Living alone predicts poor prognosis among patients with acute myocardial infarction.

BACKGROUND: Living alone as a proxy for social isolation has been considered to increase the risk of cardiovascular disease. We thus investigated the impact of living alone on mortality in acute myocardial infarction (AMI) patients. METHODS: Subjects comprised 277 AMI patients who underwent percutaneous coronary intervention (PCI). Associations between all-cause and cardiac deaths after PCI and baseline characteristics including living alone and Global Registry of Acute Coronary Events (GRACE) risk score were assessed. RESULTS: Eighty-three patients (30%) were living alone. Thirty patients died after PCI, including 20 cardiac deaths. Patients living alone showed higher incidences of both all-cause and cardiac deaths compared with patients not living alone (18% vs. 8%, P  = 0.019 and 14% vs. 4%, P  = 0.004). Multivariate Cox proportional hazards regression analysis models showed living alone [hazard ratio (HR), 2.60; 95% confidence interval (CI), 1.20-5.62; P  = 0.016 and HR, 4.17; 95% CI, 1.60-10.84; P  = 0.003] and GRACE risk score (HR, 1.02; 95% CI, 1.01-1.03; P  = 0.003 and HR, 1.03; 95% CI, 1.01-1.04; P  < 0.001) correlated significantly with all-cause and cardiac deaths. Cox proportional hazards modeling revealed that patients living alone with GRACE risk score ≥162 derived from the receiver-operating characteristic curve showed a significantly greater risk of all-cause death than patients not living alone with GRACE risk score <162 (HR 16.57; 95% CI 6.67-41.21; P  < 0.001). CONCLUSION: Among AMI patients, living alone represents an independent risk factor for all-cause and cardiac deaths after PCI, separate from GRACE risk score. Furthermore, AMI patients living alone with high GRACE risk scores may experience an additively increased risk of mortality after PCI.

Secondary rotational atherectomy is associated with reduced occurrence of prolonged ST-segment elevation following ablation.

Elevation of the ST segment after percutaneous coronary intervention (PCI) using rotational atherectomy (RA) for severely calcified lesions often persists after disappearance of the slow-flow phenomenon on angiography. We investigated clinical factors relevant to prolonged ST-segment elevation following RA among 152 patients with stable angina undergoing elective PCI. PCI procedures were divided into two strategies, RA without (primary RA strategy) or with (secondary RA strategy) balloon dilatation before RA. Incidence of prolonged ST-segment elevation after disappearance of slow-flow phenomenon was higher in the 56 patients with primary RA strategy (13%) than in the 96 patients with secondary RA strategy (3%, p = 0.039). Univariate logistic regression analysis showed levels of low-density lipoprotein cholesterol (LDL-C) (odds ratio [OR] 0.95, 95% confidence interval [CI] 0.93-0.99; p = 0.013), levels of triglycerides (OR 0.97, 95%CI 0.94-0.99; p = 0.040), and secondary RA strategy (OR 0.23, 95% CI 0.05-0.85; p = 0.028) were inversely associated with occurrence of prolonged ST-segment elevation following ablation. However, hemodialysis, diabetes mellitus, left-ventricular ejection fraction, lesion length ≥ 20 mm, and burr size did not show significant associations. Multivariate logistic regression analysis modeling revealed that secondary RA strategy was significantly associated with the occurrence of prolonged ST-segment elevation (Model 1: OR 0.24, 95% CI 0.05-0.95, p = 0.042; Model 2: OR 0.17, 95% CI 0.03-0.68, p = 0.018; Model 3: OR 0.21, 95% CI 0.03-0.87, p = 0.041) even after adjusting for levels of LDL-C and triglycerides. Secondary RA strategy may be useful to reduce the occurrence of prolonged ST-segment elevation following RA.

Environmental risks of organic fertilizer with increased heavy metals (Cu and Zn) to aquatic ecosystems adjacent to farmland in the northern biosphere of Japan.

In Abashiri, Hokkaido, northern Japan, composted sewage sludge (CSS) containing a large amount of zinc (Zn) and copper (Cu) is used as fertilizer in agriculture. The local environmental risks of Cu and Zn from such organic fertilizers were studied. The study area, especially the brackish lakes located near the farmlands, is important for inland fisheries. The risks posed by heavy metals to the brackish-water bivalve, Corbicula japonica, was therefore investigated as an example. First, the long-term effect of CSS application in agricultural fields was monitored. Second, using pot cultivation, factors influencing Cu and Zn availability in the presence of organic fertilizers were evaluated under different scenarios of SOM content. In addition, the mobility and availability of Cu and Zn in organic fertilizers were evaluated in a field experiment. In the pot cultivation, both organic and chemical fertilizers increased the availability of Cu and Zn with a decrease in pH, possibly caused by nitrification. However, this decrease in pH was inhibited by higher SOM content, i.e. SOM mitigated the heavy metal risk from organic fertilizer. In the field experiment, potato (Solanum tuberosum L.) was cultivated using CSS and pig manure (PM). As observed in the pot cultivation, the applied chemical and organic fertilizers increased the soil-soluble and 0.1 N HCl-extractable Zn with increased nitrate. Considering the habitat and the LC50 values of C. japonica that were lower than the concentration of Cu and Zn in the soil solution phase, there is no significant risk from heavy metals in the organic fertilizers. However, the Kd values for Zn were significantly lower for CSS or the PM-applied plot in the field experiment soil, indicating a higher Zn desorption rate from organically fertilized soil particles. The potential risk of heavy metals from agricultural lands under changing climate conditions must therefore be monitored carefully.

Discovery of Novel Substrate-Competitive Lysine Methyltransferase G9a Inhibitors as Anticancer Agents.

Identification of structurally novel inhibitors of lysine methyltransferase G9a has been a subject of intense research in cancer epigenetics. Starting with the high-throughput screening (HTS) hit rac-10a obtained from the chemical library of the University of Tokyo Drug Discovery Initiative, the structure-activity relationship of the unique substrate-competitive inhibitors was established with the help of X-ray crystallography and fragment molecular orbital (FMO) calculations for the ligand-protein interaction. Further optimization of the in vitro characteristics and drug metabolism and pharmacokinetics (DMPK) properties led to the identification of 26j (RK-701), which is a structurally distinct potent inhibitor of G9a/GLP (IC50 = 27/53 nM). Compound 26j exhibited remarkable selectivity against other related methyltransferases, dose-dependent attenuation of cellular H3K9me2 levels, and tumor growth inhibition in MOLT-4 cells in vitro. Moreover, compound 26j showed inhibition of tumor initiation and growth in a carcinogen-induced hepatocellular carcinoma (HCC) in vivo mouse model without overt acute toxicity.

A specific G9a inhibitor unveils BGLT3 lncRNA as a universal mediator of chemically induced fetal globin gene expression.

Sickle cell disease (SCD) is a heritable disorder caused by ß-globin gene mutations. Induction of fetal γ-globin is an established therapeutic strategy. Recently, epigenetic modulators, including G9a inhibitors, have been proposed as therapeutic agents. However, the molecular mechanisms whereby these small molecules reactivate γ-globin remain unclear. Here we report the development of a highly selective and non-genotoxic G9a inhibitor, RK-701. RK-701 treatment induces fetal globin expression both in human erythroid cells and in mice. Using RK-701, we find that BGLT3 long non-coding RNA plays an essential role in γ-globin induction. RK-701 selectively upregulates BGLT3 by inhibiting the recruitment of two major γ-globin repressors in complex with G9a onto the BGLT3 gene locus through CHD4, a component of the NuRD complex. Remarkably, BGLT3 is indispensable for γ-globin induction by not only RK-701 but also hydroxyurea and other inducers. The universal role of BGLT3 in γ-globin induction suggests its importance in SCD treatment.

Association of wound, ischemia, and foot infection clinical stage with frailty and malnutrition in chronic limb-threatening ischemia patients undergoing endovascular intervention.

OBJECTIVE: The Wound, Ischemia, and foot Infection (WIfI) clinical stage has been thought to have a prognostic value in Chronic limb-threatening ischemia (CLTI) patients, and frailty and nutritional status appear to represent pivotal factor affecting prognosis among CLTI patients. The purpose of this study was to examine clinical factors (including frailty and nutritional status) relevant to WIfI clinical stage. METHODS: This retrospective study investigated 200 consecutive CLTI patients. We individually assessed WIfI clinical stage, frailty according to the Clinical Frailty Scale (CFS) score, and malnutrition according to Geriatric Nutritional Risk Index (GNRI). We then compared mortality after endovascular intervention between a WIfI stage 1, 2 group and a stage 3, 4 group, and investigated associations between baseline characteristics (including CFS and GNRI) and WIfI clinical stage. RESULTS: Among 200 patients, 123 patients (62%) showed WIfI stage 1 or 2, and the remaining 77 patients (38%) had WIfI stage 3 or 4. CFS score was significantly higher in the WIfI stage 3, 4 group [median 6.0, interquartile range (IQR) 5.5-7.0] compared with the WIfI stage 1, 2 group (median 5.0, IQR 4.0-6.0, p < 0.001), and GNRI was significantly lower in the WIfI stage 3, 4 group (median 88, IQR 80-97) than in the WIfI stage 1, 2 (median 103, IQR 94-111, p < 0.001). Forty patients (20%) died after endovascular intervention. Incidences of all-cause and cardiac deaths were higher in the WIfI stage 3, 4 group than in the WIfI stage 1, 2 group (27% vs. 15%, p = 0.047 and 12% vs. 3%, p = 0.040, respectively). Kaplan-Meier analysis showed a significantly lower survival rate in the WIfI stage 3, 4 group than in the WIfI stage 1, 2 group (p = 0.002 by log-rank test). Multivariate logistic regression analysis using relevant factors from univariate analysis showed CFS score [odds ratio (OR) 2.06, 95% confidence interval (CI) 1.41-3.13, p < 0.001), diabetes mellitus (OR 3.17, 95%CI 1.17-8.61, p = 0.023) and GNRI (OR 0.93, 95%CI 0.89-0.97, p = 0.002) significantly associated with WIfI stage 3 or 4. In addition, multivariate ordinal logistic regression analysis for WIfI clinical stage showed CFS score (OR 1.43, 95%CI 1.09-1.89, p = 0.011), diabetes mellitus (OR 1.77, 95%CI 1.26-2.54, p < 0.001), and high-sensitivity C-reactive protein (OR 1.14, 95%CI 1.02-1.28, p = 0.041) were positively associated with WIfI clinical stage, and GNRI correlated negatively with WIfI clinical stage (OR 0.95, 95%CI 0.91-0.97, p < 0.001). CONCLUSIONS: These results indicate that CLTI patients with high WIfI clinical stage may be more frail and malnourished, and be associated with poor prognosis after endovascular intervention.

Impact of Malnutrition on Prognosis and Coronary Artery Calcification in Patients with Stable Coronary Artery Disease.

Nutritional status is an important factor affecting prognosis of cardiovascular diseases. We compared major cardiovascular and cerebrovascular events (MACCE) between the malnutrition (geriatric nutritional risk index <92) and non-malnutrition (geriatric nutritional risk index ≥92) groups in 500 stable coronary artery disease patients undergoing percutaneous coronary intervention and evaluated coronary calcification by intravascular ultrasound. Incidences of all-cause death and MACCE differed between the malnutrition and non-malnutrition groups (22% vs 5%, P < 0.001 and 24% vs 6%, P < 0.001). In multivariate Cox proportional hazards regression, malnutrition significantly correlated with all-cause death (P = 0.006) and MACCE (P = 0.010). The proportion of moderate/severe calcification differed between the malnutrition (64%) and non-malnutrition groups (33%, P < 0.001). Multivariate logistic analysis identified age (P < 0.001), malnutrition (P = 0.048), and hemodialysis (P < 0.001) as significantly related to moderate/severe calcification. Malnutrition was an independent risk factor for all-cause death and MACCE in coronary artery disease patients after percutaneous coronary intervention and was associated with moderately/severely calcified lesions.

Visualization of the dynamic interaction between nucleosomal histone H3K9 tri-methylation and HP1α chromodomain in living cells.

Histone lysine methylation is an epigenetic mark that can control gene expression. In particular, H3K9me3 contributes to transcriptional repression by regulating chromatin structure. Successful mitotic progression requires correct timing of chromatin structure changes, including epigenetic marks. However, spatiotemporal information on histone modifications in living cells remains limited. In this study, we created an FRET-based probe for live-cell imaging based on the HP1α chromodomain (HP1αCD), which binds to H3K9me3. The probe was incorporated into chromatin and the emission ratio decreased after treatment with histone methyltransferase inhibitors, indicating that it successfully traced dynamic changes in H3K9me3. Upon entry into mitosis, the probe's emission ratio transiently increased with a concomitant increase in H3K9me3, then exhibited a stepwise decrease, probably due to loss of HP1αCD binding caused by phosphorylation of H3S10 and demethylation of H3K9me3. This probe will be a useful tool for detecting dynamic changes in chromatin structure associated with HP1α.

Impact of nutritional status on prognosis in acute myocardial infarction patients undergoing percutaneous coronary intervention.

BACKGROUND: Malnutrition affects the prognosis of cardiovascular disease. Acute myocardial infarction (AMI) has been a major cause of death around the world. Thus, we investigated the impact of malnutrition as defined by Geriatric Nutritional Risk Index (GNRI) on mortality in AMI patients. METHODS: In 268 consecutive AMI patients who underwent percutaneous coronary intervention (PCI), associations between all-cause death and baseline characteristics including malnutrition (GNRI < 92.0) and Global Registry of Acute Coronary Events (GRACE) risk score were assessed. RESULTS: Thirty-three patients died after PCI. Mortality was higher in the 51 malnourished patients than in the 217 non-malnourished patients, both within 1 month after PCI (p < 0.001) and beyond 1 month after PCI (p = 0.017). Multivariate Cox proportional hazards regression modelling using age, left ventricular ejection fraction and GRACE risk score showed malnutrition correlated significantly with all-cause death within 1 month after PCI (hazard ratio [HR] 7.04; 95% confidence interval [CI] 2.30-21.51; p < 0.001) and beyond 1 month after PCI (HR 3.10; 95% CI 1.70-8.96; p = 0.037). There were no significant differences in area under the receiver-operating characteristic (ROC) curve between GRACE risk score and GNRI for predicting all-cause death within 1 month after PCI (0.90 vs. 0.81; p = 0.074) or beyond 1 month after PCI (0.69 vs. 0.71; p = 0.87). Calibration plots comparing actual and predicted mortality confirmed that GNRI (p = 0.006) was more predictive of outcome than GRACE risk score (p = 0.85) beyond 1 month after PCI. Furthermore, comparison of p-value for interaction of malnutrition and GRACE risk score for all-cause death within 1 month after PCI, beyond 1 month after PCI, and the full follow-up period after PCI were p = 0.62, p = 0.64 and p = 0.38, respectively. CONCLUSIONS: GNRI may have a potential for predicting the mortality in AMI patients especially in beyond 1 month after PCI, separate from GRACE risk score. Assessment of nutritional status may help stratify the risk of AMI mortality.

The Priority of Non-HDL-C Assessment to Predict New Lesions among Stable Angina Patients with Strong Statins.

AIM: In this study, we aim to examine the clinical meaning of low-density lipoprotein cholesterol (LDL-C) ＜70 mg/dL as assessed by Friedewald equation [LDL-C (F)] and Martin method [LDL-C (M)] and non-high-density lipoprotein cholesterol (HDL-C) ＜100 mg/dL on the occurrence of new lesions among Japanese patients with stable angina who underwent percutaneous coronary intervention (PCI) and were prescribed with strong statins. METHODS: Among the 537 consecutive stable angina patients who had underwent PCI and had been prescribed with strong statins, the association between the occurrence of new lesions with myocardial ischemia at the 9-month follow-up coronary angiography and ≤ 2 years after PCI and baseline characteristics were assessed. RESULTS: New lesions appeared 9 months and ≤ 2 years after PCI in 31 and 90 patients, respectively. Multivariate logistic regression analysis revealed diabetes mellitus (DM) was significantly associated with the occurrence of new lesions ≤ 2 years after PCI [odds ratio (OR) 1.71, 95 % confidence interval (CI) 1.06-2.83, p=0.031], and only non-HDL-C ≥ 100 mg/dL was associated with the occurrence of new lesions both at 9 months and ≤ 2 years after PCI [OR 1.80, 95 % CI 1.10-3.00, p=0.021 and OR 1.85, 95 % CI 1.13-3.07, p=0.016]. CONCLUSIONS: Non-HDL-C ≥ 100 mg/dL was determined to be the independent risk factor for the occurrence of new lesions 9 months and ≤ 2 years after PCI among stable angina patients with strong statins. Residual risk after PCI should be considered by assessing not only DM but also non-HDL-C beyond the scope of LDL-C-lowering therapy with strong statins.

Prognostic impact of malnutrition on cardiovascular events in coronary artery disease patients with myocardial damage.

BACKGROUND: Stable coronary artery disease (CAD) patients with myocardial damage have a poor prognosis compared to those without myocardial damage. Recently, malnutrition has been reported to affect the prognosis of cardiovascular diseases. However, the effects of malnutrition on prognosis of CAD patients with myocardial damage remains uncertain. We investigated the effects of malnutrition on prognosis of CAD patients with myocardial damage who received percutaneous coronary intervention (PCI). METHODS: Subjects comprised 241 stable CAD patients with myocardial damage due to myocardial ischemia or infraction. Patients underwent successful revascularization for the culprit lesion by PCI using second-generation drug-eluting stents and intravascular ultrasound. The geriatric nutritional risk index (GNRI), which is widely used as a simple method for screening nutritional status using body mass index and serum albumin, was used to assess nutritional status. Associations between major cardiovascular and cerebrovascular events (MACCE) and patient characteristics were assessed. RESULTS: Mean GNRI was 100 ± 13, and there were 55 malnourished patients (23%; GNRI < 92) and 186 non-malnourished patients (77%). MACCE occurred within 3 years after PCI in 42 cases (17%), including 34 deaths (14%), and the malnourished group showed a higher rate of MACCE (38%) compared with the non-malnourished group (11%, p < 0.001). Univariate Cox proportional hazards analyses showed that MACCE was associated with age [hazard ratio (HR), 1.04; 95% confidence interval (CI), 1.04-1.07; p = 0.004], prior heart failure (HR 2.35; 95% CI 1.10-5.01; p = 0.027), high-sensitivity C-reactive protein (HR 1.08; 95% CI 1.03-1.11; p < 0.001), hemodialysis (HR 2.63; 95% CI 1.51-4.58; p < 0.001) and malnutrition (HR 3.69; 95% CI 2.11-6.42; p < 0.001). Multivariate Cox proportional hazards analysis revealed hemodialysis (HR 2.17; 95% CI 1.19-3.93; p = 0.011) and malnutrition (HR 2.30; 95% CI 1.13-4.67; p = 0.020) as significantly associated with MACCE. Furthermore, Cox proportional hazards models using malnutrition and hemodialysis revealed that patients with malnutrition and hemodialysis were at greater risk of MACCE after PCI than patients with neither malnutrition nor hemodialysis (HR 6.91; 95% CI 3.29-14.54; p < 0.001). CONCLUSIONS: In CAD patients with myocardial damage, malnutrition (GNRI < 92) represents an independent risk factor for MACCE. Assessment of nutritional status may help stratify the risk of cardiovascular events and encourage improvements in nutritional status.

Coronary artery perforation secondary to lifesaving pericardiocentesis for cardiac tamponade: a case report.

BACKGROUND: Pericardiocentesis is frequently performed when fluid needs to be removed from the pericardial sac, for both therapeutic and diagnostic purposes, however, it can still be a high-risk procedure in inexperienced hands and/or an emergent setting. CASE PRESENTATION: A 78-year-old male made an emergency call complaining of the back pain. When the ambulance crew arrived at his home, he was in a state of shock due to cardiac tamponade diagnosed by portable echocardiography. The pericardiocentesis was performed using a puncture needle on site, and the patient was immediately transferred to our hospital by helicopter. Contrast-enhanced computed tomography showed a small protrusion of contrast media on the inferior wall of the left ventricle, suggesting cardiac rupture due to acute myocardial infarction. Emergency coronary angiography was then performed, which confirmed occlusion of the posterior descending branch of the left circumflex coronary artery. In addition, extravasation of contrast medium due to coronary artery perforation was observed in the acute marginal branch of the right coronary artery. We considered that coronary artery perforation had occurred as a complication of the pericardial puncture. We therefore performed transcatheter coil embolization of the perforated branch, and angiography confirmed immediate vessel sealing and hemostasis. After the procedure, the patient made steady progress without a further increase in pericardial effusion, and was discharged on the 50th day after admission. CONCLUSIONS: When performing pericardial drainage, it is important that the physician recognizes the correct procedure and complications of pericardiocentesis, and endeavors to minimize the occurrence of serious complications. As with the patient presented, coil embolization is an effective treatment for distal coronary artery perforation caused by pericardiocentesis.

Use of proton pump inhibitors is associated with an increase in adverse cardiovascular events in patients with hemodialysis: Insight from the kids registry.

BACKGROUND: Proton pump inhibitors (PPIs) are known to increase the risk of mortality and cardiovascular events in the general population. However, in patients with maintenance hemodialysis, PPI effects are under investigated. METHODS: We analyzed the risk of PPIs for cardiovascular events using the Kagoshima Dialysis (KIDS) registry, a prospective, multicenter, observational study in patients with maintenance hemodialysis in Japan. RESULTS: In all, 531 patients were enrolled from June 2015 to December 2018. One-year follow-up data were available for 376 patients (Use of PPIs at baseline (PPI group): 217 patients and without PPIs (No PPI group): 159 patients). The incidence of a composite outcome (all-cause mortality, non-fatal myocardial infarction, or non-fatal stroke) was higher in patients in the PPI group than the No PPI group (15.2% vs. 4.4%; hazard ratio (HR): 3.65, 95% confidence interval (CI): 1.61-8.23, P = 0.002). In the multivariate analysis, even after adjustment for covariates, the use of PPIs was an independent risk factor for a composite outcome (HR: 2.38, 95% CI: 1.02-5.54, P = 0.045). We performed propensity score matching analysis as a sensitivity analysis, showing a consistent result. The incidence of bleeding showed no difference between the two groups (15.7% vs. 11.3%; HR: 1.46, 95% CI: 0.83-2.59, P = 0.19). CONCLUSIONS: These results indicate that the use of PPIs in patients with maintenance hemodialysis might increase mortality and cardiovascular events without decreasing the risk of bleeding. Therefore, it should always be analyzed if a patient truly needs PPIs.

Malnutrition and Clopidogrel Non-Use Worsen Prognosis of Critical Limb Ischemia Patients After Revascularization.

Background: Critical limb ischemia (CLI) patients have high risk for major adverse cerebrovascular and cardiovascular events. This study investigated the risk factors of cerebrovascular or cardiovascular death in CLI patients with concomitant coronary artery disease (CAD). Methods and Results: The association between baseline characteristics and cerebrovascular or cardiovascular death ≤2 years after revascularization for CLI was investigated in 137 CLI patients who previously underwent successful revascularization for CAD before treatment for CLI. Twenty-three patients (17%) died. Geriatric nutritional risk index (GNRI) in the deceased group (DG) was significantly lower than in the surviving group (SG). On Cox proportional hazard multivariate analysis, hemodialysis (HD) and malnutrition (defined as GNRI <92) were significantly associated with cerebrovascular or cardiovascular death. Also, on Kaplan-Meier analysis, survival rate was significantly lower in CLI patients with either malnutrition or HD compared with patients without either malnutrition or HD, respectively. Furthermore, clopidogrel was less used in the DG than in the SG. The use of clopidogrel was associated with cerebrovascular or cardiovascular death. Especially, non-use of clopidogrel in the malnutrition group further increased the correlation with cerebrovascular or cardiovascular death. Conclusions: Malnutrition is a crucial risk factor for cerebrovascular and cardiovascular death in CLI patients with CAD. Nutritional status intervention and use of clopidogrel may be an important strategy for CLI.

Validity of a Novel Method for Estimating Low-Density Lipoprotein Cholesterol Levels in Cardiovascular Disease Patients Treated with Statins.

AIM: The Friedewald equation is the standard method for estimating low-density lipoprotein cholesterol (LDL-C) levels [LDL-C(F)] and fixes the ratio of triglyceride (TG) to very LDL-C at 5. However, this has been reported to underestimate LDL-C, particularly in patients with LDL-C ＜70 mg/dL. A novel method for LDL-C estimation [LDL-C(M)] using an adjustable factor instead of a fixed value of 5 has recently been proposed. The purpose of this study was to validate LDL-C(M) in Japanese patients with cardiovascular disease (CVD) treated with statins. METHODS: In 385 consecutive CVD patients treated with statins, LDL-C(M) and LDL-C(F) levels were compared with directly measured LDL-C [LDL-C(D)]. RESULTS: Mean LDL-C(D), LDL-C(F), and LDL-C(M) were 81.7±25.5, 76.4±24.6, and 79.9±24.5 mg/dL, respectively. In all patients, both LDL-C(F) and LDL-C(M) were significantly correlated with LDL-C(D) [LDL-C(F) vs. LDL-C(D): R=0.974, p＜0.001; LDL-C(M) vs. LDL-C(D): R=0.987, p＜0.001]. In patients with LDL-C(D) ＜70 mg/dL, LDL-C(M) showed a better correlation with LDLC(D) compared with LDL-C(F) [LDL-C(M) vs. LDL-C(D): R=0.935, p＜0.001; LDL-C(F) vs. LDLC(D): R=0.868, p＜0.001]. In contrast, the correlation of LDL-C(D) with LDL-C(M) or LDL-C(F) was similar in patients with LDL-C(D) ≥70 mg/dL. CONCLUSIONS: In Japanese patients with CVD treated with statins, LDL-C level estimated by this novel method might be more accurate than those estimated using the Friedewald equation for LDL-C levels ＜70 mg/dL.

Prospective Study on the Incidence of Cerebrovascular Disease After Coronary Angiography.

AIM: Previous studies have reported a 10.2%-22% rate of silent cerebral infarction and a 0.1%-1% rate of symptomatic cerebral infarction after coronary angiography (CAG). However, the risk factors of cerebral infarction after CAG have not been fully elucidated. For this reason, we investigated the incidence and risk factors of CVD complications within 48 h after CAG using magnetic resonance imaging (MRI) (Diffusion-weighted MRI) at Kagoshima University Hospital. METHODS: From September 2013 to April 2015, we examined the incidence and risk factors, including procedural data and patients characteristics, of cerebrovascular disease after CAG in consecutive 61 patients who underwent CAG and MRI in our hospital. RESULTS: Silent cerebral infarction after CAG was observed in 6 cases (9.8%), and they should not show any neurological symptoms of cerebral infarction. Only prior coronary artery bypass grafting (CABG) was more frequently found in the stroke group (n=6) than that in the non-stroke group (n=55); however, no significant difference was observed (P=0.07). After adjusting for confounders, prior CABG was a significant independent risk factor for the incidence of stroke after CAG (odds ratio: 11.7, 95% confidence interval: 1.14-129.8, P=0.04). CONCLUSIONS: We suggested that the incidence of cerebral infarction after CAG was not related to the catheterization procedure per se but may be caused by atherosclerosis with CABG.

Identification of Cyproheptadine as an Inhibitor of SET Domain Containing Lysine Methyltransferase 7/9 (Set7/9) That Regulates Estrogen-Dependent Transcription.

SET domain containing lysine methyltransferase 7/9 (Set7/9), a histone lysine methyltransferase (HMT), also methylates non-histone proteins including estrogen receptor (ER) α. ERα methylation by Set7/9 stabilizes ERα and activates its transcriptional activities, which are involved in the carcinogenesis of breast cancer. We identified cyproheptadine, a clinically approved antiallergy drug, as a Set7/9 inhibitor in a high-throughput screen using a fluorogenic substrate-based HMT assay. Kinetic and X-ray crystallographic analyses revealed that cyproheptadine binds in the substrate-binding pocket of Set7/9 and inhibits its enzymatic activity by competing with the methyl group acceptor. Treatment of human breast cancer cells (MCF7 cells) with cyproheptadine decreased the expression and transcriptional activity of ERα, thereby inhibiting estrogen-dependent cell growth. Our findings suggest that cyproheptadine can be repurposed for breast cancer treatment or used as a starting point for the discovery of an anti-hormone breast cancer drug through lead optimization.

Angiotensin-Converting Enzyme Inhibitor Prevents the Worsening of Renal Function in the Late Phase after Percutaneous Coronary Intervention.

AIM: The amount of contrast media and renal atheroemboli are risk factors for acute kidney injury after percutaneous coronary intervention (PCI). However, the chronic kidney injury after PCI has not been fully characterized. The purpose of this study was to investigate factors affecting renal function in the late phase after PCI by measuring serum Cystatin C (CysC). METHODS: In 143 consecutive patients who underwent elective PCI, CysC was evaluated at baseline and at 9 months after PCI, and the percent change in CysC (%CysC) was calculated. The association between %CysC and baseline characteristics, including medication use, was assessed. RESULTS: Of 143 patients, 86 had worsening renal function (WRF; %CysC ≥0), and 57 did not (non-WRF; %CysC <0). Only the use of angiotensin-converting enzyme inhibitor (ACEI) and baseline CysC were significantly different between WRF and non-WRF patients (15 vs. 40%, p=0.001 and 1.02±0.26 vs. 1.13±0.26 mg/L, p=0.015). In univariate analysis, the use of ACEI and CysC were negatively associated with WRF [Odds ratio (OR)=0.26, 95% confidence interval (CI)=0.12-0.57, p<0.001 and OR=0.20, 95% CI=0.05-0.73, p=0.015]. Furthermore, multivariate analysis revealed that the use of ACEI and CysC significantly correlated with WRF (OR=0.26, 95% CI=0.11-0.57, p<0.001 and OR=0.20, 95% CI=0.05-0.74, p=0.016). The %CysC in 36 patients with ACEI was significantly lower than that in 107 patients without ACEI [median: -3.8%; interquartile range (IQR), -11.0 to 4.2%; vs. median: 3.3%; IQR -2.9 to 11.0%, p=0.001]. CONCLUSION: The use of ACEI was associated with lower CysC after PCI, suggesting that ACEI prevents worsening of renal function in late phase after PCI.

Effects of regional climate changes on the planktonic ecosystem and water environment in the frozen Notoro Lagoon, northern Japan.

Diatom fossils from core sediments and living diatoms from water samples of Notoro Lagoon in northern Japan were examined to evaluate natural climate effects on lagoon environmental changes. In 1974, the artificial inlet was excavated. Immediately after, the anoxic bottom water in Notoro Lagoon began to disappear due to an increasing water exchange rate. However, chemical oxygen demand (COD) in the bottom water of Notoro Lagoon gradually increased, with fluctuations, during the last 30 years. In addition, the dominant diatom assemblages in Notoro Lagoon shifted to ice-related and spring bloom taxa after the excavation. The dominant taxa of each year in the sediment core were also strongly related to the timing of lagoon ice melting. This is because the COD in Notoro Lagoon was affected by the deposited volume of blooming diatoms, which was controlled by the duration of ice cover and the timing of ice discharge to the Okhotsk Sea likely due to an air pressure pattern change over the northern North Pacific like the Pacific Decadal Oscillation (PDO).