Phenome-wide analysis of Taiwan Biobank reveals novel glycemia-related loci and genetic risks for diabetes

To explore the complex genetic architecture of common diseases and traits, we conducted comprehensive PheWAS of ten diseases and 34 quantitative traits in the community-based Taiwan Biobank (TWB). We identified 995 significantly associated loci with 135 novel loci specific to Taiwanese population. Further analyses highlighted the genetic pleiotropy of loci related to complex disease and associated quantitative traits. Extensive analysis on glycaemic phenotypes (T2D, fasting glucose and Hb

Lack of association of genetic variants for diabetic retinopathy in Taiwanese patients with diabetic nephropathy

[[abstract]]Objective Diabetic nephropathy (DN) and diabetic retinopathy (DR) comprise major microvascular complications of diabetes that occur with a high concordance rate in patients and are considered to potentially share pathogeneses. In this case-control study, we sought to investigate whether DR-related single nucleotide polymorphisms (SNPs) exert pleiotropic effects on renal function outcomes among patients with diabetes. Research design and methods A total of 33 DR-related SNPs were identified by replicating published SNPs and via a genome-wide association study. Furthermore, we assessed the cumulative effects by creating a weighted genetic risk score and evaluated the discriminatory and prediction ability of these genetic variants using DN cases according to estimated glomerular filtration rate (eGFR) status along with a cohort with early renal functional decline (ERFD). Results Multivariate logistic regression models revealed that the DR-related SNPs afforded no individual or cumulative genetic effect on the nephropathy risk, eGFR status or ERFD outcome among patients with type two diabetes in Taiwan. Conclusion Our findings indicate that larger studies would be necessary to clearly ascertain the effects of individual genetic variants and further investigation is also required to identify other genetic pathways underlying DN.[[notice]]補正完

Perception of Stigma and Its Associated Factors Among Patients With Major Depressive Disorder: A Multicenter Survey From an Asian Population

Stigma of major depressive disorder (MDD) is an important public health problem. This study aimed to examine the level of perceived stigma and its associated factors in MDD patients in five Asian countries, including China, Korea, Malaysia, Singapore, and Thailand. A total of 547 outpatients with MDD were included from Asian countries. We used the stigma scale of the Explanatory Model Interview Catalogue (EMIC) to assess stigma. The Montgomery–Asberg Depression Rating Scale (MADRS), Symptoms Checklist 90-Revised (SCL-90-R), Fatigue Severity Scale (FSS), Sheehan Disability Scale (SDS), 36-Item Short-Form Health Survey (SF-36), and Multidimensional Scale of Perceived Social Support (MSPSS) were used to assess symptoms, clinical features, functional impairment, health status, and social support. The stigma scores of patients under 55 years old were significantly higher than those equal to or greater than 55 years old (P < 0.001). The stigma scores exhibited significant negative correlation with age; MSPSS scores of family, friends, and others; and SF-36 subscale of mental health, but significant positive correlation with MADRS, FSS, SDS, and SCL-90-R subscale scores of depression, interpersonal sensitivity, obsession–compulsion, psychoticism, and somatization. Multivariate regression analysis revealed that age, SCL-90-R interpersonal sensitivity, obsession–compulsion, psychoticism, MSPSS scores of friends and others, and SF-36 of mental health were significantly associated with the level of perceived stigma. These findings suggest that MDD patients who are young, have a high degree of interpersonal sensitivity and psychoticism, have low health-related quality of life, and have low social support are the target population for stigma interventions in Asia

Reply to V Ansu and K He

10.3945/ajcn.116.149690AMERICAN JOURNAL OF CLINICAL NUTRITION10541010-101

Free Radical-Scavenging, Anti-Inflammatory, and Antibacterial Activities of Water and Ethanol Extracts Prepared from Compressional-Puffing Pretreated Mango (Mangifera indica L.) Peels

During the processing of mango, a huge amount of peel is generated, which is environmentally problematic. In the present study, a compressional-puffing process was adopted to pretreat the peels of various mango cultivars, and then the bioactive compounds of mango peels were extracted by water or ethanol. The phenolic compound compositions as well as the free radical-scavenging, anti-inflammatory, and antibacterial activities of water extract (WE) and ethanol extract (EE) from nonpuffed (NP) and compressional-puffed (CP) mango peels were further evaluated. It was found that compressional-puffing could increase the yield of extracts obtained from most mango varieties and could augment the polyphenol content of extracts from Jinhwang and Tainoung number 1 (TN1) cultivars. The WE and EE from TN1 exhibited the highest polyphenol content and the greatest free radical-scavenging activities among the mango cultivars tested. Seven phenolic compounds (gallic acid, pyrogallol, chlorogenic acid, p-hydroxybenzoic acid, p-coumaric acid, ECG, and CG) were detected in CPWE (compressional-puffed water extract) and CPEE (compressional-puffed ethanol extract) from TN1, and antioxidant stability of both CPWE and CPEE was higher than that of vitamin C. Further biological experiments revealed that CPEE from TN1 possessed the strongest anti-inflammatory and antibacterial activities, and thus it is recommended as a multibioactive agent, which may have applications in the food, cosmetic, and nutraceutical industries

Deep Learning of Ultrasound Imaging for Evaluating Ambulatory Function of Individuals with Duchenne Muscular Dystrophy

Duchenne muscular dystrophy (DMD) results in loss of ambulation and premature death. Ultrasound provides real-time, safe, and cost-effective routine examinations. Deep learning allows the automatic generation of useful features for classification. This study utilized deep learning of ultrasound imaging for classifying patients with DMD based on their ambulatory function. A total of 85 individuals (including ambulatory and nonambulatory subjects) underwent ultrasound examinations of the gastrocnemius for deep learning of image data using LeNet, AlexNet, VGG-16, VGG-16TL, VGG-19, and VGG-19TL models (the notation TL indicates fine-tuning pretrained models). Gradient-weighted class activation mapping (Grad-CAM) was used to visualize features recognized by the models. The classification performance was evaluated using the confusion matrix and receiver operating characteristic (ROC) curve analysis. The results show that each deep learning model endows muscle ultrasound imaging with the ability to enable DMD evaluations. The Grad-CAMs indicated that boundary visibility, muscular texture clarity, and posterior shadowing are relevant sonographic features recognized by the models for evaluating ambulatory function. Of the proposed models, VGG-19 provided satisfying classification performance (the area under the ROC curve: 0.98; accuracy: 94.18%) and feature recognition in terms of physical characteristics. Deep learning of muscle ultrasound is a potential strategy for DMD characterization

LD patterns of the 5 SNPs.

<p>LD patterns based on the D’ (left side) and r² (right side) measures of the five associated SNPs for 625 individuals in the GWAS scan. The LD block built up by the rs9276370, rs7756516 and rs7453920 suggest that they were significantly associated with each other. The rs9366816 and rs9277535 SNPs were independent from each other and from the other three SNPs.</p

Haplotype association of the 5 risk SNPs rs9276370, rs7756516, rs7453920, rs9277535 and rs9366816 with persistent HBV infection.

<p>Haplotype association of the 5 risk SNPs rs9276370, rs7756516, rs7453920, rs9277535 and rs9366816 with persistent HBV infection.</p

Association of the rs9276370 genotypes with therapeutic response in three treatment groups.

a<p>CMHP: The Cochran-Mantel-Haenszel (CMH) p-value for general association was tested for the relationship between the rs9276370 genotypes and the therapeutic response after controlling for treatment.</p>b<p>The additive G allele effect on the therapeutic response (sustained vs. non-sustained) was evaluated in logistic regression analysis. For each of the three treatment groups, the P-values, ORs and CIs were adjusted for age, whereas for the entire sample, the statistics were adjusted for age and treatment.</p

Carbon Monoxide Inhibits Receptor Activator of NF-&#954;B (RANKL)-Induced Osteoclastogenesis

Background: Low concentrations of carbon monoxide (CO) have anti-inflammatory effects and can reduce bone erosion in a murine collagen-induced arthritis model. The objective of this study was to assess the effects of CO on receptor activator of NF-&#947;B ligand (RANKL), one of the key stimulators of osteoclastogenesis. Methods: The in vivo effects of CO on RANKL expression were assessed in a collagen antibody-induced arthritis model in mice. Cell proliferation and apoptosis were assessed in the RAW246.7 cell line stimulated with RANKL and exposed to either air or CO. The number of tartrate resistant acid phosphatase (TRAP)-positive RAW246.7 cells was also examined after treatment with RANKL and the peroxisome proliferator-activated receptor gamma (PPAR&#947;) agonist, Troglitazone. Results: CO reduced RANKL expression in the synovium of arthritic mice. Although CO slightly increased RAW246.7 cell proliferation, no differences in activated caspase 3 levels were detected. In addition, Troglitazone ameliorated the inhibitory effects of CO on RANKL-induced TRAP expression by RAW246.7 cells. Conclusions: CO suppresses osteoclast differentiation by inhibiting the RANKL-induced activation of PPAR-&#947;. Given the role of the PPAR-&#947;/cFos (AP-1) pathway in regulating the transcription factor, NFATc1, the master regulator of osteoclastogenesis, further studies are warranted to explore CO in treating inflammatory bone disorders