Individual and combined contributions of non-high-density lipoprotein cholesterol and brachial-ankle pulse wave velocity to cardiovascular disease risk: Results of a prospective study using the Kailuan cohort.

Objective: We aimed to characterize the relationship of a combination of circulating non-high-density lipoprotein-cholesterol (non-HDL-C) concentration and brachial-ankle pulse wave velocity (baPWV) with cardiovascular disease (CVD). Methods: We performed a prospective cohort study of the residents of the Kailuan community, with data from a total of 45,051 participants being included in the final analysis. The participants were allocated to four groups according to their non-HDL-C and baPWV status, each of which was categorized as high or normal. Cox proportional hazards models were used to explore the relationships of non-HDL-C and baPWV, individually and in combination, with the incidence of CVD. Results: During the 5.04-year follow-up period, 830 participants developed CVD. Compared with the Normal non-HDL-C group independently, the multivariable adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for CVD in the High non-HDL-C was 1.25 (1.08-1.46). Compared with the Normal baPWV group independently, the HRs and 95% CIs for CVD in the High baPWV was 1.51 (1.29-1.76). In addition, compared with the Normal both non-HDL-C and baPWV group, the HRs and 95% CIs for CVD in the High non-HDL-C and normal baPWV, Normal non-HDL-C and high baPWV, and High both non-HDL-C and baPWV groups were 1.40 (1.07-1.82), 1.56 (1.30-1.88), and 1.89 (1.53-2.35), respectively. Conclusion: High non-HDL-C concentration and high baPWV are independently associated with a higher risk of CVD, and individuals with high both non-HDL-C and baPWV are at a still higher risk of CVD.

Probabilistic-fuzzy risk assessment and source analysis of heavy metals in soil considering uncertainty: A case study of Jinling Reservoir in China.

Considering the uncertainty caused by the random error of the sample measurement, the heterogeneity of spatial and temporal distribution of pollutants, and the traditional method of selecting a single parameter for evaluation, based on fuzzy theory, Hakanson potential ecological risk index (considering heavy metal enrichment, ecotoxicity and bioavailability) and United States Environmental Protection Agency health risk assessment system, the fuzzy ecological risk and health risk assessment methods for of heavy metals in soil were established. In the soil of the Jinling Reservoir area, Cd, which has high bioavailability, had the highest average contribution rate to RI, and thus was, regarded as a priority metal for ecological risk. Sites JL9 and JL11 were the priority areas. The heavy metals did not pose a clear hazard to human health, but children had a higher health risk. Pb and As were regarded as the priority metals for health risk. Fuzzy evaluation provided the risk interval and membership degree, contained more parameter information, quantified and reduced the uncertainty of parameters, provided more comprehensive results, and compensated for the deficiency of deterministic evaluation. As the main source of heavy metals, the intensity of agricultural activities in the study area must be controlled to avoid excessive input and accumulation of heavy metals, which may damage the ecological environment and endanger human health.

[Lateral supramalleolar artery descending branch antidromic flap for the repair of soft tissue defects in the foot and ankle].

OBJECTIVE: To evaluate the effect of lateral supramalleolar artery descending branch antidromic flap for the repair of soft tissue defects in the foot and ankle. METHODS: From May 2009 to October 2013,12 patients with soft tissue defects combined with tendon and bone exposure in the foot and ankle were treated by lateral supramalleolar artery descending branch antidromic flap for the repair of soft tissue defects in the foot and ankle, including 9 males and 3 females with an average age of 37.5 years old ranging from 19 to 58 years. Ten cases had the soft tissue defects in the dorsum of foot and 2 in the ankle. The defect area of soft tissue was from 11 cm x 9 cm to 8 cm x 5 cm. RESULTS: Twelve patients were follow-up for 3 to 12 months (averaged 7.3 months). The flaps of 9 cases were survived,the flaps edges of the other 3 cases were necrosis,and healed after dressing change. The flaps were slightly swelling without ulcer occurrence. CONCLUSION: Lateral supramalleolar artery descending branch antidromic flap can repairing the damage by one-stage operation with advantage of dissection easy,rich blood supply without sacrifice of major artery.

Detection of tetrahydrobiopterin by LC-MS/MS in plasma from multiple species.

BACKGROUND: Tetrahydrobiopterin (BH4) is a naturally occurring pteridine and cofactor for a variety of enzymes, including phenylalanine-4-hydroxylase, nitric oxide synthetase and glyceryl ether monooxygenase. BH4 is readily oxidized to dihydrobiopterin and biopterin (B), however only BH4 can provide proper cofactor functions. BH4 is the active ingredient in Kuvan™ for the treatment of phenylketonuria. In order to measure BH4 in plasma from nonclinical and clinical samples with good accuracy, precision, sensitivity and robustness, an LC-MS/MS method was validated. To overcome the oxidation of BH4 in postcollection plasma, the approach was to measure the concentration of BH4 indirectly by measuring B concentration and applying an oxidation conversion ratio. Different endogenous levels of BH4 are determined in human, monkey, dog, rabbit, rat and mouse plasma. Furthermore, the conversion ratio of BH4 to B for each species is different and determined empirically. Plasma is transferred into cryogenic vials containing 0.1% dithioerythritol to prevent oxidation of BH4. The samples are then extracted and oxidized under basic conditions. B is measured with LC-MS/MS using negative ion mode. RESULTS: The method is accurate, and precise to within 15%. The lower limit of quantitation in matrix is 5, 50 or 100 ng/ml, depending on the species endogenous levels of BH4. The pharmacokinetics of a single oral dose at three concentrations of BH4 administered to C57BL/6 mice is presented. In this mouse study, the T(1/2) of BH4 in plasma was approximately 1.2 h. CONCLUSION: The validated LC-MS/MS method to determine plasma BH4 concentration described herein has been used to support many nonclinical and clinical toxicokinetic and pharmacokinetic studies. BH4 is sensitive to oxidation and has a complicated biology. The method successfully supported the approval of Kuvan for the treatment of phenylketonuria.

A method for the low-level (ng/g) determination of perfluorooctanoate in carpet by LC-MS-MS using matrix extracted standards.

Fluorotelomer-based acrylic polymers are applied to the surface of carpet to impart oil, stain, and water repellence properties. Concerns that fluorotelomer-based polymers are a possible source of "low level" exposure to humans, coupled with their widespread use have prompted the need to develop a method to detect and measure perfluorooctanoate (PFO) in carpet. A liquid chromatography tandem mass spectrometry method for the determination of PFO in carpet using a dual labeled 13C-perfluoroctanoic acid (13C-PFOA) internal standard is successfully developed and validated. Levels of PFO are determined using a gradient, reversed-phase high-performance liquid chromatography (HPLC) method with acetic acid acidified water-methanol, separated on a 50 mm Phenomenex Synergi Polar RP column. Ions monitored are 413 (parent) and 369 (daughter) for PFO and 415 (parent) and 370 (daughter) for dual labeled 13C-PFOA internal standard. Accuracy and precision over three days for 5 to 900 ng/g PFO in carpet ranged from 2.4% to 7.6% and 3.7% to 14.1%, respectively. Overall extraction efficiency for samples (n=30) fortified with 13C-PFOA at 20 ng/g and perfluorooctanoic acid (PFOA) at 5, 50, and 500 ng/g is 98.9%+/-8.1%. Specificity of the method was evaluated with two different carpet samples.

Determination of rifalazil, a potent antibacterial agent, in human plasma by liquid-liquid extraction and LC-MS/MS.

A sensitive assay for determination of rifalazil (also known as ABI-1648 and KRM-1648) in human plasma is described. The analytical method utilizes liquid-liquid extraction of plasma with methyl tert-butyl ether, followed by reversed-phase liquid chromatography with a C18 column and a mobile phase gradient utilizing 0.1% formic acid in water and acetonitrile, respectively. Electrospray mass spectrometry in the positive ion mode with selected reaction monitoring of rifalazil and an isotope labeled internal standard, 13C4-rifalazil (ABI-9901) was used for selective and sensitive detection. The calibration range was 0.050-50 ng/mL plasma using 200 microL plasma sample volume. The absolute extraction recovery of rifalazil from K2-EDTA plasma, evaluated at three concentration levels, was 88.6-97.3%, and the recovery for the internal standard was 96.8%. A study of plasma matrix effects showed a peak area response at 90-99% compared to neat solutions for both rifalazil and the internal standard. Stability evaluation of rifalazil in plasma, whole blood and methanol showed that the analyte stability was adequate when stored under study conditions. The precision, as evaluated in three validation batches, was consistent for fortified plasma quality control (QC) samples at four concentration levels, with < or =6% R.S.D. except for at the lowest quality control level where it was 10.7% R.S.D. The accuracy for QC samples (difference between found and nominal concentration) ranged from -2.3% to 5.1%. Similar precision and accuracy values were obtained over 6 months of routine application of this method. It was concluded that the performance improved markedly during routine operation by replacing a closely related structural analog internal standard with the stable isotope internal standard.