Gemcitabine plus cisplatin chemoradiotherapy followed by BCT and adjuvant gemcitabine/cisplatin chemotherapy improved survival outcomes with increased but clinically manageable toxicity when compared with standard treatment.

We investigated type 2 diabetes (T2D) genetic susceptibility in a multi-ethnic meta-analysis of 228,499 cases and 1,178,783 controls in the Million Veteran Program (MVP) and other biobanks. We identified 558 autosomal and 10 X-chromosome T2D-associated variants, of which 286 autosomal and 7 X-chromosome variants were previously unreported. Ancestry-specific analyses identified 25 additional novel T2D-susceptibility variants. Transcriptome-wide association analysis detected 3,568 T2D-associations with T2D-colocalized genetically predicted gene expression of 804 genes in 52 tissues, of which 687 are novel. Fifty-four of these genes are known to interact with FDA-approved drugs and chemical compounds. T2D polygenic risk score was strongly associated with increased the risk of T2D-related retinopathy, and additionally showed evidence for association with chronic kidney disease (CKD), neuropathy, and peripheral artery disease (PAD). We investigated the genetic etiology of T2D-related vascular outcomes in the MVP and observed statistical SNP-T2D interactions at 13 variants, including 3 for coronary heart disease, 1 for PAD, 2 for stroke, 4 for retinopathy, 2 for CKD, and 1 for neuropathy. Our findings may identify potential novel therapeutic targets for T2D and genomic pathways that link T2D and its vascular outcomes.

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Background and objective: The association between serum uric acid and ischemic heart disease remains controversial and it has not yet been established as cardiovascular risk factor. Our objective was to study the association of serum uric acid level with angiographic severity of coronary artery disease in men with acute coronary syndrome (ACS). Methods : This cross-sectional study was conducted on 100 consecutive male patients presenting with ACS at Punjab Institute of Cardiology. Hyperuricemia was defined as serum uric acid level > 6.5 mg/dl. Severity of ischemic heart disease was assessed on the basis of Gensini score, number of diseased vessels, critical lesions and total occlusions on coronary angiogram. Results: Mean age of normouricemic group (n=59) was 52.62 ± 9.46 years and mean age of hyperuricemic group (n=41) was 50.52 ± 9.40 years (p=0.273). Mean uric acid level; normouricemic group (4.75 ± 1.05), hyperuricemic group (7.61 ± 1.24), p<0.001. Mean Gensini score; normouricemic group (22.15 ± 21.52), hyperuricemic group (35.69 ± 26.80). Mann Whitney U test was applied to compare the Gensini score of two groups and it showed statistically significant difference (p value <0.006). Critical lesions, total occlusions and multi-vessel disease were more frequent in hyperuricemic group but statistically significant difference was found only for total occlusions (p=0.013) and critical lesions (p=0.046). Conclusions : Hyeruricemia is associated with higher Gensini score and more frequent total occlusions and critical lesions in men presenting with acute coronary syndrome.

Luteoviruses are economically important plant viruses, infecting almost all cereals throughout the world. Idiosyncrasies related to this virus group may be a strategic consequence of viral genome compression. However, many fundamental questions have yet to be resolved. This review summarizes selected findings covering molecular aspects of pathogenesis relating to plant-infecting RNA viruses in general, and luteoviruses in specific. These studies enhance our understanding of the replication structures and the virus infection pathways.