to identify the independent predictors. A total of 119 participants were included in the analysis, of whom 50.42% had bipolar disorder and 49.58% had unipolar depression. Multivariate analysis showed that a higher level of depression was associated with female subjects, subjects with partners, present history of psychological trauma, and drinking alcohol. Sleep disturbance was associated with subjects with partners and drinking alcohol. A higher level of subjective pain was associated with a higher level of social anxiety and a history of psychological trauma. The current study identified several predictors of psychological burden and subjective pain among inpatients with depression during the COVID-19 pandemic. Further investigations are warranted to extend the application and generalizability of our results.

Psychiatric hospitals play an important role in supporting patients with mental illness to relieve symptoms and improve functioning in a physically and psychologically safe environment. However, these hospitals are also vulnerable to emerging infectious diseases. In early 2020, a psychiatric hospital and a psychiatric unit were reported to have nosocomial coronavirus disease 2019 (COVID-19) infection. A large number of patients and staff were severely impacted. This type of nosocomial infection threatens patient safety and quality of care. By learning from previous experiences of severe acute respiratory syndrome (SARS) and previous studies, psychiatric hospitals can provide safeguards to prevent nosocomial infection among patients and staff during an epidemic or biological disaster. These strategies include a series of actions such as following national guidelines for infection control, reserving adequate support for disinfection equipment, providing relevant and sufficient pro-service and in-service education and training, establishing regular surveillance of hand hygiene habits, proper communication and health education, and providing opportunities for vaccination if possible. Based on the harm reduction concept, staff division of office breaks and ward classification and shunting are recommended and should be further implemented., (Copyright © 2020. Published by Elsevier B.V.)

The emergence of Coronavirus disease 2019 (COVID-19) had rapidly spread since FEB/MAR 2020. Policy to prevent transmission of COVDI-19 resulted in multi-dimensional impact on social interaction. We aimed to develop a beneficial survey tool with favorable quality and availability, the Societal Influences Survey Questionnaire (SISQ), to evaluate social influences on people during this pandemic. The SISQ was developed with 15 items and 4-point Likert scales consisting of five factors. These include social distance, social anxiety, social desirability, social information, and social adaptation. Construct validity and reliability were performed to verify the SISQ. A total of 1912 Taiwanese were recruited. The results demonstrated that the SISQ has acceptable reliability, with Cronbach's alphas ranging between 0.57 and 0.76. The SISQ accounted for 58.86% and satisfied the requirement of Kaiser-Mayer-Olkinvalues (0.78) and significant Bartlett's Test of sphericity. Moreover, the confirmatory factor analysis fit indices also indicated the adequacy of the model. As for multiple comparison, females scored higher than males in factor of social distance. Unemployed participants and those without partners scored higher in several domains of factors. The survey method and survey instrument prove reliable and valuable, also providing different categories of assessment results regarding social influences and their impacts. Further studies are warranted to extend the applicability of SISQ.

Background: The purpose of this study is to evaluate the prognostic factors for sperm retrieval and determine if Y chromosome deletion is associated with deleterious effects on spermatogenesis in non-mosaic Klinefelter patients. Whether Y chromosome deletion determines the sperm retrieval rate in non-mosaic Klinefelter patients has not yet been addressed., Methods: We retrospectively collected medical records of azoospermic patients from Sep 2009 to Dec 2018, and enrolled 66 non-mosaic 47, XXY patients who were receiving mTESE. The predictive values of patients age, serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, prolactin, estradiol and Y chromosome deletion were assessed for successful sperm recovery., Results: Testicular sperm recovery was successful in 24 (36.4%) of 66 men. The mean age (36.0 vs. 36.6 years), and levels of FSH (30.0 vs 36.9 IU/L), LH (17.7 vs 21.9 IU/L), testosterone (2.4 vs. 2.1 ng/ml), prolactin (9.1 vs. 8.8 ng/ml), and estradiol (19.4 vs. 22.3 pg/ml) did not show any significant difference when comparing patients with and without successful sperm retrieval. Partial deletion of azoospermic factor c (AZFc) was noted in 5 (20.8%) of 24 patients with successful sperm retrieval, including three b2/b3 and two gr/gr deletion cases, whereas 4 (9.5%) of 42 patients with unsuccessful sperm retrieval were noted to have AZFc partial deletion (one b2/b3, one sY1206 and two gr/gr deletion), though the difference was not statistically significant (p = 0.27)., Conclusion: According to present results, age and AZFc partial deletion status should not be a deterrent for azoospermic males with non-mosaic Klinefelter syndrome to undergo mTESE.

Objects: The aim of our study was to investigate whether major depressive disorder (MDD) increased the risk of hypertension using propensity score matching (PSM) in patients with MDD in Taiwan. Methods: In this study, we recruited all samples from a random sample sub-dataset of one million insured individuals from 2005. A total of 743,114 outpatients were included in our study. We used PSM (nearest neighbor matching) stratified by age, hospital level, insurance amount, and Charlson Comorbidity Index score. Results: The hazard ratio (HR) of hypertension was significantly greater in the male MDD outpatients (HR = 1.116, P = 0.004) than in the female MDD outpatients (HR = 0.93, P = 0.02). Using PSM, we selected 27,988 outpatients with hypertension and 27,988 outpatients without hypertension for a nested case-control study. In this analysis, female outpatients with MDD (relative risk = 0.852) had lower risks of hypertension. Male outpatients without/with MDD (relative risk = 1.987/3.018) showed a synergistic interaction with gender in which male patients had a higher risk of hypertension in a multiplicative model. Furthermore, MDD appeared to have an interaction effect with gender (HR = 1.82, P < 0.001) in the proportional hazards model analysis. Antidepressant use also increased the risk of hypertension (HR = 1.16, P < 0.001). Conclusions: There was gender disparity in the risk of hypertension in subjects with MDD. MDD outpatients who used antidepressants had a higher risk of suffering from hypertension. A large-scale, population-based study is warranted to generalize these results in the future.

Background: No previous studies have explored emergency medical care for children with chronic neuromuscular disorders (NMDs). We aimed to determine the major reasons for the emergency room (ER) readmission of pediatric patients with NMDs and suggest changes to the care plan to decrease readmissions., Methods: Children with chronic NMDs (aged <18 years) who visited a medical center-based ER between January 2005 and January 2015 were included. The following data were extracted from the patient's ER records: presentations; demographic data, including sex and age; NMD diagnosis; triage classification; emergency examination; initial management and outcomes. The outcomes were death inside or outside the ER, admission to the ward or pediatric intensive care unit (PICU), uneventful discharge, and repeated ER visits., Results: In 10 years, 44 children with heterogeneous NMDs (boys/girls: 30/14, mean age: 9.9 years) visited the ER for a total of 204 times. Repeated ER visits and readmissions occurred in 56.8% and 55.6% of the patients, respectively. Most NMD children belonged to triage class 3 (35.3%), with underlying congenital hereditary muscular dystrophy (44.1%). The major symptoms were usually multiple and concurrent, and primarily respiratory (62.3%) or gastrointestinal (28.9%). The most common causes of hospitalization were pneumonia (48.5%) or acute gastritis (20.4%), and approximately half of the ER visits required further hospitalization, of which 28.2% involved PICU admission. Twenty of the 36 children admitted to the ER required readmission. The most commonly prescribed examinations were complete blood count (38%) and C-reactive protein (38%), and the most common therapy was intravenous fluid administration (34%). Although respiratory compromise caused most ER visits and admissions, pulmonary assessments, including chest films (28%), pulse oximetry (15%), and blood gas analysis (11%), were performed in a relatively small proportion., Conclusion: The ER staff must recognize patients' unmet needs for respiratory and gastrointestinal care related to underlying NMDs., (Copyright © 2018. Published by Elsevier B.V.)

Background: COMT rs4680 Val158 allele is associated with high MB-COMT protein expression and elevated activity compared to the Met158 allele in post-mortem brains. A meta-analysis study suggested the link between COMT SNPs and MDD risk; in addition, MB membrane-bound (MB-COMT) specific genetic variation was reported that influences predisposition to depression amongst females., Methods: Four tagSNPs, including rs4680, were genotyped. 268 MDD subjects and 223 controls were enrolled. MDD severity was rated by HDRS. Total-COMT and MB-COMT mRNA were detected by quantitative PCR. COMT protein and activity were assayed by western blot and methyltransferase assay, respectively., Results: Haplotype TG of rs4633-rs4680, rs4646312 C, and rs4633 T allele might be linked to MDD vulnerability. Haplotype TG may interact with gender and affect MDD risk, since female haplotype TG carriers were estimated for a 9.17-fold higher risk than counterparts. COMT SNPs were not associated with HDRS scores. Haplotype TG female controls had higher MB-COMT protein, whereas non-TG female controls had higher soluble cytoplasmic (S-COMT) protein than other groups. COMT activity was much higher in controls than in MDD subjects., Limitations: Restricted numbers of homozygous TG carriers were recruited and analyzed for COMT mRNA, protein and activity. Only peripheral blood samples were used., Conclusions: A female-specific haplotype (haplotype TG)-MDD vulnerability association was found. TG female controls had higher MB-COMT protein and S-COMT. Altogether, high COMT protein and activity in female TG controls may be predisposing factors for enhanced MDD risk, though not correlated to MDD severity as rated by HDRS., (Copyright © 2018. Published by Elsevier B.V.)

Background: To evaluate the relationship of patients with a history of alcohol use disorders (AUD) and its diagnostic categories with risk of subsequent mesenteric ischemia in Taiwan., Methods: A nationwide population-based cohort study was conducted using data from the Taiwan's National Health Insurance Research Database. We identified 73,583 patients hospitalized for AUD between 2001 and 2010, and matched each case with four comparison patients based on age, gender, Charlson comorbidity index, and the index date. Cox proportional hazard models were used to evaluate the risk of mesenteric ischemia between the AUD and non-AUD cohorts. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated., Results: Patients with AUD exhibited a significantly increased risk of developing mesenteric ischemia (HR = 2.25; 95% CI 1.92-2.64) compared with those with non-AUD after adjustment for patient sociodemographic, coexisting comorbid conditions, and hospital characteristics. Furthermore, a 2.29- and 2.17-fold higher risk of mesenteric ischemia was observed in patients with alcohol abuse/dependence (HR = 2.29; 95% CI 1.94-2.71) and alcoholic psychosis (HR = 2.17; 95% CI 1.72-2.73), respectively, than in non-AUD comparisons after covariate adjustment., Conclusions: This study confirmed that the risk of mesenteric ischemia was significantly higher among patients with different diagnostic categories of AUD, particularly for those with alcohol abuse/dependence., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objectives: To investigate whether the serotonin transporter (5-HTT or SERT or SLC6A4) mRNA level could be used as a biomarker of treatment response in patients with major depression treated with different antidepressants while controlling related factors., Methods: One hundred and nineteen patients with major depression were recruited; all genotyped for the 5-HTT polymorphism concerning 5-HTTLPR, rs25531, and STin2 VNTR, provided demographic data and completed relevant questionnaires. Duloxetine and paroxetine were administered over 32 weeks to these patients. The Hamilton depression rating scale (HDRS) and 5-HTT mRNA level were evaluated at baseline (Week 0), and at 8, 16, 24 and 32 weeks., Results: Improvement in depressive symptoms (HDRS score declined) and increasing in 5-HTT mRNA level were found with longer duration of antidepressant treatment in patients with major depression. Patients with more 5-HTTPR long-form alleles and STin2.12 alleles had poor antidepressant treatment response. Duloxetine may give a better treatment response than paroxetine. Using structural equation modeling (SEM), the 5-HTTLPR long-form had a direct positive association with the 5-HTT mRNA level and an indirect adverse relationship with the 5-HTT mRNA level through neuroticism and previous suicide attempts., Conclusion: The 5-HTT mRNA level increased and correlated with the treatment response (HDRS score improvement) under 32-weeks antidepressants treatment clinical trial. We speculate that the 5-HTT mRNA level may be used as a potential biomarker of antidepressant treatment response., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: The purpose of this study was to investigate the relationship between chronic periodontitis (CP) and upper urinary tract stone (UUTS) in Taiwan by using a population-based data set., Methods: A total of 16,292 CP patients and 48,876 randomly-selected controls without chronic periodontitis were selected from the National research database and studied retrospectively. Subjects selected have not been diagnosed with UUTS previously. These subjects were prospectively followed for at least eight years. Cox regression models were used to explore the connection between risk factors and the development of UUTS., Results: The CP patients have a greater chance of developing UUTS compared to controls (1761/16292, 10.8% vs. 4775/48876, 9.8%, p -values < 0.001). Conditioned logistic regression suggested CP increases the risk of UUTS development (HR 1.14, 95% CI [1.08-1.20], p  < 0.001). After respective adjustment for age, gender, hypertension and diabetes, results showed that CP still increases the risk of developing UUTS (HR 1.14, 95% CI [1.08-1.20], p  < 0.001)., Conclusion: By using a population-based database with a minimum eight 8 follow-up of CP in Taiwan, we discovered patients with CP are more likely to develop UUTS., Competing Interests: The authors declare there are no competing interests.

Background: Urothelial carcinoma (UC) is derived from the urothelium of the urinary tract, and includes cancers of the bladder, renal pelvis and ureter. The aim of this study was to investigate the clinical and demographic features among patients with bladder cancer and urothelial carcinoma of the upper urinary tract (UTUC) in Taiwan., Methods: The present study recruited a total of 736 histopathologically confirmed UC cases, which consisted of 470 bladder cancer and 266 UTUC between September 1998 and December 2009. Clinical and demographic features were collected by an interview utilizing a structured questionnaire, and supplemented by medical chart review. This study was approved by institutional review boards of the collaborating hospitals. The multivariate Cox proportional hazards model was performed to investigate prognostic factors for disease-free survival (DFS) and overall survival (OS). All statistical analyses were performed using the Statistical Analysis Software for Windows, version 9.1 (SAS Institute, Cary, NC, USA)., Results: UTUC patients had higher proportions of advanced clinical stage (T2-4) and poor cell differentiation (G3). Bladder cancer patients with advanced clinical stages (T2-3 and T4) had increased risks of poorer OS (hazard ratio, HR = 1.7 and 3.9, respectively). UTUC patients with the advanced clinical stage (T4) had a significantly greater risk of poorer OS (HR = 8.7). Bladder cancer patients with a high grade (G2-3) had a significantly increased risk of poorer OS (HR = 3.8)., Conclusion: Based on the limited parameters and heterogeneous data, the present study merely observed that bladder cancer and UTUC patients with the higher tumor stage have a significant increased risk of poor overall survival. Therefore, the causal mechanisms of UC prognosis remained to be further explored in a larger population., (Copyright © 2017. Published by Elsevier Taiwan LLC.)

Objectives/hypothesis: Benign paroxysmal positional vertigo (BPPV) is the most common vestibular disorder with an incidence between 10.7 and 17.3 per 100,000 persons per year. The mechanism for BPPV has been postulated to involve displaced otoconia resulting in canalithiasis. Although particulate matter has been observed in the endolymph of affected patients undergoing posterior canal occlusion surgery, an otoconial origin for the disease is still questioned., Study Design: In this study, particulate matter was extracted from the posterior semicircular canal of two patients and examined with scanning electron microscopy., Methods: The samples were obtained from two patients intraoperatively during posterior semicircular canal occlusion. The particles were fixed, stored in ethanol, and chemically dehydrated. The samples were sputter coated and viewed under a scanning electron microscope. Digital images were obtained., Results: Intact and degenerating otoconia with and without linking filaments were found attached to amorphous particulate matter. Many otoconia appeared to be partially embedded in a gel matrix, presumably that which encases and anchors the otoconia within the otolith membrane, whereas others stood alone with no attached filaments and matrix. The otoconia measured roughly 2 to 8 μm in length and displayed a uniform outer shape with a cylindrical bulbous body and a 3 + 3 rhombohedral plane at each end., Conclusions: These findings suggest that the source of the particulate matter in the semicircular canals of patients with BPPV is broken off fragments of the utricular otolithic membrane with attached and detached otoconia., Level of Evidence: NA Laryngoscope, 127:709-714, 2017., (© 2016 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: Pseudomonas aeruginosa , a known biofilm-forming organism, is an opportunistic pathogen that plays an important role in chronic otitis media, tracheitis, cholesteatoma, chronic wounds, and implant infections. Eradication of biofilm infections has been a challenge because the biofilm phenotype provides bacteria with a protective environment from the immune system and antibiotics; thus, there has been great interest in adjunctive molecules that may inhibit biofilm formation or cause biofilm dispersal. There are reports that D-amino acids may inhibit biofilms. In this study, we test the ability of various D-amino acids to inhibit P. aeruginosa biofilm formation in vitro., Study Design: We evaluated the effect of D-alanine (10 mM), D-leucine (10 mM), D-methionine (10 mM), D-tryptophan (10 mM), and D-tyrosine (10 uM and 1 mM) on biofilm formation in two commonly studied laboratory strains of P. aeruginosa : PAO1 and PA14., Methods: Biofilms were grown in 24-well and 96-well tissue culture plates, documented photographically and stained with 0.1% crystal violet and solubilized in 33% glacial acetic acid for quantification., Results: In strains PAO1 and PA14, the addition of D-amino acids did not result in an inhibitory effect on biofilm growth in 24-well plates. Repeating the study in 96-well plates confirmed our findings that D-amino acids do not inhibit biofilm formation of P. aeruginosa ., Conclusion: We conclude that D-amino acids only slow the production of biofilms rather than completely prevent biofilm formation; therefore, D-amino acids represent a poor option for potential clinically therapeutic interventions., Level of Evidence: N/A.

Serotonin receptors, also known as 5-hydroxytryptamine receptors (HTRs), play a role in individuals' vulnerability to major depressive disorders (MDDs) and/or suicide attempts. In the first part of the study, we recruited 789 Taiwanese participants, which included 285 MDD patients, 191 MDD patients with a history of suicide attempts (MS), and 313 controls. The three groups were genotyped to identify HTR single nucleotide polymorphisms (SNPs) and we analyzed the correlations among the three groups. In the second part of the study, which involved a functional test of HTR1B allelic and haplotype variants, another 113 MDD patients were recruited. The rs6298-T allele was more frequent in the MS group than in the control group. The rs1923885-T allele occurred more frequently in the MS group than in the MDD group. Carriers of haplotype GT were estimated to have a 1.774-fold higher risk of suicide attempts. Younger age, alleles rs6296-C, rs6298-T and rs1923885-C, and haplotype CT were associated with a greater risk of MDD. Haplotypes GC and GT were directly associated with a lower risk of suicidal ideation. Haplotypes GC and GT also associated with higher levels of HTR1B mRNA, and haplotype GC was associated with extraversion, which caused a lower risk of suicidal ideation. The rs6296-C allele have directly and indirectly influenced a greater risk of suicidal ideation, which mediated by its negative effect on extraversion. Haplotype GT can be used to identify patients with a higher risk of suicide attempts. The rs6296-C allele lowered the level of HTR1B mRNA, causing individuals with MDD to display more hostility and aggressive behavior, which may lead to suicidal ideation., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

We characterized a cohort of patients with posterior reversible encephalopathy syndrome with spinal cord involvement. We encountered 2 children and identified an additional 19 patients from the internet databases. Of the 21 patients analyzed, 8 were children. The mean peak systolic blood pressure in adults was significantly higher than in children (221.8 ± 14.3 vs 191.4 ± 31.3 mm Hg; P < .01). Regardless of age, the most common clinical symptom was headache (90%) and the least common clinical symptom was seizures (28%). Atypical neuroimaging was more common in children (63%) than in adults (8%). Abnormal cerebrospinal fluid results were frequently found in children (83%). All children recovered uneventfully, but 3 adults had sequelae. A broader clinicoradiologic spectrum makes the diagnosis of children more complex than in adults. Awareness of the atypical features with a meticulous management of hypertension is imperative to avoid unnecessary invasive workups and to achieve an uneventful recovery.

Hypothesis: Bacterial biofilm formation within cholesteatomas is responsible for increased persistence and tissue destruction and Pseudomonas aeruginosa deficient in biofilm formation (PAO1 ΔfleQ) are less virulent than the parent bacteria., Background: Infected aural cholesteatomas have been demonstrated to be more destructive than uninfected cholesteatomas and infections are more persistent. The chronicity and persistence of infections within cholesteatomas may be because of the presence of biofilm formation., Methods: Twenty-seven mutant strains of PAO1 were screened for surface adherence. These strains were also screened for static biofilm formation. The biofilms were quantified by staining with crystal violet. Aural cholesteatomas were then induced in Mongolian gerbils by ligation of the ear canal. At the time of ligation, the ear canals were inoculated with wild-type PAO1 and a biofilm deficient PAO1 ΔfleQ strain of P. aeruginosa. A 7 weeks course of ciprofloxacin (20 mg/kg/day) was started on postoperative day 7. Eight weeks after induction of cholesteatomas, the cholesteatoma size, levels of bone destruction, and levels of bone remodeling were evaluated using microCT imaging., Results: PAO1 ΔfleQ was identified as a poorly adherent and deficient biofilm forming mutant strain of P. aeruginosa. Infected cholesteatomas had more growth, bone destruction and bone remodeling than uninfected cholesteatomas. However, there was no difference observed between cholesteatomas infected with PAO1 (biofilm competent strain) and PAO1 ΔfleQ (biofilm deficient strain)., Conclusion: We demonstrate that the biofilm phenotype is not an important virulence factor in cholesteatomas infected with P. aeruginosa.

The non-structural protein 5A (NS5A) is a hepatitis C virus (HCV) protein indispensable for the viral life cycle. Many prior papers have pinpointed several serine residues in the low complexity sequence I region of NS5A responsible for NS5A phosphorylation; however, the functions of specific phosphorylation sites remained obscure. Using phosphoproteomics, we identified three phosphorylation sites (serines 222, 235, and 238) in the NS5A low complexity sequence I region. Reporter virus and replicon assays using phosphorylation-ablated alanine mutants of these sites showed that Ser-235 dominated over Ser-222 and Ser-238 in HCV replication. Immunoblotting using an Ser-235 phosphorylation-specific antibody showed a time-dependent increase in Ser-235 phosphorylation that correlated with the viral replication activity. Ser-235 phosphorylated NS5A co-localized with double-stranded RNA, consistent with its role in HCV replication. Mechanistically, Ser-235 phosphorylation probably promotes the replication complex formation via increasing NS5A interaction with the human homologue of the 33-kDa vesicle-associated membrane protein-associated protein. Casein kinase Iα (CKIα) directly phosphorylated Ser-235 in vitro. Inhibition of CKIα reduced Ser-235 phosphorylation and the HCV RNA levels in the infected cells. We concluded that NS5A Ser-235 phosphorylated by CKIα probably promotes HCV replication via increasing NS5A interaction with the 33-kDa vesicle-associated membrane protein-associated protein., (© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.)

Vascular wall injuries account for up to 80% of childhood strokes, excluding emboli of cardiac origin. Transient cerebral arteriopathy is a recently described entity that is increasingly recognized as an important cause. The cerebral arterial wall is thought to be affected by an inflammatory process related to certain infections. The authors report a 2.5-year-old girl with sudden left hemiplegia and aphasia. The neuroimaging showed occlusion of the right middle cerebral artery and ischemic damages. Laboratory revealed positive cytomegalovirus immunoglobulin M and G in cerebrospinal fluid and in early and late sera. Treatment with ganciclovir, anticytomegalovirus immunoglobulin, and prednisolone, followed by oral aspirin, resulted in clinical improvement. The follow-up neuroimaging showed stabilization of the arterial lesions without residual stenosis. To our knowledge, this is the first report of a cytomegalovirus-associated transient cerebral arteriopathy in an immunocompetent child. Our report demonstrates the propensity for cytomegalovirus to be involved in pediatric cerebral vascular disease., Competing Interests: Declaration of Conflicting Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Malignant ectomesenchymoma (MEM) which is derived from the remnants of migratory neural crest cells (ectomesenchyme) is a rare and rapidly progressing tumor consisting of neuroectodermal and mesenchymal neoplastic elements. This tumor occurs mostly in children and adolescents, but rarely in adults. We report a 34-year-old male with left paratesticular malignant ectomesenchymoma who received radical orchiectomy and was followed by post-operative flare-up of lung metastasis within 2 weeks. We present the overall treatment strategies for this extremely rare tumor and related findings.

The present study tried to explore the effects of Paliperidone on the lipid profiles of schizophrenia patients. One hundred twenty-nine subjects diagnosed with schizophrenia were enrolled into this study and completed the lipid profile evaluation. Their blood samples were obtained on the morning following a 12-hours fast. Cholesterol and triglyceride (TG) levels in plasma were determined, and lipoproteins were determined by enzymatic methods. All participants provided written informed consent, and underwent additional venous blood withdrawal for DNA extraction for genetic study of the ApoE gene polymorphism. Under T test, TC, TG and HDL levels all declined after Paliperidone treatment although with no statistically significant difference. The ratios of TC/HDL declined after Paliperidone treatment, but without statistically significant difference. After GEE-I analysis, we found that ApoE4 genotype (β = 34.471; p < 0.001) had a positive effect on the total cholesterol (TC) level; female had positive effect on the high-density lipoprotein (HDL) level (β = 15.361; p = 0.003); and age had a positive effect on the TG level (β = 1.317; p = 0.030). Smoking (β = 0.961; p = 0.016) had a positive effect on the ratio of TC/HDL change. Lipid profiles were not increased after Paliperidone treatment under the control of ApoE gene polymorphism.

The ultrafine ZnO nanoparticles/nanowires were successfully synthesized on a flexible and transparent substrate by an ultraviolet-light decomposition process. We demonstrate that water molecules can affect the morphology of ZnO nanostructures. An ultraviolet lamp (λ ~ 380 nm, 75 mW cm(-2)) can be used to irradiate Zn(AcAc)2 and Zn(AcAc)2·H2O precursors, which rapidly synthesize ZnO nanoparticles and nanowires, respectively. High-resolution transmission electron microscopy (HRTEM) images and a selected-area electron diffraction pattern revealed that the single-crystal nanoparticles were comprised of wurtzite structure ZnO. The nanowires consisted of ultrafine nanoparticles. On the basis of the Debye-Scherrer formula, the particle size of ZnO was calculated as ~6-9 nm. The more water molecules the precursor had, the more OH(-) and Zn[(OH)4](2-) it put out. Moreover, due to the Zn[(OH)4](2-) and Zn(OH)2 species formed on the surface of the ZnO nanocrystals, they facilitated the one-dimensional nanowires during the crystal growth process. On the basis of our investigations, oxygen vacancies, hydroxyl, and zinc hydroxide all acted as key components in the formation processes that determined photoresponsive properties.

Pasting and morphology properties of starch blends composed of waxy (waxy rice and waxy corn) and non-waxy (normal corn, tapioca and potato) starches at various ratios were investigated for elucidating effect of granular characteristics on pasting of blends. Pasting profiles of blends were between those of the component starches alone, while the changes varied with starch source. Results reveal obvious water competition during pasting for blends composed of waxy starch and highly swelling non-waxy (tapioca or potato) starch. On the contrary, starch blends composed of waxy starch and non-waxy (normal corn) starch with restricted swelling showed less water competition during pasting, and the pasting attributes could be estimated from those of the component starches following the mixing ratio. Results indicate that the pasting properties of starch blends composed of waxy and non-waxy starches depend on not only the mixing ratio, but also the granular characteristics of component starch., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

A set of 13 waxy rice genotypes prepared by chemically-induced mutation of non-waxy rice variety TNG67 and 7 waxy rice varieties widely planted in Taiwan were screened for various structural and gelatinization properties of starches. Wide variation on physicochemical properties and molecular structure of amylopectin for the 20 waxy rice starches were obtained and relationship between gelatinization properties and molecular structure of starch were discussed. More attributes on swelling and gelatinization thermal properties, comparing to pasting attributes, showed significant correlation with molecular structure parameters. The swelling and gelatinization thermal properties of waxy rice starch did not show significant correlation with molecular size of amylopectin, while significant correlations were found between the swelling or gelatinization thermal properties and chain length of amylopectin. Results suggest that the swelling and pasting of waxy starch is essentially dominated by granule architecture and is dependent on the interactions among amylopectin chains., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Purpose: To evaluate the activity of lowering intraocular pressure (IOP) by Cassiae seed in the DBA/2J mouse glaucoma model., Methods: Young male (mean age: 3 months) inherited glaucoma mice (BDA/2J) were enrolled in this study. To evaluate the potential of Cassiae seed in the treatment of glaucoma, all subjects were divided into 6 groups. There were 1 sham group, positive control identified as group 2 topical brimonidine and group 3 oral acetazolamide, and groups 4-6 Cassiae seed extract (CSE) groups. The lactate dehydrogenase (LDH) level in the anterior aqueous humor and the changes of IOP were investigated. Contents of total polyphenol glycosides in the CSE were measured using a high-performance liquid chromatography (HPLC) method. Chromatographic separation was performed on a Cosmosil 5C(18)-MS reverse-phase HPLC column (4.6×250-mm i.d., 5 μm) with methanol/0.1% H(3)PO(4) as the mobile phases in a gradient elution mode at a flow rate of 1.0 mL/min and an injection volume of 10 μL. The wavelength of UV detector was set at 254 nm., Results: The LDH level in the anterior aqueous humor and IOP significantly decreased after treatment with CSE. The IOP-lowering effect of CSE was comparable to those of oral acetazolamide and brimonidine instillation. There were no abnormal findings in the external appearance, and body weight change after treatment with CSE for 5 weeks. Chrysophanol and physcion were measured by an HPLC method to obtain total polyphenol glycosides of the CSE, and were involved in the IOP-lowering function., Conclusion: Cassiae seed may be safe and beneficial for treating glaucoma due to its significant IOP- and LDH-lowering activities.

Background & Objectives: Hypoxia inducible factor-1α (HIF-1α) has been shown to play a role in the pathogenesis of renal interstitial fibrosis. However, the relationship of HIF-1α expression intensity in human renal tissue with the degree of renal function or renal fibrosis has not been investigated. We therefore, undertook this study to assess the relationship between HIF-1α expression and degree of renal impairment and renal fibrosis using renal tissue from nephrectomized kidneys from patients with chronic kidney disease., Methods: This retrospective study was performed with 70 patients undergoing unilateral or bilateral nephrectomy because of renal cell carcinoma, urothelial cell carcinoma, or renal abscess. Immunohistochemical analysis of HIF-1α expression in non-tumourous or non-abscess renal parenchyma was performed. The patients were divided into two groups: group 1 (n=37) with low intensity HIF-1α expression and group 2 (n=33) with high intensity HIF-1α expression., Results: The intensity of renal HIF-1α expression was significantly associated with serum creatinine level (P =0.005), estimated glomerular filtration rate (P=0.02), fibrosis score of the interstitium (P=0.004) and glomerular sclerosis (P=0.013). A high intensity of HIF-1α expression tended to be associated with lower serum creatinine, higher estimated glomerular filtration rate, low interstitial fibrosis score and low glomerular sclerosis. In addition, multivariate analysis by step-wise logistic regression demonstrated that interstitial fibrosis was the only independent factor associated with the intensity of renal HIF-1α expression (OR 4.107, CI 1.535-11.313, P=0.005)., Interpretation & Conclusions: This study demonstrated a correlation between intensity of HIF-1α expression and degree of renal interstitial fibrosis. The association demonstrated an elevated HIF-1α expression in less severe kidney disease. The intensity of HIF-1α renal expression plays a role in the pathogenesis of chronic kidney disease.

Background: The purpose of this study was to investigate the relationship among work stress, sex life satisfaction, and mental health of married nurses. Demographic information, work stress, sex life satisfaction, sexual desire and mental health measured using the Chinese Health Questionnaire, data were collected from 100 married nurses in Taiwan., Findings: Sex life satisfaction and age were negatively correlated, but sex life satisfaction and sexual desire were positively correlated. The mental health of over-committed nursing staff was not affected. Higher reward for effort was positively correlated with sex life satisfaction., Conclusions: No matter whether job stress was high or low, receiving a higher reward for effort led to better sex life satisfaction, which had a satisfying positive effect on the nurses' lives. To improve nursing care quality at the hospital, nursing administrators should assist nurses in confronting work stress via positive adjustment, which is associated with the nurses' sexual harmony, and quality of life.

Background: Reduced turnover of extracellular matrix has a role in renal fibrosis. Matrix metalloproteinases (MMPs) is associated with many glomerular diseases, but the histological association of MMPs and human renal fibrosis is unclear., Methods: This is a retrospective study. Institutional Review Board approval was obtained for the review of patients' medical records, data analysis and pathological specimens staining with waiver of informed consents. Specimens of forty-six patients were examined by immunohistochemical stain of MMP-9 in nephrectomized kidneys, and the association of renal expression of MMP-9 and renal fibrosis was determined. MMP-9 expression in individual renal components and fibrosis was graded as high or low based on MMP-9 staining and fibrotic scores., Results: Patients with high interstitial fibrosis scores (IFS) and glomerular fibrosis scores (GFS) had significantly higher serum creatinine, lower estimated glomerular filtration rate (eGFR), and were more likely to have chronic kidney disease (CKD) and urothelial cell carcinoma. Univariate analysis showed that IFS and GFS were negatively associated with normal and atrophic tubular cytoplasmic MMP-9 expression and IFS was positively correlated with atrophic tubular nuclear MMP-9 expression. Multivariate stepwise regression indicated that MMP-9 expression in atrophic tubular nuclei (r = 0.4, p = 0.002) was an independent predictor of IFS, and that MMP-9 expression in normal tubular cytoplasm (r = -0.465, p<0.001) was an independent predictor of GFS., Conclusions: Interstitial fibrosis correlated with MMP-9 expression in the atrophic tubular nuclei. Our results indicate that renal fibrosis is associated with a decline of MMP-9 expression in the cytoplasm of normal tubular cells and increased expression of MMP-9 in the nuclei of tubular atrophic renal tubules.

Background: Chronic kidney disease (CKD) has adverse impacts on mortality and morbidity of renal transplant recipients. Serum cystatin C (sCysC) is a novel marker in predicting the CKD. We therefore compare sCysC and serum creatinine (sCr) with the aim of improving the detection of CKD in renal transplant recipients., Methods: We enrolled 106 renal transplant recipients and estimated glomerular filtration rates (GFR) using the Cockcroft-Gault (GFR(CG)) and the abbreviated Modification of Diet in Renal Disease (GFR(aMDRD)) formulae. We defined CKD as the presence of structural or functional kidney damage, irrespective of the diagnosis. Comparisons of sCysC and sCr in detecting CKD were analyzed., Results: sCysC correlates with sCr significantly (r = 0.87; P < .001). The receiver operating characteristic curve demonstrates that sCysC has a better specificity and area under the curve, but less sensitivity than sCr in predicting CKD in renal transplant recipients if GFR is estimated by GFR(CG). Additionally, if GFR was estimated by GFR(aMDRD), the role of sCysC or sCr in prediction of CKD was comparable., Conclusion: sCysC may be better than sCr to detect CKD in renal transplant recipients using the GFR(CG)., (Copyright © 2010 Elsevier Inc. All rights reserved.)

In human tumors, fibronectin (FN) expression is positively associated with tumor metastatic potential and matrix metalloproteinase (MMP) secretion. Additionally, tissue transglutaminase (TG2) is implicated as playing an important role in tumor progression, and acts as a co-receptor for integrin-mediated cell binding to FN. This study explored the involvement of FN and TG2 in cancer cell metastasis using the recently established highly invasive A431-III subline. A431-III cells expressed significantly higher levels of FN and TG2 as compared to the parental line (A431-P). Knockdown of endogenous FN by small interfering RNA (siRNA) resulted in dramatic suppression of the migratory and invasive activity, and the secreted MMP-9 activity (but not MMP-2) in A431-III subline. Exogenous administration of FN to A431-III cells also increased the secreted activity of MMP-9 but not MMP-2. Interestingly, knockdown of TG2 by siRNA dramatically reduced the cell attachment, migration and invasion, and the secretion of MMP-9 and MMP-1 (but not MMP-2 and MMP-3) in A431-III cells as compared to A431-P cells. Furthermore, A431-III cells exhibited increased association of integrin β1 and β3 with FN and TG2, and knockdown of TG2 markedly suppressed integrin β1 interaction with FN. Together, this study suggests that FN and TG2 facilitate the metastatic activity of A431 tumor cells, and this may be partly attributed to TG2 enhancement of the association of FN and β integrin. In addition, the combined targeting of TG2 and FN may be an effective therapeutic strategy for cancer displaying increased expression of both proteins.

Structural and polymorphic variations in Neuregulin 3 (NRG3), 10q22-23 are associated with a broad spectrum of neurodevelopmental disorders including developmental delay, cognitive impairment, autism, and schizophrenia. NRG3 is a member of the neuregulin family of EGF proteins and a ligand for the ErbB4 receptor tyrosine kinase that plays pleotropic roles in neurodevelopment. Several genes in the NRG-ErbB signaling pathway including NRG1 and ErbB4 have been implicated in genetic predisposition to schizophrenia. Previous fine mapping of the 10q22-23 locus in schizophrenia identified genome-wide significant association between delusion severity and polymorphisms in intron 1 of NRG3 (rs10883866, rs10748842, and rs6584400). The biological mechanisms remain unknown. We identified significant association of these SNPs with increased risk for schizophrenia in 350 families with an affected offspring and confirmed association to patient delusion and positive symptom severity. Molecular cloning and cDNA sequencing in human brain revealed that NRG3 undergoes complex splicing, giving rise to multiple structurally distinct isoforms. RNA expression profiling of these isoforms in the prefrontal cortex of 400 individuals revealed that NRG3 expression is developmentally regulated and pathologically increased in schizophrenia. Moreover, we show that rs10748842 lies within a DNA ultraconserved element and homedomain and strongly predicts brain expression of NRG3 isoforms that contain a unique developmentally regulated 5' exon (P = 1.097E(-12) to 1.445E(-15)). Our observations strengthen the evidence that NRG3 is a schizophrenia susceptibility gene, provide quantitative insight into NRG3 transcription traits in the human brain, and reveal a probable mechanistic basis for disease association.

Polymorphisms in DNA repair genes may be associated with differences in repair capacity of DNA damage and may thereby influence an individual's susceptibility to lung cancer. We investigated the association between the -93G-->A polymorphism in the mismatch repair hMLH1 gene for its role in the susceptibility and survival of non-small cell lung cancer (NSCLC) patients. Using a case-control study design, 165 NSCLC patients and 193 controls with similar range for age, gender and smoking habit distributions were subjected to genotype analysis. The risk of lung cancer was estimated by logistic regression analysis. The Kaplan-Meier method was used to estimate the probability of survival and the log-rank test was used to assess the significance of the difference between survival probabilities. The homozygous variant A/A genotype was associated with a significantly increased risk for lung cancer compared with the other genotypes (Crude analysis P=0.003, Adjusted analysis P=0.011, using the logistic regression model). The patients with a homozygous variant A/A genotype had a trend toward poorer prognoses compared with other patients, especially smoking (P=0.05, by log-rank test), male (P=0.06), or squamous carcinoma (P=0.08) patients. This is the first case-control study to show a significant association between the hMLH1-93G-->A polymorphism and the susceptibility to and prognosis of lung cancer. The results herein may be useful for risk assessment and disease monitoring of NSCLC.

Background: The tumour supressor gene TP53 is thought to be involved in neural apoptosis. The polymorphism at codon 72 in TP53 and the long form variants of the upstream variable number of tandem repeats (uVNTR) polymorphism in the dopamine D4 receptor (DRD4) gene are reported to confer susceptibility to schizophrenia., Methods: We recruited 934 patients with schizophrenia and 433 healthy individuals, and genotyped the locus of the TP53 codon 72 and DRD4 uVNTR polymorphisms by combining the polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP) with direct sequencing., Results: No significant differences were found in the frequency of the genotype of the TP53 codon72 polymorphism between patients with schizophrenia and their controls. However, the long form alleles (> or = 5 repeats) of the DRD4 uVNTR polymorphism were more frequent in patients with schizophrenia than in controls (p = 0.001). Hence, this class of alleles might be a risk factor for enhanced vulnerability to schizophrenia (odds ratio = 3.189, 95% confidence interval = 1.535-6.622). In the logistic regression analysis, the long form variants of the DRD4 polymorphism did predict schizophrenia after the contributions of the age and gender of the subjects were included (p = 0.036, OR = 2.319), but the CC and GG genotypes of the codon 72 polymorphism of TP53 did not., Conclusions: The long form variants of the uVNTR polymorphism in DRD4 were associated with schizophrenia, in a manner that was independent of the TP53 codon 72 polymorphism. In addition, given that the genetic effect of the TP53 codon 72 polymorphism on the risk of developing schizophrenia was very small, this polymorphism is unlikely to be associated with schizophrenia. The roles that other single nucleotide polymorphisms (SNPs) in the TP53 gene or in other apoptosis-related genes play in the synaptic dysfunction involved in the pathogenesis of schizophrenia should be investigated.

Background: A potential role for the renin-angiotensin system (RAS) in mitral valve prolapse (MVP) has been reported. The RAS genes are good candidates for evaluating the association with MVP. The angiotensinogen (AGT) gene has an important role in RAS and was shown to be related to MVP. However, no study on the association of AGT M235T in men with MVP has been reported. In this article, we investigated the potential role of AGT M235T polymorphism in men with MVP., Methods: Seventy-one unrelated study subjects with MVP, 236 control subjects (matched with respect to age and sex), and 178 community subjects from southern Taiwan were included in this study. All participants were male Han Chinese population. All cases fulfilled the criteria of MVP and the new echocardiographic criteria for MVP. The AGT M235T polymorphism was detected by polymerase chain reaction-restricted fragment length polymorphism., Results: There was a statistically significant difference in the M235 allelic frequency between MVP study subjects and control subjects (chi = 4.390; P = 0.036). The chi test for trend also showed that the MM genotype frequency had a statistically significant increase with MVP study subjects (chi = 4.339; P = 0.037)., Conclusions: The results suggest a significant association between MM genotype of AGT M235T polymorphism and MVP in men. Therefore, this study indirectly supports the idea that the polymorphism of AGT M235T should be considered when interpreting and designing genetic studies which underlie differences in blood pressure.

In this study, highly invasive tumor cell lines (designated A431-I, -II and -III) derived from parental A431 tumor cells (A431-P) were isolated by three successive passages through a Boyden chamber with matrigel-coated membrane support. The invasive potential and the activity of secreted MMP-9 of each sub-line increased significantly compared to the A431-P (A431-III > A431-II > A431-I) as evidenced by the in vitro invasion assay, gelatin zymography and immunoblotting analyses. RT-PCR results also revealed the elevated expression of MMP-9 in A431-III. We further characterized the A431-III sub-line and found these cells exhibited a greater potential for attachment and spreading on fibronectin-coated substratum and for migration. The A431-III cells displayed multiple cytoplasmic extensions with focal contacts (vinculin-positive staining) during cell spreading within 30 min. We also noticed an increase in FAK phosphorylation, but no significant change in FAK protein level in the A431-III sub-line compared to those of A431-P cells. Together, these results demonstrate that the greater invasion potential exhibited by the highly invasive A431-III subline is likely attributed to an increased ability for attachment, spreading and migration, as well as increased MMP activity. Thus, A431-P and the highly invasive A431-III sub-line could be an excellent model for studying the mechanism of cancer metastasis.

Background: Explore the interaction between apolipoprotein E (Apo E), phospholipase A2 (PLA2) and beta2 adrenergic receptor (beta2-AR) gene polymorphisms and lipid profiles in an elderly Chinese population., Methods: Five hundred subjects aged 65 to 74 years were randomly selected from a community in southern Taiwan to assess the relationship between Apo E, PLA2 and beta2-AR gene polymorphisms and lipid profiles. Two hundred sixty-seven participants agreed to have venous blood drawn for DNA studies., Results: Two statistically significant differences were noted in TC and LDL-C in the Gln27Glu of the beta2-AR gene polymorphism (P = 0.007, P = 0.022). The low-income group had a higher HDL-C level (p = 0.076). The Gln27Glu polymorphism Glu/Glu or Gln/Glu subjects had lower TC levels compared to the Gln27Glu polymorphism Gln/Gln subjects (p = 0.092). Lower TC levels (p = 0.082) and lower LDL-C levels (p = 0.045) in subjects with the Cys19Arg16Glu27 haplotype. Lower TC levels (p = 0.06) were also noted in subjects with the Cys19Gly 16Glu27 haplotype. On the other hand, higher VLDL-C levels (p = 0.185) and higher triglyceride (TG) levels (p = 0.190) were noted in subjects with the Cys19Gly 16Gln27 haplotype. The epsilon2 allele combined with low income had a positive effect on HDL-C (p = 0.0011), after adding the income factor in this study., Conclusion: When the effects of Apo E and PLA2 on lipid profiles were included in this study, beta2-AR gene polymorphisms reduced significant effect on lipid profiles. Similarly, low income increased effect on HDL-C. This study appeared that the results of gene-gene and gene-environment interaction, it should be considered in further studies for lipid profiles.

Genetic polymorphisms at the genes involved in mismatch repair may determine individual's susceptibility to cancer initiation and progression. However, the prognostic significance of hMSH2 gIVS12-6T>C polymorphism (T-C substitution at the -6 intronic splice acceptor site of exon 13) in non-small cell lung cancer (NSCLC) remains unclear. Therefore, we investigated the frequency of hMSH2 gIVS12-6T>C polymorphism in 156 NSCLC patients and 235 cancer-free individuals matched for age, gender and smoking habit. The correlations between hMSH2 genotypes and protein expression and survival of the patients were also analyzed. The frequencies of hMSH2 genotypes T/T, T/C, and C/C were 37.4%, 43.0%, and 19.6%, respectively, and the variant (C) allele was represented at a significantly higher frequency in the general Taiwanese population than in non-Asian populations (P<0.0001, chi(2) test). No significant difference in hMSH2 genotype distribution was found between NSCLC patients and cancer-free controls (P=0.255, multivariate logistic regression). However, the homozygous wild-type T/T genotype was significantly associated with a poor prognosis (P=0.007, log-rank test). Our study showed that the frequency of the variant C allele was significantly higher in the general Taiwanese population than in non-Asian populations and the T/T genotype of hMSH2 gIVS12-6T>C polymorphism was a poor prognostic factor in NSCLC patients.

Priapism is a urologic emergency, and a urologic consultation should be obtained as early as possible. Its etiologies are numerous and diverse. Patients who use antipsychotic drugs should be informed about the complications of priapism, especially those patients with a history of prolonged erections associated with other alpha-adrenergic blocking agents or a history of sickle cell disease. If antipsychotic medication is considered to be needed in the treatment of patients with a history of priapism, physicians should select a drug with a low peripheral alpha-adrenergic blocking property. Physicians should be aware of this rare but potentially serious complication of antipsychotic drugs. Early intervention and appropriate treatment are essential to prevent permanent impotence and other serious complications.