The trajectory of non-depressed suicidal ideation in community-dwelling older people in a rural area in Japan: a prospective longitudinal study with a 3-year follow-up.

BACKGROUND: Suicidal ideation is closely related to severe suicidal behaviour and is an important predictor of suicide attempt and completion, including in older people. Older people tend to have many opportunities to be conscious of death, and may have vague suicidal ideation because of various loss experiences, even if they are not depressed. We hypothesised that suicidal ideation among older people might be a risk factor for later transition to depression. The present study aimed to clarify risk factors that predict the incidence of depression in older people 3 years post-baseline in a rural area of Japan, and to examine the subsequent course of depression among non-depressed older people with suicidal ideation. METHODS: In 2015 and 2018, survey questionnaires were mailed to residents aged 65 years and over living in a rural area in Japan. Participants were divided into a depression group and a non-depression group using 15-item Geriatric Depression Scale scores 3 years post-baseline. Logistic regression analysis was used to identify predictive factors of late-life depression 3 years post-baseline. RESULTS: We received 597 valid responses, with a 3-year follow-up rate of 78.8%. Regarding suicidal ideation, 6.7% of non-depressed older people exhibited suicidal ideation at baseline. Of these, 9.8% exhibited depression after 3 years post-baseline. Logistic regression analysis indicated that development of late-life depression is significantly associated with suicidal ideation, being female, and poor health-related quality of life (HRQOL). CONCLUSIONS: The results revealed that suicidal ideation, being female, and poor HRQOL were predictive factors of the development of late-life depression 3 years post-baseline in a rural area of Japan. These findings provide novel information regarding the transition to depression among community-dwelling older people who are not depressed but have suicidal ideation. Whereas suicidal ideation is considered to be a symptom of depression, the current results suggest that suicidal ideation may precede depression in some older people.

Long-term efficacy of comprehensive multidisciplinary antibiotic stewardship programs centered on weekly prospective audit and feedback.

OBJECTIVE: To evaluate the long-term effects of comprehensive antibiotic stewardship programs (ASPs) on antibiotic use, antimicrobial-resistant bacteria, and clinical outcomes. DESIGN: Before-after study. SETTING: National university hospital with 934 beds. INTERVENTION: Implementation in March 2010 of a comprehensive ASPs including, among other strategies, weekly prospective audit and feedback with multidisciplinary collaboration. METHODS: The primary outcome was the use of antipseudomonal antibiotics as measured by the monthly mean days of therapy per 1000 patient days each year. Secondary outcomes included overall antibiotic use and that of each antibiotic class, susceptibility of Pseudomonas aeruginosa, the proportion of patients isolated methicillin-resistant Staphylococcus aureus (MRSA) among all patients isolated S. aureus, the incidence of MRSA, and the 30-day mortality attributable to bacteremia. RESULTS: The mean monthly use of antipseudomonal antibiotics significantly decreased in 2011 and after as compared with 2009. Susceptibility to levofloxacin was significantly increased from 2009 to 2016 (P = 0.01 for trend). Its susceptibility to other antibiotics remained over 84% and did not change significantly during the study period. The proportion of patients isolated MRSA and the incidence of MRSA decreased significantly from 2009 to 2016 (P < 0.001 and = 0.02 for trend, respectively). There were no significant changes in the 30-day mortality attributable to bacteremia during the study period (P = 0.57 for trend). CONCLUSION: The comprehensive ASPs had long-term efficacy for reducing the use of the targeted broad-spectrum antibiotics, maintaining the antibiotic susceptibility of P. aeruginosa, and decreasing the prevalence of MRSA, without adversely affecting clinical outcome.

Inhibitory effect of bisphosphonate on osteoclast function contributes to improved skeletal pain in ovariectomized mice.

The aim of this study was to evaluate skeletal pain associated with osteoporosis and to examine the inhibitory effect of bisphosphonate (BP) on pain in an ovariectomized (OVX) mouse model. We evaluated skeletal pain in OVX mice through an examination of pain-like behavior as well as immunohistochemical findings. In addition, we assessed the effects of alendronate (ALN), a potent osteoclast inhibitor, on those parameters. The OVX mice showed a decrease in the pain threshold value, and an increase in the number of c-Fos immunoreactive neurons in laminae I-II of the dorsal horn of the spinal cord. Alendronate caused an increase in the pain threshold value and inhibited c-Fos expression. The serum level of tartrate-resistant acid phosphatase 5b, a marker of osteoclast activity, was significantly negatively correlated with the pain threshold value. Furthermore, we found that an antagonist of the transient receptor potential channel vanilloid subfamily member 1, which is an acid-sensing nociceptor, improved pain-like behavior in OVX mice. These results indicated that the inhibitory effect of BP on osteoclast function might contribute to an improvement in skeletal pain in osteoporosis patients.

A case of nosocomial Legionella pneumonia associated with a contaminated hospital cooling tower.

We report the epidemiological investigation of a nosocomial pneumonia case due to Legionella pneumophila linked to a contaminated hospital cooling tower in an immune-compromised patient. A 73-year-old female patient was diagnosed with nosocomial Legionella pneumonia proven by a culture of L. pneumophila serogroup 1 from bronchoalveolar lavage fluid. Two strains isolated from the patient and two strains isolated from two cooling towers were found to be identical using repetitive-sequence-based-PCR with a 95% probability. This Legionella pneumonia case might be caused by aerosol from cooling towers on the roof of the hospital building which was contaminated by L. pneumophila. We increased up the temperature of hot water supply appropriately for prevention of Legionella breeding in an environment of patients' living. On the other hand, as the maintenance of cooling tower, we increased the frequency of Legionella culture tests from twice a year to three times a year. In addition, we introduced an automated disinfectants insertion machine and added one antiseptic reagent (BALSTER ST-40 N, Tohzai Chemical Industry Co., Ltd., Kawasaki, Japan) after this Legionella disease, and thereafter, we have no additional cases of Legionella disease or detection of Legionella spp. from the cooling tower or hot water supply. This case demonstrates the importance of detecting the infection source and carrying out environmental maintenance in cooperation with the infection control team.

Concept, study design, and baseline nighttime blood pressure control status of the WISDOM-Night Study using a wrist-type oscillometric home blood pressure monitoring device.

There is growing evidence that nocturnal hypertension is an independent risk factor for cardiovascular diseases, including heart failure. However, brachial blood pressure (BP) measurements during sleep might themselves disturb sleep quality. We initiated a nationwide, multicenter observational prospective study using a wrist-type oscillometric nighttime BP monitoring device with new algorithms to measure supine BP accurately without sleep disturbance. This study, named the Wrist ICT-based Sleep and Circadian Blood Pressure Monitoring Program-Night BP Study (WISDOM-Night Study), was designed to clarify the impact of wrist-measured daily nighttime BPs on cardiovascular prognosis (stroke, coronary artery disease, heart failure, etc.) using 7 days of BP measurements at 2:00 a.m., 3:00 a.m., 4:00 a.m., and 4 h after bedtime. A total of 2751 patients with one or more cardiovascular risk factors were recruited between March 2021 and March 2024 and are currently being followed up for 7 years. Additionally, 1416 of the WISDOM-Night Study-enrolled patients who also agreed to participate in the WISDOM-Hypertension-Mediated Organ Damage (HMOD) Study underwent echocardiography to evaluate the association between wrist-measured BP and left ventricular structure. Data from this WISDOM-Night Study should provide the prospective association between nighttime BP and cardiovascular disease and reveal the indexes of nighttime BP with clinical pathological relevance. This first report of the WISDOM-Night Study describes the study design, baseline characteristics, and BP control status.

Impact of vascular biomarkers and supine hypertension on cardiovascular outcomes in hypertensive patients: first results from the Cardiovascular Prognostic COUPLING Study in Japan.

The prognostic impact of vascular biomarkers and supine blood pressure (BP) is not well understood. The multicenter, prospective Coupling study determined the prognostic impact of vascular biomarkers and supine BP in outpatients aged ≥30 years with ≥1 cardiovascular risk factor. Occurrence of major cardiovascular events during follow-up was recorded. The primary outcome was time to onset of a major cardiovascular event. Office and supine BP, the cardio-ankle vascular index (CAVI), and the ankle-brachial index (ABI) were determined annually. Of the 5109 participants in the Coupling study, 4716 were analyzed (51.9% male, mean age 68.5 ± 11.4 years); participants mostly had hypertension treated based on seated office/home BP according to relevant guidelines. During a median follow-up of 5.0 years (interquartile range 3.6-5.2), 231 major cardiovascular events occurred. After adjustment for age, sitting office systolic BP, and other covariates, a 1-unit increase in CAVI (hazard ratio [HR] 1.12, 95% confidence interval [CI] 1.01-1.24) and a 0.1-unit decrease in ABI (HR 1.41, 95% CI 1.18-1.68) were significantly associated with cardiovascular event risk; risk was greatest when CAVI was ≥8.0 and ABI was ≤1.10. Uncontrolled supine hypertension (≥140/90 mmHg) was also significantly associated with adjusted cardiovascular event risk (HR 1.36, 95% CI 1.02-1.81); seated office BP control was not significantly associated with cardiovascular event risk. Increased arterial stiffness, mildly lower ABI, and supine hypertension are risk factors for cardiovascular events during standard clinical practice. Supine evaluation of BP and vascular biomarkers has highlighted a blind spot in current hypertension management (Clinical trial registration: University Hospital Medical Information Network Clinical Trials Registry, UMIN000018474).

Delayed fracture healing in tetranectin-deficient mice.

Tetranectin is a plasminogen-binding protein that enhances plasminogen activation, which has been suggested to play a role in tissue remodeling. Recently, we showed that tetranectin has a role in the wound-healing process. In this study, we investigated whether tetranectin plays a role in fracture healing. The fracture-healing process was studied using a femoral osteotomy model in tetranectin-null mice, previously generated by the authors. Radiographic imaging, micro-computed tomography (µCT), and histological analysis were used to evaluate osteotomy healing. In wild-type mice, a callus was apparent from 7 days, and most samples showed marked callus formation and rebridging of the cortices at the osteotomy site at 21 days. In contrast, in the tetranectin-null mice there was no callus formation at 7 days and much less callus formation and no bridging of cortices were observed at 21 days. At 35 days, all osteotomy sites showed clear rebridging, and secondary bone formation was achieved in wild-type mice by 42 days. In contrast, no clear rebridging or secondary bone formation was observed at 42 days in the tetranectin-null mice. Analysis using µCT at 21 days after osteotomy revealed that the callus area in tetranectin-null mice was smaller than that in wild-type mice. Histological analysis also showed that soft tissue and callus formation were smaller in the tetranectin-null mice at the early stage of the healing process after drill-hole injury. These results suggested that tetranectin could have a role in the positive regulation at the early stage of the fracture-healing process, which was reflected in the delayed fracture healing in tetranectin-deficient mice.

Possibility of ex vivo animal training model for colorectal endoscopic submucosal dissection.

PURPOSE: Colorectal endoscopic submucosal dissection (ESD) has not been standardized due to technical difficulties and requires extensive training for reliability. Ex vivo animal model is convenient, but has no blood flow. The objective of this study is to evaluate the characteristics of various ex vivo animal models including a blood flow model for colorectal ESD training and the usefulness of practicing endoscopic hemostasis and closure using an animal model. METHODS: Harvested porcine cecum, rectum, and stomach and bovine cecum and rectum were analyzed regarding ease of mucosal injection, degree of submucosal elevation, and status of the proper muscle layer. Ex vivo animal model with blood flow was made using the bovine cecum. The vessel around the cecum was detached, and red ink was injected. Endoscopic hemostasis for perioperative hemorrhage and endoscopic closure for perforation were performed in this model. RESULTS: Mucosal injection was easily performed in the bovine cecum and rectum. Submucosal elevation was low in the bovine cecum, while the proper muscle layer was not tight in the porcine rectum and bovine cecum. Endoscopic hemostasis were accomplished in six (60 %) out of ten procedures of the ex vivo blood flow model. In two non-experts, the completion rates of endoscopic closure were 40 and 60 % in the first five procedures. These rates became 100 % in the last five procedures. CONCLUSIONS: We have evaluated the characteristics of various ex vivo animal models and shown the possibility of training for endoscopic hemostasis and endoscopic closure in the ex vivo animal model.

Preventive effect of aripiprazole once monthly on rehospitalization for bipolar disorder: A multicenter 1-year retrospective mirror image study.

AIM: We conducted a 1-year retrospective mirror-image study to investigate the effect of aripiprazole once monthly (AOM) on rehospitalization for bipolar disorder. METHODS: Participants were recruited from psychiatric emergency and acute care hospitals in western Japan. We included 39 participants with bipolar disorder who had been administered AOM for at least 1 year with no missing medical records during the observational period. The primary outcomes were rehospitalization rate, number of rehospitalizations, total hospitalization days, and time to rehospitalization in the context of overall psychiatric readmissions. The significance level was set at p < 0.05. RESULTS: AOM significantly reduced the rehospitalization rate from 23/39 (59%) to 7/39 (18%) (p = 0.001). The number of rehospitalizations decreased significantly from a mean of 0.85 per person-year to 0.41 per person-year (p = 0.048). The total hospitalization days significantly decreased from a mean of 34.9 days to 14.4 days (p = 0.008). AOM significantly prolonged the time to rehospitalization (p < 0.001). CONCLUSION: This study found that AOM reduces overall psychiatric rehospitalization for bipolar disorder based on data from 1 year before and after AOM administration in the real-world setting. Future studies should examine the robustness and persistence of the rehospitalization preventive effect of AOM with larger sample sizes and longer observation periods beyond 1 year.

Intravoxel Incoherent Motion Factors Affecting Collapse and Nonunion of Osteoporotic Vertebral Fracture.

STUDY DESIGN: Longitudinal study. OBJECTIVES: Intravoxel incoherent motion (IVIM), a magnetic resonance imaging (MRI) scanning technique that applies diffusion-weighted imaging (DWI), is effective for the quantitative assessment of malignant tumors of the vertebral bone. We hypothesized that IVIM parameters of vertebral bodies are associated with the prognosis of osteoporotic vertebral fracture (OVF). We aimed to explore the relationships between IVIM parameters for vertebral collapse and non-union after OVF and calculate the cut-off values of these parameters for vertebral collapse and non-union. METHODS: A total of 150 patients with acute OVF (150 women; mean age: 79.1 ± 7.4 years) were included and treated conservatively with bracing. MRI was performed at the time of injury. IVIM parameters, such as apparent diffusion coefficient (ADC), molecular diffusion coefficient (D), and perfusion-related diffusion (D*) were recorded. The patients were classified into 3 groups: low-collapse (height loss of ≤50%), high-collapse (height loss of >50%), and non-union. We compared ADC, D, and D* among the low-collapse, high-collapse, and non-union groups and performed a receiver operating characteristic (ROC) curve analysis to determine the boundary values of the high-collapse and non-union groups. RESULTS: The low-collapse, high-collapse, and non-union groups had no significant differences in ADC and D. However, D* differed significantly among the 3 groups. ROC analysis revealed cut-off values of 19.0 × 10-3 mm2/s and 12.3 × 10-3 mm2/s for the high-collapse and non-union groups, respectively. CONCLUSIONS: D* is a significant prognostic indicator for high-collapse and non-union groups with OVF. This suggests that D* should be considered when assessing OVF.

Inconsistent Control Status of Office, Home, and Ambulatory Blood Pressure All Taken Using the Same Device: The HI-JAMP Study Baseline Data.

BACKGROUND: Inconsistencies between the office and out-of-office blood pressure (BP) values (described as white-coat hypertension or masked hypertension) may be attributable in part to differences in the BP monitoring devices used. METHODS: We studied consistency in the classification of BP control (well-controlled BP vs. uncontrolled BP) among office, home, and ambulatory BPs by using a validated "all-in-one" BP monitoring device. In the nationwide, general practitioner-based multicenter HI-JAMP study, 2,322 hypertensive patients treated with antihypertensive drugs underwent office BP measurements and 24-hour ambulatory BP monitoring (ABPM), consecutively followed by 5-day home BP monitoring (HBPM), for a total of seven BP measurement days. RESULTS: Using the thresholds of the JSH2019 and ESC2018 guidelines, the patients with consistent classification of well-controlled status in the office (<140 mmHg) and home systolic BP (SBP) (<135 mmHg) (n = 970) also tended to have well-controlled 24-hour SBP (<130 mmHg) (n = 808, 83.3%). The patients with the consistent classification of uncontrolled status in office and home SBP (n = 579) also tended to have uncontrolled 24-hour SBP (n = 444, 80.9%). Among the patients with inconsistent classifications of office and home BP control (n = 803), 46.1% had inconsistent ABPM-vs.-HBPM out-of-office BP control status. When the 2017 ACC/AHA thresholds were applied as an alternative, the results were essentially the same. CONCLUSIONS: The combined assessment of the office and home BP is useful in clinical practice. Especially for patients whose office BP classification and home BP classification conflict, the complementary clinical use of both HBPM and ABPM might be recommended.

Living alone is associated with depression among the elderly in a rural community in Japan.

AIM: This study aimed to investigate factors associated with depression in a sample of elderly Japanese individuals in a rural community and to examine differences among factors associated with individuals living alone or living with others. METHODS: Using a population-based sample from rural Japan, we assessed a total of 1552 participants aged 65 years or older by mailing a survey and evaluating responses based on the Geriatric Depression Scale. Factors associated with depression were also examined. RESULTS: We received 964 valid responses. Depressed subjects comprised 20.5% of the sample. Living alone was significantly related to depression. In individuals living alone, depression was associated with loss of appetite, suicidal ideation, financial strain, and worries in life. However, multiple linear regression analyses revealed that the influence of living alone was negated by having a good social support system. CONCLUSION: These findings confirm that living alone is an important factor in depression among the elderly in a rural part of Japan. Results also confirm what others have found in Western cultures: high levels of social support, awareness of receiving social support, and willingness to receive assistance may reduce the risk of depression.

Comparative effects of topiroxostat and febuxostat on arterial properties in hypertensive patients with hyperuricemia.

Elevated serum uric acid is a cardiovascular risk factor in patients with hypertension, even when blood pressure (BP) is well controlled. Xanthine oxidoreductase inhibitors (XORi) reduce serum uric acid levels and have several other potential effects. This multicenter, randomized, open-label study compared the effects of two XORi, topiroxostat and febuxostat, on arterial stiffness, uric acid levels, and BP in hypertensive patients with hyperuricemia. Patients received topiroxostat 40-160 mg/day or febuxostat 10-60 mg/day, titrated to maintain serum uric acid <6 mg/dl, for 24 weeks. The primary endpoint was change in the cardio-ankle vascular index (CAVI) from baseline to 24 weeks. There were no significant changes in CAVI from baseline to 24 weeks (from 9.13 to 9.16 [feboxustat] and 8.98 to 9.01 [topiroxostat]). Compared with baseline, there were significant reductions in serum uric acid (-2.9 and -2.5 mg/dl; both p < 0.001) and morning home systolic BP (-3.6 and -5.1 mm Hg; both p < 0.01) after 24 weeks' treatment with febuxostat and topiroxostat. BP decreased to the greatest extent in the subgroup of patients with uncontrolled blood pressure at baseline. Topiroxostat, but not febuxostat, significantly decreased plasma xanthine oxidoreductase activity versus baseline. The urinary albumin-creatinine ratio (UACR) decreased significantly from baseline to 24 weeks with topiroxostat (-20.8%; p = 0.021), but not febuxostat (-8.8%; p = 0.362). In conclusion, neither topiroxostat nor febuxostat had any significant effects on arterial stiffness over 24 weeks' treatment.

Regulatory CD8+ T cells induced by exposure to all-trans retinoic acid and TGF-beta suppress autoimmune diabetes.

Antigen-specific regulatory CD4(+) T cells have been described but there are few reports on regulatory CD8(+) T cells. We generated islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP)-specific regulatory CD8(+) T cells from 8.3-NOD transgenic mice. CD8(+) T cells from 8.3-NOD splenocytes were cultured with IGRP, splenic dendritic cells (SpDCs), TGF-beta, and all-trans retinoic acid (ATRA) for 5days. CD8(+) T cells cultured with either IGRP alone or IGRP and SpDCs in the absence of TGF-beta and ATRA had low Foxp3(+) expression (1.7+/-0.9% and 3.2+/-4.5%, respectively). In contrast, CD8(+) T cells induced by exposure to IGRP, SpDCs, TGF-beta, and ATRA showed the highest expression of Foxp3(+) in IGRP-reactive CD8(+) T cells (36.1+/-10.6%), which was approximately 40-fold increase compared with that before induction culture. CD25 expression on CD8(+) T cells cultured with IGRP, SpDCs, TGF-beta, and ATRA was only 7.42%, whereas CD103 expression was greater than 90%. These CD8(+) T cells suppressed the proliferation of diabetogenic CD8(+) T cells from 8.3-NOD splenocytes in vitro and completely prevented diabetes onset in NOD-scid mice in cotransfer experiments with diabetogenic splenocytes from NOD mice in vivo. Here we show that exposure to ATRA and TGF-beta induces CD8(+)Foxp3(+) T cells ex vivo, which suppress diabetogenic T cells in vitro and in vivo.

Effects of luseogliflozin on arterial properties in patients with type 2 diabetes mellitus: The multicenter, exploratory LUSCAR study.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the occurrence of cardiovascular and renal complications in patients with type 2 diabetes mellitus (T2DM) and represent guideline-recommended therapy in this indication. However, precise mechanisms underlying the beneficial cardiovascular effects of SGLT2 inhibitors are not fully understood. This study investigated the effects of the SGLT2 inhibitor, luseogliflozin, on arterial properties and home blood pressure (BP) in patients with T2DM. This multicenter, single-arm study enrolled adults with T2DM, glycosylated hemoglobin (HbA1c) 6.5%-8.9% in the previous 4 weeks, and an indication for new/additional antidiabetic therapy. Luseogliflozin 2.5 mg/d was given for 12 weeks. Primary outcome was change in cardio-ankle vascular index (CAVI) from baseline to Week 4 and Week 12. Home and office BP, BP variability, and metabolic parameters were secondary endpoints. Forty-seven patients (mean age 63.5 ± 10.7 years) treated with luseogliflozin were included in the full analysis set. CAVI did not change significantly from baseline (mean [95% confidence interval] 8.67 [8.37-8.97]) to Week 12 (8.64 [8.38-8.91]; P = .750), but there were significant reductions from baseline in morning home BP, HbA1c, body weight, body mass index, and serum uric acid levels during luseogliflozin therapy. The reduction in morning home systolic BP was ≥ 5 mm Hg and was independent of baseline BP and BP control status. In conclusion, there was no change in arterial stiffness (based on CAVI) during treatment with luseogliflozin, but changes in BP and metabolic parameters were consistent with the known beneficial effects of SGLT2 inhibitors in T2DM.

Rationale, design, and baseline characteristics of the Cardiovascular Prognostic COUPLING Study in Japan (the COUPLING Registry).

Vascular biomarkers, including the cardio-ankle vascular index (CAVI), are increasingly being recognized as important indicators of cardiovascular risk. CAVI has been shown to have good discriminative ability for detecting new-onset hypertension, but results of studies investigating cardiovascular risk prediction are inconsistent. Furthermore, there is a lack of data on the prognostic value of changes in CAVI over time. The Cardiovascular Prognostic Coupling study was designed to determine the impact of baseline CAVI and changes in CAVI on cardiovascular events in a Japanese cohort. The design of the ongoing, multicenter, prospective, observational registry and baseline characteristics of the enrolled population are reported. Eligible consecutive patients were aged ≥30 years, had ≥1 cardiovascular risk factor, and were being treated according to relevant Japanese guidelines. The primary outcome is time to onset of a major cardiovascular event (a composite of cerebral infarction, cerebral hemorrhage, subarachnoid hemorrhage, stroke of unknown etiology, myocardial infarction, cardiovascular intervention for angina pectoris, and sudden death). Screening and enrollment occurred over a period of 3 years, followed by ≥7 years of follow-up, with CAVI determined annually. A total of 5279 patients were registered, of whom 5109 had baseline data available and will be included in future analyses. Mean CAVI at baseline was 8.8 ± 1.4. The proportion of patients with CAVI of <8, 8-10 or >10 was 25.3%, 57.0%, and 17.7%, respectively. Data from this registry should provide information on the significance of baseline CAVI and change in CAVI as indicators of cardiovascular prognosis in a representative patient population.

Age-related difference of the association of cardiovascular risk factors with the cardio-ankle vascular index in the Cardiovascular Prognostic Coupling Study in Japan (the Coupling Registry).

The value of the cardio-ankle vascular index (CAVI) increases with age. All large-scale studies of the CAVI have investigated patients <80 years old. Thus, the clinical characteristics of high CAVI in patients aged 80 or more remain unclear. Therefore, we investigated (1) the CAVI in very elderly patients and (2) the determinants of a high CAVI in high-risk patients, including very elderly patients. The Cardiovascular Prognostic Coupling Study in Japan (Coupling Registry) is a prospective observational study of Japanese outpatients with any cardiovascular risk factors. We enrolled 5109 patients from 30 institutions (average age 68.7 ± 11.4 years, 52.4% males). We investigated the determinants of the CAVI by separating the patients into three groups: 970 middle-aged (<60 years), 3252 elderly (60-79 years), and 887 very elderly (≥80 years) patients. The CAVI values of the males were significantly higher those of the females in all age groups (<60 years: 7.81 ± 1.11 vs. 7.38 ± 0.99, P < .001; 60-79 years: 9.20 ± 1.29 vs. 8.66 ± 1.07, P < .001; ≥80 years: 10.26 ± 1.39 vs. 9.51 ± 1.12, P < .001). In all age groups, the CAVI of the patients with diabetes/glucose tolerance disorder was higher than that of the patients without diabetes/glucose tolerance disorder (<60 years: 7.82 ± 1.22 vs 7.58 ± 1.03, P = .002; 60-79 years: 9.23 ± 1.20 vs 8.78 ± 1.19, P < .001; ≥80 years: 10.04 ± 1.24 vs 9.75 ± 1.32, P = .002). The determinants of the CAVI in these very elderly patients were age, male sex, low BMI, and mean blood pressure. Diabetes/glucose tolerance disorder and glucose were independently associated with the CAVI in the patients aged <60 years and 60-79 years, but not in those aged ≥80 years after adjusting for other covariates.

The genus Laetiporus (Basidiomycota, Polyporales) in East Asia.

Relationships among East Asian, North American and European Laetiporus sulphureus s. lat., a cosmopolitan brown rot species complex, were assessed with phylogenetic analyses and incompatibility tests. Three East Asian taxa, Laetiporus cremeiporus sp. nov., Laetiporus montanus and Laetiporus versisporus, are described and illustrated as well as compared with related taxa from Southeast Asia, North America and Europe. Phylogenetic analyses showed that L. cremeiporus and L. versisporus are clearly distinct species among Laetiporus taxa. The three conifer inhabiting species, Laetiporus conifericola, Laetiporus huroniensis and L. montanus, are closely related to each other. The European population of L. montanus exhibits two sequence variants of the EF1alpha: one is the same as observed in L. sulphureus in Europe and the other is that observed in East Asian population of L. montanus. A key to the known species of Laetiporus in the northern hemisphere is provided.

Distribution of Genets of Perenniporia subacida in Stands of Chamaecyparis obtusa (Japanese Cypress) Determined by AFLP Fingerprints and Somatic Incompatibility.

The clonal structure of Perenniporia subacida, a wood-rotting basidiomycete, was studied in a 30-year-old stand (site A; 1 ha) and a 43-year-old stand (site B; 0.5 ha) of Chamaecyparis obtusa in northern Kagawa Prefecture, Japan. A total of 110 isolates from decayed trees, stumps, wooden fences, logs, and mycelial mats were analyzed by amplified fragment length polymorphism (AFLP) and somatic incompatibility test (SIT). The results of AFLP, which agreed with those of SIT, revealed that the P. subacida population consisted of at least 17 genets at site A and 6 genets at site B. Individual genets were found in 1 to 9 trees at site A and in 1 to 7 trees at site B. One particular genet had spread over a distance of 70 m. Root contacts were observed among roots of decaying stumps and living trees at both sites. White mycelial mats were often found where roots made contact between stumps and neighboring trees. These results suggest that P. subacida spreads vegetatively over significant distances through root contacts.

Deletion analysis of the catalase-encoding gene (catB) promoter from Aspergillus oryzae.

The catalase-encoding gene (catB) is expressed strongly in Aspergillus oryzae. To identify the transcription regulatory elements involved in strong expression, we did promoter deletion analysis using beta-glucuronidase (GUS) as a reporter and an electrophoretic gel mobility shift assay (EMSA) systematically. The deletion 200-bp sequence from -1,000 to -800 in the 1,400-bp catB promoter caused a drastic decrease in GUS activity. In addition, EMSA implicated a 45-bp element from -1,000 to -956 containing cis-elements. According to detailed promoter deletion analysis, a region from -1,000 to -975, which contains putative heat shock element (HSE) and the CCAAT-box, was involved in strong expression.