Deep, rapid, and durable prostate-specific antigen decline with apalutamide plus androgen deprivation therapy is associated with longer survival and improved clinical outcomes in TITAN patients with metastatic castration-sensitive prostate cancer.

BACKGROUND: The first interim analysis of the phase III, randomized, double-blind, placebo-controlled, multinational TITAN study demonstrated improved overall survival (OS) and radiographic progression-free survival (rPFS) with apalutamide added to ongoing androgen deprivation therapy (ADT) in patients with metastatic castration-sensitive prostate cancer. The final analysis confirmed improvement in OS and other long-term outcomes. We evaluated prostate-specific antigen (PSA) kinetics and the association between PSA decline and outcomes in patients with metastatic castration-sensitive prostate cancer from TITAN. PATIENTS AND METHODS: Patients received apalutamide (240 mg/day) or placebo plus ADT (1 : 1). This post hoc exploratory analysis evaluated PSA kinetics and decline in relation to rPFS (22.7 months' follow-up) and OS, time to PSA progression, and time to castration resistance (44.0 months' follow-up) in patients with or without confirmed PSA decline using a landmark analysis, the Kaplan-Meier method, and Cox proportional hazards model. RESULTS: One thousand and fifty-two patients (apalutamide, 525; placebo, 527) were enrolled. Best confirmed PSA declines (≥50% or ≥90% from baseline or to ≤0.2 ng/ml) were achieved at any time during the study in 90%, 73%, and 68% of apalutamide-treated versus 55%, 29%, and 32% of placebo-treated patients, respectively. By 3 months of apalutamide treatment, best deep PSA decline of ≥90% or to ≤0.2 ng/ml occurred in 59% and 51% of apalutamide- and in 13% and 18% of placebo-treated patients, respectively. Achievement of deep PSA decline at landmark 3 months of apalutamide treatment was associated with longer OS [hazard ratio (HR) 0.35; 95% confidence interval (CI) 0.25-0.48), rPFS (HR 0.44; 95% CI 0.30-0.65), time to PSA progression (HR 0.31; 95% CI 0.22-0.44), and time to castration resistance (HR 0.38; 95% CI 0.27-0.52) compared with no decline (P < 0.0001 for all). Similar results were observed at landmark 6 and 12 months of apalutamide treatment. CONCLUSIONS: Apalutamide plus ADT demonstrated a robust (rapid, deep, and durable) PSA decline that was associated with improved clinical outcomes, including long-term survival.

Efficacy and safety of avelumab plus axitinib in elderly patients with advanced renal cell carcinoma: extended follow-up results from JAVELIN Renal 101.

BACKGROUND: In the phase III JAVELIN Renal 101 trial, first-line avelumab plus axitinib demonstrated a progression-free survival (PFS) and objective response rate (ORR) benefit versus sunitinib in patients with advanced renal cell carcinoma (aRCC). However, efficacy in elderly patients remains unclear. We report efficacy and safety by age group from the second interim analysis of overall survival (OS). PATIENTS AND METHODS: PFS and ORR as per blinded independent central review (RECIST 1.1), OS, and safety were assessed in patient groups aged <65, ≥65 to <75, and ≥75 years. RESULTS: In the avelumab plus axitinib and sunitinib arms, 271/138/33 and 275/128/41 patients aged <65, ≥65 to <75, and ≥75 years, respectively, were randomized. At data cut-off (January 2019), median PFS [95% confidence interval (CI)] with avelumab plus axitinib versus sunitinib in these respective age groups was 11.6 (8.4-19.4) versus 6.9 (5.6-8.4) months [hazard ratio (HR), 0.63; 95% CI 0.501-0.786], 13.8 (11.1-18.0) versus 11.0 (7.8-16.6) months (HR, 0.88; 95% CI 0.627-1.231), and 13.8 [7.0-not estimable (NE)] versus 9.8 (4.3-NE) months (HR, 0.76; 95% CI 0.378-1.511). Median OS (95% CI) in the respective age groups was not reached (NR) (NE-NE) versus 28.6 (25.5-NE) months (HR, 0.74; 95% CI 0.541-1.022), 30.0 (30.0-NE) versus NR (NE-NE) months (HR, 0.89; 95% CI 0.546-1.467), and 25.3 (19.9-NE) versus NR (19.4-NE) months (HR, 0.87; 95% CI 0.359-2.106). ORR (95% CI) in the respective age groups was 49.4% (43.3% to 55.6%) versus 27.3% (22.1% to 32.9%), 60.9% (52.2% to 69.1%) versus 28.9% (21.2% to 37.6%), and 42.4% (25.5% to 60.8%) versus 22.0% (10.6% to 37.6%). In the avelumab plus axitinib arm, grade ≥3 adverse events (AEs) and immune-related AEs occurred in 76.9%/81.2%/72.7% and 45.5%/48.1%/36.4% in the respective age groups. CONCLUSIONS: First-line avelumab plus axitinib demonstrated favorable efficacy across age groups, including patients aged ≥75 years. OS data were still immature; follow-up is ongoing. The safety profile was generally consistent across age groups.

Efficacy and safety of abiraterone acetate plus prednisolone in patients with early metastatic castration-resistant prostate cancer who failed first-line androgen-deprivation therapy: a single-arm, phase 4 study.

AIM: The aim was to evaluate the efficacy and safety of abiraterone acetate plus prednisolone in patients with chemotherapy-naïve early metastatic castration-resistant prostate cancer who failed first-line androgen deprivation therapy. METHODS: Patients with early metastatic castration-resistant prostate cancer with confirmed prostate-specific antigen progression within 1-year or prostate-specific antigen progression without having normal prostate-specific antigen level (<4.0 ng/mL) during first-line androgen deprivation therapy were enrolled and administered abiraterone acetate (1000 mg) plus prednisolone (10 mg). A minimum of 48 patients were required according to Simon's minimax design. The primary endpoint was prostate-specific antigen response rate (≥50% prostate-specific antigen decline by 12 weeks), secondary endpoints included prostate-specific antigen progression-free survival and overall survival. Safety parameters were also assessed. RESULTS: For efficacy, 49/50 patients were evaluable. Median age was 73 (range: 55-86) years. The median duration of initial androgen deprivation therapy was 32.4 (range: 13.4-84.1) weeks and 48 patients experienced prostate-specific antigen progression within 1-year after initiation of androgen deprivation therapy. prostate-specific antigen response rate was 55.1% (95% confidence interval: 40.2%-69.3%), median prostate-specific antigen-progression-free survival was 24.1 weeks, and median overall survival was 102.9 weeks (95% confidence interval: 64.86 not estimable [NE]). Most common adverse event was nasopharyngitis (15/50 patients, 30.0%). The most common ≥grade 3 adverse event was alanine aminotransferase increased (6/50 patients, 12.0%). CONCLUSIONS: Abiraterone acetate plus prednisolone demonstrated a high prostate-specific antigen response rate of 55.1%, suggesting tumor growth still depends on androgen synthesis in patients with early metastatic castration-resistant prostate cancer. However, prostate-specific antigen-progression-free survival was shorter than that reported in previous studies. Considering the benefit-risk profile, abiraterone acetate plus prednisolone would be a beneficial treatment option for patients with chemotherapy-naive metastatic prostate cancer who show early castration resistance.

Apalutamide and overall survival in non-metastatic castration-resistant prostate cancer.

BACKGROUND: In the SPARTAN study, compared with placebo, apalutamide added to ongoing androgen deprivation therapy significantly prolonged metastasis-free survival (MFS) and time to symptomatic progression in patients with high-risk non-metastatic castration-resistant prostate cancer (nmCRPC). Overall survival (OS) results at the first interim analysis (IA1) were immature, with 104 of 427 (24%) events required for planned final OS analysis. Here, we report the results of a second pre-specified interim analysis (IA2). METHODS: One thousand two hundred and seven patients with nmCRPC were randomized 2 : 1 to apalutamide (240 mg daily) or placebo. The primary end point of the study was MFS. Subsequent therapy for metastatic CRPC was permitted. When the primary end point was met, the study was unblinded. Patients receiving placebo who had not yet developed metastases were offered open-label apalutamide. At IA2, pre-specified analysis of OS was undertaken, using a group-sequential testing procedure with O'Brien-Fleming-type alpha spending function. Safety and second progression-free survival (PFS2) were assessed. RESULTS: Median follow-up was 41 months. With 285 (67% of required) OS events, apalutamide was associated with an improved OS compared with placebo (HR 0.75; 95% CI 0.59-0.96; P = 0.0197), although the P-value did not cross the pre-specified O'Brien-Fleming boundary of 0.0121. Apalutamide improved PFS2 (HR 0.55; 95% CI 0.45-0.68). At IA2, 69% of placebo-treated and 40% of apalutamide-treated patients had received subsequent life-prolonging therapy for metastatic CRPC. No new safety signals were observed. CONCLUSION: In patients with nmCRPC, apalutamide was associated with a 25% reduction in risk of death compared with placebo. This OS benefit was observed despite crossover of placebo-treated patients and higher rates of subsequent life-prolonging therapy for the placebo group.

A genome-wide association study of coping behaviors suggests FBXO45 is associated with emotional expression.

Individuals use coping behaviors to deal with unpleasant daily events. Such behaviors can moderate or mediate the pathway between psychosocial stress and health-related outcomes. However, few studies have examined the associations between coping behaviors and genetic variants. We conducted a genome-wide association study (GWAS) on coping behaviors in 14088 participants aged 35 to 69 years as part of the Japan Multi-Institutional Collaborative Cohort Study. Five coping behaviors (emotional expression, emotional support seeking, positive reappraisal, problem solving and disengagement) were measured and analyzed. A GWAS analysis was performed using a mixed linear model adjusted for study area, age and sex. Variants with suggestive significance in the discovery phase (N = 6403) were further examined in the replication phase (N = 7685). We then combined variant-level association evidence into gene-level evidence using a gene-based analysis. The results showed a significant genetic contribution to emotional expression and disengagement, with an estimation that the 19.5% and 6.6% variance in the liability-scale was explained by common variants. In the discovery phase, 12 variants met suggestive significance (P < 1 × 10-6 ) for association with the coping behaviors and perceived stress. However, none of these associations were confirmed in the replication stage. In gene-based analysis, FBXO45, a gene with regulatory roles in synapse maturation, was significantly associated with emotional expression after multiple corrections (P < 3.1 × 10-6 ). In conclusion, our results showed the existence of up to 20% genetic contribution to coping behaviors. Moreover, our gene-based analysis using GWAS data suggests that genetic variations in FBXO45 are associated with emotional expression.

A Longer History of Hemodialysis Can Lead to Sarcopenia in Renal Transplantation Patients.

BACKGROUND: Sarcopenia is a condition in which the amount of skeletal muscle decreases. Recent studies have suggested that sarcopenia is a risk factor for the incidence of postoperative complications, longer hospitalization, and a poorer prognosis. In this study, we examined the impact of sarcopenia in association with a history of hemodialysis in renal transplantation patients. METHODS: A total of 157 patients who underwent renal transplantation at Yokohama City University Medical Center (Yokohama, Japan) from 2005 to 2016 were analyzed in this study. We determined the presence of sarcopenia using the psoas muscle index (PMI). The PMI was calculated based on the left psoas muscle area of L3 (mm2) divided by the square of the body height (m2). RESULTS: The mean/median length of time that the patients received hemodialysis was 2059/850 days. The PMI in men was significantly higher than that in women (321.9 ± 10.0 vs 226.6 ± 17.3, P < .001). The group with a longer history of hemodialysis (≥851 days) showed a significantly lower PMI than the short-history group (≤850 days) (355.8 ± 15.1 vs 289.7 ± 11.3, P = .001). The PMI showed a negative correlation according to the dialysis period and a positive correlation according to the sex and triglyceride levels. CONCLUSIONS: A longer history of hemodialysis was shown to be associated with a lower PMI in renal transplantation patients. In addition, the higher PMI group showed higher serum triglyceride levels than the lower PMI group.

Long-term Survival in a Kidney Transplantation Patient With Progressive Multifocal Leukoencephalopathy: A Case Report.

Post-kidney transplantation progressive multifocal leukoencephalopathy (PML) is a rare disease on which there are very few published reports on record. PML is a demyelinating disease caused by a destructive infection of the oligodendrocytes by the JC polyomavirus. No effective therapeutic protocol has been established other than measures to revive the immune function by reducing or discontinuing the administration of immunosuppressive agents. Most cases are progressive and show a poor prognosis. We herein report a case in which renal function has been maintained for 2 years following the onset of PML, which was initially diagnosed 3 years after kidney transplantation.

Relationship between Economic Security and Self-Rated Health in Elderly Japanese Residents Living Alone.

OBJECTIVES: The purpose of this study was to assess the relationship between economic security and self-rated health for elderly Japanese residents living alone. DESIGN: A secondary analysis of a cross-sectional study. SETTING: N City, H. Prefecture, Japan. PARTICIPANTS: Survey questionnaires were distributed to 2,985 elderly residents living alone, aged ≥70 years, of which, 1,939 (65.0%) were returned and treated as valid responses. MEASUREMENTS: The survey included questions about gender, age, number of years spent in N City, self-rated health, economic security, number of years spent living alone, reason for living alone, life satisfaction, cooking frequency, frequency of seeing a doctor, long-term care service usage, as well as whether they enjoyed their lives, participated in social organizations. RESULTS: Of the respondents, 1,563 (80.6%) reported that they were economically secure, and 376 (19.4%) responded that they were insecure. The odds ratio predicting poor self-rated health for the economically insecure participants was significantly high (odds ratio: 3.19, 95%, Confidence Interval (CI): 2.53-4.02, and P < 0.001). Similarly, the adjusted odds ratio for poor self-rated health was significantly high for the economically insecure participants in multivariate analyses controlling for factors such as age, gender, cooking frequency, and social participation (adjusted odds ratio: 2.21, 95%, CI: 1.70-2.88, and P < 0.001). Furthermore, a similar trend was observed in stratified analyses based on gender and age groups. CONCLUSION: Economic security predicted self-rated health independently of confounders, including social participation and cooking frequency, among the elderly Japanese living alone in communities.

A case of a rare variant of Klinefelter syndrome, 47,XY,i(X)(q10).

Klinefelter syndrome is a condition in which a male patient has one Y chromosome and one or more extra X chromosomes. It is the most common sex chromosome disorder. Klinefelter syndrome is distinguished by many clinical features, such as infertility, high gonadotropin and low testosterone levels, increased height, and sparse body and facial hair. We report the case of a 32-year-old man who visited our hospital complaining of male infertility. Semen analysis showed azoospermia, and chromosomal analysis revealed a 47,XY,i(X)(q10) karyotype, which is a rare variant of Klinefelter syndrome. No spermatozoon was found on microdissection testicular sperm extraction, and the testis biopsy histology showed only Sertoli cells and hyalinised seminiferous tubules. 47,XY, i(X)(q10) has an additional isochromosome made of the long arm of the X chromosome, which shares some features of classical Klinefelter syndrome in many aspects, but patients are usually shorter than average height and have normal intelligence. In addition, to the best of our knowledge, no successful sperm extractions from 47,XY, i(X)(q10) patients were reported in the literature. The reports of patients who have undergone microdissection testicular sperm extraction are very rare. Further reports and studies of this chromosomal abnormality are needed.

High serum dihydrotestosterone examined by ultrasensitive LC-MS/MS as a predictor of benign prostatic hyperplasia or Gleason score 6 cancer in men with prostate-specific antigen levels of 3-10 ng/mL.

There has been no consensus on the role of serum androgen concentrations in prostate cancer detection in men with prostate-specific antigen levels of 3-10 ng/mL. In this study, testosterone and dihydrotestosterone concentrations in blood were examined by a newly developed method using ultrasensitive liquid chromatography with two serially linked mass spectrometers (LC-MS/MS). We investigated the correlation between serum androgen levels and Gleason scores at biopsy. We analyzed data of 157 men with a total prostate-specific antigen range of 3-10 ng/mL who underwent initial systematic prostate needle biopsy for suspected prostate cancer between April 2000 and July 2003. Peripheral blood testosterone and dihydrotestosterone concentrations were determined by LC-MS/MS. Blood levels of testosterone and dihydrotestosterone were compared with pathological findings by multivariate analyses. Median values of prostate-specific antigen and prostate volume measured by ultrasound were 5.7 ng/mL and 31.4 cm3 , respectively. Benign prostatic hyperplasia was diagnosed in 97 patients (61.8%), and prostate cancer was diagnosed in 60 (38.2%) patients, including 31 (19.7%) patients with a Gleason score of 6 and 29 (18.5%) patients with a Gleason score of 7-10. Median values of testosterone and dihydrotestosterone in blood were 3798.7 and 371.7 pg/mL, respectively. There was a strong correlation between serum testosterone and dihydrotestosterone. In multivariate analysis, age, prostate volume, and serum dihydrotestosterone were significant predictors of benign prostatic hyperplasia or prostate cancer with a Gleason score of 6. The area under the receiver operating characteristics curve for age, prostate volume, and serum dihydrotestosterone were 0.67, 0.67, and 0.67, respectively . We confirmed that high dihydrotestosterone blood levels can predict benign prostatic hyperplasia or prostate cancer with a Gleason score of 6 in men with prostate-specific antigen levels of 3-10 ng/mL.

Effective Treatment With Everolimus for Recurrent Granulomatous Interstitial Nephritis in a Renal Transplant Recipient: A Case Report.

BACKGROUND: Granulomatous interstitial nephritis (GIN) is a rare renal disease, and its etiology remains unknown. We report recurrent GIN in renal allograft successfully treated with everolimus (EVR). CASE REPORT: A 22-year-old man with GIN received a kidney from his mother. On follow-up 8 months later, his serum creatinine level was increased, from 1.3 mg/dL to 1.7 mg/dL, and he had microhematuria and proteinuria. A protocol graft biopsy at 1 year after transplantation showed epithelioid granuloma with multinucleated giant cells. He received steroid pulse therapy for recurrent GIN twice, but he developed allograft dysfunction, hematuria, and proteinuria. EVR was started in combination with maintenance immunosuppressants at 28 months after transplantation. Thereafter, the serum creatinine level decreased, from 2.1 mg/dL to 1.6 mg/dL, and microhematuria and proteinuria were stable despite reduction of steroid dose. CONCLUSIONS: Maintenance immunosuppressive therapy combined with EVR may be effective for the recurrence of idiopathic GIN in renal allograft.

Enhancement of Photoinduced Charge-Order Melting via Anisotropy Control by Double-Pulse Excitation in Perovskite Manganites: Pr_{0.6}Ca_{0.4}MnO_{3}.

To control the efficiency of photoinduced charge-order melting in perovskite manganites, we performed femtosecond pump-probe spectroscopy using double-pulse excitation on Pr_{0.6}Ca_{0.4}MnO_{3}. The results revealed that the transfer of the spectral weight from the near-infrared to infrared region by the second pump pulse is considerably enhanced by the first pump pulse and that the suppression of crystal anisotropy, that is, the decrease of long-range lattice deformations due to the charge order by the first pump pulse is a key factor to enhance the charge-order melting. This double-pulse excitation method can be applied to various photoinduced transitions in complex materials with electronic and structural instabilities.

Mode-selective optical packet switching in mode-division multiplexing networks.

A novel mode-selective optical packet switching, based on mode-multiplexers/demultiplexers and multi-port optical micro-electro-mechanical systems (MEMS) switches, has been proposed and experimentally demonstrated. The experimental demonstration was performed using the LP(01), LP(11a) and LP(11b) modes of a 30-km long mode-division multiplexed few-mode fiber link, utilizing 40 Gb/s, 16-QAM signals.

Arterial stiffness is increased in young women with endometriosis.

Endometriosis is a chronic gynaecological disorder that is accompanied by inflammation and oxidative stress. Atherosclerosis has a long subclinical progression in arteries of children and young adults decades before overt clinical manifestations of the disease. In this study, we determined arterial stiffness by measuring brachial-ankle pulse wave velocity (baPWV) in women with endometriosis to assess the presence of subclinical atherosclerosis. We also measured markers of inflammation and oxidative stress in women with endometriosis. baPWV in women with endometriosis aged over 30 years was significantly higher than that in women without endometriosis aged over 30 years (p < 0.05), but not in women aged less than 30. Serum high-sensitivity C-reactive protein level in women with endometriosis was significantly higher than that in controls (p < 0.05). Young women with endometriosis show significantly increased arterial stiffness, suggesting that women with endometriosis need to be cautious of the future onset of atherosclerosis.

Examination of the effect of changing to azilsartan from candesartan in renal transplant patients.

BACKGROUND: Azilsartan, an angiotensin receptor blocker (ARB), was administered to renal transplant recipients to investigate the safety and antihypertensive effect in addition to its ARB-characteristic organ-protective effect. METHODS: The subjects were 20 patients (18 males, 2 females; baseline serum creatinine 2.39 ± 1.33 mg/dL) responding poorly to candesartan, who suffered albuminuria (>0.3 g/g creatinine) and hypertension (>140/90 mm Hg) following renal transplantation. Three months after candesartan was switched to azilsartan 20 mg/d, blood pressure, creatinine-corrected urinary albumin excretion, urinary L-type acid binding protein, urinary 8-hydroxydeoxyguano-sine, serum creatinine, and estimated glomerular filtration rate were evaluated. Thirteen patients received cyclosporine (65.0%) and 7 received tacrolimus (35.0%). Another hypertensive (calcium antagonist) agent was combined in 7 (35.0%). RESULTS: Systolic blood pressure significantly decreased from 139.5 mm Hg (baseline) from 128.7 mm Hg (at 3 months), whereas no significant changes were observed for diastolic blood pressure. The percentage of patients achieving the target level of antihypertensive effect (blood pressure < 130/80 mm Hg) significantly improved from 30.0% (baseline) to 70.0% (at 3 months). No significant changes were observed in renal graft function, oxidative stress marker level, or biochemical examination findings. CONCLUSION: Sufficient antihypertensive effect was demonstrated soon after switching to azilsartan. However, no significant change was found in renal damage markers. Long-term study must be conducted to confirm the protective effect azilsartan on the transplanted kidney, as found with candesartan. The safety of azilsartan was demonstrated. If the transplanted kidney protection is demonstrated, this drug is expected to contribute to the improved long-term prognosis of renal transplant recipients.

Effect of ultra-low-dose estradiol and dydrogesterone on arterial stiffness in postmenopausal women.

Abstract Background Ultra-low-dose estradiol is known to improve menopausal symptoms and increase bone mineral density. However, the effect of ultra-low-dose estradiol on vascular function has not been clarified. Objectives We examined the effects of ultra-low-dose estradiol on brachial-ankle pulse wave velocity (baPWV) and circulating markers of cardiovascular risk. Patients and methods Twenty-eight postmenopausal women were enrolled in this study. Fourteen women received oral estradiol (0.5 mg) and dydrogesterone (5 mg) every day for 12 months (ultra-low-dose group) as hormone replacement therapy (HRT) and 14 women as a control group did not receive HRT. The baPWV, lipid profiles, homeostasis model assessment of insulin resistance (HOMA-IR) and vascular inflammatory markers were measured. Results The baPWV level significantly decreased in the ultra-low-dose group (p = 0.037), while the baPWV level did not significantly change in the control group. HOMA-IR tended to decrease in the ultra-low-dose group (p = 0.076). Systolic blood pressure and diastolic blood pressure did not change significantly in either group. Conclusion An HRT regimen using oral ultra-low-dose estradiol and dydrogesterone has an effect on arterial stiffness and insulin resistance.

Consumption of coffee, not green tea, is inversely associated with arterial stiffness in Japanese men.

BACKGROUND/OBJECTIVES: Studies on the associations between coffee and green tea consumption and arterial stiffness are rare. This study evaluated the possible relationships between coffee and green tea consumption and brachial-ankle pulse wave velocity (ba-PWV) values in Japanese men. SUBJECTS/METHODS: In total, 540 eligible men who enrolled in the baseline survey of a cohort study in Tokushima Prefecture, Japan, and who underwent ba-PWV measurement were analyzed. Information about lifestyle characteristics including coffee and green tea intake were obtained from a structural self-administered questionnaire. Multiple linear regression analyses were used to evaluate the associations between coffee and green tea consumption and ba-PWV. RESULTS: Subjects with greater coffee consumption were younger and showed higher proportions of current smoking and alcohol consumption. Subjects with greater green tea consumption were older and showed lower proportions of current smoking and alcohol consumption. Greater coffee consumption was significantly inversely associated with ba-PWV after the adjustment for probable covariates, including serum low-density lipoprotein cholesterol and high-density lipoprotein cholesterol (P for trend =0.031). After additional adjustment for serum triglycerides, this inverse association persisted, but was somewhat attenuated (P for trend =0.050). In contrast, green tea consumption was not associated with ba-PWV. CONCLUSIONS: Coffee consumption was inversely associated with arterial stiffness independent of known atherosclerotic risk factors, and this association was partly mediated by reduced circulating triglycerides. Further prospective or interventional studies are needed to confirm the causal association.

Abundant daily non-sedentary activity is associated with reduced prevalence of metabolic syndrome and insulin resistance.

BACKGROUND: Non-exercise activity thermogenesis has recently drawn attention because of its potential to prevent weight gain. AIM: This study evaluated the relationships between the duration of daily non-sedentary activities and the prevalence of metabolic syndrome and insulin resistance (IR) in the Japanese population. MATERIAL/SUBJECTS AND METHODS: A total of 518 eligible subjects (380 men and 138 women) who attended the Tokushima Prefectural General Health Checkup Center and participated in the baseline survey of a cohort study conducted in Tokushima Prefecture, Japan were analyzed. Information about lifestyle characteristics including leisure-time exercise and daily non-exercise activities was obtained from a questionnaire. Logistic and multiple linear regression analyses were performed to evaluate the associations between the duration of daily non-exercise non-sedentary activities (beyond sitting) and prevalence of metabolic syndrome (and its components) and IR. RESULTS: Subjects with longer duration of daily non-sedentary activities had significantly lower adjusted odds ratios for metabolic syndrome (p for trend =0.024), abdominal obesity (p for trend =0.023), and low HDLcholesterol levels (p for trend =0.002), after adjustment for sex, age, and other probable covariates including leisure-time exercise. Longer duration of daily non-sedentary activities was further associated with lower homeostasis model of assessment- IR (HOMA-IR) values (p for trend =0.009). CONCLUSIONS: Our results suggest that abundant daily non-sedentary activity might be associated with a lower prevalence of metabolic syndrome, especially for the components of central obesity and low HDL-cholesterol levels, and with a lower prevalence of IR, independent of leisure-time exercise.

Difference in the ratio of high-molecular weight (HMW) to total adiponectin and HMW adiponectin in late post-menopausal women.

OBJECTIVE: High-molecular weight (HMW) isoform level and HMW ratio have been shown to be better predictors of insulin sensitivity and metabolic syndrome than total adiponectin level.We examined the changes in circulating levels of HMW adiponectin and ratios of HMW to total adiponectin in women during the menopausal transition. METHODS: We conducted a cross-sectional study in 217 healthy women and divided them into 4 stages: 58 women in pre-menopausal, 69 women in perimenopausal, 62 women in early post-menopausal and 28 women in late post-menopausal phase. Serum levels of total adiponectin and HMW adiponectin were measured by an enzyme-linked immunosorbent assay. RESULTS: In late post-menopausal women, HMW adiponectin level was significantly higher than that in peri-menopausal women and the HMW to total adiponectin ratio was significantly lower than that in early post-menopausal women. In peri-menopausal women, HMW adiponectin level was significantly lower than that in pre-menopausal women and HMW to total adiponectin ratio was significantly lower than the ratios in pre-menopausal and early post-menopausal women. CONCLUSION: The ratio of HMW to total adiponectin is low in late post-menopausal women, though both levels of total and HMW adiponectin were high after menopause in our cross-sectional study.