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The field of aging biology, which aims to extend healthy lifespans and prevent age-related diseases, has turned its focus to the Callithrix jacchus (common marmoset) to understand the aging process better. This study utilized magnetic resonance imaging (MRI) to non-invasively analyze the brains of 216 marmosets, investigating age-related changes in brain structure; the relationship between body weight and brain volume; and potential differences between males and females. The key findings revealed that, similar to humans, Callithrix jacchus experiences a reduction in total intracranial volume, cortex, subcortex, thalamus, and cingulate volumes as they age, highlighting site-dependent changes in brain tissue. Notably, the study also uncovered sex differences in cerebellar volume. These insights into the structural connectivity and volumetric changes in the marmoset brain throughout aging contribute to accumulating valuable knowledge in the field, promising to inform future aging research and interventions for enhancing healthspan., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Type A acute aortic dissection (AAD) complicated by coronary malperfusion is a life-threatening disease. In the present study, we compared the clinical characteristics and prognostic impact of treatment strategies including surgical treatment and percutaneous coronary intervention (PCI) in type A AAD patients with RCA and LCA involvement., Methods: This multicenter registry included 220 patients with type A AAD and either RCA or LCA involvement. Treatment strategies were left to treating physicians. The primary endpoint was in-hospital death., Results: Of 220 patients, 115 (52.3%) and 105 (47.7%) had RCA and LCA involvement. Patients with LCA involvement were more1 likely to present with Killip class IV on admission than those with RCA involvement. Coronary angiography was performed in 52 of 220 (23.6%) patients, among whom 39 (75.0%) underwent subsequent PCI. During the hospitalization, 93 (42.3%) patients died. Patients with LCA involvement had an increased risk of in-hospital mortality compared to those with RCA involvement (54.3% vs. 31.3%, p < 0.001). In patients with RCA involvement, multivariable analysis identified Killip class IV and no surgical treatment as predictors of in-hospital death, while PCI and surgical treatment were indicated as factors associated with lower in-hospital mortality in patients with LCA involvement., Conclusions: The rates of RCA and LCA involvement were similar in type A AAD. Immediate PCI as a bridge to subsequent surgical treatment might improve survival in patients with type A AAD complicated by coronary malperfusion, especially in those with LCA involvement., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Several predictors are available to guide patient selection for transcatheter aortic valve replacement (TAVR) to achieve better outcomes, and the essential frailty toolset (EFT) has been reported as one of those predictors. This study investigated whether a modified EFT could independently predict all-cause mortality following TAVR., Methods: The study population comprised 176 consecutive patients with severe aortic stenosis whose frailty was assessed with a modified EFT prior to TAVR at the Sakakibara Heart Institute between 2013 and 2018. The primary endpoint was all-cause mortality following TAVR. To understand the association between the modified EFT and all-cause mortality, multivariate Cox regression analysis was performed. In addition, to understand its predictive performance, we conducted a receiver operating characteristic (ROC) analysis., Results: Patients were elderly, relatively frail, and were likely to have significant heart failure symptoms. By the modified EFT definition, 40 patients (22.7%) were considered frail. With a median follow up of 1145 days, all-cause mortality at 1, 2, and 3 years was 6.2%, 10.2%, and 18.3%, respectively. Patients assessed as more frail on the clinical frailty scale had higher modified EFT scores. In ROC analysis, the area under the curve for predicting all-cause mortality at 1, 2, and 3 years was 0.79 [95% confidence interval (CI) 0.68-0.90]; 0.74 (95% CI 0.62-0.84); and 0.67 (95% CI 0.56-0.79), respectively, with the best cut-off modified EFT score of 1/2., Conclusions: The modified EFT score was independently associated with all-cause mortality and had excellent predictive performance for all-cause mortality at 1 year., (Copyright © 2020 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background: Several predictors are available to guide patient selection for transcatheter aortic valve replacement (TAVR) to achieve better outcomes, and cognitive function is one of these predictors. This study investigated whether the revised Hasegawa's dementia scale (HDS-R) could independently predict mid-term outcomes following TAVR., Methods: The study population comprised 455 patients with severe aortic stenosis who underwent TAVR at the Sakakibara Heart Institute between 2010 and 2018. The primary endpoint was all-cause mortality following TAVR. Patients were dichotomized into two groups according to the receiver operating characteristic analysis (HDS-R ≤23 and >23)., Results: Patients with HDS-R ≤23 were older, were more frail, were more likely to have peripheral artery disease, had lower serum albumin levels, had lower ejection fractions, and had smaller aortic valve areas than those with HDS-R >23. By definition, 81 of the 455 patients (17.8%) were considered to have dementia (HDS-R ≤20) before TAVR. The discriminatory performance for predicting all-cause mortality at 3 years was greater for dichotomization with 23/24 than that with 20/21 [area under the curve (AUC): 0.63, 95% confidence interval (CI): 0.50-0.76, p=0.047 vs. AUC: 0.52, 95% CI: 0.39-0.65, p=0.713]. From the Kaplan-Meier analysis, patients with HDS-R ≤23 had higher mortality rates than those with HDS-R >23 (86.8±3.3% and 75.4±4.7% at 3 years, respectively; log-rank p=0.001). The multivariate Cox regression analysis found that the HDS-R was independently associated with all-cause mortality (hazard ratio 2.11, 95% CI 1.21-3.69, p=0.008)., Conclusions: Patients with HDS-R ≤23 were sicker and more frail and had greater cognitive impairment. Additionally, HDS-R could independently predict mid-term outcomes following TAVR., (Copyright © 2019 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

We used a bivariate animal model to investigate the genetic correlations between yield traits or days open (DO) as characters measured in cows and semen production traits as characters measured in bulls. Lactation records of 305-day milk, fat, and protein yields, and DO, from 386 809 first-lactation Holstein cows in Hokkaido, Japan, that calved between 2008 and 2014 were used. Semen production records were collected between 2005 and 2014 and included volume per ejaculate (VOL), sperm concentration (CON), number of sperm per ejaculate (NUM), progressive motility index of sperm (MOT), and MOT after freeze-thawing (A-MOT). Number of sperm per ejaculate was log-transformed into a NUM score (NUMS). A total of 30 373 semen production records from 1196 bulls were obtained. The pedigree file used for analysing the records was involving 885 345 animals. Heritability was estimated for VOL (0.42), CON (0.12), NUMS (0.37), MOT (0.08), and A-MOT (0.11). Weak and negative genetic correlations were recorded between yield traits measured in cows and VOL, CON or NUMS measured in bulls. Moderate and negative genetic correlations were obtained between DO and MOT (-0.42) or A-MOT (-0.43). Selection focused on MOT or A-MOT measured in bulls may therefore improve DO measured in cows.

Pregnancy and calving are elements indispensable for dairy production, but the daily milk yield of cows decline as pregnancy progresses, especially during the late stages. Therefore, the effect of stage of pregnancy on daily milk yield must be clarified to accurately estimate the breeding values and lifetime productivity of cows. To improve the genetic evaluation model for daily milk yield and determine the effect of the timing of pregnancy on productivity, we used a test-day model to assess the effects of stage of pregnancy on variance component estimates, daily milk yields and 305-day milk yield during the first three lactations of Holstein cows. Data were 10 646 333 test-day records for the first lactation; 8 222 661 records for the second; and 5 513 039 records for the third. The data were analyzed within each lactation by using three single-trait random regression animal models: one model that did not account for the stage of pregnancy effect and two models that did. The effect of stage of pregnancy on test-day milk yield was included in the model by applying a regression on days pregnant or fitting a separate lactation curve for each days open (days from calving to pregnancy) class (eight levels). Stage of pregnancy did not affect the heritability estimates of daily milk yield, although the additive genetic and permanent environmental variances in late lactation were decreased by accounting for the stage of pregnancy effect. The effects of days pregnant on daily milk yield during late lactation were larger in the second and third lactations than in the first lactation. The rates of reduction of the 305-day milk yield of cows that conceived fewer than 90 days after the second or third calving were significantly (P<0.05) greater than that after the first calving. Therefore, we conclude that differences between the negative effects of early pregnancy in the first, compared with later, lactations should be included when determining the optimal number of days open to maximize lifetime productivity in dairy cows.

Aims: Landiolol hydrochloride, an ultra-short-acting highly cardio-selective β-1 blocker, has become useful for various medical problems. Recent studies have demonstrated that co-treatment with landiolol protects against acute lung injury and cardiac dysfunction in rats of lipopolysaccharide (LPS)-induced systemic inflammation, and was also associated with a significant reduction in serum levels of the inflammation mediator HMGB-1 and histological lung damage. Endothelin (ET)-1, a potent vasoconstrictor, has been implicated in pathogenesis of sepsis and sepsis-induced multiple organ dysfunction syndrome. Here, we investigated whether landiolol hydrochloride can play important roles in ameliorating LPS-induced alterations in cardiac ET system of septic rats., Main Methods: Eight-week-old male Wistar rats were administered LPS only for 3 h and the rest were treated with LPS as well as with landiolol non-stop for 3 h., Key Findings: At 3 h after LPS (only) administration, circulatory tumor necrosis factor (TNF)-α level, blood lactate concentration and percentage of fractional shortening of heart were significantly increased. In addition, LPS induced a significant expression of various components of cardiac ET-1 system compared to control. Finally, treatment of LPS-administered rats with landiolol for 3 h normalized LPS-induced blood lactate levels and cardiac functional compensatory events, without altering levels of plasma TNF-α and ET-1. Most strikingly, landiolol treatment significantly normalized various components of cardiac ET-1 signaling system in septic rat., Significance: Taken together, these data led us to conclude that landiolol may be cardio-protective in septic rats by normalizing the expression of cardiac vasoactive peptide such as ET, without altering the circulatory levels of inflammatory cytokines., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Aims: Endothelin (ET)-1 is the best known potent vasoconstrictor and has been implicated in pathogenesis of sepsis-associated acute kidney injury (AKI) in human or lipopolysaccharide (LPS)-induced AKI in animal models. We have previously shown that ET-1 is highly up-regulated in renal tissues and in plasma after LPS administration. Here, we investigated whether landiolol hydrochloride, an ultra-short-acting beta-blocker, can play an important role in ameliorating levels of LPS-induced up-regulation of renal HIF-1α-ET-1 system and inflammatory cytokines in a rat model of endotoxemia., Main Methods: Male Wistar rats at 8 weeks of age were either administered with: a) lipopolysaccharide (LPS) only for three hours (3 h) or b) LPS, followed by continuous administration of landiolol for 3 h; c) third group was only treated with vehicle., Key Findings: At 3 h after LPS administration there was: a) minimal injury in kidney tissues; b) circulatory levels of creatinine, blood urea nitrogen and NGAL increased and c) expression of inflammatory cytokines, such as TNF-α, IL-6 and iNOS increased at the level of both circulatory and renal tissues. In addition, LPS significantly induced renal expression of ET-1 and HIF-1α compared to control. Finally, treatment of LPS-administered rats with landiolol for 3 h normalized elevated serum markers of renal injury and up-regulated levels of renal HIF-1α-ET-1 system with normalization of TNF-α., Significance: Taken together, these data led us to conclude that landiolol ameliorates the up-regulation of HIF-1α-ET-1 system in minimally morphologically-injured kidney and normalizes biomarkers of renal injury in early hours of endotoxemia of a rat model., (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)

The aim of this study was to estimate genetic correlations between milk yield, somatic cell score (SCS), mastitis, and claw and leg disorders (CLDs) during first lactation in Holstein cows by using a threshold-linear random regression test-day model. We used daily records of milk, fat and protein yields; somatic cell count (SCC); and mastitis and CLD incidences from 46 771 first-lactation Holstein cows in Hokkaido, Japan, that calved between 2000 and 2009. A threshold animal model for binary records (mastitis and CLDs) and linear animal model for yield traits were applied in our multiple trait analysis. For both liabilities and yield traits, additive genetic effects were used as random regression on cubic Legendre polynomials of days on milk. The highest positive genetic correlations between yields and disease incidences (0.36 for milk and mastitis, 0.56 for fat and mastitis, 0.24 for protein and mastitis, 0.32 for milk and CLD, 0.44 for fat and CLD and 0.31 for protein and CLD) were estimated at about the time of peak milk yield (36 to 65 days in milk). Selection focused on early lactation yield may therefore increase the risk of mastitis and CLDs. The positive genetic correlations of SCS with mastitis or CLD incidence imply that selection to reduce SCS in the early stages of lactation would decrease the incidence of both mastitis and CLD.

We investigated the relationships between conception rates (CRs) at first service in Japanese Holstein heifers (i.e. animals that had not yet had their first calf) and cows and their test-day (TD) milk yields. Data included records of artificial insemination (AI) for heifers and cows that had calved for the first time between 2000 and 2008 and their TD milk yields at 6 through 305 days in milk (DIM) from first through third lactations. CR was defined as a binary trait for which first AI was a failure or success. A threshold-linear animal model was applied to estimate genetic correlations between CRs of heifers or cows and TD milk yield at various lactation stages. Two-trait genetic analyses were performed for every combination of CR and TD milk yield by using the Bayesian method with Gibbs sampling. The posterior means of the heritabilities of CR were 0.031 for heifers, 0.034 for first-lactation cows and 0.028 for second-lactation cows. Heritabilities for TD milk yield increased from 0.324 to 0.433 with increasing DIM but decreased slightly after 210 DIM during first lactation. These heritabilities from the second and third lactations were higher during late stages of lactation than during early stages. Posterior means of the genetic correlations between heifer CR and all TD yields were positive (range, 0.082 to 0.287), but those between CR of cows and milk yields during first or second lactation were negative (range, -0.121 to -0.250). Therefore, during every stage of lactation, selection in the direction of increasing milk yield may reduce CR in cows. The genetic relationships between CR and lactation curve shape were quite weak, because the genetic correlations between CR and TD milk yield were constant during the lactation period.