Predictive performance of CHA2DS2-VASc-HS score and Framingham risk scores for coronary disease severity in ischemic heart disease patients with invasive coronary angiography.

OBJECTIVE: The objective of this study was to determine the predictive performance and compatibility of CHA2DS2-VASc-HS scores and Framingham risk scores (FRS) in patients with coronary angiography. PATIENTS AND METHODS: This cross-sectional analysis study enrolled 98 patients with ischemic heart disease who were indicated for invasive coronary angiography. Sensitivity and specificity were determined using the cut-off values of the ROC curve. The Gensini score was used to evaluate the correlation. RESULTS: The cut-off value of the Congestive heart failure, hypertension, age 75 years, diabetes mellitus, stroke, vascular disease, age 65-74 years, sex category - hyperlipidemia, smoking (CHA2DS2-VASc-HS) score was 2.5, and for FRS, it was 14.5. The area under the curve (95% CI) for the CHA2DS2-VASc-HS score and FRS were 0.76 (0.66, 0.85) and 0.80 (0.71, 0.85), respectively. For every 1-point increase in the CHA2DS2-VASc-HS score, the Gensini score increased by 0.44 (r = 0.56; R2 = 0.19, Beta = 0.44, p < 0.01), and the number of stenosis coronary branches increased by 0.55 (r = 0.56; R2 = 0.30, Beta = 0.55, p < 0.01). For every 10-point increase in FRS, the Gensini score increased by 3.8 (r = 0.57; R2 = 0.14, Beta = 0.38, p < 0.01), and the number of stenosis coronary branches increased by 5 (r = 0.53; R2 = 0.25, Beta = 0.5, p < 0.01). CONCLUSIONS: Our study demonstrated a high predictive performance of coronary artery injury using the CHA2DS2-VASc-HS score and Framingham risk scores. These scores could be applied in predicting ischemic heart disease in non-symptomatic cases where invasive coronary angiography is not indicated.

Cellular transcription factors enhance herpes simplex virus type 1 oriS-dependent DNA replication.

The herpes simplex virus type 1 (HSV-1) origin of DNA replication, oriS, contains three binding sites for the viral origin binding protein (OBP) flanked by transcriptional regulatory elements of the immediate-early genes encoding ICP4 and ICP22/47. To assess the role of flanking sequences in oriS function, plasmids containing oriS and either wild-type or mutant flanking sequences were tested in transient DNA replication assays. Although the ICP4 and ICP22/47 regulatory regions were shown to enhance oriS function, most individual elements in these regions, including the VP16-responsive TAATGARAT elements, were found to be dispensable for oriS function. In contrast, two oriS core-adjacent regulatory (Oscar) elements, OscarL and OscarR, at the base of the oriS palindrome were shown to enhance oriS function significantly and additively. Specifically, mutational disruption of either element reduced oriS-dependent DNA replication by 60 to 70%, and disruption of both elements reduced replication by 90%. The properties of protein-DNA complexes formed in gel mobility shift assays using uninfected and HSV-1-infected Vero cell nuclear extracts demonstrated that both OscarL and OscarR are binding sites for cellular proteins. Whereas OscarR does not correspond to the consensus binding site of any known transcription factor, OscarL contains a consensus binding site for the transcription factor Sp1. Gel mobility shift and supershift experiments using antibodies directed against members of the Sp1 family of transcription factors demonstrated the presence of Sp1 and Sp3, but not Sp2 or Sp4, in the protein-DNA complexes formed at OscarL. The abilities of OscarL and OscarR to bind their respective cellular proteins correlated directly with the efficiency of oriS-dependent DNA replication. Cooperative interactions between the Oscar-binding factors and proteins binding to adjacent OBP binding sites were not observed. Notably, Oscar element mutations that impaired oriS-dependent DNA replication had no detectable effect on either basal or induced levels of transcription from the ICP4 and ICP22/47 promoters, as determined by RNase protection assays. The Oscar elements thus appear to provide binding sites for cellular proteins that facilitate oriS-dependent DNA replication but have no effect on transcription of oriS-flanking genes.

Prototype breast coil for MR-guided needle localization.

OBJECTIVE: Evaluation of breast lesions detected by MR alone is a problem: Preoperative MR-guided localization is difficult, since the breast is not accessible by a needle within the breast coil. Magnetic resonance-guided core biopsy and needle aspiration are impossible. Together with Siemens Erlangen, a prototype localization breast coil has been developed and tested. MATERIALS AND METHODS: The device consists of a circular polarized coil, which contains two plates for mediolateral breast compression. They are perforated with numerous holes and thus allow access to the breast from both sides. By means of bushings, which fit into the holes, sterile needle insertion in a horizontal path is possible. RESULTS: So far, precise needle insertion has been possible in 10 of 11 lesions, allowing exact needle insertion into 5 invasive carcinomas (1 MR-detected), 1 MR-detected additional focus, 2 in situ carcinomas (1 MR-detected), and 3 benign lesions. CONCLUSION: Our studies show that MR-guided needle localization is possible.

Weakener of white (Wow), a gene that modifies the expression of the white eye color locus and that suppresses position effect variegation in Drosophila melanogaster.

A locus is described in Drosophila melanogaster that modifies the expression of the white eye color gene. This trans-acting modifier reduces the expression of the white gene in the eye, but elevates the expression in other adult tissues. Because of the eye phenotype in which the expression of white is lessened but not eliminated, the newly described locus is called the Weakener of white (Wow). Northern analysis reveals that Wow can exert an inverse or direct modifying effect depending upon the developmental stage. Two related genes, brown and scarlet, that are coordinately expressed with white, are also affected by Wow. In addition, Wow modulates the steady state RNA level of the retrotransposon, copia. When tested with a white promoter-Alcohol dehydrogenase reporter. Wow confers the modifying effect to the reporter, suggesting a requirement of the white regulatory sequences for mediating the response. In addition to being a dosage sensitive regulator of white, brown, scarlet and copia, Wow acts as a suppressor of position effect variegation. There are many dosage sensitive suppressors of position effect variegation and many dosage-sensitive modifiers of gene expression. The Wow mutations provide evidence for an overlap between the two types of modifiers.

A trans-acting regulatory gene that inversely affects the expression of the white, brown and scarlet loci in Drosophila.

A trans-acting regulatory gene, Inr-a, that alters the level of expression of the white eye color locus as an inverse function of the number of its functional copies is described. Several independent lines of evidence demonstrate that this regulatory gene interacts with white via the promoter sequences. Among these are the observations that the inverse regulatory effect is conferred to the Adh gene when fused to the white promoter and that cis-regulatory mutants of white fail to respond. The phenotypic response to Inr-a is found in all tissues in which white is expressed, and mutants of the regulator exhibit a recessive lethality during larval periods. Increased white messenger RNA levels in pupal stages are found in Inr-a/+ individuals versus +/+ and a coordinate response is observed for mRNA levels from the brown and scarlet loci. All are structurally related and participate in pigment deposition. These experiments demonstrate that a single regulatory gene can exert an inverse effect on a target structural locus, a situation postulated from segmental aneuploid studies of gene expression and dosage compensation.