Lpl-C310R mutation is associated with impaired glucose tolerance and endoplasmic reticulum stress in skeletal muscle.

Primary Hypertriglyceridemia refers to a loss-of-function genetic defect which prevents the triglyceride (TG) in chylomicrons (CM) from lipolysis, leading to the accumulation of TG. The mutation of lipoprotein lipase (LPL) gene has been recognized as the main cause of primary hypertriglyceridemia. Recently, a new LPL gene mutation p.C310R(c. T928C) was identified in a family with hypertriglyceridemia. The proband was manifested by severe hypertriglyceridemia and diabetes. Skeletal muscle is the major LPL-synthesizing tissue and insulin response target tissue. However, little is known about the effects of LPL gene mutation on skeletal muscle. This study is intended to observe the effects of LPL-C310R mutation on glycolipid metabolism and skeletal muscle. We found that a significantly decreased LPL plasma concentration, activity and the expression levels in skeletal muscle were observed in LplC310R/+ mice comparing to wild type mice. Those mutant mice also exhibited increased fasting plasma TG, free fat acids (FFA) and insulin, as well as FFA in muscle, and decreased glucose tolerance. Enhanced expression of BIP and elevated phosphorylation of IRE1α were observed in skeletal muscle, suggesting increased endoplasmic reticulum stress (ERS). Consistent with this, increased phosphorylation of JNK was also observed. Meanwhile, remarkably enhanced phosphorylation of IRS-1 (Ser307) and decreased phosphorylation of AKT were observed in skeletal muscle of mutant mice, suggesting impaired insulin signaling. Significant lipid deposition and morphological changes in endoplasmic reticulum and mitochondria were observed in the skeletal muscle of mutant mice but not in wild type control. Results demonstrate Lpl C310R mutation caused impaired glucose tolerance, ER stress and impaired insulin signaling in skeletal muscle.

Development of genic SSR markers from transcriptome sequencing of pear buds.

A total of 8375 genic simple sequence repeat (SSR) loci were discovered from a unigene set assembled from 116282 transcriptomic unigenes in this study. Dinucleotide repeat motifs were the most common with a frequency of 65.11%, followed by trinucleotide (32.81%). A total of 4100 primer pairs were designed from the SSR loci. Of these, 343 primer pairs (repeat length ≥15 bp) were synthesized with an M13 tail and tested for stable amplification and polymorphism in four Pyrus accessions. After the preliminary test, 104 polymorphic genic SSR markers were developed; dinucleotide and trinucleotide repeats represented 97.11% (101) of these. Twenty-eight polymorphic genic SSR markers were selected randomly to further validate genetic diversity among 28 Pyrus accessions. These markers displayed a high level of polymorphism. The number of alleles at these SSR loci ranged from 2 to 17, with a mean of 9.43 alleles per locus, and the polymorphism information content (PIC) values ranged from 0.26 to 0.91. The UPGMA (unweighted pair-group method with arithmetic average) cluster analysis grouped the 28 Pyrus accessions into two groups: Oriental pears and Occidental pears, which are congruent to the traditional taxonomy, demonstrating their effectiveness in analyzing Pyrus phylogenetic relationships, enriching rare Pyrus EST-SSR resources, and confirming the potential value of a pear transcriptome database for the development of new SSR markers.

Real-time continuous glucose monitoring shows high accuracy within 6 hours after sensor calibration: a prospective study.

Accurate and timely glucose monitoring is essential in intensive care units. Real-time continuous glucose monitoring system (CGMS) has been advocated for many years to improve glycemic management in critically ill patients. In order to determine the effect of calibration time on the accuracy of CGMS, real-time subcutaneous CGMS was used in 18 critically ill patients. CGMS sensor was calibrated with blood glucose measurements by blood gas/glucose analyzer every 12 hours. Venous blood was sampled every 2 to 4 hours, and glucose concentration was measured by standard central laboratory device (CLD) and by blood gas/glucose analyzer. With CLD measurement as reference, relative absolute difference (mean±SD) in CGMS and blood gas/glucose analyzer were 14.4%±12.2% and 6.5%±6.2%, respectively. The percentage of matched points in Clarke error grid zone A was 74.8% in CGMS, and 98.4% in blood gas/glucose analyzer. The relative absolute difference of CGMS obtained within 6 hours after sensor calibration (8.8%±7.2%) was significantly less than that between 6 to 12 hours after calibration (20.1%±13.5%, p<0.0001). The percentage of matched points in Clarke error grid zone A was also significantly higher in data sets within 6 hours after calibration (92.4% versus 57.1%, p<0.0001). In conclusion, real-time subcutaneous CGMS is accurate in glucose monitoring in critically ill patients. CGMS sensor should be calibrated less than 6 hours, no matter what time interval recommended by manufacturer.

Cost-effectiveness analysis of neonatal hearing screening program in China: should universal screening be prioritized?

BACKGROUND: Neonatal hearing screening (NHS) has been routinely offered as a vital component of early childhood care in developed countries, whereas such a screening program is still at the pilot or preliminary stage as regards its nationwide implementation in developing countries. To provide significant evidence for health policy making in China, this study aims to determine the cost-effectiveness of NHS program implementation in case of eight provinces of China. METHODS: A cost-effectiveness model was conducted and all neonates annually born from 2007 to 2009 in eight provinces of China were simulated in this model. The model parameters were estimated from the established databases in the general hospitals or maternal and child health hospitals of these eight provinces, supplemented from the published literature. The model estimated changes in program implementation costs, disability-adjusted life years (DALYs), average cost-effectiveness ratio (ACER), and incremental cost-effectiveness ratio (ICER) for universal screening compared to targeted screening in eight provinces. RESULTS AND DISCUSSION: A multivariate sensitivity analysis was performed to determine uncertainty in health effect estimates and cost-effectiveness ratios using a probabilistic modeling technique. Targeted strategy trended to be cost-effective in Guangxi, Jiangxi, Henan, Guangdong, Zhejiang, Hebei, Shandong, and Beijing from the level of 9%, 9%, 8%, 4%, 3%, 7%, 5%, and 2%, respectively; while universal strategy trended to be cost-effective in those provinces from the level of 70%, 70%, 48%, 10%, 8%, 28%, 15%, 4%, respectively. This study showed although there was a huge disparity in the implementation of the NHS program in the surveyed provinces, both universal strategy and targeted strategy showed cost-effectiveness in those relatively developed provinces, while neither of the screening strategy showed cost-effectiveness in those relatively developing provinces. This study also showed that both strategies especially universal strategy achieve a good economic effect in the long term costs. CONCLUSIONS: Universal screening might be considered as the prioritized implementation goal especially in those relatively developed provinces of China as it provides the best health and economic effects, while targeted screening might be temporarily more realistic than universal screening in those relatively developing provinces of China.