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Aims/Introduction: The purpose of this study was to investigate the impact of vision and hearing impairments on the risk of adverse cardiovascular outcomes and mortality in patients with type 2 diabetes using a nationwide longitudinal cohort. Materials and Methods: We enrolled 771,128 patients with type 2 diabetes who underwent the National Health Screening Program in 2009. We carried out Cox proportional hazards regression analyses to calculate the hazard ratios (HR) of myocardial infarction (MI), stroke, and mortality in those with or without vision and hearing impairments. Subgroup analyses of patients stratified by age, sex and diabetic retinopathy were carried out. Results: Diabetes patients with either vision or hearing impairment showed higher risk of MI, stroke or death compared with those without. Among the combinations of impairments, patients with both vision and hearing impairments had the highest risk for MI (adjusted HR [aHR] 1.362, 95% confidence interval [CI] 1.252–1.481) and mortality (aHR 1.591, 95% CI 1.532–1.651). Those with only vision impairment showed higher risk of MI (aHR 1.324, 95% CI 1.275–1.375 and aHR 1.117, 95% CI 1.066–1.170, respectively), stroke (aHR 1.318, 95% CI 1.276–1.362 and aHR 1.134 95% CI 1.089–1.180, respectively) and mortality (aHR 1.417, 95% CI 1.390–1.446 and aHR 1.163, 95% CI 1.135–1.191, respectively) compared with those with only hearing impairment. Conclusions: Vision and hearing impairments are independently important risk factors for adverse cardiovascular events and mortality in patients with type 2 diabetes. Vision and hearing impairments synergistically increased the risk of MI and all‐cause deaths, but not stroke. In addition, in patients aged <65 years, the HR of vision impairment was higher than those with vision and hearing impairments. [ABSTRACT FROM AUTHOR]

Background: Given the usefulness of rats as an experimental system, an efficient method for generating rat induced pluripotent stem (iPS) cells would provide researchers with a powerful tool for studying human physiology and disease. Here, we report direct reprogramming of rat neural precursor (NP) cells and rat embryonic fibroblasts (REF) into iPS cells by retroviral transduction using either three (Oct3/4, Sox2, and Klf4), four (Oct3/4, Sox2, Klf4, and c-Myc), or five (Oct3/4, Sox2, Klf4, c-Myc, and Nanog) genes. Methodology and Principal Findings: iPS cells were generated from both NP and REF using only three (Oct3/4, Sox2, and Klf4) genes without c-Myc. Two factors were found to be critical for efficient derivation and maintenance of rat iPS cells: the use of rat instead of mouse feeders, and the use of small molecules specifically inhibiting mitogen-activated protein kinase and glycogen synthase kinase 3 pathways. In contrast, introduction of embryonic stem cell (ESC) extracts induced partial reprogramming, but failed to generate iPS cells. However, when combined with retroviral transduction, this method generated iPS cells with significantly higher efficiency. Morphology, gene expression, and epigenetic status confirmed that these rat iPS cells exhibited ESC-like properties, including the ability to differentiate into all three germ layers both in vitro and in teratomas. In particular, we found that these rat iPS cells could differentiate to midbrain-like dopamine neurons with a high efficiency. Conclusions/Significance: Given the usefulness of rats as an experimental system, our optimized method would be useful for generating rat iPS cells from diverse tissues and provide researchers with a powerful tool for studying human physiology and disease.