Randomized Comparative Study of the Effects of Treatment with Once-Daily, Niacin Extended-Release/Lovastatin and with Simvastatin on Lipid Profile and Fibrinolytic Parameters in Taiwan

Hyperlipidemia can be effectively treated either with niacin or HMG-CoA reductase inhibitor (statin), or a combination of both. Few reports showed the effects of the combination regimen with niacin and statin on hemostatic functions. We conducted a single-center, double-blind, double-dummy, randomized, two-arm study to assess the effects of the niacin extended-release/lovastatin therapy in a fixed-dose formulation and of simvastatin on lipid lowering and two fibrinolytic parameters, fibrinogen and d-dimer. All patients were enrolled according to NCEP-ATP III guidelines and underwent a placebo run-in period of 4 weeks before being randomized to either niacin extended-release/lovastatin tablets (500/20 mg) once daily (n = 36) or simvastatin capsule (20 mg) once daily (n = 34). After 16 weeks of treatment, both groups of patients showed significantly reduced low-density lipoprotein cholesterol and total cholesterol (LDL-C, p < 0.001 and < 0.001, respectively, p = 0.159 between the groups; TC, p < 0.001 and < 0.001, respectively, p = 0.018 between the groups). Both drugs were well tolerated. Only in the group treated with niacin extended-release/lovastatin was fibrinogen concentration significantly reduced after treatment (2.48 ± 0.65 to 1.99 ± 0.62 g/L, p = 0.008). No difference was found with d-dimer in either group. This study shows that both niacin extended-release/ lovastatin and simvastatin are effective and well-tolerated lipid-lowering drugs in Taiwanese patients with dyslipidemia. A combinational treatment with niacin extended-release/lovastatin may provide additional benefit in fibrinolysis

Secure Adaptive Topology Control for Wireless Ad-Hoc Sensor Networks

This paper presents a secure decentralized clustering algorithm for wireless ad-hoc sensor networks. The algorithm operates without a centralized controller, operates asynchronously, and does not require that the location of the sensors be known a priori. Based on the cluster-based topology, secure hierarchical communication protocols and dynamic quarantine strategies are introduced to defend against spam attacks, since this type of attacks can exhaust the energy of sensor nodes and will shorten the lifetime of a sensor network drastically. By adjusting the threshold of infected percentage of the cluster coverage, our scheme can dynamically coordinate the proportion of the quarantine region and adaptively achieve the cluster control and the neighborhood control of attacks. Simulation results show that the proposed approach is feasible and cost effective for wireless sensor networks

Evaluation of prognostic factors and the role of chemotherapy in unfavorable carcinoma of unknown primary site: a 10-year cohort study

<p>Abstract</p> <p>Background</p> <p>Carcinoma of unknown primary site (CUP) has a poor prognosis and the prognostic factors in these patients are not well established. Furthermore, there are no selection criteria for patients who should benefit from chemotherapy.</p> <p>Methods</p> <p>The medical records of 179 CUP patients who were treated at Taipei Veterans General Hospital from 2000 to 2009 were reviewed. Factors associated with survival were determined by Kaplan-Meier analysis. Differences between the groups with and without palliative chemotherapy were analyzed.</p> <p>Results</p> <p>Univariate analysis revealed multiple prognostic factors, including performance status, lung metastasis, number of metastatic organs, serum albumin, corrected serum calcium, lactate dehydrogenase (LDH), sodium, and cholesterol levels, palliative chemotherapy, and white blood cell and lymphocyte counts. Multivariate analysis showed that performance status < 2, serum albumin level ≥ 3.5 g/dl, corrected serum calcium level < 10.7 mg/dl, single metastatic organ, and palliative chemotherapy were independent factors of better prognosis. Patients with better performance status, higher serum albumin, and lower serum LDH levels had significantly greater benefit from palliative chemotherapy.</p> <p>Conclusions</p> <p>Certain patients with unfavorable CUP will have better survival. Identification of patients with unfavorable CUP who could benefit from palliative chemotherapy warrants future prospective studies.</p

Association of ORAI1 Haplotypes with the Risk of HLA-B27 Positive Ankylosing Spondylitis

Ankylosing spondylitis (AS) is a chronic inflammation of the sacroiliac joints, spine and peripheral joints. The aetiology of ankylosing spondylitis is still unclear. Previous studies have indicated that genetics factors such as human leukocyte antigen HLA-B27 associates to AS susceptibility. We carried out a case-control study to determine whether the genetic polymorphisms of ORAI1 gene, a major component of store-operated calcium channels that involved the regulation of immune system, is a susceptibility factor to AS in a Taiwanese population. We enrolled 361 AS patients fulfilled the modified New York criteria and 379 controls from community. Five tagging single nucleotides polymorphisms (tSNPs) at ORAI1 were selected from the data of Han Chinese population in HapMap project. Clinical statuses of AS were assessed by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), and Bath Ankylosing Spondylitis Global Index (BAS-G). Our results indicated that subjects carrying the minor allele homozygote (CC) of the promoter SNP rs12313273 or TT homozygote of the SNP rs7135617 had an increased risk of HLA-B27 positive AS. The minor allele C of 3′UTR SNP rs712853 exerted a protective effect to HLA-B27 positive AS. Furthermore, the rs12313273/rs7135617 pairwise allele analysis found that C-G (OR 1.69, 95% CI 1.27, 2.25; p = 0.0003) and T-T (OR 1.75, 95% CI 1.36, 2.27; p<0.0001) haplotypes had a significantly association with the risk of HLA-B27-positive AS in comparison with the T-G carriers. This is the first study that indicate haplotypes of ORAI1 (rs12313273 and rs7135617) are associated with the risk of HLA-B27 positive AS

Serotonin receptor HTR6-mediated mTORC1 signaling regulates dietary restriction-induced memory enhancement

Dietary restriction (DR; sometimes called calorie restriction) has profound beneficial effects on physiological, psychological, and behavioral outcomes in animals and in humans. We have explored the molecular mechanism of DR-induced memory enhancement and demonstrate that dietary tryptophan-a precursor amino acid for serotonin biosynthesis in the brain-and serotonin receptor 5-hydroxytryptamine receptor 6 (HTR6) are crucial in mediating this process. We show that HTR6 inactivation diminishes DR-induced neurological alterations, including reduced dendritic complexity, increased spine density, and enhanced long-term potentiation (LTP) in hippocampal neurons. Moreover, we find that HTR6-mediated mechanistic target of rapamycin complex 1 (mTORC1) signaling is involved in DR-induced memory improvement. Our results suggest that the HTR6-mediated mTORC1 pathway may function as a nutrient sensor in hippocampal neurons to couple memory performance to dietary intake

High levels of serum macrophage migration inhibitory factor and interleukin 10 are associated with a rapidly fatal outcome in patients with severe sepsis

SummaryObjectivesThe aim of this study was to delineate the association between high macrophage migration inhibitory factor (MIF) and interleukin 10 (IL-10) levels in the early phase of sepsis and rapidly fatal outcome.MethodsOne hundred and fifty-three adult subjects with the main diagnosis of severe sepsis (including septic shock) admitted directly from the emergency department of two tertiary medical centers and one regional teaching hospital between January 2009 and December 2011, were included prospectively. MIF and IL-10 levels were measured and outcomes were analyzed by Cox regression analysis according to the following outcomes: rapidly fatal outcome (RFO, death within 48h), late fatal outcome (LFO, death between 48h and 28 days), and survival at 28 days.ResultsAmong the three outcome groups, IL-10 levels were significantly higher in the RFO group (p < 0.001) and no significant differences were seen between the LFO and survivor groups. After Cox regression analysis, each incremental elevation of 1000 pg/ml in both IL-10 and MIF was independently associated with RFO in patients with severe sepsis. Each incremental elevation of 1000 pg/ml in IL-10 increased the RFO risk by a factor of 1.312 (95% confidence interval 1.094–1.575; p=0.003); this was the most significant factor leading to RFO in patients with severe sepsis.ConclusionsPatients with RFO exhibited simultaneously high MIF and IL-10 levels in the early phase of severe sepsis. Incremental increases in both IL-10 and MIF levels were associated with RFO in this patient group, and of the two, IL-10 was the most significant factor linked to RFO

An Improved PSO Algorithm for Generating Protective SNP Barcodes in Breast Cancer

BACKGROUND: Possible single nucleotide polymorphism (SNP) interactions in breast cancer are usually not investigated in genome-wide association studies. Previously, we proposed a particle swarm optimization (PSO) method to compute these kinds of SNP interactions. However, this PSO does not guarantee to find the best result in every implement, especially when high-dimensional data is investigated for SNP-SNP interactions. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we propose IPSO algorithm to improve the reliability of PSO for the identification of the best protective SNP barcodes (SNP combinations and genotypes with maximum difference between cases and controls) associated with breast cancer. SNP barcodes containing different numbers of SNPs were computed. The top five SNP barcode results are retained for computing the next SNP barcode with a one-SNP-increase for each processing step. Based on the simulated data for 23 SNPs of six steroid hormone metabolisms and signalling-related genes, the performance of our proposed IPSO algorithm is evaluated. Among 23 SNPs, 13 SNPs displayed significant odds ratio (OR) values (1.268 to 0.848; p<0.05) for breast cancer. Based on IPSO algorithm, the jointed effect in terms of SNP barcodes with two to seven SNPs show significantly decreasing OR values (0.84 to 0.57; p<0.05 to 0.001). Using PSO algorithm, two to four SNPs show significantly decreasing OR values (0.84 to 0.77; p<0.05 to 0.001). Based on the results of 20 simulations, medians of the maximum differences for each SNP barcode generated by IPSO are higher than by PSO. The interquartile ranges of the boxplot, as well as the upper and lower hinges for each n-SNP barcode (n = 3∼10) are more narrow in IPSO than in PSO, suggesting that IPSO is highly reliable for SNP barcode identification. CONCLUSIONS/SIGNIFICANCE: Overall, the proposed IPSO algorithm is robust to provide exact identification of the best protective SNP barcodes for breast cancer