Is dual-energy absorptiometry accurate in the assessment of bone status of patients with chronic kidney disease?

Several patients with chronic kidney disease (CKD) have deteriorated bone status. Estimation of bone status using DXA has limitations especially in patients with CKD accompanying aortic calcifications. Quantitative CT and the trabecular bone score could be more accurate methods to estimate bone status for patients with CKD and vascular calcifications. INTRODUCTION: It remains unclear whether dual-energy absorptiometry (DXA) is appropriate for the assessment of bone status in patients with chronic kidney disease (CKD), a disease that impacts bone health. The aims of this study were to compare DXA and central quantitative computed tomography (cQCT) and to evaluate bone status in patients with pre-dialysis CKD. METHODS: This retrospective study included 363 healthy control subjects whose bone mineral density (BMD) was evaluated with DXA and 117 CKD patients whose BMD was evaluated using both cQCT and DXA. Diagnostic discordance was assessed between the lumbar spine (LS) and femur neck (FN) from DXA or between two modalities. The trabecular bone score (TBS) was extracted from DXA images. The volume of abdominal aortic calcification (AAC) was calculated using CT images from cQCT. RESULTS: Using LS DXA T-score, osteoporosis was less common in the CKD group than in controls. Patients with normal LS BMD using DXA were reclassified into osteopenia or osteoporosis using cQCT in CKD patients. Among discordant subjects between FN and LS in DXA, a higher BMD of LS was more common in CKD patients than in controls. CKD patients had lower TBS than controls despite having the same diagnosis using DXA. AAC volume negatively correlated with BMD from cQCT and with TBS but not with BMD from DXA. CONCLUSIONS: TBS and cQCT could accurately assess bone status in CKD patients since DXA may overestimate LS BMD, likely due to an increased AAC volume.

RESPONSE OF DOSEMETERS IN FIELDS GENERATED BY LASER-ACCELERATED PROTONS.

In laser-driven acceleration, ultra-short and intense laser pulses are focussed on targets to generate beams of ionising radiation. One of the most important issues to be addressed is personal monitoring. While traditional dosemeters were designed primarily for measurements in continuous fields, dosemeters for laser laboratories must be capable of working in pulsed fields of pulse length below 1 ps, in a single-shot regime up to the repetition rate of 1 kHz. Responses of conventional dosemeters (films, polyallyldiglycol carbonate, electronic personal dosemeter) to proton bunches of up to 30 MeV energy produced by South Korean PW laser system at the Advanced Photonics Research Institute, Gwangju Institute of Science and Technology were studied, both by means of Monte Carlo simulations and experimentally.

Association between eNOS polymorphisms and risk of coronary artery disease in a Korean population: a meta-analysis.

Coronary artery disease (CAD), a multifactorial disease, is a common cause of mortality in humans. Polymorphisms in the endothelial nitric oxide synthase (eNOS) gene (-786T>C, 4a4b, and 894G>T) have been previously associated with increased CAD risk. However, the sample size of this previous study was too small and limited to comprehensively define an association between eNOS polymorphisms and CAD; therefore, this analysis was duplicated with a larger population. The study was conducted on 559 patients with CAD and 574 healthy controls. Genetic DNA was extracted using the commercial G-DEX blood extraction kit and statistical analyses were performed on the GraphPad prism 4.0 and MedCalc 12.0 statistical software platforms. No single variant of the eNOS polymorphism was associated with CAD risk. The combination genotypes of eNOS -786TT/4a4b+4a4a [adjusted odds ratio (AOR) = 0.122; 95% confidence interval (CI): 0.042-0.358] and eNOS -786TC+CC/4b4b (AOR = 0.379; 95%CI: 0.147-0.979) were associated with decreased CAD incidence. Haplotype analysis revealed that the T-4a haplotype of eNOS -786T>C and 4a4b exerted a protective effect against CAD. The association between eNOS -786T>C and increased CAD risk was not replicated in this (larger) population. However, some combined genotypes showed a meaningful association with CAD risk.

Low pulmonary function is related with a high risk of sarcopenia in community-dwelling older adults: the Korea National Health and Nutrition Examination Survey (KNHANES) 2008-2011.

UNLABELLED: Sarcopenia is the age-related reduction of skeletal muscle mass in older individuals. Respiratory muscle strength may be related to skeletal muscle mass and, thus, the present study attempted to estimate the risk of sarcopenia relative to decreased pulmonary function. The present findings demonstrated that low pulmonary function was associated with low muscle mass in community-dwelling older adults. INTRODUCTION: Lean body mass is related to pulmonary function in patients with chronic obstructive pulmonary disease (COPD). However, the relationship between muscle mass and pulmonary function in healthy older adults has yet to be clarified. Thus, the present study investigated the association of pulmonary function with muscle mass in an older community-dwelling Korean population. METHODS: This study included 463 disease-free subjects over 65 years of age who underwent anthropometric measurements, laboratory tests, spirometry, and the estimation of appendicular skeletal muscle (ASM) mass in the 2008-2011 Korea National Health and Nutrition Examination Survey (KNHANES). Low muscle mass was defined as the value of ASM divided by height squared (ASM/height(2)) that was less than two standard deviations (SD) below the sex-specific mean of the young reference group. RESULTS: Forced expiratory volume in 1 s (FEV1[L]) and forced vital capacity (FVC[L]) were positively correlated with ASM/height(2) in males (p < 0.001 and p = 0.001, respectively) but not in females (p = 0.360 and p = 0.779, respectively). A univariate logistic regression analysis revealed that males with low FEV1 or FVC were more likely to have low muscle mass (odds ratio [OR] = 3.11, 95% confidence interval [CI] 1.62-5.99 for FEV1; OR = 1.99, 95% CI 1.13-3.53 for FVC); similar results were found for females, but the significance was lower (OR = 11.37, 95% CI 0.97-132.91 for FEV1; OR = 7.31, 95% CI 1.25-42.74 for FVC). After adjusting for age, smoking, and moderate physical activity, a low FEV1 value was associated with low muscle mass in both males (OR = 2.90, 95% CI 1.50-5.63) and females (OR = 9.15, 95% CI 1.53-54.77). CONCLUSIONS: Using nationally representative data from the 2008-2011 KNHANES, low pulmonary function was found to be associated with low muscle mass in community-dwelling older Korean adults.

The relationship between pulmonary function and bone mineral density in healthy nonsmoking women: the Korean National Health and Nutrition Examination Survey (KNHANES) 2010.

UNLABELLED: The aim of this study was to examine the association between pulmonary function and bone mineral density (BMD) in subjects who had never smoked. Pulmonary function was associated with BMD in premenopausal, but not postmenopausal, women. INTRODUCTION: It has been reported that low bone mass is common in patients with pulmonary disorders such as chronic obstructive pulmonary disease. However, in healthy nonsmoking women, the relationship between bone mass and pulmonary function has yet to be clarified. The object of this study was to determine whether pulmonary function is related to BMD in healthy nonsmoking women based on menopausal status. METHODS: This study was a cross-sectional study based on data obtained from the Korean National Health and Nutrition Examination Survey (KNHANES), a nationwide representative survey conducted by the Korean Ministry of Health and Welfare in 2010. This study included 456 subjects who had never smoked and analyzed data concerning pulmonary function and BMD. RESULTS: Functional vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were correlated with BMD at lumbar spine, femur neck (FN), and total hip in premenopausal women (p = 0.030, p = 0.003, p = 0.019, respectively, for FVC; p = 0.015, p = 0.006, p = 0.059, respectively, for FEV1). However, FVC and FEV1 were only correlated with BMD at FN in postmenopausal women (p = 0.003 for FVC; p = 0.006 for FEV1). Body mass index (BMI), FVC, and FEV1 were significantly related with BMD at FN, even after adjusting for age and other confounding factors (ß = 0.334, p < 0.001; ß = 0.145, p = 0.017; and ß = 0.129, p = 0.037, respectively) in premenopausal women. However, only age and BMI were correlated with BMD at FN (ß = -0.268, p = 0.001 and ß = 0.384, p > 0.001) in postmenopausal women after adjusting for confounding factors. CONCLUSIONS: Pulmonary function, including FVC and FEV1 are associated with BMD at FN in healthy nonsmoking premenopausal women but not in postmenopausal women.

Targeting Gli transcription activation by small molecule suppresses tumor growth.

Targeted inhibition of Hedgehog signaling at the cell membrane has been associated with anticancer activity in preclinical and early clinical studies. Hedgehog signaling involves activation of Gli transcription factors that can also be induced by alternative pathways. In this study, we identified an interaction between Gli proteins and a transcription coactivator TBP-associated factor 9 (TAF9), and validated its functional relevance in regulating Gli transactivation. We also describe a novel, synthetic small molecule, FN1-8, that efficiently interferes with Gli/TAF9 interaction and downregulate Gli/TAF9-dependent transcriptional activity. More importantly, FN1-8 suppresses cancer cell proliferation in vitro and inhibits tumor growth in vivo. Our results suggest that blocking Gli transactivation, an important control point of multiple oncogenic pathways, may be an effective anticancer strategy.

HOXB13 downregulates intracellular zinc and increases NF-κB signaling to promote prostate cancer metastasis.

Characteristically, prostate cancer (PCa) cells exhibit marked decrease in intracellular zinc; however, the mechanism responsible is not clearly understood. HOXB13 is involved in PCa progression and is overexpressed in castration-resistant PCa. DNA microarray analysis of LNCaP Pca cells showed that ZnT zinc output transporters were strikingly upregulated among androgen-independent HOXB13 target genes. Furthermore, exogenous HOXB13 caused intracellular zinc concentrations to fall in PCa cells, stimulated NF-κB-mediated signaling by reducing inhibitor of NF-κB alpha (IκBα) and enhanced the nuclear translocation of RelA/p65. Human prostate tumors also exhibited strong inverse correlation between the protein expressions of HOXB13 and IκBα. Consequently, HOXB13 stimulated PCa cell invasion, and this was inhibited by the suppression of ZnT4. In addition, studies in a PC3 orthotopic mouse model of PCa metastasis showed that HOXB13 is a strong metastatic stimulator. Taken together, these results show that HOXB13 promotes PCa invasion and metastasis by decreasing intracellular zinc levels, thus stimulating NF-κB signals, and suggest that HOXB13 acts as a modulator of intracellular zinc levels that promotes the malignant characteristics of PCa.

Splenic FDG uptake predicts poor prognosis in patients with unresectable cholangiocarcinoma.

AIM: Diffuse splenic 18F-Fluorodeoxyglucose (FDG) uptake has shown to be associated with concurrent inflammation. We evaluated the prognostic value of diffuse splenic FDG uptake for predicting prognosis in cholangiocarcinoma patients. PATIENTS, METHODS: Sixty-four patients with unresectable cholangiocarcinoma performed Positron emission tomography/computed tomography (PET/CT) using FDG between July 2009 and April 2012. Patients were divided into two groups according to splenic FDG uptake relative to hepatic FDG uptake. Eleven patients showing splenic FDG uptake exceeding hepatic uptake were included in group A, while 53 patients with hepatic FDG uptake exceeding splenic uptake were included in group B. Prognostic factors for overall survival were evaluated using log-rank test. Variables with a probability of less than or equal to 0.1 on univariate analysis were considered as possible independent factors. Cox-proportional hazards model was used to analyze univariate and multivariate analysis. RESULTS: Mean standardized uptake value of the liver (Liver SUVmean)/Spleen SUVmean (L/S) ratio <1 (p = 0.0034), WBC > 10 000 (p = 0.1155) and CEA >30 (p = 0.0946) were predictors of overall survival on univariate analysis. In a subsequent multivariate analysis, L/S ratio <1 remained a significant independent predictor of poor prognosis (HR 6.0153, 95% CI, 1.7193-21.0460, p = 0.0052). CONCLUSION: Our study has shown that splenic FDG uptake could be a predictor of overall survival of unresectable cholangiocarcinoma patients.

Association between bone marrow lesions detected by magnetic resonance imaging and knee pain in community residents in Korea.

OBJECTIVE: To describe the frequency of bone marrow lesions (BMLs) detected by magnetic resonance imaging (MRI), and to examine the association of BMLs with knee pain severity in community residents in Korea. METHODS: Participants were randomly chosen from the population-based Hallym Aging Study, irrespective of whether they had knee osteoarthritis (OA) or pain. Demographic and knee pain data were obtained by questionnaire. Radiographic evaluations consisted of weight-bearing knee anteroposterior radiographs and 1.5-T MRI scans. MRI was performed in the dominant knees of subjects without knee pain and in the more symptomatic knees of subjects with knee pain. BMLs were graded according to the whole-organ MRI score. RESULTS: The mean age of the 358 study subjects was 71.8 years, and 34.5% of subjects had radiographically detected knee OA. The prevalences of BMLs and large BMLs in the tibiofemoral compartments were 80.3% and 40.4%, respectively. After adjusting for age, sex, and body mass index, total and medial compartment BML scores were significantly associated with the presence of knee pain, and the association was stronger as the summary score for BML increased. In proportional regression analysis, knee pain severity increased with BML severity in any compartment and in the medial compartment. CONCLUSION: BMLs detected by MRI were highly prevalent in this elderly Asian population. BMLs were significantly linked to knee pain, and BML severity correlated with knee pain severity. BMLs may be important surrogate targets for monitoring pain and structure modification in OA therapeutics.

Accurate measurement of bromine contents in plastic samples by instrumental neutron activation analysis.

Accurate measurements of bromine contents in plastic samples were made by the direct comparator instrumental neutron activation analysis (INAA). Individual factors affecting the measurements were comprehensively evaluated and compensated, including the volatility loss of bromine from standard comparators, the background bromine level in the filter papers used for preparation of the standard comparators, nuclear interference, γ-ray spectral interference and the variance among replicates of the samples. Uncertainty contributions from those factors were thoroughly evaluated and included in the uncertainty budgeting of the INAA measurement. (81)Br was chosen as the target isotope, and the INAA measurements for bromine were experimentally confirmed to exhibit good linearity within a bromine content range of 10-170 µg. The established method has been applied to the analysis of eight plastic samples: four commercially available certified reference materials (CRMs) of polyethylene and polystyrene and four acrylonitrile butadiene styrene (ABS) samples prepared as the candidate reference materials (KRISS CRM 113-01-012, -013, -014 and -015). The bromine contents of the samples were calculated at three different γ-ray energies and compared, showing good agreement. The results of the four CRMs also showed good consistency with their certified values within the stated uncertainties. Finally, the bromine contents of the ABS samples were determined with expanded uncertainties (at a 95% level of confidence) between 2.5% and 5% in a bromine content range of 25-900 mg kg(-1).

Research to improve extension ladder angular positioning.

A leading cause for extension ladder fall incidents is a slide-out event usually related to suboptimal ladder inclination. An improved ladder positioning method or procedure could reduce the risk of ladder stability failure and the related fall injury. The objective of the study was to comparatively evaluate the effectiveness of a multimodal angle indicator with other existing methods for extension ladder angular positioning. Twenty experienced and 20 inexperienced ladder users participated in the study. Four ladder positioning methods were tested in a controlled laboratory environment with 4.88 m (16 ft) and 7.32 m (24 ft) ladders in extended and retracted positions. The positioning methods included a no-instruction method, the current standard anthropometric method, and two instrumental methods - a bubble level indicator, and a multimodal indicator providing direct feedback with visual and sound signals. Performance measures included positioning angle and time. The results indicated that the anthropometric method was effective in improving the extension ladder positioning angle (p < 0.001); however, it was associated with considerable variability and required 50% more time than no-instruction. The bubble level indicator was an accurate positioning method (with very low variability), but required more than double the time of the no-instruction method (p < 0.001). The multimodal indicator improved the ladder angle setting as compared to the no-instruction and anthropometry methods (p < 0.001) and required the least time for ladder positioning among the tested methods (p < 0.001). An indicator with direct multimodal feedback is a viable approach for quick and accurate ladder positioning. The main advantage of the new multimodal method is that it provides continuous feedback on the angle of the device and hence does not require repositioning of the ladder. Furthermore, this indicator can be a valuable tool for training ladder users to correctly apply the current ANSI A14 standard anthropometric method in ladder angular positioning. The multimodal indicator concept has been further developed to become a hand-held tool in the form of a smart phone application.

Absolute energy calibration for relativistic electron beams with pointing instability from a laser-plasma accelerator.

The pointing instability of energetic electron beams generated from a laser-driven accelerator can cause a serious error in measuring the electron spectrum with a magnetic spectrometer. In order to determine a correct electron spectrum, the pointing angle of an electron beam incident on the spectrometer should be exactly defined. Here, we present a method for absolutely calibrating the electron spectrum by monitoring the pointing angle using a scintillating screen installed in front of a permanent dipole magnet. The ambiguous electron energy due to the pointing instability is corrected by the numerical and analytical calculations based on the relativistic equation of electron motion. It is also possible to estimate the energy spread of the electron beam and determine the energy resolution of the spectrometer using the beam divergence angle that is simultaneously measured on the screen. The calibration method with direct measurement of the spatial profile of an incident electron beam has a simple experimental layout and presents the full range of spatial and spectral information of the electron beams with energies of multi-hundred MeV level, despite the limited energy resolution of the simple electron spectrometer.

Hipk2 cooperates with p53 to suppress γ-ray radiation-induced mouse thymic lymphoma.

A genome-wide screen for genetic alterations in radiation-induced thymic lymphomas generated from p53+/- and p53-/- mice showed frequent loss of heterozygosity (LOH) on chromosome 6. Fine mapping of these LOH regions revealed three non-overlapping regions, one of which was refined to a 0.2 Mb interval that contained only the gene encoding homeobox-interacting protein kinase 2 (Hipk2). More than 30% of radiation-induced tumors from both p53+/- and p53-/- mice showed heterozygous loss of one Hipk2 allele. Mice carrying a single inactive allele of Hipk2 in the germline were susceptible to induction of tumors by γ-radiation, but most tumors retained and expressed the wild-type allele, suggesting that Hipk2 is a haploinsufficient tumor suppressor gene for mouse lymphoma development. Heterozygous loss of both Hipk2 and p53 confers strong sensitization to radiation-induced lymphoma. We conclude that Hipk2 is a haploinsufficient lymphoma suppressor gene.

Laser-driven proton acceleration enhancement by nanostructured foils.

Nanostructured thin plastic foils have been used to enhance the mechanism of laser-driven proton beam acceleration. In particular, the presence of a monolayer of polystyrene nanospheres on the target front side has drastically enhanced the absorption of the incident 100 TW laser beam, leading to a consequent increase in the maximum proton energy and beam charge. The cutoff energy increased by about 60% for the optimal spheres' diameter of 535 nm in comparison to the planar foil. The total number of protons with energies higher than 1 MeV was increased approximately 5 times. To our knowledge this is the first experimental demonstration of such advanced target geometry. Experimental results are interpreted and discussed by means of 2(1/2)-dimensional particle-in-cell simulations.

Prediction of survival and cancer recurrence using F-18 FDG PET/CT in patients with surgically resected early stage (Stage I and II) non-small cell lung cancer.

The aim of the current study was to investigate the prognostic value of SUV(max) in patients with completely resected early stage (stage I and II) NSCLC. A retrospective review identified 76 patients with surgically resected early (stage I and II) NSCLC who received F-18 FDG PET/CT at diagnosis of cancer. Survival analysis was conducted using Kaplan-Meier analysis, and survival curves stratified by age, sex, mediastinal lymph node involvement, SUV(max), and TNM staging were generated for estimation of overall survival and disease free survival (DFS). Independent predictive factors for survival were determined using Cox proportional hazard model. For overall survival, the median survival of the patients with tumor SUV(max)≤ 6.7 was 48.9 months and was significantly longer than the patients with tumor SUV(max)>6.7 (Log rank test, Χ²=18.01, p5.9. The median survival of the patients with tumor SUV(max)≤ 5.9 was 31.7 months (Log rank test, Χ²=16, p=0.0001). In conclusion, high FDG uptake measured by F-18 FDG PET/CT might have a prognostic value for overall survival and DFS in surgically resected early stage (stage I and II) NSCLC even after stratified by pathologic stages.

Clinical implication of (18)F-FDG PET/CT in carcinoma of unknown primary.

The value of (18)F-Fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in the detection of carcinoma of unknown primary (CUP) differs among the studies. This study aimed to evaluate the role of (18)F-FDG PET/CT in CUP. Fifty-one patients (19 women, 32 men) with metastasis confirmed by histopathology from an unknown primary tumor were included in this study. Patients received 370 MBq of (18)F-FDG intravenously, and PET/CT was performed at 60 minutes after injection. Primary tumor sites were detected in 5 of 51 patients (9.6%): in 2 patients with carcinoma of the lung, in 1 patient with carcinoma of the gallbladder, in 1 patient with carcinoma of the esophagus, and in 1 patient with carcinoma of the stomach. No primary tumor was discovered in the remaining 46 patients (90.4%) during the follow-up. The sensitivity, specificity, and accuracy of (18)F-FDG PET/CT were 100%, 80.4%, and 82.4%. The positive and negative predictive values were 35.7 and 100%, respectively. Based on the data presented, (18)F-FDG PET/CT has a clinical implicative value in detecting the primary tumor of CUP. PET/CT can be useful to rule out the possibility of detecting the primary tumor during the follow-up.

Prognostic stratification using F-18 FDG PET/CT in patients with advanced stage (stage III and IV) non-small cell lung cancer.

F-18 FDG PET could provide prognostic information in patients with advanced resectable NSCLC. In the current study, we investigated the prognostic implication of F-18 FDG PET after chemotherapy in patients with advanced stage III and IV NSCLC. A retrospective review identified 19 patients with advanced stage (stage III and IV) NSCLC who received F-18 FDG PET/CT at diagnosis of cancer and after chemotherapy. The visual response and changes of SUV max before and after treatment on survival was investigated using Kaplan-Meier and Cox proportional hazard regression analyses. The median follow-up time was overall 24.8 month (range, 9.4-59.8 month), for surviving patients 41 month (range, 34.1-59.8 month), and for deceased patients 16.6 month (range, 9.4-29.4 month). Overall survival after baseline F-18 FDG PET/CT at 1 year was 73.7% and at 2 year was 47.4%. Comparing patients with and without F-18 FDG PET/CT response, there was statistically significant difference in overall survival between the 2 groups (median survival time, responder, 29.4 month; non-responder, 14.2 month, Chi(2)=3.91, p=0.048). Also, using the %DeltaSUV(max) for the comparison, significant difference was existed in overall survival between 2 groups (Chi(2)=12.6, p=0.0004). When the tumor reveals more than 17.85% reduction of %DeltaSUV(max), the survival could be predicted (AUC, 0857; standard error, 0.0866; 95% confidence interval, 0.622-0.971; sensitivity, 75%; specificity, 100%; p=0.0001). With Cox proportional hazard model, %DeltaSUV(max) was determined to be a potent prognostic factor for survival (Chi(2), 12.09; p=0.0005). In conclusion, using the visual and quantitative analyses of F-18 FDG PET/CT, the responder to chemotherapy in advanced stage NSCLC patients had a better prognosis. Moreover, the potent predictor of prognosis in advanced stage NSCLC patients was %DeltaSUV(max).

The influence of diabetes on the relationship between N-terminal pro-B-type natriuretic peptide and body mass index.

This study evaluated the influence of diabetes on the relationship between N-terminal pro-B-type natriuretic peptide (NT-proBNP) and body mass index (BMI). Simultaneous NT-proBNP and echocardiographic Doppler examinations were performed in 1117 patients with dyspnoea undergoing cardiac catheterization. Patients were divided into BMI > or =25 kg/m2 (obese), 23-25 kg/m2 (overweight) and <23 kg/m2 (non-obese) groups. In the 803 non-diabetic patients, mean plasma NT-proBNP levels in non-obese, overweight and obese patients showed a significant negative correlation with BMI (862.3 +/- 228.8 pg/ml, 611.5 +/- 149.7 pg/ml, 278.3 +/- 172.5 pg/ml, respectively). In the 314 patients with diabetes, there was no correlation between BMI and NT-proBNP. This study demonstrated that obese patients had reduced concentrations of NT-proBNP compared with non-obese patients, despite having higher left ventricular filling pressures. NT-proBNP was not reduced in obese patients with diabetes. These results suggest that factors other than cardiac status impact on NT-proBNP concentration.

Thermal analysis of titanium drive-in target for D-D neutron generation.

Thermal analysis was performed for a titanium drive-in target of a D-D neutron generator. Computational fluid dynamics code CFX-5 was used in this study. To define the heat flux term for the thermal analysis, beam current profile was measured. Temperature of the target was calculated at some of the operating conditions. The cooling performance of the target was evaluated by means of the comparison of the calculated maximum target temperature and the critical temperature of titanium.