Robustanic acid as a glutaminase and Na+, K+-ATPase inhibitor from leaves of Eucalyptus globulus.

This study was to compare glutaminase and Na+, K+-ATPase inhibitory activities of 20 herbal extracts and investigate the isolation, structural elucidation and those inhibitory activities of three triterpenes from the selected extract of Eucalyptus globulus Labill. Three triterpenes, ursolic acid (1), robustanic acid (2) and ursolic acid lactone (3), were identified by analyzing their NMR and MS spectral data and comparison of these with reported data. The IC50 values of 1-3 and the control compound against glutaminase, 6-diazo-5-oxo-l-norleucine (DON), were 443 µM, 334 µM, 963 µM and 134 µM, respectively. The IC50 values of 1, 2 and the control compound against Na+, K+-ATPase and ouabain, were 180 µM, 56 µM and 0.5 µM, respectively. Compounds 1 and 2 may serve as potential lead compounds for the prevention and treatment of neurodegenerative and lifestyle-related diseases by targeting glutaminase and Na+, K+-ATPase. This is the first report on glutaminase and Na+, K+-ATPase inhibitory activities of 2.

Contribution of Gamma-Aminobutyric Amino Acid and Free Amino Acids to Low-Salt Whole-Wheat Bread through the Addition of Spice Extracts-An Approach Based on Taste Quality.

Given the link between excessive salt consumption and hypertension, reducing salt levels in bread, an important staple food in Japan, is essential. γ-Aminobutyric acid (GABA) has a salty taste-enhancing effect in vivo, and its production is influenced by the type of spice extract in vitro. However, the effects of spices on GABA levels, total free amino acid composition, and taste quality in whole-wheat bread remain unclear. Therefore, this study aimed to investigate whether the addition of spice extracts, which do not affect bread flavor and taste, can increase the GABA level in low-salt whole-wheat bread and whether free amino acid content affects the taste quality of bread using an automatic home bread maker. Through free amino acid composition analysis and sensory testing, we evaluated the influence of six spice extracts on the composition of free amino acids, including GABA, in whole-wheat bread. We found that cumin and anise extracts were effective in increasing the GABA level to approximately twice that in whole-wheat bread. Moreover, both the preference and saltiness of the bread were favorable, indicating that these extracts are useful for reducing the salt content of whole-wheat bread. This study provides a theoretical basis for guiding industrial production.

Size of Self-Expandable Transcatheter Heart Valve and Mid-Term Adverse Events After Transcatheter Aortic Valve Replacement.

The hemodynamic performance of self-expandable valves (SEVs) is a preferable choice for small aortic annuli in transcatheter aortic valve replacement (TAVR). However, no data are, so far, available regarding the relation between the size of SEVs and clinical outcomes. This study aimed to evaluate the impact of prosthesis size on adverse events after TAVR using SEVs. We retrospectively analyzed 1,400 patients (23-mm SEV: 13.6%) who underwent TAVR using SEVs at 12 centers. The impact of SEV size on all-cause death and heart failure (HF) after TAVR was evaluated by multivariate Cox regression and propensity score (PS) matching analysis. During the follow-up period (median 511 days), 201 all-cause deaths and 87 HF rehospitalizations were observed. The incidence of all-cause death was comparable between small- (23-mm SEV) and larger-sized (26- or 29-mm SEV) (16.8% vs 13.9%, log-rank p = 0.29). The size of SEV was not associated with a higher incidence of all-cause death (hazard ratio [HR] 1.21, 95% confidence interval [CI] 0.79 to 1.86 in Cox regression; HR 1.31, 95% CI 0.77 to 2.23 in PS matching) and HF after TAVR (subdistribution HR 0.79, 95% CI 0.37 to 1.72 in Cox regression; subdistribution HR 1.00, 95% CI 0.44 to 2.30 in PS matching). The multivariate model including postprocedural prosthesis-patient mismatch showed consistent results. In conclusion, small SEVs had comparable midterm clinical outcomes to larger-sized SEVs, even if the prosthesis-patient mismatch was observed after TAVR.

Comparative Data of Procedural and Midterm Outcomes in Patients Who Underwent Percutaneous Left Atrial Appendage Closure Between the WATCHMAN FLX and WATCHMAN 2.5 Devices　- Insight From the OCEAN-LAAC Registry.

BACKGROUND: Limited data are available regarding clinical outcomes after percutaneous left atrial appendage closure using WATCHMAN FLX (WM-FLX) and WATCHMAN-2.5 (WM2.5) devices in Asian patients.Methods and Results: Data of 1,464 consecutive patients (WM-FLX, n=909; WM2.5, n=555) were extracted from a Japanese multicenter registry, and clinical data were compared between the 2 groups. No in-hospital deaths, periprocedural stroke, or device embolization occurred. Procedural success was significantly higher in the WM-FLX than WM2.5 group (95.8% vs. 91.9%; P=0.002) owing to the lower incidence of periprocedural pericardial effusion (0.55% vs. 1.8%; P=0.021). No significant differences in all-cause death, postprocedural stroke, and device-related thrombus were observed between the 2 groups. However, the cumulative bleeding rate at 1 year was substantially lower in the WM-FLX group (7.8% vs. 16.4%; P<0.001). Landmark analysis of bleeding events highlighted lower bleeding rates in the WM-FLX than WM2.5 group within the first 6 months (6.4% vs. 14.8%; P<0.001), with comparable bleeding rates over the 6- to 12-month period (1.5% vs. 3.2%, respectively; P=0.065). CONCLUSIONS: This study demonstrated higher early safety and lower 1-year bleeding rates in the WM-FLX than WM2.5 group. The lower bleeding events with WM-FLX are likely due to multiple factors other than purely difference in devices, such as postprocedural drug regimen.

Dairy consumption, bone turnover biomarkers, and osteo sono assessment index in Japanese adults: A cross-sectional analysis of data from the Iwaki Health Promotion Project.

Purpose: Dairy foods are nutritional sources of calcium, phosphorus, protein, and other nutrients that improve bone health. However, the effects of dairy consumption on bone biomarkers in the Japanese population remain unclear. This study explored the association between dairy consumption and bone biomarkers in Japanese adults. Methods: This cross-sectional study was conducted as part of the Iwaki Health Promotion Project in Aomori, Japan. In total, 1063 adults were included in the analysis. Bone turnover marker levels were measured in local citizens during their annual medical checkups. The calcaneus osteo sono assessment index (OSI) was calculated using a quantitative ultrasound technique. The dietary intake of foods and nutrients was estimated using a food frequency questionnaire. Linear regression models were established using dairy consumption and bone biomarkers with adjustments. Statistic significance was considered by P < 0.05. Results: In multivariate models, the tartrate-resistant acid phosphatase 5b and parathyroid hormone concentrations were inversely associated with dietary dairy consumption after adjusting for age and sex. The undercarboxylated osteocalcin, a procollagen type I N-terminal peptide to bone alkaline phosphatase ratio, and OSI were the directly associated with dairy consumption in multivariate models with adjustment. Conclusions: Dairy consumption is partially associated with bone turnover biomarkers and OSI in adult Japanese participants. Habitual consumption of dairy foods may contribute to the nutritional supplementation for maintaining bone health, including turnover and structure. Clinical trial registry number and website where it was obtained: The Japanese Clinical Trials Registry (UMIN000040459), https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000046175.

Performance and outcomes of the SAPIEN 3 Ultra RESILIA transcatheter heart valve in the OCEAN-TAVI registry.

BACKGROUND: Data on the performance of the latest-generation SAPIEN 3 Ultra RESILIA (S3UR) valve in patients who undergo transcatheter aortic valve replacement (TAVR) are scarce. AIMS: We aimed to assess the clinical outcomes, including valve performance, of the S3UR. METHODS: Registry data of 618 consecutive patients with S3UR and of a historical pooled cohort of 8,750 patients who had a SAPIEN 3 (S3) valve and underwent TAVR were collected. The clinical outcomes and haemodynamics, including patient-prosthesis mismatch (PPM), were compared between the 2 groups and in a propensity-matched cohort. RESULTS: The incidence of in-hospital death, vascular complications, and new pacemaker implantation was similar between the S3UR and the S3 groups (allp>0.05). However, both groups showed significant differences in the degrees of paravalvular leakage (PVL) (none-trivial: 87.0% vs 78.5%, mild: 12.5% vs 20.5%, ≥moderate: 0.5% vs 1.1%; p<0.001) and the incidence of PPM (none: 94.3% vs 85.1%, moderate: 5.2% vs 12.8%, severe: 0.5% vs 2.0%; p<0.001). The prevalence of a mean pressure gradient ≥20 mmHg was significantly lower in the S3UR group (1.6% vs 6.2%; p<0.001). Better haemodynamics were observed with the smaller 20 mm and 23 mm S3UR valves. The results were consistent in a matched cohort of patients with S3UR and with S3 (n=618 patients/group). CONCLUSIONS: The S3UR has equivalent procedural complications to the S3 but with lower rates of PVL and significantly better valve performance. The better valve performance of the S3UR, particularly in smaller valve sizes, overcomes the remaining issue of balloon-expandable valves after TAVR.

Impella support for refractory cardiogenic shock accompanied by diabetic ketoacidosis: a case report.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are strongly recommended in patients with heart failure, regardless of the presence of diabetes mellitus. A 74 year-old woman with a reduced left ventricular ejection fraction and diabetes mellitus (the types were unknown), receiving insulin and SGLT2 inhibitor, was hospitalized for altered consciousness with systemic hypotension. Upon admission, she was diagnosed with cardiogenic shock due to diabetic ketoacidosis. Intensive fluid resuscitation under Impella CP support successively improved her metabolic acidosis, preventing worsening pulmonary congestion by mechanically unloading the heart. After hemodynamic stabilization, she was diagnosed with type 1 diabetes mellitus for the first time. She was discharged on day 54 and was followed for 6 months without any recurrences. We must remain vigilant regarding the risk of diabetic ketoacidosis in patients using SGLT2 inhibitors, particularly those on insulin therapy or with diabetes mellitus of unknown types. Impella device shows promise as a circulatory support system in alleviating the left ventricle's workload and averting exacerbated pulmonary congestion, especially in cases where patients necessitate aggressive fluid replacement therapy, such as in the treatment of diabetic ketoacidosis concurrent with compromised cardiac function.

Paradoxical prognostic impact of severe aortic stenosis following trans-catheter aortic valve implantation.

BACKGROUND: Aortic valve replacement is recommended for patients with "very severe" aortic stenosis (AS), irrespective of symptomatic manifestation. Nonetheless, the prognostic ramifications of "very severe" AS, as opposed to "severe" AS, subsequent to trans-catheter aortic valve implantation (TAVI) remain enigmatic. METHODS: We enrolled consecutive patients who received TAVI at our institute between May 2015 and April 2021. We scrutinized the impact of baseline "very severe" AS upon 3-year all-cause death or heart failure hospitalization following TAVI, in comparison to "severe" AS. RESULTS: A total of 239 patients (84.8 ±â€¯5.4 years old, 58 men) were included. Baseline "very severe" AS was observed in 65 (27 %) patients, who exhibited more advanced hypertrophy and higher B-type natriuretic peptide levels compared to those with "severe" AS (p < 0.05 for both). Baseline "very severe" AS was paradoxically associated with higher freedom from the primary endpoint following TAVI compared to those with "severe" AS (p = 0.01). CONCLUSIONS: The presence of baseline "very severe" AS was paradoxically associated with improved clinical outcomes subsequent to TAVI, in contrast to the cases of "severe" AS.

Prognostic impact of insomnia in patients receiving trans-catheter aortic valve replacement.

BACKGROUND: The presence of insomnia exhibits a profound association with diverse cardiovascular pathologies. However, its prognostic implications in patients undergoing transcatheter aortic valve replacement (TAVR) for severe aortic stenosis remain ambiguous. METHODS: This retrospective study enrolled patients who underwent TAVR for severe aortic stenosis at a prominent academic center from 2015 to 2022. The impact of insomnia, operationally defined as the prescription of soporific agents, on the two-year composite primary outcome comprising all-cause mortality and hospital readmissions was scrutinized. RESULTS: A cohort of 345 patients (median age 85 years, 99 males) was encompassed in the analysis. All subjects underwent successful TAVR and subsequent discharge. The presence of insomnia (N = 91) emerged as an independent predictor of the two-year composite endpoint, with an adjusted hazard ratio of 1.66 (95 % confidence interval 1.08-2.57, p = 0.022), significantly delineating the two-year cumulative incidence of the primary endpoint (40 % versus 30 %, p = 0.035). CONCLUSION: Approximately one-fourth of TAVR candidates manifested symptoms of insomnia, a condition autonomously correlated with heightened mortality and morbidity following the TAVR procedure. The optimal strategy for addressing insomnia in TAVR candidates constitutes a paramount consideration for future interventions.

Pre-Existing Left Bundle Branch Block and Clinical Outcomes After Transcatheter Aortic Valve Replacement.

Background: Few reports on pre-existing left bundle branch block (LBBB) in patients undergoing transcatheter aortic valve replacement (TAVR) are currently available. Further, no present studies compare patients with new onset LBBB with those with pre-existing LBBB. Objectives: This study aimed to investigate the association between pre-existing or new onset LBBB and clinical outcomes after TAVR. Methods: Using data from the Japanese multicenter registry, 5,996 patients who underwent TAVR between October 2013 and December 2019 were included. Patients were classified into 3 groups: no LBBB, pre-existing LBBB, and new onset LBBB. The 2-year clinical outcomes were compared between 3 groups using Cox proportional hazards models and propensity score analysis to adjust the differences in baseline characteristics. Results: Of 5,996 patients who underwent TAVR, 280 (4.6%) had pre-existing LBBB, while 1,658 (27.6%) experienced new onset LBBB. Compared with the no LBBB group, multivariable Cox regression analysis showed that pre-existing LBBB was associated not only with a higher 2-year all-cause (adjusted HR: 1.39; 95% CI: 1.06-1.82; P = 0.015) and cardiovascular (adjusted HR: 1.60; 95% CI: 1.04-2.48; P = 0.031) mortality, but also with higher all-cause (adjusted HR: 1.43, 95% CI: 1.07-1.91; P = 0.016) and cardiovascular (adjusted HR: 1.81, 95% CI:1.12-2.93; P = 0.014) mortality than the new onset LBBB group. Heart failure was the most common cause of cardiovascular death, with more heart failure deaths in the pre-existing LBBB group. Conclusions: Pre-existing LBBB was independently associated with poor clinical outcomes, reflecting an increased risk of cardiovascular mortality after TAVR. Patients with pre-existing LBBB should be carefully monitored.

Cardiac Damage in Degenerative Mitral Regurgitation Treated With Transcatheter Mitral Edge-to-Edge Repair.

BACKGROUND: The extent of cardiac damage and its association with clinical outcomes in patients undergoing transcatheter edge-to-edge repair (TEER) for degenerative mitral regurgitation remains unclear. This study was aimed to investigate cardiac damage in patients with degenerative mitral regurgitation treated with TEER and its association with outcomes. METHODS: We analyzed patients with degenerative mitral regurgitation treated with TEER in the Optimized Catheter Valvular Intervention-Mitral registry, which is a prospective, multicenter observational data collection in Japan. The study subjects were classified according to the extent of cardiac damage at baseline: no extravalvular cardiac damage (stage 0), mild left ventricular or left atrial damage (stage 1), moderate left ventricular or left atrial damage (stage 2), or right heart damage (stage 3). Two-year mortality after TEER was compared using Kaplan-Meier analysis. RESULTS: Out of 579 study participants, 8 (1.4%) were classified as stage 0, 76 (13.1%) as stage 1, 319 (55.1%) as stage 2, and 176 (30.4%) as stage 3. Two-year survival was 100% in stage 0, 89.5% in stage 1, 78.9% in stage 2, and 75.3% in stage 3 (P=0.013). Compared with stage 0 to 1, stage 2 (hazard ratio, 3.34 [95% CI, 1.03-10.81]; P=0.044) and stage 3 (hazard ratio, 4.51 [95% CI, 1.37-14.85]; P=0.013) were associated with increased risk of 2-year mortality after TEER. Significant reductions in heart failure rehospitalization rate and New York Heart Association functional scale were observed following TEER (both, P<0.001), irrespective of the stage of cardiac damage. CONCLUSIONS: Advanced cardiac damage is associated with an increased risk of mortality in patients undergoing TEER for degenerative mitral regurgitation. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: UMIN000023653.

Long-term prognostic value of the H2FPEF score in patients undergoing transcatheter aortic valve implantation.

AIMS: A considerable proportion of candidates for transcatheter aortic valve implantation (TAVI) have underlying heart failure (HF) with preserved ejection fraction (HFpEF), which can be challenging for diagnosis because significant valvular heart disease should be excluded before diagnosing HFpEF. This study investigated the long-term prognostic value of the pre-procedural H2FPEF score in patients with preserved ejection fraction (EF) undergoing TAVI. METHODS AND RESULTS: Patients who underwent TAVI between October 2013 and May 2017 were enrolled from the Optimized CathEter vAlvular iNtervention-Transcatheter Aortic Valve Implantation Japanese multicentre registry. After excluding 914 patients, 1674 patients with preserved EF ≥ 50% (median age: 85 years, 72% female) were selected for calculation of the H2FPEF score and were dichotomized into two groups: the low H2FPEF score [0-5 points; n = 1399 (83.6%)] group and the high H2FPEF score [6-9 points; n = 275 (16.4%)] group. Patients with high H2FPEF scores were associated with a higher prevalence of New York Heart Association Functional Class III/IV (59.3% vs. 43.7%, P < 0.001), diabetes (24.4% vs. 18.5%, P = 0.03), and paradoxical low-flow, low-gradient aortic stenosis (15.9% vs. 6.2%, P < 0.001). These patients showed worse prognoses than those with low H2FPEF scores regarding the cumulative 2 year all-cause mortality (26.3% vs. 15.5%, log-rank P < 0.001), cardiovascular mortality (10.5% vs. 5.4%, log-rank P < 0.001), HF hospitalization (16.2% vs. 6.7%, log-rank P < 0.001), and the composite endpoint of cardiovascular mortality and HF hospitalization (23.8% vs. 10.8%, log-rank P < 0.001). After adjustment for several confounders, the high H2FPEF scores were independently associated with increased risk for all-cause mortality [adjusted hazard ratio (HR), 1.48; 95% confidence interval (CI), 1.09-2.00; P = 0.011] and for the composite endpoint of cardiovascular mortality and HF hospitalization (adjusted HR, 1.95; 95% CI, 1.38-2.74; P < 0.001). Subgroup analysis confirmed the excess risk of high H2FPEF scores relative to low H2FPEF scores for the composite endpoint of cardiovascular mortality and HF hospitalization increased with a lower Society of Thoracic Surgeons (STS) score (STS score <8%: adjusted HR, 2.40; 95% CI, 1.50-3.85; P < 0.001; STS score ≥8%: adjusted HR, 1.34; 95% CI, 0.79-2.28; P = 0.28; Pinteraction = 0.030). CONCLUSIONS: The H2FPEF score is useful for predicting long-term adverse outcomes after TAVI, including all-cause mortality, cardiovascular mortality, and HF hospitalization for patients with preserved EF. More aggressive interventions targeting HFpEF in addition to the TAVI procedure might be relevant in patients with high H2FPEF scores, particularly in those with a lower surgical risk.

Enhanced reactivity of Li+@C60 toward thermal [2 + 2] cycloaddition by encapsulated Li+ Lewis acid.

Lithium ion-endohedral fullerene (Li+@C60), a member of the burgeoning family of ion-endohedral fullerenes, holds substantial promise for diverse applications owing to its distinctive ionic properties. Despite the high demand for precise property tuning through chemical modification, there have been only a few reports detailing synthetic protocols for the derivatization of this novel material. In this study, we report the synthesis of Li+@C60 derivatives via the thermal [2 + 2] cycloaddition reaction of styrene derivatives, achieving significantly higher yields of monofunctionalized Li+@C60 compared to previously reported reactions. Furthermore, by combining experimental and theoretical approaches, we clarified the range of applicable substrates for the thermal [2 + 2] cycloaddition of Li+@C60, highlighting the expanded scope of this straightforward and selective functionalization method.

Engineering of IF1 -susceptive bacterial F1 -ATPase.

IF1 , an inhibitor protein of mitochondrial ATP synthase, suppresses ATP hydrolytic activity of F1 . One of the unique features of IF1 is the selective inhibition in mitochondrial F1 (MF1 ); it inhibits catalysis of MF1 but does not affect F1 with bacterial origin despite high sequence homology between MF1 and bacterial F1 . Here, we aimed to engineer thermophilic Bacillus F1 (TF1 ) to confer the susceptibility to IF1 for elucidating the molecular mechanism of selective inhibition of IF1 . We first examined the IF1 -susceptibility of hybrid F1 s, composed of each subunit originating from bovine MF1 (bMF1 ) or TF1 . It was clearly shown that only the hybrid with the ß subunit of mitochondrial origin has the IF1 -susceptibility. Based on structural analysis and sequence alignment of bMF1 and TF1 , the five non-conserved residues on the C-terminus of the ß subunit were identified as the candidate responsible for the IF1 -susceptibility. These residues in TF1 were substituted with the bMF1 residues. The resultant mutant TF1 showed evident IF1 -susceptibility. Reversely, we examined the bMF1 mutant with TF1 residues at the corresponding sites, which showed significant suppression of IF1 -susceptibility, confirming the critical role of these residues. We also tested additional three substitutions with bMF1 residues in α and γ subunits that further enhanced the IF1 -susceptibility, suggesting the additive role of these residues. We discuss the molecular mechanism by which IF1 specifically recognizes F1 with mitochondrial origin, based on the present result and the structure of F1 -IF1 complex. These findings would help the development of the inhibitors targeting bacterial F1 .

Midterm outcomes of transcatheter aortic valve replacement in patients with active cancer.

OBJECTIVES: The clinical outcomes of transcatheter aortic valve replacement (TAVR) in patients with aortic stenosis (AS) and concomitant active cancer remain insufficiently explored. This study aimed to assess the midterm outcomes of TAVR in patients diagnosed with AS and active cancer. METHODS: Data from the OCEAN-TAVI, a prospective Japanese registry of TAVR procedures, was analysed to compare prognoses and clinical outcomes in patients with and without active cancer at the time of TAVR. RESULTS: Of the 2336 patients who underwent TAVR from October 2013 to July 2017, 89 patients (3.8%) had active cancer, whereas 2247 did not. Among patients with active cancer, 49 had limited-stage cancer (stage 1 or 2). The prevalent cancers identified before TAVR were colon (21%), prostate (18%), lung (15%), liver (11%) and breast (9%). Although the periprocedural complications and 30-day mortality rates were comparable between the groups, the 3-year survival rate after TAVR was notably lower in patients with active cancer (64.7%) than in those without active cancer (74.7%; p=0.016). Nevertheless, the 3-year survival rate of patients with limited-stage cancer (stage 1 or 2) did not significantly differ from those without cancer (70.6% vs 74.7%, p=0.50). CONCLUSIONS: The patients with active cancer exhibited significantly reduced midterm survival rates. However, no distinct disparity existed in those with limited-stage cancer (stage 1 or 2). Although TAVR is a viable treatment in patients with AS with active cancer, the type and stage of cancer and prognosis should be carefully weighed in the decision-making process.

Prognostic impact of residual pulmonary congestion assessed by remote dielectric sensing system in patients admitted for heart failure.

AIMS: Remote dielectric sensing (ReDS) represents a contemporary non-invasive technique reliant on electromagnetic energy to quantify pulmonary congestion. Its prognostic significance within the context of heart failure (HF) patients remains elusive. This study aimed to assess the prognostic implications of residual pulmonary congestion, as gauged by the ReDS system, among patients admitted due to congestive HF. METHODS AND RESULTS: We enrolled hospitalized HF patients who underwent ReDS assessments upon admission and discharge in a blinded manner, independent of attending physicians. We evaluated the prognostic impact of the ReDS ratio between admission and discharge on the primary outcome, which encompassed all-cause mortality and HF-related re-hospitalizations. A cohort of 133 patients (median age 78 [72, 84] years, 78 male [59%]) was included. Over a median observation period of 363 days post-index discharge, an escalated ReDS group (ReDS ratio > 100%), determined through statistical calculation, emerged as an independent predictor of the primary outcome, exhibiting an adjusted hazard ratio of 4.37 (95% confidence interval 1.13-16.81, P = 0.032). The cumulative incidence of the primary outcome was notably higher in the increased ReDS group compared with the decreased ReDS group (50.1% vs. 8.5%, P = 0.034). CONCLUSIONS: Elevated ReDS ratios detected during the index hospitalization could serve as a promising prognostic indicator in HF patients admitted for treatment. The clinical ramifications of ReDS-guided HF management warrant validation in subsequent studies.

Predictive Factors of Cardiac Mortality Following TEER in Patients with Secondary Mitral Regurgitation.

Background: Transcatheter edge-to-edge mitral valve repair (TEER) has emerged as a viable approach to addressing substantial secondary mitral regurgitation. In the contemporary landscape where ultimate heart failure-specific therapies, such as cardiac replacement modalities, are available, prognosticating a high-risk cohort susceptible to early cardiac mortality post-TEER is pivotal for formulating an effective therapeutic regimen. Methods: Our study encompassed individuals with secondary mitral regurgitation and chronic heart failure enlisted in the multi-center (Optimized CathEter vAlvular iNtervention (OCEAN)-Mitral registry. We conducted an assessment of baseline variables associated with cardiac death within one year following TEER. Results: Amongst the 1517 patients (median age: 78 years, 899 males), 101 experienced cardiac mortality during the 1-year observation period after undergoing TEER. Notably, a history of heart failure-related admissions within the preceding year, utilization of intravenous inotropes, and elevated plasma B-type natriuretic peptide levels emerged as independent prognosticators for the primary outcome (p < 0.05 for all). Subsequently, we devised a novel risk-scoring system encompassing these variables, which significantly stratified the cumulative incidence of the 1-year primary outcome (16%, 8%, and 4%, p < 0.001). Conclusions: Our study culminated in the development of a new risk-scoring system aimed at predicting 1-year cardiac mortality post-TEER.

Label-Free Liquid Chromatography-Mass Spectrometry Quantitation of Relative N- and O-Glycan Concentrations in Human Milk in Japan.

Human milk is abundant in carbohydrates and includes human milk oligosaccharides (HMOs) and N/O-glycans conjugated to proteins. HMO compositions and concentrations vary in individuals according to the maternal secretor status based on the fucosyltransferase 2 genotype; however, the profile of N/O-glycans remains uninvestigated because of the analytical complexity. Herein, we applied a label-free chromatography-mass spectrometry (LC-MS) technique to elucidate the variation in the composition and concentration of N/O-glycans in human milk. We used label-free LC-MS to relatively quantify 16 N-glycans and 12 O-glycans in 200 samples of Japanese human milk (1-2 months postpartum) and applied high performance anion exchange chromatography with pulsed amperometric detection to absolutely quantify the concentrations of 11 representative HMOs. Cluster analysis of the quantitative data revealed that O-glycans and several HMOs were classified according to the presence or absence of fucose linked to galactose while N-glycans were classified into a different group from O-glycans and HMOs. O-glycans and HMOs with fucose linked to galactose were more abundant in human milk from secretor mothers than from nonsecretor mothers. Thus, secretor status influenced the composition and concentration of HMOs and O-glycans but not those of N-glycans in human milk.

Left Atrial Stiffness Increases after Trans-Catheter Atrial Septal Closure.

BACKGROUND: Transcatheter atrial septal closures for secundum atrial septal defects (ASD) have demonstrated favorable clinical outcomes. However, the impact of device implantation on the stiffness of the left atrium remains unclear. METHOD: Patients with secundum ASD undergoing transcatheter closure and follow-up right heart catheterization at six months were included. We investigated the relationship between post-procedural (E/e' ratio)/(LAs strain) ratio, an index of left atrial stiffness, and baseline characteristics, including echocardiographic and hemodynamic parameters. RESULTS: Forty patients were included (median 69 (56, 75) years, 12 men, and pulmonary systemic flow ratio 2.27 (1.96, 2.86)). Trans-catheter ASD closure was successfully performed without any major complications, accompanying a significant reduction in right ventricular to left ventricular size ratio from 1.04 (0.87, 1.13) to 0.74 (0.66, 0.86) (p < 0.01). The (E/e' ratio)/(LAs strain) ratio was markedly elevated the day after the procedure and was further increased 6 months later (before: 0.25 (0.17, 0.34), 1 day later: 0.34 (0.27, 0.50), 6 months later: 0.43 (0.27, 0.76), p < 0.01). The groups with higher (E/e' ratio)/(LAs strain) ratios at 6 months had significantly more severe heart failure conditions including lower cardiac output and higher plasma B-type natriuretic peptides. CONCLUSIONS: Patients undergoing transcatheter ASD closure experienced improvement in hemodynamics and clinical symptoms but an elevation in left atrial stiffness post-procedure. The clinical ramifications of this finding, particularly during the longer-term observation period subsequent to ASD closure, warrant further investigation.

Mice Recognise Mice in Neighbouring Rearing Cages and Change Their Social Behaviour.

Mice are social animals that change their behaviour primarily in response to visual, olfactory, and auditory information from conspecifics. Rearing conditions such as cage size and colour are important factors influencing mouse behaviour. In recent years, transparent plastic cages have become standard breeding cages. The advantage of using a transparent cage is that the experimenter can observe the mouse from outside the cage without touching the cage. However, mice may recognise the environment outside the cage and change their behaviour. We speculated that mice housed in transparent cages might recognise mice in neighbouring cages. We used only male mice in this experiment. C57BL/6 mice were kept in transparent rearing cages with open lids, and the cage positions were maintained for 3 weeks. Subsequently, we examined how mice behaved toward cagemate mice, mice from neighbouring cages, and mice from distant cages. We compared the level of interest in mice using a social preference test. Similar to previous reports, subject mice showed a high degree of interest in unfamiliar mice from distant cages. By contrast, subject mice reacted to mice from neighbouring cages as familiar mice, similar to cagemate mice. This suggests that mice housed in transparent cages with open lids perceive the external environment and identify mice in neighbouring cages. Researchers should pay attention to the environment outside the mouse cage, especially for the social preference test.