BACKGROUND:The increased health risks associated with obesity have been found to occur in Asians at lower body mass indices (BMIs). To determine the optimal cut-off values for overweight or obesity in Taiwan, we examined the relationships between four anthropometric indices and cardiovascular risk factors. METHODS: The data were collected from four health-screening centers from 1998 to 2000 in Taiwan. Included were 55 563 subjects (26 359 men and 29 204 women, mean age ¼ 37.3 AE 10.9 and 37.0 AE 11.1 y, respectively). None had known major systemic diseases or were taking medication. Individual body weight, height, waist circumference (WC), and a series of tests related to cardiovascular risk (blood pressure, fasting plasma glucose, triglycerides, total cholesterol, low-and high-density lipoprotein cholesterol) were assessed and their relationships were examined. Receiver operating characteristic (ROC) analysis was used to find out the optimal cut-off values of various anthropometric indices to predict hypertension, diabetes mellitus and dyslipidemia. RESULTS: Of the four anthropometric indices we studied, waist-to-height ratio (WHtR) in women was found to have the largest areas under the ROC curve (women ¼ 0.755, 95% CI 0.748 -0.763) relative to at least one risk factor (ie hypertension or diabetes or dyslipidemia). The optimal cut-off values for overweight or obesity from our study in men and women showed that BMIs of 23.6 and 22.1 kg=m 2 , WCs of 80.5 and 71.5 cm, waist-to-hip ratios (WHpR) of 0.85 and 0.76, and WHtR of 0.48 and 0.45, respectively, may be more appropriate in Taiwan. CONCLUSIONS: WHtR may be a better indicator for screening overweight-or obesity-related CVD risk factors than the other three indexes (BMI, WC and WHpR) in Taiwan. Our study also supported the hypothesis that the cut-off values using BMI and WC to define obesity should be much lower in Taiwan than in Western countries.

BackgroundFew randomized controlled trials (RCTs) report interventions targeting improvement of frailty status as an outcome.MethodsThis RCT enrolled 117 older adults (65-79 years of age) in Toufen, Taiwan who scored 3-6 on The Chinese Canadian Study of Health and Aging Clinical Frailty Scale Telephone Version and then score ≥1 on the Cardiovascular Health Study Phenotypic Classification of Frailty (CHS_PCF). With a two by two factorial design, subjects were randomly assigned to interventions (Exercise and nutrition, EN, n = 55 or problem solving therapy, PST, n = 57) or controls (non-EN, n = 62 or non-PST, n = 60). Educational booklets were provided to all. EN group subjects received nutrition consultation and a thrice-weekly exercise-training program while PST group subjects received 6 sessions in 3 month. Subjects were followed at 3, 6, and 12 months. Primary outcome was improvement of the CHS_PCF by at least one category (from pre-frail to robust, or from frail to pre-frail or robust) from baseline assessments. One hundred and one completed final assessments. Intention-to-treat analysis with the generalized estimating equation model was applied with adjustment for time and treatment-by-time interactions.ResultsMean age was 71.4 ± 3.7 years, with 59% females. Baseline characteristic were generally comparable between groups. EN group subjects had a higher improvement rate on the primary outcome than non-EN group subjects (45% vs 27%, adjusted p = 0.008) at 3 months, but not 6 or 12 months. They also had more increase of serum 25(OH) vitamin D level (4.9 ± 7.7 vs 1.2 ± 5.4, p = 0.006) and lower percentage of osteopenia (74% vs 89% p = 0.042) at 12 months. PST group subjects had better improvement (2.7 ± 6.1 vs 0.2 ± 6.7, p = 0.035, 6-month) and less deterioration (−3.5 ± 9.7 vs −7.1 ± 8.7, p = 0.036, 12-month) of dominant leg extension power than non-PST subjects. Some secondary outcomes were also improved in control groups (non-EN or non-PST). No adverse effects were reported.ConclusionsThe three-month EN intervention resulted in short-term (3-month) frailty status improvement and long-term effect on bone mineral density and serum vitamin D (12-month) among Taiwanese community-dwelling elders. The effect of PST was less pronounce.Trial registrationClinicalTrials.gov: EC0970301

This study reports a histone deacetylation-independent mechanism whereby histone deacetylase (HDAC) inhibitors sensitize prostate cancer cells to DNA-damaging agents by targeting Ku70 acetylation. Ku70 represents a crucial component of the nonhomologous end joining repair machinery for DNA double-strand breaks (DSB). Our data indicate that pretreatment of prostate cancer cells with HDAC inhibitors (trichostatin A, suberoylanilide hydroxamic acid, MS-275, and OSU-HDAC42) led to increased Ku70 acetylation accompanied by reduced DNA-binding affinity without disrupting the Ku70/ Ku80 heterodimer formation. As evidenced by increased Ser 139 -phosphorylated histone H2AX (;H2AX), impaired Ku70 function diminished cellular capability to repair DNA DSBs induced by bleomycin, doxorubicin, and etoposide, thereby enhancing their cell-killing effect. This sensitizing effect was most prominent when cells were treated with HDAC inhibitors and DNA-damaging agents sequentially. Mimicking acetylation was done by replacing K282, K317, K331, K338, K539, or K542 with glutamine via site-directed mutagenesis, which combined with computer docking analysis was used to analyze the role of these lysine residues in the interactions of Ku70 with DNA broken ends. Mutagenesis of K282, K338, K539, or K542 suppressed the activity of Ku70 to bind DNA, whereas mutagenesis of K317 or K331 with glutamine had no significant effect. Moreover, overexpression of K282Q or K338Q rendered DU-145 cells more susceptible to the effect of DNA-damaging agents on ;H2AX formation and cell killing. Overall, the ability of HDAC inhibitors to regulate cellular ability to repair DNA damage by targeting Ku70 acetylation underlies the viability of their combination with DNAdamaging agents as a therapeutic strategy for prostate cancer.