Effect of Patient's Symptom Interpretation on In-Hospital Mortality in Acute Coronary Syndrome.

BACKGROUND: The association between symptom interpretation and prognosis has not been investigated well among patients with acute coronary syndrome (ACS). As such, the present study evaluated the effect of heart disease awareness among patients with ACS on in-hospital mortality.Methods and Results: We performed a post hoc analysis of 1,979 consecutive patients with ASC with confirmed symptom interpretation on admission between 2014 and 2018, focusing on patient characteristics, recanalization time, and clinical outcomes. Upon admission, 1,264 patients interpreted their condition as cardiac disease, whereas 715 did not interpret their condition as cardiac disease. Although no significant difference was observed in door-to-balloon time between the 2 groups, onset-to-balloon time was significantly shorter among those who interpreted their condition as cardiac disease (254 vs. 345 min; P<0.001). Moreover, the hazard ratio (HR) for in-hospital mortality was significantly higher among those who did not interpret their condition as cardiac disease based on the Cox regression model adjusted for established risk factors (HR 1.73; 95% confidence interval 1.08-2.76; P=0.022). CONCLUSIONS: This study demonstrated that prehospital symptom interpretation was significantly associated with in-hospital clinical outcomes among patients with ACS. Moreover, the observed differences in clinical prognosis were not related to door-to-balloon time, but may be related to onset-to-balloon time.

Detailed Lipid Profiles and Lipid-related Residual Risk after 12-week 10 mg Rosuvastatin Treatment for Acute Myocardial Infarction.

Objective We aimed to reveal detailed on-treatment lipid profiles, lipid-related surrogate markers, and factors predicting failure to achieve the guideline-recommended lipid management goal following guideline-recommended statin treatment in Japanese patients with acute myocardial infarction (AMI). Methods and Results Sixty AMI patients who underwent coronary intervention and had received rosuvastatin 10 mg/day since the start of their hospitalization were assessed for on-treatment lipid-related profiles, including high-sensitivity C-reactive protein, small dense low-density lipoprotein cholesterol (sd LDL-C), and lipoprotein (a), at the 12-week follow-up. Patients who failed to achieve the guideline-recommended lipid management at 12 weeks were defined as the "unachieved group." Univariate and multivariate logistic regression analyses were performed to evaluate the predictors of inclusion in the unachieved group after high-dose statin treatment. Despite the use of high-dose rosuvastatin, 61.7% of the enrolled AMI patients were included in the unachieved group. In addition, the unachieved group had higher sd LDL-C and lipoprotein (a) levels than the achieved group. Logistic regression analyses demonstrated that low baseline high-density lipoprotein cholesterol (HDL-C) levels and the absence of diabetes were predictors of inclusion in the unachieved group. Conclusion More than half of the Japanese AMI patients treated with rosuvastatin 10 mg/day did not achieve the guideline-recommended goal of lipid management and still had lipid-related residual risk at 12 weeks. Particular attention should be paid to patients with low baseline HDL-C levels and those without diabetes with regard to their on-treatment lipid profiles.

Contribution of the yeast bi-chaperone system in the restoration of the RNA helicase Ded1 and translational activity under severe ethanol stress.

Preexposure to mild stress often improves cellular tolerance to subsequent severe stress. Severe ethanol stress (10% v/v) causes persistent and pronounced translation repression in Saccharomyces cerevisiae. However, it remains unclear whether preexposure to mild stress can mitigate translation repression in yeast cells under severe ethanol stress. We found that the translational activity of yeast cells pretreated with 6% (v/v) ethanol was initially significantly repressed under subsequent 10% ethanol but was then gradually restored even under severe ethanol stress. We also found that 10% ethanol caused the aggregation of Ded1, which plays a key role in translation initiation as a DEAD-box RNA helicase. Pretreatment with 6% ethanol led to the gradual disaggregation of Ded1 under subsequent 10% ethanol treatment in wild-type cells but not in fes1Δhsp104Δ cells, which are deficient in Hsp104 with significantly reduced capacity for Hsp70. Hsp104 and Hsp70 are key components of the bi-chaperone system that play a role in yeast protein quality control. fes1Δhsp104Δ cells did not restore translational activity under 10% ethanol, even after pretreatment with 6% ethanol. These results indicate that the regeneration of Ded1 through the bi-chaperone system leads to the gradual restoration of translational activity under continuous severe stress. This study provides new insights into the acquired tolerance of yeast cells to severe ethanol stress and the resilience of their translational activity.

Severe ethanol stress induces the preferential synthesis of mitochondrial disaggregase Hsp78 and formation of DUMPs in Saccharomyces cerevisiae.

Severe ethanol stress (>9% v/v) induces pronounced translation repression in yeast cells. However, some proteins, which are exceptionally synthesized even under translation repression, play important roles in ethanol tolerance. These proteins are expected to provide important clues for elucidating the survival strategies of yeast cells under severe ethanol stress. In this study, we identified Hsp78 as a protein effectively synthesized under severe ethanol stress. As Hsp78 is involved in mitochondrial protein quality control, we investigated the effect of severe ethanol stress on mitochondrial proteins and found that Ilv2, Kgd1, and Aco1 aggregated with Hsp78 under severe ethanol stress, forming mitochondrial deposition sites for denatured proteins, called DUMPs (Deposits of Unfolded Mitochondrial Proteins). Aggregation of mitochondrial proteins and formation of DUMPs were accelerated in hsp78∆ cells compared with those in wild-type cells. During the recovery process after ethanol removal, aggregated Ilv2 and DUMP levels rapidly decreased in wild-type cells but were maintained for a long time (>180 min) in hsp78Δ cells. Furthermore, the frequency of respiration-deficient mutants caused by severe ethanol stress was higher in hsp78∆ cells than in wild-type cells. These results indicate that severe ethanol stress damaged mitochondrial proteins and that Hsp78 was preferentially synthesized to cope with the damage, thereby suppressing the rapid increase in aggregated protein levels under stress and achieving proper clearance of aggregated proteins during the recovery process. This study provides novel insights into the adverse effects of ethanol on mitochondria and yeast response to severe ethanol stress.

Kounis syndrome caused by protamine shock after coronary intervention: A case report.

We report a case of Kounis syndrome that led to shock after protamine administration during percutaneous coronary intervention (PCI). A man in his 50s was admitted to the nearest hospital following the onset of acute myocardial infarction. Coronary angiography showed a single-vessel lesion in the left anterior descending artery (LAD). He was admitted for PCI. After heparin administration, the procedure was completed by implantation of a coronary stent with the usual procedure. For hemostasis, following protamine administration, the patient went into shock. Subsequently, electrocardiography showed bradycardia with ST-segment elevation at leads II, III, aVF, and V3-6. Cardiopulmonary resuscitation was started immediately. As pulseless electrical activity continued, extracorporeal membrane oxygenation (ECMO) was introduced. Coronary angiography demonstrated coronary spasm in the LAD. He was withdrawn from the ECMO on day 7. His intradermal tests were positive for protamine in the convalescent phase. The patient was diagnosed with protamine shock and type I Kounis syndrome. Protamine shock is not uncommon, but Kounis syndrome may be hidden in it. Thus, similar cases should not be treated as a simple protamine shock. .

High-definition intravascular ultrasound versus optical frequency domain imaging for the detection of calcium modification and fracture in heavily calcified coronary lesion.

While optical frequency domain imaging (OFDI) can delineate calcium modification and fracture, the capability of high-definition intravascular ultrasound (HD-IVUS) for detecting these remains unclear. This study evaluated diagnostic accuracy of HD-IVUS for assessing calcium modification and fracture as compared to OFDI. HD-IVUS and OFDI were used during orbital or rotational atherectomy procedures conducted for 21 heavily calcified coronary lesions in 19 patients. With OFDI assessment used as the gold standard, diagnostic accuracies of HD-IVUS for calcium modification and fracture were compared every 1 mm to the matched pre-stenting images (n = 1129). Calcium modification, as assessed by OFDI, was defined as polished and concave-shaped calcium. For HD-IVUS, calcium modification was defined as the presence of reverberation with concave-shaped calcium. In both assessments, the definition of calcium fracture was defined as a slit or complete break in the calcium plate. Calcified plaque was found in 86.4% of analyzed OFDI images. Calcium modification and fracture were detected in 20.6% and 11.0% of detected calcified plaques. Sensitivity, specificity, positive and negative predictive values of HD-IVUS detection for calcium modification and fracture were 54.4%, 97.8%, 86.7%, 89.1% and 86.0%, 94.5%, 58.2%, 96.8%, respectively. Discordance cases between both assessments demonstrated that heterogeneous calcium visualized by OFDI, separated calcium, and guide wire artifact can be misdiagnosed. Diagnostic accuracies of HD-IVUS for assessing calcium modification and fracture were acceptable as compared to OFDI. Such findings can be of utility during imaging guided interventional procedures with atherectomy.

Safety and feasibility of retrograde INOUE-BALLOON for balloon aortic valvuloplasty without rapid ventricular pacing during transcatheter aortic valve replacement.

Rapid ventricular pacing (RVP) is commonly employed during transcatheter aortic valve replacement (TAVR); however, frequent TAVR is associated with worse prognoses. The retrograde INOUE-BALLOON® (IB) allows balloon aortic valvuloplasty (BAV) without RVP. The aim of this study was to evaluate the feasibility of retrograde IB for TAVR preparation. The study population included 178 consecutive patients (mean age, 84 ± 5 years; male, 47%) who underwent retrograde BAV before prosthetic valve replacement via the transfemoral approach. Patients were divided into a retrograde IB group without RVP (n = 74) and a conventional balloon (CB) group with RVP (n = 104). The primary endpoint was prolonged hypotension after BAV (reduced systolic pressure < 80 mmHg for over 1 min or vasopressor drug requirement). The incidence of prolonged hypotension after BAV was significantly lower in the IB group compared with the CB group (4% vs. 16%, p = 0.011). Balloons were able to penetrate and expand the aortic valve in both groups. RVP was used less for total TAVR in the IB group compared with the CB group. The aortic valve area-index after BAV was not significantly different between the two groups (0.72 ± 0.14 cm2/m2 vs. 0.71 ± 0.12 cm2/m2; p = 0.856). Multivariate analysis demonstrated that IB use was associated with avoidance of prolonged hypotension (OR, 0.27 [0.059-0.952]; p = 0.041). In conclusion, BAV using retrograde IB without RVP is both safe and feasible. More stable hemodynamics were achieved using retrograde IB by avoiding RVP during TAVR.

Prevalence, clinical characteristics, and impact of active cancer in patients with acute myocardial infarction: data from an all-comer registry.

BACKGROUND: Although a history of cancer is a poor prognostic factor in patients with acute myocardial infarction (AMI), the clinical importance of coexisting active cancer remains unclear. METHODS: In this single-center retrospective study, we reviewed an AMI registry and assessed the prevalence and predictors of active cancer, 1-year incidence of cardiac death or major bleeding events (defined as a Bleeding Academy Research Consortium type 3 or 5), and the impact of coexisting active cancer on clinical outcomes. Active cancer was defined as either an already-diagnosed or undiagnosed occult cancer. RESULTS: Between January 2012 and December 2017, 1140 AMI patients (median age, 69 years; male, 76.0%) were enrolled. Active and historical cancers were diagnosed in 63 patients (5.5%) and 50 patients (4.4%), respectively. The most common location was the urinary tract (n=21). In the Kaplan-Meier analysis, the active cancer group had a higher incidence of 1-year cardiac death (17.5% vs. 5.3%, p < 0.001) and major bleeding events (19.0% vs. 5.6%, p < 0.001) than the non-cancer group. In the multivariate Cox proportional hazards regression models, active cancer was an independent predictor of both cardiac death and major bleeding at 1 year. Specifically, gastrointestinal tract and advanced-stage cancers had the poorest outcomes. Compared to the non-cancer group, the 1-year major bleeding rate was higher for all cancer types and stages. In contrast, early-stage cancers had a weaker impact on the 1-year cardiac mortality compared to advanced-stage cancers. Similarly, cardiac death during 1-year also occurred less frequently in occult cancers than in already-known cancers. CONCLUSIONS: In patients with AMI, coexisting active cancer was rare, but it significantly impacted cardiac death and major bleeding events.

Impact of the Great East Japan Earthquake and Tsunami on the Incidence of Takotsubo Syndrome Using a Multicenter, Long-Term Regional Registry.

BACKGROUND: This study aimed to clarify the incidence of takotsubo syndrome (TTS) after the Great East Japan earthquake (GEJ-E) between inland and coastal areas.Methods and Results:Consecutive hospitalized patients with TTS were registered between 2009 and 2016 in Iwate Prefecture. Patients were divided into 2 groups, by whether they lived inland or in the coastal area (both max. seismic intensity, 6-). The incidence of TTS was calculated using the standardized incidence ratio (SIR) before and after the earthquake. The long-term prognosis of the 2 groups was compared by Kaplan-Meier analysis. A total of 112 patients with TTS were registered from the acute coronary syndrome records of each hospital (n=4,163); 9 patients with TTS were registered within 2 months of the earthquake. A significant monthly variation was observed in March and April 2011 compared with the other months (P=0.029). At 2 years after the earthquake, the SIR was significantly increased in the coastal area (P<0.01), but decreased after ≥3 years. There were no significant differences in the long-term prognosis between the 2 groups (P=0.20). CONCLUSIONS: The incidence of TTS was increased in the acute phase after the GEJ-E, particularly in the coastal area. The magnitude of the tsunami damage is presumed to be a factor in the increased incidence of TTS, even though the seismic intensity in both areas was comparable.

Sex-Related Differences in Cardiac Remodeling and Reverse Remodeling After Transcatheter Aortic Valve Implantation in Patients with Severe Aortic Stenosis in a Japanese Population.

Left ventricular (LV) remodeling with aortic stenosis (AS) appears to differ according to sex, but reverse remodeling after transcatheter aortic valve implantation (TAVI) has not been elucidated in a Japanese population. This study aims to determine whether any sex-related differences in LV or reverse remodeling after TAVI exist in the context of severe AS.Of 208 patients who received TAVI for severe AS in our institution, 100 (men, 42; mean age, 83.0 ± 4.9 years) underwent transthoracic echocardiography before and 3 months after TAVI. Despite similar valvular gradients, women with severe AS had lower indexed LV mass (LVMi) than did men (152.3 ± 35.4 versus 173.2 ± 44.6 g/m2, P = 0.005), with smaller indexed LV end-diastolic (LVEDVi) (50.2 ± 13.3 versus 61.4 ± 20.7 mL/m2, P = 0.001) and end-systolic (LVESVi; 17.9 ± 8.7 versus 24.3 ± 13.8 mL/m2, P = 0.006) volumes. After TAVI, women (-6.0% ± 14.4%) had higher reduction in the rate of change of relative wall thickness (RWT) than did men (4.4% ± 19.0%, P = 0.003). Men (-8.9% ± 3.9%) had higher reduction in the rate of change of LVEDVi than did women (1.5% ± 3.3%, P = 0.045). Incidence of LV reverse remodeling defined as a reduction in LVESV of >15% was significantly higher in men (50%) than in women (26%, P = 0.013).In addition to sex differences in the pattern of LV remodeling with AS, reverse LV remodeling after TAVI also differed between sexes.

Amino acid homeostatic control by TORC1 in Saccharomyces cerevisiae under high hydrostatic pressure.

Mechanical stresses, including high hydrostatic pressure, elicit diverse physiological effects on organisms. Gtr1, Gtr2, Ego1 (also known as Meh1) and Ego3 (also known as Slm4), central regulators of the TOR complex 1 (TORC1) nutrient signaling pathway, are required for the growth of Saccharomyces cerevisiae cells under high pressure. Here, we showed that a pressure of 25 MPa (∼250 kg/cm2) stimulates TORC1 to promote phosphorylation of Sch9, which depends on the EGO complex (EGOC) and Pib2. Incubation of cells at this pressure aberrantly increased glutamine and alanine levels in the ego1Δ, gtr1Δ, tor1Δ and pib2Δ mutants, whereas the polysome profiles were unaffected. Moreover, we found that glutamine levels were reduced by combined deletions of EGO1, GTR1, TOR1 and PIB2 with GLN3 These results suggest that high pressure leads to the intracellular accumulation of amino acids. Subsequently, Pib2 loaded with glutamine stimulates the EGOC-TORC1 complex to inactivate Gln3, downregulating glutamine synthesis. Our findings illustrate the regulatory circuit that maintains intracellular amino acid homeostasis and suggest critical roles for the EGOC-TORC1 and Pib2-TORC1 complexes in the growth of yeast under high hydrostatic pressure.

A multicenter study on the clinical characteristics and risk factors of in-hospital mortality in patients with mechanical complications following acute myocardial infarction.

Mechanical complications (MCs) following acute myocardial infarction (AMI), such as ventricular septal rupture (VSR), free-wall rupture (FWR), and papillary muscle rupture (PMR), are fatal. However, the risk factors of in-hospital mortality among patients with MCs have not been previously reported in Japan. The purpose of this study was to evaluate the prognostic factors of in-hospital mortality in these patients. The study cohort consisted of 233 consecutive patients with MCs from the registry of 10 facilities in the Cardiovascular Research Consortium-8 Universities (CIRC-8U) in East Japan between 1997 and 2014 (2.3% of 10,278 AMI patients). The authors conducted a retrospective observational study to analyse the correlation between the subtypes of MCs with in-hospital mortality, clinical data, and medical treatment. We observed a decreasing incidence of MC (1997-2004: 3.7%, 2005-2010: 2.1%, 2011-2014: 1.9%, p < 0.001). In-hospital mortality among patients with MCs was 46%. Thirty-three percent of patients with MCs were not able to undergo surgical repair due to advanced age or severe cardiogenic shock. In-hospital mortality among patients who had undergone surgical repair was 29% (VSR: 21%, FWR: 33%, PMR: 60%). In patients with MCs, hazard ratio for in-hospital mortality according to multivariate analysis of without surgical repair was 5.63 (95% CI 3.54-8.95). In patients with surgical repair, the hazard ratios of blow-out-type FWR (5.53, 95% confidence interval (CI) 2.22-13.76), those with renal dysfunction (3.11, 95% CI 1.37-7.05), and those receiving venoarterial extracorporeal membrane oxygenation (VA-ECMO) (3.79, 95% CI 1.81-7.96) were significantly high. Although primary percutaneous coronary intervention (PCI) is associated with decreased incidence of MCs, high in-hospital mortality persisted in patients with MCs that also presented with renal dysfunction and in those requiring VA-ECMO. Early detection and surgical repair of MCs are essential.

Contrast Mechanisms of Solution-Dispersed Graphene Compounds in Twilight Fluorescence Microscopy.

Twilight fluorescence microscopy is a newly developed technique that is capable of imaging a single-layer graphene compound dispersed in a liquid. A graphene solution mixed with a highly concentrated dye is placed on a glass plate and is irradiated by the excitation beam with an incident angle that has a finite width around the total internal reflection angle. Both the evanescence field and the faint refracted beam decay exponentially as they travel from the glass surface. The dye fluorescence excited by both beams is used as illumination. A simplified theory for dark contrast of graphene compounds is developed based on absorption and Förster resonance energy transfer (FRET), assuming that (1) FRET has a sharp cutoff distance, (2) FRET is independent of the number of layers, and (3) Dexter electron transfer is negligible. The contrast of a reduced graphene oxide multilayer, whose layer heights have been determined by atomic force microscopy, shows good agreement with the simplified theory under various dye concentrations. The FRET cutoff distance is found to be much shorter than one expected for graphene and similar to the distance between two small molecules. This short cutoff distance is the main reason for the assumption to be valid.

A Low Early High-density Lipoprotein Cholesterol Level Is an Independent Predictor of In-hospital Death in Patients with Acute Coronary Syndrome.

Objective In patients with acute coronary syndrome (ACS), low high-density lipoprotein cholesterol (HDL-C) levels in samples collected after an overnight fast are diagnostic indicators and well-established predictors of adverse outcomes. However, the relationship between the HDL-C levels in samples collected just after arrival (early HDL-C) and in-hospital mortality remains unknown. The purposes of the present ACS study were to (1) evaluate the association between the early HDL-C levels of patients and in-hospital mortality and (2) compare the early HDL-C level with other well-known determinants associated with in-hospital mortality. Methods This retrospective study surveyed 638 consecutive ACS patients and then assessed the possible determinants of in-hospital mortality. All initial blood samples, including that for early HDL-C, were drawn within one hour of arrival. Results In the present study, the overall in-hospital mortality was 5.9%. A multivariable analysis showed that a low early HDL-C [odds ratio (OR) 2.53, 95% confidence interval (CI) 1.14-5.62], elevated troponin T (OR 4.40, 95% CI 1.26-15.29) and high Killip class (OR 15.41, 95% CI 7.29-32.59) were independent predictors of in-hospital mortality. A Kaplan-Meier survival analysis indicated that there the in-hospital outcome for the low early HDL-C group was significantly worse than that for the high early HDL-C group (age- and gender-adjusted hazard ratio 2.40, 95% CI 1.15-5.00, p=0.02). Conclusion ACS patients with low early HDL-C levels had higher in-hospital mortalities than those who did not have low early HDL-C levels. In addition to the already well-known determinants, low early HDL-C should also be considered as an independent predictor of in-hospital mortality in ACS patients who present to a cardiac care unit.

Optimized interpretation of fractional flow reserve derived from computed tomography: Comparison of three interpretation methods.

BACKGROUND: An optimal system for interpreting fractional flow reserve (FFR) values derived from CT (FFRCT) is lacking. We sought to evaluate performance of three FFRCT measurements in detecting ischemia by comparing them with invasive FFR. METHODS: For 73 vessels in 50 patients who underwent coronary CT angiography (CCTA) and FFRCT analysis followed by invasive FFR, the greatest diameter stenosis on CCTA, FFRCT difference between distal and proximal to the stenosis (ΔFFRCT), FFRCT 2 cm distal to the stenosis (lesion-specific FFRCT), and the lowest FFRCT in distal vessel tip were calculated. Significant obstruction (≥50% diameter stenosis) and ischemia (lesion-specific FFRCT ≤0.80, the lowest FFRCT ≤0.80, or ΔFFRCT ≥0.12 based on the greatest Youden index) were compared with invasive FFR (≤0.80). RESULTS: Forty (55%) vessels demonstrated ischemia during invasive FFR. On multivariable generalized estimating equations, ΔFFRCT (odds ratio [OR] 10.2, p < 0.01) remained a predictor of ischemia over CCTA (OR 2.9), lesion-specific FFRCT (OR 3.1), and the lowest FFRCT (OR 0.9) (p > 0.05 for all). Area under the curve (AUC) of ΔFFRCT (0.86) was higher than CCTA (0.66), lesion-specific FFRCT (0.71), and the lowest FFRCT (0.65) (p < 0.01 for all). Addition of each FFRCT measure to CCTA showed improvement of AUC and significant net reclassification improvement (NRI): ΔFFRCT (AUC 0.84, NRI 1.24); lesion-specific FFRCT (AUC 0.77, NRI 0.83); and the lowest FFRCT (AUC 0.76, NRI 0.59) (p < 0.01 for all). CONCLUSIONS: Compared with diameter stenosis, ΔFFRCT, lesion-specific FFRCT, and the lowest FFRCT improved ischemia discrimination and reclassification, with ΔFFRCT being superior in identifying and discriminating ischemia.

Impact of Water- and Lipid-Soluble Statins on Nonculprit Lesions in Patients with Acute Coronary Syndrome.

Statins can be differentiated into two types, based on their solubility, which have potentially differing effects on the coronary artery wall. However, suspected differences in statins' effects on plaque composition have not been systemically investigated.Sixty-seven patients with acute coronary syndrome (ACS) were randomly assigned to either atorvastatin (10 mg/day) or rosuvastatin (2.5 mg/day). Intravascular ultrasound (IVUS) and integrated backscatter (IB)-IVUS, an established tool to quantify each plaque's components, were performed immediately after emergent percutaneous coronary intervention (PCI). Follow-up IVUS was performed between 6 and 12 months after PCI. Serial changes in serum lipid profiles and plaque composition volumes were compared between the two groups.Thirty-five patients were eligible for serial IB-IVUS analyses. The mean low-density lipoprotein-cholesterol level significantly decreased in the atorvastatin and rosuvastatin groups (P < 0.001); plaque volumes were also significantly reduced from 82.0 ± 46.2 to 74.9 ± 41.3 mm3 (P = 0.01) and from 74.7 ± 35.3 to 67.7 ± 27.0 mm3 (P = 0.02), respectively. IB-IVUS revealed a significant reduction in fibrous volume from 33.8 ± 20.0 to 27.5 ± 14.9 mm3 (P < 0.01) and from 29.6 ± 13.6 to 24.8 ± 7.6 mm3 (P < 0.05), respectively; however, significant changes were not noted in the volume of the lipid pool for the atorvastatin group and the rosuvastatin group, respectively.Water- and lipid-soluble statins may be similarly effective in reducing coronary plaques in patients with ACS as judged qualitatively and quantitatively. Further study is needed to determine whether differences between water- and lipid-soluble statins affect plaque components.

Biogenesis of sperm acrosome is regulated by pre-mRNA alternative splicing of Acrbp in the mouse.

Proper biogenesis of a sperm-specific organelle, the acrosome, is essential for gamete interaction. An acrosomal matrix protein, ACRBP, is known as a proacrosin-binding protein. In mice, two forms of ACRBP, wild-type ACRBP-W and variant ACRBP-V5, are generated by pre-mRNA alternative splicing of Acrbp Here, we demonstrate the functional roles of these two ACRBP proteins. ACRBP-null male mice lacking both proteins showed a severely reduced fertility, because of malformation of the acrosome. Notably, ACRBP-null spermatids failed to form a large acrosomal granule, leading to the fragmented structure of the acrosome. The acrosome malformation was rescued by transgenic expression of ACRBP-V5 in ACRBP-null spermatids. Moreover, exogenously expressed ACRBP-W blocked autoactivation of proacrosin in the acrosome. Thus, ACRBP-V5 functions in the formation and configuration of the acrosomal granule during early spermiogenesis. The major function of ACRBP-W is to retain the inactive status of proacrosin in the acrosome until acrosomal exocytosis.

Favorable Effects of Oxygen Inhalation in Patients After Bidirectional Glenn Procedure as Assessed by Cardiovascular Magnetic Resonance Flow Measurement.

BACKGROUND: Home oxygen therapy (HOT) is used to adapt patients to the bidirectional Glenn (BDG) physiology. However, the precise cardiovascular effect of oxygen inhalation is still unknown. We used phase-contrast MRI to evaluate the cardiovascular effects of oxygen inhalation in young patients with BDG physiology. METHODS AND RESULTS: The 56 sessions of cardiac MRI were performed in 36 patients with BDG circulation. Oxygen saturation (SpO2) and heart rate (HR) were monitored under both room air and nasal 100% oxygen inhalation, and the blood flow volumes of the ascending aorta (AA), superior vena cava (SVC), and inferior vena cava (IVC) were measured by phase-contrast MRI. Systemic-to-pulmonary collateral flow (SPCF) volumes were calculated by subtracting the sum of flow volumes through the SVC and IVC from the flow volume through the AA, and used for further comparative examination. Under nasal oxygen inhalation, SpO2significantly increased from 82% to 89%, while HR decreased from 115 to 110 beats/min. AA (5.0 vs. 4.9 L·min(-1)·m(-2)), SVC (1.85 vs. 1.77 L·min(-1)·m(-2)), and systemic blood flow volume (=SVC+IVC) significantly decreased (3.60 vs. 3.46 L·min(-1)·m(-2)). In contrast, SPCF and the pulmonary-to-systemic blood flow ratio (Qp/Qs) remained unchanged. CONCLUSIONS: Oxygen inhalation improved arterial blood oxygenation and lowered HR in patients with BDG circulation without an increase in Qp/Qs. HOT would be protective of the cardiovascular system in patients with BDG circulation. (Circ J 2016; 80: 1378-1385).

Surfing and Swimming of Ejaculated Sperm in the Mouse Oviduct.

To accomplish fertilization in the oviductal ampulla, ejaculated sperm are required to migrate through the female reproductive tract. However, this fundamental process largely remains unknown. In this study, we focused on the role of oviductal smooth muscle (myosalpinx) contractions in the sperm migration. Administration of prifinium bromide, padrin, to mice effectively suppressed myosalpinx contractions, resulting in a decreased rate of fertilization in a dose-dependent manner, and an abrogation of high-speed back-and-forth/shuttling flows of oviductal fluids around the isthmus. Regardless of padrin administration, no shuttling flows were found near the ampulla. In the isthmus, sperm formed a tight assemblage that was synchronized with the shuttling flows. The sperm assemblage was gradually loosened and then completely abolished near the ampulla. No sperm assemblage was formed in the isthmus when padrin was administrated. These results suggest that myosalpinx contractions play important roles in the formation of sperm assemblage in the isthmus, and in the transport of the assemblage to the middle region of the oviduct. It is also suggested that the motility of sperm is essential for the migration of sperm from the middle oviductal region to the ampulla.