Flavonoids from the peels of Citrus unshiu Markov. and their inhibitory effects on RANKL-induced osteoclastogenesis through the downregulation of c-Fos signaling in vitro.

Phytochemical investigation of Citrus unshiu peels led to the isolation of eight new flavonols (7-9, 11-15) and sixteen known compounds (1-6, 10, 16-24). Their structures were elucidated using spectroscopic analysis (1D, 2D NMR, and HR-MS). Besides, all isolated compounds (1-24) were evaluated for their inhibitory effects on receptor activator of RANKL-induced osteoclastogenesis in BMMs. Among them, dimethylmikanin (1), quercetogetin (2), 3,3',4',5,7,8-hexamethoxyflavone (3), 3-methoxynobiletin (4) showed a significant inhibitory effect on RANKL-induced osteoclast differentiation at a concentration of 10 µM. Moreover, 3-methoxynobiletin (4) suppressed RANKL-induced osteoclastogenesis by decreasing the number of osteoclasts and osteoclast actin-ring formation in a dose-dependent manner without causing any cytotoxic effects on BMMs. At the molecular level, 3-methoxynobiletin (4) inhibited RANKL-induced c-Fos expression and subsequently NFATc1 activation, as well as the expression of osteoclastogenesis-related marker genes c-Src and CtsK. These findings suggested that 3-methoxynobiletin (4) attenuated osteoclast differentiation by inhibiting RANKL-mediated c-Fos signaling and that it may have therapeutic potential for treating or preventing bone resorption-related diseases, such as osteoporosis.

Fully automated measurements of volumetric breast density adapted for BIRADS 5th edition: a comparison with visual assessment.

BACKGROUND: Since the 5th edition of BI-RADS was released, prior studies have compared BI-RADS and quantitative fully automated volumetric assessment, but with software packages that were not recalibrated according to the 5th edition. PURPOSE: To investigate mammographic density assessment of automated volumetric measurements recalibrated according to the BI-RADS 5th edition compared with visual assessment. MATERIAL AND METHODS: A total of 4000 full-field digital mammographic examinations were reviewed by three radiologists for the BI-RADS 5th edition density category by consensus after individual assessments. Volumetric density data obtained using Quantra and Volpara software were collected. The comparison of visual and volumetric density assessments was performed in total and according to the presence of cancer. RESULTS: Among 4000 examinations, 129 were mammograms of breast cancer. Compared to visual assessment, volumetric measurements showed higher category B (40.6% vs. 19.8%) in Quantra, and higher category D (40.4% vs. 14.7%) and lower category A (0.2% vs. 5.0%) in Volpara (P < 0.0001). All volumetric data showed a difference according to visually assessed categories and were correlated between the two volumetric measurements (P < 0.0001). The group with cancer showed a lower proportion of fatty breast than that without cancer: 17.8% vs. 46.9% for Quantra (P < 0.0001) and 9.3% vs. 21.5% for Volpara (P = 0.003). Both measurements showed significantly higher mean density data in the group with cancer than without cancer (P < 0.005 for all). CONCLUSION: Automated volumetric measurements adapted for the BI-RADS 5th edition showed different but correlated results with visual assessment and each other. Recalibration of volumetric measurement has not completely reflected the visual assessment.

Comparison of Visual Assessment of Breast Density in BI-RADS 4th and 5th Editions With Automated Volumetric Measurement.

OBJECTIVE: The purpose of this study was to compare visual assessments of mammographic breast density by radiologists using BI-RADS 4th and 5th editions in correlation with automated volumetric breast density measurements. MATERIALS AND METHODS: A total of 337 consecutive full-field digital mammographic examinations with standard views were retrospectively assessed by two radiologists for mammographic breast density according to BI-RADS 4th and 5th editions. Fully automated measurement of the volume of fibroglandular tissue and total breast and percentage breast density was performed with a commercially available software program. Interobserver and intraobserver agreement was assessed with kappa statistics. The distributions of breast density categories for both editions of BI-RADS were compared and correlated with volumetric data. RESULTS: Interobserver agreement on breast density category was moderate to substantial (κ = 0.58-0.63) with use of BI-RADS 4th edition and substantial (κ = 0.63-0.66) with use of the 5th edition but without significant difference between the two editions. For intraobserver agreement between the two editions, the distributions of density category were significantly different (p < 0.0001), the proportions of dense breast increased, and the proportion of fatty breast decreased with use of the 5th edition compared with the 4th edition (p < 0.0001). All volumetric breast density data, including percentage breast density, were significantly different among density categories (p < 0.0001) and had significant correlation with visual assessment for both editions of BI-RADS (p < 0.01). CONCLUSION: Assessment using BI-RADS 5th edition revealed a higher proportion of dense breast than assessment using BI-RADS 4th edition. Nevertheless, automated volumetric density assessment had good correlation with visual assessment for both editions of BI-RADS.

Automated Volumetric Breast Density Measurements in the Era of the BI-RADS Fifth Edition: A Comparison With Visual Assessment.

OBJECTIVE: The purpose of this study is to evaluate automated volumetric measurements in comparison with visual assessment of mammographic breast density by use of the fifth edition of BI-RADS. MATERIALS AND METHODS: A total of 1185 full-field digital mammography examinations with standard views were retrospectively analyzed. All images were visually assessed by two blinded radiologists according to breast density category in the fifth edition of the BI-RADS lexicon. Automated volumetric breast density assessment was performed using two different software programs, Quantra and Volpara. A weighted kappa value was calculated to assess the degree of agreement among the visual and volumetric assessments of the density category. The volumes of fibroglandular tissue or total breast and the percentage breast density provided by the two software programs were compared. RESULTS: Compared with a visual assessment, the agreement of density category ranged from moderate to substantial in Quantra (κ = 0.54-0.61) and fair to moderate in Volpara (κ = 0.32-0.43). The distribution of density category was statistically significantly different among visual and volumetric measurements (p < 0.0001). Quantra assigned category A and B (43.5%) more frequently than did the radiologists (25.6%) or Volpara (16.0%). Volpara assigned category D (42.1%) more frequently than did the radiologists (19.5%) or Quantra (15.4%). Between the two software programs, the means of all volumetric data were statistically significantly different (p < 0.0001), but were well correlated (γ = 0.79-0.99; p < 0.0001). CONCLUSION: More mammographic examinations were classified as nondense breast tissue using the Quantra software and as dense breast tissue using the Volpara software, as compared with visual assessments according to the BI-RADS fifth edition.

Preoperative assessment of extrathyroidal extension of papillary thyroid carcinoma: comparison of 2- and 3-dimensional sonography.

OBJECTIVES: The purpose of this study was to evaluate the diagnostic performance and interobserver agreement of 2-dimensional (2D) and 3-dimensional (3D) sonography for evaluating extrathyroidal extension of papillary thyroid carcinoma. METHODS: A total of 79 papillary thyroid carcinomas in 79 patients who underwent both 2D and 3D sonography for preoperative staging of papillary thyroid carcinoma were included. When the lesion was abutting on the thyroid capsule on 2D sonography, 3D sonography was performed. Three radiologists reviewed 3 data sets: 2D sonography, 3D sonography, and a combined set of both for tumor staging. The diagnostic performance, including sensitivity, specificity, positive predictive value, negative predictive value, and accuracy, for extrathyroidal extension was analyzed. Interobserver agreement of the 3 radiologists was assessed with κ values. RESULTS: The overall accuracy rates for 2D sonography, 3D sonography, and the combined set in predicting extrathyroidal extension were 60.8%, 66.2%, and 67.9%, respectively. The accuracy of the combined set was significantly higher than that of 2D sonography (P = .016). The interobserver agreement of the 3 reviewers was fair (κ = 0.33) for 2D sonography and moderate for 3D sonography (κ = 0.46) and the combined set (κ = 0.49). CONCLUSIONS: Adding 3D sonography to 2D sonography could improve the accuracy and interobserver agreement for predicting extrathyroidal extension of papillary thyroid carcinoma.

Clinical application of qualitative assessment for breast masses in shear-wave elastography.

PURPOSE: To evaluate the interobserver agreement and the diagnostic performance of various qualitative features in shear-wave elastography (SWE) for breast masses. MATERIALS AND METHODS: A total of 153 breast lesions in 152 women who underwent B-mode ultrasound and SWE before biopsy were included. Qualitative analysis in SWE was performed using two different classifications: E values (Ecol; 6-point color score, Ehomo; homogeneity score and Esha; shape score) and a four-color pattern classification. Two radiologists reviewed five data sets: B-mode ultrasound, SWE, and combination of both for E values and four-color pattern. The BI-RADS categories were assessed B-mode and combined sets. Interobserver agreement was assessed using weighted κ statistics. Areas under the receiver operating characteristic curve (AUC), sensitivity, and specificity were analyzed. RESULTS: Interobserver agreement was substantial for Ecol (κ=0.79), Ehomo (κ=0.77) and four-color pattern (κ=0.64), and moderate for Esha (κ=0.56). Better-performing qualitative features were Ecol and four-color pattern (AUCs, 0.932 and 0.925) compared with Ehomo and Esha (AUCs, 0.857 and 0.864; P<0.05). The diagnostic performance of B-mode ultrasound (AUC, 0.950) was not significantly different from combined sets with E value and with four color pattern (AUCs, 0.962 and 0.954). When all qualitative values were negative, leading to downgrade the BI-RADS category, the specificity increased significantly from 16.5% to 56.1% (E value) and 57.0% (four-color pattern) (P<0.001) without improvement in sensitivity. CONCLUSION: The qualitative SWE features were highly reproducible and showed good diagnostic performance in suspicious breast masses. Adding qualitative SWE to B-mode ultrasound increased specificity in decision making for biopsy recommendation.

Radiologist assessment of breast density by BI-RADS categories versus fully automated volumetric assessment.

OBJECTIVE: The objective of our study was to estimate mammographic breast density using a fully automated volumetric breast density measurement method in comparison with BI-RADS breast density categories determined by radiologists. MATERIALS AND METHODS: A total of 791 full-field digital mammography examinations with standard views were evaluated by three blinded radiologists as BI-RADS density categories 1-4. For fully automated volumetric analysis, volumetric breast density was calculated with fully automated software. The volume of fibroglandular tissue, the volume of the breast, and the volumetric percentage density were provided. RESULTS: The weighted overall kappa was 0.48 (moderate agreement) for the three radiologists' estimates of BI-RADS density. Pairwise comparisons of the radiologists' measurements of BI-RADS density revealed moderate to substantial agreement, with kappa values ranging from 0.51 to 0.64. There was a significant difference in mean volumetric breast density among the BI-RADS density categories, and the mean volumetric breast density increased as the BI-RADS density category increased (p<0.001). A significant positive correlation was found between BI-RADS categories and fully automated volumetric breast density (ρ=0.765, p<0.001). CONCLUSION: Our study showed good correlation of the fully automated volumetric method with radiologist-assigned BI-RADS density categories. Mammographic density assessment with the fully automated volumetric method may be used to assign BI-RADS density categories.

Quantitative assessment of shear-wave ultrasound elastography in thyroid nodules: diagnostic performance for predicting malignancy.

OBJECTIVES: To evaluate the predictability of shear-wave ultrasound elastography (SWE) for thyroid malignancy and to compare the diagnostic performances of SWE and B-mode US. METHODS: Retrospective review of 99 patients who underwent SWE before US-guided fine-needle aspiration of thyroid nodules was performed. SWE elasticity indices of the mean (Emean ), maximum (Emax), and minimum (Emin) of nodules were measured. Diagnostic performance of SWE was compared with that of B-mode US. RESULTS: Among a total of 99 nodules, 21 were papillary thyroid carcinoma (PTC) and 78 were benign. Emean, Emax, and Emin were significantly higher in PTCs than in benign nodules (P < 0.001). Sensitivity and specificity for predicting malignancy were 76.1 %, 64.1 % with Emax (65 kPa), 61.9 %, 76.1 % with Emin (53 kPa), and 66.6 %, 71.6 % with Emean (62 kPa). Areas under the ROC curves (Az) of SWE values were not significantly different from those of US categories on B-mode US. However, combining Emean and Emin with B-mode US of probably benign lesions improved the specificity (P = 0.02, 0.007) for predicting PTC. CONCLUSIONS: The quantitative parameter of SWE was significantly higher in PTC than in benign nodules, and combined use of quantitative SWE and B-mode US provided higher specificity for predicting malignancy. KEY POINTS: • Quantitative shear-wave elastography (SWE) helps differentiate benign from malignant nodules • SWE and conventional ultrasound have comparable diagnostic performance for predicting thyroid malignancy • Combined quantitative SWE and B-mode ultrasound is highly specific for thyroid malignancy.

Value of the US BI-RADS final assessment following mastectomy: BI-RADS 4 and 5 lesions.

BACKGROUND: Clinical examination is not entirely sufficient for evaluation of the postoperative site for follow-up of patients with mastectomy. A few studies have reported that postoperative follow-up US evaluation allows early detection and proper management of local tumor recurrence. PURPOSE: To evaluate the diagnostic performance of the American College of Radiology (ACR) ultrasonographic (US) Breast Imaging Reporting and Data System (BI-RADS) categories 4 and 5 breast lesions at the mastectomy site. MATERIAL AND METHODS: Our institutional review board approved this study and waived the need for informed consent. We retrospectively reviewed the consecutive post-mastectomy US exams for palpable and non-palpable lesions in the post-mastectomy chest wall that were categorized as BI-RADS 4 (subcategorized 4a, 4b, and 4c) or 5 between January 2007 and April 2010. The positive predictive value (PPV) for final assessment was evaluated. RESULTS: From 2681 post-mastectomy US examinations, we obtained a study population of 50 patients with 50 lesions (20 palpable, 30 non-palpable). There were nine (45%) malignancies among the palpable lesions and six (20%) malignancies among the non-palpable lesions. The palpability showed no significant correlation with malignancy in overall subcategorization (P >0.05). The PPVs of categories 4 and 5 were 14.3% for category 4a, 62.5% for category 4b, 100% for category 4c, and 100% for category 5. CONCLUSION: The ACR US BI-RADS categorization of 4a, 4b, 4c, and 5 for breast lesions at the mastectomy site is a feasible method for predicting local recurrence. All lesions should be managed according to US characteristics during evaluation of local recurrence at the mastectomy site, regardless of palpability.

[Quality of life in low income Korean aged].

PURPOSE: The purpose of this study was to identify the quality of life and its predictors in low income Korean aged. METHODS: This was a predictive correlational study. An accessible sample from the population of people who were 65 and over and were supported by the basic livelihood security system was 1,040. Quota sampling with strata of state division in the nation was chosen. Quality of life and its predictors in the subjects were measured. RESULTS: The mean quality of life in the subjects was 47.0+/-10.7. Predictors of this study significantly explained 54.3% of the total variance of quality of life. Depression was the most significant predictor of quality of life. Health problems, district, social support, leisure activity, and health behavior had effects on quality of life. CONCLUSION: This finding indicates that quality of life in lower income Korean aged is different from other populations by economic status. Demographics, health status and social status were predictors of quality of life in the aged with a small income.