Anti-inflammatory effect of rosiglitazone is not reflected in expression of NFκB-related genes in peripheral blood mononuclear cells of patients with type 2 diabetes mellitus

Background

The aim of this study is to perform a cost-effectiveness comparison between palpation-guided thyroid fine-needle aspiration biopsies (P-FNA) and ultrasound-guided thyroid FNA biopsies (USG-FNA).

Methods

Each nodule was considered as a case. Diagnostic steps were history and physical examination, TSH measurement, Tc^99m thyroid scintigraphy for nodules with a low TSH level, initial P-FNA versus initial USG-FNA, repeat USG-FNA for nodules with initial inadequate P-FNA or USG-FNA, hemithyroidectomy for inadequate repeat USG-FNA. American Thyroid Association thyroid nodule management guidelines were simulated in estimating the cost of P-FNA strategy. American Association of Clinical Endocrinologists guidelines were simulated for USG-FNA strategy. Total costs were estimated by adding the cost of each diagnostic step to reach a diagnosis for 100 nodules. Strategy cost was found by dividing the total cost to 100. Incremental cost-effectiveness ratio (ICER) was calculated by dividing the difference between strategy cost of USG-FNA and P-FNA to the difference between accuracy of USG-FNA and P-FNA. A positive ICER indicates more and a negative ICER indicates less expense to achieve one more additional accurate diagnosis of thyroid cancer for USG-FNA.

Results

Seventy-eight P-FNAs and 190 USG-FNAs were performed between April 2003 and May 2008. There were no differences in age, gender, thyroid function, frequency of multinodular goiter, nodule location and diameter (median nodule diameter: 18.4 mm in P-FNA and 17.0 mm in USG-FNA) between groups. Cytology results in P-FNA versus USG-FNA groups were as follows: benign 49% versus 62% (p = 0.04), inadequate 42% versus 29% (p = 0.03), malignant 3% (p = 1.00) and indeterminate 6% (p = 0.78) for both. Eleven nodules from P-FNA and 18 from USG-FNA group underwent surgery. The accuracy of P-FNA was 0.64 and USG-FNA 0.72. Unit cost of P-FNA was 148 Euros and USG-FNA 226 Euros. The cost of P-FNA strategy was 534 Euros and USG-FNA strategy 523 Euros. Strategy cost includes the expense of repeat USG-FNA for initial inadequate FNAs and surgery for repeat inadequate USG-FNAs. ICER was -138 Euros.

Conclusion

Universal application of USG-FNA for all thyroid nodules is cost-effective and saves 138 Euros per additional accurate diagnosis of benign versus malignant thyroid nodular disease.

Trial registration

ClinicalTrials.gov, NCT00571090     

Development of a Rapid Assay for Determining the Relative Abundance of Bacteria

A sandwich hybridization assay for high-throughput, rapid, simple, and inexpensive quantification of specific microbial populations was evaluated. The assay is based on the hybridization of a target rRNA with differentially labeled capture and detector probes. Betaproteobacterial ammonia-oxidizing bacteria (AOB) were selected as the target group for the study, since they represent a phylogenetically coherent group of organisms that perform a well-defined geochemical function in natural and engineered environments. Reagent concentrations, probe combinations, and washing, blocking, and hybridization conditions were optimized to improve signal and reduce background. The detection limits for the optimized RNA assay were equivalent to approximately 10³ to 10⁴ and 10⁴ to 10⁵ bacterial cells, respectively, for E. coli rRNA and RNA extracted from activated sludge, by using probes targeting the majority of bacteria. Furthermore, the RNA assay had good specificity, permitted discrimination of rRNA sequences that differed by a 2-bp mismatch in the probe target region, and could distinguish the sizes of AOB populations in nitrifying and nonnitrifying wastewater treatment plants.     

Synthetic oligoureas of metaphenylenediamine mimic host defence peptides in their antimicrobial behaviour

Oligomeric ureas of m-phenylenediamine target anionic DMPG (dimyristoylphosphatidylglycerol) and possess promise as antimicrobial agents. Their similar size, shape and hydrophobicity to helical antimicrobial peptides (AMPs) may be important for activity to exist and the ability of these compounds to insert into a well ordered lipid environment.     

Identifying wheat genomic regions for improving grain protein concentration independently of grain yield using multiple inter-related populations

Grain yield (GY) and grain protein concentration (GPC) are two major traits contributing to the economic value of the wheat crop. These are, consequently, major targets in wheat breeding programs, but their simultaneous improvement is hampered by the negative correlation between GPC and GY. Identifying the genetic determinants of GPC and GY through quantitative trait loci (QTL) analysis would be one way to identify chromosomal regions, allowing improvement of GPC without reducing GY using marker-assisted selection. Therefore, QTL detection was carried out for GY and GPC using three inter-connected doubled haploid populations grown in a large multi-environment trial network. Chromosomes 2A, 2D, 3B, 7B and 7D showed co-location of QTL for GPC and GY with antagonistic effects, thus contributing to the negative GPC–GY relationship. Nonetheless, genomic regions determining GPC independently of GY across experiments were found on chromosomes 3A and 5D and could help breeders to move the GPC–GY relationship in a desirable direction.     

Persistence of bactericidal antibodies following early infant vaccination with a serogroup B meningococcal vaccine and immunogenicity of a preschool booster dose

Background:

The multicomponent serogroup B meningococcal (4CMenB) vaccine was recently licensed for use in Europe. There are currently no data on the persistence of bactericidal antibodies induced by use of this vaccine in infants. Our objective was to evaluate serogroup B–specific bactericidal antibodies in children aged 40–44 months previously vaccinated at 2, 4, 6 and 12 months of age.

Methods:

Participants given 4 doses of 4CMenB as infants received a fifth dose of the vaccine at 40–44 months of age. Age-matched participants who were MenB vaccine–naive received 4CMenB and formed the control group. We evaluated human complement serum bactericidal activity (hSBA) titres at baseline and 1 month after each dose of 4CMenB.

Results:

Before a booster dose at enrolment, 41%–76% of 17 participants previously vaccinated with 4CMenB in infancy had hSBA titres of 4 or greater against 4 reference strains. Before vaccination in the control group (n = 40) these proportions were similar for strains 44/76-SL (63%) and {"type":"entrez-nucleotide","attrs":{"text":"M10713","term_id":"209124","term_text":"M10713"}}M10713 (68%) but low for strains NZ98/254 (0%) and 5/99 (3%). A booster dose in the 4CMenB-primed participants generated greater increases in hSBA titres than in controls.

Interpretation:

As has been observed with other meningococcal vaccines, bactericidal antibodies waned after vaccination with 4CMenB administered according to an approved infant vaccination schedule of 2, 4, 6 and 12 months of age, but there was an anamnestic response to a booster dose at 40–44 months of age. If 4CMenB were introduced into routine vaccination schedules, assessment of the need for a booster dose would require data on the impact of these declining titres on vaccine effectiveness. ClinicalTrials.gov, no. {"type":"clinical-trial","attrs":{"text":"NCT01027351","term_id":"NCT01027351"}}NCT01027351A vaccine against serogroup B meningococcus has recently been licensed for use in Europe¹ and is being considered for licensure in Canada. This vaccine, known as multicomponent serogroup B meningococcal (4CMenB) vaccine, consists of 3 recombinant proteins: factor H binding protein (fHbp), Neisseria adhesin A (NadA) and Neisseria heparin binding antigen (NHBA) combined with detoxified outer membrane vesicles from the strain responsible for an epidemic of serogroup B meningococcal disease in New Zealand (NZ98/254). Clinical trials of 4CMenB have shown it to be immunogenic against reference strains selected to speciScally express one of the vaccine antigens.^2–6 On the basis of these trials, the approved schedule for infants aged 2 to 5 months is 3 doses given at least 1 month apart, with a booster dose given at 12 to 23 months of age.⁷ The persistence of vaccine-induced antibodies throughout childhood following this booster dose is unknown, but it is particularly relevant because the incidence of invasive serogroup B meningococcal disease in children aged 1 to 4 years is second only to the incidence in children less than 1 year of age.⁸In this study, we assessed the persistence of these bactericidal antibodies in children aged 40–44 months who had previously received either 4CMenB or a vaccine containing the recombinant proteins alone (recombinant protein serogroup B meningococcal [rMenB] vaccine) at 2, 4, 6 and 12 months of age.³ We also assessed the immunogenicity and reactogenicity of a booster dose.     

A partial genome assay for quantitative trait loci in wheat (Triticum aestivum) using different analytical techniques

F₁ plants between two intervarietal chromosome substitution lines of European spring wheat varieties, Sicco (Chinese Spring 5B) and Highbury (Chinese Spring 5B), were used to produce 114 doubled haploid lines, 45 by the Hordeum bulbosum technique and 69 by anther culture. These two sets of lines were characterized for variation at a range of morphological, isozyme and RFLP marker loci, and genetic maps were developed with emphasis on chromosomes 6B, 7A, 7B and 7D. A subset of lines, scored for production traits in field trials in 1986 and 1987, were analysed for quantitative trait loci (QTL). The performance of the lines for the quantitative traits studied showed no overall differences due to the method of production of the lines. QTL were located on the linkage map for ear emergence time, height, tiller weight, yield and 50-grain weight using four analytical methods. Many of these effects showed genotype x year interaction.     

The eukaryotic translation elongation factor 1A regulation of actin stress fibers is important for infectious RSV production

Cellular protein eukaryotic translation elongation factor 1A (eEF1A) is an actin binding protein that plays a role in the formation of filamentous actin (F-actin) bundles. F-Actin regulates multiple stages of respiratory syncytial virus (RSV) replication including assembly and budding. Our previous study demonstrated that eEF1A knock-down significantly reduced RSV replication. Here we investigated if the eEF1A function in actin bundle formation was important for RSV replication and release. To investigate this, eEF1A function was impaired in HEp-2 cells by either knock-down of eEF1A with siRNA, or treatment with an eEF1A inhibitor, didemnin B (Did B). Cell staining and confocal microscopy analysis showed that both eEF1A knock-down and treatment with Did B resulted in disruption of cellular stress fiber formation and elevated accumulation of F-actin near the plasma membrane. When treated cells were then infected with RSV, there was also reduced formation of virus-induced cellular filopodia. Did B treatment, similarly to eEF1A knock-down, reduced the release of infectious RSV, but unlike eEF1A knock-down, did not significantly affect RSV genome replication. The lower infectious virus production in Did B treated cells also reduced RSV-induced cell death. In conclusion, the cellular factor eEF1A plays an important role in the regulation of F-actin stress fiber formation required for RSV assembly and release.     

The pCLEAN dual binary vector system for Agrobacterium-mediated plant transformation

The development of novel transformation vectors is essential to the improvement of plant transformation technologies. Here, we report the construction and testing of a new multifunctional dual binary vector system, pCLEAN, for Agrobacterium-mediated plant transformation. The pCLEAN vectors are based on the widely used pGreen/pSoup system and the pCLEAN-G/pCLEAN-S plasmids are fully compatible with the existing pGreen/pSoup vectors. A single Agrobacterium can harbor (1) pCLEAN-G and pSoup, (2) pGreen and pCLEAN-S, or (3) pCLEAN-G and pCLEAN-S vector combination. pCLEAN vectors have been designed to enable the delivery of multiple transgenes from distinct T-DNAs and/or vector backbone sequences while minimizing the insertion of superfluous DNA sequences into the plant nuclear genome as well as facilitating the production of marker-free plants. pCLEAN vectors contain a minimal T-DNA (102 nucleotides) consisting of direct border repeats surrounding a 52-nucleotide-long multiple cloning site, an optimized left-border sequence, a double left-border sequence, restriction sites outside the borders, and two independent T-DNAs. In addition, selectable and/or reporter genes have been inserted into the vector backbone sequence to allow either the counter-screening of backbone transfer or its exploitation for the production of marker-free plants. The efficiency of the different pCLEAN vectors has been assessed using transient and stable transformation assays in Nicotiana benthamiana and/or Oryza sativa.     

黄檗丛枝菌根真菌鉴定

目的：利用形态学特征与Nested-PCR技术鉴定黄檗丛枝菌根真菌。方法：采用酸性品红染色法挑选黄檗丛枝菌根。同时,利用湿筛法获得AM真菌孢子,进行形态学鉴定。运用Nested-PCR技术,对黄檗粗提DNA进行特异性扩增,采用blastn进行序列相似性比较。并构建系统进化树,确定侵染黄檗根系的AM真菌。结果：编号为HDAM-1的AM真菌孢子,形态特征与G．intraradices的特征描述一致。Nested-PCR检测到约455bp的目的片段,其序列与G．intraradices（DQ469118）相似性最高,达97．8％,有11个碱基的差异。系统进化树显示该序列在基于25S rDNA的进化树中与G．intraradices（DQ469118．1）处于同一分支,确定G．intraradices侵染黄檗根系。结论：将形态学特征与Nested-PCR技术相结合鉴定AM真菌,不仅简易、经济,而且能够提高研究结果的可靠性。