Association between evacuation and becoming overweight after the Great East Japan Earthquake: a 7-year follow-up of the Fukushima Health Management Survey.

OBJECTIVES: Disaster evacuation increases the risk of becoming overweight or obese owing to lifestyle changes and psychosocial factors. This study evaluated the effect of evacuation on becoming overweight during a 7-year follow-up among residents of Fukushima Prefecture during the Great East Japan Earthquake. STUDY DESIGN: This was a prospective cohort study. METHODS: We analysed data collected from 18,977 non-overweight Japanese participants who completed the 'Comprehensive Health Checkup Program' and 'Mental Health and Lifestyle Survey', as part of the Fukushima Health Management Survey, between July 2011 and November 2012. An evacuation was defined as the moving out of residents of municipalities designated as an evacuation zone by the government or having a self-reported experience of moving into shelters or temporary housing. Follow-up examinations were conducted in March 2018 to identify patients who became overweight. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated using a Cox proportional hazards regression model. RESULTS: Among 15,875 participants (6091 men and 9784 women; mean age 63.0 ± 11.1 years) who received follow-up examination (mean follow-up, 4.29 years), 2042 (856 men and 1186 women) became overweight. Age-, baseline body mass index-, lifestyle-, and psychosocial status-adjusted HRs (95% CIs) for becoming overweight after evacuation were 1.44 (1.24-1.66) for men and 1.66 (1.47-1.89) for women. CONCLUSION: Evacuation was associated with the risk of becoming overweight 7 years after the disaster. Thus, maintaining physical activity, healthy diet, and sleep quality and removing barriers to healthy behaviour caused by disasters, including anxiety concerning radiation, may prevent this health risk among evacuees.

Guideline adherence by physicians for management of glucocorticoid-induced osteoporosis in Japan: a nationwide health insurance claims database study.

Risk of fracture due to glucocorticoid-induced osteoporosis (GIO) can be reduced by anti-osteoporosis (OP) medications. The proportion of patients on long-term glucocorticoid therapy who received anti-OP medications according to the GIO management guidelines has increased in recent years, but is still suboptimal. INTRODUCTION: Adherence of physicians to guidelines for glucocorticoid (GC)-induced osteoporosis (GIO) management is currently unclear. This study aimed to clarify the state of guideline adherence by physicians in Japan and identify factors associated with guideline adherence using a nationwide health insurance claims database (NDBJ). METHODS: Patients aged ≥ 50 years who were prescribed GC for ≥ 90 days after 180 days without a GC prescription and who were followed up for osteoporosis (OP) management for the subsequent 360 days during the period spanning 2012-2018 were selected from the NDBJ. Guideline adherence was evaluated with the proportion of patients who received OP management as recommended by the Japanese guidelines. Information on previous vertebral and hip fractures, dementia, and polypharmacy was obtained. Factors associated with OP management were evaluated by logistic regression analysis. RESULTS: A total of 512,296 patients were considered to be at high risk of fracture according to the guidelines. Proportions of patients receiving OP management (BMD testing or anti-OP medications) have increased in recent years. In 2017, 33.7% of men and 55.3% of women received OP management in the initial 90 days of GC therapy. Female sex, previous anti-OP medications, polypharmacy, and higher GC dose were significantly associated with receiving OP management, while dementia showed an inverse association. A prior history of hip fracture, a strong risk factor for future fracture, was not significantly associated with receiving OP management. CONCLUSIONS: Although guideline adherence by physicians has increased in recent years, it remains suboptimal. Further efforts to improve guideline adherence are necessary. TRIAL REGISTRATION NUMBER: The present study is not registered.

Predictive ability of novel volumetric and geometric indices derived from dual-energy X-ray absorptiometric images of the proximal femur for hip fracture compared with conventional areal bone mineral density: the Japanese Population-based Osteoporosis (JPOS) Cohort Study.

Areal BMD (aBMD) from DXA is not a sufficiently accurate predictor of fracture. Novel volumetric BMD derived from 3D modeling of the hip from DXA images significantly improved the predictive ability for hip fracture relative to aBMD at the femoral neck, but not aBMD at the total hip. INTRODUCTION: To clarify whether volumetric and geometric indices derived from novel three-dimensional (3D) modeling of the hip using dual-energy X-ray absorptiometric (DXA) images improve hip fracture prediction relative to areal bone mineral density (aBMD). METHODS: We examined 1331 women who had completed the baseline survey and at least one follow-up survey over 20 years (age 40-79 years at baseline). Each survey included aBMD measurement at the hip by DXA. Volumetric and geometric indices of the hip at baseline and the 10-year follow-up were estimated from DXA images using a 3D modeling algorithm. Incident hip fractures during the 20-year follow-up period were identified through self-report. Cox proportional hazards regression models allowing for repeated measurements of predictors and outcomes were constructed, and their predictive ability for hip fracture was evaluated using areas under receiver operating characteristic curves (AUCs) and net reclassification improvement (NRI) over aBMD at the femoral neck (FN) and total hip (TH) as references. RESULTS: During a median follow-up of 19.8 years, 68 incident hip fractures were identified (2.22/1000 person-years). A significantly larger AUC of trabecular volumetric BMD (vBMD) at the total hip (AUC = 0.741), femoral neck (AUC = 0.748), and intertrochanter (AUC = 0.738) and significant NRI (0.177, 0.149, and 0.195, respectively) were observed compared with FN-aBMD (AUC = 0.701), but not TH-aBMD. CONCLUSIONS: vBMD obtained from 3D modeling using routinely obtained hip DXA images significantly improved hip fracture risk prediction over conventional FN-aBMD, but not TH-aBMD. TRIAL REGISTRATION: The Japanese Population-Based Osteoporosis (JPOS) Cohort Study was retrospectively registered as UMIN000032869 in the UMIN Clinical Trials Registry on July 1, 2018.

Estimates of hip fracture incidence in Japan using the National Health Insurance Claim Database in 2012-2015.

Using the nationwide health insurance claims database, we found that the age-standardized hip fracture incidence rates in Japan indicated significant increase in males but no significant change in females during 2012-2015. The fracture risk in subjects aged 75-84 years indicated decrease in females but no change in males. INTRODUCTION: Nationwide registry data on hip fractures have not yet been established in Japan. Using the newly developed National Database of Health Insurance Claims (NDB), which covers the entire Japanese population, we investigated the incidence rates of hip fractures and the associated regional differences. We also assessed the frequency of osteoporosis prescriptions, bone turnover marker (BTM) level, and bone mineral density (BMD) measurements. METHODS: The annual numbers of hip fractures, osteoporosis prescriptions, and BTM level and BMD measurements by prefecture from 2012 to 2015 were obtained from NDB data. We calculated the standardized claims-data ratio (SCR) in each prefecture. RESULTS: The age-standardized incidence rates from 2012 to 2015 indicated no significant change in females and significant increase in males (p value for trend; 0.920, 0.002, respectively). The fracture risk decreased in females aged 75-84 years and indicated no increase in females aged 85-89 years during 2012-2015, while the fracture risk indicated no change in males aged 75-84 years and increased in males aged 85-89 years. The frequency of osteoporosis prescriptions, BTM level measurements, and BMD measurements in the general population in the corresponding period increased with statistical or marginal significance in females and males. West-east regional differences were observed in the incidence rates; the highest SCR values in the western prefectures were approximately double the lowest values in the eastern prefectures. CONCLUSIONS: The age-standardized hip fracture incidence rates indicated no significant change in females and significant increase in males in Japan from 2012 to 2015.

Quantification of Turbulent Driving Forces for the Geodesic Acoustic Mode in the JFT-2M Tokamak.

We investigate spatial structures of turbulence and turbulent transport modulated by the geodesic acoustic mode (GAM), from which the excitation mechanism of the GAM is discussed. The GAM is found to be predominantly excited through a localized Reynolds stress force, rather than the dynamic shearing force. The evaluated growth rate is larger than the linear damping coefficients and is on the same order of magnitude as the effective growth rate evaluated from time evolution in the GAM kinetic energy.

Prognostic usefulness of arm circumference and nutritional screening tools in older patients with cardiovascular disease.

BACKGROUND AND AIM: Arm circumference (AC) and nutritional screening tools have been shown to have prognostic capability in patients with cardiovascular disease (CVD). This study aimed to compare the prognostic predictive capabilities of AC and nutritional screening tools in older patients with CVD. METHODS AND RESULTS: The study population consisted of 949 admitted patients ≥60 years old with CVD. Patients underwent AC measurement and nutritional screening before hospital discharge. We used the controlling nutritional status index (CONUT), the geriatric nutritional risk index (GNRI), and the prognostic nutritional index (PNI) as nutritional screening tools. The end point of the study was all-cause mortality. The mean age of the study population was 72.3 ± 7.2 years, and 68.2% of the patients were male. A total of 130 deaths occurred over a median follow-up period of 2.2 years (interquartile range, 1.1-3.8 years). After adjusting for other prognostic factors, AC (hazard ratio [HR]: 0.59; p < 0.001), CONUT (HR: 0.82; p = 0.016), GNRI (HR: 0.77; p = 0.040), and PNI (HR: 0.80; p = 0.014) were significant predictors of mortality. However, adding AC to the multivariate-adjusted model (0.739 vs. 0.714, respectively; p = 0.037), but not CONUT, GNRI, or PNI (0.724, 0.717, and 0.723 vs. 0.714; p = 0.072, p = 0.306, and p = 0.127, respectively), significantly increased the area under the curve on receiver operating characteristic curve. CONCLUSIONS: AC, but not nutritional screening tools, plays a complementary role to preexisting prognostic factors for predicting prognosis in older patients with CVD.

The Vitamin D3 analogue calcipotriol suppresses CpG-activated TLR9-MyD88 signalling in murine plasmacytoid dendritic cells.

BACKGROUND: Plasmacytoid dendritic cells (pDCs) are involved in the pathogenesis of psoriasis by secreting interferon-α. Vitamin D3 analogues are widely used to treat psoriasis, and the representative analogue calcipotriol (CAL) uniquely downregulates the cytokine production and chemotactic activity of pDCs. However, the molecular mechanism of action of CAL is not well understood. AIM: To investigate effects of CAL on the Toll-like receptor 9-myeloid differentiation primary response gene 88 (TLR9-MyD88) signalling pathway, which induces cytokine production, in murine pDCs. METHODS: pDCs were isolated from mouse spleen cells by negative selection or were generated from mouse bone-marrow cells, and were stimulated with CpG-oligodeoxynucleotide (ODN) with or without CAL for 24 h. mRNA expression of TLR9 and MyD88 was assessed by real-time PCR, and the amount of TLR9 was measured by western blotting. RESULTS: CAL suppressed the CpG-ODN-induced increased expression of MyD88 and TLR9 in pDCs. CONCLUSIONS: CAL may downregulate pDCs by inhibiting TLR9-MyD88 signalling.

Epitope analysis of antidesmoglein 1 autoantibodies from patients with pemphigus foliaceus across different activity stages.

BACKGROUND: Pemphigus foliaceus (PF) and pemphigus vulgaris (PV) are closely related, but clinically distinct, autoimmune blistering diseases caused by autoantibodies against desmoglein (Dsg)1 and Dsg3, respectively. Using ethylenediaminetetraacetic acid (EDTA)-treated Dsg3 enzyme-linked immunosorbent assay (ELISA) we have shown that the proportion of anti-Dsg3 antibodies against calcium-dependent epitopes decreased upon shifting to the inactive phase in patients with PV. OBJECTIVES: To analyse the epitope profiles of anti-Dsg1 antibodies across the different activity stages of PF. METHODS: We evaluated five patients with PF who retained high serum levels of anti-Dsg1 antibodies in the inactive phase. Sera were obtained in both the active and inactive phases, and were analysed by EDTA-treated and exfoliative toxin-treated ELISAs. To map the epitopes of anti-Dsg1 antibodies, immunoprecipitation-immunoblotting was performed using a set of Dsg1/Dsg2 domain-swapped molecules. RESULTS: Anti-Dsg1 antibodies against the calcium-dependent epitopes of Dsg1 were the predominant antibodies in both the active and inactive phases. The proportion of anti-Dsg1 antibodies against the calcium-dependent epitopes did not change upon shifting to the inactive phase. The results of immunoprecipitation-immunoblotting showed that most of the anti-Dsg1 antibodies bound to the extracellular domains (EC)1-2 of Dsg1. CONCLUSIONS: In patients with PF, the calcium-dependent epitopes on EC1 and EC2 of Dsg1 contained definitively pathogenic and nonpathogenic epitopes. The disease activity might be differentially controlled by the antibodies between PF and PV depending on the presence or absence of the nonpathogenic epitope.

Longitudinal analysis of antibody profiles against plakins in severe drug eruptions: emphasis on correlation with tissue damage in drug-induced hypersensitivity syndrome and drug reaction with eosinophilia and systemic symptoms.

BACKGROUND: The evidence for severe drug eruption as a trigger for autoimmune disease has recently increased. No information is available on how tissue damage in severe drug eruptions can induce autoimmune responses. OBJECTIVES: To investigate whether the generation of autoantibodies (autoAbs) against plakin family proteins could be the cause or result of tissue damage in patients with severe drug eruptions and whether the generation of autoAbs could be prevented by systemic corticosteroids during the acute stage. METHODS: We retrospectively analysed alterations of serum levels of autoAbs against plakin family proteins in patients with Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) and drug-induced hypersensitivity syndrome (DiHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) during the acute stage and long after resolution over a period of more than 10 years. RESULTS: AutoAbs against plakin family proteins were detected in patients with either SJS/TEN or DiHS/DRESS regardless of the epidermal damage in the acute stage, and were sustained even long after resolution in DiHS/DRESS, indicating that those autoAbs are neither the cause nor the consequence of epidermal damage, at least in DiHS/DRESS. Severe liver damage and noncorticosteroid therapy during the early and acute stages of DiHS/DRESS were associated with the subsequent generation of these autoAbs. CONCLUSIONS: These autoAbs are neither necessarily the cause nor the result of epidermal damage in DiHS/DRESS, because the presence of these autoAbs was not restricted to patients with SJS/TEN but was also observed in those with DiHS/DRESS, which is characterized by lack of epidermal damage. Severe liver damage and/or immune responses that could be prevented by corticosteroids in the acute stage of DiHS/DRESS are among the causal factors contributing to the generation of autoimmune responses.

Spatiotemporal structures of edge limit-cycle oscillation before L-to-H transition in the JFT-2M tokamak.

In this Letter, we report analyses of spatiotemporal dynamics of turbulence and structure in the limit-cycle oscillation (LCO) that precedes an L-to-H transition. Zonal flows are not observed during LCO, and the oscillation is the periodic generations or decays of barrier with edge-localized mean flow. Oscillatory Reynolds stress is found to be too small to accelerate the LCO flow, by considering the dielectric constant in magnetized toroidal plasmas. Propagation of changes of the density gradient and turbulence amplitude into the core is also observed.

Association between Dairy Product intake and Risk of Osteoporotic Fractures in Postmenopausal Japanese Women: Secondary Analysis of 15-Year Follow-Up data from the Japanese Population-Based Osteoporosis (JPOS) Cohort Study.

OBJECTIVES: Few prospective cohort studies have evaluated the relationship between dairy product intake frequency and risk of osteoporotic fractures in Asians. This study aimed to investigate the association between habitual dairy product intake and risk of osteoporotic fractures. DESIGN: Secondary analysis of prospective cohort study. SETTING: Five municipalities of Japan. PARTICIPANTS: This study included 1,429 postmenopausal Japanese women (age ≥45 years at baseline). MEASUREMENTS: Baseline milk-intake frequency was obtained using nurse-administered questionnaires. Intakes of yogurt and cheese, and estimated calcium intake, were assessed using a validated food frequency questionnaire. Osteoporotic fracture was defined as a clinical fracture diagnosed using radiography. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. RESULTS: Over a median follow-up period of 15.1 years (interquartile range [IQR], 10.1-15.4 years; total, 18,118 person-years), 172 women sustained at least one osteoporotic fracture. The proportions of participants with milk intakes <1, 1, and ≥2 cups/d were 34.4%, 48.0%, and 17.6%, respectively. After adjustment for age, frequency of yogurt intake, frequency of cheese intake, body mass index, history of osteoporotic fractures, and frequency of natto intake, the HRs compared with that for milk intake <1 cup/d were 0.71 (95% CI: 0.51-0.98) and 0.57 (95% CI: 0.35-0.92) for 1 cup/d and ≥2 cups/d, respectively. After adjustment for bone mineral density, HR significance for milk intakes ≥2 cups/d remained significant. Yogurt and cheese intakes were not related to the risk of osteoporotic fractures. CONCLUSION: High habitual milk intake, but not a habitual yogurt or cheese intake is associated with a decreased risk of osteoporotic fractures, independent of bone mineral density, in postmenopausal Japanese women.

Reduction of ion thermal diffusivity inside a magnetic island in JT-60U tokamak plasma.

A peaked ion temperature profile is observed inside the magnetic island during mode locking after the back transition from H mode to L mode in JT-60U. The thermal diffusivity evaluated inside the magnetic island is 0.1 m(2)/s, which is much smaller than that outside the magnetic island by an order of magnitude. The present experiment gives clear evidence that ion heat transport inside a magnetic island can bifurcate and the transport level can be suppressed to the very low level associated with the strong flow shear at the boundary.

Detection of antibodies against the non-calcium-dependent epitopes of desmoglein 3 in pemphigus vulgaris and their pathogenic significance.

BACKGROUND: Antidesmoglein (anti-Dsg) 3 serum antibody titres are usually correlated with the disease activity of pemphigus vulgaris (PV), but some patients retain high titres even in remission. OBJECTIVES: The aim of our study was to determine whether anti-Dsg3 antibodies in PV sera recognized calcium (Ca(2+) )-dependent or non-Ca(2+) -dependent epitopes, and to evaluate their pathogenicity. METHODS: Dsg3 baculoprotein-coated enzyme-linked immunosorbent assay (ELISA) plates were treated with 0.5 mmol L(-1) ethylenediaminetetraacetic acid (EDTA). The binding ability of anti-Dsg3 monoclonal antibodies (mAbs) was analysed. Eight of the 83 patients with PV who were screened had elevated Dsg3 ELISA index values > 00 in remission. The binding ability of these PV sera was analysed. We evaluated the pathogenicity of anti-Dsg3 serum antibodies against the non-Ca(2+) -dependent epitopes using a dissociation assay. RESULTS: The reactivity of pathogenic anti-Dsg3 mAbs against the Ca(2+) -dependent epitopes diminished markedly in the EDTA-treated ELISA, whereas no such reduction was observed in mAbs against the non-Ca(2+) -dependent epitopes. The sera of all the patients contained antibodies against both Ca(2+) -dependent and non-Ca(2+) -dependent epitopes. In six out of the eight patients, the ratio of antibodies against Ca(2+) -dependent to non-Ca(2+) -dependent epitopes decreased in remission. EDTA-treated Dsg3 baculoproteins adsorbed anti-Dsg3 serum antibodies against the non-Ca(2+) -dependent epitopes, but the remnant PV antibodies retained the ability to induce acantholysis in the dissociation assay. CONCLUSIONS: We have established an assay to measure indirectly the titres of anti-Dsg3 serum antibodies against the Ca(2+) -dependent epitopes, based on the differences between EDTA-untreated and EDTA-treated ELISA index values, as a routine laboratory test to reflect the pathogenic anti-Dsg3 serum antibody titres more accurately.

ACTIVATION OF HUMAN FIBROBLASTS BY CHRONIC RADIATION RATHER THAN ACUTE RADIATION.

Cancer-associated fibroblast (CAF), an activated type of fibroblast, is a major stromal cell that contributes to tumor initiation and development in the tumor microenvironment (TME). We previously reported that fractionated radiation rather than acute radiation causes progressive damage to mitochondria and increases the generation of reactive oxygen species, playing an important role in the fibroblast activation in normal tissue injury. Activated fibroblasts then become CAF by interacting with tumor cells, promoting tumor growth in vivo. We here examined the chronic radiation effect on fibroblast activation. Acute radiation (<2.5 Gy) did not increase alpha-Smooth muscle actin, a CAF marker expression in healthy human cells, whereas chronic radiation (2.5 Gy) did. It can be concluded that the induction of fibroblast activation changes across acute radiation, fractionated radiation, and chronic radiation depending on the irradiation technique. This study highlights that radiation activates fibroblasts, playing a role in radiation-related tumor development via TME formation.

Observation of a complex multistage transition in the JT-60U H-mode edge.

A complex multistage transition of the edge radial electric field is observed in JT-60U H-mode phase without edge localized mode. An interesting feature is that the poloidal rotation velocity of the carbon impurity ions changes in the later H-phase without a comparable change in the main ion pressure gradient, indicating a change in the parallel momentum (and particle) balance channel.

Role of Ca2+ mobilization and Ca2+ sensitization in 8-iso-PGF 2 alpha-induced contraction in airway smooth muscle.

BACKGROUND: Isoprostanes are prostaglandin (PG)-like compounds synthesized by oxidative stress, not by cyclooxygenase, and increase in bronchoalveolar lavage fluid of patients with asthma. The airway inflammation implicated in this disease may be amplified by oxidants. Although isoprostanes are useful biomarkers for oxidative stress, the action of these agents on airways has not been fully elucidated. OBJECTIVE: This study was designed to determine the intracellular mechanisms underlying the effects of oxidative stress on airway smooth muscle, focused on Ca(2+) signalling pathways involved in the effect of 8-iso-PGF(2 alpha). METHODS: Using simultaneous recording of isometric tension and F(340)/F(380) (an indicator of intracellular concentrations of Ca(2+), [Ca(2+)]i, we examined the correlation between tension and [Ca(2+)]i in response to 8-iso-PGF(2 alpha) in the fura-2 loaded tracheal smooth muscle. RESULTS: Augmented tension and F(340)/F(380) by 8-iso-PGF(2 alpha) were attenuated by ICI-192605, an antagonist of thromboxane A(2) receptors (TP receptors). Moreover, D609, an antagonist of phosphatidylcholine-specific phospholipase C, markedly reduced both the tension and F(340)/F(380) induced by 8-iso-PGF(2 alpha), whereas U73122, an antagonist of phosphatidylinositol-specific phospholipase C, modestly inhibited them by 8-iso-PGF(2 alpha). SKF96365, a non-selective antagonist of Ca(2+) channels, markedly reduced both tension and F(340)/F(380) by 8-iso-PGF(2 alpha). However, diltiazem and verapamil, voltage-dependent Ca(2+) channel inhibitors, modestly attenuated tension although their reduction of F(340)/F(380) was not different from that by SKF96365. Y-27632, an inhibitor of Rho-kinase, significantly attenuated contraction induced by 8-iso-PGF(2 alpha) without reducing F(340)/F(380), whereas GF109203X and Go6983, protein kinase C inhibitors, did not markedly antagonize them although reducing F(340)/F(380) with a potency similar to Y-27632. CONCLUSION: 8-iso-PGF(2 alpha) causes airway smooth muscle contraction via activation of TP receptors. Ca(2+) mobilization by SKF96365- and D609-sensitive Ca(2+) influx and Ca(2+) sensitization by Rho-kinase contribute to the intracellular mechanisms underlying the action of 8-iso-PGF(2 alpha). Rho-kinase may be a therapeutic target for the physiologic abnormalities induced by oxidative stress in airways.

High population differentiation and unusual haplotype structure in a shade-intolerant pioneer tree species, Zanthoxylum ailanthoides (Rutaceae) revealed by analysis of DNA polymorphism at four nuclear loci.

Differences in demographic history, life-history traits, and breeding systems affect nucleotide variation patterns. It is expected that shade-intolerant pioneer tree species have different patterns of genetic polymorphism and population structure than climax species. We studied patterns of nucleotide polymorphism at four putative starch pathway loci (agpSA, agpSB, agpL, and GBSSI) in Zanthoxylum ailanthoides, a shade-intolerant pioneer tree species that occupies forest gaps in warm-temperate forests of East Asia. Genetic diversity was lower within each population than among populations, and differentiation among populations was high across the loci (F(ST) = 0.32-0.64), as expected from the insect-pollinated breeding system and the metapopulation structure of this pioneer species. Numbers of haplotypes were smaller than those expected from the observed numbers of segregating sites. Single haplotypes accounted for more than 47% of all the sampled genes at the respective loci. These variation patterns were incompatible with neutral predictions for populations of a finite island model. Complex population dynamics, such as bottleneck and/or admixture, in the history of this pioneer tree species might have resulted in the observed patterns of genetic variation and population structure, which are different from those of climax wind-pollinated tree species, such as conifers. In contrast to the other loci investigated in this study, agpL showed nearly no variation in Z. ailanthoides (one singleton only), but there was some extent of variation in a closely related species, Zanthoxylum schinifolium. This suggests possibly a recent selective sweep at or near the locus in Z. ailanthoides.

Predictive value of von Willebrand factor for adverse clinical outcome in hypertensive patients with mild-to-moderate aortic regurgitation.

Plasma levels of von Willebrand factor (vWF), a marker of endothelial dysfunction/damage, are elevated in high-risk hypertensive patients and in patients with severe aortic regurgitation (AR). Patients with mild-to-moderate AR, frequently detected in hypertensive elderly, have additional left ventricular morphological and functional dysfunctions. We hypothesized that hypertensive patients with mild-to-moderate AR may have enhanced endothelial and/or left ventricular dysfunctions that may lead to a deteriorated prognosis. We measured vWF, prothrombin F1+2 (F 1+2) as a marker of thrombin generation, brain natriuretic peptide (BNP) in 104 hypertensive patients with mild-to-moderate AR and 66 hypertensive patients without AR. The left ventricular diameter at systole (LVDs) and left ventricular posterior wall thickness (LVWT) were determined by echocardiography and indexed by body surface area (LVDs/BSA and LVWT/BSA). VWF (median, interquartile range (IQR) 154, 120-196%) and BNP (34.7 pg ml(-1), 15-65%) levels were greater in patients with AR than in those without AR (135, 98-175% and 20, 10.3-49 pg ml(-1)). All patients were prospectively followed up for cardiac events during the period of median 43 months (IQR 31-81). Patients with AR had an increased risk of cardiac events (regression ratio (RR) 1.87, 95% confidence interval 1.28-2.87) when compared to those without AR. A multivariate Cox hazard analysis indicated that log vWF (RR 4.93) and log BNP (RR 1.9) were independent predictors in patients with AR. VWF was an independent predictor of clinical outcome in hypertensive patients with mild-to-moderate AR.

Association of aortic valve sclerosis with thrombin generation in hypertensive patients.

Aortic valve sclerosis (AVS) may predispose to a prothrombotic state, as AVS is predictor of cardiovascular events in hypertensive populations. Thrombin exerts non-thrombotic effects such as vessel tone regulation, progression of atherosclerosis and stimulation of atrial natriuretic peptide (ANP) secretion. We hypothesized that hypertensive patients with AVS may have a persistently activated thrombin generation. We studied 234 asymptomatic never-treated hypertensive patients (73 of them with AVS). Prothrombin F1+2 (F1+2), as a marker of thrombin generation and fibrin D-dimer, as a marker of thrombus formation, ANP and brain natriuretic peptide (BNP) were measured. Presence of AVS, aortic jet velocity and left ventricular diameter at diastole were determined by echocardiography. Glomerular filtration rate was estimated using the Modification of Diet in Renal Disease formula. F1+2 (median and interquartile range (IQR) = 1.05, 0.87-1.38 nM vs. 0.93, 0.72-1.16) and ANP (22, 14-37 pg ml(-1) vs. 17, 11-25) levels were greater, and glomerular filtration rate values (65+/-9 ml min(-1)/1.73 m2 vs. 68+/-11) were lower in hypertensive patients with AVS than in those without AVS. F1+2 (odds ratio, 95% CI = 2.94, 1.07-8.6) was independently associated with AVS after being adjusted for age, gender and the variables of cardiorenal functions measured. After 6 months of treatment using valsartan, F1+2 levels remained elevated in hypertensive patients with AVS (1.14, 0.83-1.42 nM vs. 1.07, 0.84-1.5, n=19), but decreased in those without AVS (1.01, 0.85-1.31 vs. 0.8, 0.84-1.78, n=27). Thrombin generation was associated with AVS in untreated hypertensive patients, and this association was persistent after blood-pressure-lowering treatment using valsartan.