The mammary gland is a sensitive pubertal target in CD-1 and C57Bl/6 mice following perinatal perfluorooctanoic acid (PFOA) exposure

Perfluorooctanoic acid (PFOA) is a developmental toxicant in mice, with varied strain outcomes depending on dose and period of exposure. The impact of PFOA on female mouse pubertal development at low doses (≤1 mg/kg) has yet to be determined. Therefore, female offspring from CD-1 and C57Bl/6 dams exposed to PFOA, creating serum concentrations similar to humans, were examined for pubertal onset, including mammary gland development. Pups demonstrated a shorter PFOA elimination half-life than that reported for adult mice. Prenatal exposure to PFOA caused significant mammary developmental delays in female offspring in both strains. Delays started during puberty and persisted into young adulthood; severity was dose-dependent. Also an evaluation of female serum hormone levels and pubertal timing onset revealed no effects of PFOA compared to controls in either strain. These data suggest that the mammary gland is more sensitive to early low level PFOA exposures compared to other pubertal endpoints, regardless of strain.     

Impact of serum uric acid on subclinical myocardial injury in general population

Background and aimsHyperuricemia is widely thought as a risk factor for myocardial infarction (MI) and all-cause mortality; however, the relation of serum uric acid (sUA) and subclinical myocardial injury (SCeMI) remains unclear. We hypothesize that sUA is associated with subclinical myocardial injury.Methods and resultsA total of 5880 adult individuals (57.9 ± 13.0 years, 54.23% women) without known cardiovascular disease from National Health and Nutrition Examination Survey (NHANES) III were included. Determined by Cardiac Infarction Injury Score (CIIS) from 12-lead electrocardiogram, SCeMI was defined by CIIS ≥10 units. The relationship between sUA and SCeMI was analyzed by using logistic regression models and the smooth curve fitting. Subgroup analyses were conducted. After adjusting for potential confounding variables, the smooth curve fitting revealed a non-linear relationship between sUA level and SCeMI. When sUA was above the inflection point 266.5 μmol/L, each 100 unit increase in sUA increase the risk of SCeMI by 15%. In women group, when sUA>340.3 μmol/L, each 100 unit increase in sUA increase the risk of SCeMI by 71%, but no significant correlation was observed in men group.ConclusionsOur findings confirm that sUA is an independent risk factor for subclinical myocardial injury after adjusting for potential confounding variables, and existence of such an association in women only, which require more random control trials to confirm the strategy of cardiovascular disease prevention based on sUA reduction in female.     

Subclinical and clinical atherosclerosis in non-alcoholic fatty liver disease is associated with the presence of hypertension

Background and aimsNon-alcoholic fatty liver disease (NAFLD) is associated with increased cardiovascular (CV) risk. However, it is unclear whether NAFLD contributes independently to the development of CV disease. Our study aimed at assessing the differences in several indices of atherosclerosis, arterial stiffness and cardiac morphology among patients with isolated NAFLD, isolated hypertension (HT) or a combination of the two conditions.Methods and resultsA total of 169 participants (mean age = 50.4 ± 10.2 yrs; males = 73.6%) were divided according to the presence of NAFLD and HT into three groups: only NAFLD (55 patients), only HT (49 patients), and NAFLD + HT (65 patients). Exclusion criteria were a BMI≥35 kg/m² and a diagnosis of diabetes mellitus. Carotid ultrasonography was performed to measure markers of atherosclerosis and arterial stiffness. Cardiac remodeling was analyzed using echocardiography. The prevalence of subclinical and overt atherosclerosis was significantly higher in the NAFLD + HT patients as compared to the other two groups (atherosclerotic plaques: 43.1%, 10.9%, and 22.4% (p < 0.001) in NAFLD + HT, NAFLD, and HT groups, respectively). No differences were found among indices of arterial stiffening and cardiac remodeling across the three groups. In multivariate regression analysis, the coexistence of NAFLD and HT was an independent risk factor for overt atherosclerosis (OR = 4.88, CI 95% 1.14–20.93), while no association was found when either NAFLD or HT was considered alone.ConclusionOvert atherosclerosis was significantly present only in NAFLD + HT patients, but not in patients with isolated NAFLD. This implies that the impact of NAFLD on vascular structure and function could depend on the coexistence of other major CV risk factors, such as HT.     

Relation of genetic polymorphisms in microRNAs with diastolic and systolic function in type 2 diabetes mellitus

Background and aimsType 2 diabetes mellitus (T2DM) has high risk of developing cardiac dysfunction, increasing of either cardiovascular death or hospitalization for heart failure. MicroRNAs (miRNA) affect cardiac function of T2DM. The aim of this study was to investigate the relationships between five miRNA single nucleotide polymorphisms (SNP) and diastolic and systolic function of T2DM.Methods and resultsThree hundred untreated T2DM subjects were included. Each subject underwent SNP genotyping, conventional echocardiography, tissue doppler imaging, and speckle tracking imaging. The effects of miRNA SNPs on diastolic and systolic function were evaluated. The diastolic function of T2DM subjects with miR-133a-1-rs8089787 wild genotype or let-7f-rs10877887 variant genotype was lower than those with miR-133a-1-rs8089787 variant genotype or let-7f-rs10877887 wild genotype, manifesting as higher left atrial volume index, lower mean E′, and higher E/E’ (P < 0.05). There were no significant effects of miR-133a-2-rs13040413, let-7a-1-rs13293512 and miR-27a-rs895819 on the diastolic function of T2DM subjects (P > 0.05). These five miRNA SNPs had no effect on the systolic function of T2DM subjects (P > 0.05).ConclusionsMiRNA-133a-1-rs8089787 and let-7f-rs10877887 were associated with impaired cardiac diastolic function in T2DM. The findings may be a promising therapeutic targets for preventing diastolic dysfunction in T2DM.     

Quantitative Metabolomics Reveals Heart Failure With Midrange Ejection Fraction as a Distinct Phenotype of Heart Failure

BackgroundHeart failure with midrange ejection fraction (HFmrEF) has been recently acknowledged as a separate phenotype, but metabolomics evaluation of this subtype remains largely unexamined.MethodsA quantitative metabolomics study on amino acids and acylcarnitines was performed to characterize different states of heart failure (HF) in 628 participants. Both multivariate orthogonal partial least squares- discriminant analysis and univariate Mann-Whitney U test were used to explore reliable metabolic profiles associated with different HF states. The resulting metabolites were further refined to obtain diagnostic metabolite scores (DMSs) with the use of ordinal logistic regression. Lasso-penalized regression was applied to produce a survival-associated prognostic metabolite score (PMS). The Cox proportional hazards model, Kaplan-Meier curves, and time-dependent receiver operating characteristics were used for a comprehensive assessment of prognostic value using PMS versus traditional clinical biomarkers.ResultsThe optimized models identified a panel of 15 differential metabolites that were shared across different HF states, whereas some metabolites were associated with a specific state. PMS consisting of 9 metabolites demonstrated an appreciably better prognostic value (hazard ratio [HR] 1.62, 95% confidence interval [CI] 1.25-2.1) vs the natural logarithm of N-terminal pro–B-type natriuretic peptide (Ln[NT-proBNP]; HR 1.23, 95% CI 0.94-1.61; P < 0.001). The overall area under the receiver operating characteristic curve value of PMS was superior to that of Ln(NT-proBNP) in risk prediction for patients with HFmrEF and HF with reduced ejection fraction (HFrEF) subtypes (P < 0.001).ConclusionsTargeted metabolomics has provided a novel understanding of the molecular mechanism underlying HF. Both DMS and PMS clearly demonstrated HFmrEF as a distinct phenotype between a mild HF with preserved ejection fraction state and a severe HFrEF state. PMS exhibited superior prognostic value than Ln(NT-proBNP). Further investigation is needed with independent large-scale validation.     

Associations of peroxisome proliferator-activated receptor-γ Pro12Ala polymorphism with non-alcoholic fatty liver disease: A meta-analysis

BackgroundPolymorphisms in peroxisome proliferator-activated receptor-γ pro12Ala (PPAR-γ Pro12Ala) have been associated with Non-alcoholic Fatty Liver Disease (NAFLD) in several studies. However, the results of these studies are not entirely consistent. Thus, we performed a meta-analysis to investigate the association between the PPAR-γ Pro12Ala polymorphisms and NAFLD.MethodsStudies were identified by searching PubMed database and manual assessment of the cited references in the retrieved articles. Study-specific relative risks (RRs) and 95 % confidence intervals (CIs) were estimated using a random-effect model. Study quality was assessed using the Newcastle–Ottawa scale.ResultsRelevant medical researches show that 11 studies have been conducted on the analysis of NAFLD for meta-analysis, with a total of 2404 cases and 3959 participating controls. Meta-analysis results show that PPAR-γ Pro12Ala polymorphism and NALAD Ala alleles[no association between dominance model (OR = 0.968, 95%CI: 0.734–1.276, P = 0.815); Pro/Ala vs. Pro/Pro (OR = 0.930, 95 % CI: 0.701–1.233, P = 0.612); Ala/Ala vs. Pro/Pro (OR = 1.220, 95 % CI: 0.668–2.230, P = 0.518); recessive model (OR = 0.907, 95 % CI: 0.516–1.596, P = 0.736)]. Moreover, stratification by ethnicity also revealed that no matter it is in Caucasian populations or in Asian populations, NAFLD has no association with the PPAR-γ Pro12Ala polymorphism.ConclusionsAccording to the meta-analysis, both in Asians and Caucasian populations, the PPAR-γ Pro12Ala polymorphism can't be demonstrated to have any link with susceptibility to NAFLD.     

Fetuin-A to adiponectin ratio is an independent indicator of subclinical atherosclerosis in patients with newly diagnosed type 2 diabetes mellitus

AimsThe purpose of this research was to explore the associations of fetuin-A, adiponectin, and fetuin-A/adiponectin ratio (F/A ratio) with subclinical atherosclerosis as evaluated by carotid intima-media thickness (CIMT) in cases with newly diagnosed type 2 diabetes mellitus (T2DM).MethodsA total of 283 newly diagnosed T2DM patients were enrolled in this study. Serum fetuin-A and adiponectin levels were determined with an ELISA method. Other clinical and biochemical parameters were also collected.ResultsSignificant linear increases in waist-to-hip ratio (WHR), systolic blood pressure (SBP), diastolic blood pressure, homoeostasis model assessment of insulin resistance, C-reactive protein (CRP) and F/A ratio, and a significant linear decrease in adiponectin with increasing tertiles of CIMT were observed (P for trends <0.05). However, no significant correlation between fetuin-A and CIMT was detected (P > 0.05). In multivariate logistic regression models, WHR, SBP and F/A ratio were independently correlated with higher CIMT. Receiver operating characteristic curve analysis indicated that F/A ratio had a better predictive power for higher CIMT than adiponectin and fetuin-A, with an area under the curve of 0.802, 0.713 and 0.646, respectively.ConclusionF/A ratio is an independent indicator of subclinical atherosclerosis in patients with newly diagnosed T2DM.     

Laparoscopic versus open pancreatoduodenectomy: an individual participant data meta-analysis of randomized controlled trials

BackgroundRandomized trials have compared laparoscopic pancreatoduodenectomy (LPD) to open pancreatoduodenectomy (OPD) with conflicting results. An IPDMA may give more insight into the differences between LPD and OPD, and could identify high-risk subgroups.MethodsA systematic literature search was performed in the Pubmed, Embase, and the Cochrane library databases (October 2019). Out of 1410 studies, three randomized trials were identified. Primary outcome was major complications (Clavien-Dindo grade ≥ III). Subgroup analyses were performed for high-risk subgroups including patients with BMI of ≥25 kg/m2, pancreatic duct <3 mm, age ≥70 years, and malignancy.ResultsData from 224 patients were collected. After LPD, major complications occurred in 33/114 (29%) patients compared to 34/110 (31%) patients after OPD (adjusted odds ratio (OR) 0.62; 95% confidence interval (CI) 0.3–1.4, P = 0.257). No differences were seen for major complications and 90-day mortality LPD 8 (7%) vs OPD 4 (4%) (adjusted OR 0.2; 95% CI 0.02–1.3, P = 0.080). With LPD, operative time was longer (420 vs 318 min, p < 0.001) and hospital stay was shorter (mean difference ?6.97 days). Outcomes remained stable in the high-risk subgroups.ConclusionLPD did not reduce the rate of major postoperative complications as compared to OPD. LPD increased operative time and shortened hospital stay with 7 days.