Transrectal ultrasound-guided targeted biopsy of transition zone prostate cancer under cognitive registration with prebiopsy MRI and sonographic findings.

AIM: To evaluate retrospectively the diagnostic usefulness of transrectal ultrasound (TRUS)-guided targeted biopsy (TB) for transition zone (TZ) prostate cancer (PCa) in patients with prebiopsy magnetic resonance imaging (MRI). MATERIALS AND METHODS: A consecutive series of 38 patients who underwent TRUS-guided TB of TZ lesions were evaluated. TB (mean core number, 2.4±0.6; range, 2-4) was performed by a single experienced radiologist under cognitive registration between prebiopsy MRI and TRUS. Tumour echogenicity on TRUS and Prostate Imaging-Reporting and Data System version 2 (PI-RADSv2) scoring on MRI for targeted TZ lesions were assessed. The interrupted midline sign was defined as a focal lesion traversing the midline of the TZ leading to discontinuity of the midline on both MRI and TRUS. TZ PCa with a Gleason score of 7 or greater was defined as clinically significant PCa (csPCa). RESULTS: The cancer detection rate of TRUS-guided TB for TZ lesions was 78.9% (30/38) for any PCa and 42.1% (16/38) for csPCa. Echogenicity of TZ PCa on TRUS was various and half did not show low echogenicity (low, 50%; intermediate, 26.7%; and high, 23.3%). The interrupted midline sign was identified in 50% (19/38) of patients, which was highly predictive of TZ PCa (94.7%, 18/19). CONCLUSION: TRUS-guided TB under cognitive registration based on prebiopsy MRI findings is useful to detect TZ PCa. Knowledge of the sonographic features of TZ PCa may help to target TZ PCa accurately under cognitive registration.

Low free T3 to free T4 ratio was associated with low muscle mass and impaired physical performance in community-dwelling aged population.

In aged population, the association of thyroid hormones on physical performance, especially within their normal range, has yet to be elucidated. In this study, individuals with low serum free T3/free T4 were likely to have low muscle mass and impaired physical performance. PURPOSE: We aimed to evaluate the associations of muscle mass, strength, and physical performance with thyroid hormone in an aged euthyroid population from a community-based cohort. METHODS: We examined 918 men aged over 60 years and 1215 postmenopausal women from the Ansung cohort study. Appendicular skeletal muscle mass divided by square of height (ASM/ht2) was used as the muscle mass index. Hand grip strength was measured using a hydraulic dynamometer. Physical performance was assessed using the short physical performance battery (SPPB). RESULTS: Participants with higher tertiles of free T3 and free T3/free T4 were younger and had higher ASM/ht2, stronger hand grip strength, and higher SPPB scores than those in the lower tertiles. In adjusted models, men within higher tertiles of free T3 had higher ASM/ht2 compared with those within lower tertiles (p = 0.033), whereas subjects with higher tertiles of free T4 had lower ASM/ht2 compared with those within lower tertiles (p = 0.043). Subjects within higher tertiles of free T3/free T4 had higher ASM/ht2 (p < 0.001) and better physical performance (p = 0.048) than those within lower tertiles after adjustments. However, free T3, free T4, or free T3/free T4 was not related to hand grip strength after adjustment for covariates. CONCLUSION: Our results thus indicate that in an aged euthyroid population, low serum free T3/free T4 was a better index for low muscle mass and impaired physical performance than serum free T3 or free T4 alone.

PI-RADS version 2: optimal time range for determining positivity of dynamic contrast-enhanced MRI in peripheral zone prostate cancer.

AIM: To analyse the optimal time cut-off for determining positivity of dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) in peripheral zone (PZ) prostate cancer (PCa). MATERIALS AND METHODS: A consecutive series of 89 patients with PZ PCa who had undergone diffusion-weighted imaging (DWI) and subtraction DCE MRI were included. An experienced reader visually analysed the earliest time after contrast medium injection to visualise the best contrast between an index tumour and normal PZ on DCE MRI (i.e., best contrast time). The best contrast time cut-off for clinically significant cancer (csPCa) according to Epstein criteria or International Society of Urological Pathology (ISUP) grade ≥2 was analysed by an experienced reader, and applied to a less-experienced reader. For the index lesion of DWI category 3, the added value of DCE MRI (increased true positive and negative rates of PI-RADSv2 for csPCa) was evaluated using the cut-off time. RESULTS: The best contrast time cut-off for csPCa was ≤72 seconds for Epstein criteria and ≤56 seconds for ISUP grade ≥2 by an experienced reader. The weighted kappa to determine positivity of DCE MRI was 0.622 for ≤72 seconds and 0.527 for ≤56 seconds between the two readers. The added value of DCE MRI was 55-75% by an experienced reader and 39.1-69.6% by a less-experienced reader. CONCLUSION: For interpreting PI-RADSv2, imaging findings within 60-72 seconds following contrast media injection seem to reliably determine positivity of DCE MRI in PZ, and have added value for detecting csPCa.

IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045.

INTRODUCTION: Since the year 2000, IDF has been measuring the prevalence of diabetes nationally, regionally and globally. AIM: To produce estimates of the global burden of diabetes and its impact for 2017 and projections for 2045. METHODS: A systematic literature review was conducted to identify published studies on the prevalence of diabetes, impaired glucose tolerance and hyperglycaemia in pregnancy in the period from 1990 to 2016. The highest quality studies on diabetes prevalence were selected for each country. A logistic regression model was used to generate age-specific prevalence estimates or each country. Estimates for countries without data were extrapolated from similar countries. RESULTS: It was estimated that in 2017 there are 451 million (age 18-99 years) people with diabetes worldwide. These figures were expected to increase to 693 million) by 2045. It was estimated that almost half of all people (49.7%) living with diabetes are undiagnosed. Moreover, there was an estimated 374 million people with impaired glucose tolerance (IGT) and it was projected that almost 21.3 million live births to women were affected by some form of hyperglycaemia in pregnancy. In 2017, approximately 5 million deaths worldwide were attributable to diabetes in the 20-99 years age range. The global healthcare expenditure on people with diabetes was estimated to be USD 850 billion in 2017. CONCLUSION: The new estimates of diabetes prevalence, deaths attributable to diabetes and healthcare expenditure due to diabetes present a large social, financial and health system burden across the world.

IDF Diabetes Atlas: Global estimates for the prevalence of diabetes for 2015 and 2040.

AIM: To produce current estimates of the national, regional and global impact of diabetes for 2015 and 2040. METHODS: A systematic literature review was conducted to identify data sources on the prevalence of diabetes from studies conducted in the period from 1990 to 2015. An analytic hierarchy process was used to select the most appropriate studies for each country, and estimates for countries without data were modelled using extrapolation from similar countries that had available data. A logistic regression model was used to generate smoothed age-specific estimates, which were applied to UN population estimates. RESULTS: 540 data sources were reviewed, of which 196 sources from 111 countries were selected. In 2015 it was estimated that there were 415 million (uncertainty interval: 340-536 million) people with diabetes aged 20-79years, 5.0 million deaths attributable to diabetes, and the total global health expenditure due to diabetes was estimated at 673 billion US dollars. Three quarters (75%) of those with diabetes were living in low- and middle-income countries. The number of people with diabetes aged 20-79years was predicted to rise to 642 million (uncertainty interval: 521-829 million) by 2040. CONCLUSION: Diabetes prevalence, deaths attributable to diabetes, and health expenditure due to diabetes continue to rise across the globe with important social, financial and health system implications.

High-normal free thyroxine levels are associated with low trabecular bone scores in euthyroid postmenopausal women.

UNLABELLED: Trabecular bone scores (TBS) have recently been developed as a diagnostic tool to assess bone texture. We studied thyroid status and TBS in a population-based cohort and demonstrated that high-normal thyroxine levels are associated with low TBS in healthy euthyroid postmenopausal women. INTRODUCTION: Increased thyroid hormone levels affect bone mineral density (BMD) and, if untreated, increase the risk of fracture. However, the relationship between thyroid function and bone microarchitecture has not yet been established. Trabecular bone scores (TBS) are gray-level textural measurements of dual energy X-ray absorptiometry (DXA) images. The TBS has been proposed as an indirect index of bone microarchitecture. The goal of this study was to characterize the relationship between thyroid function and TBS in euthyroid men and postmenopausal euthyroid women. METHODS: A total of 1376 euthyroid subjects (648 postmenopausal women and 728 men) were recruited from a community-based cohort in Korea. Free thyroxine (fT4) levels, thyroid stimulating hormone (TSH) levels, BMD, and TBS were measured and compared. RESULTS: There was no significant relationship between either fT4 or TSH levels and BMD in men and women. Multiple linear regression analysis showed that high-normal fT4 levels were negatively correlated with TBS (ß = -0.111; P = 0.002, after adjusting for both age and body mass index [BMI]) in postmenopausal women. In men, however, there was no significant correlation between fT4 levels and TBS. TSH levels were not significantly associated with TBS in either men or women. CONCLUSION: Higher fT4 levels within the normal reference range are associated with deterioration of trabecular microarchitecture in healthy euthyroid postmenopausal women.

Regional body fat depots differently affect bone microarchitecture in postmenopausal Korean women.

SUMMARY: In a prospective community-based cohort study, we investigated the relationship between trabecular bone score (TBS) and regional fat depots in 1474 Korean postmenopausal women. TBS was positively related with subcutaneous fat and negatively related with visceral fat. INTRODUCTION: The effect of fat distribution (visceral/subcutaneous) on bone quality or microarchitecture has rarely been investigated due to measurement difficulty. We aimed to investigate the relationship between TBS reflecting bone microarchitecture and regional fat depots in Korean women. METHODS: Cross-sectional data evaluation was made from subjects participating in an ongoing prospective community-based cohort study since 2001. A total of 1474 postmenopausal women in the Ansung cohort were analyzed. Regional body fat mass, bone mineral density (BMD) at the lumbar spine, and total hip and lumbar spine TBS were measured by dual energy X-ray absorptiometry (DXA). RESULTS: In an age-adjusted partial correlation analysis, TBS was not associated with total fat mass, but negatively associated with trunk fat mass. However, TBS was positively related with leg (r = 0.102, P < 0.05) and gynoid fat mass (r = 0.086, P < 0.05) and negatively related with android fat mass (r = -0.106; P < 0.05). In linear regression models controlling age, BMI, and physical activity, android fat was inversely associated with TBS (ß = -0.595, P < 0.001), whereas gynoid fat was positively associated with TBS (ß = 0.216, P < 0.001). Lumbar spine and total hip BMDs revealed positive associations with total and all regional fat depots regardless of fat distribution. CONCLUSION: Our findings suggest that relatively large visceral fat and small subcutaneous fat may have a detrimental effect on TBS, a bone microarchitecture index.

Comparing diabetic patient characteristics related to stated medication adherence in a rural vs. urban community in Korea.

WHAT IS KNOWN AND OBJECTIVE: Diabetes mellitus (DM) is major cause of death and disability, and regular administration of medications is important in its management. A better understanding of the factors associated with medication non-adherence or underuse may help to improve adherence. This study was performed to identify and compare possible risk factors associated with medication adherence to antidiabetic medication in two different community-based populations in Korea. METHODS: In this large, cross-sectional study, data on DM patients from the rural area of Ansung and the urban area of Ansan obtained during biennial health examinations in 2011-2012 were analysed. Demographic information and anthropometric and laboratory test results were collected. The study population consisted of rural and urban communities which were each categorized into two groups according to medication adherence: those who were currently on antidiabetic medication (adherent group), and those who did not take the medication despite knowing that they are diabetic (non-adherent group). RESULTS AND DISCUSSION: A total of 1675 inhabitants who were diagnosed as diabetic were included in this study comprised of 803 patients from the rural community and 872 patients from the urban community. Over half of the study population (55·76%, 934 patients) belonged to the non-adherent group. Adherence was greater in the rural (52·43%) than in the urban (36·70%) group. There were significant associations between medication non-adherence and age, male gender, alcohol consumption, high blood pressure, high total cholesterol and lack of family history of diabetes, but not with income, smoking status, exercise, marital status and occupation. WHAT IS NEW AND CONCLUSION: Despite the proven beneficial effects of antidiabetic medications in the management of DM, we observed low rates of medication adherence, particularly in the urban area. Further study to identify barriers to adherence among urban residents is needed. In addition, there is a need for effective strategies that will lead to improved medication adherence.

Pathway analysis of genome-wide association datasets of personality traits.

Although several genome-wide association (GWA) studies of human personality have been recently published, genetic variants that are highly associated with certain personality traits remain unknown, due to difficulty reproducing results. To further investigate these genetic variants, we assessed biological pathways using GWA datasets. Pathway analysis using GWA data was performed on 1089 Korean women whose personality traits were measured with the Revised NEO Personality Inventory for the 5-factor model of personality. A total of 1042 pathways containing 8297 genes were included in our study. Of these, 14 pathways were highly enriched with association signals that were validated in 1490 independent samples. These pathways include association of: Neuroticism with axon guidance [L1 cell adhesion molecule (L1CAM) interactions]; Extraversion with neuronal system and voltage-gated potassium channels; Agreeableness with L1CAM interaction, neurotransmitter receptor binding and downstream transmission in postsynaptic cells; and Conscientiousness with the interferon-gamma and platelet-derived growth factor receptor beta polypeptide pathways. Several genes that contribute to top-ranked pathways in this study were previously identified in GWA studies or by pathway analysis in schizophrenia or other neuropsychiatric disorders. Here we report the first pathway analysis of all five personality traits. Importantly, our analysis identified novel pathways that contribute to understanding the etiology of personality traits.

The IDF Diabetes Atlas methodology for estimating global prevalence of hyperglycaemia in pregnancy.

INTRODUCTION: Hyperglycaemia is one of the most prevalent metabolic disorders occurring during pregnancy. Limited data are available on the global prevalence of hyperglycaemia in pregnancy. The International Diabetes Federation (IDF) has developed a methodology for generating estimates of the prevalence of hyperglycaemia in pregnancy, including hyperglycaemia first detected in pregnancy and live births to women with known diabetes, among women of childbearing age (20-49 years). METHODS: A systematic review of the literature for studies reporting the prevalence of gestational diabetes was conducted. Studies were evaluated and scored to favour those that were representative of a large population, conducted recently, reported age-specific estimates, and case identification was based on blood test. Age-specific prevalence data from studies were entered to produce estimates for five-year age groups using logistic regression to smooth curves, with age as the independent variable. The derived age-specific prevalence was adjusted for differences in diagnostic criteria in the underlying data. Cases of hyperglycaemia in pregnancy were derived from age-specific estimates of fertility and age-specific population estimates. Country-specific estimates were generated for countries with available data. Regional and global estimates were generated based on aggregation and extrapolation for 219 countries and territories. Available fertility rates and diabetes prevalence estimates were used to estimate the proportion of hyperglycaemia in pregnancy that may be due to total diabetes in pregnancy - pregnancy in women with known diabetes and diabetes first detected in pregnancy. RESULTS: The literature review identified 199 studies that were eligible for characterisation and selection. After scoring and exclusion requirements, 46 studies were selected representing 34 countries. More than 50% of selected studies came from Europe and North America and Caribbean. The smallest number of identified studies came from sub-Saharan Africa. The majority of studies were for high-income countries, although low- and middle-income countries were also represented. CONCLUSION: Prevalence estimates of hyperglycaemia in pregnancy are sensitive to the data from which they are derived. The IDF methodology is a transparent, reproducible, and modifiable method for estimating the burden of hyperglycaemia in pregnancy. More data are needed, in particular from developing countries, to strengthen the methodology.

Global estimates of the prevalence of hyperglycaemia in pregnancy.

AIMS: We estimated the number of live births worldwide and by IDF Region who developed hyperglycaemia in pregnancy in 2013, including total diabetes in pregnancy (known and previously undiagnosed diabetes) and gestational diabetes. METHODS: Studies reporting prevalence of hyperglycaemia first-detected in pregnancy (formerly termed gestational diabetes) were identified using PubMed and through a review of cited literature. A simple scoring system was developed to characterise studies on diagnostic criteria, year study was conducted, study design, and representation. The highest scoring studies by country with sufficient detail on methodology for characterisation and reporting at least three age-groups were selected for inclusion. Forty-seven studies from 34 countries were used to calculate age-specific prevalence of hyperglycaemia first-detected in pregnancy in women 20-49 years. Adjustments were then made to account for heterogeneity in screening method and blood glucose diagnostic threshold in studies and also to align with recently published diagnostic criteria as defined by the WHO for hyperglycaemia first detected in pregnancy. Prevalence rates were applied to fertility and population estimates to determine regional and global prevalence of hyperglycaemia in pregnancy for 2013. An estimate of the proportion of cases of hyperglycaemia in pregnancy due to total diabetes in pregnancy was calculated using age- and sex-specific estimates of diabetes from the IDF Diabetes Atlas and applied to age-specific fertility rates. RESULTS: The global prevalence of hyperglycaemia in pregnancy in women (20-49 years) is 16.9%, or 21.4 million live births in 2013. An estimated 16.0% of those cases may be due to total diabetes in pregnancy. The highest prevalence was found in the South-East Asia Region at 25.0% compared with 10.4% in the North America and Caribbean Region. More than 90% of cases of hyperglycaemia in pregnancy are estimated to occur in low- and middle-income countries. CONCLUSION: These are the first global estimates of hyperglycaemia in pregnancy and conform to the new WHO recommendations regarding diagnosis and also include estimates of live births in women with known diabetes. They indicate the importance of the disease from a public health and maternal and child health perspective, particularly in developing countries.

Replication of Caucasian loci associated with bone mineral density in Koreans.

SUMMARY: Most bone mineral density (BMD) loci were reported in Caucasian genome-wide association studies (GWAS). This study investigated the association between 59 known BMD loci (+200 suggestive SNPs) and DXA-derived BMD in East Asian population with respect to sex and site specificity. We also identified four novel BMD candidate loci from the suggestive SNPs. INTRODUCTION: Most GWAS have reported BMD-related variations in Caucasian populations. This study investigates whether the BMD loci discovered in Caucasian GWAS are also associated with BMD in East Asian ethnic samples. METHODS: A total of 2,729 unrelated Korean individuals from a population-based cohort were analyzed. We selected 747 single-nucleotide polymorphisms (SNPs). These markers included 547 SNPs from 59 loci with genome-wide significance (GWS, p value less than 5 × 10(-8)) levels and 200 suggestive SNPs that showed weaker BMD association with p value less than 5 × 10(-5). After quality control, 535 GWS SNPs and 182 suggestive SNPs were included in the replication analysis. RESULTS: Of the 535 GWS SNPs, 276 from 25 loci were replicated (p < 0.05) in the Korean population with 51.6 % replication rate. Of the 182 suggestive variants, 16 were replicated (p < 0.05, 8.8 % of replication rate), and five reached a significant combined p value (less than 7.0 × 10(-5), 0.05/717 SNPs, corrected for multiple testing). Two markers (rs11711157, rs3732477) are for the same signal near the gene CPN2 (carboxypeptidase N, polypeptide 2). The other variants, rs6436440 and rs2291296, were located in the genes AP1S3 (adaptor-related protein complex 1, sigma 3 subunit) and RARB (retinoic acid receptor, beta). CONCLUSION: Our results illustrate ethnic differences in BMD susceptibility genes and underscore the need for further genetic studies in each ethnic group. We were also able to replicate some SNPs with suggestive associations. These SNPs may be BMD-related genetic markers and should be further investigated.

Identifying genes related to radiation resistance in oral squamous cell carcinoma cell lines.

Radioresistance is one of the main determinants of treatment outcome in oral cancer, but the prediction of radioresistance is difficult. The authors aimed to establish radioresistant oral squamous cell carcinoma (OSCC) cell lines to identify genes with altered expression in response to radioresistance. To induce radioresistant cell lines, the authors treated OSCC cell lines with an accumulated dosage of 60Gy over 30 cycles of radiotherapy. They compared the results from cDNA arrays and proteomics between non-radiated and radioresistant cell lines in order to identify changes in gene expression. Western blot analysis was used to validate the results. The cDNA array revealed 265 commonly up-regulated genes and 268 commonly down-regulated genes in radioresistant cell lines, 30 of which were cancer-related genes. Proteomics identified 51 proteins with commonly altered expression in radioresistant cell lines, 18 of which were cancer-related proteins. Both the cDNA array and proteomics indicated that NM23-H1 and PA2G4 were over-expressed. Western blot analysis showed increased expression of NM23-H1, but not PA2G4, in radioresistant cell lines. The authors concluded that NM23-H1 may be a radioresistance-related gene and over-expression of NM23-H1 could serve as a biomarker to predict radioresistance in OSCC.

Dietary information improves cardiovascular disease risk prediction models.

BACKGROUND/OBJECTIVES: Data are limited on cardiovascular disease (CVD) risk prediction models that include dietary predictors. Using known risk factors and dietary information, we constructed and evaluated CVD risk prediction models. SUBJECTS/METHODS: Data for modeling were from population-based prospective cohort studies comprised of 9026 men and women aged 40-69 years. At baseline, all were free of known CVD and cancer, and were followed up for CVD incidence during an 8-year period. We used Cox proportional hazard regression analysis to construct a traditional risk factor model, an office-based model, and two diet-containing models and evaluated these models by calculating Akaike information criterion (AIC), C-statistics, integrated discrimination improvement (IDI), net reclassification improvement (NRI) and calibration statistic. RESULTS: We constructed diet-containing models with significant dietary predictors such as poultry, legumes, carbonated soft drinks or green tea consumption. Adding dietary predictors to the traditional model yielded a decrease in AIC (delta AIC=15), a 53% increase in relative IDI (P-value for IDI <0.001) and an increase in NRI (category-free NRI=0.14, P <0.001). The simplified diet-containing model also showed a decrease in AIC (delta AIC=14), a 38% increase in relative IDI (P-value for IDI <0.001) and an increase in NRI (category-free NRI=0.08, P<0.01) compared with the office-based model. The calibration plots for risk prediction demonstrated that the inclusion of dietary predictors contributes to better agreement in persons at high risk for CVD. C-statistics for the four models were acceptable and comparable. CONCLUSIONS: We suggest that dietary information may be useful in constructing CVD risk prediction models.

Association between arachidonate 5-lipoxygenase-activating protein (ALOX5AP) and lung function in a Korean population.

Arachidonate 5-lipoxygenase-activating protein (ALOX5AP) plays a role in the 5-lipoxygenase (LO) pathway, which includes the LTC(4), LTD(4), LTE(4) and LTB(4). These leukotrienes are known causative factors of asthma, allergy, atopy and cardiovascular diseases. ALOX5AP lacks enzyme activity and acts by helping 5-LO function. In this study, healthy and general subjects who live in rural and urban areas of Korea were tested for the association of ALOX5AP polymorphisms with lung function. Lung function was also estimated by calculating the predicted values for forced expiratory volume in one second (FEV(1) _%PRED) and the proportion of the forced vital capacity exhaled in the first second (FEV(1) /FVC_PRED). The linear regression was adjusted for residence area, gender, age, height and smoking status. The analysis revealed associations between FEV(1) and the single-nucleotide polymorphism (SNP) rs9506352 and the haplotype TCAC (permuted P-value < 0.05). The linkage disequilibrium block that included the significant SNPs overlapped with SNPs that were revealed previously to associate with myocardial infarction and asthma and to affect lung function. This study is the first to demonstrate the association between lung function and ALOX5AP polymorphisms in a healthy and general population.

Fat mass is negatively associated with bone mineral content in Koreans.

SUMMARY: Although obesity and osteoporosis are important public health problems, the effect of fat mass on bone mass remains controversial. This study demonstrated that fat mass was inversely related to bone mineral content, and abdominal obesity was significantly associated with bone mineral content independent of total fat mass. INTRODUCTION: Obesity and osteoporosis, two disorders of body composition, have become increasingly important public health problems throughout the world. However, the effect of fat mass on bone mass remains controversial. This study investigates the effect of fat mass and regional fat distribution on bone mass within a community-dwelling cohort. METHODS: A total of 3,042 subjects (1,284 men, 362 premenopausal women, and 1,396 postmenopausal women) were studied. Fat mass, percent fat mass, lean mass, percent lean mass, and bone mineral content (BMC) were measured by dual energy X-ray absorptiometry. RESULTS: Fat mass and percent fat mass decreased significantly across increasing tertiles of BMC in all three subgroups (men, premenopausal and postmenopausal women). In contrast, lean mass and percent lean mass increased significantly across tertiles of BMC in men, and a similar trend was also identified in postmenopausal women. Interestingly, although correlation analysis showed a positive association between fat mass and BMC (p < 0.05), this association became negative after controlling for age and weight (p < 0.05). Finally, in premenopausal and postmenopausal women, subjects with the lowest waist circumference (WC) had the highest BMC in the higher three quartiles of percent fat mass after adjusting for age and weight (p < 0.05), indicating that abdominal obesity is associated with BMC independent of total fat mass. CONCLUSION: This study demonstrated that fat mass was inversely related to BMC after removing the mechanical loading effect in Korean men and women. Moreover, abdominal obesity as measured by WC was significantly associated with BMC independent of total fat mass.

The gene expression profile of matrix metalloproteinases and their inhibitors in children with Henoch-Schönlein purpura.

BACKGROUND: Because inflammatory cytokines are known to be potent inducers of matrix metalloproteinases (MMPs), and MMPs themselves can promote inflammation, we speculated that MMP activation might be involved in the pathogenesis of Henoch-Schönlein purpura (HSP) vasculitis. OBJECTIVES: To investigate the gene expression profile of all known MMPs and tissue inhibitors of metalloproteinases (TIMPs) in children with HSP and to examine the role, if any, of MMPs in the pathogenesis of HSP. METHODS: Peripheral blood samples were obtained from 10 patients with HSP (nine were in the acute stage, one had HSP nephritis) and four healthy controls. Peripheral blood samples were also taken from the nine patients with HSP when they reached the convalescent stage of the disease. From these samples, total RNA was purified and gene expressions were measured using real-time polymerase chain reaction. RESULTS: MMP-8 expression was decreased in patients with arthralgia (P = 0·038), and MMP-3 (P = 0·03) and TIMP-4 expressions (P = 0·016) were elevated in HSP patients with nephritis. Soft tissue oedema was associated with decreased expressions of MMP-26 (P = 0·038) and MMP-28 (P = 0·038). MMP-1, MMP-8, MMP-9, MMP-10, MMP-13, MMP-16 and MMP-26 levels were significantly higher in patients in the acute stage of HSP than in normal controls (P < 0·05). MMP-9 (P = 0·097) and MMP-19 (P = 0·054) levels decreased to borderline significance in patients in the convalescent stage compared with those in the acute stage. The duration of steroid administration was negatively correlated with MMP-1, MMP-2, MMP-7, MMP-10, MMP-12, MMP-19, MMP-23 and TIMP-1 levels (P < 0·05), suggesting a suppressive effect of steroids on the expressions of MMPs and TIMPs. CONCLUSIONS: This is the first study to describe the expression profile of all known MMPs and TIMPs in children with HSP, and our results suggested that abnormal levels of MMP and TIMP activity may have a role in the pathogenesis of HSP.

Relevance of human papilloma virus (HPV) infection to carcinogenesis of oral tongue cancer.

Human papilloma virus (HPV) infection is controversial as a causative factor in oral tongue cancer. This study aimed to clarify whether HPV directly affects the carcinogenesis and biological behaviour of oral tongue cancer by analyzing HPV prevalence, the physical status of the virus and clinicopathological parameters. Archival tissue was obtained from 36 patients diagnosed with T1 and T2 oral tongue cancer and 25 normal controls. HPV genotyping chip and real-time polymerase chain reaction were used to determine the prevalence, phenotype and physical status of HPV to clarify whether HPV directly affects oncogenesis. The results were also compared with clinicopathological parameters. HPV was detected in 36% (13/36) of oral tongue cancer patients, compared with 4% (1/25) of the control. In the HPV-positive group of oral tongue cancers, HPV-16 was the most common type and its prevalence rate was 85% (11/13). Of the HPV-16 infected oral tongue cancers, the integration rate of HPV-16 was 55% (6/11). The HPV-16 positive group showed shallower stromal invasion than the HPV-16 negative group (p=0.045). HPV-16 may be one of the causative factors in early squamous cell oral tongue carcinoma and be associated with its depth of invasion.

CD24+ cells from hierarchically organized ovarian cancer are enriched in cancer stem cells.

Cancer stem cells (CSCs) have been identified in solid tumors and cancer cell lines. In this study, we isolated a series of cancer cell clones, which were heterogeneous in growth rate, cell cycle distribution and expression profile of genes and proteins, from ovarian tumor specimens of a patient and identified a sub-population enriched for ovarian CSCs defined by CD24 phenotype. Experiments in vitro demonstrated CD24(+) sub-population possessed stem cell-like characteristics of remaining quiescence and more chemoresistant compared with CD24(-) fraction, as well as a specific capacity for self-renewal and differentiation. In addition, injection of 5 x 10(3) CD24(+) cells was able to form tumor xenografts in nude mice, whereas equal number of CD24(-) cells remained nontumorigenic. We also found that CD24(+) cells expressed higher mRNA levels of some 'stemness' genes, including Nestin, beta-catenin, Bmi-1, Oct4, Oct3/4, Notch1 and Notch4 which were involved in modulating many functions of stem cells, and lower E-cadherin mRNA level than CD24(-) cells. Altogether, these observations suggest human ovarian tumor cells are organized as a hierarchy and CD24 demarcates an ovarian cancer-initiating cell population. These findings will have important clinical applications for developing effective therapeutic strategies to treat ovarian cancer.