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Proteinuria is one of the well-known risk factors for cardiovascular disease. However the impact of proteinuria on the incidence of atrial fibrillation (AF) is unclear. In this study, we investigated the association between proteinuria detected using urine dipstick test and the risk of AF. A total of 18,201,275 individuals were analyzed, who had no prior AF and had received biennial health checkups provided by the National Health Insurance Service between 2005 and 2008 in Korea. Incidences of AF were ascertained through the end of 2015. During a mean follow-up of 9.6 years, a total of 324,764 (1.8%) developed AF (1.86 per 1,000 person-years). In Cox regression models, proteinuria was associated with an increased risk of AF: adjusted HR and 95% CI of AF occurrence were 1.13 (1.10-1.16), 1.34 (1.31-1.38), 1.53 (1.48-1.58), 1.82 (1.71-1.94), and 1.86 (1.61-2.16) in individuals with trace, 1+, 2+, 3+, and 4+ proteinuria, respectively, compared with those without proteinuria. The result was consistent even after additional adjustment for estimated glomerular filtration rate. In addition, the risk of AF further increased or decreased according to the follow-up dipstick test results. Thus, proteinuria measured with a dipstick test might be considered a potent risk factor for AF development.
Proteinuria Detected by Urine Dipstick Test as a Risk Factor for Atrial Fibrillation: A Nationwide Population-Based Study
Woo-Hyun Lim,1 Eue -Keun Choi,corresponding author2 Kyung-Do Han,3 Tae-Min Rhee,2 Hyun-Jung Lee,2 So-Ryoung Lee,2 Si-Hyuck Kang,4 Myung-Jin Cha,2 and Seil Oh2
Our study aims to determine the value of diffusion-weighted imaging (DWI) combined with conventional magnetic resonance imaging (MRI) in the diagnosis of thecomas/fibrothecomas and their differential diagnosis with malignant pelvic solid tumors.
In total, 36 thecomas/fibrothecomas and 40 malignant pelvic solid tumors were included in our study. All patients underwent 1.5 T conventional MRI and DWI examinations except one patient with a fibrothecoma in whom DWI examination was not performed. The clinical features and characteristics of conventional MRI and DWI of these two groups were analyzed. Apparent diffusion coefficient (ADC) values were measured and compared between groups. Univariate analysis, multivariate logistic regression analysis, and the receiver operating characteristic curve were used for statistical analysis.
All the thecomas/fibrothecomas showed isointensity on T1 weighted imaging (T1WI) and 77.8 % (28/36) lesions showed hypo- to isointensity on T2 weighted imaging (T2WI). After administration of contrast medium, 94.4 % (34/36) tumors appeared as minor to mild enhancement. On DWI, they showed a diversity of low to very high signal intensity. All malignant pelvic masses manifested as hyperintensity on T2WI and 87.5 % (35/40) tumors showed very high signal (grade 3) on DWI. Higher area under the curve (AUC) and specificity could be achieved by using the lowest ADC value than the mean ADC value. Multivariate logistic regression analysis showed that shape, signal intensity on T2WI, capsule, and the lowest ADC value were the important indicators in discriminating thecomas/fibrothecomas from malignant pelvic solid tumors.
The combination of DWI and conventional MRI is of great value in the diagnosis of thecomas/fibrothecomas and their differential diagnosis with malignant pelvic solid tumors.
Thecoma, Malignant pelvic solid tumors, Conventional magnetic resonance imaging, Diffusion-weighted imaging, Apparent diffusion coefficient value
Value of diffusion-weighted imaging combined with conventional magnetic resonance imaging in the diagnosis of thecomas/fibrothecomas and their differential diagnosis with malignant pelvic solid tumors
Bing Yin,1 Wenhua Li,corresponding author1 Yanfen Cui,1 Caiting Chu,1 Ming Ding,1 Jian Chen,1 Ping Zhang,2 and Xiangru Wu3
As previously shown, 11 loci are required to complement human cytomegalovirus (HCMV) DNA replication in a transient-transfection assay (G. S. Pari and D. G. Anders, J. Virol. 67:6979-6988, 1993). Six of these loci encode known or candidate replication fork proteins, as judged by sequence and biochemical similarities to herpes simplex virus homologs of known function; three encode known immediate early regulatory proteins (UL36-38, IRS1/TRS1, and the major immediate early region spanning UL122-123); and two encode early, nucleus-localized proteins of unknown functions (UL84 and UL112-113). We speculated that proteins of the latter five loci might cooperate to promote and regulate expression of the six replication fork proteins. To test this hypothesis we made luciferase reporter plasmids for each of the replication fork gene promoters and measured their activation by the candidate effectors, expressed under the control of their respective native promoters, using a transient-cooperativity assay in which the candidate effectors were subtracted individually from a transfection mixture containing all five loci. The combination of UL36-38, UL112-113, IRS1, or TRS1 and the major immediate early region produced as much as 100-fold-higher expression than the major immediate early region alone; omitting any one of these four loci from complementing mixtures produced a significant reduction in expression. In contrast, omitting UL84 had insignificant (less than twofold), promoter-dependent effects on reporter activity, and these data do not implicate UL84 in regulating HCMV early-gene expression. Most of the effector interactions showed significant positive cooperativity, producing synergistic enhancement of expression. Similar responses to these effectors were observed for the each of the promoters controlling expression of replication fork proteins. However, subtracting UL112-113 had little if any effect on expression by the UL112-113 promoter or by the simian virus 40 promoter-enhancer under the same conditions. Several lines of evidence argue that the cooperative interactions observed in our transient-transfection assays are important to viral replication in permissive cells. Therefore, the data suggest a model in which coordinate expression of multiple essential replication proteins during permissive infection is vitally dependent upon the cooperative regulatory interactions of proteins encoded by multiple loci and thus have broad implications for our understanding of HCMV biology.
Four of eleven loci required for transient complementation of human cytomegalovirus DNA replication cooperate to activate expression of replication genes.
A C Iskenderian, L Huang, A Reilly, R M Stenberg, and D G Anders