Victims of major electrical trauma frequently suffer extensive skeletal muscle and nerve damage, which is postulated to be principally mediated by electroporation and/or thermally driven cell membrane permeabilization. We have investigated the efficacy oftwo blood-compatible chemical surfactants for sealing electroporated muscle membranes. In studies using cultured skeletal muscle cells, poloxamer 188 (P188; an 8. Membrane damage is often manifested clinically by release of intracellular contents into the intravascular space (5), one of the clinical hallmarks of major electrical trauma. Skeletal muscle and peripheral nerve necrosis appears to be the primary cause of the high amputation rates associated with electrical trauma. We have postulated that, in the majority of victims, cell membrane permeabilization is the most important pathophysiologic event leading to tissue death (4,6,7) and, therefore, effective therapy for victims of electric shock must reestablish cell membrane structural integrity.Because membranes form spontaneously when surfactants (amphiphiles) are mixed in an aqueous solvent at sufficient concentration, we hypothesized that it may be possible to seal damaged cell membranes by exposing them to adequate concentrations of a noncytotoxic nonionic surfactant, possibly by incorporation of the surfactant into the membrane defects. In a preliminary test of this concept, we found that an 8.4-kDa nonionic synthetic surfactant, poloxamer 188 (P188), which has been clinically accepted for human intravenous administration, effectively sealed electroporated membranes of cultured skeletal muscle cells when used in concentrations >0.5 mg/ml (8, 9). We also noted that sealing the membrane enhanced cell survival as measured by vital dye [i.e., carboxyfluorescein (CF) and trypan blue] assays. The ability of P188 to bind to damaged membranes has been suggested in previous studies (10, 11).The purposes of this investigation were to determine whether the observed membrane effects of P188 on isolated cells were relatively specific to its molecular properties by comparing P188 with a neutral polysaccharide known to adsorb on the lipid bilayer (12), to determine whether the P188 and neutral polysaccharide would also reach damaged cell membranes in situ via intravenous administration and seal them after electropermeabilization, and, most important, to determine whether membrane sealing could prevent tissue necrosis following electrical injury.
MATERIALS AND METHODS
Chronic hepatitis B virus (HBV) infection is a major health issue, especially in Asia.A recent genome-wide association study (GWAS) implicated genetic variants in the human leukocyte antigen (HLA)-DP locus associated with chronic hepatitis B in Japanese and Thai populations. To confirm whether the polymorphisms at the HLA-DP genes are associated with persistent chronic HBV infection in Han Chinese, we conducted an independent casecontrol study using 521 persistent chronic HBV carriers and 819 controls that included 571 persons with HBV natural clearance and 248 never HBV-infected (healthy) individuals. Eleven single nucleotide polymorphisms (SNPs) in a region including HLA-DPA and HLA-DPB and an adjacent SNP in strong linkage disequilibrium (LD) with a neighboring HLA-DR13 locus were genotyped using the TaqMan SNP genotyping assay. Eleven variants at HLA-DP showed a strong association with persistent chronic HBV carrier status (P 5 1.82 3 10 212 to 0.01). We also stratified the analysis by HBV clearance status to test the association between these polymorphisms and HBV natural clearance; similar results were obtained (P 5 2.70 3 10 211 to 0.003). Included SNPs define highly structured haplotypes that were also strongly associated with HBV chronic infection (block 1: odds ratio [OR] 5 0.54, P 5 8.73 3 10 27 ; block 2: OR 5 1.98, P 5 1.37 3 10 210 ). These results further confirm that genetic variants in the HLA-DP locus are strongly associated with persistent HBV infection in the Han Chinese population. (HEPATOLOGY 2011;53:422-428)
BackgroundCucumber, Cucumis sativus L., is an economically important vegetable crop which is processed or consumed fresh worldwide. However, the narrow genetic base in cucumber makes it difficult for constructing high-density genetic maps. The development of massively parallel genotyping methods and next-generation sequencing (NGS) technologies provides an excellent opportunity for developing single nucleotide polymorphisms (SNPs) for linkage map construction and QTL analysis of horticultural traits. Specific-length amplified fragment sequencing (SLAF-seq) is a recent marker development technology that allows large-scale SNP discovery and genotyping at a reasonable cost. In this study, we constructed a high-density SNP map for cucumber using SLAF-seq and detected fruit-related QTLs.ResultsAn F2 population of 148 individuals was developed from an intra-varietal cross between CC3 and NC76. Genomic DNAs extracted from two parents and 148 F2 individuals were subjected to high-throughput sequencing and SLAF library construction. A total of 10.76 Gb raw data and 75,024,043 pair-end reads were generated to develop 52,684 high-quality SLAFs, out of which 5,044 were polymorphic. 4,817 SLAFs were encoded and grouped into different segregation patterns. A high-resolution genetic map containing 1,800 SNPs was constructed for cucumber spanning 890.79 cM. The average distance between adjacent markers was 0.50 cM. 183 scaffolds were anchored to the SNP-based genetic map covering 46% (168.9 Mb) of the cucumber genome (367 Mb). Nine QTLs for fruit length and weight were detected, a QTL designated fl3.2 explained 44.60% of the phenotypic variance. Alignment of the SNP markers to draft genome scaffolds revealed two mis-assembled scaffolds that were validated by fluorescence in situ hybridization (FISH).ConclusionsWe report herein the development of evenly dispersed SNPs across cucumber genome, and for the first time an SNP-based saturated linkage map. This 1,800-locus map would likely facilitate genetic mapping of complex QTL loci controlling fruit yield, and the orientation of draft genome scaffolds.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2164-15-1158) contains supplementary material, which is available to authorized users.
Results from this study demonstrate enhanced uptake of 2-DG-labeled gold nanoparticle by cancer cells in vitro and warrant further experiments to study the exact molecular mechanism by which the AuNP-DG is internalized and retained in the tumor cells.
AimsTo test the hypothesis that delivery of integrated care augmented by a web‐based disease management programme and nurse coordinator would improve treatment target attainment and health‐related behaviour.MethodsThe web‐based Joint Asia Diabetes Evaluation (JADE) and Diabetes Monitoring Database (DIAMOND) portals contain identical built‐in protocols to integrate structured assessment, risk stratification, personalized reporting and decision support. The JADE portal contains an additional module to facilitate structured follow‐up visits. Between January 2009 and September 2010, 3586 Chinese patients with Type 2 diabetes from six sites in China were randomized to DIAMOND (n = 1728) or JADE, plus nurse‐coordinated follow‐up visits (n = 1858) with comprehensive assessments at baseline and 12 months. The primary outcome was proportion of patients achieving ≥ 2 treatment targets (HbA1c < 53 mmol/mol (7%), blood pressure < 130/80 mmHg and LDL cholesterol < 2.6 mmol/l).ResultsOf 3586 participants enrolled (mean age 57 years, 54% men, median disease duration 5 years), 2559 returned for repeat assessment after a median (interquartile range) follow‐up of 12.5 (4.6) months. The proportion of participants attaining ≥ 2 treatment targets increased in both groups (JADE 40.6 to 50.0%; DIAMOND 38.2 to 50.8%) and there were similar absolute reductions in HbA1c [DIAMOND −8 mmol/mol vs JADE −7 mmol/mol (−0.69 vs −0.62%)] and LDL cholesterol (DIAMOND −0.32 mmol/l vs JADE −0.28 mmol/l), with no between‐group difference. The JADE group was more likely to self‐monitor blood glucose (50.5 vs 44.2%; P = 0.005) and had fewer defaulters (25.6 vs 32.0%; P < 0.001).ConclusionsIntegrated care augmented by information technology improved cardiometabolic control, with additional nurse contacts reducing the default rate and enhancing self‐care. (Clinical trials registry no.: NCT01274364)
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