Suspect, Nontarget Screening, and Toxicity Prediction of Per- and Polyfluoroalkyl Substances in the Landfill Leachate.

Landfills are the final stage of urban wastes containing perfluoroalkyl and polyfluoroalkyl substances (PFASs). PFASs in the landfill leachate may contaminate the surrounding groundwater. As major environmental pollutants, emerging PFASs have raised global concern. Besides the widely reported legacy PFASs, the distribution and potential toxic effects of numerous emerging PFASs remain unclear, and unknown PFASs still need discovery and characterization. This study proposed a comprehensive method for PFAS screening in leachate samples using suspect and nontarget analysis. A total of 48 PFASs from 10 classes were identified; nine novel PFASs including eight chloroperfluoropolyether carboxylates (Cl-PFPECAs) and bistriflimide (HNTf2) were reported for the first time in the leachate, where Cl-PFPECA-3,1 and Cl-PFPECA-2,2 were first reported in environmental media. Optimized molecular docking models were established for prioritizing the PFASs with potential activity against peroxisome proliferator-activated receptor α and estrogen receptor α. Our results indicated that several emerging PFASs of N-methyl perfluoroalkyl sulfonamido acetic acids (N-MeFASAAs), n:3 fluorotelomer carboxylic acid (n:3 FTCA), and n:2 fluorotelomer sulfonate (n:2 FTSA) have potential health risks that cannot be ignored.

Effect of renal denervation on cardiac remodelling and function in rats with chronic intermittent hypoxia.

Chronic intermittent hypoxia (CIH) mimicking obstructive sleep apnea elicits divergent outcomes in the cardiovascular systems. The effect of renal denervation (RDN) on the heart during CIH remains unclear. We aimed to explore the effect of RDN on cardiac remodelling in rats exposed to CIH and to discuss the underlying mechanisms. Adult Sprague Dawley rats were divided into four groups: control, control+RDN, CIH (CIH exposure for 6 weeks, nadir of 5%-7% to peak of 21% O2, 20 cycles/h, 8 h/day) and CIH+ RDN group. Echocardiography, cardiac fibrosis, left ventricle (LV) expressions of nuclear factor-E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway and inflammatory factors were tested at the end of the study. Cardiac structural remodelling and dysfunction were induced by CIH and attenuated by RDN. Myocardial fibrosis was more severe in the CIH group than in the control group and improved in the CIH + RDN group. Sympathetic activity reflected by tyrosine hydroxylase (TH) expression and noradrenaline were significantly elevated after CIH but blunted by RDN. CIH downregulated LV protein expressions of Nrf2 and HO-1, which was activated by RDN. The downstream of Nrf2/HO-1, such as NQO1 and SOD expression, elevated following RDN. RDN also decreased the mRNA expression of IL-1ß and IL-6. Notably, control+RDN did not affect cardiac remodelling and Nrf2/HO-1 compared with the control. Taken together, we found that RDN exerted cardio-protective effects in a rat model of CIH involving Nrf2/HO-1 pathway and inflammation.

Sacubitril/valsartan mitigated intermittent hypoxia related intestinal microbiota alteration and aortic injury.

OBJECTIVE: To investigate the influence of sacubitril valsartan sodium (SVS) on chronic intermittent hypoxia (IH) related gut microbiome composition alteration and aortic injury. METHODS: Experiments were performed using SD rats, which were divided into three groups: control, IH, and SVS group. O2 concentration was decreased to 7-8% at nadir approximately every 3 min in IH group (8 h per day for 6 weeks) or was left unchanged in control group. Rats in SVS group were orally gavaged with SVS at the dosage of 30 mg/kg/day (2 weeks after chronic IH exposure). At week 6, fecal and aortic samples were harvested for 16 s rDNA analysis and histological analysis, respectively. RESULTS: Principal coordinate analysis and non-metric multidimensional scaling analysis indicated that the bacterial community was altered by chronic IH exposure, while SVS treatment restored the intestinal microbial communities. Further analysis showed that IH decreased the relative abundance of Lactobacillus and Prevotella, while rats treated with SVS was enriched with Firmicutes, Bacilli, Prevotellaceae, and Lactobacillus, which was similar to control rats. Immunohistochemical staining showed that SVS prevented the upregulation of transforming growth factor-ß1 and tumor necrosis factor-alpha in the aorta. CONCLUSION: SVS prevented aortic adverse response to IH, possibly through modulating intestinal microbiota.

Thermoresponsive Polymeric Nanolenses Magnify the Thermal Sensitivity of Single Upconverting Nanoparticles.

Lanthanide-based upconverting nanoparticles (UCNPs) are trustworthy workhorses in luminescent nanothermometry. The use of UCNPs-based nanothermometers has enabled the determination of the thermal properties of cell membranes and monitoring of in vivo thermal therapies in real time. However, UCNPs boast low thermal sensitivity and brightness, which, along with the difficulty in controlling individual UCNP remotely, make them less than ideal nanothermometers at the single-particle level. In this work, it is shown how these problems can be elegantly solved using a thermoresponsive polymeric coating. Upon decorating the surface of NaYF4 :Er3+ ,Yb3+ UCNPs with poly(N-isopropylacrylamide) (PNIPAM), a >10-fold enhancement in optical forces is observed, allowing stable trapping and manipulation of a single UCNP in the physiological temperature range (20-45 °C). This optical force improvement is accompanied by a significant enhancement of the thermal sensitivity- a maximum value of 8% °C+1 at 32 °C induced by the collapse of PNIPAM. Numerical simulations reveal that the enhancement in thermal sensitivity mainly stems from the high-refractive-index polymeric coating that behaves as a nanolens of high numerical aperture. The results in this work demonstrate how UCNP nanothermometers can be further improved by an adequate surface decoration and open a new avenue toward highly sensitive single-particle nanothermometry.

Infant Exposure to PCBs and PBDEs Revealed by Hair and Human Milk Analysis: Evaluation of Hair as an Alternative Biomatrix.

Human hair, as an emerging biological monitoring matrix, has begun to be used in various human exposure studies, but little research has been done on persistent organic pollutants (POPs), especially for the body burden of POPs in infants. In this study, 36 breast-fed infants in Shanghai were recruited for a study to determine their exposure to POPs, including 12 dioxin-like polychlorinated biphenyls (dl-PCBs), 6 indicator PCBs, and 8 polybrominated diphenyl ethers (PBDEs) in the inner layer (internal) and outer layer (external) of infant hair and human milk. The similarity or difference of the POP distribution pattern or concentration among these matrices was investigated, and only weak correlations (r < 0.4) were observed between the POP concentration in human milk and infant hair (internal or external). POPs in human milk have a different profile than those in infant hair, while they have stable concentration ratios (0.58-2.72), similar distribution patterns, fine Spearman's rank correlations, and tangled principal component analysis (PCA) plots in each POP family between external and internal hair samples. The result suggested that POPs in internal hair can be easily affected by those in external hair, but POPs in human milk seem to have little contribution to the POP profile in internal hair. Although infant hair cannot reflect the POPs from diet or from body burden, it can be an ideal biomatrix that estimates infant exposure to POPs from exogenous sources like house dust when considering the similar pattern of POPs and their proper accumulation period in hair.

Multiple mediation effects on association between prenatal triclosan exposure and birth outcomes.

BACKGROUND: Triclosan is a broad-spectrum antimicrobial, and was thought to affect intrauterine development, but the mechanism remains unclear. OBJECTIVE: To explore the association between prenatal triclosan exposure and birth outcomes. METHODS: Based on 726 mother-child pairs from the Sheyang Mini Birth Cohort Study (SMBCS), we used the available (published) data of triclosan in maternal urines, the hormones including thyroid-related hormones, gonadal hormones in cord blood, and adipokines, trimethylamine-N-oxide (TMAO) and its precursors in cord blood to explore possible health effects of triclosan on birth outcomes through assessing different hormones and parameters, using Bayesian mediation analysis. RESULTS: Maternal triclosan exposure was associated with ponderal index (ß = 0.317) and head circumference (ß = -0.172) in generalized linear models. In Bayesian mediation analysis of PI model, estradiol (ß = 0.806) and trimethylamine (TMA, ß = 0.164) showed positive mediation effects, while total thyroxine (TT4, ß = -0.302), leptin (ß = -2.023) and TMAO (ß = -0.110) showed negative mediation effects. As for model of head circumference, positive mediation effects were observed in free thyroxine (FT4, ß = 0.493), TMA (ß = 0.178), and TMAO (ß = 0.683), negative mediation effects were observed in TT4 (ß = -0.231), testosterone (ß = -0.331), estradiol (ß = -1.153), leptin (ß = -2.361), choline (ß = -0.169), betaine (ß = -0.104), acetyl-L-carnitine (ß = -0.773). CONCLUSION: The results indicated triclosan can affect intrauterine growth by interfering thyroid-related hormones, gonadal hormones, adipokines, TMAO and its precursors.

Flurochloridone induces responses of free radical reactions and energy metabolism disorders to BRL-3A cell.

Flurochloridone (FLC), a wildly used herbicide, could induce hepatotoxicity after long-term exposure to male rat, in addition to its reactive oxygen species (ROS)-dependent reproductive toxicity. The hepatotoxicity effect and mechanism was investigeted using 1, 10 and 100 µmol L-1 FLC treated BRL-3A liver cell in this study. The function of mitochondrial respiration, glycolysis rate and real time ATP production rate are determined by seahorse XF analyzer, and the bio-transformers of FLC, intermediates of TCA cycle and glycolysis, and related amino acids are determined and identified by [U-13C] Glucose metabolic flux technology based on UPLC-HRMS. The mRNA expression of cytochrome P450s and the key regulatory enzymes of glucose metabolism and γ- glutamyl cycle pathway. The protein expressions of protein kinase B (AKT) and glycogen synthase kinase-3 beta (GSK-3ß) were determined. The results show dechlorination and glutathione (GSH) conjugate products of FLC are predominant bio-transformmers after 24 h treatment in BRL-3A cell. FLC could enhance glycolysis function and inhibit mitochondrial aerobic respiratory, which is accompanied by the decreased total ATP level and ATP produced rate. Increased glucose-6-phosphate, fructose-6-phosphate, pyruvate and lactate levels, and elevated level of GSH and its precursor 5-glutamate-cysteine (γ-Glu-Cys) are observed in FLC treated cells, which indicates that energy metabolism dysfunction and GSH accumulation could be potentially mediated by activating γ- Glutamyl cycle pathway. Conclusively, FLC induced hepatotoxicity could be potentially related to some free radical reactions, including inhibiting mitochondrial function, glucose metabolism via glycolysis, regulating γ- glutamyl cycle pathway to promote reactive oxygen species (ROS) level, and then induced cell apoptosis by inhibiting AKT/GSK-3ß signal.

Urinary para-nitrophenol levels of pregnant women and cognitive and motor function of their children aged 2 years: Evidence from the SMBCS (China).

BACKGROUND: Urinary para-nitrophenol (PNP), an exposure biomarker of ethyl parathion (EP) and methyl parathion (MP) pesticides, was still pervasively detected in the general population even after global restriction for years. And the concern whether there is an association of PNP level with child development of the nervous system is increasing. The current study aimed to evaluate the maternal urinary PNP concentrations during late pregnancy and the associations of PNP levels with cognitive and motor function of their children at the age of 2 years. METHODS: 323 mother-child pairs from the Sheyang Mini Birth Cohort Study were included in the current study. Gas chromatography-tandem mass spectrometry was used to measure concentrations of PNP, the specific metabolite of EP and MP, in maternal urine samples during pregnancy. Developmental quotients (DQs) scores measured with Gesell Developmental Scales were employed to evaluate cognitive and motor function of children aged 2 years. Generalized linear models were performed to analyze the associations of PNP concentrations in pregnant women's urine samples with cognitive and motor function of their children. RESULTS: Maternal PNP was detected in all urine samples with a median of 4.11 µg/L and a range from 0.57 µg/L to 109.13 µg/L, respectively. Maternal urinary PNP concentrations showed a negative trend with DQ of motor area [regression coefficient (ß) = - 1.35; 95 % confidence interval (95 %CI): - 2.37, - 0.33; P < 0.01], and the children whose mothers were in the fourth quartile exposure group performed significantly worse compared to the reference group (ß = - 1.11; 95 %CI: - 1.80, - 0.42; P < 0.01). As for average DQ score, children with their mothers' urinary PNP concentrations in the third quartile group had higher scores than those in the first quartile group (ß = 0.39; 95 %CI: 0.03, 0.75; P = 0.04). In sex-stratified analyses, a negative trend between maternal urinary PNP concentrations and DQ scores in motor area of children was only observed in boys (ß = - 1.62; 95 %CI: - 2.80, - 0.43; P < 0.01). Boys in the third quartile group had higher DQ average scores than those in the lowest quartile as reference (ß = 0.53; 95 %CI: 0.02, 1.04; P = 0.04). CONCLUSIONS: The mothers from SMBCS may be widely exposed to EP and/or MP, which were associated with the cognitive and motor function of their children aged 2 years in a sex-specific manner. Our results might provide epidemiology evidence on the potential effects of prenatal exposure to EP and/or MP on children's cognitive and motor function.

The association between preoperative blood calcium and postoperative blood loss in patients undergoing heart valve replacement surgery.

INTRODUCTION: Bleeding after heart valve surgery is a serious clinical challenge. Hypocalcemia has been associated with the extent of bleeding in patients with spontaneous intracerebral hemorrhage. However, the association between blood calcium levels and bleeding extent in heart valve replacement patients has not been clearly established. This study aimed at determining the association between blood calcium levels and perioperative hemorrhage after heart valve replacement therapy. METHODS: Based on preoperative blood calcium levels, patients were grouped into the hypocalcemia group and normocalcemia group. Postoperative bleeding, blood product use, and complications were monitored during hospitalization. The association between blood calcium levels and major bleeding was determined by multivariable logistic regression models. RESULTS: In the first 12 h after surgery, bleeding in hypocalcemia group was significantly larger than that of the normocalcemia group (338 ± 234 mL vs 232 ± 96 mL; p = .024). The outcome was the same when the overall chest tube output was considered (950 ± 447 mL vs 738 ± 220 mL; p = .038). The incidence of major bleeding was 65.91% in the hypocalcemia group and 18.97% in the normocalcemia group (p = .001). Postoperative complications in the two groups were similar. After adjusting for multiple covariates, the adjusted odds ratios (OR) for participants in hypocalcemia group was 10.01 (95% CI 3.35-34.82), compared with that in normocalcemia group (p < .001). CONCLUSION: In patients undergoing heart valve surgery, preoperative blood concentrations of calcium are associated with postoperative blood loss. Hypocalcemia before operation may increase the risk of postoperative bleeding. When patients with valvular heart disease present with hypocalcemia before surgery, prompt intervention may lead to better control of postoperative bleeding.

Novel Strategy for Mining and Identification of Acylcarnitines Using Data-Independent-Acquisition-Based Retention Time Prediction Modeling and Pseudo-Characteristic Fragmentation Ion Matching.

It is a challenging work to screen, identify, and quantify acylcarnitines in complex biological samples. A method, based on the retention time (RT) prediction and data-independent acquisition strategies, was proposed for the large-scale identification of acylcarnitines using liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS). Relative cumulative eluotropic strength was introduced as a novel descriptor in building a linear prediction model, which not only solves the problem that acylcarnitines with long carbon chains cannot be well predicted in traditional models but also proves its robustness and transferability across instruments in two data sets that were acquired in distinct chromatography conditions. The accessibility of both predictive RT and MS2 spectra of suspect features effectively reduced about 30% false-positive results, and consequently, 150 and 186 acylcarnitines were identified in the rat liver and human plasma (NIST SRM 1950), respectively. This method provides a new approach in large-scale analysis of acylcarnitine in lipidomic studies and can also be extended to the analysis of other lipids.

Nanojet Trapping of a Single Sub-10 nm Upconverting Nanoparticle in the Full Liquid Water Temperature Range.

Upconverting nanoparticles (UCNPs) have been used as optical probes in a great variety of scenarios ranging from cells to animal models. When optically trapped, a single UCNP can be remotely manipulated making possible, for instance, thermal scanning in the surroundings of a living cell. When conventional optics is used, the stability of an optically trapped UCNP is very limited. Its reduced size leads to optical potentials comparable to thermal energy, and up to now, stable optical trapping of a UCNP has been demonstrated only close to room temperature. This fact limits their use above room temperature, for instance, the use to investigate protein denaturalization that occurs in the 40-50 °C range. In this work, stable optical trapping of a single UCNP in the 20-90 °C range has been demonstrated by using a photonic nanojet. The use of an optically trapped microsphere makes it possible to overcome the diffraction limit producing another optical trap of smaller size and enhanced strength. This simple strategy leads not only to an improvement in the thermal stability of the optical trap but also to an enhancement of the emission intensity generated by the optically trapped UCNP.

The relationship between arterial stiffness index and coronary heart disease and its severity.

BACKGROUND: Arterial stiffness index (ASI) is closely related to coronary atherosclerosis. This study aims to explore whether ASI can predict coronary heart disease (CHD) and its severity. METHODS: In this study, a total of 726 patients with suspected CHD were recruited. Based on coronary angiography results, the subjects were assigned into three groups: the control group (without obvious coronary artery disease), single-vessel disease group, and multi-vessel disease group (the number of vessels diseased ≥ 2). At the same time, according to the results of angiography, myocardial enzyme spectrum, electrocardiogram, color Doppler echocardiography and clinical manifestations, these patients were divided into four groups: the control group, stable angina (SA) Group, unstable angina (UA) group, and acute myocardial infarction (AMI) group. We have compared whether there were differences in ASI and related baseline data between groups. Receiver operating curve (ROC) analysis was conducted to determine whether ASI could predict CHD and evaluate the severity. RESULTS: ASI was positively correlated with the number of diseased branches of coronary artery. The value of ASI was increased as the number of the diseased branches increased. The ASI value in the SA group was significantly higher compared with the control group. Furthermore, the ASI value in the UA and AMI groups was remarkably increased compared with the control and SA groups. The results of ROC analysis indicated that the sensitivity and specificity of ASI was 71.0% and 85.4% in diagnosing CHD, respectively. While ASI was used in predicting the severity of CHD, the sensitivity was 72.1% and specificity 57.9%. CONCLUSION: ASI is of great value in the diagnosis of coronary heart disease and the prediction of its severity.

Exploring Single-Nanoparticle Dynamics at High Temperature by Optical Tweezers.

The experimental determination of the velocity of a colloidal nanoparticle (vNP) has recently became a hot topic. The thermal dependence of vNP is still left to be explored although it is a valuable source of information allowing, for instance, the discernment between ballistic and diffusive regimes. Optical tweezers (OTs) constitute a tool especially useful for the experimental determination of vNP although they have only been capable of determining it at room temperature. In this work, we demonstrate that it is possible to determine the temperature dependence of the diffusive velocity of a single colloidal nanoparticle by analyzing the temperature dependence of optical forces. The comparison between experimental results and theoretical predictions allowed us to discover the impact that the anomalous temperature dependence of water properties has on the dynamics of colloidal nanoparticles in this temperature range.

Intestinal PPARα Protects Against Colon Carcinogenesis via Regulation of Methyltransferases DNMT1 and PRMT6.

BACKGROUND & AIMS: Many genetic and environmental factors, including family history, dietary fat, and inflammation, increase risk for colon cancer development. Peroxisome proliferator-activated receptor alpha (PPARα) is a nuclear receptor that regulates systemic lipid homeostasis. We explored the role of intestinal PPARα in colon carcinogenesis. METHODS: Colon cancer was induced in mice with intestine-specific disruption of Ppara (PparaΔIE), Pparafl/fl (control), and mice with disruption of Ppara that express human PPARA (human PPARA transgenic mice), by administration of azoxymethane with or without dextran sulfate sodium (DSS). Colons were collected from mice and analyzed by immunoblots, quantitative polymerase chain reaction, and histopathology. Liquid chromatography coupled with mass spectrometry-based metabolomic analyses were performed on urine and colons. We used molecular biology and biochemical approaches to study mechanisms in mouse colons, primary intestinal epithelial cells, and colon cancer cell lines. Gene expression data and clinical features of patients with colorectal tumors were obtained from Oncomine, and human colorectal-tumor specimens and adjacent normal tissues were collected and analyzed by immunohistochemistry. RESULTS: Levels of Ppara messenger RNA were reduced in colon tumors from mice. PparaΔIE mice developed more and larger colon tumors than control mice following administration of azoxymethane, with or without DSS. Metabolomic analyses revealed increases in methylation-related metabolites in urine and colons from PparaΔIE mice, compared with control mice, following administration of azoxymethane, with or without DSS. Levels of DNA methyltransferase 1 (DNMT1) and protein arginine methyltransferase 6 (PRMT6) were increased in colon tumors from PparaΔIE mice, compared with colon tumors from control mice. Depletion of PPARα reduced the expression of retinoblastoma protein, resulting in increased expression of DNMT1 and PRMT6. DNMT1 and PRMT6 decreased expression of the tumor suppressor genes Cdkn1a (P21) and Cdkn1b (p27) via DNA methylation and histone H3R2 dimethylation-mediated repression of transcription, respectively. Fenofibrate protected human PPARA transgenic mice from azoxymethane and DSS-induced colon cancer. Human colon adenocarcinoma specimens had lower levels of PPARA and retinoblastoma protein and higher levels of DNMT1 and PRMT6 than normal colon tissues. CONCLUSIONS: Loss of PPARα from the intestine promotes colon carcinogenesis by increasing DNMT1-mediated methylation of P21 and PRMT6-mediated methylation of p27 in mice. Human colorectal tumors have lower levels of PPARA messenger RNA and protein than nontumor tissues. Agents that activate PPARα might be developed for chemoprevention or treatment of colon cancer.

Effects of prenatal exposure to five parabens on neonatal thyroid function and birth weight: Evidence from SMBCS study.

BACKGROUND: Parabens, suspected as endocrine-disrupting chemicals, are nearly ubiquitous in the human body and exposure to these chemicals during pregnancy may disrupt thyroid hormones homeostasis and even affect fetal growth, although the impacts are still unclear. OBJECTIVES: We aimed to estimate associations of maternal urinary paraben concentrations with cord serum thyroid hormones and birth weight. METHODS: A subset of 437 mother-newborn pairs were included from a prospective birth cohort with five parabens quantified in maternal urine and seven thyroid function indicators measured in cord serum samples. Multivariable linear regression models and elastic net regression (ENR) models were applied to explore associations between individual and mixtures of prenatal urinary paraben concentrations and thyroid hormones and birth weight, respectively. RESULTS: Maternal urinary ethyl-paraben (EtP) concentrations were associated with increased cord serum total triiodothyronine levels (TT3) [percent change: 1.51%; 95% confidence interval (CI): 0.20%, 2.74%; p=0.017]. Urinary propyl-paraben (PrP) levels predicted higher thyroid peroxidase antibodies (percent change: 4.19%, 95%CI: 0.20%, 8.44%; p=0.041). Maternal urinary EtP and butyl-paraben (BuP) concentrations were significantly positively associated with birth weight [regression coefficient, (ß)=40.9g, 95%CI: 3.99, 76.6; p=0.030; ß=62.1g, 95%CI: 8.70, 115; p=0.023, for EtP and BuP, respectively]. In sex-stratified analyses, positive relationship between EtP levels and birth weight was observed in boys. Urinary EtP concentrations predicted higher TT3 levels in cord serum samples, assessing parabens as a chemical mixture with ENR models. CONCLUSIONS: Prenatal exposure to parabens may affect thyroid hormone indicators with increased serum TT3 levels and associate with higher birth weight, especially in boys. The underlying biological mechanisms and effects of prenatal paraben exposures on disruption of thyroid function homeostasis and potential impacts of childhood growth and development needed to be further investigated.

Single-Cell Biodetection by Upconverting Microspinners.

Near-infrared-light-mediated optical tweezing of individual upconverting particles has enabled all-optical single-cell studies, such as intracellular thermal sensing and minimally invasive cytoplasm investigations. Furthermore, the intrinsic optical birefringence of upconverting particles renders them light-driven luminescent spinners with a yet unexplored potential in biomedicine. In this work, the use of upconverting spinners is showcased for the accurate and specific detection of single-cell and single-bacteria attachment events, through real-time monitoring of the spinners rotation velocity of the spinner. The physical mechanisms linking single-attachment to the angular deceleration of upconverting spinners are discussed in detail. Concomitantly, the upconversion emission generated by the spinner is harnessed for simultaneous thermal sensing and thermal control during the attachment event. Results here included demonstrate the potential of upconverting particles for the development of fast, high-sensitivity, and cost-effective systems for single-cell biodetection.

Exposure to carbamate and neurodevelopment in children: Evidence from the SMBCS cohort in China.

BACKGROUND: Carbamate pesticides exposure have been linked with adverse health effects during developmental period. Based on 377 mother-child pairs from Sheyang Mini Birth Cohort Study, the present study aimed to assess carbofuranphenol exposure of three-year-old children and explore the associations between prenatal or postnatal carbofuranphenol exposures and neurodevelopmental indicators. METHODS: Urinary carbofuranphenol concentrations were measured by gas chromatography-tandem mass spectrometry. Neural developmental quotient (DQ) of children was evaluated using Gesell Developmental Schedules. Generalized linear models were used to examine the associations between carbofuranphenol concentrations and neurodevelopment. RESULTS: Geometric mean, geometric standard deviation, median, inter quartile range of postnatal urinary carbofuranphenol concentrations were 0.653 µg/L, 9.345 µg/L, 0.413 µg/L, 0.150-1.675 µg/L, respectively. Postnatal carbofuranphenol level showed negatively significant trend in language DQ [beta (ß) = -0.121; 95% confidence interval (95% CI): 0.212, -0.031; p value (p) = 0.008] and total average DQ (ß = -0.059, 95% CI: 0.115, -0.003; p = 0.035). Prenatal carbofuranphenol level showed negative correlations with children's adaptive DQ (ß = -0.755; 95% CI: 1.257, -0.254; p = 0.003), social DQ (ß = -0.341; 95% CI: 0.656, -0.027; p = 0.032) and total average DQ (ß = -0.349; 95% CI: 0.693, -0.005; p = 0.047). CONCLUSION: The results of the present study supposed children in agricultural region of China are widely exposed to carbamate pesticides, and both prenatal and postnatal exposure to carbamate pesticides may lead to neurodevelopmental effect.

Renal Denervation Effects on Myocardial Fibrosis and Ventricular Arrhythmias in Rats with Ischemic Cardiomyopathy.

BACKGROUND/AIMS: To investigate the impact of renal denervation (RDN) on myocardial fibrosis and ventricular arrhythmias (VAs) in rats with ischemic cardiomyopathy. METHODS: An ischemic cardiomyopathy model was reproduced with myocardial infarction (MI) in adult Sprague-Dawley male rats. The RDN/Sham-RDN procedure was performed at 2 weeks after MI. Sham-MI and sham-RDN rats served as the control group. At 4 weeks after RDN, programmed electrical stimulation (PES) was used to induce VAs, including ventricular tachycardia and ventricular fibrillation, in all 3 groups (MI+RDN, MI, and control groups). At the end of PES, heart and kidney samples were harvested. Immunofluorescence labeling was used to investigate the distribution of connexin 43 (Cx43) in the infarcted border zone. Masson's trichrome stain was adopted to determine the degree of cardiac fibrosis. Western blotting was performed to identify the expression of transforming growth factor beta 1 (TGF-ß1), α-smooth muscle actin (α-SMA), and Cx43. An enzyme-linked immunosorbent assay (ELISA) was used to detect the serum levels of B-type natriuretic peptide (BNP) and the amino-terminal pro-peptides of type I and III collagen (PINP and PIIINP, respectively) and the expression level of renal norepinephrine. RESULTS: Compared with the MI group, RDN significantly decreased the inducibility of VAs (MI+RDN 3/8 rats vs. MI 8/9 rats, P < 0.05; control 1/8 rats) with PES, reduced myocardial fibrosis estimated by collagen volume fraction (MI+RDN 31.10 ± 3.97% vs. MI 54.80 ± 16.39%, P < 0.001; control 4.41 ± 0.92% ), suppressed TGF-ß1 (P < 0.01) and α-SMA (P < 0.001) levels, and attenuated both PINP (MI+RDN 41.44 ± 10.10 ng/mL vs. MI 95.49 ± 24.83 ng/mL, P < 0.001; control 11.90 ± 4.96 ng/mL) and PIIINP (MI+RDN 82.12 ± 30.79 ng/mL vs. MI 124.60 ± 26.64 ng/mL, P < 0.05; control 64.69 ± 23.84 ng/mL) levels. Moreover, RDN reversed the abnormal myocardial distribution of Cx43 and its reduction by MI damage (P < 0.01). CONCLUSIONS: RDN reduced myocardial fibrosis and suppressed VAs in a rat model of ischemic cardiomyopathy.

Cardiac resynchronization therapy improves left ventricular remodeling and function compared with right ventricular pacing in patients with atrioventricular block.

Right ventricular pacing (RVP) exerts a detrimental effect on left ventricular (LV) remodeling. In patients with atrioventricular block (AVB) that require ventricular pacing, the effect of biventricular pacing (BiVP) versus RVP on LV remodeling and function has not been comprehensively assessed in a meta-analysis. Electric databases MEDLINE and Cochrane Library were retrieved for randomized controlled trials (RCT) comparing RVP and BiVP in patients with AVB. Data on left ventricular ejection fraction (LVEF) and LV volumes were analyzed, stratified by different time points. Eleven RCTs were included in the final analysis. There was a significant reduction of LV end-systolic volume in BiVP compared with RVP, at 3, 6, 12, and 24 months follow-up (P < 0.05 for all). BiVP was associated with a decreased LV end-diastolic volume in comparison to RVP at 3, 6, and 12 months. Compared with RVP, BiVP had a higher LVEF at all follow-up visits, with mean difference of 5.91, 3.29, 3.9, 6.66, and 8.69% at 3, 6, 12, 24, and beyond 24 months follow-up, respectively. The results were not significantly changed in sensitivity analysis after removal of studies with mean baseline LVEF < 50% or excluding studies with ablation-induced AVB. In patients with AVB and bradycardia that require ventricular pacing, BiVP is superior to RVP in improving LV remodeling and function.

Clinical outcomes with biventricular versus right ventricular pacing in patients with atrioventricular conduction defects.

There have been increasing concerns about the unexpected effects of right ventricular (RV) pacing. We aimed to systematically evaluate the effect of biventricular (BiV) versus RV pacing on clinical events in patients with impaired AV conduction. We searched PubMed, EMBASE, and Cochrane Library for studies comparing BiV pacing with RV pacing in patients with AV block, through April 2017. We selected randomized controlled trials (RCTs) reporting data on mortality, hospitalization for heart failure (HF), and/or 6-min walk distance (6MWD). A total of 12 RCTs were finally included. Pooled analysis suggested that BiV pacing was associated with a significantly reduced all-cause mortality in contrast to RV pacing (risk ratio (RR) = 0.77, 95% confidence interval (CI) 0.62 to 0.95, I2 = 9.6%). BiV pacing, compared with RV pacing, significantly reduced the rate of HF hospitalization (RR = 0.74, 95% CI 0.59 to 0.93, I2 = 10.1%). Sensitivity analyses by excluding studies with AV nodal ablation showed that BiV pacing still had a lower mortality and non-significant reduced HF hospitalization. Patients in BiV and RV pacing mode had a similar 6WMD at follow-up (mean difference = 4.99 m, 95% CI - 11.34 to 21.33 m, I2 = 0%). Meta-regression analysis showed that the effect size of all-cause mortality or HF hospitalization was not significantly associated with mean LVEF value at baseline. In patients with impaired AV conduction that need frequent ventricular pacing, BiV pacing was associated with reduced mortality and hospitalization for HF, compared with traditional RV pacing mode.