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Background: Left atrial (LA) function and strain patterns by magnetic resonance imaging (MRI) have been investigated as markers of several cardiovascular pathologies, including cardiac amyloidosis (CA). However, associations with clinical outcomes have not been investigated. Purpose: To compare LA function and strain by MRI in CA patients to a matched cohort of patients without cardiovascular disease (CVD) and evaluate the association with long‐term clinical outcomes in CA patients. Study Type: Retrospective case control. Population: A total of 51 patients with CA and 51 age‐, gender‐, and race‐matched controls without CVD who underwent MRI in sinus rhythm. Field Strength/Sequence: ECG‐gated balanced steady‐state free precession sequence at 1.5 T. Assessment: All measurements were completed by one investigator (M.M.B.). LA function and strain parameters were measured including LA indexed minimum and maximum volumes, LA reservoir (R), contractile (CT), and conduit (CD) strain. We compared groups after adjusting for age, hypertension, New York Heart Association class, modified staging system (troponin‐I, BNP, estimated GFR) and left ventricular ejection fraction (LVEF) for an endpoint of all‐cause mortality and a composite endpoint of heart failure hospitalization (HFH) or death. Statistical Tests: Differences between groups were evaluated with t tests for continuous variables or χ2 tests for categorical variables. A multivariable regression model was used to assess the associations of the P values—two‐sided tests—<0.05 were considered statistically significant. Results: CA patients with median follow up of 4.9 (8.5) months had significantly lower LA strain and higher LA volumes in comparison to the matched cohort. In the multivariable analysis, only LVEF was significantly associated with death while ƐCT (OR 0.6, CI: 0.41–0.89), indexed minimum LA volume (OR 1.06, CI: 1.02–1.13) and indexed maximum LA volume (OR 1.08, CI: 1.01–1.15) were significantly associated with the composite outcome of death or HFH. Conclusion: In this retrospective study of CA patients, ƐCT and indexed minimum and maximum LA volumes were significantly associated with the composite outcome of death or HFH. Evidence Level: 3 Technical Efficacy: Stage 3 [ABSTRACT FROM AUTHOR]

2-hydroxy-6-tridecylbenzoic acid is alkylsalicylic acid monomer compound, abundantly existed in the ginkgo biloba extracts, however, the underlying mechanism of its anti-migration and anti-invasion effects in triple-negative breast cancer (TNBC) is not clear. Here, 2-hydroxy-6 -tridecylbenzoic acid inhibited MDA-MB-231 and 4 T-1 cells growth without toxicity to MCF-10A normal breast cells. Meanwhile, 2-hydroxy-6-tridecylbenzoic acid inhibited cells migration and invasion as well as EMT with the increase of E-cadherin expression accompanied by the decrease of N-cadherin, Vimentin, Snail, MMP-2 and MMP-9 expression. The inhibition was further demonstrated by the enhancement of cytochrome P450 (CYP) 1B1 expression through the activation of AMP activated protein kinase (AMPK) in MDA-MB-231 and 4 T-1 cells. Silencing of CYP1B1 and AMPK with siRNA blocked the inhibitory effects of migration and invasion, and reversed the EMT related genes. These findings may provide a novel mechanism of the 2-hydroxy-6-tridecylbenzoic acid as a molecular-targeted therapeutic drug for TNBC patients. [ABSTRACT FROM AUTHOR]

Purpose: Smoking is a major public health issue, and its effect on cardiovascular outcomes is well established. This study evaluates the impact of donor smoking on heart transplant (HT) outcomes. Methods: HT recipients between January 1, 2005, and December 31, 2016, with known donor smoking status were queried from the International Society of Heart and Lung Transplantation (ISHLT) registry. The primary outcome was all‐cause mortality, and secondary endpoints were graft failure, acute rejection, and cardiac allograft vasculopathy. We utilized propensity‐score matching to identify cohorts of recipients with and without a history of donor smoking. Hazard ratios for post‐transplant outcomes for the matched sample were estimated from separate Cox proportional hazard models. Results: Of 26 390 patients in the cohort, 18.9% had history of donor smoking. Donors with history of smoking were older, predominantly male and had higher incidence of diabetes, hypertension, cocaine use, and "high‐risk" status. In propensity‐matched analysis, recipients with a history of donor smoking had increased risk of death (HR 1.11, 95% CI 1.03‐1.20) and higher risk of graft failure (HR 1.11, 95% CI 1.03‐1.20). Conclusion: Donor smoking was associated with increased mortality and higher incidence of graft failure following HT. Consideration of donor smoking history is warranted while evaluating donor hearts. [ABSTRACT FROM AUTHOR]

In Brief: During the morula to blastocyst transformation, polarity establishment in outer cells is a prerequisite for trophectoderm lineage specification. This study reveals the roles of polarity proteins PATJ and MPDZ in trophectoderm lineage fate decision., Abstract: In mouse preimplantation embryos, cell polarity plays a crucial role in the first lineage specification. PATJ and its homolog MPDZ are the main members of CRB-PALS1-PATJ (CRUMBS-Protein associated with Lin7 1-Pals-associated tight junction protein) apical polarity complex. They act as adaptor proteins connecting CRB-PALS1 and tight junction proteins, making them essential for cell polarization and stabilization of apical junctions. However, their roles in regulating trophectoderm differentiation and blastocyst development remain unclear. In this study, PATJ and/or MPDZ were downregulated by the microinjection of specific RNA interference constructs into zygotes. Downregulation of PATJ alone did not severely affect early embryonic development and trophectoderm lineage differentiation although it slowed down the blastocyst formation. Depletion of PATJ and MPDZ did not affect compaction and morula development but impaired blastocyst formation. Furthermore, the expression of trophectoderm-specific transcription factors and trophoblast differentiation was compromised in the absence of PATJ/MPDZ. These abnormalities might result from the breakdown of apical domain in the outer cells of the embryo. The loss of PATJ/MPDZ caused the breakdown of CRB and PAR polarity complexes as well as deficiencies in tight junctions and actin filaments. These defects led to ectopic activation of Hippo signaling in the outer cells of developing embryos, ultimately suppressing Cdx2 expression and trophectoderm differentiation. Altogether, PATJ and MPDZ are essential for trophectoderm lineage differentiation and normal blastocyst morphogenesis via the regulation of the establishment of apical domain, formation of tight junctions, phosphorylation and localization of YAP, and expression of trophectoderm-specific transcription factors.

Gastrointestinal bleeding (GIB) is a common cause of morbidity among patients supported by left ventricular assist devices (LVADs). The aim of this study was to identify if pre-LVAD right ventricular (RV) dysfunction is associated with risk of GIB after LVAD implantation. Of 398 patients implanted with LVADs between July 2008 and July 2016, 130 (33%) developed GIB at a median of 2.6 months following LVAD implantation. Arteriovenous malformations (AVMs) were found in 42 (34%) GIB patients. Patients with GIB were older and more likely to have hypertension, diabetes, and ischemic cardiomyopathy. On pre-LVAD echocardiography, GIB patients had increased RV diastolic dimension (4.7 ± 0.8 vs. 4.4 ± 0.9 cm, p = 0.02), a higher rate of greater than mild tricuspid valve (TV) regurgitation (73 [60%] vs. 120 [47%], p = 0.006), and underwent TV repair more often (38 [30%] vs. 43 [16%], p = 0.0006) during LVAD implantation. After multivariable adjustment, preoperative greater than mild RV enlargement (hazard ratio [HR] 2.32, 95% CI 1.12-5.03; p = 0.03), TV regurgitation (HR 1.83, CI 1.02-3.44; p = 0.01), and TV repair (HR 3.76, confidence interval [CI] 1.02-4.44; p = 0.01) remained associated with risk of GIB. This finding was driven by the AVM-GIB subgroup. Preoperative RV enlargement and TV regurgitation are associated with post-LVAD AVM-related GIB., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2020.)

Mice may share similar mechanism with human underlying reproductive toxicity induced by di(2-ethylhexyl) phthalate (DEHP), which is not supposed to be associated with decreased testicular testosterone. Pregnant mice were exposed to DEHP by gavage, with the dosage regime beginning at human relevant exposure level. After in utero DEHP exposure, loss of Sertoli cells and germ cells were observed in the male pups at postnatal days 21. And SRY-related HMG box 9 (SOX9), Fibroblast growth factor-9 (FGF9), and Double-sex and Mab-3 related transcripttion factor 1 (DMRT1) proteins were significantly downregulated by DEHP at 2 mg/kg/d and above, suggesting the depression of Sertoli cell differentiation. The repression of Sox9 genes expression was supported by whole-mount in situ hybridization and real-time real-time-quantitative PCR. The expressions of Cyp11α1 and Star were not significantly affected by in utero DEHP exposure, indicating the absence of effects on testosterone biosynthesis. Furthermore, the testosterone-independent pathway regulating Sertoli cells differentiation was disturbed in fetus by DEHP at 2 mg/kg/d and above during the critical time window of sex determination, involving Gadd45g → Gata4/Fog2 → Sry → Sox9 → Fgf9 The results suggest that in utero DEHP exposure damaged Sertoli cells in the postnatal life of mice offspring via disturbance of the differentiation regulating pathway, potentially inducing declines in spermatogenesis., (© The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Objective: Our study aimed to investigate the association of ABCA1 polymorphisms with plasma lipid variability and CHD risk in the Chinese Han population., Methods: 754 CHD patients and 760 controls were included in this case-control study. Three SNPs (rs363717, rs4149339, and rs4149338) in ABCA1 3'UTR and one nonsynonymous SNP (rs2230808) in ABCA1 exon 35 were selected and genotyped. The analysis of genetic data was performed using the SNPstats program and the SPSS17.0 software., Results: Significant associations were observed between SNP rs363717 and CHD risk under different genetic models before or after Bonferroni corrections (codominant model: OR = 0.70, P = 0.003 for AG vs. AA; dominant model: OR = 0.71, P = 0.003 for GG + AG vs. AA). The nonsynonymous SNP rs2230808 was associated with higher total cholesterol levels (P = 0.047). The GCC haplotype (consisting of alleles of SNPs rs363717, rs4149339, and rs4149338) was associated with a decreased risk of CHD (OR = 0.8, P = 0.027). Three ABCA1 SNPs interacted with high triglyceride levels to increase CHD risk (P values of interactions were 0.010 for rs363717, 0.010 for rs4149339, and 0.020 for rs4149338, respectively)., Conclusions: Our results suggest that ABCA1 polymorphisms influence plasma lipid variability and CHD risk. ABCA1 polymorphisms could also modify the effects of plasma lipids on CHD risk.

Background: Nuclear receptor coactivator 2 (NCOA2) gene plays an important role in adipogenesis and lipid metabolism. NCOA2 gene null mice exhibited less fat accumulation and lower serum lipid levels, and were protected against obesity. Few studies are known to have analyzed the association of NCOA2 gene single nucleotide polymorphisms with obesity and serum lipid profile. Our study aimed to evaluate the association of NCOA2 gene polymorphisms with the risk of obesity and dyslipidemia in the Chinese Han population., Methods: Two NCOA2 gene polymorphisms (rs41391448 and rs10504473) were selected and genotyped in a Chinese Han cohort with 529 participants. The effect of different genotypes on BMI and serum lipid levels (TG, TC, LDL-C and HDL-C) was performed by the analysis of covariance. Association of NCOA2 polymorphisms with obesity and dyslipidemia was assessed by odds ratios (OR) and 95% confidence intervals (CI) under the unconditional logistic regression analysis., Results: Significant association was observed between rs10504473 polymorphism and obesity under the recessive model (OR = 1.88, 95% CI 1.02-3.45, P = 0.047; adjusted OR = 1.87, 95% CI 1.02-3.44, P = 0.048). However, no association remained significant after Bonferroni correction., Conclusion: Our study suggests a possible association between NCOA2 rs10504473 polymorphism and obesity, and this SNP may influence the susceptibility of obesity in the Chinese Han population.