Association of serum triglyceride-to-HDL cholesterol ratio with carotid artery intima-media thickness,insulin resistance and nonalcoholic fatty liver disease in children and adolescents

Background and aimsThe triglyceride (TG)/high-density lipoprotein-cholesterol (HDL-C) ratio has been reported as a useful marker of atherogenic lipid abnormalities, insulin resistance, and cardiovascular disease. We evaluated in a large sample of children and adolescents the association of TG/HDL-C ratio with early signs of morphological vascular changes and cardiometabolic risk factors including nonalcoholic fatty liver disease (NAFLD).Methods and resultsThe study population, including 548 children (aged 6–16 years), of whom 157 were normal-weight, 118 overweight, and 273 obese, had anthropometric, laboratory, liver and carotid ultrasonography (carotid artery intima-media thickness-cIMT) data collected. Subjects were stratified into tertiles of TG/HDL-C. There was a progressive increase in body mass index (BMI), BMI-SD score (SDS), waist circumference, blood pressure (BP), liver enzymes, glucose, insulin, homeostasis model assessment of insulin resistance, high-sensitivity C-reactive protein (hsCRP), and cIMT values across TG/HDL-C tertiles. The odds ratios for central obesity, insulin resistance, high hsCRP, NAFLD, metabolic syndrome, and elevated cIMT increased significantly with the increasing tertile of TG/HDL-C ratio, after adjustment for age, gender, pubertal status, and BMI-SDS. In a stepwise multivariate logistic regression analysis, increased cIMT was associated with high TG/HDL-C ratio [OR, 1.81 (95% CI, 1.08–3.04); P < 0.05], elevated BP [5.13 (95% CI, 1.03–15.08); P < 0.05], insulin resistance [2.16 (95% CI, 1.30–3.39); P < 0.01], and NAFLD [2.70 (95% CI, 1.62–4.56); P < 0.01].ConclusionTG/HDL-C ratio may help identify children and adolescents at high risk for structural vascular changes and metabolic derangement.     

Mediterranean diet,overweight and body composition in children from eight European countries: Cross-sectional and prospective results from the IDEFICS study

Background & aimsA Mediterranean-like dietary pattern has been shown to be inversely associated with many diseases, but its role in early obesity prevention is not clear. We aimed to determine if this pattern is common among European children and whether it is associated with overweight and obesity.Methods and resultsThe IDEFICS study recruited 16,220 children aged 2–9 years from study centers in eight European countries. Weight, height, waist circumference, and skinfolds were measured at baseline and in 9114 children of the original cohort after two years. Diet was evaluated by a parental questionnaire reporting children's usual consumption of 43 food items. Adherence to a Mediterranean-like diet was calculated by a food frequency-based Mediterranean Diet Score (fMDS).The highest fMDS levels were observed in Sweden, the lowest in Cyprus. High scores were inversely associated with overweight including obesity (OR = 0.85, 95% CI: 0.77; 0.94) and percent fat mass (β = −0.22, 95% CI: −0.43; −0.01) independently of age, sex, socioeconomic status, study center and physical activity. High fMDS at baseline protected against increases in BMI (OR = 0.87, 95% CI: 0.78; 0.98), waist circumference (OR = 0.87, 95% CI: 0.77; 0.98) and waist-to-height ratio (OR = 0.88, 95% CI: 0.78; 0.99) with a similar trend observed for percent fat mass (p = 0.06).ConclusionsAlthough a Mediterranean dietary pattern is inversely associated with childhood obesity, it is not common in children living in the Mediterranean region and should therefore be advocated as part of EU obesity prevention strategies.     

Evaluation of waist-to-height ratio to predict 5 year cardiometabolic risk in sub-Saharan African adults

Background and aimsSimple, low-cost central obesity measures may help identify individuals with increased cardiometabolic disease risk, although it is unclear which measures perform best in African adults. We aimed to: 1) cross-sectionally compare the accuracy of existing waist-to-height ratio (WHtR) and waist circumference (WC) thresholds to identify individuals with hypertension, pre-diabetes, or dyslipidaemia; 2) identify optimal WC and WHtR thresholds to detect CVD risk in this African population; and 3) assess which measure best predicts 5-year CVD risk.Methods and resultsBlack South Africans (577 men, 942 women, aged >30years) were recruited by random household selection from four North West Province communities. Demographic and anthropometric measures were taken. Recommended diagnostic thresholds (WC > 80 cm for women, >94 cm for men; WHtR > 0.5) were evaluated to predict blood pressure, fasting blood glucose, lipids, and glycated haemoglobin measured at baseline and 5 year follow up. Women were significantly more overweight than men at baseline (mean body mass index (BMI) women 27.3 ± 7.4 kg/m², men 20.9 ± 4.3 kg/m²); median WC women 81.9 cm (interquartile range 61–103), men 74.7 cm (63–87 cm), all P < 0.001). In women, both WC and WHtR significantly predicted all cardiometabolic risk factors after 5 years. In men, even after adjusting WC threshold based on ROC analysis, WHtR better predicted overall 5-year risk. Neither measure predicted hypertension in men.ConclusionsThe WHtR threshold of >0.5 appears to be more consistently supported and may provide a better predictor of future cardiometabolic risk in sub-Saharan Africa.     

The application of Gammatone frequency cepstral coefficients for forensic voice comparison under noisy conditions

ABSTRACT

Compared with humans, who have more powerful auditory ability in discriminating and identifying speakers in noisy environments, traditional forensic automatic speaker recognizers do not perform well when dealing with noisy recordings. This paper proposes a GMM-UBM Forensic Automatic Speaker Recognition (FASR) System to reduce the effect of noise on performance. The system uses Gammatone Frequency Cepstral Coefficients (GFCC) based on an auditory periphery model and also incorporates a Principal Component Analysis (PCA) algorithm. The system was tested and validated using Mandarin voice databases compromised with different levels of white noise and office noise. The performance of the system was compared with a baseline system using Mel Frequency Cepstral Coefficients (MFCC) and also PCA under the same conditions. The results show that the performance of the combined GFCC system achieved a substantial improvement when compared with the baseline MFCC system under conditions of a high level of office noise.     

阳性淋巴结对数比对食管癌术后患者不同辅助治疗疗效的评估作用

目的 分析阳性淋巴结对数比（LODDS）对食管癌术后患者预后的影响,并分析LODDS对接受不同术后辅助治疗方案患者疗效评估的作用。方法 收集在河北医科大学第四医院接受治疗的1 546例食管癌术后患者,回顾性分析LODDS对患者预后的影响,并进一步分析LODDS对术后患者选择不同术后辅助治疗方案的意义。结果 全组患者1、3、5年总生存率分别为87.5%、61.7%和52.2%。受试者工作特征曲线（ROC）分析结果显示-1.354 1为LODDS最佳截点值。多因素分析结果显示,患者性别、年龄、病变部位、病变粘连程度、术后辅助治疗方式、pTNM分期和LODDS为影响患者预后的独立性因素（P<0.05）。不同治疗模式的3组患者进行1：1：1的倾向得分匹配法分析（PSM）后,每组205例,多因素分析结果显示,患者性别、病变粘连程度、术后辅助治疗方式、pTNM分期和LODDS为影响患者独立性预后因素（P<0.05）。分层分析结果显示,LODDS数值较小组患者接受术后辅助性治疗的OS优于单纯手术组患者（χ²=81.470、5.182,P<0.05）,但术后化疗（POCT）与术后放化疗（POCRT）对患者预后的差异无统计学意义（P>0.05）;而在LODDS数值较大组显示POCRT组患者的OS优于其他两组（χ²=4.151、24.020,P<0.05）,且POCT与POCRT两组患者之间差异有统计学意义（χ²=8.728,P<0.05）。结论 LODDS为食管鳞癌术后患者的独立性预后影响因素,并在一定程度上可以指导术后辅助治疗方式的选择。这一结论需要进一步临床研究证实。     

In Vitro and In Vivo Correlation of Hepatic Fraction of Metabolism by P450 in Dogs

1-Aminobenzotriazole (ABT) has been widely used as a nonspecific mechanism-based inhibitor of cytochrome P450 (P450) enzymes. It is extensively used in preclinical studies to determine the relative contribution of oxidative metabolism mediated by P450 in vitro and in vivo. The aim of present study was to understand the translation of fraction metabolized by P450 in dog hepatocytes to in vivo using ABT, for canagliflozin, known to be cleared by P450-mediated oxidation and UDP-glucuronosyltransferases–mediated glucuronidation, and 3 drug discovery project compounds mainly cleared by hepatic metabolism. In a dog hepatocyte, intrinsic clearance assay with and without preincubation of ABT, 3 Lilly compounds exhibited a wide range of fraction metabolized by P450. Subsequent metabolite profiling in dog hepatocytes demonstrated a combination of metabolism by P450 and UDP-glucuronosyltransferases. In vivo, dogs were pretreated with 50 mg/kg ABT or vehicle at 2 h before intravenous administration of canagliflozin and Lilly compounds. The areas under the concentration-time curve (AUC) were compared for the ABT-pretreated and vehicle-pretreated groups. The measured AUC_ABT/AUC_veh ratios were correlated to fraction of metabolism by P450 in dog hepatocytes, suggesting that in vitro ABT inhibition in hepatocytes is useful to rank order compounds for in vivo fraction of metabolism assessment.     

The Impact of Endogenous Breast Cancer Resistance Protein on Human P-Glycoprotein-Mediated Transport Assays Using LLC-PK1 Cells Transfected With Human P-Glycoprotein

Lilly Laboratories cell porcine kidney 1 (LLC-PK1) cells transfected with human P-glycoprotein (LLC-PK1-P-gp) are widely used in transport assays to identify drug candidates that function as substrates of this efflux transporter. Endogenous transporters expressed in LLC-PK1 cells may complicate the interpretation of findings from P-gp-mediated transport assays. We investigated the impact of porcine breast cancer resistance protein (Bcrp) in P-gp-mediated transport assays in LLC-PK1 cells. Porcine Bcrp mRNA was detected in both LLC-PK1 wildtype (WT) and LLC-PK1-P-gp cells by quantitative RT-PCR. To investigate the activity and impact of porcine Bcrp, we conducted transport assays using 6 typical BCRP substrates in LLC-PK1 cells. Efflux ratios (ER) of the 6 BCRP substrates in LLC-PK1 WT cells were >2, and were reduced in the presence of the BCRP inhibitor Ko143. The efflux activities of the 6 BCRP substrates were confirmed using MDCKII cells transfected with human BCRP. Net ERs of prazosin and fluvastatin, dual substrates of P-gp and BCRP, determined by dividing ERs in LLC-PK1-P-gp cells by those in LLC-PK1 WT cells, were <2, but increased to >2 in the presence of Ko143. These results indicated that endogenous Bcrp in LLC-PK1 cells was involved in the transport of BCRP substrates and may interfere with the identification of P-gp substrates.     

Estrogen receptor α is not a candidate gene for metabolic syndrome in Caucasian elderly subjects

Objective

Variants of estrogen receptor α (ERα) have been associated with obesity, dyslipidemia, diabetes and blood pressure. The Middle East registers some of the highest rate of metabolic syndrome worldwide. The aim of this study is to investigate the relationship between metabolic syndrome, a clustered combination of these metabolic factors, and polymorphisms PvuII and XbaI of ERα in Lebanese Caucasian elderly overweight subjects.

Material/Methods

250 Caucasian Lebanese unrelated elderly men and women, median age 71 years, were studied. ERα intronic polymorphisms variants, PvuII and XbaI diplotypes and genotypes, were examined. Associations with metabolic syndrome, defined by the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI), and its components, namely high density lipoprotein (HDL), fasting glucose levels, blood pressure, and waist circumference were evaluated in regression models.

Results

ER α diplotypes and genotypes distributions were similar between participants with and without metabolic syndrome, in the overall group of subjects, and by gender. No consistent associations between the diplotypes and genotypes tested and metabolic syndrome, or its components, could be detected.

Conclusions

Genetic variants in ERα were not associated with metabolic syndrome or its components, in a group of 250 Lebanese Caucasian elderly participants, a group with a high prevalence of metabolic syndrome.     

Subclinical albuminuria is linked to gray matter atrophy in type 2 diabetes mellitus

Objective

Microalbuminuria (MA), a marker of renal microvascular disease, is associated with brain atrophy and neurovascular changes in older adults with type 2 diabetes mellitus (DM). We evaluated the relationship between urine albumin-to-creatinine ratio (UACR) and regional brain volumes to determine whether subclinical albuminuria may indicate early structural brain changes in type 2 DM.

Materials/Methods

We studied UACR and brain volumes in 85 type 2 DM patients (64.8 ± 8.3 years) and 40 age-matched controls using 3D magnetization prepared rapid acquisition with gradient echo (MP-RAGE) MRI (magnetic resonance imaging) at 3 Tesla. The relationship between UACR and brain volumes was analyzed using the least square models.

Results

In DM patients, UACR ≥ 5 mg/g, UACR ≥ 10 mg/g and clinically significant MA (UACR ≥ 17 mg/g [males] and 25 mg/g [females]) were associated with lower gray matter (GM) volume in the frontal lobe (r²_adj = 0.2–0.4, P = 0.01–0.05) and UACR ≥ 5 mg/g was also related to global GM atrophy (r²_adj = 0.1, P = 0.04), independent of DM duration, glucose levels, HbA_1c and hypertension. For UACR ≥ 5 mg/g, a lower global GM volume was related to worse executive function (P = 0.04) in the DM group. No associations were found for UACR (< 5 mg/g) and controls.

Conclusions

Subclinical albuminuria (UACR ≥ 5 mg/g) is associated with lower GM volume that has clinical impact on cognitive function in older diabetic patients, and these relationships are independent of DM control and hypertension. Therefore, UACR levels may serve as an additional marker of DM-related brain structural changes.     

Neutrophil to lymphocyte ratio in relation to risk of all-cause mortality and cardiovascular events among patients undergoing angiography or cardiac revascularization: A meta-analysis of observational studies

Objective

The aim of this study was to investigate whether neutrophil to lymphocyte ratio (NLR) was an independent predictor for all-cause mortality or cardiovascular events in patients undergoing angiography or cardiac revascularization with observational studies by meta-analysis.

Methods

Pubmed and Embase were searched without language restrictions for cohort studies published prior to November 2013. Citations were independently screened by 2 authors, and those meeting the inclusion criteria defined a priori were retained. Data on authors, year of publication, location, target participant, comparison of NLR, outcome assessment, number of event and sample size, duration and statistical adjustments were abstracted.

Results

Eight studies were identified that reported on all-cause mortality and five studies were identified that reported on cardiovascular events. The pooled relative risk (RR) of all-cause mortality was 2.33 (95% CI 1.88–2.88) and the RR of cardiovascular events was 1.89 (95% CI 1.42, 2.52) comparing the highest with the lowest category of NLR.

Conclusions

The meta-analysis indicates that NLR is a predictor of all-cause mortality and cardiovascular events. Further well-designed trials are warranted to confirm this association.