Association between vitiligo and risk of retinal detachment: a population-based cohort study in Taiwan.

BACKGROUND: Vitiligo is reportedly associated with several ocular abnormalities. However, the relationship between vitiligo and retinal detachment (RD) remains unclear. OBJECTIVES: To examine the risk of RD in patients with vitiligo. METHODS: A nationwide population-based cohort study was conducted using data from the Taiwan National Health Insurance Database from 2007 to 2018. A total of 21 132 patients with vitiligo were matched in a 1 : 4 ratio with people without vitiligo by age, sex and comorbidity propensity score. Cumulative incidence and Cox proportional hazard models were used to investigate the risk of RD in patients with vitiligo. Subgroup analysis was performed. RESULTS: The cohort with vitiligo had a significantly higher rate of RD than the cohort without vitiligo [adjusted hazard ratio (aHR) 1.44, 95% confidence interval (CI) 1.20-1.72; P < 0.001]. Patients with vitiligo who required treatments such as phototherapy, systemic corticosteroids or immunosuppressants exhibited an even greater risk of RD (aHR 1.57, 95% CI 1.16-2.14; P = 0.004). CONCLUSIONS: Our study revealed a 1.44-fold increased risk of RD in patients with vitiligo, with an even higher risk in patients receiving phototherapy, systemic corticosteroids or immunosuppressants. The risk remained consistently higher over a 10-year follow-up period.

Fluorescence detection of apolipoprotein E gene polymorphisms based on oligonucleotide ligation and magnetic separation.

Alzheimer's disease is a progressive neurodegenerative condition that causes brain cell death and is the leading cause of dementia. Most patients with Alzheimer's disease are diagnosed with late-onset Alzheimer's disease (LOAD), with apolipoprotein E (APOE) genotypes being highly associated with the frequency of LOAD risk. A fluorescence detection system coupled with oligonucleotide ligation and magnetic separation was developed to identify two single-nucleotide polymorphisms (SNPs) for the APOE gene and recognize APOE alleles for LOAD. The system utilized a fluorescence probe with one base-discriminating nucleoside for SNP (F probe) and a perfectly complementary biotin-modified sequence against the target DNA (P probe). When the F and P probes matched the target DNA sequences, DNA ligation occurred, and ligation products were produced. Streptavidin magnetic beads were subsequently employed to remove the ligation products, and a decrease in fluorescence intensity was observed in the supernatant compared to when there was no target DNA. This system detected two SNPs of APOE alleles, namely rs429358 and rs7412. The results indicated that the R-values ((F0 - F1)/F0) for rs429358 were 0.92 ± 0.002 for the T/T target, 0.47 ± 0.004 for the T/C target and 0.11 ± 0.004 for the C/C target, respectively. The R-values for rs7412 were 0.73 ± 0.009 for the C/C target, 0.42 ± 0.001 for the C/T target and 0.16 ± 0.007 for the T/T target, respectively. F0 and F1 represent the fluorescence intensity of the F probe without and with target DNA, respectively. Based on fluorescence intensity, the fluorescence detection system was able to identify the genotypes of the APOE gene accurately to evaluate the risk of Alzheimer's disease.

Determinants of Employment Outcome for the People with Schizophrenia Using the WHODAS 2.0.

Purpose Since the vocational outcomes of people with schizophrenia should be viewed in a holistic way, the second edition of the World Health Organization Disability Assessment Schedule (WHODAS 2.0) might provide an evaluation regarding employment potential. To determine whether the WHODAS 2.0 scores can be used to predict employment status, we examined the probabilistic cut-off values of the scores and analyzed the relationship between work status and demographic characteristics. Methods We selected 31,793 people aged between 18 and 65 with schizophrenia or schizoaffective disorder from the disability evaluation database in Taiwan and separated them into two groups based on employment status (employed and unemployed). We used logistic regression to explore the association between employment and demographic characteristics. Moreover, we conducted a receiver operating characteristic (ROC) analysis to determine the cut-off point to assist in determining employment potential based on the WHODAS 2.0 score. Results Among the 31,793 participants, 3367 were employed and 18,801 were unemployed. The unemployed participants accounted for a higher percentage of disability in each domain of the WHODAS. The ROC analysis revealed that the optimal cut-off point of the WHODAS score to distinguish the people who were employed and unemployed was 25.78 (area under curve = 0.80). Conclusions The present study indicated that work status can be determined by the total score across the six domains of the WHODAS score. Furthermore, the probability of employment may be determined initially by the cut-off point of the WHODAS score in order to economize evaluation time and prepare prevocational training for those with scores above 25.78.

Chemical derivatization combined with capillary LC or MALDI-TOF MS for trace determination of lipoic acid in cosmetics and integrated protein expression profiling in human keratinocytes.

Lipoic acid (LA) is an essential cofactor in mitochondrial enzymes and an ideal antioxidant in prokaryotic and eukaryotic cells. Capillary liquid chromatography coupled with ultraviolet detection (CapLC-UV) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) are two environmentally friendly methods for determining LA. In this study, a pre-column microwave-assisted derivatization with 4-bromomethyl-6,7-dimethoxycoumarin enhanced the UV absorbance of LA and was monitored at 345 nm by CapLC-UV. Gradient separation was performed using a reversed-phase C18 column with a mobile phase consisting of acetonitrile-0.1% formic acid solution. The ionization of LA was increased, and the LA derivative was detected by MALDI-TOF MS at m/z 683 with an α-cyano-4-hydroxycinnamic acid matrix. The linear response ranged from 0.1 to 40 µM with a correlation coefficient of 0.999. The CapLC-UV and MALDI-TOF MS had detection limits of 5 and 4 fmol, respectively. These methods effectively detected LA in dietary supplements and cosmetics. Cellular proteomes of a human keratinocyte cell line (HaCaT) irradiated with UV radiation were also compared with and without LA treatment. The cellular proteomes were identified by nanoultra performance LC with LTQ Orbitrap system after trypsin digestion. Protein identification was performed by simultaneous peptide sequencing and MASCOT search. The analysis revealed changes in several proteins, including CDC42, TPI1, HNRPA2B1, PRDX1, PTGES3 and MYL6.

Butein Inhibits Angiogenesis of Human Endothelial Progenitor Cells via the Translation Dependent Signaling Pathway.

Compelling evidence indicates that bone marrow-derived endothelial progenitor cells (EPCs) can contribute to postnatal neovascularization and tumor angiogenesis. EPCs have been shown to play a "catalytic" role in metastatic progression by mediating the angiogenic switch. Understanding the pharmacological functions and molecular targets of natural products is critical for drug development. Butein, a natural chalcone derivative, has been reported to exert potent anticancer activity. However, the antiangiogenic activity of butein has not been addressed. In this study, we found that butein inhibited serum- and vascular endothelial growth factor- (VEGF-) induced cell proliferation, migration, and tube formation of human EPCs in a concentration dependent manner without cytotoxic effect. Furthermore, butein markedly abrogated VEGF-induced vessels sprouting from aortic rings and suppressed microvessel formation in the Matrigel implant assay in vivo. In addition, butein concentration-dependently repressed the phosphorylation of Akt, mTOR, and the major downstream effectors, p70S6K, 4E-BP1, and eIF4E in EPCs. Taken together, our results demonstrate for the first time that butein exhibits the antiangiogenic effect both in vitro and in vivo by targeting the translational machinery. Butein is a promising angiogenesis inhibitor with the potential for treatment of cancer and other angiogenesis-related diseases.

Resting-state fMRI mapping of cerebellar functional dysconnections involving multiple large-scale networks in patients with schizophrenia.

BACKGROUND: Recent findings have indicated that patients with schizophrenia have altered cortico-cerebellar connectivity, but the nature of these network dysconnections remains unclear. AIMS: We applied a network-based approach to investigate the functional connectivity (FC) of the cerebellum in patients with schizophrenia. METHODS: Thirty-six patients with schizophrenia and 36 healthy controls underwent resting functional magnetic resonance imaging. We derived the following 6 major networks by applying group independent component analysis: (1) the cingulo-opercular network (CON); (2) the dorsal default-mode networks (dDMN); (3) the ventral default-mode network (vDMN); (4) the left frontoparietal networks (lFPN); (5) the right frontoparietal network (rFPN); and (6) the motor network (MOT). We defined 12 regions of interest (ROIs) by selecting the first 2 peaks of each network in the cerebellum. The FC map of all ROIs was calculated for each participant and compared between groups. RESULTS: The schizophrenic patients showed a decrease in FC between the cerebellar ROIs and the thalamus in all networks except the MOT. The FC decreased between cerebellar ROIs and the frontal cortex in the CON, rFPN, and MOT. However, the FC increased with the precentral gyrus and postcentral gyrus for the CON, lFPN, and dDMN. An increased FC with the occipital fusiform gyrus and the temporal occipital fusiform gyrus was also noted in the dDMN, vDMN, and MOT. CONCLUSIONS: The dysconnection of the cerebellum in the examined patients with schizophrenia was network-specific. The cerebellar-thalamic dysconnections were the most prominent findings and were common to all cognitive-related networks, whereas the cortico-cerebellar connectivity involved both an increase and decrease in FC, and depended more on the nature of the specific network.

Transformation of cinnamic acid from trans- to cis-form raises a notable bactericidal and synergistic activity against multiple-drug resistant Mycobacterium tuberculosis.

Tuberculosis (TB) is a contagious disease caused by Mycobacterium tuberculosis. The long course of treatments on TB with a combination of antibiotics leads unfavorable side effects and poor patient compliance which contributes to sustaining multiple-drug resistant tuberculosis (MDR-TB). Therefore, the development of a new effective drug or synergist to reduce the prevalence of MDR-TB is urgent to date. Cinnamic acid (CA) is a natural occurring phenolic compound with anti-microbial activity. Both trans- and cis-isoforms of CA exist in planta, and cis-cinnamic acid (c-CA) can be transformed from trans-cinnamic acid (t-CA) under sunlight. Due to the unavailability of c-CA, the literature regarding the biological functions of c-CA is still limited. We had previously developed a practicable method for the transformation of c-CA from t-CA and the isolation of c-CA. Using the techniques, sufficient c-CA was obtained to evaluate its antituberculosis activity against a MDR M. tuberculosis strain. Moreover, the synergistic effects of c-CA and t-CA with two first-line anti-TB antibiotics, isoniazid (INH) and rifampicin (RIF), were also determined. Although both of c-CA and t-CA decreased the viability of MDR-TB bacilli in a dose-dependent manner, the antituberculosis activity of c-CA was approximately 120-fold of t-CA. Furthermore, the c-CA exhibited higher synergistic effect with INH or RIF against tuberculosis than t-CA. The micrographs of scanning electron microscope (SEM) display that c-CA caused an injury on the out-layer of MDR-TB bacilli. The c-CA might be a potential anti-mycobacterial or synergistic agent that can be developed to against tuberculosis.

Propofol depresses angiotensin II-induced cell proliferation in rat cardiac fibroblasts.

BACKGROUND: Propofol may have beneficial effects on the prevention of angiotensin II (Ang II)-induced cardiac fibroblast proliferation via its antioxidative properties. The authors hypothesized that propofol may alter Ang II-induced cell proliferation and aimed to identify the putative underlying signaling pathways in rat cardiac fibroblasts. METHODS: Cultured rat cardiac fibroblasts were pretreated with propofol then stimulated with Ang II; cell proliferation and endothelin-1 gene expression were examined. The effect of propofol on Ang II-induced nicotinamide adenine dinucleotide phosphate-oxidase activity, reactive oxygen species formation, extracellular signal-regulated kinase phosphorylation, and activator protein 1-mediated reporter activity were also examined. The effect of propofol on nitric oxide production and protein kinase B and endothelial nitric oxide synthase phosphorylations were also tested to elucidate the intracellular mechanism of propofol in proliferation. RESULTS: Ang II (100 nm) increased cell proliferation and endothelin-1 expression, which were partially inhibited by propofol (10 or 30 microm). Propofol also inhibited Ang II-increased nicotinamide adenine dinucleotide phosphate-oxidase activity, reactive oxygen species formation, extracellular signal-regulated kinase phosphorylation, and activator protein 1-mediated reporter activity. Propofol was also found to increase nitric oxide generation and protein kinase B and nitric oxide synthase phosphorylations. Nitric oxide synthase inhibitor (N-nitro-L-arginine methylester) and the short interfering RNA transfection for protein kinase B or endothelial nitric oxide synthase markedly attenuated the inhibitory effect of propofol on Ang II-induced cell proliferation. CONCLUSIONS: The authors' results suggest that propofol prevents cardiac fibroblast proliferation by interfering with the generation of reactive oxygen species and involves the activation of the protein kinase B-endothelial nitric oxide synthase-nitric oxide pathway.