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Sample records for addition significant associations

  1. Addition of Cryoprotectant Significantly Alters the Epididymal Sperm Proteome

    PubMed Central

    Yoon, Sung-Jae; Rahman, Md Saidur; Kwon, Woo-Sung; Park, Yoo-Jin; Pang, Myung-Geol

    2016-01-01

    Although cryopreservation has been developed and optimized over the past decades, it causes various stresses, including cold shock, osmotic stress, and ice crystal formation, thereby reducing fertility. During cryopreservation, addition of cryoprotective agent (CPA) is crucial for protecting spermatozoa from freezing damage. However, the intrinsic toxicity and osmotic stress induced by CPA cause damage to spermatozoa. To identify the effects of CPA addition during cryopreservation, we assessed the motility (%), motion kinematics, capacitation status, and viability of epididymal spermatozoa using computer-assisted sperm analysis and Hoechst 33258/chlortetracycline fluorescence staining. Moreover, the effects of CPA addition were also demonstrated at the proteome level using two-dimensional electrophoresis. Our results demonstrated that CPA addition significantly reduced sperm motility (%), curvilinear velocity, viability (%), and non-capacitated spermatozoa, whereas straightness and acrosome-reacted spermatozoa increased significantly (p < 0.05). Ten proteins were differentially expressed (two decreased and eight increased) (>3 fold, p < 0.05) after CPA, whereas NADH dehydrogenase flavoprotein 2, f-actin-capping protein subunit beta, superoxide dismutase 2, and outer dense fiber protein 2 were associated with several important signaling pathways (p < 0.05). The present study provides a mechanistic basis for specific cryostresses and potential markers of CPA-induced stress. Therefore, these might provide information about the development of safe biomaterials for cryopreservation and basic ground for sperm cryopreservation. PMID:27031703

  2. Significant Association Between Adiponutrin and Hepatocellular Carcinoma Risk.

    PubMed

    Li, Hong-Guang; Liu, Fang-Feng; Zhu, Hua-Qiang; Zhou, Xu; Lu, Jun; Chang, Hong; Hu, Jin-Hua

    2015-11-01

    ADPN I148M polymorphism has been consistently reported to play a role in liver-associated diseases, such as alcoholic liver disease, chronic hepatitis C, and liver fat and fibrosis in nonalcoholic fatty liver disease. This significant association was also indicated in a series of hepatocellular carcinoma (HCC) studies, where the significance may be affected due to the small sample sizes. The aim of this study was to reexamine the ADPN-HCC association by use of meta-analysis. Biweekly computer-based literature searches plus manual screening were undertaken in an effort to identify all studies that met the predefined inclusion criteria. The Mantel-Haenszel method was selected to estimate risk effects (odds ratio [OR] and 95% confidence interval [CI]). To examine reliability of the pooled risk effects, we additionally performed sensitivity analysis and publication bias tests. Ten studies (1335 HCC patients and 2927 HCC-free controls) were identified for the meta-analysis. We found significantly increased risk of HCC attributable to presence of ADPN I148M polymorphism, with the highest risk associated with the M/M genotype under the recessive model of inheritance (OR = 2.23, 95% CI = 1.87-2.67, between-study heterogeneity: P = 0.468). The significant increase persisted in Caucasian and African when data were stratified by ethnicity. Subgroup analysis according to source of controls revealed similar risk effects. Our meta-analysis indicates that I148M polymorphism in the ADPN gene may independently contribute to the progression of HCC irrespective of the etiologies. PMID:26632699

  3. Clinical Significance of Additional Ablation of Atrial Premature Beats after Catheter Ablation for Atrial Fibrillation

    PubMed Central

    Kim, In-Soo; Yang, Pil-Sung; Kim, Tae-Hoon; Park, Junbeum; Park, Jin-Kyu; Uhm, Jae Sun; Joung, Boyoung; Lee, Moon Hyoung

    2016-01-01

    Purpose The clinical significance of post-procedural atrial premature beats immediately after catheter ablation for atrial fibrillation (AF) has not been clearly determined. We hypothesized that the provocation of immediate recurrence of atrial premature beats (IRAPB) and additional ablation improves the clinical outcome of AF ablation. Materials and Methods We enrolled 200 patients with AF (76.5% males; 57.4±11.1 years old; 64.3% paroxysmal AF) who underwent catheter ablation. Post-procedure IRAPB was defined as frequent atrial premature beats (≥6/min) under isoproterenol infusion (5 µg/min), monitored for 10 min after internal cardioversion, and we ablated mappable IRAPBs. Post-procedural IRAPB provocations were conducted in 100 patients. We compared the patients who showed IRAPB with those who did not. We also compared the IRAPB provocation group with 100 age-, sex-, and AF-type-matched patients who completed ablation without provocation (No-Test group). Results 1) Among the post-procedural IRAPB provocation group, 33% showed IRAPB and required additional ablation with a longer procedure time (p=0.001) than those without IRAPB, without increasing the complication rate. 2) During 18.0±6.6 months of follow-up, the patients who showed IRAPB had a worse clinical recurrence rate than those who did not (27.3% vs. 9.0%; p=0.016), in spite of additional IRAPB ablation. 3) However, the clinical recurrence rate was significantly lower in the IRAPB provocation group (15.0%) than in the No-Test group (28.0%; p=0.025) without lengthening of the procedure time or raising complication rate. Conclusion The presence of post-procedural IRAPB was associated with a higher recurrence rate after AF ablation. However, IRAPB provocation and additional ablation might facilitate a better clinical outcome. A further prospective randomized study is warranted. PMID:26632385

  4. Assessing statistical significance in multivariable genome wide association analysis

    PubMed Central

    Buzdugan, Laura; Kalisch, Markus; Navarro, Arcadi; Schunk, Daniel; Fehr, Ernst; Bühlmann, Peter

    2016-01-01

    Motivation: Although Genome Wide Association Studies (GWAS) genotype a very large number of single nucleotide polymorphisms (SNPs), the data are often analyzed one SNP at a time. The low predictive power of single SNPs, coupled with the high significance threshold needed to correct for multiple testing, greatly decreases the power of GWAS. Results: We propose a procedure in which all the SNPs are analyzed in a multiple generalized linear model, and we show its use for extremely high-dimensional datasets. Our method yields P-values for assessing significance of single SNPs or groups of SNPs while controlling for all other SNPs and the family wise error rate (FWER). Thus, our method tests whether or not a SNP carries any additional information about the phenotype beyond that available by all the other SNPs. This rules out spurious correlations between phenotypes and SNPs that can arise from marginal methods because the ‘spuriously correlated’ SNP merely happens to be correlated with the ‘truly causal’ SNP. In addition, the method offers a data driven approach to identifying and refining groups of SNPs that jointly contain informative signals about the phenotype. We demonstrate the value of our method by applying it to the seven diseases analyzed by the Wellcome Trust Case Control Consortium (WTCCC). We show, in particular, that our method is also capable of finding significant SNPs that were not identified in the original WTCCC study, but were replicated in other independent studies. Availability and implementation: Reproducibility of our research is supported by the open-source Bioconductor package hierGWAS. Contact: peter.buehlmann@stat.math.ethz.ch Supplementary information: Supplementary data are available at Bioinformatics online. PMID:27153677

  5. Novel loci and pathways significantly associated with longevity.

    PubMed

    Zeng, Yi; Nie, Chao; Min, Junxia; Liu, Xiaomin; Li, Mengmeng; Chen, Huashuai; Xu, Hanshi; Wang, Mingbang; Ni, Ting; Li, Yang; Yan, Han; Zhang, Jin-Pei; Song, Chun; Chi, Li-Qing; Wang, Han-Ming; Dong, Jie; Zheng, Gu-Yan; Lin, Li; Qian, Feng; Qi, Yanwei; Liu, Xiao; Cao, Hongzhi; Wang, Yinghao; Zhang, Lijuan; Li, Zhaochun; Zhou, Yufeng; Wang, Yan; Lu, Jiehua; Li, Jianxin; Qi, Ming; Bolund, Lars; Yashin, Anatoliy; Land, Kenneth C; Gregory, Simon; Yang, Ze; Gottschalk, William; Tao, Wei; Wang, Jian; Wang, Jun; Xu, Xun; Bae, Harold; Nygaard, Marianne; Christiansen, Lene; Christensen, Kaare; Franceschi, Claudio; Lutz, Michael W; Gu, Jun; Tan, Qihua; Perls, Thomas; Sebastiani, Paola; Deelen, Joris; Slagboom, Eline; Hauser, Elizabeth; Xu, Huji; Tian, Xiao-Li; Yang, Huanming; Vaupel, James W

    2016-01-01

    Only two genome-wide significant loci associated with longevity have been identified so far, probably because of insufficient sample sizes of centenarians, whose genomes may harbor genetic variants associated with health and longevity. Here we report a genome-wide association study (GWAS) of Han Chinese with a sample size 2.7 times the largest previously published GWAS on centenarians. We identified 11 independent loci associated with longevity replicated in Southern-Northern regions of China, including two novel loci (rs2069837-IL6; rs2440012-ANKRD20A9P) with genome-wide significance and the rest with suggestive significance (P < 3.65 × 10(-5)). Eight independent SNPs overlapped across Han Chinese, European and U.S. populations, and APOE and 5q33.3 were replicated as longevity loci. Integrated analysis indicates four pathways (starch, sucrose and xenobiotic metabolism; immune response and inflammation; MAPK; calcium signaling) highly associated with longevity (P ≤ 0.006) in Han Chinese. The association with longevity of three of these four pathways (MAPK; immunity; calcium signaling) is supported by findings in other human cohorts. Our novel finding on the association of starch, sucrose and xenobiotic metabolism pathway with longevity is consistent with the previous results from Drosophilia. This study suggests protective mechanisms including immunity and nutrient metabolism and their interactions with environmental stress play key roles in human longevity. PMID:26912274

  6. Novel loci and pathways significantly associated with longevity

    PubMed Central

    Zeng, Yi; Nie, Chao; Min, Junxia; Liu, Xiaomin; Li, Mengmeng; Chen, Huashuai; Xu, Hanshi; Wang, Mingbang; Ni, Ting; Li, Yang; Yan, Han; Zhang, Jin-Pei; Song, Chun; Chi, Li-Qing; Wang, Han-Ming; Dong, Jie; Zheng, Gu-Yan; Lin, Li; Qian, Feng; Qi, Yanwei; Liu, Xiao; Cao, Hongzhi; Wang, Yinghao; Zhang, Lijuan; Li, Zhaochun; Zhou, Yufeng; Wang, Yan; Lu, Jiehua; Li, Jianxin; Qi, Ming; Bolund, Lars; Yashin, Anatoliy; Land, Kenneth C.; Gregory, Simon; Yang, Ze; Gottschalk, William; Tao, Wei; Wang, Jian; Wang, Jun; Xu, Xun; Bae, Harold; Nygaard, Marianne; Christiansen, Lene; Christensen, Kaare; Franceschi, Claudio; Lutz, Michael W.; Gu, Jun; Tan, Qihua; Perls, Thomas; Sebastiani, Paola; Deelen, Joris; Slagboom, Eline; Hauser, Elizabeth; Xu, Huji; Tian, Xiao-Li; Yang, Huanming; Vaupel, James W.

    2016-01-01

    Only two genome-wide significant loci associated with longevity have been identified so far, probably because of insufficient sample sizes of centenarians, whose genomes may harbor genetic variants associated with health and longevity. Here we report a genome-wide association study (GWAS) of Han Chinese with a sample size 2.7 times the largest previously published GWAS on centenarians. We identified 11 independent loci associated with longevity replicated in Southern-Northern regions of China, including two novel loci (rs2069837-IL6; rs2440012-ANKRD20A9P) with genome-wide significance and the rest with suggestive significance (P < 3.65 × 10−5). Eight independent SNPs overlapped across Han Chinese, European and U.S. populations, and APOE and 5q33.3 were replicated as longevity loci. Integrated analysis indicates four pathways (starch, sucrose and xenobiotic metabolism; immune response and inflammation; MAPK; calcium signaling) highly associated with longevity (P ≤ 0.006) in Han Chinese. The association with longevity of three of these four pathways (MAPK; immunity; calcium signaling) is supported by findings in other human cohorts. Our novel finding on the association of starch, sucrose and xenobiotic metabolism pathway with longevity is consistent with the previous results from Drosophilia. This study suggests protective mechanisms including immunity and nutrient metabolism and their interactions with environmental stress play key roles in human longevity. PMID:26912274

  7. The environment associated with significant tornadoes in Bangladesh

    NASA Astrophysics Data System (ADS)

    Bikos, Dan; Finch, Jonathan; Case, Jonathan L.

    2016-01-01

    This paper investigates the environmental parameters favoring significant tornadoes in Bangladesh through a simulation of ten high-impact events. A climatological perspective is first presented on classifying significant tornadoes in Bangladesh, noting the challenges since reports of tornadoes are not documented in a formal manner. The statistical relationship between United States and Bangladesh tornado-related deaths suggests that significant tornadoes do occur in Bangladesh so this paper identifies the most significant tornadic events and analyzes the environmental conditions associated with these events. Given the scarcity of observational data to assess the near-storm environment in this region, high-resolution (3-km horizontal grid spacing) numerical weather prediction simulations are performed for events identified to be associated with a significant tornado. In comparison to similar events over the United States, significant tornado environments in Bangladesh are characterized by relatively high convective available potential energy, sufficient deep-layer vertical shear, and a propensity for deviant (i.e., well to the right of the mean flow) storm motion along a low-level convergence boundary.

  8. Meconium in perinatal imaging: associations and clinical significance.

    PubMed

    Jerdee, Theodore; Newman, Beverley; Rubesova, Erika

    2015-04-01

    An abnormal location, distribution, volume, or appearance of meconium is associated with a spectrum of bowel abnormalities, including atresia, obstruction, perforation, fistula, aganglionosis, immaturity, and absorptive dysfunction. This review discusses the fetal and perinatal imaging of these entities, their differential diagnoses, clinical significance, and appropriate imaging workup. Understanding the spectrum of normal and abnormal, specific and nonspecific appearances of meconium and its associated abnormalities on imaging will provide a practical, useful framework for performing and interpreting imaging studies and guiding clinical management. PMID:26001945

  9. Papuloerythroderma associated with monoclonal gammopathy of undetermined significance.

    PubMed

    Fujimura, Taku; Okuyama, Ryuhei; Ogawa, Eisaku; Aiba, Setsuya

    2009-04-01

    We describe a 73-year-old Japanese man with papuloerythroderma overlapped with monoclonal gammopathy of undetermined significance (MGUS). Clinically, prominent erythroderma was associated with disseminated pruriginous papules, which were characteristically spared on the axillary and inguinal regions, the cubital and popliteal fossae as well as abdominal and small positional folds. Histopathologically, there was a significant perivascular infiltrate of lymphohistiocytic cells intermingled with eosinophils in the upper dermis. A biochemical profile revealed the presence of immunoglobulin G kappa chain type monoclonal protein in the serum but the absence of hematological neoplasms. We diagnosed the patient as papuloerythroderma with MGUS, and treated him with narrow-band ultraviolet B and topical steroid. His skin changes were improved, but the sharp gamma-globulin peak remained in the electrophoresis of serum protein. This case suggests an association between papuloerythroderma and MGUS. PMID:19348662

  10. Statistically significant deviations from additivity: What do they mean in assessing toxicity of mixtures?

    PubMed

    Liu, Yang; Vijver, Martina G; Qiu, Hao; Baas, Jan; Peijnenburg, Willie J G M

    2015-12-01

    There is increasing attention from scientists and policy makers to the joint effects of multiple metals on organisms when present in a mixture. Using root elongation of lettuce (Lactuca sativa L.) as a toxicity endpoint, the combined effects of binary mixtures of Cu, Cd, and Ni were studied. The statistical MixTox model was used to search deviations from the reference models i.e. concentration addition (CA) and independent action (IA). The deviations were subsequently interpreted as 'interactions'. A comprehensive experiment was designed to test the reproducibility of the 'interactions'. The results showed that the toxicity of binary metal mixtures was equally well predicted by both reference models. We found statistically significant 'interactions' in four of the five total datasets. However, the patterns of 'interactions' were found to be inconsistent or even contradictory across the different independent experiments. It is recommended that a statistically significant 'interaction', must be treated with care and is not necessarily biologically relevant. Searching a statistically significant interaction can be the starting point for further measurements and modeling to advance the understanding of underlying mechanisms and non-additive interactions occurring inside the organisms. PMID:26188643

  11. Genome-wide significant risk associations for mucinous ovarian carcinoma.

    PubMed

    Kelemen, Linda E; Lawrenson, Kate; Tyrer, Jonathan; Li, Qiyuan; Lee, Janet M; Seo, Ji-Heui; Phelan, Catherine M; Beesley, Jonathan; Chen, Xiaoqing; Spindler, Tassja J; Aben, Katja K H; Anton-Culver, Hoda; Antonenkova, Natalia

    2015-08-01

    Genome-wide association studies have identified several risk associations for ovarian carcinomas but not for mucinous ovarian carcinomas (MOCs). Our analysis of 1,644 MOC cases and 21,693 controls with imputation identified 3 new risk associations: rs752590 at 2q13 (P = 3.3 × 10(-8)), rs711830 at 2q31.1 (P = 7.5 × 10(-12)) and rs688187 at 19q13.2 (P = 6.8 × 10(-13)). We identified significant expression quantitative trait locus (eQTL) associations for HOXD9 at 2q31.1 in ovarian (P = 4.95 × 10(-4), false discovery rate (FDR) = 0.003) and colorectal (P = 0.01, FDR = 0.09) tumors and for PAX8 at 2q13 in colorectal tumors (P = 0.03, FDR = 0.09). Chromosome conformation capture analysis identified interactions between the HOXD9 promoter and risk-associated SNPs at 2q31.1. Overexpressing HOXD9 in MOC cells augmented the neoplastic phenotype. These findings provide the first evidence for MOC susceptibility variants and insights into the underlying biology of the disease. PMID:26075790

  12. Genome-wide significant risk associations for mucinous ovarian carcinoma

    PubMed Central

    Kelemen, Linda E.; Lawrenson, Kate; Tyrer, Jonathan; Li, Qiyuan; M. Lee, Janet; Seo, Ji-Heui; Phelan, Catherine M.; Beesley, Jonathan; Chen, Xiaoqin; Spindler, Tassja J.; Aben, Katja K.H.; Anton-Culver, Hoda; Antonenkova, Natalia; Baker, Helen; Bandera, Elisa V.; Bean, Yukie; Beckmann, Matthias W.; Bisogna, Maria; Bjorge, Line; Bogdanova, Natalia; Brinton, Louise A.; Brooks-Wilson, Angela; Bruinsma, Fiona; Butzow, Ralf; Campbell, Ian G.; Carty, Karen; Chang-Claude, Jenny; Chen, Y. Ann; Chen, Zhihua; Cook, Linda S.; Cramer, Daniel W.; Cunningham, Julie M.; Cybulski, Cezary; Dansonka-Mieszkowska, Agnieszka; Dennis, Joe; Dicks, Ed; Doherty, Jennifer A.; Dörk, Thilo; du Bois, Andreas; Dürst, Matthias; Eccles, Diana; Easton, Douglas T.; Edwards, Robert P.; Eilber, Ursula; Ekici, Arif B.; Engelholm, Svend Aage; Fasching, Peter A.; Fridley, Brooke L.; Gao, Yu-Tang; Gentry-Maharaj, Aleksandra; Giles, Graham G.; Glasspool, Rosalind; Goode, Ellen L.; Goodman, Marc T.; Grownwald, Jacek; Harrington, Patricia; Harter, Philipp; Hasmad, Hanis Nazihah; Hein, Alexander; Heitz, Florian; Hildebrandt, Michelle A.T.; Hillemanns, Peter; Hogdall, Estrid; Hogdall, Claus; Hosono, Satoyo; Iversen, Edwin S.; Jakubowska, Anna; Jensen, Allan; Ji, Bu-Tian; Karlan, Beth Y; Kellar, Melissa; Kelley, Joseph L.; Kiemeney, Lambertus A.; Krakstad, Camilla; Kjaer, Susanne K.; Kupryjanczyk, Jolanta; Lambrechts, Diether; Lambrechts, Sandrina; Le, Nhu D.; Lee, Alice W.; Lele, Shashi; Leminen, Arto; Lester, Jenny; Levine, Douglas A.; Liang, Dong; Lissowska, Jolanta; Lu, Karen; Lubinski, Jan; Lundvall, Lene; Massuger, Leon F.A.G.; Matsuo, Keitaro; McGuire, Valerie; McLaughlin, John R.; McNeish, Iain; Menon, Usha; Modugno, Francesmary; Moes-Sosnowska, Joanna; Moysich, Kirsten B.; Narod, Steven A.; Nedergaard, Lotte; Ness, Roberta B.; Nevanlinna, Heli; Azmi, Mat Adenan Noor; Odunsi, Kunle; Olson, Sara H.; Orlow, Irene; Orsulic, Sandra; Weber, Rachel Palmieri; Paul, James; Pearce, Celeste Leigh; Pejovic, Tanja; Pelttari, Liisa M.; Permuth-Wey, Jennifer; Pike, Malcolm C.; Poole, Elizabeth M.; Ramus, Susan J.; Risch, Harvey A.; Rosen, Barry; Rossing, Mary Anne; Rothstein, Joseph H.; Rudolph, Anja; Runnebaum, Ingo B.; Rzepecka, Iwona K.; Salvesen, Helga B.; Schildkraut, Joellen M.; Schwaab, Ira; Shu, Xiao-Ou; Shvetsov, Yurii B; Siddiqui, Nadeem; Sieh, Weiva; Song, Honglin; Southey, Melissa C.; Sucheston, Lara; Tangen, Ingvild L.; Teo, Soo-Hwang; Terry, Kathryn L.; Thompson, Pamela J; Tworoger, Shelley S.; van Altena, Anne M.; Van Nieuwenhuysen, Els; Vergote, Ignace; Vierkant, Robert A.; Wang-Gohrke, Shan; Walsh, Christine; Wentzensen, Nicolas; Whittemore, Alice S.; Wicklund, Kristine G.; Wilkens, Lynne R.; Wlodzimierz, Sawicki; Woo, Yin-Ling; Wu, Xifeng; Wu, Anna H.; Yang, Hannah; Zheng, Wei; Ziogas, Argyrios; Sellers, Thomas A.; Freedman, Matthew L.; Chenevix-Trench, Georgia; Pharoah, Paul D.; Gayther, Simon A.; Berchuck, Andrew

    2015-01-01

    Genome-wide association studies have identified several risk associations for ovarian carcinomas (OC) but not for mucinous ovarian carcinomas (MOC). Genotypes from OC cases and controls were imputed into the 1000 Genomes Project reference panel. Analysis of 1,644 MOC cases and 21,693 controls identified three novel risk associations: rs752590 at 2q13 (P = 3.3 × 10−8), rs711830 at 2q31.1 (P = 7.5 × 10−12) and rs688187 at 19q13.2 (P = 6.8 × 10−13). Expression Quantitative Trait Locus (eQTL) analysis in ovarian and colorectal tumors (which are histologically similar to MOC) identified significant eQTL associations for HOXD9 at 2q31.1 in ovarian (P = 4.95 × 10−4, FDR = 0.003) and colorectal (P = 0.01, FDR = 0.09) tumors, and for PAX8 at 2q13 in colorectal tumors (P = 0.03, FDR = 0.09). Chromosome conformation capture analysis identified interactions between the HOXD9 promoter and risk SNPs at 2q31.1. Overexpressing HOXD9 in MOC cells augmented the neoplastic phenotype. These findings provide the first evidence for MOC susceptibility variants and insights into the underlying biology of the disease. PMID:26075790

  13. PADI2 Is Significantly Associated with Rheumatoid Arthritis

    PubMed Central

    Chang, Xiaotian; Xia, Yifang; Pan, Jihong; Meng, Qingsong; Zhao, Yan; Yan, Xinfeng

    2013-01-01

    Citrullination, a posttranslational modification of peptidyl arginine to citrulline, plays an essential role in rheumatoid arthritis (RA). Citrullination is catalyzed by a group of peptidylarginine deiminases (PADs) including PADI 1, 2, 3, 4 and 6. Many studies have indicated that the gene encoding PADI4 is a factor in susceptibility to RA. Some studies have detected PADI2 expression in RA synovial tissues, suggesting that PADI2 also plays an important role in the disease. This study evaluated the possible association between the PADI2-encoding gene and RA. Seventeen tag SNPs across the PAD locus were genotyped using a custom-designed Illumina 96-SNP VeraCode microarray. Peripheral blood samples were collected from patients with RA (n = 267), ankylosing spondylitis (AS, n = 51) and healthy controls (n = 160). The results of genotyping were verified using Sequenom MassARRAY in an independent cohort of 307 patients with RA, 324 patients with AS and 509 healthy controls. A western blot analysis was performed using synovial tissue from patients with RA (n = 7), osteoarthritis (OA, n = 7) and AS (n = 5) to determine the levels of expression of PADI2. A microarray analysis revealed a significant association between three selected PADI2 SNPs (rs2235926, rs2057094, rs2076616) and the presence of RA. The increased susceptibility to RA associated with rs2235926 (OR = 1.706733, 95% CI = [1.576366–1.866587], p = 0.000839) and rs2057094 (OR = 1.360432, 95% CI = [1.065483–1.869482], p = 0.003291) was further confirmed by the Sequenom MassARRAY. No tag SNPs in the PADI2 locus showed a significant association with AS. Increased expression of PADI2 was detected in RA synovial tissues compared with samples from patients with OA and AS. PADI2 is significantly associated with RA and may be involved in the pathogenesis of the disease. PMID:24339914

  14. Pregnancy-associated breast cancer: significance of early detection.

    PubMed

    Ulery, Maryann; Carter, Linnette; McFarlin, Barbara L; Giurgescu, Carmen

    2009-01-01

    Pregnancy-associated breast cancer (PABC) is defined as cancer of the breast diagnosed during pregnancy and up to 1 year postpartum. Delays in diagnosis are frequently associated with increased morbidity and mortality. The aim of this article is to determine the significance of early detection of PABC and to alert health care providers to include PABC in the differential diagnosis when evaluating a breast mass in the perinatal period. This integrative literature review evaluated 15 research studies by using the hypothetical deductive model of clinical reasoning to determine factors related to diagnosis of PABC. As women delay childbearing, the incidence of PABC increases with age. In the reviewed studies, breast cancer was diagnosed with greater frequency in the postpartum period than during any trimester in pregnancy. Delay in diagnosis is complicated by axillary lymph node metastasis, high-grade tumors at diagnosis, and poor outcomes. Early detection is a significant predictor of improved outcomes. Diagnostic modalities such as ultrasound, mammography, and biopsy can be safely used for diagnostic purposes in the evaluation of potential cases of PABC during pregnancy. PMID:19720336

  15. Additive effect of Lygodium venustum SW. in association with gentamicin.

    PubMed

    Morais-Braga, Maria F B; Souza, Teógenes M; Santos, Karla K A; Guedes, Gláucia M M; Andrade, Jacqueline C; Tintino, Saulo R; Sobral-Souza, Celestina E; Costa, José G M; Saraiva, Antonio A F; Coutinho, Henrique D M

    2016-08-01

    The aim of this work was to evaluate the interactions between gentamicin and the ethanol extract of the fern Lygodium venustum SW (EELV). The ethanol extract of L. venustum was obtained, the phytocompounds were identified and the EELV was assayed by the checkerboard method with gentamicin against two bacterial strains multiresistant to antibiotics. The antibiotic activity of gentamicin, when associated with the extract, was enhanced in an additive manner against both strains. The results indicated that L. venustum can be a source of secondary metabolites to be used in association with antibiotics as aminoglycosides in the antibiotic chemotherapy against resistant bacteria. PMID:26284428

  16. Significantly improved cyclability of lithium manganese oxide under elevated temperature by an easily oxidized electrolyte additive

    NASA Astrophysics Data System (ADS)

    Zhu, Yunmin; Rong, Haibo; Mai, Shaowei; Luo, Xueyi; Li, Xiaoping; Li, Weishan

    2015-12-01

    Spinel lithium manganese oxide, LiMn2O4, is a promising cathode for lithium ion battery in large-scale applications, because it possesses many advantages compared with currently used layered lithium cobalt oxide (LiCoO2) and olivine phosphate (LiFePO4), including naturally abundant resource, environmental friendliness and high and long work potential plateau. Its poor cyclability under high temperature, however, limits its application. In this work, we report a significant cyclability improvement of LiMn2O4 under elevated temperature by using dimethyl phenylphonite (DMPP) as an electrolyte additive. Charge/discharge tests demonstrate that the application of 0.5 wt.% DMPP yields a capacity retention improvement from 16% to 82% for LiMn2O4 after 200 cycles under 55 °C at 1 C (1C = 148 mAh g-1) between 3 and 4.5 V. Electrochemical and physical characterizations indicate that DMPP is electrochemically oxidized at the potential lower than that for lithium extraction, forming a protective cathode interphase on LiMn2O4, which suppresses the electrolyte decomposition and prevents LiMn2O4 from crystal destruction.

  17. TLR3 Plays Significant Roles against HBV-Associated HCC

    PubMed Central

    Chen, Xiao-lan; Xu, Yu-yin; Chen, Li; Wang, Gui-lan; Shen, Yin

    2015-01-01

    Toll-like receptor 3 (TLR3) is a pattern-recognizing receptor that is involved in immune signaling and plays a crucial role in survival by being able to recognize various viral components including double-stranded RNA (dsRNA). The role of TLR3 in hepatocellular carcinoma (HCC) with hepatitis B virus (HBV) infections is not well understood. To investigate the ability of TLR3 in regulating HBV replication in HCC, 80 cases of human HCC were collected and their tissue microarray was made. In HCC cells, the expression and location of TLR3, hepatitis-associated virus, and interstitial immunoreactive cells were assayed with immunohistochemical staining. The apoptosis of tumor cells was also detected by TUNEL stain. Correlations between TLR3 expression and HBV infection, interstitial immunoreactive cells, and cells apoptosis in HCC were investigated. In addition, we explored whether TLR3 agonist dsRNA can inhibit HepG2.2.15 cells secreting HBV. We found that the cytoplasmic expression of TLR3 in HCC is positively related to HBsAg infection and HCC with cirrhosis and promotes interstitial immunoreactive cells infiltration and cancer cells apoptosis. In HepG2.2.15 cells, dsRNA inhibited the secretion of HBV and induced apoptosis. These results indicate that TLR3 signaling activity may be involved in immune responses against HBV in HCC. PMID:25983748

  18. No significant association between malignancy and topical use of pimecrolimus

    PubMed Central

    Margolis, David J; Abuabara, Katrina; Hoffstad, Ole; Wan, Joy; Raimondo, Denise; Bilker, Warren

    2015-01-01

    Importance A black box warning describes a potential risk of malignancy associated with the topical use of pimecrolimus to treat atopic dermatitis (AD) due to its similarity to oral calcineurin inhibitors used in solid organ transplantation and spontaneous reporting of malignancies including lymphomas and cutaneous malignancies. Objective The goal of this study was to evaluate the risk of malignancy in a post marketing study of children exposed to pimecrolimus. Design A longitudinal cohort study. Setting A nation-wide ongoing long-term cohort of children with AD. Participants Children enrolled in the Pediatric Eczema Elective Registry (PEER) who had a history of AD and pimecrolimus use. Main outcome Reports of malignancy in those in PEER as compared to expected rates from the Surveillance Research (SEER) Program. Results 7,457 subjects were enrolled in the PEER study for a total of 26,792 person-years. Children used a mean of 793 (SD 1356) grams of pimecrolimus while enrolled in the study. As of May 2014, 5 malignancies had been reported. These include 2 leukemias, 1 osteosarcoma, and 2 lymphomas. No skin cancers were reported. The Standardized Incidence Ratio (SIR) for all malignancies (primary outcome) based on the age standardized SEER population was 1.2 (0.5, 2.8). As secondary analyses, the SIR (based on 2 cases for each) for lymphoma was 2.9 (0.7, 11.7) and for leukemia was 2.0 (0.5, 8.2). None of these findings were statistically significant. Conclusions and Relevance Based on more than 25,000 person-years of follow-up it seems unlikely that topical pimecrolimus as it was used in the PEER cohort to treat AD is associated with an increased risk of malignancy. PMID:25692459

  19. Additives

    NASA Technical Reports Server (NTRS)

    Smalheer, C. V.

    1973-01-01

    The chemistry of lubricant additives is discussed to show what the additives are chemically and what functions they perform in the lubrication of various kinds of equipment. Current theories regarding the mode of action of lubricant additives are presented. The additive groups discussed include the following: (1) detergents and dispersants, (2) corrosion inhibitors, (3) antioxidants, (4) viscosity index improvers, (5) pour point depressants, and (6) antifouling agents.

  20. Significant reserve additions from oligocene Hackberry Sands utilizing 3-D seismic, upper Texas and Louisiana Gulf Coast

    SciTech Connect

    Zamboras, R.L.

    1995-10-01

    The Oligocene Hackberry sands of the Hackberry Embayment represent a complex and elusive exploration target. 3-D seismic evaluation along the headward erosional limits of the embayment provides a reconstructive framework of tectonic and sedimentation patterns which facilitate hydrocarbon exploration. The 3-D seismic along the Orange County, Texas portion of the Oligocene Hackberry trend indicates: (1) similarities of Hackberry structural and depositional setting to that of the underlying Eocene Yegua Formation; (2) four distinct cyclical sedimentation episodes associated with basin floor slump faulting: (3) the usefulness of seismic attributes as direct hydrocarbon indicators, and (4) the potential for significant oil and gas reserves additions in a mature trend. The Hackberry embayment represents a microcosm of the basin structural and depositional processes. Utilizing 3-D seismic to lower risk and finding cost will renew interest in trends such as the Hackberry of the Upper Texas-Louisiana Gulf Coast.

  1. Investigation of smart inspection of critical layer reticles using additional designer data to determine defect significance

    NASA Astrophysics Data System (ADS)

    Volk, William W.; Hess, Carl; Ruch, Wayne; Yu, Zongchang; Ma, Weimin; Fisher, Lisa; Vickery, Carl; Ma, Z. Mark

    2003-12-01

    With expected implementation of low k1 lithography on 193nm scanners for 65nm node wafer production, high resolution defect inspection will be needed to insure reticle quality and reticle manufacture process monitoring. Reticle cost and reticle defectivity are both increasing with each shrink to the next node. Simultaneously, system on chip (SoC) designs are increasing in which a large area of the exposure field typically contains dummy patterns and other features which are not electrically active. Knowing which defects will electrically impact device yield and performance can improve reticle manufacturing yield and cycle time -- resulting in lower reticle costs. This investigation examines the feasibility of using additional design data layers for die-to-database reticle inspection to determine in real time the relevance of a reticle defect by its location in the device (Smart InspectionTM). The impact to data preparation and inspection throughput is evaluated. The current prototype algorithm is built on the XPA and XPE die-to-database algorithms for chrome-on-glass and EPSM reticles, respectively. The algorithms implement variable sensitivity based on the additional design data regions. During defect review the defects are intelligently binned into the different predetermined design regions. Tests show the new Smart Inspection algorithm provides the capability of using higher than normal sensitivity in critical regions while reducing sensitivity in less critical regions to filter total defect counts and allow for the review of just defects that matter. Performance characterization of a variable sensitivity Smart Inspection algorithm is discussed in addition to the filtering of the total defect count during review to show the defects that matter to device performance. Using seven critical layer production reticles from a system on chip device we examine the applications of Smart Inspection by layer including active, poly, contact, metal and via layers. Data volume

  2. Significant increase in travel-associated dengue fever in Germany.

    PubMed

    Allwinn, Regina

    2011-08-01

    Increasing numbers of dengue fever (DF) cases reflect the increasing travel mobility together with the expanding geographical distribution of the vector Aedes aegypti. Compared with earlier surveys in Germany, higher incidences occur and correlate well with ongoing outbreaks. Therefore, we investigated 767 serum samples from 594 returning travellers with suspected DF between 2005 and 2010, which where sent from different hospitals in the drainage area Frankfurt/Main. Established diagnostic assays were ELISA, immunofluorescence and chromatographic tests. We obtained 112 dengue-seropositive serum samples from totally 60 patients: the detection rate was 10.1% (60 out of 594). A significant increase was found in 2010. Most patients were aged between 40 and 49, and indirect immunofluorescence technique indicated mainly DF serotype 2. Actual data reveal a significant rise in imported DF cases in 2010 according to an increasing risk to acquire DF virus infection. Nevertheless, dengue haemorrhagic fever and dengue shock syndrome are still rare in travellers, but those with a history of dengue should be tested for DF serotypes and advised to protect themselves well from mosquitoes when travelling to endemic areas. PMID:21311908

  3. Penile tuberculosis associated with monoclonal gammopathy of undetermined significance.

    PubMed

    Wu, Wilfred C H; Chen, Shyh-Chyan; Hsieh, Ju-Ton; Chen, Jun; Chang, Hong-Chiang

    2006-09-01

    Mycobacterium tuberculosis (TB) infection of the penis is a rare but serious problem. We report a case of penile TB in a 75-year-old man who presented with fever and dyspnea. No active lung lesions except pleural and pericardial effusion were found on chest X-ray. Monoclonal gammopathy of undetermined significance was diagnosed after serum and urine electrophoresis studies, and repeated bone marrow studies. Genital examination showed diffuse papulonecrotic skin ulcers involving the whole penile shaft, extending ventrally to the median raphe of the scrotum. Pus smear showed positive acid-fast stain, and culture yielded M. tuberculosis. Culture of pleural and pericardial effusion was also positive for M. tuberculosis. Anti-TB treatment was given with isoniazid, ethambutol, rifampin and pyrazinamide, and the cutaneous lesion was noted to be healed at follow-up 6 months later. Although rare, the possibility of TB as a cause of genital ulcer should be kept in mind. PMID:16959623

  4. Association of Arterial Pressure Volume Index With the Presence of Significantly Stenosed Coronary Vessels

    PubMed Central

    Ueda, Takashi; Miura, Shin-ichiro; Suematsu, Yasunori; Shiga, Yuhei; Kuwano, Takashi; Sugihara, Makoto; Ike, Amane; Iwata, Atsushi; Nishikawa, Hiroaki; Fujimi, Kanta; Saku, Keijiro

    2016-01-01

    Background A blood pressure (BP) monitoring system (PASESA®) can be used to easily analyze the characteristics of central and peripheral arteries during the measurement of brachial BP. Methods We enrolled 108 consecutive patients (M/F = 86/22, age 70 ± 10 years) who underwent coronary angiography (CAG) due to suspected coronary artery disease (CAD) in whom we could measure various parameters using PASESA® in addition to brachial-ankle pulse wave velocity (baPWV). The patients were divided into two groups: patients who did not have significantly stenosed coronary vessel disease (n = 33, non-SVD group) and those who had at least one significantly stenosed coronary vessel (n = 75, SVD group). The characteristics of central and peripheral arteries (arterial velocity pulse index (AVI) and arterial pressure volume index (API), respectively) and baPWV were measured. Estimated central BP (eCBP) was calculated from the data obtained from PASESA®, and CBP was also measured simultaneously by invasive catheterization. Results API, but not AVI and baPWV, in the SVD group was significantly higher than that in the non-SVD group. Although eCBP was significantly associated with CBP, there was no difference in eCBP between the groups. There were significant associations among API, AVI and baPWV, albeit these associations were relatively weak. A multivariate logistic regression revealed that API and β-blocker were significant independent variables that were associated with the presence of significant coronary stenosis. The cut-off level of API that gave the greatest sensitivity and specificity for the presence of SVD was 24 units (sensitivity 0.636 and specificity 0.667). Conclusion In conclusion, API, but not AVI or baPWV, is associated with the presence of significant coronary stenosis. PMID:27429681

  5. Additional red and reddened stars in Cyg OB2 association

    NASA Technical Reports Server (NTRS)

    Parthasarathy, M.; Jain, S. K.

    1989-01-01

    Several new red and reddened stars are detected in the most heavily reddened associations Cyg OB2. About 47 IRAS sources are detected in Cyg OB2. Their flux distributions, and colors, suggest that they are young stellar objects embedded in dust envelopes or disks (some of them may be proto stars) and are most likely members of the Cyg OB2 association. The large values of the flux ratio L sub IR/L sub VIS suggests that the central objects are obscured because of very large extinction.

  6. How significant is the ‘significant other’? Associations between significant others’ health behaviors and attitudes and young adults’ health outcomes

    PubMed Central

    2012-01-01

    Background Having a significant other has been shown to be protective against physical and psychological health conditions for adults. Less is known about the period of emerging young adulthood and associations between significant others’ weight and weight-related health behaviors (e.g. healthy dietary intake, the frequency of physical activity, weight status). This study examined the association between significant others’ health attitudes and behaviors regarding eating and physical activity and young adults’ weight status, dietary intake, and physical activity. Methods This study uses data from Project EAT-III, a population-based cohort study with emerging young adults from diverse ethnic and socioeconomic backgrounds (n = 1212). Logistic regression models examining cross-sectional associations, adjusted for sociodemographics and health behaviors five years earlier, were used to estimate predicted probabilities and calculate prevalence differences. Results Young adult women whose significant others had health promoting attitudes/behaviors were significantly less likely to be overweight/obese and were more likely to eat ≥ 5 fruits/vegetables per day and engage in ≥ 3.5 hours/week of physical activity, compared to women whose significant others did not have health promoting behaviors/attitudes. Young adult men whose significant other had health promoting behaviors/attitudes were more likely to engage in ≥ 3.5 hours/week of physical activity compared to men whose significant others did not have health promoting behaviors/attitudes. Conclusions Findings suggest the protective nature of the significant other with regard to weight-related health behaviors of young adults, particularly for young adult women. Obesity prevention efforts should consider the importance of including the significant other in intervention efforts with young adult women and potentially men. PMID:22469471

  7. Pre-treatment factors associated with detecting additional brain metastases at stereotactic radiosurgery.

    PubMed

    Wardak, Zabi; Augustyn, Alexander; Zhu, Hong; Mickey, Bruce E; Whitworth, Louis A; Madden, Christopher J; Barnett, Samuel L; Abdulrahman, Ramzi E; Nedzi, Lucien A; Timmerman, Robert D; Choe, Kevin S

    2016-06-01

    The number of brain metastases identified on diagnostic magnetic resonance imaging (MRI) is a key factor in consideration of stereotactic radiosurgery (SRS). However, additional lesions are often detected on high-resolution SRS-planning MRI. We investigated pre-treatment clinical characteristics that are associated with finding additional metastases at SRS. Patients treated with SRS for brain metastases between the years of 2009-2014 comprised the study cohort. All patients underwent frame-fixed, 1 mm thick MRI on the day of SRS. Patient, tumor, and treatment characteristics were analyzed for an association with increase in number of metastases identified on SRS-planning MRI. 289 consecutive SRS cases were analyzed. 725 metastases were identified on pre-treatment MRI and 1062 metastases were identified on SRS-planning MRI. An increase in the number of metastases occurred in 34 % of the cases. On univariate analysis, more than four metastases and the diameter of the largest lesion were significantly associated with an increase in number of metastases on SRS-planning MRI. When stratified by the diameter of the largest lesion into <2, 2-3, or ≥3 cm, additional metastases were identified in 37, 29, and 18 %, respectively. While this increase in the number of metastases is largely due to the difference in imaging technique, the number and size of the metastases were also associated with finding additional lesions. These clinical factors may be considered when determining treatment options for brain metastases. PMID:26966096

  8. Developmental changes in the association between approximate number representations and addition skills in elementary school children

    PubMed Central

    Lonnemann, Jan; Linkersdörfer, Janosch; Hasselhorn, Marcus; Lindberg, Sven

    2013-01-01

    The approximate number system (ANS) is assumingly related to mathematical learning but evidence supporting this assumption is mixed. The inconsistent findings might be attributed to the fact that different measures have been used to assess the ANS and mathematical skills. Moreover, associations between the performance on a measure of the ANS and mathematical skills may be discontinuous, i.e., stronger for children with lower math scores than for children with higher math scores, and may change with age. The aim of the present study was to examine the development of the ANS and arithmetic skills in elementary school children and to investigate how the relationship between the ANS and arithmetic skills develops. Individual markers of children's ANS (internal Weber fractions and mean reaction times in a non-symbolic numerical comparison task) and addition skills were assessed in their first year of school and 1 year later. Children showed improvements in addition performance and in the internal Weber fractions, whereas mean reaction times in the non-symbolic numerical comparison task did not change significantly. While children's addition performance was associated with the internal Weber fractions in the first year, it was associated with mean reaction times in the non-symbolic numerical comparison task in the second year. These associations were not found to be discontinuous and could not be explained by individual differences in reasoning, processing speed, or inhibitory control. The present study extends previous findings by demonstrating that addition performance is associated with different markers of the ANS in the course of development. PMID:24167498

  9. Mechanical and Electrical Properties of a Polyimide Film Significantly Enhanced by the Addition of Single-Wall Carbon Nanotubes

    NASA Technical Reports Server (NTRS)

    Meador, Michael A.

    2005-01-01

    Single-wall carbon nanotubes have been shown to possess a combination of outstanding mechanical, electrical, and thermal properties. The use of carbon nanotubes as an additive to improve the mechanical properties of polymers and/or enhance their thermal and electrical conductivity has been a topic of intense interest. Nanotube-modified polymeric materials could find a variety of applications in NASA missions including large-area antennas, solar arrays, and solar sails; radiation shielding materials for vehicles, habitats, and extravehicular activity suits; and multifunctional materials for vehicle structures and habitats. Use of these revolutionary materials could reduce vehicle weight significantly and improve vehicle performance and capabilities.

  10. A significant association between BDNF promoter methylation and the risk of drug addiction.

    PubMed

    Xu, Xuting; Ji, Huihui; Liu, Guili; Wang, Qinwen; Liu, Huifen; Shen, Wenwen; Li, Longhui; Xie, Xiaohu; Zhou, Wenhua; Duan, Shiwei

    2016-06-10

    As a member of the neurotrophic factor family, brain derived neurotrophic factor (BDNF) plays an important role in the survival and differentiation of neurons. The aim of our work was to evaluate the role of BDNF promoter methylation in drug addiction. A total of 60 drug abusers (30 heroin and 30 methylamphetamine addicts) and 52 healthy age- and gender-matched controls were recruited for the current case control study. Bisulfite pyrosequencing technology was used to determine the methylation levels of five CpGs (CpG1-5) on the BDNF promoter. Among the five CpGs, CpG5 methylation was significantly lower in drug abusers than controls. Moreover, significant associations were found between CpG5 methylation and addictive phenotypes including tension-anxiety, anger-hostility, fatigue-inertia, and depression-dejection. In addition, luciferase assay showed that the DNA fragment of BDNF promoter played a key role in the regulation of gene expression. Our results suggest that BDNF promoter methylation is associated with drug addiction, although further studies are needed to understand the mechanisms by which BDNF promoter methylation contributes to the pathophysiology of drug addiction. PMID:26976342

  11. Factors associated with an increased risk of vertebral fracture in monoclonal gammopathies of undetermined significance.

    PubMed

    Piot, J M; Royer, M; Schmidt-Tanguy, A; Hoppé, E; Gardembas, M; Bourrée, T; Hunault, M; François, S; Boyer, F; Ifrah, N; Renier, G; Chevailler, A; Audran, M; Chappard, D; Libouban, H; Mabilleau, G; Legrand, E; Bouvard, B

    2015-01-01

    Monoclonal gammopathies of undetermined significance (MGUS) have been shown to be associated with an increased risk of fractures. This study describes prospectively the bone status of MGUS patients and determines the factors associated with vertebral fracture. We included prospectively 201 patients with MGUS, incidentally discovered, and with no known history of osteoporosis: mean age 66.6±12.5 years, 48.3% women, 51.7% immunoglobulin G (IgG), 33.3% IgM and 10.4% IgA. Light chain was kappa in 64.2% patients. All patients had spinal radiographs and bone mineral density measurement in addition to gammopathy assessment. At least one prevalent non-traumatic vertebral fracture was discovered in 18.4% patients and equally distributed between men and women. Fractured patients were older, had a lower bone density and had also more frequently a lambda light chain isotype. Compared with patients with κ light chain, the odds ratio of being fractured for patients with λ light chain was 4.32 (95% confidence interval 1.80-11.16; P=0.002). These results suggest a high prevalence of non-traumatic vertebral fractures in MGUS associated with lambda light chain isotype and not only explained by low bone density. PMID:26314987

  12. Factors associated with an increased risk of vertebral fracture in monoclonal gammopathies of undetermined significance

    PubMed Central

    Piot, J M; Royer, M; Schmidt-Tanguy, A; Hoppé, E; Gardembas, M; Bourrée, T; Hunault, M; François, S; Boyer, F; Ifrah, N; Renier, G; Chevailler, A; Audran, M; Chappard, D; Libouban, H; Mabilleau, G; Legrand, E; Bouvard, B

    2015-01-01

    Monoclonal gammopathies of undetermined significance (MGUS) have been shown to be associated with an increased risk of fractures. This study describes prospectively the bone status of MGUS patients and determines the factors associated with vertebral fracture. We included prospectively 201 patients with MGUS, incidentally discovered, and with no known history of osteoporosis: mean age 66.6±12.5 years, 48.3% women, 51.7% immunoglobulin G (IgG), 33.3% IgM and 10.4% IgA. Light chain was kappa in 64.2% patients. All patients had spinal radiographs and bone mineral density measurement in addition to gammopathy assessment. At least one prevalent non-traumatic vertebral fracture was discovered in 18.4% patients and equally distributed between men and women. Fractured patients were older, had a lower bone density and had also more frequently a lambda light chain isotype. Compared with patients with κ light chain, the odds ratio of being fractured for patients with λ light chain was 4.32 (95% confidence interval 1.80–11.16; P=0.002). These results suggest a high prevalence of non-traumatic vertebral fractures in MGUS associated with lambda light chain isotype and not only explained by low bone density. PMID:26314987

  13. Serum Homocysteine Concentration Is Significantly Associated with Inflammatory/Immune Factors

    PubMed Central

    Yang, Xiaobo; Zhang, Haiying; Qin, Xue; Hu, Yanling; Mo, Zengnan

    2015-01-01

    Recent studies suggest that serum homocysteine (HCY) level is correlated to inflammatory/immune factors that influence the development and progression of many diseases, such as cardiovascular disease. However, the association between serum HCY level and inflammatory/immune factors in healthy populations has not been systematically investigated. This study was conducted based on the Fangchenggang Area Male Health and Examination Survey (FAMHES) project. After comprehensive baseline analysis, we could not find any significant association between HCY level and inflammatory/immune factors. However, in the next linear regression analysis, serum C4 [age-adjusted: Beta = -0.053, 95%CI = (-3.798, -0.050), P = 0.044; multivariate adjusted: Beta = -0.064, 95%CI = (-4.271, -0.378), P = 0.019] and C-reactive protein (CRP) concentration [unadjusted: Beta = 0.056, 95%CI = (0.037, 0.740), P = 0.030] were positively related with HCY. In further binary regression analysis, a significant correlation was confirmed for C4 and HCY [age-adjusted: OR = 0.572, 95%CI = (0.359, 0.911); multivariate adjusted: OR = 0.558, 95%CI = (0.344, 0.905)]. In order to discover more potential associations, multivariate logistic regression analysis was applied and suggested that HCY and C4 were significantly correlated [age-adjusted: OR = 0.703, 95%CI = (0.519, 0.951); multivariate adjusted: OR = 0.696, 95%CI = (0.509, 0.951)]. In addition, immunoglobulin M (IgM) may influence the HCY level to some extent [unadjusted: OR = 1.427, 95%CI = (1.052, 1.936); age-adjusted: OR = 1.446, 95%CI = (1.061, 1.970); multivariate adjusted: OR = 1.447, 95%CI = (1.062, 1.973)]. Combining our results with recent studies, we propose that C4, CRP, and IgM in serum are significantly associated with HCY concentration. Further studies are needed on the mechanism of the interaction, especially among cardiovascular disease subjects. PMID:26367537

  14. Appropriate Fe (II) Addition Significantly Enhances Anaerobic Ammonium Oxidation (Anammox) Activity through Improving the Bacterial Growth Rate

    PubMed Central

    Liu, Yiwen; Ni, Bing-Jie

    2015-01-01

    The application of anaerobic ammonium oxidation (Anammox) process is often limited by the slow growth rate of Anammox bacteria. As the essential substrate element that required for culturing Anammox sludge, Fe (II) is expected to affect Anammox bacterial growth. This work systematically studied the effects of Fe (II) addition on Anammox activity based on the kinetic analysis of specific growth rate using data from batch tests with an enriched Anammox sludge at different dosing levels. Results clearly demonstrated that appropriate Fe (II) dosing (i.e., 0.09 mM) significantly enhanced the specific Anammox growth rate up to 0.172 d−1 compared to 0.118 d−1 at regular Fe (II) level (0.03 mM). The relationship between Fe (II) concentration and specific Anammox growth rate was found to be well described by typical substrate inhibition kinetics, which was integrated into currently well-established Anammox model to describe the enhanced Anammox growth with Fe (II) addition. The validity of the integrated Anammox model was verified using long-term experimental data from three independent Anammox reactors with different Fe (II) dosing levels. This Fe (II)-based approach could be potentially implemented to enhance the process rate for possible mainstream application of Anammox technology, in order for an energy autarchic wastewater treatment. PMID:25644239

  15. Appropriate Fe (II) Addition Significantly Enhances Anaerobic Ammonium Oxidation (Anammox) Activity through Improving the Bacterial Growth Rate

    NASA Astrophysics Data System (ADS)

    Liu, Yiwen; Ni, Bing-Jie

    2015-02-01

    The application of anaerobic ammonium oxidation (Anammox) process is often limited by the slow growth rate of Anammox bacteria. As the essential substrate element that required for culturing Anammox sludge, Fe (II) is expected to affect Anammox bacterial growth. This work systematically studied the effects of Fe (II) addition on Anammox activity based on the kinetic analysis of specific growth rate using data from batch tests with an enriched Anammox sludge at different dosing levels. Results clearly demonstrated that appropriate Fe (II) dosing (i.e., 0.09 mM) significantly enhanced the specific Anammox growth rate up to 0.172 d-1 compared to 0.118 d-1 at regular Fe (II) level (0.03 mM). The relationship between Fe (II) concentration and specific Anammox growth rate was found to be well described by typical substrate inhibition kinetics, which was integrated into currently well-established Anammox model to describe the enhanced Anammox growth with Fe (II) addition. The validity of the integrated Anammox model was verified using long-term experimental data from three independent Anammox reactors with different Fe (II) dosing levels. This Fe (II)-based approach could be potentially implemented to enhance the process rate for possible mainstream application of Anammox technology, in order for an energy autarchic wastewater treatment.

  16. Non-additive genome-wide association scan reveals a new gene associated with habitual coffee consumption.

    PubMed

    Pirastu, Nicola; Kooyman, Maarten; Robino, Antonietta; van der Spek, Ashley; Navarini, Luciano; Amin, Najaf; Karssen, Lennart C; Van Duijn, Cornelia M; Gasparini, Paolo

    2016-01-01

    Coffee is one of the most consumed beverages world-wide and one of the primary sources of caffeine intake. Given its important health and economic impact, the underlying genetics of its consumption has been widely studied. Despite these efforts, much has still to be uncovered. In particular, the use of non-additive genetic models may uncover new information about the genetic variants driving coffee consumption. We have conducted a genome-wide association study in two Italian populations using additive, recessive and dominant models for analysis. This has uncovered a significant association in the PDSS2 gene under the recessive model that has been replicated in an independent cohort from the Netherlands (ERF). The identified gene has been shown to negatively regulate the expression of the caffeine metabolism genes and can thus be linked to coffee consumption. Further bioinformatics analysis of eQTL and histone marks from Roadmap data has evidenced a possible role of the identified SNPs in regulating PDSS2 gene expression through enhancers present in its intron. Our results highlight a novel gene which regulates coffee consumption by regulating the expression of the genes linked to caffeine metabolism. Further studies will be needed to clarify the biological mechanism which links PDSS2 and coffee consumption. PMID:27561104

  17. Non-additive genome-wide association scan reveals a new gene associated with habitual coffee consumption

    PubMed Central

    Pirastu, Nicola; Kooyman, Maarten; Robino, Antonietta; van der Spek, Ashley; Navarini, Luciano; Amin, Najaf; Karssen, Lennart C.; Van Duijn, Cornelia M; Gasparini, Paolo

    2016-01-01

    Coffee is one of the most consumed beverages world-wide and one of the primary sources of caffeine intake. Given its important health and economic impact, the underlying genetics of its consumption has been widely studied. Despite these efforts, much has still to be uncovered. In particular, the use of non-additive genetic models may uncover new information about the genetic variants driving coffee consumption. We have conducted a genome-wide association study in two Italian populations using additive, recessive and dominant models for analysis. This has uncovered a significant association in the PDSS2 gene under the recessive model that has been replicated in an independent cohort from the Netherlands (ERF). The identified gene has been shown to negatively regulate the expression of the caffeine metabolism genes and can thus be linked to coffee consumption. Further bioinformatics analysis of eQTL and histone marks from Roadmap data has evidenced a possible role of the identified SNPs in regulating PDSS2 gene expression through enhancers present in its intron. Our results highlight a novel gene which regulates coffee consumption by regulating the expression of the genes linked to caffeine metabolism. Further studies will be needed to clarify the biological mechanism which links PDSS2 and coffee consumption. PMID:27561104

  18. Association Mapping in Turkish Olive Cultivars Revealed Significant Markers Related to Some Important Agronomic Traits.

    PubMed

    Kaya, Hilal Betul; Cetin, Oznur; Kaya, Hulya Sozer; Sahin, Mustafa; Sefer, Filiz; Tanyolac, Bahattin

    2016-08-01

    Olive (Olea europaea L.) is one of the most important fruit trees especially in the Mediterranean countries due to high consumption of table olive and olive oil. In olive breeding, the phenotypic traits associated to fruit are the key factors that determine productivity. Association mapping has been used in some tree species and a lot of crop plant species, and here, we perform an initial effort to detect marker-trait associations in olive tree. In the current study, a total of 96 olive genotypes, including both oil and table olive genotypes from Turkish Olive GenBank Resources, were used to examine marker-trait associations. For olive genotyping, SNP, AFLP, and SSR marker data were selected from previously published study and association analysis was performed between these markers and 5 yield-related traits. Three different approaches were used to check for false-positive results in association tests, and association results obtained from these models were compared. Using the model utilizing both population structure and relative kinship, eleven associations were significant with FDR ≤ 0.05. The largest number of significant associations was detected for fruit weight and stone weight. Our results suggested that association mapping could be an effective approach for identifying marker-trait associations in olive genotypes, without the development of mapping populations. This study shows for the first time the use of association mapping for identifying molecular markers linked to important traits in olive tree. PMID:27209034

  19. Fat mass and obesity-associated gene rs11642015 polymorphism is significantly associated with prediabetes and type 2 diabetes subsequent to adjustment for body mass index

    PubMed Central

    HAN, LIYUAN; TANG, LINLIN; WANG, CHANGYI; CHEN, ZHONGWEI; ZHANG, TAO; CHEN, SIHAN; LIU, SHENGYUAN; PENG, XIAOLIN; MAI, YIFENG; DUAN, SHIWEI

    2014-01-01

    The association of the fat mass and obesity-associated gene (FTO) rs11642015 polymorphism with prediabetes, type 2 diabetes and obesity in certain populations has not been previously reported. A population-based study was conducted that included 490 type 2 diabetic, 471 prediabetic and 575 normal subjects. The main outcomes of the study were prediabetes, type 2 diabetes and obesity. Binary logistic regression was performed to estimate the association of FTO rs11642015 with the risk of prediabetes, type 2 diabetes and obesity following adjustment for the corresponding confounders. A meta-analysis was also conducted to evaluate the association between FTO rs11642015 and obesity. FTO rs11642015 was significantly associated with prediabetes in the whole sample under the additive model [odds ratio (OR), 1.50; 95% confidence interval (CI), 1.17–1.93; P=0.002], particularly in females. The polymorphism remained consistently significant following adjustment for age and body mass index (BMI), showing an increased prediabetes risk with an additive effect (OR, 1.55; 95% CI, 1.19–2.01; P=0.001). In addition, a significant association was found for rs11642015 with prediabetes and type 2 diabetes under the dominant model. However, under the stringent Bonferroni’s correction there was no evidence of positive associations for FTO rs11642015 with obesity in the whole sample, females or males. Findings of the meta-analysis showed that FTO rs11642015 was not predisposed to obesity. In conclusion, the T allele of FTO rs11642015 is positively associated with an increased risk of prediabetes, even after adjustment for age and BMI, particularly in females. Subjects carrying the CT + TT genotype are predisposed to prediabetes and type 2 diabetes. Therefore, results of the population-based study and follow-up meta-analysis suggested that FTO rs11642015 is not significantly associated with susceptibility to obesity. PMID:25054011

  20. Association between micronucleus frequency and cervical intraepithelial neoplasia grade in Thinprep cytological test and its significance.

    PubMed

    Shi, Yong-Hua; Wang, Bo-Wei; Tuokan, Talaf; Li, Qiao-Zhi; Zhang, Ya-Jing

    2015-01-01

    A micronucleus is an additional small nucleus formed due to chromosomes or chromosomal fragments fail to be incorporated into the nucleus during cell division. In this study, we assessed the utility of micronucleus counting as a screening tool in cervical precancerous lesions in Thinprep cytological test smears under oil immersion. High risk HPV was also detected by hybrid capture-2 in Thinprep cytological test smears. Our results showed that micronucleus counting was significantly higher in high-grade squamous intraepithelial lesion (HSIL) and invasive carcinoma cases compared to low-grade squamous intraepithelial lesion (LSIL) and non-neoplastic cases. Receiver operating characteristic (ROC) curve analysis revealed that micronucleus counting possessed a high degree of sensitivity and specificity for identifying HSIL and invasive carcinoma. Cut-off of 7.5 for MN counting gave a sensitivity of 89.6% and a specificity of 66.7% (P = 0.024 and AUC = 0.892) for detecting HSIL and invasive carcinoma lesions. Multiple linear regression analysis showed that only HSIL and invasive cancer lesions not age, duration of marital life and number of pregnancy are significantly associated with MN counting. The positive rate of high risk HPV was distinctly higher in LSIL, HSIL and invasive cancer than that in non-neoplstic categories. In conclusions, MN evaluation may be viewed as an effective biomarker for cervical cancer screening. The combination of MN count with HPV DNA detection and TCT may serve as an effective means to screen precancerous cervical lesions in most developing nations. PMID:26339413

  1. Significance of Circulating and Crevicular Matrix Metalloproteinase-9 in Rheumatoid Arthritis-Chronic Periodontitis Association

    PubMed Central

    Silosi, Isabela; Cojocaru, Manole; Foia, Lili; Boldeanu, Mihail Virgil; Petrescu, Florin; Biciusca, Viorel

    2015-01-01

    In the recent years, statistically significant associations between rheumatoid arthritis (RA) and periodontal disease have been identified. Emerging as a chronic inflammatory joint disease, RA displays various features and pathogenetic events similar to chronic periodontitis (CP). The purpose of this study was to evaluate the utility of determining systemic and crevicular levels of metalloproteinase-9 (MMP-9) as potential biomarkers for association between RA and CP. A total of fifty-six patients were included in the study. The subjects were categorized into four groups as follows: healthy-control (n = 21), active RA (n = 16), CP (n = 14), and RA-CP association (n = 12). Assessment of serum and crevicular concentrations of total MMP-9 (active and pro-MMP-9) was based on ELISA technique. The results of this study showed statistically significant differences of serum MMP-9 between patients groups and control. Serum levels of MMP-9 were similar in RA and RA-CP associated patients. Gingival crevicular fluid (GCF) recorded increased MMP-9 levels in RA-CP association subjects as compared to CP. Considering that RA-CP association is characterized by a disregulation of the inflammatory response, MMP-9 may play a role in the pathogenesis of RA-CP association. MMP-9 is therefore a sensitive tool in the diagnosis and management of patients affected by this binomial association. PMID:25821836

  2. Significance of circulating and crevicular matrix metalloproteinase-9 in rheumatoid arthritis-chronic periodontitis association.

    PubMed

    Silosi, Isabela; Cojocaru, Manole; Foia, Lili; Boldeanu, Mihail Virgil; Petrescu, Florin; Surlin, Petra; Biciusca, Viorel

    2015-01-01

    In the recent years, statistically significant associations between rheumatoid arthritis (RA) and periodontal disease have been identified. Emerging as a chronic inflammatory joint disease, RA displays various features and pathogenetic events similar to chronic periodontitis (CP). The purpose of this study was to evaluate the utility of determining systemic and crevicular levels of metalloproteinase-9 (MMP-9) as potential biomarkers for association between RA and CP. A total of fifty-six patients were included in the study. The subjects were categorized into four groups as follows: healthy-control (n = 21), active RA (n = 16), CP (n = 14), and RA-CP association (n = 12). Assessment of serum and crevicular concentrations of total MMP-9 (active and pro-MMP-9) was based on ELISA technique. The results of this study showed statistically significant differences of serum MMP-9 between patients groups and control. Serum levels of MMP-9 were similar in RA and RA-CP associated patients. Gingival crevicular fluid (GCF) recorded increased MMP-9 levels in RA-CP association subjects as compared to CP. Considering that RA-CP association is characterized by a disregulation of the inflammatory response, MMP-9 may play a role in the pathogenesis of RA-CP association. MMP-9 is therefore a sensitive tool in the diagnosis and management of patients affected by this binomial association. PMID:25821836

  3. Using Py-GC/MS to fingerprint additives associated with paper mill effluent toxicity episodes.

    PubMed

    Sithole, B Bruce; Pimentel, Jorge; Gibbons, Sharon; Watanabe, Chu

    2012-10-26

    Understanding the cause of effluent toxicity is an important requirement for its prevention, remediation and return to compliance. One component of the strategy entails identification and fingerprinting of additives or components in additives that may be the cause of the toxicity episodes. A number of additives used in pulp and papermaking are polymeric compounds that are suspect in effluent toxicity. Their analysis and detection is difficult as they are not amenable to analysis by normal techniques applicable to mill effluents such as gas chromatography. Py-GC/MS is a powerful analytical technique that can be used to fingerprint these additives. The presence of the additives is confirmed by fingerprint pyrograms of the additives (or components in the formulations of the additives) in conjunction with mass spectrometry. The technique has been used to fingerprint and quantify polymeric additives associated with mill effluent toxicity episodes. PMID:22930350

  4. Determining the significance of associations between two series of discrete events : bootstrap methods /

    SciTech Connect

    Niehof, Jonathan T.; Morley, Steven K.

    2012-01-01

    We review and develop techniques to determine associations between series of discrete events. The bootstrap, a nonparametric statistical method, allows the determination of the significance of associations with minimal assumptions about the underlying processes. We find the key requirement for this method: one of the series must be widely spaced in time to guarantee the theoretical applicability of the bootstrap. If this condition is met, the calculated significance passes a reasonableness test. We conclude with some potential future extensions and caveats on the applicability of these methods. The techniques presented have been implemented in a Python-based software toolkit.

  5. Gluten-free dough-making of specialty breads: Significance of blended starches, flours and additives on dough behaviour.

    PubMed

    Collar, Concha; Conte, Paola; Fadda, Costantino; Piga, Antonio

    2015-10-01

    The capability of different gluten-free (GF) basic formulations made of flour (rice, amaranth and chickpea) and starch (corn and cassava) blends, to make machinable and viscoelastic GF-doughs in absence/presence of single hydrocolloids (guar gum, locust bean and psyllium fibre), proteins (milk and egg white) and surfactants (neutral, anionic and vegetable oil) have been investigated. Macroscopic (high deformation) and macromolecular (small deformation) mechanical, viscometric (gelatinization, pasting, gelling) and thermal (gelatinization, melting, retrogradation) approaches were performed on the different matrices in order to (a) identify similarities and differences in GF-doughs in terms of a small number of rheological and thermal analytical parameters according to the formulations and (b) to assess single and interactive effects of basic ingredients and additives on GF-dough performance to achieve GF-flat breads. Larger values for the static and dynamic mechanical characteristics and higher viscometric profiles during both cooking and cooling corresponded to doughs formulated with guar gum and Psyllium fibre added to rice flour/starch and rice flour/corn starch/chickpea flour, while surfactant- and protein-formulated GF-doughs added to rice flour/starch/amaranth flour based GF-doughs exhibited intermediate and lower values for the mechanical parameters and poorer viscometric profiles. In addition, additive-free formulations exhibited higher values for the temperature of both gelatinization and retrogradation and lower enthalpies for the thermal transitions. Single addition of 10% of either chickpea flour or amaranth flour to rice flour/starch blends provided a large GF-dough hardening effect in presence of corn starch and an intermediate effect in presence of cassava starch (chickpea), and an intermediate reinforcement of GF-dough regardless the source of starch (amaranth). At macromolecular level, both chickpea and amaranth flours, singly added, determined

  6. Frailty severity is significantly associated with electrocardiographic QRS duration in chronic dialysis patients

    PubMed Central

    Chao, Chia-Ter

    2015-01-01

    End-stage renal disease (ESRD) patients are at increased risk of sudden cardiac death, the risk of which is presumably related to arrhythmia. Electrocardiographic (ECG) parameters have been found to correlate with arrhythmia and predict cardiovascular outcomes in ESRD patients. Frailty is also a common feature in this population. We investigate whether the severity of dialysis frailty is associated with ECG findings, including PR interval, QRS duration, and QTc interval. Presence and severity of frailty was ascertained using six different self-report questionnaires with proven construct validity. Correlation analysis between frailty severity and ECG was made, and those with significant association entered into multiple regression analysis for confirmation. Among a cohort of chronic hemodialysis patients, we found that frailty severity, assessed by the Edmonton frailty scale, is significantly associated with QRS duration (r = − 0.3, p < 0.05). Dialysis patients with QRS longer than 120 ms had significantly lower severity of frailty than those with QRS less than 120 ms (p = 0.01 for the Edmonton frailty scale and 0.05 for simple FRAIL scale). Regression analysis showed that frailty severity, assessed by the Edmonton frailty scale and simple FRAIL scale, was significantly associated with QRS duration independent of serum electrolyte levels. In conclusion, a significant relationship exists between the severity of frailty and QRS duration in ESRD patients. This might be an under-recognized link between frailty and its adverse cardiovascular impact in these patients. PMID:26528415

  7. American Vocational Education Research Association Members' Perceptions of Statistical Significance Tests and Other Statistical Controversies.

    ERIC Educational Resources Information Center

    Gordon, Howard R. D.

    A random sample of 113 members of the American Vocational Education Research Association (AVERA) was surveyed to obtain baseline information regarding AVERA members' perceptions of statistical significance tests. The Psychometrics Group Instrument was used to collect data from participants. Of those surveyed, 67% were male, 93% had earned a…

  8. The functional significance of EEG microstates--Associations with modalities of thinking.

    PubMed

    Milz, P; Faber, P L; Lehmann, D; Koenig, T; Kochi, K; Pascual-Marqui, R D

    2016-01-15

    . Contrary to associations suggested by previous reports, parameters were increased for class A during visualization, and class B during verbalization. In line with previous reports, microstate D parameters were increased during no-task resting compared to the three internal, goal-directed tasks. Topographic differences between conditions included particular sub-regions of components of the metabolic default mode network. Modality-specific personal parameters did not consistently correlate with microstate parameters except verbal cognitive style which correlated negatively with microstate class A duration and positively with class C occurrence. This is the first study that aimed to induce EEG microstate class parameter changes based on their hypothesized functional significance. Beyond the associations of microstate classes A and B with visual and verbal processing, respectively, our results suggest that a finely-tuned interplay between all four EEG microstate classes is necessary for the continuous formation of visual and verbal thoughts. Our results point to the possibility that the EEG microstate classes may represent the head-surface measured activity of intra-cortical sources primarily exhibiting inhibitory functions. However, additional studies are needed to verify and elaborate on this hypothesis. PMID:26285079

  9. Trigonal pyramidal carbon geometry as model for electrophilic addition-substitution and elimination reactions and its significance in enzymatic processes

    NASA Astrophysics Data System (ADS)

    Buck, Henk M.

    Various examples are given in which compounds are characterized as products or intermediates in a (distorted) trigonal pyramidal (TP) geometry. These observations have taken place mainly in the field of carbocation chemistry. Special attention is given to carbenium ions formed by halogen addition to 1,1-diarylsubstituted ethylenes focused on the electronic effects of the C-halogen bond as axial bond in a TP geometry with regard to the ?-distribution in the rest of the molecular system. The experimental verification is accompanied by quantum chemical calculations. We also used the TP structure as a reactive model for specific enzymatic reactions. The relevance of this geometry is shown for the dehalogenation reaction of the nucleophilic displacement in dichloroethane catalyzed by haloalkane dehalogenase and for the decarboxylation of L-ornithine with ornithine decarboxylase under loss of carbon dioxide.

  10. The clinical significance and management of patients with incomplete coronary angiography and the value of additional computed tomography coronary angiography.

    PubMed

    Pregowski, Jerzy; Kepka, Cezary; Kruk, Mariusz; Mintz, Gary S; Kalinczuk, Lukasz; Ciszewski, Michal; Kochanowski, Lukasz; Wolny, Rafal; Chmielak, Zbigniew; Jastrzębski, Jan; Klopotowski, Mariusz; Zalewska, Joanna; Demkow, Marcin; Karcz, Maciej; Witkowski, Adam

    2014-04-01

    To assess the anatomical background and significance of incomplete invasive coronary angiography (ICA) and to evaluate the value of coronary computed tomography angiography (CTA) in this scenario. The current study is an analysis of high volume center experience with prospective registry of coronary CTA and ICA. The target population was identified through a review of the electronic database. We included consecutive patients referred for coronary CTA after ICA, which did not visualize at least one native coronary artery or by-pass graft. Between January 2009 and April 2013, 13,603 diagnostic ICA were performed. There were 45 (0.3 %) patients referred for coronary CTA after incomplete ICA. Patients were divided into 3 groups: angina symptoms without previous coronary artery by-pass grafting (CABG) (n = 11,212), angina symptoms with previous CABG (n = 986), and patients prior to valvular surgery (n = 925). ICA did not identify by-pass grafts in 21 (2.2 %) patients and in 24 (0.2 %) cases of native arteries. The explanations for an incomplete ICA included: 11 ostium anomalies, 2 left main spasms, 5 access site problems, 5 ascending aorta aneurysms, and 2 tortuous take-off of a subclavian artery. However, in 20 (44 %) patients no specific reason for the incomplete ICA was identified. After coronary CTA revascularization was performed in 11 (24 %) patients: 6 successful repeat ICA and percutaneous intervention and 5 CABG. Incomplete ICA constitutes rare, but a significant clinical problem. Coronary CTA provides adequate clinical information in these patients. PMID:24623270

  11. Early repolarization is associated with significant coronary artery stenosis in asymptomatic adults.

    PubMed

    Suh, Beomseok; Park, Sehhoon; Shin, Dong Wook; Ahn, Hongkeun; Cho, Seongcheol; Lee, Seung-Pyo; Park, Eun-Ah; Lee, Hyejin; Park, Jin Ho; Cho, BeLong

    2016-02-01

    The aim of our study was to investigate the relationship between early repolarization (ERP) and coronary heart disease (CHD) by evaluating its association with coronary artery stenosis and plaques. Consecutive asymptomatic adults aged 30 or more without CHD were investigated (n = 3100). Adjusting for major cardiovascular risk factors, ERP was significantly associated with significant coronary stenosis with incremental predictive value (aOR 1.71, 95% CI 1.13-2.60; ROC AUC 0.763 vs. 0.723, P < 0.001; NRI 4.86%, P = 0.042; IDI 0.0030, P = 0.040), specifically in intermediate risk group (aOR 2.33, 95% CI 1.29-4.20; ROC AUC 0.753 vs. 0.708, P = 0.001). ERP was shown to be especially associated with significant coronary stenosis with non-calcified plaque (aOR 2.26, 95% CI 1.28-3.98). Our study is the first to directly show the association of ERP with CHD. Future studies are needed to replicate our results and investigate whether it would be beneficial to include ERP in risk algorithms for CHD screening. PMID:26694693

  12. Molecular Analysis and Clinical Significance of Lactobacillus spp. Recovered from Clinical Specimens Presumptively Associated with Disease

    PubMed Central

    Martinez, Raquel M.; Hulten, Kristina G.; Bui, Uyen

    2014-01-01

    Lactobacillus spp. are part of the normal human flora and are generally assumed to be nonpathogenic. We determined the genotypic identification of >100 Lactobacillus isolates from clinical specimens in the context of presumed pathogenic potential (e.g., recovered as the single/predominant isolate from a sterile site or at ≥105 CFU/ml from urine). This study assessed the clinical significance and the frequency of occurrence of each Lactobacillus sp. We identified 16 species of Lactobacillus by 16S rRNA gene sequence analysis, 10 of which could not be associated with disease. While Lactobacillus rhamnosus, Lactobacillus gasseri, and Lactobacillus paracasei were associated with infections, L. gasseri was also a common colonizing/contaminating species. Lactobacillus casei, Lactobacillus johnsonii, and Lactobacillus delbrueckii were associated with at least one infection. Species commonly used in probiotic products (e.g., L. rhamnosus and L. casei) were identical, by 16S rRNA gene sequencing, to our isolates associated with disease. Human isolates of Lactobacillus spp. have differing site associations and levels of clinical significance. Knowing the niche and pathogenic potential of each Lactobacillus sp. can be of importance to both clinical microbiology and the food and probiotic supplement industry. PMID:24131686

  13. Effects of litter addition on ectomycorrhizal associates of a lodgepole pine (Pinus contorta) stand in Yellowstone National Park

    NASA Technical Reports Server (NTRS)

    Cullings, Kenneth W.; New, Michael H.; Makhija, Shilpa; Parker, V. Thomas

    2003-01-01

    Increasing soil nutrients through litter manipulation, pollution, or fertilization can adversely affect ectomycorrhizal (EM) communities by inhibiting fungal growth. In this study, we used molecular genetic methods to determine the effects of litter addition on the EM community of a Pinus contorta stand in Yellowstone National Park that regenerated after a stand-replacing fire. Two controls were used; in unmodified control plots nothing was added to the soil, and in perlite plots perlite, a chemically neutral substance, was added to maintain soil moisture and temperature at levels similar to those under litter. We found that (i) species richness did not change significantly following perlite addition (2.6 +/- 0.3 species/core in control plots, compared with 2.3 +/- 0.3 species/core in perlite plots) but decreased significantly (P < 0.05) following litter addition (1.8 +/- 0.3 species/core); (ii) EM infection was not affected by the addition of perlite but increased significantly (P < 0.001) in response to litter addition, and the increase occurred only in the upper soil layer, directly adjacent to the added litter; and (iii) Suillus granulatus, Wilcoxina mikolae, and agaricoid DD were the dominant organisms in controls, but the levels of W. mikolae and agaricoid DD decreased significantly in response to both perlite and litter addition. The relative levels of S. granulatus and a fourth fungus, Cortinariaceae species 2, increased significantly (P < 0.01 and P < 0.05, respectively) following litter addition. Thus, litter addition resulted in some negative effects that may be attributable to moisture-temperature relationships rather than to the increased nutrients associated with litter. Some species respond positively to litter addition, indicating that there are differences in their physiologies. Hence, changes in the EM community induced by litter accumulation also may affect ecosystem function.

  14. 75 FR 61572 - Additional Identifying Information Associated With Persons Whose Property and Interests in...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-05

    ...The Treasury Department's Office of Foreign Assets Control (``OFAC'') is publishing additional identifying information associated with the eight individuals listed in the Annex to the Executive Order of September 28, 2010, ``Blocking Property of Certain Persons With Respect to Serious Human Rights Abuses by the Government of Iran and Taking Certain Other Actions,'' whose property and interests......

  15. Significant association between parathyroid hormone and uric acid level in men

    PubMed Central

    Chin, Kok-Yong; Ima Nirwana, Soelaiman; Wan Ngah, Wan Zurinah

    2015-01-01

    Background Previous reports of patients undergoing parathyroidectomy and of patients receiving teriparatide as antiosteoporotic treatment have suggested a plausible relationship between parathyroid hormone (PTH) and uric acid. However, similar data at population level were lacking. The current study aimed to determine the relationship between PTH and uric acid in a group of apparently healthy Malaysian men. Methods A cross-sectional study was conducted among 380 Malay and Chinese men aged 20 years and above, residing in the Klang Valley, Malaysia. Their body anthropometry was measured, and their fasting blood samples were collected for biochemical analysis. The relationship between PTH and uric acid was analyzed using regression analysis. Results Increased serum PTH level was significantly associated with increased serum uric acid level (β=0.165; P=0.001). Increased PTH level was also significantly associated with the condition of hyperuricemia in the study population (odds ratio [OR], 1.045; 95% confidence interval [CI], 1.017–1.075; P=0.002). All analyses were adjusted for age, body mass index, vitamin D, total calcium, inorganic phosphate, blood urea nitrogen and creatinine levels. Conclusion There is a significant positive relationship between PTH level and uric acid level in Malaysian men. This relationship and its clinical significance should be further investigated in a larger longitudinal study. PMID:26346636

  16. Significant alterations in reported clinical practice associated with increased oversight of organ transplant center performance.

    PubMed

    Schold, Jesse D; Arrington, Charlotte J; Levine, Greg

    2010-09-01

    In the past several years, emphasis on quality metrics in the field of organ transplantation has increased significantly, largely because of the new conditions of participation issued by the Centers for Medicare and Medicaid Services. These regulations directly associate patients' outcomes and measured performance of centers with the distribution of public funding to institutions. Moreover, insurers and marketing ventures have used publicly available outcomes data from transplant centers for business decision making and advertisement purposes. We gave a 10-question survey to attendees of the Transplant Management Forum at the 2009 meeting of the United Network for Organ Sharing to ascertain how centers have responded to the increased oversight of performance. Of 63 responses, 55% indicated a low or near low performance rating at their center in the past 3 years. Respondents from low-performing centers were significantly more likely to indicate increased selection criteria for candidates (81% vs 38%, P = .001) and donors (77% vs 31%, P < .001) as well as alterations in clinical protocols (84% vs 52%, P = .007). Among respondents indicating lost insurance contracts (31%), these differences were also highly significant. Based on respondents' perceptions, outcomes of performance evaluations are associated with significant changes in clinical practice at transplant centers. The transplant community and policy makers should practice vigilance that performance evaluations and regulatory oversight do not inadvertently lead to diminished access to care among viable candidates or decreased transplant volume. PMID:20929114

  17. Identification of Significant Association and Gene-Gene Interaction of GABA Receptor Subunit Genes in Autism

    PubMed Central

    Ma, D. Q.; Whitehead, P. L.; Menold, M. M.; Martin, E. R.; Ashley-Koch, A. E.; Mei, H.; Ritchie, M. D.; DeLong, G. R.; Abramson, R. K.; Wright, H. H.; Cuccaro, M. L.; Hussman, J. P.; Gilbert, J. R.; Pericak-Vance, M. A.

    2005-01-01

    Autism is a common neurodevelopmental disorder with a significant genetic component. Existing research suggests that multiple genes contribute to autism and that epigenetic effects or gene-gene interactions are likely contributors to autism risk. However, these effects have not yet been identified. Gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the adult brain, has been implicated in autism etiology. Fourteen known autosomal GABA receptor subunit genes were studied to look for the genes associated with autism and their possible interactions. Single-nucleotide polymorphisms (SNPs) were screened in the following genes: GABRG1, GABRA2, GABRA4, and GABRB1 on chromosome 4p12; GABRB2, GABRA6, GABRA1, GABRG2, and GABRP on 5q34-q35.1; GABRR1 and GABRR2 on 6q15; and GABRA5, GABRB3, and GABRG3 on 15q12. Intronic and/or silent mutation SNPs within each gene were analyzed in 470 white families with autism. Initially, SNPs were used in a family-based study for allelic association analysis—with the pedigree disequilibrium test and the family-based association test—and for genotypic and haplotypic association analysis—with the genotype-pedigree disequilibrium test (geno-PDT), the association in the presence of linkage (APL) test, and the haplotype family-based association test. Next, with the use of five refined independent marker sets, extended multifactor-dimensionality reduction (EMDR) analysis was employed to identify the models with locus joint effects, and interaction was further verified by conditional logistic regression. Significant allelic association was found for markers RS1912960 (in GABRA4; P = .01) and HCV9866022 (in GABRR2; P = .04). The geno-PDT found significant genotypic association for HCV8262334 (in GABRA2), RS1912960 and RS2280073 (in GABRA4), and RS2617503 and RS12187676 (in GABRB2). Consistent with the allelic and genotypic association results, EMDR confirmed the main effect at RS1912960 (in GABRA4). EMDR also identified a

  18. Factors associated with significant liver necroinflammation in chronic hepatitis B patients with cirrhosis.

    PubMed

    Chen, Sheng-Sen; Yu, Kang-Kang; Ling, Qing-Xia; Huang, Chong; Li, Ning; Zheng, Jian-Ming; Bao, Su-Xia; Cheng, Qi; Zhu, Meng-Qi; Chen, Ming-Quan

    2016-01-01

    We determined the association between various clinical parameters and significant liver necroinflammation in patients with chronic hepatitis B (CHB) related cirrhosis. Two hundred patients with CHB related cirrhosis were recruited in the final analysis. Clinical laboratory values and characteristics were obtained from the medical record. We performed analyses of the relationships between independent variables and significant liver necroinflammation by using binary logistic regression analysis and discriminant analysis. Significant liver necroinflammation (grade≥2) was found in 58.0% (80/138) of antiviral therapy patients and 48.4% (30/62) of non antiviral therapy patients respectively. Also, there were some significant differences in serum hepatitis B surface antigen (HBsAg), serum hepatitis B e antigen (HBeAg) and serum hepatitis B virus (HBV) DNA between antiviral therapy and non antiviral therapy patients. After that, aspartate aminotransferase (AST), total bilirubin (TBIL), total bile acid (TBA), prothrombin time (PT), aspartate aminotransferase to platelet ratio index (APRI) and serum HBV DNA were confirmed as independent predictors of significant liver necroinflammation in CHB patients with cirrhosis by univariate analysis and multivariate analysis (p = 0.002, 0.044, 0.001, 0.014, 0.01 and 0.02 respectively). Finally, receiver operating characteristic (ROC) curve analysis and discriminant analysis validated that these six variables together have strong predictive power to evaluate significant liver necroinflammation. PMID:27615602

  19. Occurrence and significance of tumor-associated neutrophils in patients with colorectal cancer.

    PubMed

    Galdiero, Maria Rosaria; Bianchi, Paolo; Grizzi, Fabio; Di Caro, Giuseppe; Basso, Gianluca; Ponzetta, Andrea; Bonavita, Eduardo; Barbagallo, Marialuisa; Tartari, Silvia; Polentarutti, Nadia; Malesci, Alberto; Marone, Gianni; Roncalli, Massimo; Laghi, Luigi; Garlanda, Cecilia; Mantovani, Alberto; Jaillon, Sébastien

    2016-07-15

    Inflammatory cells are an essential component of the tumor microenvironment. Neutrophils have emerged as important players in the orchestration and effector phase of innate and adaptive immunity. The significance of tumor-associated neutrophils (TAN) in colorectal cancer (CRC) has been the subject of conflicting reports and the present study was designed to set up a reliable methodology to assess TAN infiltration in CRC and to evaluate their clinical significance. CD66b and myeloperoxidase (MPO) were assessed as candidate neutrophil markers in CRC using immunohistochemistry. CD66b was found to be a reliable marker to identify TAN in CRC tissues, whereas MPO also identified a subset of CD68(+) macrophages. CRC patients (n = 271) (Stages I-IV) were investigated retrospectively by computer-assisted imaging on whole tumor sections. TAN density dramatically decreases in Stage IV patients as compared to Stage I-III. At Cox analysis, higher TAN density was associated with better prognosis. Importantly, multivariate analysis showed that prognostic significance of TAN can be influenced by clinical stage and 5-fluorouracil(5-FU)-based chemotherapy. On separate analysis of Stage III patients (n = 178), TAN density had a dual clinical significance depending on the use of 5-FU-based chemotherapy. Unexpectedly, higher TAN density was associated with better response to 5-FU-based chemotherapy. Thus, TAN are an important component of the immune cell infiltrate in CRC and assessment of TAN infiltration may help identify patients likely to benefit from 5-FU-based chemotherapy. These results call for a reassessment of the role of neutrophils in cancer using rigorous quantitative methodology. PMID:26939802

  20. Stress Exposure in Significant Relationships Is Associated with Lymph Node Status in Breast Cancer

    PubMed Central

    Renzi, Chiara; Vadilonga, Valeria; Gandini, Sara; Perinel, Giada; Rotmensz, Nicole; Didier, Florence; Rescigno, Maria; Pravettoni, Gabriella

    2016-01-01

    Objective Life stress exposure may impact on health and disease. Previous literature showed that stressful life events are associated with cancer incidence, survival and mortality. In animal models, patterns of maternal care have been shown to critically affect stress sensitivity and immunity trajectories later in life, by modifying DNA methylation during critical periods early in life. However, the role of parental care in breast cancer progression and survival has only limitedly been explored. Here, we investigated whether these factors may be linked to biological prognostic variables. Methods One hundred twenty-three women hospitalized for surgery of primary breast cancer completed a questionnaire assessing parental bonding. Stressful events throughout the life span were also assessed. Results We found that the absence of optimal parental relationships is significantly associated with an increased risk of lymph node involvement, adjusting for confounders, while cumulative stress in the area of sentimental relationships is borderline significantly associated with the same prognostic factor. Conclusions Our results suggest that parental bonding and sentimental relations may have a role in breast cancer progression. These variables represent an important evolutionary aspect which may modulate cancer progression through psycho-physiological stress pathways and influence the immune system. PMID:26910901

  1. Inter-professional education unveiling significant association between asthma knowledge and inhaler technique

    PubMed Central

    Basheti, Iman A.; Hamadi, Salim A.; Reddel, Helen K.

    2015-01-01

    Objectives: To explore whether an association exists between health care professionals’ (HCPs) asthma knowledge and inhaler technique demonstration skills. Methods: HCPs’ asthma knowledge and inhaler technique demonstration skills were assessed at baseline at an inter-professional educational workshop focusing on asthma medication use. Asthma knowledge was assessed via a published questionnaire. Correct inhaler technique for the three inhalers, the Accuhaler, Turbuhaler and pressurized Metered Dose Inhaler (pMDI) was assessed using published checklists. Results: Two hundred HCPs agreed to participate: 10 specialists (medical doctors specialized in respiratory diseases) (5%), 46 general practitioners (23%), 79 pharmacists (39%), 15 pharmacists’ assistants (8%), 40 nurses (20%) and 10 respiratory therapists (5%). Backwards stepwise multiple regression conducted to determine predictors of HCPs’ inhaler technique, showed that out of many independent variables (asthma knowledge score, profession, age, gender, place of work, years in practice and previous personal use of the study inhaler/s), asthma knowledge score was the only variable showing significant association with inhaler technique (R2=0.162, p<0.001). Conclusion: This study revealed significant associations between asthma knowledge and inhaler technique scores for all HCPs. Providing inter-professional workshops for all HCPs involved integrating education on asthma knowledge and practice of inhaler technique skills are looked-for. PMID:27011779

  2. The significance of caudate volume for age-related associative memory decline.

    PubMed

    Bauer, E; Toepper, M; Gebhardt, H; Gallhofer, B; Sammer, G

    2015-10-01

    Aging comes along with reduced gray matter (GM) volume in several cerebral areas and with cognitive performance decline in different cognitive domains. Moreover, regional GM volume is linked to specific cognitive sub processes in older adults. However, it remains unclear which regional changes in older individuals are directly associated with decreased cognitive performance. Moreover, most of the studies on this topic focused on hippocampal and prefrontal brain regions and their relation to memory and executive functioning. Interestingly, there are only a few studies that reported an association between striatal brain volume and cognitive performance. This is insofar surprising that striatal structures are (1) highly affected by age and (2) involved in different neural circuits that serve intact cognition. To address these issues, voxel-based morphometry (VBM) was used to analyze GM volume in 18 younger and 18 older adults. Moreover, several neuropsychological tests from different neuropsychological test batteries were applied to assess a broad range of cognitive domains. Older adults showed less GM volume than younger adults within frontal, striatal, and cerebellar brain regions. In the group of older adults, significant correlations were found between striatal GM volume and memory performance and between prefrontal/temporal GM volume and executive functioning. The only direct overlap between brain regions associated with regional atrophy and cognitive performance in older adults was found for the right caudate: older adults showed reduced caudate volume relative to younger adults. Moreover, caudate volume was positively correlated with associative memory accuracy in older adults and older adults showed poorer performances than younger adults in the respective associative memory task. Taken together, the current findings indicate the relevance of the caudate for associative memory decline in the aging brain. PMID:26119913

  3. Significant association between long non-coding RNA HOTAIR polymorphisms and cancer susceptibility: a meta-analysis

    PubMed Central

    Zhang, Jian; Liu, Xu; You, Liang-Hao; Zhou, Rui-Zhi

    2016-01-01

    HOTAIR, a well-known long non-coding RNA, is involved in carcinogenesis and progression of multiple cancers. Molecular epidemiological studies suggest that HOTAIR polymorphisms may be associated with cancer susceptibility, but the results remain controversial. To derive a more precise evaluation, we performed a meta-analysis focused on the associations between HOTAIR polymorphisms and cancer risk for the first time. PubMed, Embase, China National Knowledge Infrastructure, and Wanfang databases were searched. Odds ratios (ORs) with 95% confidence interval (CI) were applied to assess the association between HOTAIR rs920778 C>T, rs4759314 A>G, rs7958904 G>C, and rs1899663 G>T polymorphisms and cancer susceptibility. Analyses were conducted to detect heterogeneity, sensitivity, and publication bias in order to measure the robustness of our findings. Overall, 13 related studies involving 7,151 patients and 8,740 control samples were analyzed. Significant associations between the HOTAIR rs920778 polymorphism and cancer risk were observed (T vs C: OR =1.33, 95% CI =1.17–1.53; TT vs TC + CC: OR =1.55, 95% CI =1.21–2.00; TC + TT vs CC: OR =1.33, 95% CI =1.11–1.59; TT vs CC: OR =2.02, 95% CI =1.31–3.10) in the total population, as well as in subgroup analyses. For rs4759314 A>G polymorphism, a similarly increased risk was found in the gastric cancer group. However, significant decreases in cancer risk were observed both in the overall population and colorectal cancer group for rs7958904 G>C polymorphism. In addition, no significant association was detected between rs1899663 G>T polymorphism and cancer susceptibility. In conclusion, our meta-analyses suggest that HOTAIR polymorphisms may be associated with the risk of cancer development. PMID:27330313

  4. Significant Beneficial Association of High Dietary Selenium Intake with Reduced Body Fat in the CODING Study

    PubMed Central

    Wang, Yongbo; Gao, Xiang; Pedram, Pardis; Shahidi, Mariam; Du, Jianling; Yi, Yanqing; Gulliver, Wayne; Zhang, Hongwei; Sun, Guang

    2016-01-01

    Selenium (Se) is a trace element which plays an important role in adipocyte hypertrophy and adipogenesis. Some studies suggest that variations in serum Se may be associated with obesity. However, there are few studies examining the relationship between dietary Se and obesity, and findings are inconsistent. We aimed to investigate the association between dietary Se intake and a panel of obesity measurements with systematic control of major confounding factors. A total of 3214 subjects participated in the study. Dietary Se intake was determined from the Willett food frequency questionnaire. Body composition was measured using dual-energy X-ray absorptiometry. Obese men and women had the lowest dietary Se intake, being 24% to 31% lower than corresponding normal weight men and women, classified by both BMI and body fat percentage. Moreover, subjects with the highest dietary Se intake had the lowest BMI, waist circumference, and trunk, android, gynoid and total body fat percentages, with a clear dose-dependent inverse relationship observed in both gender groups. Furthermore, significant negative associations discovered between dietary Se intake and obesity measurements were independent of age, total dietary calorie intake, physical activity, smoking, alcohol, medication, and menopausal status. Dietary Se intake alone may account for 9%–27% of the observed variations in body fat percentage. The findings from this study strongly suggest that high dietary Se intake is associated with a beneficial body composition profile. PMID:26742059

  5. Genetic Polymorphisms of the Bovine NOV Gene Are Significantly Associated with Carcass Traits in Korean Cattle

    PubMed Central

    Kim, B. S.; Kim, S. C.; Park, C. M.; Lee, S. H.; Cho, S. H.; Kim, N. K.; Jang, G. W.; Yoon, D. H.; Yang, B. S.; Hong, S. K.; Seong, H. H.; Choi, B. H.

    2013-01-01

    The objective of this study was to investigate single nucleotide polymorphisms (SNPs) in the bovine nephroblastoma overexpressed (NOV) gene and to evaluate whether these polymorphisms affect carcass traits in the Korean cattle population. We resequenced to detect SNPs from 24 unrelated individuals and identified 19 SNPs within the full 8.4-kb gene, including the 1.5-kb promoter region. Of these 19 SNPs, four were selected for genotyping based on linkage disequilibrium (LD). We genotyped 429 steers to assess the associations of these four SNPs with carcass traits. Statistical analysis revealed that g.7801T>C and g.8379A>C polymorphisms in the NOV gene were associated with carcass weight (p = 0.012 and 0.008, respectively), and the g.2005A>G polymorphism was associated with the back fat thickness (BF) trait (p = 0.0001). One haplotype of the four SNPs (GGTA) was significantly associated with BF (p = 0.0005). Our findings suggest that polymorphisms in the NOV gene may be among the important genetic factors affecting carcass yield in beef cattle. PMID:25049850

  6. A significant causal association between C-reactive protein levels and schizophrenia

    PubMed Central

    Inoshita, Masatoshi; Numata, Shusuke; Tajima, Atsushi; Kinoshita, Makoto; Umehara, Hidehiro; Nakataki, Masahito; Ikeda, Masashi; Maruyama, Souichiro; Yamamori, Hidenaga; Kanazawa, Tetsufumi; Shimodera, Shinji; Hashimoto, Ryota; Imoto, Issei; Yoneda, Hiroshi; Iwata, Nakao; Ohmori, Tetsuro

    2016-01-01

    Many observational studies have shown elevated blood CRP levels in schizophrenia compared with controls, and one population-based prospective study has reported that elevated plasma CRP levels were associated with late- and very-late-onset schizophrenia. Furthermore, several clinical studies have reported the efficacy of anti-inflammatory drugs on the symptoms in patients with schizophrenia. However, whether elevated CRP levels are causally related to schizophrenia is not still established because of confounding factors and reverse causality. In the present study, we demonstrated that serum CRP levels were significantly higher in patients with schizophrenia than in the controls by conducting a case-control study and a meta-analysis of case-control studies between schizophrenia and serum CRP levels. Furthermore, we provided evidence for a causal association between elevated CRP levels and increased schizophrenia risk by conducting a Mendelian randomization analysis. Our findings suggest that elevated CRP itself may be a causal risk factor for schizophrenia. PMID:27193331

  7. A significant causal association between C-reactive protein levels and schizophrenia.

    PubMed

    Inoshita, Masatoshi; Numata, Shusuke; Tajima, Atsushi; Kinoshita, Makoto; Umehara, Hidehiro; Nakataki, Masahito; Ikeda, Masashi; Maruyama, Souichiro; Yamamori, Hidenaga; Kanazawa, Tetsufumi; Shimodera, Shinji; Hashimoto, Ryota; Imoto, Issei; Yoneda, Hiroshi; Iwata, Nakao; Ohmori, Tetsuro

    2016-01-01

    Many observational studies have shown elevated blood CRP levels in schizophrenia compared with controls, and one population-based prospective study has reported that elevated plasma CRP levels were associated with late- and very-late-onset schizophrenia. Furthermore, several clinical studies have reported the efficacy of anti-inflammatory drugs on the symptoms in patients with schizophrenia. However, whether elevated CRP levels are causally related to schizophrenia is not still established because of confounding factors and reverse causality. In the present study, we demonstrated that serum CRP levels were significantly higher in patients with schizophrenia than in the controls by conducting a case-control study and a meta-analysis of case-control studies between schizophrenia and serum CRP levels. Furthermore, we provided evidence for a causal association between elevated CRP levels and increased schizophrenia risk by conducting a Mendelian randomization analysis. Our findings suggest that elevated CRP itself may be a causal risk factor for schizophrenia. PMID:27193331

  8. Chronic Subdural Hematomas Associated with Arachnoid Cysts: Significance in Young Patients with Chronic Subdural Hematomas

    PubMed Central

    TAKIZAWA, Ken; SORIMACHI, Takatoshi; HONDA, Yumie; ISHIZAKA, Hideo; BABA, Tanefumi; OSADA, Takahiro; NISHIYAMA, Jun; INOUE, Go; MATSUMAE, Mitsunori

    2015-01-01

    Although arachnoid cysts (ACs) are associated with chronic subdural hematomas (CSDHs), especially in young patients, the detailed features of CSDHs associated with ACs remain poorly understood. The objective of this study was to clarify the relationship between the location of CSDHs and ACs and the significance of ACs in young patients with CSDHs. We retrospectively assessed 605 consecutive patients 7 years of age and older who were diagnosed with a CSDH between 2002 and 2014. Twelve patients (2%) had ACs, and 10 of the 12 patients were 7–40 years of age. Patients with ACs as a complication of CSDHs were significantly younger than those without ACs (p < 0.05). Three different relationships between the location of CSDHs and ACs were found: a CSDH contacting an AC, an ipsilateral CSDH apart from an AC, and a CSDH contralateral to an AC. In 21 patients with CSDHs who were 7–40 years of age, 10 (47.6%) had ACs (AC group) and 7 (33.3%) had no associated illnesses (non-AC group). All 10 young patients with ACs showed ipsilateral CSDHs including a CSDH apart from an AC. All 17 patients in both the AC and non-AC groups showed headache but no paresis at admission. The pathogenesis of CSDHs associated with ACs may be different among the three types of locations. The clinical characteristics of patients with a combination of a CSDH and an AC including headache as a major symptom may be attributed to young age in the majority of patients with ACs. PMID:26345665

  9. Factors Associated with Significant Ocular Injury in Conservatively Treated Orbital Fractures

    PubMed Central

    Layton, Christopher J.

    2014-01-01

    Purpose. To determine factors associated with the presence of significant ocular injury in subjects with orbital fractures. Subjects. A consecutive prospective cohort of 161 patients presenting to a general tertiary referral hospital with orbital fractures and undergoing initial conservative treatment was identified. Subjects were assessed at time of injury for the need for emergency surgery, and those initially treated conservatively were subsequently followed up by the Ophthalmology Department to assess for ocular injury requiring ophthalmic management at 1–7 days after injury. Associations between ocular injury and age, sex, visual acuity, presence of blowout fracture, extent of orbital involvement, and presence of distant facial fractures were assessed. Results. 142 male (average age of 32 [95% CI 30–35]) and 19 female (average age of 49 [95% CI 39–59]) subjects were identified. 17 subjects were diagnosed with significant ocular injury. Ocular injury was significantly associated with LogMAR VA worse than 0.2 (OR 49 [95% CI 11–217, P < 0.0001]), but no relationship was noted for age, sex, presence of blowout fracture, extent of fractures, or presence of distal facial fractures. LogMAR visual acuity worse than or equal to 0.2 had a 98% negative predictive value for ocular injury in the setting of orbital fractures. Conclusions. Demographic and nonophthalmic fracture characteristics were not useful predictors of ocular injury in orbital fractures. LogMAR visual acuity worse than or equal to 0.2 is a highly sensitive and useful guide of the need for ophthalmic referral in subjects with orbital fractures. PMID:25580279

  10. Factors associated with significant ocular injury in conservatively treated orbital fractures.

    PubMed

    Layton, Christopher J

    2014-01-01

    Purpose. To determine factors associated with the presence of significant ocular injury in subjects with orbital fractures. Subjects. A consecutive prospective cohort of 161 patients presenting to a general tertiary referral hospital with orbital fractures and undergoing initial conservative treatment was identified. Subjects were assessed at time of injury for the need for emergency surgery, and those initially treated conservatively were subsequently followed up by the Ophthalmology Department to assess for ocular injury requiring ophthalmic management at 1-7 days after injury. Associations between ocular injury and age, sex, visual acuity, presence of blowout fracture, extent of orbital involvement, and presence of distant facial fractures were assessed. Results. 142 male (average age of 32 [95% CI 30-35]) and 19 female (average age of 49 [95% CI 39-59]) subjects were identified. 17 subjects were diagnosed with significant ocular injury. Ocular injury was significantly associated with LogMAR VA worse than 0.2 (OR 49 [95% CI 11-217, P < 0.0001]), but no relationship was noted for age, sex, presence of blowout fracture, extent of fractures, or presence of distal facial fractures. LogMAR visual acuity worse than or equal to 0.2 had a 98% negative predictive value for ocular injury in the setting of orbital fractures. Conclusions. Demographic and nonophthalmic fracture characteristics were not useful predictors of ocular injury in orbital fractures. LogMAR visual acuity worse than or equal to 0.2 is a highly sensitive and useful guide of the need for ophthalmic referral in subjects with orbital fractures. PMID:25580279

  11. Elizabethkingia anophelis bacteremia is associated with clinically significant infections and high mortality

    PubMed Central

    Lau, Susanna K. P.; Chow, Wang-Ngai; Foo, Chuen-Hing; Curreem, Shirly O. T.; Lo, George Chi-Shing; Teng, Jade L. L.; Chen, Jonathan H. K.; Ng, Ricky H. Y.; Wu, Alan K. L.; Cheung, Ingrid Y. Y.; Chau, Sandy K. Y.; Lung, David C.; Lee, Rodney A.; Tse, Cindy W. S.; Fung, Kitty S. C.; Que, Tak-Lun; Woo, Patrick C. Y.

    2016-01-01

    Unlike Elizabethkingia meningoseptica, the clinical importance of E. anophelis is poorly understood. We determined the clinical and molecular epidemiology of bacteremia caused by Elizabethkingia-like species from five regional hospitals in Hong Kong. Among 45 episodes of Elizabethkingia-like bacteremia, 21 were caused by Elizabethkingia, including 17 E. anophelis, three E. meningoseptica and one E. miricola; while 24 were caused by other diverse genera/species, as determined by 16S rRNA gene sequencing. Of the 17 cases of E. anophelis bacteremia, 15 (88%) were clinically significant. The most common diagnosis was pneumonia (n = 5), followed by catheter-related bacteremia (n = 4), neonatal meningitis (n = 3), nosocomial bacteremia (n = 2) and neutropenic fever (n = 1). E. anophelis bacteremia was commonly associated with complications and carried 23.5% mortality. In contrast, of the 24 episodes of bacteremia due to non-Elizabethkingia species, 16 (67%) were clinically insignificant. Compared to non-Elizabethkingia bacteremia, Elizabethkingia bacteremia was associated with more clinically significant infections (P < 0.01) and positive cultures from other sites (P < 0.01), less polymicrobial bacteremia (P < 0.01), and higher complication (P < 0.05) and mortality (P < 0.05) rates. Elizabethkingia bacteremia is predominantly caused by E. anophelis instead of E. meningoseptica. Elizabethkingia bacteremia, especially due to E. anophelis, carries significant morbidity and mortality, and should be considered clinically significant unless proven otherwise. PMID:27185741

  12. Associativity and Understanding of the Operation of Addition in Children with Learning Differences.

    ERIC Educational Resources Information Center

    Grobecker, Betsey; Lawrence, Frank

    2000-01-01

    Twenty-seven children (ages 7-10) with learning disabilities and 42 controls were tested on three different mathematics tasks. Significantly more controls abstracted composite unit structures suggestive of operational logic on modified nonverbal and associativity of length tasks. On a flash card task, children with learning disabilities achieved…

  13. Position Weight Matrix, Gibbs Sampler, and the Associated Significance Tests in Motif Characterization and Prediction

    PubMed Central

    Xia, Xuhua

    2012-01-01

    Position weight matrix (PWM) is not only one of the most widely used bioinformatic methods, but also a key component in more advanced computational algorithms (e.g., Gibbs sampler) for characterizing and discovering motifs in nucleotide or amino acid sequences. However, few generally applicable statistical tests are available for evaluating the significance of site patterns, PWM, and PWM scores (PWMS) of putative motifs. Statistical significance tests of the PWM output, that is, site-specific frequencies, PWM itself, and PWMS, are in disparate sources and have never been collected in a single paper, with the consequence that many implementations of PWM do not include any significance test. Here I review PWM-based methods used in motif characterization and prediction (including a detailed illustration of the Gibbs sampler for de novo motif discovery), present statistical and probabilistic rationales behind statistical significance tests relevant to PWM, and illustrate their application with real data. The multiple comparison problem associated with the test of site-specific frequencies is best handled by false discovery rate methods. The test of PWM, due to the use of pseudocounts, is best done by resampling methods. The test of individual PWMS for each sequence segment should be based on the extreme value distribution. PMID:24278755

  14. Multiparametric PET/CT-perfusion does not add significant additional information for initial staging in lung cancer compared with standard PET/CT

    PubMed Central

    2014-01-01

    Background The purpose of this study was to assess the relationship of CT-perfusion (CTP), 18F-FDG-PET/CT and histological parameters, and the possible added value of CTP to FDG-PET/CT in the initial staging of lung cancer. Methods Fifty-four consecutive patients (median age 65 years, 15 females, 39 males) with suspected lung cancer were evaluated prospectively by CT-perfusion scan and 18F-FDG-PET/CT scan. Overall, 46 tumors were identified. CTP parameters blood flow (BF), blood volume (BV), and mean transit time (MTT) of the tumor tissue were calculated. Intratumoral microvessel density (MVD) was assessed quantitatively. Differences in CTP parameters concerning tumor type, location, PET positivity of lymph nodes, TNM status, and UICC stage were analyzed. Spearman correlation analyses between CTP and 18F-FDG-PET/CT parameters (SUVmax, SUVmean, PETvol, and TLG), MVD, tumor size, and tumor stage were performed. Results The mean BF (mL/100 mL min-1), BV (mL/100 mL), and MTT (s) was 35.5, 8.4, and 14.2, respectively. The BF and BV were lower in tumors with PET-positive lymph nodes (p = 0.02). However, the CTP values were not significantly different among the N stages. The CTP values were not different, depending on tumor size and location. No significant correlation was found between CTP parameters and MVD. Conclusions Overall, the CTP information showed only little additional information for the initial staging compared with standard FDG-PET/CT. Low perfusion in lung tumors might possibly be associated with metabolically active regional lymph nodes. Apart from that, both CTP and 18F-FDG-PET/CT parameter sets may reflect different pathophysiological mechanisms in lung cancer. PMID:24450990

  15. Origin and significance of a late Wisconsin glacigenic sequence and associated periglacial features at Cary, Illinois

    SciTech Connect

    Hooyer, T.S.; Tulaczyk, S.M.; Stravers, J.A. . Dept. of Geology)

    1993-03-01

    The glacigenic sequence exposed in Cary, Illinois, provides insight into the depositional processes that shaped the Woodstock End Moraine of the Lake Michigan Lobe. The Moraine was formed by a short re-advance which occurred during the last deglaciation approximately 15,000--16,000 years B.P. In order to determine the sedimentary processes that dominated this ice marginal setting, the authors described lithofacies and their associations, glaciotectonic and sedimentary structures, as well as clast fabric. In addition, they performed laboratory analyses of grain size, lithology and shape. The glacigenic sequence represents one single ice advance/retreat as represented by five distinct facies. The complex of deposits that overlie the homogeneous diamicton layer originate from a stagnant ice environment. Their presence extends the northern limit for documented relict patterned ground in NE Illinois.

  16. Breast cancer-associated metastasis is significantly increased in a model of autoimmune arthritis

    PubMed Central

    Das Roy, Lopamudra; Pathangey, Latha B; Tinder, Teresa L; Schettini, Jorge L; Gruber, Helen E; Mukherjee, Pinku

    2009-01-01

    Introduction Sites of chronic inflammation are often associated with the establishment and growth of various malignancies including breast cancer. A common inflammatory condition in humans is autoimmune arthritis (AA) that causes inflammation and deformity of the joints. Other systemic effects associated with arthritis include increased cellular infiltration and inflammation of the lungs. Several studies have reported statistically significant risk ratios between AA and breast cancer. Despite this knowledge, available for a decade, it has never been questioned if the site of chronic inflammation linked to AA creates a milieu that attracts tumor cells to home and grow in the inflamed bones and lungs which are frequent sites of breast cancer metastasis. Methods To determine if chronic inflammation induced by autoimmune arthritis contributes to increased breast cancer-associated metastasis, we generated mammary gland tumors in SKG mice that were genetically prone to develop AA. Two breast cancer cell lines, one highly metastatic (4T1) and the other non-metastatic (TUBO) were used to generate the tumors in the mammary fat pad. Lung and bone metastasis and the associated inflammatory milieu were evaluated in the arthritic versus the non-arthritic mice. Results We report a three-fold increase in lung metastasis and a significant increase in the incidence of bone metastasis in the pro-arthritic and arthritic mice compared to non-arthritic control mice. We also report that the metastatic breast cancer cells augment the severity of arthritis resulting in a vicious cycle that increases both bone destruction and metastasis. Enhanced neutrophilic and granulocytic infiltration in lungs and bone of the pro-arthritic and arthritic mice and subsequent increase in circulating levels of proinflammatory cytokines, such as macrophage colony stimulating factor (M-CSF), interleukin-17 (IL-17), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), and tumor necrosis factor

  17. Interpretation of Genetic Association Studies: Markers with Replicated Highly Significant Odds Ratios May Be Poor Classifiers

    PubMed Central

    Jakobsdottir, Johanna; Gorin, Michael B.; Conley, Yvette P.; Ferrell, Robert E.; Weeks, Daniel E.

    2009-01-01

    Recent successful discoveries of potentially causal single nucleotide polymorphisms (SNPs) for complex diseases hold great promise, and commercialization of genomics in personalized medicine has already begun. The hope is that genetic testing will benefit patients and their families, and encourage positive lifestyle changes and guide clinical decisions. However, for many complex diseases, it is arguable whether the era of genomics in personalized medicine is here yet. We focus on the clinical validity of genetic testing with an emphasis on two popular statistical methods for evaluating markers. The two methods, logistic regression and receiver operating characteristic (ROC) curve analysis, are applied to our age-related macular degeneration dataset. By using an additive model of the CFH, LOC387715, and C2 variants, the odds ratios are 2.9, 3.4, and 0.4, with p-values of 10−13, 10−13, and 10−3, respectively. The area under the ROC curve (AUC) is 0.79, but assuming prevalences of 15%, 5.5%, and 1.5% (which are realistic for age groups 80 y, 65 y, and 40 y and older, respectively), only 30%, 12%, and 3% of the group classified as high risk are cases. Additionally, we present examples for four other diseases for which strongly associated variants have been discovered. In type 2 diabetes, our classification model of 12 SNPs has an AUC of only 0.64, and two SNPs achieve an AUC of only 0.56 for prostate cancer. Nine SNPs were not sufficient to improve the discrimination power over that of nongenetic predictors for risk of cardiovascular events. Finally, in Crohn's disease, a model of five SNPs, one with a quite low odds ratio of 0.26, has an AUC of only 0.66. Our analyses and examples show that strong association, although very valuable for establishing etiological hypotheses, does not guarantee effective discrimination between cases and controls. The scientific community should be cautious to avoid overstating the value of association findings in terms of

  18. CNTNAP2 Is Significantly Associated With Speech Sound Disorder in the Chinese Han Population.

    PubMed

    Zhao, Yun-Jing; Wang, Yue-Ping; Yang, Wen-Zhu; Sun, Hong-Wei; Ma, Hong-Wei; Zhao, Ya-Ru

    2015-11-01

    Speech sound disorder is the most common communication disorder. Some investigations support the possibility that the CNTNAP2 gene might be involved in the pathogenesis of speech-related diseases. To investigate single-nucleotide polymorphisms in the CNTNAP2 gene, 300 unrelated speech sound disorder patients and 200 normal controls were included in the study. Five single-nucleotide polymorphisms were amplified and directly sequenced. Significant differences were found in the genotype (P = .0003) and allele (P = .0056) frequencies of rs2538976 between patients and controls. The excess frequency of the A allele in the patient group remained significant after Bonferroni correction (P = .0280). A significant haplotype association with rs2710102T/+rs17236239A/+2538976A/+2710117A (P = 4.10e-006) was identified. A neighboring single-nucleotide polymorphism, rs10608123, was found in complete linkage disequilibrium with rs2538976, and the genotypes exactly corresponded to each other. The authors propose that these CNTNAP2 variants increase the susceptibility to speech sound disorder. The single-nucleotide polymorphisms rs10608123 and rs2538976 may merge into one single-nucleotide polymorphism. PMID:25895914

  19. On Efficient and Accurate Calculation of Significance P-Values for Sequence Kernel Association Testing of Variant Set.

    PubMed

    Wu, Baolin; Guan, Weihua; Pankow, James S

    2016-03-01

    The objective of this paper is to discuss and develop alternative computational methods to accurately and efficiently calculate significance P-values for the commonly used sequence kernel association test (SKAT) and adaptive sum of SKAT and burden test (SKAT-O) for variant set association. We show that the existing software can lead to either conservative or inflated type I errors. We develop alternative and efficient computational algorithms that quickly compute the SKAT P-value and have well-controlled type I errors. In addition, we derive an alternative and simplified formula for calculating the significance P-value of SKAT-O, which sheds light on the development of efficient and accurate numerical algorithms. We implement the proposed methods in the publicly available R package that can be readily used or adapted to large-scale sequencing studies. Given that more and more large-scale exome and whole genome sequencing or re-sequencing studies are being conducted, the proposed methods are practically very important. We conduct extensive numerical studies to investigate the performance of the proposed methods. We further illustrate their usefulness with application to associations between rare exonic variants and fasting glucose levels in the Atherosclerosis Risk in Communities (ARIC) study. PMID:26757198

  20. Carbonic anhydrase IX is a clinically significant tissue and serum biomarker associated with renal cell carcinoma

    PubMed Central

    TAKACOVA, MARTINA; BARTOSOVA, MARIA; SKVARKOVA, LUCIA; ZATOVICOVA, MIRIAM; VIDLICKOVA, IVANA; CSADEROVA, LUCIA; BARATHOVA, MONIKA; BREZA, JAN; BUJDAK, PETER; PASTOREK, JAROMIR; BREZA, JAN; PASTOREKOVA, SILVIA

    2013-01-01

    Carbonic anhydrase IX (CA IX) is regarded as one of the most prominent markers of tumor hypoxia with potential to serve as a diagnostic biomarker, prognostic indicator as well as tumor therapeutic target. The aim of the present study was to perform an in-depth analysis of CA IX expression in blood and tissue samples and to evaluate the significance of CA IX status for different renal cell carcinomas (RCCs). The expression of CA IX was determined in blood and tissue samples from 74 kidney cancer patients using reverse transcription polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), Western blotting (WB) and immunohistochemistry (IHC). The CA IX status was correlated with RCC type and tumor stage. IHC and WB provided evidence for a significantly higher expression of CA IX in clear cell RCC (CCRCC) specimens compared to other RCCs. RT-PCR assay revealed that 32.42% of all RCC patients possess CA9-positive cells in peripheral blood and three-quarters of CA9-positive patients were diagnosed with CCRCC. When the patients were subdivided according to tumor stage, decreased positivity was observed with higher tumor stage (50% in T1 vs. 17% in T3). Serum CA IX levels determined by ELISA were significantly higher in CCRCC patients than in non-CCRCC. A significant association between s-CA IX and CCRCC tumor stage was also determined (T1-87.51 vs. T3-341.98 pg/ml, p=0.046). We demonstrated that the CA IX expression profiles in blood and tissue samples from 74 kidney cancer patients are closely correlated with their histological subtypes. This is the first study reporting CA IX expression in blood and tissue samples from kidney cancer patients determined by four different methods. PMID:23255918

  1. Significant association of HLA-DQ5 with autoimmune hepatitis in Taiwan.

    PubMed

    Koay, Lok-Beng; Sun, Chi-Shu; Tsai, Sun-Lung; Lin, Ching-Yih

    2007-12-01

    Genetic predisposition is known to be an important etiopathogenic factor of autoimmune hepatitis (AIH). HLA antigens associated with AIH have been well studied in Western countries and Japan, but there is no HLA typing data of AIH patients in Taiwan. We therefore investigated HLA phenotypes and their association with AIH patients and compared the results with those of normal subjects and patients with chronic liver disease. Group 1 consisted of 22 AIH patients. All were born in Taiwan with no history of blood transfusion. Group 2 consisted of 19 chronic liver disease patients. Group 3 consisted of 81 unrelated healthy subjects who were normal blood donors. All three groups were tested for HLA phenotypes (HLAA, B, C, DR, DQ) using the polymerase chain reaction-sequence specific probe method. The statistical method used was Fisher's exact test. We found that HLA-DQ5 was significantly more frequent in the AIH group compared to the control group (RR, 2.03; p = 0.034). Low frequency of A1 (n = 2/22), B8 (n = 1/22) and DR3 (n = 0/22) were noted compared to results from the West; only HLA-DR4 showed a higher rate in our AIH patients (n = 8/22). This is a preliminary report of our study of HLA antigens in AIH patients. Further investigation to characterize AIH patients into HLA allelic subgroups is being done. PMID:18194915

  2. Ultimate strength performance of tankers associated with industry corrosion addition practices

    NASA Astrophysics Data System (ADS)

    Kim, Do Kyun; Kim, Han Byul; Zhang, Xiaoming; Li, Chen Guang; Paik, Jeom Kee

    2014-09-01

    In the ship and offshore structure design, age-related problems such as corrosion damage, local denting, and fatigue damage are important factors to be considered in building a reliable structure as they have a significant influence on the residual structural capacity. In shipping, corrosion addition methods are widely adopted in structural design to prevent structural capacity degradation. The present study focuses on the historical trend of corrosion addition rules for ship structural design and investigates their effects on the ultimate strength performance such as hull girder and stiffened panel of double hull oil tankers. Three types of rules based on corrosion addition models, namely historic corrosion rules (pre-CSR), Common Structural Rules (CSR), and harmonised Common Structural Rules (CSRH) are considered and compared with two other corrosion models namely UGS model, suggested by the Union of Greek Shipowners (UGS), and Time-Dependent Corrosion Wastage Model (TDCWM). To identify the general trend in the effects of corrosion damage on the ultimate longitudinal strength performance, the corrosion addition rules are applied to four representative sizes of double hull oil tankers namely Panamax, Aframax, Suezmax, and VLCC. The results are helpful in understanding the trend of corrosion additions for tanker structures

  3. Neurohumoral mechanisms associated with orthostasis: reaffirmation of the significant contribution of the heart rate response

    PubMed Central

    Convertino, Victor A.

    2014-01-01

    The inability to compensate for acute central hypovolemia underlies the clinical development of orthostatic hypotension and instability (e.g., syncope). Although neuro-humoral control of both cardiac output and peripheral vascular resistance contributes to hemodynamic stability during orthostasis, a notion has been proposed that the failure of adequate peripheral vascular constriction rather than cardiac responses represents the primary mechanism underlying the development of orthostatic intolerance. This review article provides an opportunity to present compelling evidence captured over the past 30 years in our laboratory to support the concept that neural-mediated tachycardia during orthostasis in healthy individuals represents a critical response to tolerating acute reduction in central blood volume in addition to, and independent of, peripheral vascular constriction. In this review paper, data are presented from experiments using graded lower body negative pressure (LBNP) as a method to induce orthostatic intolerance in two experimental human models: (1) comparison of heart rate and autonomic responses in individuals with relatively high and low tolerance to LBNP; and (2) vagal and sympathetic blockade of cardiac neural control. These experiments revealed that: (1) greater elevations in heart rate are associated with higher orthostatic (LBNP) tolerance; (2) higher orthostatic heart rate is associated with greater sympathetic nerve activity and withdrawal of vagally-mediated cardiac baroreflex response; and (3) non-specific sympathetic blockade causes a pronounced reduction in heart rate and LBNP tolerance. Cardiac parasympathetic withdrawal contributes to protection against development of hypotension during the initial seconds of transition to an orthostatic challenge, while the primary mechanism by which tachycardia defends orthostatic stability in healthy subjects for extended durations is mediated predominantly through sympathetic adrenergic control. PMID

  4. Clinical Significance of Tumor-Associated Inflammatory Cells in Metastatic Neuroblastoma

    PubMed Central

    Asgharzadeh, Shahab; Salo, Jill A.; Ji, Lingyun; Oberthuer, André; Fischer, Matthias; Berthold, Frank; Hadjidaniel, Michael; Liu, Cathy Wei-Yao; Metelitsa, Leonid S.; Pique-Regi, Roger; Wakamatsu, Peter; Villablanca, Judith G.; Kreissman, Susan G.; Matthay, Katherine K.; Shimada, Hiroyuki; London, Wendy B.; Sposto, Richard; Seeger, Robert C.

    2012-01-01

    Purpose Children diagnosed at age ≥ 18 months with metastatic MYCN-nonamplified neuroblastoma (NBL-NA) are at high risk for disease relapse, whereas those diagnosed at age < 18 months are nearly always cured. In this study, we investigated the hypothesis that expression of genes related to tumor-associated inflammatory cells correlates with the observed differences in survival by age at diagnosis and contributes to a prognostic signature. Methods Tumor-associated macrophages (TAMs) in localized and metastatic neuroblastomas (n = 71) were assessed by immunohistochemistry. Expression of 44 genes representing tumor and inflammatory cells was quantified in 133 metastatic NBL-NAs to assess age-dependent expression and to develop a logistic regression model to provide low- and high-risk scores for predicting progression-free survival (PFS). Tumors from high-risk patients enrolled onto two additional studies (n = 91) served as independent validation cohorts. Results Metastatic neuroblastomas had higher infiltration of TAMs than locoregional tumors, and metastatic tumors diagnosed in patients at age ≥ 18 months had higher expression of inflammation-related genes than those in patients diagnosed at age < 18 months. Expression of genes representing TAMs (CD33/CD16/IL6R/IL10/FCGR3) contributed to 25% of the accuracy of a novel 14-gene tumor classification score. PFS at 5 years for children diagnosed at age ≥ 18 months with NBL-NA with a low- versus high-risk score was 47% versus 12%, 57% versus 8%, and 50% versus 20% in three independent clinical trials, respectively. Conclusion These data suggest that interactions between tumor and inflammatory cells may contribute to the clinical metastatic neuroblastoma phenotype, improve prognostication, and reveal novel therapeutic targets. PMID:22927533

  5. PERSONAL AND ENVIRONMENTAL RISK FACTORS SIGNIFICANTLY ASSOCIATED WITH ELEVATED BLOOD LEAD LEVELS IN RURAL THAI CHILDREN.

    PubMed

    Swaddiwudhipong, Witaya; Kavinum, Suporn; Papwijitsil, Ratchadaporn; Tontiwattanasap, Worawit; Khunyotying, Wanlee; Umpan, Jiraporn; BoonthuM, Ratchaneekorn; Kaewnate, Yingyot; Boonmee, Sasis; Thongchub, Winai; Rodsung, Thassanee

    2014-11-01

    A community-based study was conducted to determine personal risk factors and environmental sources of lead exposure for elevated blood lead levels (≥ 10 µg/dl, EBLLs) among rural children living at the Thailand-Myanmar border in Tak Province, northwestern Thailand. Six hundred ninety-five children aged 1-14 years old were screened for BLLs. Environmental specimens for lead measurements included samples of water from the streams, taps, and household containers, house floor dust, and foods. Possible lead release from the cooking ware was determined using the leaching method with acetic acid. The overall prevalence of EBLLs was 47.1% and the geometric mean level of blood lead was 9.16 µg/dl. Personal risk factors significantly associated with EBLLs included being male, younger age, anemia, and low weight-for-age. Significant environmental risk factors were exposure to a lead-acid battery of solar energy system and use of a non-certified metal cooking pot. Some families whose children had high BLLs reported production of lead bullets from the used batteries at home. About one-third of the house dust samples taken near batteries contained lead content above the recommended value, compared with none of those taken from other areas and from the houses with no batteries. The metal pots were safe for cooking rice but might be unsafe for acidic food preparation. Both nutritional intervention and lead exposure prevention programs are essential to reduce EBLLs in this population. PMID:26466436

  6. Postranslational modifications significantly alter the binding-folding pathways of proteins associating with DNA

    NASA Astrophysics Data System (ADS)

    Papoian, Garegin

    2012-02-01

    Many important regulators of gene activity are natively disordered, but fully or partially order when they bind to their targets on DNA. Interestingly, the ensembles of disordered states for such free proteins are not structurally featureless, but can qualitatively differ from protein to protein. In particular, in random coil like states the chains are swollen, making relatively few contacts, while in molten globule like states a significant collapse occurs, with ensuing high density of intra-protein interactions. Furthermore, since many DNA binding proteins are positively charged polyelectrolytes, the electrostatic self-repulsion also influences the degree of collapse of the chain and its conformational preferences in the free state and upon binding to DNA. In our work, we have found that the nature of the natively disordered ensemble significantly affects the way the protein folds upon binding to DNA. In particular, we showed that posttranslational modifications of amino acid residues, such as lysine acetylation, can alter the degree of collapse and conformational preferences for a free protein, and also profoundly impact the binding affinity and pathways for the protein DNA association. These trends will be discussed in the context of DNA interacting with various histone tails and the p53 protein.

  7. Gastrointestinal angiodysplasia is associated with significant gastrointestinal bleeding in patients with continuous left ventricular assist devices

    PubMed Central

    Cochrane, Justin; Jackson, Christian; Schlepp, Greg; Strong, Richard

    2016-01-01

    Background and study aims: Patients with a continuous-flow left ventricular assist device (LVAD) have a 65 % incidence of bleeding events within the first year. The majority of gastrointestinal bleeding (GIB) is from gastrointestinal angiodyplasia (GIAD). The primary aim of the study was to determine whether GIAD was associated with a higher rate of significant bleeding, an increased number of bleeding events per year, and a higher rate of transfusion compared to non-GIAD sources. Patients and methods: This retrospective cohort study included 118 individuals who received a LVAD at a tertiary medical center from 2006 through 2014. Patients were subdivided into GIB and non-GIB for comparison of patient demographics, comorbid conditions, and laboratory data. GIB was further divided into sources of GIB, GIAD, obscure, or non-GIAD to establish severity of bleeding, rate of re-bleeding, and transfusion rate. Results: GIAD is associated with an increased number of bleeding events compared to non-GIAD sources of GIB (2.07 vs 1.23, P = 0.01) and a higher number of bleeding events per year (0.806 vs. 0.455 P = 0.001). GIAD compared to non-GIAD sources of GIB was associated with an increased incidence of major bleeding (100 % vs 60 %, P = 0.006) and increased rates of transfusion (8.8 vs 2.95 units, P = 0.0004). Cox Regression analysis between non-GIB and GIAD demonstrated increased risk with age (P = 0.001), history of chronic kidney disease (P = 0.005), and length of stay after LVAD implantation of more than 45 days (P = 0.04). History of hypertension (P = 0.045), diabetes mellitus (P = 0.016), and male gender was associated with decreased risk (P = 0.04). Conclusion: Patients with a continuous-flow LVAD who develop a GIB secondary to GIAD have a higher rate of major bleeding, multiple bleeding events, and require more transfusions to achieve stabilization compared to patients who do not have GIAD. PMID

  8. Identifying significant microRNA-mRNA pairs associated with breast cancer subtypes.

    PubMed

    Bhattacharyya, Malay; Nath, Joyshree; Bandyopadhyay, Sanghamitra

    2016-07-01

    MicroRNAs (miRNAs) are small non-coding RNAs that help in post-transcriptional gene silencing. These endogenous RNAs develop a post-transcriptional gene-regulatory network by binding to complementary sequences of target mRNAs and essentially degrade them. Cancer is a class of diseases that is caused by the uncontrolled cell growth, thereby resulting into a gradual degradation of cell structure. Earlier researches have shown that miRNAs have significant biological involvement in cancer. Prolonged research in this genre has led to the identification of the functions of numerous miRNAs in cancer development. Studying the differential expression profiles of miRNAs and mRNAs together could help us in recognizing the significant miRNA-mRNA pairs from cancer samples. In this paper, we have analyzed the simultaneous over-expression of miRNAs and under-expression of mRNAs and vice versa to establish their association with cancer. This study focuses on breast tumor samples and the miRNA-mRNA target pairs that have a visible signature in such breast tumor samples. We have been able to identify the differentially expressed miRNAs and mRNAs, and further established relations between them to extract the miRNA-mRNA pairs that might be significant in the breast cancer types. This gives us the clue about the potential biomarkers for the breast cancer subtypes that can further help in understanding the progression of each of the subtypes separately. This might be helpful for the joint miRNA-mRNA biomarker identification. PMID:27245063

  9. Colon cancer associated genes exhibit signatures of positive selection at functionally significant positions

    PubMed Central

    2012-01-01

    Background Cancer, much like most human disease, is routinely studied by utilizing model organisms. Of these model organisms, mice are often dominant. However, our assumptions of functional equivalence fail to consider the opportunity for divergence conferred by ~180 Million Years (MY) of independent evolution between these species. For a given set of human disease related genes, it is therefore important to determine if functional equivalency has been retained between species. In this study we test the hypothesis that cancer associated genes have different patterns of substitution akin to adaptive evolution in different mammal lineages. Results Our analysis of the current literature and colon cancer databases identified 22 genes exhibiting colon cancer associated germline mutations. We identified orthologs for these 22 genes across a set of high coverage (>6X) vertebrate genomes. Analysis of these orthologous datasets revealed significant levels of positive selection. Evidence of lineage-specific positive selection was identified in 14 genes in both ancestral and extant lineages. Lineage-specific positive selection was detected in the ancestral Euarchontoglires and Hominidae lineages for STK11, in the ancestral primate lineage for CDH1, in the ancestral Murinae lineage for both SDHC and MSH6 genes and the ancestral Muridae lineage for TSC1. Conclusion Identifying positive selection in the Primate, Hominidae, Muridae and Murinae lineages suggests an ancestral functional shift in these genes between the rodent and primate lineages. Analyses such as this, combining evolutionary theory and predictions - along with medically relevant data, can thus provide us with important clues for modeling human diseases. PMID:22788692

  10. Genome-Wide Association Study of CSF Levels of 59 Alzheimer's Disease Candidate Proteins: Significant Associations with Proteins Involved in Amyloid Processing and Inflammation

    PubMed Central

    Kauwe, John S. K.; Bailey, Matthew H.; Ridge, Perry G.; Perry, Rachel; Wadsworth, Mark E.; Hoyt, Kaitlyn L.; Staley, Lyndsay A.; Karch, Celeste M.; Harari, Oscar; Cruchaga, Carlos; Ainscough, Benjamin J.; Bales, Kelly; Pickering, Eve H.; Bertelsen, Sarah; Fagan, Anne M.; Holtzman, David M.; Morris, John C.; Goate, Alison M.

    2014-01-01

    Cerebrospinal fluid (CSF) 42 amino acid species of amyloid beta (Aβ42) and tau levels are strongly correlated with the presence of Alzheimer's disease (AD) neuropathology including amyloid plaques and neurodegeneration and have been successfully used as endophenotypes for genetic studies of AD. Additional CSF analytes may also serve as useful endophenotypes that capture other aspects of AD pathophysiology. Here we have conducted a genome-wide association study of CSF levels of 59 AD-related analytes. All analytes were measured using the Rules Based Medicine Human DiscoveryMAP Panel, which includes analytes relevant to several disease-related processes. Data from two independently collected and measured datasets, the Knight Alzheimer's Disease Research Center (ADRC) and Alzheimer's Disease Neuroimaging Initiative (ADNI), were analyzed separately, and combined results were obtained using meta-analysis. We identified genetic associations with CSF levels of 5 proteins (Angiotensin-converting enzyme (ACE), Chemokine (C-C motif) ligand 2 (CCL2), Chemokine (C-C motif) ligand 4 (CCL4), Interleukin 6 receptor (IL6R) and Matrix metalloproteinase-3 (MMP3)) with study-wide significant p-values (p<1.46×10−10) and significant, consistent evidence for association in both the Knight ADRC and the ADNI samples. These proteins are involved in amyloid processing and pro-inflammatory signaling. SNPs associated with ACE, IL6R and MMP3 protein levels are located within the coding regions of the corresponding structural gene. The SNPs associated with CSF levels of CCL4 and CCL2 are located in known chemokine binding proteins. The genetic associations reported here are novel and suggest mechanisms for genetic control of CSF and plasma levels of these disease-related proteins. Significant SNPs in ACE and MMP3 also showed association with AD risk. Our findings suggest that these proteins/pathways may be valuable therapeutic targets for AD. Robust associations in cognitively normal

  11. Gut microbiota associated with HIV infection is significantly enriched in bacteria tolerant to oxygen

    PubMed Central

    Dubourg, Grégory; Lagier, Jean-Christophe; Hüe, Sophie; Surenaud, Mathieu; Bachar, Dipankar; Robert, Catherine; Michelle, Caroline; Ravaux, Isabelle; Mokhtari, Saadia; Million, Matthieu; Stein, Andreas; Brouqui, Philippe; Levy, Yves; Raoult, Didier

    2016-01-01

    Objectives Gut microbiota modifications occurring during HIV infection have recently been associated with inflammation and microbial translocation. However, discrepancies between studies justified a comprehensive analysis performed on a large sample size. Design and methods In a case–control study, next-generation sequencing of the 16S rRNA gene was applied to the faecal microbiota of 31 HIV-infected patients, of whom 18 were treated with antiretroviral treatment (ART), compared with 27 healthy controls. 21 sera samples from HIV-infected patients and 7 sera samples from control participants were used to test the presence of 25 markers of inflammation and/or immune activation. Results Diversity was significantly reduced in HIV individuals when compared with controls and was not restored in the ART group. The relative abundance of several members of Ruminococcaceae such as Faecalibacterium prausnitzii was critically less abundant in the HIV-infected group and inversely correlated with inflammation/immune activation markers. Members of Enterobacteriaceae and Enterococcaceae were found to be enriched and positively correlated with these markers. There were significantly more aerotolerant species enriched in HIV samples (42/52 species, 80.8%) when compared with the control group (14/87 species, 16.1%; χ2 test, p<10−5, conditional maximum-likelihood estimate (CMLE) OR=21.9). Conclusions Imbalance between aerobic and anaerobic flora observed in HIV faecal microbiota could be a consequence of the gut impairment classically observed in HIV infection via the production of oxygen. Overgrowth of proinflammatory aerobic species during HIV infection raises the question of antioxidant supplementation, such as vitamin C, E or N-acetylcysteine. PMID:27547442

  12. The Unique and Additive Associations of Family Functioning and Parenting Practices with Disordered Eating Behaviors in Diverse Adolescents

    PubMed Central

    Berge, Jerica M.; Wall, Melanie; Larson, Nicole; Eisenberg, Marla E.; Loth, Katie A.; Neumark-Sztainer, Dianne

    2012-01-01

    Objective To examine the unique and additive associations of family functioning and parenting practices with adolescent disordered eating behaviors (i.e., dieting, unhealthy weight control behaviors, binge eating). Methods Data from EAT (Eating and Activity in Teens) 2010, a population-based study assessing eating and activity among racially/ethnically and socio-economically diverse adolescents (n = 2,793; mean age = 14.4, SD = 2.0; age range = 11–19) was used. Logistic regression models were used to examine associations between adolescent dieting and disordered eating behaviors and family functioning and parenting variables, including interactions. All analyses controlled for demographics and body mass index. Results Higher family functioning, parent connection, and parental knowledge about child’s whereabouts (e.g. who child is with, what they are doing, where they are at) were significantly associated with lower odds of engaging in dieting and disordered eating behaviors in adolescents, while parent psychological control was associated with greater odds of engaging in dieting and disordered eating behaviors. Although the majority of interactions were non-significant, parental psychological control moderated the protective relationship between family functioning and disordered eating behaviors in adolescent girls. Conclusions Clinicians and health care providers may want to discuss the importance of balancing specific parenting behaviors, such as increasing parent knowledge about child whereabouts while decreasing psychological control in order to enhance the protective relationship between family functioning and disordered eating behaviors in adolescents. PMID:23196919

  13. A genome scan revealed significant associations of growth traits with a major QTL and GHR2 in tilapia

    PubMed Central

    Liu, Feng; Sun, Fei; Xia, Jun Hong; Li, Jian; Fu, Gui Hong; Lin, Grace; Tu, Rong Jian; Wan, Zi Yi; Quek, Delia; Yue, Gen Hua

    2014-01-01

    Growth is an important trait in animal breeding. However, the genetic effects underpinning fish growth variability are still poorly understood. QTL mapping and analysis of candidate genes are effective methods to address this issue. We conducted a genome-wide QTL analysis for growth in tilapia. A total of 10, 7 and 8 significant QTLs were identified for body weight, total length and standard length at 140 dph, respectively. The majority of these QTLs were sex-specific. One major QTL for growth traits was identified in the sex-determining locus in LG1, explaining 71.7%, 67.2% and 64.9% of the phenotypic variation (PV) of body weight, total length and standard length, respectively. In addition, a candidate gene GHR2 in a QTL was significantly associated with body weight, explaining 13.1% of PV. Real-time qPCR revealed that different genotypes at the GHR2 locus influenced the IGF-1 expression level. The markers located in the major QTL for growth traits could be used in marker-assisted selection of tilapia. The associations between GHR2 variants and growth traits suggest that the GHR2 gene should be an important gene that explains the difference in growth among tilapia species. PMID:25435025

  14. A genome scan revealed significant associations of growth traits with a major QTL and GHR2 in tilapia.

    PubMed

    Liu, Feng; Sun, Fei; Xia, Jun Hong; Li, Jian; Fu, Gui Hong; Lin, Grace; Tu, Rong Jian; Wan, Zi Yi; Quek, Delia; Yue, Gen Hua

    2014-01-01

    Growth is an important trait in animal breeding. However, the genetic effects underpinning fish growth variability are still poorly understood. QTL mapping and analysis of candidate genes are effective methods to address this issue. We conducted a genome-wide QTL analysis for growth in tilapia. A total of 10, 7 and 8 significant QTLs were identified for body weight, total length and standard length at 140 dph, respectively. The majority of these QTLs were sex-specific. One major QTL for growth traits was identified in the sex-determining locus in LG1, explaining 71.7%, 67.2% and 64.9% of the phenotypic variation (PV) of body weight, total length and standard length, respectively. In addition, a candidate gene GHR2 in a QTL was significantly associated with body weight, explaining 13.1% of PV. Real-time qPCR revealed that different genotypes at the GHR2 locus influenced the IGF-1 expression level. The markers located in the major QTL for growth traits could be used in marker-assisted selection of tilapia. The associations between GHR2 variants and growth traits suggest that the GHR2 gene should be an important gene that explains the difference in growth among tilapia species. PMID:25435025

  15. Significant associations among hemostatic parameters, adipokines, and components of the metabolic syndrome in Japanese preschool children.

    PubMed

    Horigome, Hitoshi; Katayama, Yasutomi; Yoshinaga, Masao; Kato, Yoshiaki; Takahashi, Hideto; Sumazaki, Ryo

    2012-01-01

    Development of cardiovascular diseases could originate in early childhood. However, reference values of hemostatic parameters and adipokines in preschool children remain to be explored. We measured blood levels of adipokines and parameters of the hemostatic/fibrinolytic systems in 167 healthy children aged 4 to 6 years at 9:00 to 10:30 am after a strictly enforced overnight fast. Participants with body mass index (BMI) values ≥90th percentile had significantly higher values of systolic blood pressure and heart rate, as well as blood levels of insulin, coagulation factor (F) VII, FX, protein S, leptin, and homeostasis model assessment of insulin resistance (HOMA-IR), and lower values of desacyl-ghrelin than children with BMI < 90th percentile. Circulating levels of fibrinogen and leptin increased with increased number of cardiovascular risk factors. Stepwise regression analysis identified many hematological variables to be associated with features of the metabolic syndrome. The results implicated the hemostatic/fibrinolytic system or adipokines in the insidious progression of cardiovascular diseases from an early age. PMID:21949035

  16. Expression and clinical significance of miRNAs that may be associated with the FHIT gene in breast cancer.

    PubMed

    Sevinc, Elif Demirdogen; Cecener, Gulsah; Ak, Secil; Tunca, Berrin; Egeli, Unal; Gokgoz, Sehsuvar; Tolunay, Sahsine; Tasdelen, Ismet

    2016-09-30

    The dysregulation of miRNA expression has frequently been observed in breast cancer. Therefore, we investigated the expression profile of miRNAs that may be associated with expression of the FHIT gene in breast cancer and assessed their clinicopathological significance. The expression levels of miR-143, miR-663a, miR-668, miR-922 and FHIT were analyzed in normal and malignant breast tissues from 65 patients with breast cancer. We studied the correlation between the expression of miR-143, miR-663a, miR-668, miR-922 and FHIT and the clinicopathological features presented by the patients. The expression levels of the miRNAs and FHIT were downregulated in breast cancer tissue. The expression levels of miR-143, miR-663a and miR-668 were significantly reduced in FHIT downregulated tumors. miR-668 expression was also significantly altered relative to FHIT down- and up- regulated tumor tissues. Reduced miR-663a expression was statistically associated with high-grade ER/PR (+) status, benign reactive hyperplasia, lymph-node metastasis, in-situ component >25% and Ki 67>15% compared with non-tumor tissues. Additionally, reduced miR-668 expression was significantly different between tumors with and without lymph-node metastasis. miR-668 may play an important role in breast cancer development and progression by regulating the expression of FHIT. Furthermore, miR-668 and miR-663a may be potential prognostic biomarkers for breast cancer. PMID:27236032

  17. Two Cases of Generalized Seizures and the Velocardiofacial Syndrome - A Clinically Significant Association?

    ERIC Educational Resources Information Center

    El Tahir, M. O.; Kerr, M.; Jones, R. G.

    2004-01-01

    Velocardiofacial syndrome (VCFS) is caused by a micro deletion of chromosome 22q11 and associated with multiple system abnormalities. There is an increasing recognition of associations with psychiatric disorders. Neurological and brain abnormalities have been reported but to date no association with generalized epilepsy has been reported in…

  18. Revealing Significant Relations between Chemical/Biological Features and Activity: Associative Classification Mining for Drug Discovery

    ERIC Educational Resources Information Center

    Yu, Pulan

    2012-01-01

    Classification, clustering and association mining are major tasks of data mining and have been widely used for knowledge discovery. Associative classification mining, the combination of both association rule mining and classification, has emerged as an indispensable way to support decision making and scientific research. In particular, it offers a…

  19. No Clinically Significant Association Between CFH and ARMS2 Genotypes and Response to Nutritional Supplements

    PubMed Central

    Chew, Emily Y.; Klein, Michael L.; Clemons, Traci E.; Agrón, Elvira; Ratnapriya, Rinki; Edwards, Albert O.; Fritsche, Lars G.; Swaroop, Anand; Abecasis, Gonçalo R.

    2014-01-01

    Objective To determine whether genotypes at two major loci associated with late age-related macular degeneration (AMD), complement factor H (CFH) and Age-Related Maculopathy Susceptibility 2 (ARMS2), influenced the relative benefits of Age-Related Eye Disease Study (AREDS) supplements. Design Unplanned retrospective evaluation of a prospective, randomized, placebo-controlled clinical trial of vitamins and minerals for the treatment of AMD. Subjects AREDS participants (mean age of 69 years) who were at risk for developing late AMD and who were randomized to the 4 arms of the AREDS supplements. Methods Analyses were performed using the Cox proportional hazards model to predict progression to late AMD (neovascular or central geographic atrophy). Statistical models, adjusted for age, gender, smoking status and baseline AMD severity, were used to examine the influence of genotypes on the response to therapy with 4 randomly assigned arms of AREDS supplement components: placebo, antioxidants (vitamins C, E, beta-carotene), zinc with copper, or the combination. Main Outcome Measures The influence of the genotype on the relative treatment response to the randomized components of the AREDS supplement, measured as progression to late AMD. Results Of the 1237 genotyped AREDS participants of Caucasian ethnicity, 385 (31.1%) developed late AMD during the mean follow-up period of 6.6 years. As previously demonstrated, both CFH genotype (p=0.005), ARMS2 (<0.0001) and supplement were each individually associated with progression to late AMD. An interaction analysis found no evidence that the relative benefits of AREDS supplementation varied by genotype. Analysis of (1) CFH rs1061170 and rs1410996 combined with ARMS2 rs10490924, with the 4 randomly assigned arms of AREDS supplement and (2) analysis of the combination of CFH rs412852 and rs3766405 with ARMS2 c.372_815del443ins54 with the AREDS components resulted in no interaction (p=0.06 and p=0.45, respectively, before multiplicity

  20. Human disodium octaborate tetrahydrate exposure following carpet flea treatment is not associated with significant dermal absorption.

    PubMed

    Krieger, R I; Dinoff, T M; Peterson, J

    1996-01-01

    Disodium octaborate tetrahydrate is used for indoor flea control on carpets and furniture. Disodium octaborate tetrahydrate was applied to a 100% nylon carpet as a solution using a powered rug brush at a rate of approximately 200 micrograms/cm2 carpet. Two randomly chosen groups of volunteers (18 females, 4 males) wore either bathing suits which provided 75% or more skin exposure or whole-body, cotton dosimeters consisting of socks, union suits, and gloves. The volunteers performed a 20-minute set of Jazzercise routines. The availability of boron was demonstrated by covering portions of the carpet with a cotton dosimeter and rolling it with a weighted roller. Additionally, disodium octaborate tetrahydrate was transferred to the whole-body dosimeter. Volunteers also collected 24-hour urine specimens prior to and following the exercise period. The specimens were analyzed for total boron by inductively coupled plasma emission spectroscopy. No evidence of contact transfer and dermal absorption was obtained. The mean daily boron levels (mg/g creatinine) were 1.17, 1.33, and 1.31 for the group with exposed skin and 1.26, 1.12, and 1.26 for those who wore dosimeters which prevented contact. Daily urine boron levels were not significantly different when compared using a two sample t-test assuming equal variances (P > 0.05). Direct dermal contact with disodium octaborate tetrahydrate-treated carpet at a nominal rate of 200 micrograms/cm2 did not produce any adverse effects or change urinary boron clearance. PMID:8889949

  1. Selection of human p75NTR tag SNPs and its biological significance for clinical association studies.

    PubMed

    Wang, Yong-Tang; Lu, Xiu-Min; Shu, Ya-Hai; Xiao, Lan; Chen, Kai-Ting

    2014-01-01

    To select tag single nucleotide polymorphisms (SNPs) within and around human p75 neurotrophin receptor (p75NTR) gene in Chinese Han population, the sequence involving p75NTR gene as well as the upstream and downstream of the gene was identified according to the data from National Center for Biotechnology Information (NCBI) GenBank database, and the SNP genotype data involving 63 SNPs in the regions were obtained from Chinese Han Beijing (CHB) population of HapMap database. Then, Haploview (version 4.2) was used to calculate linkage disequilibrium (LD) statistics for the selected 32 common SNPs with a minor allele frequence (MAF) more than 0.05. Haplotype blocks were constructed throughout the p75NTR gene according to the upper and the lower 95% confidence bound of D' value, and the tag SNPs were selected based on the r2 and LOD values between SNPs as well as the results of bioinformatics analysis. The results indicated that five haplotype blocks were constructed within and around p75NTR gene and 12 tag SNPs including rs2537710, rs603769, rs614455, rs2537706, rs534561, rs2072445, rs2072446, rs7219709, rs734194, rs741071, rs741073 and rs2671641 were selected to represent the other 51 SNPs in p75NTR gene. Therefore, the 12 selected SNPs may act as tag SNPs for the entire p75NTR gene in Chinese Han population, which will provide an effective way to select tag SNPs in a whole gene, and its biological significance is to further guide the clinical association studies between the candidate gene and disease susceptibility. PMID:25227100

  2. Performance on paced serial addition tasks indicates an associative network for calculation.

    PubMed

    Hiscock, M; Caroselli, J S; Kimball, L E; Panwar, N

    2001-06-01

    Although paced serial addition (PSA) tasks are considered to be tests of general information-processing capacity, recent work suggests that performance on such tasks is influenced by arithmetic-specific variables. We designed two visual PSA experiments to determine whether the performance of normal adults would support predictions derived from the cognitive psychology of calculation. Experiment 1 showed that mixing familiar (Arabic numeral) and less familiar (Roman numeral) stimulus formats reduced scores below the averaged scores for pure Arabic and Roman lists. The Roman-Arabic order of addends was more difficult than the Arabic-Roman order. Experiment 2, which involved only Arabic numerals as addends, showed that performance could be impaired by constraining the trial-to-trial variability of sums. The results of both experiments confirm the importance of arithmetic-specific variables in PSA and provide support for an associative network model of calculation. In addition, the findings implicate interference from extraneous addends and responses as the performance-limiting factor. PMID:11404809

  3. Phthalates and other additives in plastics: human exposure and associated health outcomes

    PubMed Central

    Meeker, John D.; Sathyanarayana, Sheela; Swan, Shanna H.

    2009-01-01

    Concern exists over whether additives in plastics to which most people are exposed, such as phthalates, bisphenol A or polybrominated diphenyl ethers, may cause harm to human health by altering endocrine function or through other biological mechanisms. Human data are limited compared with the large body of experimental evidence documenting reproductive or developmental toxicity in relation to these compounds. Here, we discuss the current state of human evidence, as well as future research trends and needs. Because exposure assessment is often a major weakness in epidemiological studies, and in utero exposures to reproductive or developmental toxicants are important, we also provide original data on maternal exposure to phthalates during and after pregnancy (n = 242). Phthalate metabolite concentrations in urine showed weak correlations between pre- and post-natal samples, though the strength of the relationship increased when duration between the two samples decreased. Phthalate metabolite levels also tended to be higher in post-natal samples. In conclusion, there is a great need for more human studies of adverse health effects associated with plastic additives. Recent advances in the measurement of exposure biomarkers hold much promise in improving the epidemiological data, but their utility must be understood to facilitate appropriate study design. PMID:19528058

  4. Using Haplotype Analysis to Elucidate Significant Associations between Genes and Hodgkin Lymphoma

    PubMed Central

    D’Amelio, Anthony M.; Monroy, Claudia; El-Zein, Randa; Etzel, Carol J.

    2012-01-01

    In this study, we estimated the association between the inferred haplotypes in the inflammation, DNA repair, and folate pathways, and developed risk models for Hodgkin Lymphoma. The study population consisted of 200 Hodgkin Lymphoma cases and 220 controls. A susceptible association was observed on the XPC gene with Haplotype CT (rs2228001 and rs2228000), and a protective association was observed on the IL4R gene with Haplotype TCA (rs1805012, rs1805015, and rs1801275). These results can provide the necessary tools to identify high-risk individuals after validation in large data sets. PMID:22902050

  5. Tribological characteristics of bisphenol AF bis(diphenyl phosphate) as an antiwear additive in polyalkylene glycol and polyurea grease for significantly improved lubrication

    NASA Astrophysics Data System (ADS)

    Zhu, Lili; Wu, Xinhu; Zhao, Gaiqing; Wang, Xiaobo

    2016-02-01

    A new antiwear additive of Bisphenol AF bis(diphenyl phosphate) (BAFDP) was synthesized and characterized. The tribological behaviors of the additive for polyalkylene glycol (PAG) and polyurea grease (PG) application in steel/steel contacts were evaluated on an Optimol SRV-IV oscillating reciprocating friction and wear tester at elevated temperature. The results revealed that BAFDP could drastically reduce friction and wear of sliding pairs in both PAG and also in PG at 100 °C. The tribological properties of BAFDP are superior to the normally used zinc dialkyldithiophosphate-based additive package (ZDDP) in PAG and PG. Moreover, BAFDP as additive for PAG and PG displays relatively significant tribological properties in temperature-ramp tests by performing well at 50-300 °C, indicating the excellent high temperature friction reduction and anti-wear capacity of BAFDP. XPS results showed that boundary lubrication films composed of Fe(OH)O, Fe3O4, FePO4, FeF2, FeF3, compounds containing the Psbnd O bonds, nitrogen oxide, and so forth, were formed on the worn surface, which contributed to excellent friction reduction and antiwear performance.

  6. Lack of significant association between spina bifida and the fragile X syndrome

    SciTech Connect

    Schiano, C.M.; Demb, H.B.; Brown, W.T.

    1995-12-04

    Folic acid is involved in two common disorders associated with developmental disabilities. Spina bifida is a malformation that may be associated with mental retardation, learning disabilities, and epilepsy. Its incidence can be reduced by the ingestion of folic acid before, and at the time of, conception. The fragile X syndrome is a genetic disorder which is the most common form of inherited mental retardation. This disorder can be diagnosed by the induction of fragile sites on the X chromosome which is cultured in a medium deficient in folic acid. In several studies, folic acid was reported to alleviate some of the developmental and behavioral manifestations associated in the fragile X syndrome, while in others, it has no effect. 9 refs.

  7. Scoliosis and vertebral anomalies: additional abnormal phenotypes associated with chromosome 16p11.2 rearrangement.

    PubMed

    Al-Kateb, Hussam; Khanna, Geetika; Filges, Isabel; Hauser, Natalie; Grange, Dorothy K; Shen, Joseph; Smyser, Christopher D; Kulkarni, Shashikant; Shinawi, Marwan

    2014-05-01

    The typical chromosome 16p11.2 rearrangements are estimated to occur at a frequency of approximately 0.6% of all samples tested clinically and have been identified as a major cause of autism spectrum disorders, developmental delay, behavioral abnormalities, and seizures. Careful examination of patients with these rearrangements revealed association with abnormal head size, obesity, dysmorphism, and congenital abnormalities. In this report, we extend this list of phenotypic abnormalities to include scoliosis and vertebral anomalies. We present detailed characterization of phenotypic and radiological data of 10 new patients, nine with the 16p11.2 deletion and one with the duplication within the coordinates chr16:29,366,195 and 30,306,956 (hg19) with a minimal size of 555 kb. We discuss the phenotypical and radiological findings in our patients and review 5 previously reported patients with 16p11.2 rearrangement and similar skeletal abnormalities. Our data suggest that patients with the recurrent 16p11.2 rearrangement have increased incidence of scoliosis and vertebral anomalies. However, additional studies are required to confirm this observation and to establish the incidence of these anomalies. We discuss the potential implications of our findings on the diagnosis, surveillance and genetic counseling of patients with 16p11.2 rearrangement. PMID:24458548

  8. Significance of Additional Non-Mass Enhancement in Patients with Breast Cancer on Preoperative 3T Dynamic Contrast Enhanced MRI of the Breast

    PubMed Central

    Cho, Yun Hee; Cho, Kyu Ran; Park, Eun Kyung; Seo, Bo Kyoung; Woo, Ok Hee; Cho, Sung Bum; Bae, Jeoung Won

    2016-01-01

    Background In preoperative assessment of breast cancer, MRI has been shown to identify more additional breast lesions than are detectable using conventional imaging techniques. The characterization of additional lesions is more important than detection for optimal surgical treatment. Additional breast lesions can be included in focus, mass, and non-mass enhancement (NME) on MRI. According to the fifth edition of the breast imaging reporting and data system (BI-RADS®), which includes several changes in the NME descriptors, few studies to date have evaluated NME in preoperative assessment of breast cancer. Objectives We investigated the diagnostic accuracy of BI-RADS descriptors in predicting malignancy for additional NME lesions detected on preoperative 3T dynamic contrast enhanced MRI (DCE-MRI) in patients with newly diagnosed breast cancer. Patients and Methods Between January 2008 and December 2012, 88 patients were enrolled in our study, all with NME lesions other than the index cancer on preoperative 3T DCE-MRI and all with accompanying histopathologic examination. The MRI findings were analyzed according to the BI-RADS MRI lexicon. We evaluated the size, distribution, internal enhancement pattern, and location of NME lesions relative to the index cancer (i.e., same quadrant, different quadrant, or contralateral breast). Results On histopathologic analysis of the 88 NME lesions, 73 (83%) were malignant and 15 (17%) were benign. Lesion size did not differ significantly between malignant and benign lesions (P = 0.410). Malignancy was more frequent in linear (P = 0.005) and segmental (P = 0.011) distributions, and benignancy was more frequent in focal (P = 0.004) and regional (P < 0.001) NME lesions. The highest positive predictive value (PPV) for malignancy occurred in segmental (96.8%), linear (95.1%), clustered ring (100%), and clumped (92.0%) enhancement. Asymmetry demonstrated a high positive predictive value of 85.9%. The frequency of malignancy was higher

  9. Quercetin phospholipid complex significantly protects against oxidative injury in ARPE-19 cells associated with activation of Nrf2 pathway.

    PubMed

    Xu, Xin-Rong; Yu, Hai-Tao; Yang, Yan; Hang, Li; Yang, Xue-Wen; Ding, Shu-Hua

    2016-01-01

    Age-related macular degeneration (AMD) is a major cause of blindness worldwide. Oxidative stress plays a crucial role in the pathogenesis of dry AMD. Quercetin has potent anti-oxidative activities, but poor bioavailability limits its therapeutic application. Herein, we prepared the phospholipid complex of quercetin (quercetin-PC), characterized its structure by differential scanning calorimetry, infrared spectrum and x-ray diffraction. Quercetin-PC had equilibrium solubility of 38.36 and 1351.27μg/ml in water and chloroform, respectively, which was remarkably higher than those of quercetin alone. Then we established hydrogen peroxide (H2O2)-induced oxidative injury model in human ARPE-19 cells to examine the effects of quercetin-PC. Quercetin-PC, stronger than quercetin, promoted cell proliferation, and the proliferation rate was increased to be 78.89% when treated with Quercetin-PC at 400μM. Moreover, quercetin-PC effectively prevented ARPE-19 cells from apoptosis, and the apoptotic rate was reduced to be 3.1% when treated with Quercetin-PC at 200μM. In addition, quercetin-PC at 200μM significantly increased the activities of SOD, CAT and GSH-PX, and reduced the levels of reactive oxygen species and MDA in H2O2-treated ARPE-19 cells, but quercetin at 200μM failed to do so. Molecular examinations revealed that quercetin-PC at 200μM significantly activated Nrf2 nuclear translocation and significantly enhanced the expression of target genes HO-1, NQO-1 and GCL by different folds at both mRNA and protein levels. Our current data collectively indicated that quercetin-PC had stronger protective effects against oxidative-induced damages in ARPE-19 cells, which was associated with activation of Nrf2 pathway and its target genes implicated in antioxidant defense. PMID:26643168

  10. Clinical spectrum associated with MOG autoimmunity in adults: significance of sharing rodent MOG epitopes.

    PubMed

    Sepúlveda, Maria; Armangue, Thaís; Martinez-Hernandez, Eugenia; Arrambide, Georgina; Sola-Valls, Nuria; Sabater, Lidia; Téllez, Nieves; Midaglia, Luciana; Ariño, Helena; Peschl, Patrick; Reindl, Markus; Rovira, Alex; Montalban, Xavier; Blanco, Yolanda; Dalmau, Josep; Graus, Francesc; Saiz, Albert

    2016-07-01

    The aim of this study was to report the clinical spectrum associated with antibodies to myelin oligodendrocyte glycoprotein (MOG) in adult patients, and to assess whether phenotypic variants are dependent on recognition of rodent MOG epitopes. We retrospectively analyzed the features, course and outcome of 56 patients whose samples were investigated by brain tissue immunohistochemistry and cell-based assays using human and rodent MOG. The median age at symptom onset was 37 years (range 18-70); 35 patients (63 %) were female. After a median follow-up of 43 months (range 4-554), only 14 patients (25 %) developed a neuromyelitis optica spectrum disorder (NMOSD), 27 patients (47 %) retained the initial diagnosis of isolated optic neuritis, 7 (12 %) of longitudinally extensive transverse myelitis, and 2 (4 %) of acute disseminated encephalomyelitis; 6 patients (11 %) developed atypical demyelinating syndromes (4 had relapsing episodes of short myelitis lesions which in one occurred with optic neuritis; 1 had relapsing brainstem symptoms, and 1 relapsing demyelinating encephalomyelitis). The course was frequently associated with relapses (71 %) and good outcome. Twenty-seven patients (49 %) had antibodies that recognized rodent MOG epitopes, and 9 of them (16 %) showed a myelin staining pattern in rodent tissue. Only the myelin staining pattern was linked to NMOSD (p = 0.005). In conclusion, MOG autoimmunity in adult patients associates with a clinical spectrum wider than the one expected for patients with suspected NMOSD and overall good outcome. Antibodies to rodent MOG epitopes do not associate with any phenotypic variant. PMID:27147513

  11. BACTERIA OF PUBLIC HEALTH SIGNIFICANCE ASSOCIATED WITH FISH REARED IN TREATED WASTEWATER

    EPA Science Inventory

    The suitability of tertiary wastewater ponds for aquaculture was evaluated in terms of fish productions obtained and the significance of bacteria in the wastewater and from fish. Silver carp (Hypothalmichthyes molitrix) were stocked into tertiary wastewater ponds at 10,000 fish p...

  12. 76 FR 74069 - Central Utah Project Completion Act; Finding of No Significant Impact Associated With the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-30

    ...On September 27, 2011, the Department of the Interior signed a Finding of No Significant Impact which documents the selection of the Proposed Action as presented in the Final Environmental Assessment for the Block Notice 1A Heber Sub-Area Agricultural Water to Municipal & Industrial Water...

  13. A significant association between religiosity and happiness in a sample of Kuwaiti students.

    PubMed

    Abdel-Khalek, Ahmed M; Lester, David

    2009-10-01

    In a sample of 162 Kuwaiti undergraduates (33 men, 129 women; M age = 20.1 yr., SD = 1.9), self-ratings of happiness were significantly and positively correlated with self-ratings of religiosity and strength of religious belief as well as scores on Hoge's Scale of Intrinsic Religious Motivation (1972). The present data provide evidence that, among a sample of Kuwaiti Muslim undergraduates, religious people are happier. PMID:19928598

  14. A Study to Determine if Addition of Palatal Petechiae to Centor Criteria Adds More Significance to Clinical Diagnosis of Acute Strep Pharyngitis in Children.

    PubMed

    Nibhanipudi, Kumara V

    2016-01-01

    Objective. A study to determine if addition of palatal petechiae to Centor criteria adds more value for clinical diagnosis of acute strep pharyngitis in children. Hypothesis. In children, Centor Criteria does not cover all the symptoms and signs of acute strep pharyngitis. We hypothesize that addition of palatal petechiae to Centor Criteria will increase the possibility of clinical diagnosis of group A streptococcal pharyngitis in children. Methods. One hundred patients with a complaint of sore throat were enrolled in the study. All the patients were examined clinically using the Centor Criteria. They were also examined for other signs and symptoms like petechial lesions over the palate, abdominal pain, and skin rash. All the patients were given rapid strep tests, and throat cultures were sent. No antibiotics were given until culture results were obtained. Results. The sample size was 100 patients. All 100 had fever, sore throat, and erythema of tonsils. Twenty of the 100 patients had tonsillar exudates, 85/100 had tender anterior cervical lymph nodes, and 86/100 had no cough. In total, 9 out of the 100 patients had positive throat cultures. We observed that petechiae over the palate, a very significant sign, is not included in the Centor Criteria. Palatal petechiae were present in 8 out of the 100 patients. Six out of these 8 with palatal petechiae had positive throat culture for strep (75%). Only 7 out of 20 with exudates had positive strep culture. Sixteen out of the 100 patients had rapid strep test positive. Those 84/100 who had negative rapid strep also had negative throat culture. Statistics. We used Fisher's exact test, comparing throat culture positive and negative versus presence of exudates and palatal hemorrhages with positive and negative throat cultures and the resultant P value <.0001. Conclusion. Our study concludes that addition of petechiae over the palate to Centor Criteria will increase the possibility of diagnosing acute group A streptococcal

  15. A Study to Determine if Addition of Palatal Petechiae to Centor Criteria Adds More Significance to Clinical Diagnosis of Acute Strep Pharyngitis in Children

    PubMed Central

    Nibhanipudi, Kumara V.

    2016-01-01

    Objective. A study to determine if addition of palatal petechiae to Centor criteria adds more value for clinical diagnosis of acute strep pharyngitis in children. Hypothesis. In children, Centor Criteria does not cover all the symptoms and signs of acute strep pharyngitis. We hypothesize that addition of palatal petechiae to Centor Criteria will increase the possibility of clinical diagnosis of group A streptococcal pharyngitis in children. Methods. One hundred patients with a complaint of sore throat were enrolled in the study. All the patients were examined clinically using the Centor Criteria. They were also examined for other signs and symptoms like petechial lesions over the palate, abdominal pain, and skin rash. All the patients were given rapid strep tests, and throat cultures were sent. No antibiotics were given until culture results were obtained. Results. The sample size was 100 patients. All 100 had fever, sore throat, and erythema of tonsils. Twenty of the 100 patients had tonsillar exudates, 85/100 had tender anterior cervical lymph nodes, and 86/100 had no cough. In total, 9 out of the 100 patients had positive throat cultures. We observed that petechiae over the palate, a very significant sign, is not included in the Centor Criteria. Palatal petechiae were present in 8 out of the 100 patients. Six out of these 8 with palatal petechiae had positive throat culture for strep (75%). Only 7 out of 20 with exudates had positive strep culture. Sixteen out of the 100 patients had rapid strep test positive. Those 84/100 who had negative rapid strep also had negative throat culture. Statistics. We used Fisher’s exact test, comparing throat culture positive and negative versus presence of exudates and palatal hemorrhages with positive and negative throat cultures and the resultant P value <.0001. Conclusion. Our study concludes that addition of petechiae over the palate to Centor Criteria will increase the possibility of diagnosing acute group A streptococcal

  16. Significance of the Sm-Nd isotopic systematics of the Akilia Association

    NASA Technical Reports Server (NTRS)

    Gruau, G.; Nutman, A.; Jahn, B. M.

    1986-01-01

    Samarium-Neodymium analyses were carried out on fourteen samples of basic to ultrabasic metavolcanics from several enclaves of the Amitsoq gneisses (T = to or approximately 3,700 Ma). Field observations suggest that all the analyzed rocks belong to the pre-Amitsoq Akilia Association. Consequently, a minimum age of 3,700 Ma is postulated for the emplacement of their protoliths. When all the data points are put together in a conventional isochron diagram, no clear isochron relationship can be discerned. However, the points seem to fall within a band broadly corresponding to an age of 3,600 Ma. The isotopic results are difficult to interpret satisfactorily. Two contrasting interpretations are offered and summarized: (1) data scatter as a result of open system behavior; and (2) data scatter due to a melange of data sets defining two distinct isochrons.

  17. Heterozygous colon cancer-associated mutations of SAMHD1 have functional significance.

    PubMed

    Rentoft, Matilda; Lindell, Kristoffer; Tran, Phong; Chabes, Anna Lena; Buckland, Robert J; Watt, Danielle L; Marjavaara, Lisette; Nilsson, Anna Karin; Melin, Beatrice; Trygg, Johan; Johansson, Erik; Chabes, Andrei

    2016-04-26

    Even small variations in dNTP concentrations decrease DNA replication fidelity, and this observation prompted us to analyze genomic cancer data for mutations in enzymes involved in dNTP metabolism. We found that sterile alpha motif and histidine-aspartate domain-containing protein 1 (SAMHD1), a deoxyribonucleoside triphosphate triphosphohydrolase that decreases dNTP pools, is frequently mutated in colon cancers, that these mutations negatively affect SAMHD1 activity, and that several SAMHD1 mutations are found in tumors with defective mismatch repair. We show that minor changes in dNTP pools in combination with inactivated mismatch repair dramatically increase mutation rates. Determination of dNTP pools in mouse embryos revealed that inactivation of one SAMHD1 allele is sufficient to elevate dNTP pools. These observations suggest that heterozygous cancer-associated SAMHD1 mutations increase mutation rates in cancer cells. PMID:27071091

  18. Reframing the association and significance of co-morbidities in heart failure.

    PubMed

    Triposkiadis, Filippos; Giamouzis, Gregory; Parissis, John; Starling, Randall C; Boudoulas, Harisios; Skoularigis, John; Butler, Javed; Filippatos, Gerasimos

    2016-07-01

    Several co-existing diseases and/or conditions (co-morbidities) are present in patients with heart failure (HF), with diverse clinical relevance. Multiple mechanisms may underlie the co-existence of HF and co-morbidities, including direct causation, associated risk factors, heterogeneity, and independence. The complex inter-relationship of co-morbidities and their impact on the cardiovascular system contribute to the features of HF, both with reduced (HFrEF) and preserved ejection fraction (HFpEF). The purpose of this work is to provide an overview of the contribution of major cardiac and non-cardiac co-morbidities to HF development and outcomes, in the context of both HFpEF and HFrEF. Accordingly, epidemiological evidence linking co-morbidities to HF and the effect of prevalent and incident co-morbidities on HF outcome will be reviewed. PMID:27358242

  19. Heterozygous colon cancer-associated mutations of SAMHD1 have functional significance

    PubMed Central

    Rentoft, Matilda; Lindell, Kristoffer; Tran, Phong; Chabes, Anna Lena; Watt, Danielle L.; Marjavaara, Lisette; Nilsson, Anna Karin; Melin, Beatrice; Trygg, Johan; Johansson, Erik

    2016-01-01

    Even small variations in dNTP concentrations decrease DNA replication fidelity, and this observation prompted us to analyze genomic cancer data for mutations in enzymes involved in dNTP metabolism. We found that sterile alpha motif and histidine-aspartate domain-containing protein 1 (SAMHD1), a deoxyribonucleoside triphosphate triphosphohydrolase that decreases dNTP pools, is frequently mutated in colon cancers, that these mutations negatively affect SAMHD1 activity, and that several SAMHD1 mutations are found in tumors with defective mismatch repair. We show that minor changes in dNTP pools in combination with inactivated mismatch repair dramatically increase mutation rates. Determination of dNTP pools in mouse embryos revealed that inactivation of one SAMHD1 allele is sufficient to elevate dNTP pools. These observations suggest that heterozygous cancer-associated SAMHD1 mutations increase mutation rates in cancer cells. PMID:27071091

  20. Clinical significance of glycoprotein nonmetastatic B and its association with HER2 in breast cancer

    PubMed Central

    Kanematsu, Masako; Futamura, Manabu; Takata, Masafumi; Gaowa, Siqin; Yamada, Atsuko; Morimitsu, Kasumi; Morikawa, Akemi; Mori, Ryutaro; Hara, Hideaki; Yoshida, Kazuhiro

    2015-01-01

    Glycoprotein nonmetastatic B (GPNMB) is a potential oncogene that is particularly expressed in melanoma and breast cancer (BC). To clarify its clinical significance in BC, we measured serum GPNMB in vivo and investigated its cross talk with human epidermal growth factor 2 (HER2). GPNMB was expressed in four of six breast cell lines (SK-BR-3, BT-474, MDA-MD-231, and MDA-MD-157), two of six colorectal cell lines, and two of four gastric cancer (GC) cell lines. We established a GPNMB quantification system using enzyme-linked immunosorbent assay (ELISA) for these cell lines. We measured serum GPNMB in vivo in 162 consecutive BC patients and in 88 controls (50 colorectal cancer [CC] and 38 GC patients). The GPNMB concentration in BC, CC and GC was 8.163, 5.751 and 6.55 ng/mL, respectively. The GPNMB level was significantly higher in BC patients than in CC patients (P = 0.021). The HER2-rich subtype of BC patients had significantly higher GPNMB levels than other subtypes (vs. Luminal; P = 0.038; vs. DCIS; P = 0.0195). These high GPNMB levels decreased after treatment (surgery/chemotherapy). Next, we examined the relationship between GPNMB and HER2 in vitro using SK-BR3 and BT-474 (HER2-positive/GPNMB-positive) cells. GPNMB depletion by small interfering RNA (siRNA) increased both HER2 expression and phosphorylation. Trastuzumab (Tra) in combination with docetaxel promoted cell growth inhibition, and treatment with Tra or an Extracellular signal-related kinase (ERK) inhibitor enhanced GPNMB expression. These results indicate that GPNMB might be a surrogate marker for BC and may cross talk with the HER2 signal pathway. GPNMB may therefore emerge as an important player in anti-HER2 therapy. PMID:26077887

  1. Significant discharge of CO2 from hydrothermalism associated with the submarine volcano of El Hierro Island

    NASA Astrophysics Data System (ADS)

    Santana-Casiano, J. M.; Fraile-Nuez, E.; González-Dávila, M.; Baker, E. T.; Resing, J. A.; Walker, S. L.

    2016-05-01

    The residual hydrothermalism associated with submarine volcanoes, following an eruption event, plays an important role in the supply of CO2 to the ocean. The emitted CO2 increases the acidity of seawater. The submarine volcano of El Hierro, in its degasification stage, provided an excellent opportunity to study the effect of volcanic CO2 on the seawater carbonate system, the global carbon flux, and local ocean acidification. A detailed survey of the volcanic edifice was carried out using seven CTD-pH-ORP tow-yo studies, localizing the redox and acidic changes, which were used to obtain surface maps of anomalies. In order to investigate the temporal variability of the system, two CTD-pH-ORP yo-yo studies were conducted that included discrete sampling for carbonate system parameters. Meridional tow-yos were used to calculate the amount of volcanic CO2 added to the water column for each surveyed section. The inputs of CO2 along multiple sections combined with measurements of oceanic currents produced an estimated volcanic CO2 flux = 6.0 105 ± 1.1 105 kg d‑1 which is ~0.1% of global volcanic CO2 flux. Finally, the CO2 emitted by El Hierro increases the acidity above the volcano by ~20%.

  2. Consumption of Red/Processed Meat and Colorectal Carcinoma: Possible Mechanisms Underlying the Significant Association.

    PubMed

    Hammerling, Ulf; Bergman Laurila, Jonas; Grafström, Roland; Ilbäck, Nils-Gunnar

    2016-03-11

    Epidemiology and experimental studies provide an overwhelming support of the notion that diets high in red or processed meat accompany an elevated risk of developing pre-neoplastic colorectal adenoma and frank colorectal carcinoma (CRC). The underlying mechanisms are disputed; thus several hypotheses have been proposed. A large body of reports converges, however, on haem and nitrosyl haem as major contributors to the CRC development, presumably acting through various mechanisms. Apart from a potentially higher intestinal mutagenic load among consumers on a diet rich in red/processed meat, other mechanisms involving subtle interference with colorectal stem/progenitor cell survival or maturation are likewise at play. From an overarching perspective, suggested candidate mechanisms for red/processed meat-induced CRC appear as three partly overlapping tenets: (i) increased N-nitrosation/oxidative load leading to DNA adducts and lipid peroxidation in the intestinal epithelium, (ii) proliferative stimulation of the epithelium through haem or food-derived metabolites that either act directly or subsequent to conversion, and (iii) higher inflammatory response, which may trigger a wide cascade of pro-malignant processes. In this review, we summarize and discuss major findings of the area in the context of potentially pertinent mechanisms underlying the above-mentioned association between consumption of red/processed meat and increased risk of developing CRC. PMID:25849747

  3. Significant discharge of CO2 from hydrothermalism associated with the submarine volcano of El Hierro Island

    PubMed Central

    Santana-Casiano, J. M.; Fraile-Nuez, E.; González-Dávila, M.; Baker, E. T.; Resing, J. A.; Walker, S. L.

    2016-01-01

    The residual hydrothermalism associated with submarine volcanoes, following an eruption event, plays an important role in the supply of CO2 to the ocean. The emitted CO2 increases the acidity of seawater. The submarine volcano of El Hierro, in its degasification stage, provided an excellent opportunity to study the effect of volcanic CO2 on the seawater carbonate system, the global carbon flux, and local ocean acidification. A detailed survey of the volcanic edifice was carried out using seven CTD-pH-ORP tow-yo studies, localizing the redox and acidic changes, which were used to obtain surface maps of anomalies. In order to investigate the temporal variability of the system, two CTD-pH-ORP yo-yo studies were conducted that included discrete sampling for carbonate system parameters. Meridional tow-yos were used to calculate the amount of volcanic CO2 added to the water column for each surveyed section. The inputs of CO2 along multiple sections combined with measurements of oceanic currents produced an estimated volcanic CO2 flux = 6.0 105 ± 1.1 105 kg d−1 which is ~0.1% of global volcanic CO2 flux. Finally, the CO2 emitted by El Hierro increases the acidity above the volcano by ~20%. PMID:27157062

  4. Significant discharge of CO2 from hydrothermalism associated with the submarine volcano of El Hierro Island.

    PubMed

    Santana-Casiano, J M; Fraile-Nuez, E; González-Dávila, M; Baker, E T; Resing, J A; Walker, S L

    2016-01-01

    The residual hydrothermalism associated with submarine volcanoes, following an eruption event, plays an important role in the supply of CO2 to the ocean. The emitted CO2 increases the acidity of seawater. The submarine volcano of El Hierro, in its degasification stage, provided an excellent opportunity to study the effect of volcanic CO2 on the seawater carbonate system, the global carbon flux, and local ocean acidification. A detailed survey of the volcanic edifice was carried out using seven CTD-pH-ORP tow-yo studies, localizing the redox and acidic changes, which were used to obtain surface maps of anomalies. In order to investigate the temporal variability of the system, two CTD-pH-ORP yo-yo studies were conducted that included discrete sampling for carbonate system parameters. Meridional tow-yos were used to calculate the amount of volcanic CO2 added to the water column for each surveyed section. The inputs of CO2 along multiple sections combined with measurements of oceanic currents produced an estimated volcanic CO2 flux = 6.0 10(5) ± 1.1 10(5 )kg d(-1) which is ~0.1% of global volcanic CO2 flux. Finally, the CO2 emitted by El Hierro increases the acidity above the volcano by ~20%. PMID:27157062

  5. Physical exercise associated with NO production: signaling pathways and significance in health and disease

    PubMed Central

    Dyakova, Elena Y.; Kapilevich, Leonid V.; Shylko, Victor G.; Popov, Sergey V.; Anfinogenova, Yana

    2015-01-01

    Here we review available data on nitric oxide (NO)-mediated signaling in skeletal muscle during physical exercise. Nitric oxide modulates skeletal myocyte function, hormone regulation, and local microcirculation. Nitric oxide underlies the therapeutic effects of physical activity whereas the pharmacological modulators of NO-mediated signaling are the promising therapeutic agents in different diseases. Nitric oxide production increases in skeletal muscle in response to physical activity. This molecule can alter energy supply in skeletal muscle through hormonal modulation. Mitochondria in skeletal muscle tissue are highly abundant and play a pivotal role in metabolism. Considering NO a plausible regulator of mitochondrial biogenesis that directly affects cellular respiration, we discuss the mechanisms of NO-induced mitochondrial biogenesis in the skeletal muscle cells. We also review available data on myokines, the molecules that are expressed and released by the muscle fibers and exert autocrine, paracrine and/or endocrine effects. The article suggests the presence of putative interplay between NO-mediated signaling and myokines in skeletal muscle. Data demonstrate an important role of NO in various diseases and suggest that physical training may improve health of patients with diabetes, chronic heart failure, and even degenerative muscle diseases. We conclude that NO-associated signaling represents a promising target for the treatment of various diseases and for the achievement of better athletic performance. PMID:25883934

  6. Examining the association between rumination, negative affectivity, and negative affect induced by a paced auditory serial addition task.

    PubMed

    Feldner, Matthew T; Leen-Feldner, Ellen W; Zvolensky, Michael J; Lejuez, C W

    2006-09-01

    The present study examined the relations among a depressive ruminative response style, a general propensity to experience negative affectivity, and negative affect induced by a paced serial auditory addition task (PASAT). Ninety nonclinical individuals completed a computerized version of the PASAT, which elicits a generalized negative affect response [Lejuez, C. W., Kahler, C. W., & Brown, R. A. (2003). A modified computer version of the paced auditory serial addition task (PASAT) as a laboratory-based stressor: Implications for behavioral assessment. Behavior Therapist, 26, 290-292]. As hypothesized, there was a moderate correlation between depressive rumination and a propensity to experience negative affect, as indexed both by a significant association with a negative affect personality factor and the prediction of negative affect elicited during the provocation. Findings also suggested that dispositional negative affectivity moderated the effects of a depressive ruminative response style on the valence but not arousal dimensions of emotional responding to the challenge. These findings are discussed in terms of improving our understanding of rumination and its potential role in emotional vulnerability processes. PMID:16139240

  7. Thrombospondin-1 expression in breast cancer: prognostic significance and association with p53 alterations, tumour angiogenesis and extracellular matrix components.

    PubMed

    Ioachim, E; Damala, K; Tsanou, E; Briasoulis, E; Papadiotis, E; Mitselou, A; Charhanti, A; Doukas, M; Lampri, L; Arvanitis, D L

    2012-02-01

    Thrombospondin (TSP-1) is a 450-kd adhesive glycoprotein that was initially discovered in platelets and subsequently in a variety of cell types. Several reports suggest that TSP-1 possesses tumour suppressor function, through its ability to inhibit tumour neovascularization. In this study we investigated tissue sections from 124 breast carcinomas for the immuno-histochemical expression of TSP-1 protein and its relationship to several clinicopathological parameters. The possible relationship to hormone receptors content, p53 protein, proliferation associated indices, angiogenesis, VEGF expression and extracellular matrix components (tenascin, fibronectin, laminin, collagen type IV and syndecan-1) was also estimated. TSP-1 was detected in the perivascular tissue, at the epithelial-stromal junction, in the stroma and in the tumour cells. High tumour cell TSP-1 expression was observed in 9.7%, moderate in 17.7%, mild in 10.5%, while 62.1% of the cases were negative for TSP-1 expression. The survival analysis showed an increased risk of recurrence associated with low TSP-1 tumour cell expression. High stromal TSP-1 expression was observed in 3.2% of the cases, moderate in 3.3%, mild in 27.4%, while 63.6% of the cases showed absence of TSP-1 expression. This expression was higher in invasive lobular type of breast cancer and inversely correlated with the lymph node involvement and the estrogen receptor content. Stromal TSP-1 expression was also positively correlated with extracellular matrix components expression, tenascin, fibronectin, collagen type IV, laminin, and syndecan-1. The relationship of TSP-1 expression with tumor angiogenesis, growth fraction and p53 protein expression was not significant. Our data suggest that TSP-1 expression seems to be associated with favorable biological behavior and may have clinical value in terms of predicting the risk of recurrence. In addition, TSP-1 might not be a direct anti-angiogenic factor, although it seems to be implicated

  8. Genome-Wide Association Study of Intelligence: Additive Effects of Novel Brain Expressed Genes

    ERIC Educational Resources Information Center

    Loo, Sandra K.; Shtir, Corina; Doyle, Alysa E.; Mick, Eric; McGough, James J.; McCracken, James; Biederman, Joseph; Smalley, Susan L.; Cantor, Rita M.; Faraone, Stephen V.; Nelson, Stanley F.

    2012-01-01

    Objective: The purpose of the present study was to identify common genetic variants that are associated with human intelligence or general cognitive ability. Method: We performed a genome-wide association analysis with a dense set of 1 million single-nucleotide polymorphisms (SNPs) and quantitative intelligence scores within an ancestrally…

  9. Early detection of illness associated with poisonings of public health significance.

    PubMed

    Wolkin, Amy F; Patel, Manish; Watson, William; Belson, Martin; Rubin, Carol; Schier, Joshua; Kilbourne, Edwin M; Crawford, Carol Gotway; Wattigney, Wendy; Litovitz, Toby

    2006-02-01

    Since September 11, 2001, concern about potential terrorist attacks has increased in the United States. To reduce morbidity and mortality from outbreaks of illness from the intentional release of chemical agents, we examine data from the Toxic Exposure Surveillance System (TESS). TESS, a national system for timely collection of reports from US poison control centers, can facilitate early recognition of outbreaks of illness from chemical exposures. TESS data can serve as proxy markers for a diagnosis and may provide early alerts to potential outbreaks of covert events. We use 3 categories of information from TESS to detect potential outbreaks, including call volume, clinical effect, and substance-specific data. Analysis of the data identifies aberrations by comparing the observed number of events with a threshold based on historical data. Using TESS, we have identified several events of potential public health significance, including an arsenic poisoning at a local church gathering in Maine, the TOPOFF 2 national preparedness exercise, and contaminated food and water during the northeastern US blackout. Integration of poison control centers into the public health network will enhance the detection and response to emerging chemical threats. Traditionally, emergency physicians and other health care providers have used poison control centers for management information; their reporting to these centers is crucial in poisoning surveillance efforts. PMID:16431230

  10. Significant association of periodontal disease with anti-citrullinated peptide antibody in a Japanese healthy population - The Nagahama study.

    PubMed

    Terao, Chikashi; Asai, Keita; Hashimoto, Motomu; Yamazaki, Toru; Ohmura, Koichiro; Yamaguchi, Akihiko; Takahashi, Katsu; Takei, Noriko; Ishii, Takanori; Kawaguchi, Takahisa; Tabara, Yasuharu; Takahashi, Meiko; Nakayama, Takeo; Kosugi, Shinji; Sekine, Akihiro; Fujii, Takao; Yamada, Ryo; Mimori, Tsuneyo; Matsuda, Fumihiko; Bessho, Kazuhisa

    2015-05-01

    Anti-citrullinated peptide antibody (ACPA) is a highly specific autoantibody to rheumatoid arthritis (RA). Recent studies have revealed that periodontal disease (PD) is closely associated with RA and production of ACPA in RA. Analyses of associations between PD and ACPA production in a healthy population may deepen our understandings. Here, we analyzed a total of 9554 adult healthy subjects. ACPA and IgM-rheumatoid factor (RF) was quantified and PD status was evaluated using the number of missing teeth (MT), the Community Periodontal Index (CPI) and Loss of Attachment (LA) for these subjects. PD status was analyzed for its association with the positivity and categorical levels of ACPA and RF conditioned for covariates which were shown to be associated with PD, ACPA or RF. As a result, all of MT, CPI and LA showed suggestive or significant associations with positivity (p = 0.024, 0.0042 and 0.037, respectively) and levels of ACPA (p ≤ 0.00031), but none of the PD parameters were associated with those of RF. These association patterns were also observed when we analyzed 6206 non-smokers of the participants. The significant associations between PD parameters and positivity and levels of ACPA in healthy population support the fundamental involvement of PD with ACPA production. PMID:25819755

  11. Temporal and spatial paleoproductivity patterns associated with Eastern Mediterranean sapropels: paleoceanographic significance.

    NASA Astrophysics Data System (ADS)

    Gallego-Torres, D.; Martinez-Ruiz, F.; Meyers, P. A.; Paytan, A.; Jimenez-Espejo, F. J.; Ortega-Huertas, M.

    2007-12-01

    Deposition of Eastern Mediterranean sapropels has been discussed in terms of enhanced primary productivity and/or preferential preservation due to anoxic conditions in the deep basin. However, formation of these organic enriched layers is not homogeneous across the basin and through time, and temporal and spatial patterns can be observed in organic carbon concentrations and depositional conditions. We used a transect of ODP sites in the Eastern Mediterranean for the study of such variations, covering the area of major influence of the European continent and incoming waters from the Western Mediterranean basin (Ionian basin, Site 964), a region of influence of the Nile River (Levantine basin, Site 967), the central region of the basin with minor continental influence (Mediterranean Ridge, Site 969), and shallower bathymetries (Eratosthenes Seamount, Site 966). A set of paleoproductivity related proxies has been applied in order to reconstruct the paleoceanographic conditions that led to the formation of sapropels. As a whole, sapropel formation corresponds to wetter periods occurring during precessional minima and appears associated to increased productivity, evidenced by Ba/Al, and TOC-Ba mass accumulation rates maxima. δ13C data indicate intensified carbon fixation during organic carbon entrapment in sediment, where as low δ15N values provide evidence of nitrogen fixation through cyanobacteria activity as a source of increased primary and export productivity. This overwhelming export productivity led to the depletion of deep water dissolved oxygen, thus improving organic matter preservation. The above mentioned proxies show that sapropels represent periods of high productivity in an otherwise oligotrophic basin. This productivity was initiated and sustained by a change in bacterial community to nitrogen-fixing organism favored by intensified continental drainage and nutrient input. In agreement to this observation, sapropel onset generally occurred earlier in

  12. MTUS1 and its targeting miRNAs in colorectal carcinoma: significant associations.

    PubMed

    Ozcan, Onder; Kara, Murat; Yumrutas, Onder; Bozgeyik, Esra; Bozgeyik, Ibrahim; Celik, Ozgur Ilhan

    2016-05-01

    Deregulated microRNA (miRNA) expression has been shown to be involved in the pathogenesis of several types of cancers including colorectal cancer (CRC). Thus, determining miRNA targets of genes that play critical role in the malignant transformation is very important. Here, expression levels of tumor suppressor microtubule-associated tumor suppressor 1 (MTUS1) and its regulatory miRNAs were reported. Predicted and validated targets of MTUS1 gene was determined by a computational approach. Expressions of MTUS1 and miRNAs were determined by using 96.96 Dynamic Array™ integrated fluidic circuit (Fluidigm). As a result, MTUS1 levels were found to be diminished in formalin-fixed, paraffin-embedded (FFPE) tissue samples of CRC patients compared to controls. Also, several of MTUS1 targeting miRNAs were found to be upregulated in CRC samples (miR-373-3p, 183-5p, 142-5p, 200c-3p, 19a-3p, -20a-5p, -181a-5p, -184, -181d-5p, -372-3p, 27b-3p, 98-5p, -let-7i-5p, -let-7d-5p, -let-7g-5p, -let-7b-5p, and -let-7c-5p). Of these miRNAs, miR-135b-5p, -373-3p, 183-5p, 142-5p, 200c-3p, 19a-3p showed marked expression levels. In contrast, expression levels of let-7a-5p, 7e-5p, 7f-5p, hsa-miR-125a-5p, and 125b-5p were found to be downregulated in CRC tissues. Accordingly, some of the overexpressed miRNAs especially the miR-135b-5p, -373-3p, 183-5p, 142-5p, 200c-3p, and 19a-3p may play key roles in CRC pathophysiology through MTUS1. In contrast, let-7a-5p, 7e-5p, 7f-5p, miR-125a-5p, and 125b-5p may play important roles in CRC carcinogenesis independent from the MTUS1. In conclusion, MTUS1 targeting miRNAs may play key roles in the development of CRC by downregulating tumor suppressor MTUS1. PMID:26643896

  13. MDS-associated somatic mutations and clonal hematopoiesis are common in idiopathic cytopenias of undetermined significance

    PubMed Central

    Kwok, Brian; Hall, Jeff M.; Witte, John S.; Xu, Yin; Reddy, Prashanti; Lin, Keming; Flamholz, Rachel; Dabbas, Bashar; Yung, Aine; Al-Hafidh, Jenan; Balmert, Emily; Vaupel, Christine; El Hader, Carlos; McGinniss, Matthew J.; Nahas, Shareef A.; Kines, Julie

    2015-01-01

    Establishing a diagnosis in patients suspected of having a myelodysplastic syndrome (MDS) can be challenging and could be informed by the identification of somatic mutations. We performed a prospective study to examine the frequency and types of mutations encountered in 144 patients with unexplained cytopenias. Based on bone marrow findings, 17% were diagnosed with MDS, 15% with idiopathic cytopenias of undetermined significance (ICUS) and some evidence of dysplasia, and 69% with ICUS and no dysplasia. Bone marrow DNA was sequenced for mutations in 22 frequently mutated myeloid malignancy genes. Somatic mutations were identified in 71% of MDS patients, 62% of patients with ICUS and some dysplasia, and 20% of ICUS patients and no dysplasia. In total, 35% of ICUS patients carried a somatic mutation or chromosomal abnormality indicative of clonal hematopoiesis. We validated these results in a cohort of 91 lower-risk MDS and 249 ICUS cases identified over a 6-month interval. Mutations were found in 79% of those with MDS, in 45% of those with ICUS with dysplasia, and in 17% of those with ICUS without dysplasia. The spectrum of mutated genes was similar with the exception of SF3B1 which was rarely mutated in patients without dysplasia. Variant allele fractions were comparable between clonal ICUS (CCUS) and MDS as were mean age and blood counts. We demonstrate that CCUS is a more frequent diagnosis than MDS in cytopenic patients. Clinical and mutational features are similar in these groups and may have diagnostic utility once outcomes in CCUS patients are better understood. PMID:26429975

  14. Addition of a third field significantly increases dose to the brachial plexus for patients undergoing tangential whole-breast therapy after lumpectomy

    SciTech Connect

    Stanic, Sinisa; Mathai, Mathew; Mayadev, Jyoti S.; Do, Ly V.; Purdy, James A.; Chen, Allen M.

    2012-07-01

    Our goal was to evaluate brachial plexus (BP) dose with and without the use of supraclavicular (SCL) irradiation in patients undergoing breast-conserving therapy with whole-breast radiation therapy (RT) after lumpectomy. Using the standardized Radiation Therapy Oncology Group (RTOG)-endorsed guidelines delineation, we contoured the BP for 10 postlumpectomy breast cancer patients. The radiation dose to the whole breast was 50.4 Gy using tangential fields in 1.8-Gy fractions, followed by a conedown to the operative bed using electrons (10 Gy). The prescription dose to the SCL field was 50.4 Gy, delivered to 3-cm depth. The mean BP volume was 14.5 {+-} 1.5 cm{sup 3}. With tangential fields alone, the median mean dose to the BP was 0.57 Gy, the median maximum dose was 1.93 Gy, and the irradiated volume of the BP receiving 40, 45, and 50 Gy was 0%. When the third (SCL field) was added, the dose to the BP was significantly increased (P = .01): the median mean dose to the BP was 40.60 Gy, and the median maximum dose was 52.22 Gy. With 3-field RT, the median irradiated volume of the BP receiving 40, 45, and 50 Gy was 83.5%, 68.5%, and 24.6%, respectively. The addition of the SCL field significantly increases dose to the BP. The possibility of increasing the risk of BP morbidity should be considered in the context of clinical decision making.

  15. Patient Outcomes in Association With Significant Other Responses to Chronic Fatigue Syndrome: A Systematic Review of the Literature

    PubMed Central

    Band, Rebecca; Wearden, Alison; Barrowclough, Christine

    2015-01-01

    Social processes have been suggested as important in the maintenance of chronic fatigue syndrome (also known as myalgic encephalomyelitis; CFS/ME), but the specific role of close interpersonal relationships remains unclear. We reviewed 14 articles investigating significant other responses to close others with CFS/ME and the relationships between these responses and patient outcomes. Significant other beliefs attributing patient responsibility for the onset and ongoing symptoms of CFS/ME were associated with increased patient distress. Increased symptom severity, disability, and distress were also associated with both solicitous and negative significant other responses. Specific aspects of dyadic relationship quality, including high Expressed Emotion, were identified as important. We propose extending current theoretical models of CFS/ME to include two potential perpetuating interpersonal processes; the evidence reviewed suggests that the development of significant other–focused interventions may also be beneficial. PMID:26617440

  16. Upregulation of colonic and hepatic tumor overexpressed gene is significantly associated with the unfavorable prognosis marker of human hepatocellular carcinoma.

    PubMed

    Yu, Jun-Xiong; Chen, Qian; Yu, Ya-Qun; Li, Shu-Qun; Song, Jian-Fei

    2016-01-01

    Colonic hepatic tumor overexpressed gene (ch-TOG), a member of the highly conserved XMAP215 family of microtubule-associated proteins (MAPs), plays a crucial role in bipolar mitotic spindle assembly. Here, we performed proof-of-principle studies targeting ch-TOG for the development of HCC and further compared its prognostic significance with the clinicopathologic features of HCC. Quantitative real-time PCR was used to measure the expression level of ch-TOG mRNA in 207 cases of paired HCC and adjacent noncancerous liver tissues (ANLT). Additionally, immunohistochemistry was employed to identify ch-TOG protein in 71 HCC tissues. All HCC patients were divided into two groups according to the expression level of ch-TOG. Cumulative progression-free survival (PFS) and overall survival (OS) curves were estimated using the Kaplan-Meier method, and the prognostic value of ch-TOG was further evaluated using the Cox proportional hazards regression model. Our studies suggested that ch-TOG is overexpressed in HCC tissues compared with ANLT. The ch-TOG level was correlated with other prognostic factors, including the hepatitis B surface antigen (HBsAg) (p = 0.030), median size (p = 0.008), clinical tumor-node-metastasis (TNM) stage (p = 0.002), and alpha-fetoprotein (AFP) level (p = 0.030). Kaplan-Meier survival analysis showed that increased ch-TOG was associated with reduced PFS (p = 0.002) and OS (p = 0.004). Multivariate Cox proportional hazards analysis identified ch-TOG as an independent prognostic factor for the PFS (hazard ratio [HR] = 1.479, 95% confidence interval [CI] = 1.028-2.127, p = 0.035) and OS (HR = 1.609, 95% CI = 1.114-2.325, p = 0.011) of the HCC patients. Increased ch-TOG represents a powerful marker for predicting poorer prognosis in the clinical management of HCC, and may serve as a potential molecular target for HCC therapies in the future. PMID:27152245

  17. Upregulation of colonic and hepatic tumor overexpressed gene is significantly associated with the unfavorable prognosis marker of human hepatocellular carcinoma

    PubMed Central

    Yu, Jun-Xiong; Chen, Qian; Yu, Ya-Qun; Li, Shu-Qun; Song, Jian-Fei

    2016-01-01

    Colonic hepatic tumor overexpressed gene (ch-TOG), a member of the highly conserved XMAP215 family of microtubule-associated proteins (MAPs), plays a crucial role in bipolar mitotic spindle assembly. Here, we performed proof-of-principle studies targeting ch-TOG for the development of HCC and further compared its prognostic significance with the clinicopathologic features of HCC. Quantitative real-time PCR was used to measure the expression level of ch-TOG mRNA in 207 cases of paired HCC and adjacent noncancerous liver tissues (ANLT). Additionally, immunohistochemistry was employed to identify ch-TOG protein in 71 HCC tissues. All HCC patients were divided into two groups according to the expression level of ch-TOG. Cumulative progression-free survival (PFS) and overall survival (OS) curves were estimated using the Kaplan-Meier method, and the prognostic value of ch-TOG was further evaluated using the Cox proportional hazards regression model. Our studies suggested that ch-TOG is overexpressed in HCC tissues compared with ANLT. The ch-TOG level was correlated with other prognostic factors, including the hepatitis B surface antigen (HBsAg) (p = 0.030), median size (p = 0.008), clinical tumor-node-metastasis (TNM) stage (p = 0.002), and alpha-fetoprotein (AFP) level (p = 0.030). Kaplan-Meier survival analysis showed that increased ch-TOG was associated with reduced PFS (p = 0.002) and OS (p = 0.004). Multivariate Cox proportional hazards analysis identified ch-TOG as an independent prognostic factor for the PFS (hazard ratio [HR] = 1.479, 95% confidence interval [CI] = 1.028-2.127, p = 0.035) and OS (HR = 1.609, 95% CI = 1.114-2.325, p = 0.011) of the HCC patients. Increased ch-TOG represents a powerful marker for predicting poorer prognosis in the clinical management of HCC, and may serve as a potential molecular target for HCC therapies in the future. PMID:27152245

  18. Weak hierarchies associated with similarity measures--an additive clustering technique.

    PubMed

    Bandelt, H J; Dress, A W

    1989-01-01

    A new and apparently rather useful and natural concept in cluster analysis is studied: given a similarity measure on a set of objects, a sub-set is regarded as a cluster if any two objects a, b inside this sub-set have greater similarity than any third object outside has to at least one of a, b. These clusters then form a closure system which can be described as a hypergraph without triangles. Conversely, given such a system, one may attach some weight to each cluster and then compose a similarity measure additively, by letting the similarity of a pair be the sum of weights of the clusters containing that particular pair. The original clusters can be reconstructed from the obtained similarity measure. This clustering model is thus located between the general additive clustering model of Shepard and Arabie (1979) and the standard hierarchical model. Potential applications include fitting dendrograms with few additional nonnested clusters and simultaneous representation of some families of multiple dendrograms (in particular, two-dendrogram solutions), as well as assisting the search for phylogenetic relationships by proposing a somewhat larger system of possibly relevant "family groups", from which an appropriate choice (based on additional insight or individual preferences) remains to be made. PMID:2706398

  19. An additional fluorenylmethoxycarbonyl (Fmoc) moiety in di-Fmoc-functionalized L-lysine induces pH-controlled ambidextrous gelation with significant advantages.

    PubMed

    Reddy, Samala Murali Mohan; Shanmugam, Ganesh; Duraipandy, Natarajan; Kiran, Manikantan Syamala; Mandal, Asit Baran

    2015-11-01

    In recent years, several fluorenylmethoxycarbonyl (Fmoc)-functionalized amino acids and peptides have been used to construct hydrogels, which find a wide range of applications. Although several hydrogels have been prepared from mono Fmoc-functionalized amino acids, herein, we demonstrate the importance of an additional Fmoc-moiety in the hydrogelation of double Fmoc-functionalized L-lysine [Fmoc(Nα)-L-lysine(NεFmoc)-OH, (Fmoc-K(Fmoc))] as a low molecular weight gelator (LMWG). Unlike other Fmoc-functionalized amino acid gelators, Fmoc-K(Fmoc) exhibits pH-controlled ambidextrous gelation (hydrogelation at different pH values as well as organogelation), which is significant among the gelators. Distinct fibrous morphologies were observed for Fmoc-K(Fmoc) hydrogels formed at different pH values, which are different from organogels in which Fmoc-K(Fmoc) showed bundles of long fibers. In both hydrogels and organogels, the self-assembly of Fmoc-K(Fmoc) was driven by aromatic π-π stacking and hydrogen bonding interactions, as evidenced from spectroscopic analyses. Characterization of Fmoc-K(Fmoc) gels using several biophysical methods indicates that Fmoc-K(Fmoc) has several advantages and significant importance as a LMWG. The advantages of Fmoc-K(Fmoc) include pH-controlled ambidextrous gelation, pH stimulus response, high thermal stability (∼100 °C) even at low minimum hydrogelation concentration (0.1 wt%), thixotropic property, high kinetic and mechanical stability, dye removal properties, cell viability to the selected cell type, and as a drug carrier. While single Fmoc-functionalized L-lysine amino acids failed to exhibit gelation under similar experimental conditions, the pH-controlled ambidextrous gelation of Fmoc-K(Fmoc) demonstrates the benefit of a second Fmoc moiety in inducing gelation in a LMWG. We thus strongly believe that the current findings provide a lead to construct or design various new synthetic Fmoc-based LMW organic gelators for several

  20. CNV-based genome wide association study reveals additional variants contributing to meat quality in swine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Pork quality is important both to the meat processing industry and consumers’ purchasing attitudes. Copy number variation (CNV) is a burgeoning kind of variant that may influence meat quality. Herein, a genome-wide association study (GWAS) was performed between CNVs and meat quality traits in swine....

  1. [Intravesical instillation of bacillus Calmette-Guerin for superficial bladder carcinoma: study on significance of additional maintenance instillations of bacillus Calmette-Guerin].

    PubMed

    Yabusaki, N; Komatsu, H; Tago, K; Yamada, Y; Ueno, A

    1991-02-01

    The efficacy of maintenance bacillus Calmette-Guerin (BCG) instillations for superficial bladder tumors was studied by prospective randomized trial. From June 1985 to October 1988, 42 newly diagnosed patients with superficial bladder carcinoma (pTa or pT1) were treated by transurethral tumor resection and subsequent five daily instillations of mitomycin C. Then they were divided into non-maintenance group (22 patients) and maintenance group (20 patients) by randomization. The patients received six weekly instillations of 80 mg of BCG. Tokyo strain (Japan BCG manufacturing Co., Tokyo, Japan), suspended in 40 ml of physiological saline, and the patients in the maintenance group received four additional instillations of BCG every three months. We could not complete the six-week course of BCG instillations in three patients due to adverse effects (two in non-maintenance group and one in maintenance group) and we lost six patients from follow-up within one year (one in non-maintenance group and five in maintenance group). The mean follow-up period of the remaining 33 patients was 28.1 months. Of these 33 patients, six patients had been found to have recurrent tumors, and the over-all three-year non-recurrence rate was 82%. Before employing BCG, when we used only mitomycin C after TUR-Bt, the three year non-recurrence rate was 58%. This indicates prophylactic effect of BCG instillations. The stage of the initial tumor of the six recurrent cases were all pT1b. The non-recurrence rate of the patients with pT1b tumor was significantly lower than that of the patients with pTa and pT1a tumor. However, multiplicity and grade of tumors did not affect the non-recurrence rate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1904120

  2. Haplotypes of the D-Amino Acid Oxidase Gene Are Significantly Associated with Schizophrenia and Its Neurocognitive Deficits

    PubMed Central

    Hwu, Hai-Gwo; Fann, Cathy Shen-Jang; Yang, Ueng-Cheng; Yang, Wei-Chih; Hsu, Pei-Chun; Chang, Chien-Ching; Wen, Chun-Chiang; Tsai-Wu, Jyy-Jih; Hwang, Tzung-Jeng; Hsieh, Ming H.; Liu, Chen-Chung; Chien, Yi-Ling; Fang, Chiu-Ping; Faraone, Stephen V.; Tsuang, Ming T.; Chen, Wei J.; Liu, Chih-Min

    2016-01-01

    D-amino acid oxidase (DAO) has been reported to be associated with schizophrenia. This study aimed to search for genetic variants associated with this gene. The genomic regions of all exons, highly conserved regions of introns, and promoters of this gene were sequenced. Potentially meaningful single-nucleotide polymorphisms (SNPs) obtained from direct sequencing were selected for genotyping in 600 controls and 912 patients with schizophrenia and in a replicated sample consisting of 388 patients with schizophrenia. Genetic associations were examined using single-locus and haplotype association analyses. In single-locus analyses, the frequency of the C allele of a novel SNP rs55944529 located at intron 8 was found to be significantly higher in the original large patient sample (p = 0.016). This allele was associated with a higher level of DAO mRNA expression in the Epstein-Barr virus-transformed lymphocytes. The haplotype distribution of a haplotype block composed of rs11114083-rs2070586-rs2070587-rs55944529 across intron 1 and intron 8 was significantly different between the patients and controls and the haplotype frequencies of AAGC were significantly higher in patients, in both the original (corrected p < 0.0001) and replicated samples (corrected p = 0.0003). The CGTC haplotype was specifically associated with the subgroup with deficits in sustained attention and executive function and the AAGC haplotype was associated with the subgroup without such deficits. The DAO gene was a susceptibility gene for schizophrenia and the genomic region between intron 1 and intron 8 may harbor functional genetic variants, which may influence the mRNA expression of DAO and neurocognitive functions in schizophrenia. PMID:26986737

  3. Random Forests approach for identifying additive and epistatic single nucleotide polymorphisms associated with residual feed intake in dairy cattle.

    PubMed

    Yao, C; Spurlock, D M; Armentano, L E; Page, C D; VandeHaar, M J; Bickhart, D M; Weigel, K A

    2013-10-01

    Feed efficiency is an economically important trait in the beef and dairy cattle industries. Residual feed intake (RFI) is a measure of partial efficiency that is independent of production level per unit of body weight. The objective of this study was to identify significant associations between single nucleotide polymorphism (SNP) markers and RFI in dairy cattle using the Random Forests (RF) algorithm. Genomic data included 42,275 SNP genotypes for 395 Holstein cows, whereas phenotypic measurements were daily RFI from 50 to 150 d postpartum. Residual feed intake was defined as the difference between an animal's feed intake and the average intake of its cohort, after adjustment for year and season of calving, year and season of measurement, age at calving nested within parity, days in milk, milk yield, body weight, and body weight change. Random Forests is a widely used machine-learning algorithm that has been applied to classification and regression problems. By analyzing the tree structures produced within RF, the 25 most frequent pairwise SNP interactions were reported as possible epistatic interactions. The importance scores that are generated by RF take into account both main effects of variables and interactions between variables, and the most negative value of all importance scores can be used as the cutoff level for declaring SNP effects as significant. Ranking by importance scores, 188 SNP surpassed the threshold, among which 38 SNP were mapped to RFI quantitative trait loci (QTL) regions reported in a previous study in beef cattle, and 2 SNP were also detected by a genome-wide association study in beef cattle. The ratio of number of SNP located in RFI QTL to the total number of SNP in the top 188 SNP chosen by RF was significantly higher than in all 42,275 whole-genome markers. Pathway analysis indicated that many of the top 188 SNP are in genomic regions that contain annotated genes with biological functions that may influence RFI. Frequently occurring

  4. Identification of a significant association of a single nucleotide polymorphism in TNXB with systemic lupus erythematosus in a Japanese population.

    PubMed

    Kamatani, Yoichiro; Matsuda, Koichi; Ohishi, Tetsuya; Ohtsubo, Shigeru; Yamazaki, Keiko; Iida, Aritoshi; Hosono, Naoya; Kubo, Michiaki; Yumura, Wako; Nitta, Kosaku; Katagiri, Toyomasa; Kawaguchi, Yasushi; Kamatani, Naoyuki; Nakamura, Yusuke

    2008-01-01

    Systemic lupus erythematosus (SLE) is one of the common autoimmune diseases, with complex genetic components. Here, we report on a case-control association study of 178 SLE patients and 899 control subjects, using genome-wide gene-based single nucleotide polymorphism (SNP) markers. An SNP, rs3130342, in a 5' flanking region of the TNXB gene revealed a significant association with SLE [P = 0.000000930, odds ratio (OR) 3.11, with 95% confidence interval (95%CI) of 1.89-5.28] in a Japanese population. This association was replicated independently with 203 cases and 294 controls (P = 0.0440, OR 1.52, with 95%CI of 1.01-2.78). Although a copy number variation (CNV) of the C4 gene adjacent to the TNXB gene was reported to be associated with SLE, our analysis on this CNV revealed that the association of CNV of the C4 gene was weaker than the SNP in the TNXB gene and likely to reflect the linkage disequilibrium between C4 CNV and this particular SNP. Stratified analysis also revealed that the association of SNP rs3130342 with SLE was independent of the HLA-DRB1*1501 allele that has been shown to be associated with SLE. Our findings strongly imply that the TNXB gene is a candidate gene susceptible to SLE in the Japanese population. PMID:18058064

  5. Clinically Significant Fatigue: Prevalence and Associated Factors in an International Sample of Adults with Multiple Sclerosis Recruited via the Internet

    PubMed Central

    Weiland, Tracey J.; Jelinek, George A.; Marck, Claudia H.; Hadgkiss, Emily J.; van der Meer, Dania M.; Pereira, Naresh G.; Taylor, Keryn L.

    2015-01-01

    Background Fatigue contributes a significant burden of disease for people with multiple sclerosis (PwMS). Modifiable lifestyle factors have been recognized as having a role in a range of morbidity outcomes in PwMS. There is significant potential to prevent and treat fatigue in PwMS by addressing modifiable risk factors. Objectives To explore the associations between clinically significant fatigue and demographic factors, clinical factors (health-related quality of life, disability and relapse rate) and modifiable lifestyle, disease-modifying drugs (DMD) and supplement use in a large international sample of PwMS. Methods PwMS were recruited to the study via Web 2.0 platforms and completed a comprehensive survey measuring demographic, lifestyle and clinical characteristics, including health-related quality of life, disability, and relapse rate. Results Of 2469 participants with confirmed MS, 2138 (86.6%) completed a validated measure of clinically significant fatigue, the Fatigue Severity Scale. Participants were predominantly female from English speaking countries, with relatively high levels of education, and due to recruitment methods may have been highly pro-active about engaging in lifestyle management and self-help. Approximately two thirds of our sample (1402/2138; 65.6% (95% CI 63.7–67.7)) screened positive for clinically significant fatigue. Bivariate associations were present between clinically significant fatigue and several demographic, clinical, lifestyle, and medication variables. After controlling for level of disability and a range of stable socio-demographic variables, we found increased odds of fatigue associated with obesity, DMD use, poor diet, and reduced odds of fatigue with exercise, fish consumption, moderate alcohol use, and supplementation with vitamin D and flaxseed oil. Conclusion This study supports strong and significant associations between clinically significant fatigue and modifiable lifestyle factors. Longitudinal follow-up of this

  6. Isoprenoid addition to Ras protein is the critical modification for its membrane association and transforming activity.

    PubMed Central

    Kato, K; Cox, A D; Hisaka, M M; Graham, S M; Buss, J E; Der, C J

    1992-01-01

    We have introduced a variety of amino acid substitutions into carboxyl-terminal CA1A2X sequence (C = cysteine; A = aliphatic; X = any amino acid) of the oncogenic [Val12]Ki-Ras4B protein to identify the amino acids that permit Ras processing (isoprenylation, proteolysis, and carboxyl methylation), membrane association, and transformation in cultured mammalian cells. While all substitutions were tolerated at the A1 position, substitutions at A2 and X reduced transforming activity. The A2 residue was important for both isoprenylation and AAX proteolysis, whereas the X residue dictated the extent and specificity of isoprenoid modification only. Differences were observed between Ras processing in living cells and farnesylation efficiency in a cell-free system. Finally, one farnesylated mutant did not undergo either proteolysis or carboxyl methylation but still displayed efficient membrane association (approximately 50%) and transforming activity, indicating that farnesylation alone can support Ras transforming activity. Since both farnesylation and carboxyl methylation are critical for yeast a-factor biological activity, the three CAAX-signaled modifications may have different contributions to the function of different CAAX-containing proteins. Images PMID:1631135

  7. Instructions for additional qualitative scoring of the initial-letter Word-association Test.

    PubMed

    Zivković, M

    1994-04-01

    An additional scoring method is based on grouping test-words according to whether the same sign is given by subjects to the test-words. In this way five test-word categories are formed, Eros (test-words with double plus signs), demi-Eros (single plus sign), demi-Thanatos (single minus), Thanatos (double minus), and Deviant (+/- and theta signs). The next step in scoring is to count the number of test-words in a given scoring category whose meanings do not conform. The greater the discrepancy between the test-word category and its meaning, the less well adapted is the subject. Several illustrative protocols are discussed. PMID:8022674

  8. Ractopamine, a Livestock Feed Additive, Is a Full Agonist at Trace Amine–Associated Receptor 1

    PubMed Central

    Grandy, David K.; Janowsky, Aaron

    2014-01-01

    Ractopamine (RAC) is fed to an estimated 80% of all beef, swine, and turkey raised in the United States. It promotes muscle mass development, limits fat deposition, and reduces feed consumption. However, it has several undesirable behavioral side effects in livestock, especially pigs, including restlessness, agitation, excessive oral-facial movements, and aggressive behavior. Numerous in vitro and in vivo studies suggest RAC’s physiological actions begin with its stimulation of β1- and β2-adrenergic receptor–mediated signaling in skeletal muscle and adipose tissue; however, the molecular pharmacology of RAC’s psychoactive effects is poorly understood. Using human cystic fibrosis transmembrane conductance regulator (hCFTR) chloride channels as a sensor for intracellular cAMP, we found that RAC and p-tyramine (TYR) produced concentration-dependent increases in chloride conductance in oocytes coexpressing hCFTR and mouse trace amine–associated receptor 1 (mTAAR1), which was completely reversed by the trace amine–associated receptor 1 (TAAR1)–selective antagonist EPPTB [N-(3-ethoxyphenyl)-4-pyrrolidin-1-yl-3-trifluoromethylbenzamide]. Oocytes coexpressing hCFTR and the human β2-adrenergic receptor showed no response to RAC or TYR. These studies demonstrate that, contrary to expectations, RAC is not an agonist of the human β2-adrenergic receptor but rather a full agonist for mTAAR1. Since TAAR1-mediated signaling can influence cardiovascular tone and behavior in several animal models, our finding that RAC is a full mTAAR1 agonist supports the idea that this novel mechanism of action influences the physiology and behavior of pigs and other species. These findings should stimulate future studies to characterize the pharmacological, physiological, and behavioral actions of RAC in humans and other species exposed to this drug. PMID:24799633

  9. Ractopamine, a livestock feed additive, is a full agonist at trace amine-associated receptor 1.

    PubMed

    Liu, Xuehong; Grandy, David K; Janowsky, Aaron

    2014-07-01

    Ractopamine (RAC) is fed to an estimated 80% of all beef, swine, and turkey raised in the United States. It promotes muscle mass development, limits fat deposition, and reduces feed consumption. However, it has several undesirable behavioral side effects in livestock, especially pigs, including restlessness, agitation, excessive oral-facial movements, and aggressive behavior. Numerous in vitro and in vivo studies suggest RAC's physiological actions begin with its stimulation of β1- and β2-adrenergic receptor-mediated signaling in skeletal muscle and adipose tissue; however, the molecular pharmacology of RAC's psychoactive effects is poorly understood. Using human cystic fibrosis transmembrane conductance regulator (hCFTR) chloride channels as a sensor for intracellular cAMP, we found that RAC and p-tyramine (TYR) produced concentration-dependent increases in chloride conductance in oocytes coexpressing hCFTR and mouse trace amine-associated receptor 1 (mTAAR1), which was completely reversed by the trace amine-associated receptor 1 (TAAR1)-selective antagonist EPPTB [N-(3-ethoxyphenyl)-4-pyrrolidin-1-yl-3-trifluoromethylbenzamide]. Oocytes coexpressing hCFTR and the human β2-adrenergic receptor showed no response to RAC or TYR. These studies demonstrate that, contrary to expectations, RAC is not an agonist of the human β2-adrenergic receptor but rather a full agonist for mTAAR1. Since TAAR1-mediated signaling can influence cardiovascular tone and behavior in several animal models, our finding that RAC is a full mTAAR1 agonist supports the idea that this novel mechanism of action influences the physiology and behavior of pigs and other species. These findings should stimulate future studies to characterize the pharmacological, physiological, and behavioral actions of RAC in humans and other species exposed to this drug. PMID:24799633

  10. Significant Association Between CAV1 Variant rs3807989 on 7p31 and Atrial Fibrillation in a Chinese Han Population

    PubMed Central

    Chen, Shanshan; Wang, Chuchu; Wang, Xiaojing; Xu, Chengqi; Wu, Manman; Wang, Pengxia; Tu, Xin; Wang, Qing K

    2015-01-01

    Background Recent genome-wide association studies (GWAS) in European ancestry populations revealed several genomic loci for atrial fibrillation (AF). We previously replicated the 4q25 locus (PITX2) and 16q22 locus (ZFHX3) in the Chinese population, but not the KCNN3 locus on 1q21. With single-nucleotide polymorphism rs3807989 in CAV1 encoding caveolin-1, however, controversial results were reported in 2 Chinese replication studies. Methods and Results Six remaining AF genetic loci from GWAS, including rs3807989/CAV1, rs593479/PRRX1, rs6479562/C9orf3, rs10824026/SYNPO2L, rs1152591/SYNE2, and rs7164883/HCN4, were analyzed in a Chinese Han population with 941 cases and 562 controls. Only rs3807989 showed significant association with AF (Padj=4.77×10−5), and the finding was replicated in 2 other independent populations with 709 cases and 2175 controls, 463 cases and 644 controls, and the combined population with a total of 2113 cases and 3381 controls (Padj=2.20×10−9; odds ratio [OR]=1.34 for major allele G). Meta-analysis, together with data from previous reports in Chinese and Japanese populations, also showed a significant association between rs3807989 and AF (P=3.40×10−4; OR=1.24 for allele G). We also found that rs3807989 showed a significant association with lone AF in 3 independent populations and in the combined population (Padj=3.85×10−8; OR=1.43 for major allele G). Conclusions The data in this study revealed a significant association between rs3807989 and AF in the Chinese Han population. Together with the findings that caveolin-1 interacts with potassium channels Kir2.1, KCNH2, and HCN4 and sodium channels Nav1.5 and Nav1.8, CAV1 becomes a strong candidate susceptibility gene for AF across different ethnic populations. This study is the first to show a significant association between rs3807989 and lone AF. PMID:25953654

  11. Significant association between rare IPO11-HTR1A variants and attention deficit hyperactivity disorder in Caucasians.

    PubMed

    Zuo, Lingjun; Saba, Laura; Lin, Xiandong; Tan, Yunlong; Wang, Kesheng; Krystal, John H; Tabakoff, Boris; Luo, Xingguang

    2015-10-01

    We comprehensively examined the rare variants in the IPO11-HTR1A region to explore their roles in neuropsychiatric disorders. Five hundred seventy-three to 1,181 rare SNPs in subjects of European descent and 1,234-2,529 SNPs in subjects of African descent (0 < minor allele frequency (MAF) < 0.05) were analyzed in a total of 49,268 subjects in 21 independent cohorts with 11 different neuropsychiatric disorders. Associations between rare variant constellations and diseases and associations between individual rare variants and diseases were tested. RNA expression changes of this region were also explored. We identified a rare variant constellation across the entire IPO11-HTR1A region that was associated with attention deficit hyperactivity disorder (ADHD) in Caucasians (T5: P = 7.9 × 10(-31) ; Fp: P = 1.3 × 10(-32) ), but not with any other disorder examined; association signals mainly came from IPO11 (T5: P = 3.6 × 10(-10) ; Fp: P = 3.2 × 1 0(-10) ) and the intergenic region between IPO11 and HTR1A (T5: P = 4.1 × 10(-30) ; Fp: P = 5.4 × 10(-32) ). One association between ADHD and an intergenic rare variant, i.e., rs10042956, exhibited region- and cohort-wide significance (P = 5.2 × 10(-6) ) and survived correction for false discovery rate (q = 0.006). Cis-eQTL analysis showed that, 29 among the 41 SNPs within or around IPO11 had replicable significant regulatory effects on IPO11 exon expression (1.5 × 10(-17) ≤P < 0.002) in human brain or peripheral blood mononuclear cell tissues. We concluded that IPO11-HTR1A was a significant risk gene region for ADHD in Caucasians. PMID:26079129

  12. Significant association between rare IPO11-HTR1A variants and attention deficit hyperactivity disorder in Caucasians

    PubMed Central

    Zuo, Lingjun; Saba, Laura; Lin, Xiandong; Tan, Yunlong; Wang, Kesheng; Krystal, John H.; Tabakoff, Boris; Luo, Xingguang

    2016-01-01

    Objective We comprehensively examined the rare variants in the IPO11-HTR1A region to explore their roles in neuropsychiatric disorders. Method Five hundred seventy-three to 1,181 rare SNPs in subjects of European descent and 1,234-2,529 SNPs in subjects of African descent (0 < minor allele frequency (MAF) < 0.05) were analyzed in a total of 49,268 subjects in 21 independent cohorts with 11 different neuropsychiatric disorders. Associations between rare variant constellations and diseases and associations between individual rare variants and diseases were tested. RNA expression changes of this region were also explored. Results We identified a rare variant constellation across the entire IPO11-HTR1A region that was associated with attention deficit hyperactivity disorder (ADHD) in Caucasians (T5: p=7.9×10−31; Fp: p=1.3×10−32), but not with any other disorder examined; association signals mainly came from IPO11 (T5: p=3.6×10−10; Fp: p=3.2×10−10) and the intergenic region between IPO11 and HTR1A (T5: p=4.1×10−30; Fp: p=5.4×10−32). One association between ADHD and an intergenic rare variant, i.e., rs10042956, exhibited region- and cohort-wide significance (p=5.2×10−6) and survived correction for false discovery rate (q=0.006). Cis-eQTL analysis showed that, 29 among the 41 SNPs within or around IPO11 had replicable significant regulatory effects on IPO11 exon expression (1.5×10−17≤p<0.002) in human brain or peripheral blood mononuclear cell tissues. Conclusion We concluded that IPO11-HTR1A was a significant risk gene region for ADHD in Caucasians. PMID:26079129

  13. Frequencies of polymorphisms associated with BSE resistance differ significantly between Bos taurus, Bos indicus, and composite cattle

    PubMed Central

    Brunelle, Brian W; Greenlee, Justin J; Seabury, Christopher M; Brown, Charles E; Nicholson, Eric M

    2008-01-01

    Background Transmissible spongiform encephalopathies (TSEs) are neurodegenerative diseases that affect several mammalian species. At least three factors related to the host prion protein are known to modulate susceptibility or resistance to a TSE: amino acid sequence, atypical number of octapeptide repeats, and expression level. These factors have been extensively studied in breeds of Bos taurus cattle in relation to classical bovine spongiform encephalopathy (BSE). However, little is currently known about these factors in Bos indicus purebred or B. indicus × B. taurus composite cattle. The goal of our study was to establish the frequency of markers associated with enhanced susceptibility or resistance to classical BSE in B. indicus purebred and composite cattle. Results No novel or TSE-associated PRNP-encoded amino acid polymorphisms were observed for B. indicus purebred and composite cattle, and all had the typical number of octapeptide repeats. However, differences were observed in the frequencies of the 23-bp and 12-bp insertion/deletion (indel) polymorphisms associated with two bovine PRNP transcription regulatory sites. Compared to B. taurus, B. indicus purebred and composite cattle had a significantly lower frequency of 23-bp insertion alleles and homozygous genotypes. Conversely, B. indicus purebred cattle had a significantly higher frequency of 12-bp insertion alleles and homozygous genotypes in relation to both B. taurus and composite cattle. The origin of these disparities can be attributed to a significantly different haplotype structure within each species. Conclusion The frequencies of the 23-bp and 12-bp indels were significantly different between B. indicus and B. taurus cattle. No other known or potential risk factors were detected for the B. indicus purebred and composite cattle. To date, no consensus exists regarding which bovine PRNP indel region is more influential with respect to classical BSE. Should one particular indel region and

  14. Polymyxin Resistance Caused by mgrB Inactivation Is Not Associated with Significant Biological Cost in Klebsiella pneumoniae

    PubMed Central

    Cannatelli, Antonio; Santos-Lopez, Alfonso; Giani, Tommaso; Gonzalez-Zorn, Bruno

    2015-01-01

    The inactivation of the mgrB gene, which encodes a negative-feedback regulator of the PhoPQ signaling system, was recently shown to be a common mutational mechanism responsible for acquired polymyxin resistance among carbapenemase-producing Klebsiella pneumoniae strains from clinical sources. In this work, we show that mgrB mutants can easily be selected in vitro from different K. pneumoniae lineages, and mgrB inactivation is not associated with a significant biological cost. PMID:25691629

  15. Dissection of the genetics of Parkinson's disease identifies an additional association 5′ of SNCA and multiple associated haplotypes at 17q21

    PubMed Central

    Spencer, Chris C.A.; Plagnol, Vincent; Strange, Amy; Gardner, Michelle; Paisan-Ruiz, Coro; Band, Gavin; Barker, Roger A.; Bellenguez, Celine; Bhatia, Kailash; Blackburn, Hannah; Blackwell, Jennie M.; Bramon, Elvira; Brown, Martin A.; Brown, Matthew A.; Burn, David; Casas, Juan-Pablo; Chinnery, Patrick F.; Clarke, Carl E.; Corvin, Aiden; Craddock, Nicholas; Deloukas, Panos; Edkins, Sarah; Evans, Jonathan; Freeman, Colin; Gray, Emma; Hardy, John; Hudson, Gavin; Hunt, Sarah; Jankowski, Janusz; Langford, Cordelia; Lees, Andrew J.; Markus, Hugh S.; Mathew, Christopher G.; McCarthy, Mark I.; Morrison, Karen E.; Palmer, Colin N.A.; Pearson, Justin P.; Peltonen, Leena; Pirinen, Matti; Plomin, Robert; Potter, Simon; Rautanen, Anna; Sawcer, Stephen J.; Su, Zhan; Trembath, Richard C.; Viswanathan, Ananth C.; Williams, Nigel W.; Morris, Huw R.; Donnelly, Peter; Wood, Nicholas W.

    2011-01-01

    We performed a genome-wide association study (GWAS) in 1705 Parkinson's disease (PD) UK patients and 5175 UK controls, the largest sample size so far for a PD GWAS. Replication was attempted in an additional cohort of 1039 French PD cases and 1984 controls for the 27 regions showing the strongest evidence of association (P< 10−4). We replicated published associations in the 4q22/SNCA and 17q21/MAPT chromosome regions (P< 10−10) and found evidence for an additional independent association in 4q22/SNCA. A detailed analysis of the haplotype structure at 17q21 showed that there are three separate risk groups within this region. We found weak but consistent evidence of association for common variants located in three previously published associated regions (4p15/BST1, 4p16/GAK and 1q32/PARK16). We found no support for the previously reported SNP association in 12q12/LRRK2. We also found an association of the two SNPs in 4q22/SNCA with the age of onset of the disease. PMID:21044948

  16. A novel CFTR disease-associated mutation causes addition of an extra N-linked oligosaccharide.

    PubMed

    Hämmerle, M M; Aleksandrov, A A; Chang, X B; Riordan, J R

    2000-11-01

    We have examined the influence of a novel missense mutation in the fourth extracytoplasmic loop (EL4) of CFTR detected in a patient with cystic fibrosis. This substitution (T908N) creates a consensus sequence (N X S/T) for addition of an N-linked oligosaccharide chain near the C-terminal end of EL4. Oligosaccharyl transferase generally does not have access to this consensus sequence if it is closer than about twelve amino acids from the membrane. However, the T908N site is used, even though it is within four residues of the predicted membrane interface and the oligosaccharide chain added binds calnexin, a resident chaperone of the ER membrane. The chloride channel activity of this variant CFTR is abnormal as evidenced by a reduced rate of (36)Cl(-) efflux and a noisy single channel open state. This may reflect some displacement of the membrane spanning sequence C-terminal of EL4 since it contains residues influencing the ion pore. PMID:11443282

  17. Benefits and concerns associated with biotechnology-derived foods: can additional research reduce children health risks?

    PubMed

    Cantani, A

    2006-01-01

    The development of techniques devised for the genetic manipulation of foods poses new risks for children with food allergy (FA). The introduction of foreign allergenic proteins from different foods into previously tolerated foods may trigger allergic reactions, often complicating with anaphylactic shock in a subset of allergic babies. Children with FA, even if subjected to preventative diets, always challenge the risk of developing allergic manifestations after unintentional intake of a non tolerated food in restaurant settings, with relatives or schoolmates, etc, where product labelling is necessarily lacking. The introduction of potentially allergenic proteins into foods generally considered safe for allergic children can be done deliberately, by either substantially altering the food ingredients, or by genetic manipulation which change the composition or transfer allergens, or unintentionally by quality-control failures, due to contaminations in the production process, or to genetic mismanipulation. There is a controversy between multinationals often favored by governments and consumer association resistance, thus an equidistant analysis poses some unprecedented impediments. The importance of FA and the potential of transgenic plants to bring food allergens into the food supply should not be disregarded. The expression in soybeans of a Brazil nut protein resulted in a food allergen expressed in widely used infant formulas, so paving the way to an often reported multinational debacle. Genetic engineering poses innovative ethical and social concerns, as well as serious challenges to the environment, human health, animal welfare, and the future of agriculture. In this paper will be emphasized practical concepts more crucial for pediatricians. PMID:16910351

  18. Benefits and concerns associated with biotechnology-derived foods: can additional research reduce children health risks?

    PubMed

    Cantani, A

    2009-01-01

    The development of techniques devised for the genetic manipulation of foods poses new risks for children with food allergy (FA). The introduction of foreign allergenic proteins from different foods into previously tolerated foods may trigger allergic reactions, often complicating with anaphylactic shock in a subset of allergic babies. Children with FA, even if subjected to preventative diets, always challenge the risk of developing allergic manifestations after unintentional intake of a non tolerated food in restaurant settings, with relatives or schoolmates, etc, where product labelling is necessarily lacking. The introduction of potentially allergenic proteins into foods generally considered safe for allergic children can be done deliberately, by either substantially altering the food ingredients, or by genetic manipulation which change the composition or transfer allergens, or unintentionally by qualitycontrol failures, due to contaminations in the production process, or to genetic mismanipulation. There is a controversy between multinationals often favored by governments and consumer association resistance, thus an equidistant analysis poses some unprecedented impediments. The importance of FA and the potential of transgenic plants to bring food allergens into the food supply should not be disregarded. The expression in soybeans of a Brazil nut protein resulted in a food allergen ex-pressed in widely used infant formulas, so paving the way to an often reported multinational debacle. Genetic engineering poses innovative ethical and social concerns, as well as serious challenges to the environment, human health, animal welfare, and the future of agriculture. In this paper will be emphasized practical concepts more crucial for pediatricians. PMID:19364084

  19. Immunohistologic detection of estrogen receptor alpha in canine mammary tumors: clinical and pathologic associations and prognostic significance.

    PubMed

    Nieto, A; Peña, L; Pérez-Alenza, M D; Sánchez, M A; Flores, J M; Castaño, M

    2000-05-01

    Eighty-nine canine mammary tumors and dysplasias of 66 bitches were investigated to determine the immunohistochemical expression of classical estrogen receptor (ER-alpha) and its clinical and pathologic associations and prognostic value. A complete clinical examination was performed and reproductive history was evaluated. After surgery, all animals were followed-up for 18 months, with clinical examinations every 3-4 months. ER-alpha expression was higher in tumors of genitally intact and young bitches (P < 0.01, P < 0.01) and in animals with regular estrous periods (P = 0.03). Malignant tumors of the bitches with a previous clinical history of pseudopregnancy expressed significantly more ER-alpha (P = 0.04). Immunoexpression of ER-alpha decreased significantly with tumor size (P = 0.05) and skin ulceration (P = 0.01). Low levels of ER-alpha were significantly associated with lymph node involvement (P < 0.01). Malignant tumors had lower ER-alpha expression than did benign tumors (P < 0.01). Proliferation index measured by proliferating cell nuclear antigen immunostaining was inversely correlated with ER-alpha scores (P = 0.05) in all tumors. Low ER-alpha levels in primary malignant tumors were significantly associated with the occurrence of metastases in the follow-up (P = 0.03). Multivariate analyses were performed to determine the prognostic significance of some follow-up variables. ER-alpha value, Ki-67 index, and age were independent factors that could predict disease-free survival. Lymph node status, age, and ER-alpha index were independent prognostic factors for the overall survival. The immunohistochemical detection of ER-alpha in canine mammary tumors is a simple technique with prognostic value that could be useful in selecting appropriate hormonal therapy. PMID:10810988

  20. Clinical Significance of Pregnancies Complicated by Velamentous Umbilical Cord Insertion Associated With Other Umbilical Cord/Placental Abnormalities

    PubMed Central

    Suzuki, Shunji; Kato, Masahiko

    2015-01-01

    Background We examined the clinical significance of pregnancies complicated by velamentous cord insertion (VCI) associated with other umbilical cord/placental abnormalities. Methods Data were collected from 168 deliveries complicated by VCI and from 16,797 unaffected controls. All placentae were screened identically by trained staff. In this study, we examined the presence of excessively long umbilical cord (longer than 70 cm), vasa previa, single umbilical artery, circumvallate placenta, succenturiate placenta, lobed placenta, placenta previa, low lying placenta and placenta accrete as the other umbilical cord/placental abnormalities. Results Using a multivariate analysis, the pregnancies complicated by VCI were independently associated with in vitro fertilization use (P < 0.01), maternal smoking (P = 0.03), preterm delivery (P = 0.03), fetal asphyxia (P = 0.01) and small-for-gestational-age infants (P = 0.02). It was also independently associated with vasa previa (P < 0.01), single umbilical artery (P = 0.04), lobed placenta (P = 0.01) and placenta previa (P = 0.03). However, these umbilical cord/placental abnormalities were not associated with the further adverse outcomes of the pregnancies complicated by VCI. Conclusion VCI is associated with an increased risk of adverse perinatal outcomes irrespective of the presence of other umbilical cord/placental abnormalities. Routine identification of the placental cord insertion site should be considered. PMID:26491497

  1. Significant associations of stearoyl-CoA desaturase (SCD1) gene with fat deposition and composition in skeletal muscle.

    PubMed

    Jiang, Zhihua; Michal, Jennifer J; Tobey, David J; Daniels, Tyler F; Rule, Daniel C; Macneil, Michael D

    2008-01-01

    Gene expression studies in humans and animals have shown that elevated stearoyl-CoA desaturase (SCD1) activity is associated with increased fat accumulation and monounsaturation of saturated fatty acids in skeletal muscle. However, results of the two reported association studies in humans are inconsistent. In the present study, we annotated the bovine SCD1 gene and identified 3 single nucleotide polymorphisms (SNPs) in its 3'untranslated region (UTR). Genotyping these SNPs on a Wagyu x Limousin reference population revealed that the SCD1 gene was significantly associated with six fat deposition and fatty acid composition traits in skeletal muscle, but not with subcutaneous fat depth and percent kidney-pelvic-heart fat. In particular, we confirmed that the high stearoyl-CoA desaturase activities/alleles were positively correlated with beef marbling score, amount of monounsaturated fatty acids and conjugated linoleic acid content, but negatively with amount of saturated fatty acids. The inconsistent associations between human studies might be caused by using different sets of markers because we observed that most associated markers are located near the end of 3'UTR. We found that the proximity of the polyadenylation signal site is highly conserved among human, cattle and pig, indicating that the region might contain functional elements involved in posttranscriptional control of SCD1 activity. In conclusion, our cross species study provided solid evidence to support SCD1 gene as a critical player in skeletal muscle fat metabolism. PMID:18825276

  2. Addition of an N-terminal epitope tag significantly increases the activity of plant fatty acid desaturases expressed in yeast cells

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Saccharomyces cerevisiae shows great potential for development of bioreactor systems geared towards the production of high-value lipids such as polyunsaturated omega-3 fatty acids, the yields of which are largely dependent on the activity of ectopically-expressed enzymes. Here we show that the addit...

  3. Significant association of GRM7 and GRM8 genes with schizophrenia and major depressive disorder in the Han Chinese population.

    PubMed

    Li, Wenjin; Ju, Kang; Li, Zhiqiang; He, Kuanjun; Chen, Jianhua; Wang, Qingzhong; Yang, Beimeng; An, Lin; Feng, Guoyin; Sun, Weiming; Zhou, Juan; Zhang, Shasha; Song, Pingping; Khan, Raja; Ji, Weidong; Shi, Yongyong

    2016-01-01

    Metabotropic glutamate receptor type 7 (GRM7) and type 8 (GRM8) are involved in the neurotransmission of glutamate which is supposed to play an important role in the development of schizophrenia (SCZ) and major depressive disorders (MDD). We designed this study to investigate whether common DNA variants or their genetic interactions within GRM7 and GMR8 genes were associated with these disorders in the Han Chinese population. Fourteen SNPs in GRM7 and GRM8 were selected within a sample set comprising 1235 SCZ patients, 1045 MDD patients and 1235 normal controls. Significant association in SCZ case-control subjects was observed for rs2229902 (permutated Pallele=0.0005, OR=1.492 [95% CI=1.231-1.807]) and rs9870680 (permutated Pallele=0.0023, OR=1.262 [95% CI=1.116-1.426]) in GRM7 and rs2237781 (permutated Pallele=0.0027, OR=1.346 [95% CI=1.149-1.575]) in GRM8. Association analysis for MDD case-control subjects revealed positive results in rs779706 (permutated Pallele=0.0099, OR=1.237 [95% CI=1.093-1.399]) of GRM7 and in rs1361995 (permutated Pallele=0.0017, OR=1.488 [95% CI=1.215-1.823]) of GRM8. Moreover, a three-locus model, constituted by polymorphisms in GRM7 and GRM8 significantly correlated with MDD in the gene-gene interaction analysis. Meta-analysis and haplotype analysis further confirmed our significant results. We demonstrated the genetic association of GRM7 and GRM8 with SCZ and MDD in the Han Chinese population. We also found susceptibility interactive effects of these two genes with both psychiatric disorders, which might provide new insights into the etiology of them. PMID:26655190

  4. Anti-dsDNA, anti-Sm antibodies, and the lupus anticoagulant: significant factors associated with lupus nephritis

    PubMed Central

    Alba, P; Bento, L; Cuadrado, M; Karim, Y; Tungekar, M; Abbs, I; Khamashta, M; D'Cruz, D; Hughes, G

    2003-01-01

    Background: Lupus nephritis (LN) is a common manifestation in patients with systemic lupus erythematosus (SLE). Autoantibodies and ethnicity have been associated with LN, but the results are controversial. Objective: To study the immunological and demographic factors associated with the development of LN. Patients and methods: A retrospective case-control study of 127 patients with biopsy-proven LN, and 206 randomly selected patients with SLE without nephritis as controls was designed. All patients had attended our lupus unit during the past 12 years. Standard methods were used for laboratory testing. Results: Patients with LN were significantly younger than the controls at the time of SLE diagnosis (mean (SD) 25.6 (8.8) years v 33.7 (12.5) years; p<0.0001). The proportion of patients of black ethnic origin was significantly higher in the group with nephritis (p=0.02). There were no differences in sex distribution or duration of follow up. A higher proportion of anti-dsDNA, anti-RNP, anti-Sm, and lupus anticoagulant (LA) was seen in the group with nephritis (p=0.002; p=0.005; p=0.0001; p=0.01, respectively). In univariate, but not in multivariate, analysis male sex and absence of anti-dsDNA were associated with earlier onset of renal disease (p=0.03; p=0.008). In multivariate analysis the only factors associated with nephritis were younger age at diagnosis of SLE, black race, presence of anti-dsDNA, anti-Sm, and LA. No demographic or immunological associations were seen with WHO histological classes. Conclusions: Young, black patients with anti-dsDNA, anti-Sm antibodies, and positive LA, appear to have a higher risk of renal involvement. These patients should be carefully monitored for the development of LN. PMID:12759294

  5. Interaction Between the FOXO1A-209 Genotype and Tea Drinking Is Significantly Associated with Reduced Mortality at Advanced Ages.

    PubMed

    Zeng, Yi; Chen, Huashuai; Ni, Ting; Ruan, Rongping; Nie, Chao; Liu, Xiaomin; Feng, Lei; Zhang, Fengyu; Lu, Jiehua; Li, Jianxin; Li, Yang; Tao, Wei; Gregory, Simon G; Gottschalk, William; Lutz, Michael W; Land, Kenneth C; Yashin, Anatoli; Tan, Qihua; Yang, Ze; Bolund, Lars; Ming, Qi; Yang, Huanming; Min, Junxia; Willcox, D Craig; Willcox, Bradley J; Gu, Jun; Hauser, Elizabeth; Tian, Xiao-Li; Vaupel, James W

    2016-06-01

    On the basis of the genotypic/phenotypic data from Chinese Longitudinal Healthy Longevity Survey (CLHLS) and Cox proportional hazard model, the present study demonstrates that interactions between carrying FOXO1A-209 genotypes and tea drinking are significantly associated with lower risk of mortality at advanced ages. Such a significant association is replicated in two independent Han Chinese CLHLS cohorts (p = 0.028-0.048 in the discovery and replication cohorts, and p = 0.003-0.016 in the combined dataset). We found the associations between tea drinking and reduced mortality are much stronger among carriers of the FOXO1A-209 genotype compared to non-carriers, and drinking tea is associated with a reversal of the negative effects of carrying FOXO1A-209 minor alleles, that is, from a substantially increased mortality risk to substantially reduced mortality risk at advanced ages. The impacts are considerably stronger among those who carry two copies of the FOXO1A minor allele than those who carry one copy. On the basis of previously reported experiments on human cell models concerning FOXO1A-by-tea-compounds interactions, we speculate that results in the present study indicate that tea drinking may inhibit FOXO1A-209 gene expression and its biological functions, which reduces the negative impacts of FOXO1A-209 gene on longevity (as reported in the literature) and offers protection against mortality risk at oldest-old ages. Our empirical findings imply that the health outcomes of particular nutritional interventions, including tea drinking, may, in part, depend upon individual genetic profiles, and the research on the effects of nutrigenomics interactions could potentially be useful for rejuvenation therapies in the clinic or associated healthy aging intervention programs. PMID:26414954

  6. Involvement of the PRKCB1 gene in autistic disorder: significant genetic association and reduced neocortical gene expression.

    PubMed

    Lintas, C; Sacco, R; Garbett, K; Mirnics, K; Militerni, R; Bravaccio, C; Curatolo, P; Manzi, B; Schneider, C; Melmed, R; Elia, M; Pascucci, T; Puglisi-Allegra, S; Reichelt, K-L; Persico, A M

    2009-07-01

    Protein kinase C enzymes play an important role in signal transduction, regulation of gene expression and control of cell division and differentiation. The fsI and betaII isoenzymes result from the alternative splicing of the PKCbeta gene (PRKCB1), previously found to be associated with autism. We performed a family-based association study in 229 simplex and 5 multiplex families, and a postmortem study of PRKCB1 gene expression in temporocortical gray matter (BA41/42) of 11 autistic patients and controls. PRKCB1 gene haplotypes are significantly associated with autism (P<0.05) and have the autistic endophenotype of enhanced oligopeptiduria (P<0.05). Temporocortical PRKCB1 gene expression was reduced on average by 35 and 31% for the PRKCB1-1 and PRKCB1-2 isoforms (P<0.01 and <0.05, respectively) according to qPCR. Protein amounts measured for the PKCbetaII isoform were similarly decreased by 35% (P=0.05). Decreased gene expression characterized patients carrying the 'normal' PRKCB1 alleles, whereas patients homozygous for the autism-associated alleles displayed mRNA levels comparable to those of controls. Whole genome expression analysis unveiled a partial disruption in the coordinated expression of PKCbeta-driven genes, including several cytokines. These results confirm the association between autism and PRKCB1 gene variants, point toward PKCbeta roles in altered epithelial permeability, demonstrate a significant downregulation of brain PRKCB1 gene expression in autism and suggest that it could represent a compensatory adjustment aimed at limiting an ongoing dysreactive immune process. Altogether, these data underscore potential PKCbeta roles in autism pathogenesis and spur interest in the identification and functional characterization of PRKCB1 gene variants conferring autism vulnerability. PMID:18317465

  7. Performance of the American Urological Association Symptom Index With and Without an Additional Urge Incontinence Item

    PubMed Central

    Barry, Michael J.; Avins, Andrew L.; Meleth, Sreelatha

    2011-01-01

    Purpose To examine the value of adding an urge incontinence question to the AUA Symptom Index (AUASI) among men in the Complementary and Alternative Medicine for Urological Symptoms (CAMUS) trial. Materials and Methods CAMUS is a randomized trial of Saw palmetto fruit extract versus placebo among men ≥ 45 years old with an AUASI score ≥ 8 and ≤ 24. Baseline measurements included the AUASI, a question about urge incontinence (UI), the International Prostate Symptom Score Quality of Life (IPSS QOL) question, and the BPH Impact Index (BII). We correlated the items and scales, and examined whether adding the UI question resulted in better prediction of disease-specific health status. Results Mean age of the 369 men in CAMUS was 61 and mean baseline AUASI score was 14.6. UI was reported infrequently; about 82% of respondents answered the question “not at all” or “less than 1 time in 5.” UI was significantly correlated with all other AUASI items except for weak stream; the strongest correlation was to urgency (R=0.51, P<.0001). The correlation between AUASI and the AUASI+UI was 0.98 (P<0.0001). In a logistic regression predicting IPSS QOL, adding UI to the AUASI slightly increased discriminating ability (c statistic increased from 0.77 to 0.78, P<0.0001). Similarly, in a linear regression predicting BII scores, adding UI to the AUASI slightly increased predictive ability (R2 statistic increased from 0.22 to 0.26, P<0.0001). Conclusion Based on our analysis in the CAMUS population, the value of adding a UI question to the AUASI in terms of predicting bother seemed small at best. PMID:21741692

  8. Phase stabilization of magnetite (Fe3O4) nanoparticles with B2O3 addition: A significant enhancement on the phase transition temperature

    NASA Astrophysics Data System (ADS)

    Topal, Uğur; Aksan, Mehmet Ali

    2016-05-01

    Magnetite nanoparticles (MNPs) are extensively investigated for biomedical applications, particularly as contrast agents for Magnetic Resonance Imaging and as drug delivery agent and heat mediators for cancer therapy. Tuning the magnetic properties of the magnetite nanoparticles with doping of foreign atoms has a crucial importance for determining the application areas of these materials and so attracts much interests. On the other hand the doping with foreign atoms requires high temperature annealing, and it causes a phase transition to the hematite phase above 400 °C. In this work the phase transition temperature from the magnetite to the hematite phase has been increased by 200 °C, which is the highest enhancement reported in literature. It was achieved by addition of the appropriate amounts of B2O3. Our experiments indicates that the 5.0 wt% of B2O3 addition stabilizes and keeps the existence of single phase magnetite up to 600 °C.

  9. Many QTLs with minor additive effects are associated with a large difference in growth between two selection lines in chickens.

    PubMed

    Jacobsson, Lina; Park, Hee-Bok; Wahlberg, Per; Fredriksson, Robert; Perez-Enciso, Miguel; Siegel, Paul B; Andersson, Leif

    2005-10-01

    Two growth-selected lines in chickens have been developed from a single founder population by divergent selection for body weight at 56 days of age. After more than 40 generations of selection they show a nine-fold difference in body weight at selection age and large differences in growth rate, appetite, fat deposition and metabolic characteristics. We have generated a large intercross between these lines comprising more than 800 F2 birds. QTL mapping revealed 13 loci affecting growth. The most striking observation was that the allele in the high weight line in all cases was associated with enhanced growth, but each locus explained only a small proportion of the phenotypic variance using a standard QTL model (1.3-3.1%). This result is in sharp contrast to our previous study where we reported that the two-fold difference in adult body size between the red junglefowl and White Leghorn domestic chickens is explained by a small number of QTLs with large additive effects. Furthermore, no QTLs for anorexia or antibody response were detected despite large differences for these traits between the founder lines. The result is an excellent example where a large phenotypic difference between populations occurs in the apparent absence of any single locus with large phenotypic effects. The study underscores the need for powerful experimental designs in genetic studies of multifactorial traits. No QTL at all would have reached genome-wide significance using a less powerful design (e.g. approx. 200 F2 individuals) regardless of the nine-fold phenotypic difference between the founder lines for the selected trait. PMID:16356285

  10. Significance, Nature, and Direction of the Association Between Child Sexual Abuse and Conduct Disorder: A Systematic Review.

    PubMed

    Maniglio, Roberto

    2015-07-01

    To elucidate the significance, nature, and direction of the potential relationship between child sexual abuse and conduct disorder, all the pertinent studies were reviewed. Ten databases were searched. Blind assessments of study eligibility and quality were performed by two independent researchers. Thirty-six studies including 185,358 participants and meeting minimum quality criteria that were enough to ensure objectivity and to not invalidate results were analyzed. Across the majority of studies, conduct disorder was significantly and directly related to child sexual abuse, especially repeated sexual molestation and abuse involving penetration, even after controlling for various sociodemographic, family, and clinical variables. The association between child sexual abuse and conduct disorder was not confounded by other risk factors, such as gender, socioeconomic status, school achievement, substance problems, physical abuse, parental antisocial behavior or substance problems, parent-child relationships, and family disruption, conflict, or violence. Evidence for a significant interactive effect between child sexual abuse and monoamine oxidase A gene on conduct disorder was scant. Early sexual abuse might predispose to the subsequent onset of conduct disorder which, in turn, may lead to further sexual victimization through association with sexually abusive peers or involvement in dangerous situations or sexual survival strategies. PMID:24626460

  11. Irrigation Is Significantly Associated with an Increased Prevalence of Listeria monocytogenes in Produce Production Environments in New York State.

    PubMed

    Weller, Daniel; Wiedmann, Martin; Strawn, Laura K

    2015-06-01

    Environmental (i.e., meteorological and landscape) factors and management practices can affect the prevalence of foodborne pathogens in produce production environments. This study was conducted to determine the prevalence of Listeria monocytogenes, Listeria species (including L. monocytogenes), Salmonella, and Shiga toxin-producing Escherichia coli (STEC) in produce production environments and to identify environmental factors and management practices associated with their isolation. Ten produce farms in New York State were sampled during a 6-week period in 2010, and 124 georeferenced samples (80 terrestrial, 33 water, and 11 fecal) were collected. L. monocytogenes, Listeria spp., Salmonella, and STEC were detected in 16, 44, 4, and 5% of terrestrial samples, 30, 58, 12, and 3% of water samples, and 45, 45, 27, and 9% of fecal samples, respectively. Environmental factors and management practices were evaluated for their association with terrestrial samples positive for L. monocytogenes or other Listeria species by univariate logistic regression; analysis was not conducted for Salmonella or STEC because the number of samples positive for these pathogens was low. Although univariate analysis identified associations between isolation of L. monocytogenes or Listeria spp. from terrestrial samples and various water-related factors (e.g., proximity to wetlands and precipitation), multivariate analysis revealed that only irrigation within 3 days of sample collection was significantly associated with isolation of L. monocytogenes (odds ratio = 39) and Listeria spp. (odds ratio = 5) from terrestrial samples. These findings suggest that intervention at the irrigation level may reduce the risk of produce contamination. PMID:26038903

  12. Polymorphisms involving gain or loss of CpG sites are significantly enriched in trait-associated SNPs

    PubMed Central

    Zhou, Dan; Li, Zhenli; Yu, Dan; Wan, Ledong; Zhu, Yimin; Lai, Maode; Zhang, Dandan

    2015-01-01

    Some single nucleotide polymorphisms (SNPs) influence the existence of CpG sites, the basis of DNA modification such as methylation and hydroxymethylation. These polymorphisms can lead to gain or loss of CpG sites and were defined as CpG site related SNPs (cgSNPs) in this study. The cgSNPs change DNA sequence and might potentially affect DNA modification such as methylation. However, the functional consequence of cgSNPs is poorly understood. We observed that a considerable proportion (23.0%) of common variants were cgSNPs in human genome. Mutations involving loss of CpG sites were associated with reduced levels of methylation (~20.2%) using The Cancer Genome Atlas (TCGA) data. Using public databases (SCAN and seeQTL) of expression quantitative trait loci (eQTLs), we found that the cgSNPs were significantly enriched in eQTLs via logistic regression and simulation test. Furthermore, we observed that cgSNPs were more likely to be trait-associated loci especially cancers using a catalog of published genome-wide association studies (GWAS) recorded by National Human Genome Research Institute (NHGRI). Our results indicated that cgSNP might be meaningful as annotation either in SNP functional prediction or in screening for trait-associated SNPs. PMID:26503467

  13. Associations between Marijuana Use During Emerging Adulthood and Aspects of the Significant Other Relationship in Young Adulthood

    PubMed Central

    Brook, Judith S.; Pahl, Kerstin; Cohen, Patricia

    2013-01-01

    A prospective design was used to examine the association of marijuana use during the transition from late adolescence to early adulthood with reported relationship quality with significant other in the mid- to late twenties. The community-based sample consisted of 534 young adults (mean age = 27) from upstate New York. The participants were interviewed at four points in time at mean ages 14, 16, 22, and 27 years. Marijuana use during the transition from late adolescence to early adulthood was associated with less relationship cohesion and harmony, and with more relationship conflict with control on variables reflecting the participants’ early interpersonal adjustment and the quality of the relationships with their parents. Findings suggest that marijuana use during emerging adulthood predicts diminished relationship quality with a partner in the mid- to late twenties. PMID:23667303

  14. The prion protein gene polymorphisms associated with bovine spongiform encephalopathy susceptibility differ significantly between cattle and buffalo.

    PubMed

    Zhao, Hui; Du, Yanli; Chen, Shunmei; Qing, Lili; Wang, Xiaoyan; Huang, Jingfei; Wu, Dongdong; Zhang, Yaping

    2015-12-01

    Prion protein, encoded by the prion protein gene (PRNP), plays a crucial role in the pathogenesis of transmissible spongiform encephalopathies (TSEs). Several polymorphisms within the PRNP are known to be associated with influencing bovine spongiform encephalopathy (BSE) susceptibility in cattle, namely two insertion/deletion (indel) polymorphisms (a 23-bp indel in the putative promoter and a 12-bp indel in intron 1), the number of octapeptide repeats (octarepeats) present in coding sequence (CDS) and amino acid polymorphisms. The domestic buffaloes, Bubalus bubalis, are a ruminant involved in various aspects of agriculture. It is of interest to ask whether the PRNP polymorphisms differ between cattle and buffalo. In this study, we analyzed the previously reported polymorphisms associated with BSE susceptibility in Chinese buffalo breeds, and compared these polymorphisms in cattle with BSE, healthy cattle and buffalo by pooling data from the literature. Our analysis revealed three significant findings in buffalo: 1) extraordinarily low deletion allele frequencies of the 23- and 12-bp indel polymorphisms; 2) significantly low allelic frequencies of six octarepeats in CDS and 3) the presence of S4R, A16V, P54S, G108S, V123M, S154N and F257L substitutions in buffalo CDSs. Sequence alignments comparing the buffalo coding sequence to other species were analyzed using the McDonald-Kreitman test to reveal five groups (Bison bonasus, Bos indicus, Bos gaurus, Boselaphus tragocamelus, Syncerus caffer caffer) with significantly divergent non-synonymous substitutions from buffalo, suggesting potential divergence of buffalo PRNP and others. To the best of our knowledge this is the first study of PRNP polymorphisms associated with BSE susceptibility in Chinese buffalo. Our findings have provided evidence that buffaloes have a unique genetic background in the PRNP gene in comparison with cattle. PMID:26319996

  15. Significant Promotion Effect of Mo Additive on a Novel Ce-Zr Mixed Oxide Catalyst for the Selective Catalytic Reduction of NO(x) with NH3.

    PubMed

    Ding, Shipeng; Liu, Fudong; Shi, Xiaoyan; Liu, Kuo; Lian, Zhihua; Xie, Lijuan; He, Hong

    2015-05-13

    A novel Mo-promoted Ce-Zr mixed oxide catalyst prepared by a homogeneous precipitation method was used for the selective catalytic reduction (SCR) of NO(x) with NH3. The optimal catalyst showed high NH3-SCR activity, SO2/H2O durability, and thermal stability under test conditions. The addition of Mo inhibited growth of the CeO2 particle size, improved the redox ability, and increased the amount of surface acidity, especially the Lewis acidity, all of which were favorable for the excellent NH3-SCR performance. It is believed that the catalyst is promising for the removal of NO(x) from diesel engine exhaust. PMID:25894854

  16. Significant associations between hemostatic/fibrinolytic systems and accumulation of cardiovascular risk factors in Japanese elementary schoolchildren.

    PubMed

    Lin, Lisheng; Horigome, Hitoshi; Kato, Yoshiaki; Kikuchi, Toshihiro; Nakahara, Satoko; Sumazaki, Ryo

    2015-01-01

    The aim of this study was to establish the reference values of hemostatic/fibrinolytic markers and investigate their relationship with physical constitution and cardiovascular risk factors in a normal schoolchildren population. This study comprised 148 healthy Japanese children aged 9-10 years (males 73; females 75). We performed laboratory tests including blood levels of leptin, high-sensitive C-reactive protein (hs-CRP), hemostatic and fibrinolytic markers [plasminogen activator inhibitor 1 (PAI-1), coagulation factor VII (FVII), coagulation factor X (FX), fibrinogen (Fbg), protein C, protein S], as well as common biochemical markers in the morning after an overnight fast. We investigated the mean, 10th, 50th and 90th percentile values of these markers. All parameters were compared between two groups, that is those with body mass index (BMI) 90th percentile or higher and BMI less than 90th percentile, and between subgroups based on the number of cardiovascular risk factors. Multiple-linear regression was used to assess associations between these hematological parameters and the components related to metabolic syndrome (MetS). Alanine aminotransferase (ALT), uric acid, leptin, hs-CRP, and all hemostatic/fibrinolytic markers (PAI-1, FVII, FX, Fbg, protein C, protein S) tested were significantly higher in the group with BMI 90th percentile or higher, and increased with accumulation of cardiovascular risk factors. Multiple-linear regression analysis showed that these values were associated with one or more components related to MetS. Reference values of hemostatic/fibrinolytic markers in Japanese schoolchildren were obtained. Many hemostatic/fibrinolytic markers showed significant association with BMI and accumulation of cardiovascular risk factors in normal Japanese schoolchildren. PMID:25185676

  17. Significant Modifications of the Salivary Proteome Potentially Associated with Complications of Down Syndrome Revealed by Top-down Proteomics*

    PubMed Central

    Cabras, Tiziana; Pisano, Elisabetta; Montaldo, Caterina; Giuca, Maria Rita; Iavarone, Federica; Zampino, Giuseppe; Castagnola, Massimo; Messana, Irene

    2013-01-01

    People with Down syndrome, a frequent genetic disorder in humans, have increased risk of health problems associated with this condition. One clinical feature of Down syndrome is the increased prevalence and severity of periodontal disease in comparison with the general population. Because saliva plays an important role in maintaining oral health, in the present study the salivary proteome of Down syndrome subjects was investigated to explore modifications with respect to healthy subjects. Whole saliva of 36 Down syndrome subjects, divided in the age groups 10–17 yr and 18–50 yr, was analyzed by a top-down proteomic approach, based on the high performance liquid chromatography-electrospray ionization–MS analysis of the intact proteins and peptides, and the qualitative and quantitative profiles were compared with sex- and age-matched control groups. The results showed the following interesting features: 1) as opposed to controls, in Down syndrome subjects the concentration of the major salivary proteins of gland origin did not increase with age; as a consequence concentration of acidic proline rich proteins and S cystatins were found significantly reduced in older Down syndrome subjects with respect to matched controls; 2) levels of the antimicrobial α-defensins 1 and 2 and histatins 3 and 5 were significantly increased in whole saliva of older Down syndrome subjects with respect to controls; 3) S100A7, S100A8, and S100A12 levels were significantly increased in whole saliva of Down syndrome subjects in comparison with controls. The increased level of S100A7 and S100A12 may be of particular interest as a biomarker of early onset Alzheimer's disease, which is frequently associated with Down syndrome. PMID:23533003

  18. Postural tachycardia syndrome is associated with significant symptoms and functional impairment predominantly affecting young women: a UK perspective

    PubMed Central

    McDonald, Claire; Koshi, Sharon; Busner, Lorna; Kavi, Lesley; Newton, Julia L

    2014-01-01

    Objective To examine a large UK cohort of patients with postural tachycardia syndrome (PoTS), to compare demographic characteristics, symptoms and treatment of PoTS at one centre compared to the largest patient group PoTS UK and to verify if their functional limitation is similar to patients with chronic fatigue syndrome (CFS). Design A cross-sectional study assessed the frequency of symptoms and their associated variables. Patients and setting Two PoTS cohorts were: (1) recruited via PoTS UK, (2) diagnosed at Newcastle Hospitals National Health Service (NHS) Foundation Trust 2009–2012. Patients with PoTS were then compared to a matched cohort with CFS. Main outcome measures Patients’ detailed demographics, time to diagnosis, education, disability, medications, comorbidity and precipitants. Symptom assessment tools captured, Fatigue Impact Scale, Epworth Sleepiness Scale, Orthostatic Grading Scale (OGS), Hospital Anxiety and Depression Scale, Health Assessment Questionnaire, Cognitive Failures Questionnaire. Results 136 patients with PoTS participated (84 members of PoTS UK (170 cohort; 50% return) and 52 (87 cohort; 60%) from Newcastle Clinics). The PoTS UK population was significantly younger than the clinic patients, with significantly fewer men (p=0.005). Over 60% had a university or postgraduate degree. Significantly more of the PoTS UK cohort were working, with hours worked being significantly higher (p=0.001). Time to diagnosis was significantly longer in the PoTS UK cohort (p=0.04). Symptom severity was comparable between cohorts. The PoTS total group was compared with a matched CFS cohort; despite comparable levels of fatigue and sleepiness, autonomic symptom burden (OGS) was statistically significantly higher. The most common treatment regime included β-blockers. Overall, 21 treatment combinations were described. Up to 1/3 were taking no treatment. Conclusions Patients with PoTS are predominantly women, young, well educated and have significant and

  19. Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease, and shows evidence for additional susceptibility genes

    PubMed Central

    Harold, Denise; Abraham, Richard; Hollingworth, Paul; Sims, Rebecca; Gerrish, Amy; Hamshere, Marian; Singh Pahwa, Jaspreet; Moskvina, Valentina; Dowzell, Kimberley; Williams, Amy; Jones, Nicola; Thomas, Charlene; Stretton, Alexandra; Morgan, Angharad; Lovestone, Simon; Powell, John; Proitsi, Petroula; Lupton, Michelle K; Brayne, Carol; Rubinsztein, David C.; Gill, Michael; Lawlor, Brian; Lynch, Aoibhinn; Morgan, Kevin; Brown, Kristelle; Passmore, Peter; Craig, David; McGuinness, Bernadette; Todd, Stephen; Holmes, Clive; Mann, David; Smith, A. David; Love, Seth; Kehoe, Patrick G.; Hardy, John; Mead, Simon; Fox, Nick; Rossor, Martin; Collinge, John; Maier, Wolfgang; Jessen, Frank; Schürmann, Britta; van den Bussche, Hendrik; Heuser, Isabella; Kornhuber, Johannes; Wiltfang, Jens; Dichgans, Martin; Frölich, Lutz; Hampel, Harald; Hüll, Michael; Rujescu, Dan; Goate, Alison; Kauwe, John S.K.; Cruchaga, Carlos; Nowotny, Petra; Morris, John C.; Mayo, Kevin; Sleegers, Kristel; Bettens, Karolien; Engelborghs, Sebastiaan; De Deyn, Peter; van Broeckhoven, Christine; Livingston, Gill; Bass, Nicholas J.; Gurling, Hugh; McQuillin, Andrew; Gwilliam, Rhian; Deloukas, Panagiotis; Al-Chalabi, Ammar; Shaw, Christopher E.; Tsolaki, Magda; Singleton, Andrew; Guerreiro, Rita; Mühleisen, Thomas W.; Nöthen, Markus M.; Moebus, Susanne; Jöckel, Karl-Heinz; Klopp, Norman; Wichmann, H-Erich; Carrasquillo, Minerva M.; Pankratz, V. Shane; Younkin, Steven G.; Holmans, Peter; O'Donovan, Michael; Owen, Michael J.; Williams, Julie

    2010-01-01

    We undertook a two-stage genome-wide association study of Alzheimer's disease involving over 16,000 individuals. In stage 1 (3,941 cases and 7,848 controls), we replicated the established association with the APOE locus (most significant SNP: rs2075650, p= 1.8×10−157) and observed genome-wide significant association with SNPs at two novel loci: rs11136000 in the CLU or APOJ gene (p= 1.4×10−9) and rs3851179, a SNP 5′ to the PICALM gene (p= 1.9×10−8). Both novel associations were supported in stage 2 (2,023 cases and 2,340 controls), producing compelling evidence for association with AD in the combined dataset (rs11136000: p= 8.5×10−10, odds ratio= 0.86; rs3851179: p= 1.3×10−9, odds ratio= 0.86). We also observed more variants associated at p< 1×10−5 than expected by chance (p=7.5×10−6), including polymorphisms at the BIN1, DAB1 and CR1 loci. PMID:19734902

  20. The Association of Peroxisome Proliferator-Activated Receptor δ and Additional Gene-Gene Interaction with C-Reactive Protein in Chinese Population

    PubMed Central

    Ding, Xiao-Ying; Yuan, Hao-Zheng; Gu, Ru; Gao, Yan-Feng; Liu, Xiao-Gang; Gao, Ya

    2016-01-01

    Aims. To examine the association between 4 single nucleotide polymorphisms (SNPs) of peroxisome proliferator-activated receptors δ (PPARδ) polymorphisms and C-reactive protein (CRP) level and additional gene-gene interaction. Methods. Line regression analysis was performed to verify polymorphism association between SNP and CRP levels. Generalized multifactor dimensionality reduction (GMDR) was employed to analyze the interaction. Results. A total of 1028 subjects (538 men, 490 women) were selected. The carriers of the C allele (TC or CC) of rs2016520 were associated with a significant decreased level of CRP, regression coefficients was −0.338, and standard error was 0.104 (p = 0.001). The carriers of the G allele (CG or GG) of rs9794 were also significantly associated with decreased level of CRP, regression coefficients was −0.219, and standard error was 0.114 (p = 0.012). We also found a potential gene-gene interaction between rs2016520 and rs9794. Subjects with rs2016520-TC or CC, rs9794-CG or GG genotypes have lowest CRP level, difference (95% CI) = −0.50 (−0.69 to −0.21) (p < 0.001), compared to subjects with rs2016520-TT and rs9794-CC genotypes. Conclusions. rs2016520 and rs9794 minor allele of PPARδ and combined effect between the two SNP were associated with decreased CRP level. PMID:26884762

  1. Serum Vitamin D Is Significantly Inversely Associated with Disease Severity in Caucasian Adults with Obstructive Sleep Apnea Syndrome

    PubMed Central

    Kerley, Conor P.; Hutchinson, Katrina; Bolger, Kenneth; McGowan, Aisling; Faul, John; Cormican, Liam

    2016-01-01

    Study Objectives: To evaluate vitamin D (25(OH)D) levels in obstructive sleep apnea syndrome (OSAS) and possible relationships to OSAS severity, sleepiness, lung function, nocturnal heart rate (HR), and body composition. We also aimed to compare the 25(OH)D status of a subset of OSAS patients compared to controls matched for important determinants of both OSAS and vitamin D deficiency (VDD). Methods: This was a cross-sectional study conducted at an urban, clinical sleep medicine outpatient center. We recruited newly diagnosed, Caucasian adults who had recently undergone nocturnal polysomnography. We compared body mass index (BMI), body composition (bioelectrical impedance analysis), neck circumference, sleepiness (Epworth Sleepiness Scale), lung function, and vitamin D status (serum 25-hydrpoxyvitamin D (25(OH)D) across OSAS severity categories and non-OSAS subjects. Next, using a case-control design, we compared measures of serum 25(OH)D from OSAS cases to non-OSAS controls who were matched for age, gender, skin pigmentation, sleepiness, season, and BMI. Results: 106 adults (77 male; median age = 54.5; median BMI = 34.3 kg/m2) resident in Dublin, Ireland (latitude 53°N) were recruited and categorized as non-OSAS or mild/moderate/severe OSAS. 98% of OSAS cases had insufficient 25(OH)D (< 75 nmol/L), including 72% with VDD (< 50 nmol/L). 25(OH)D levels decreased with OSAS severity (P = 0.003). 25(OH)D was inversely correlated with BMI, percent body fat, AHI, and nocturnal HR. Subsequent multivariate regression analysis revealed that 25(OH)D was independently associated with both AHI (P = 0.016) and nocturnal HR (P = 0.0419). Our separate case-control study revealed that 25(OH)D was significantly lower in OSAS cases than matched, non-OSAS subjects (P = 0.001). Conclusions: We observed widespread vitamin D deficiency and insufficiency in a Caucasian, OSAS population. There were significant, independent, inverse relationships between 25(OH)D and AHI as well as

  2. Event-Level Relationship between Methamphetamine Use Significantly Associated with Non-adherence to Pharmacologic Trial Medications in Event-Level Analyses

    PubMed Central

    Santos, Glenn-Milo; Vittinghoff, Eric; Santos, Deirdre; Colfax, Grant; Coffin, Phillip

    2014-01-01

    Background Methamphetamine use has been previously associated with poor medication adherence, but, to date, there have been no studies that have conducted event-level analyses on correlates of medication adherence in studies of pharmacologic agents for methamphetamine dependence. Methods We pooled data from two previous, randomized controlled trials (using bupropion and mirtazapine, respectively) for methamphetamine dependence and used a mixed effects logistic model to examine correlates of daily opening of the medication event monitoring system (MEMS) cap as a repeated measure. We explored whether periods of observed methamphetamine use via urine testing were associated with study medication adherence based on MEMS cap openings. Results We found a significant negative association between methamphetamine-urine positivity and event-level study medication adherence as measured by MEMS cap openings (AOR: 0.69; 95% CI: 0.49–0.98). In addition, age (AOR: 1.07; 95% CI: 1.02–1.11) and depressive symptoms (AOR: 0.78; 95% CI: 0.64–0.90) were significantly associated with adherence. Finally, participants were more likely to open their study medication bottles on days when they presented for in-person urine testing. Conclusions Our event-level analysis shows that methamphetamine use can be associated with reduced medication adherence as measured by MEMS cap openings in pharmacologic trials, which corroborates prior research. These findings may suggest that medication adherence support in pharmacologic trials among methamphetamine users may be needed to improve study compliance and could be targeted towards periods of time when there are more likely to not open their study medication pill bottles. PMID:25156227

  3. Significant association between FasL gene -844T/C polymorphism and risk to hepatocellular carcinoma in Egyptian patients.

    PubMed

    Khalifa, Rania H; Bahgat, Dina M Rasheed; Darwish, Hatem Abdel Hamid; Shahin, Rasha Mohamad Hosny

    2016-04-01

    Fas/Fas ligand (FasL) system is the most critical apoptotic signaling entity in the extrinsic apoptotic pathway; hence mutations affecting this pathway may prevent the immune system from the removal of newly-formed tumor cells, and thus lead to tumor formation. The present study investigated the association between the FasL -844T/C polymorphism and the risk of hepatocellular carcinoma (HCC) in a cohort of Egyptian patients and explored the relationship of various clinical and pathological parameters with this single nucleotide polymorphism (SNP). Blood samples were withdrawn from hundred HCC patients and 100 age-, sex- and ethnically matched controls. The FasL -844T/C (rs763110) gene polymorphism was typed from genomic DNA using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay. Genotype distributions and allelic frequencies between patients and control subjects showed that the TT homozygous patients were two times more likely to develop HCC (p=0.011). Also, the T allele was found to be a significant risk factor for the disease (OR 1.970, 95% CI 1.250-3.105, p=0.003). No association was detected between different parameters of the disease and the SNP. For the first time, our results suggest that the -844T/C polymorphism in the FasL gene confers risk to HCC. The alarming increase in the incidence of HCC in Egypt encourages further studies to document our results in a larger sample, and recommends more genetic studies hoping to define a genomic risk prediction specific to this cancer in our population. PMID:26891954

  4. Taurolidine-citrate lock solution (TauroLock) significantly reduces CVAD-associated grampositive infections in pediatric cancer patients

    PubMed Central

    Simon, Arne; Ammann, Roland A; Wiszniewsky, Gertrud; Bode, Udo; Fleischhack, Gudrun; Besuden, Mette M

    2008-01-01

    Background Taurolidin/Citrate (TauroLock™), a lock solution with broad spectrum antimicrobial activity, may prevent bloodstream infection (BSI) due to coagulase-negative staphylococci (CoNS or 'MRSE' in case of methicillin-resistant isolates) in pediatric cancer patients with a long term central venous access device (CVAD, Port- or/Broviac-/Hickman-catheter type). Methods In a single center prospective 48-months cohort study we compared all patients receiving anticancer chemotherapy from April 2003 to March 2005 (group 1, heparin lock with 200 IU/ml sterile normal saline 0.9%; Canusal® Wockhardt UK Ltd, Wrexham, Wales) and all patients from April 2005 to March 2007 (group 2; taurolidine 1.35%/Sodium Citrate 4%; TauroLock™, Tauropharm, Waldbüttelbrunn, Germany). Results In group 1 (heparin), 90 patients had 98 CVAD in use during the surveillance period. 14 of 30 (47%) BSI were 'primary Gram positive BSI due to CoNS (n = 4) or MRSE (n = 10)' [incidence density (ID); 2.30 per 1000 inpatient CVAD-utilization days]. In group 2 (TauroLock™), 89 patients had 95 CVAD in use during the surveillance period. 3 of 25 (12%) BSI were caused by CoNS. (ID, 0.45). The difference in the ID between the two groups was statistically significant (P = 0.004). Conclusion The use of Taurolidin/Citrate (TauroLock™) significantly reduced the number and incidence density of primary catheter-associated BSI due to CoNS and MRSE in pediatric cancer patients. PMID:18664278

  5. Stomatin-like protein 2 overexpression in papillary thyroid carcinoma is significantly associated with high-risk clinicopathological parameters and BRAFV600E mutation.

    PubMed

    Bartolome, Aleksandar; Boskovic, Srdjan; Paunovic, Ivan; Bozic, Vesna; Cvejic, Dubravka

    2016-04-01

    Stomatin-like protein 2 (SLP-2), a member of the stomatin protein family, has emerged as a potential molecular hallmark of tumor progression in several human malignancies. The aim of this study was to analyze SLP-2 expression pattern in benign and malignant thyroid tumors (n = 210) and to examine its relationship with clinicopathological parameters and BRAFV600E mutation in thyroid cancer. SLP-2 immunohistochemical expression was not detected in benign adenomas and was absent/weak in follicular and anaplastic carcinomas. High expression levels of SLP-2, found only in papillary thyroid carcinoma (PTC), particularly in the classical variant, were significantly associated with adverse clinicopathological parameters: lymph node metastasis (p = 0.002), extrathyroid invasion (p < 0.001), pT status (p < 0.001), and advanced tumor stage (p = 0.001). Additional genotyping of PTC cases for the BRAFV600E mutation revealed for the first time a close relation between SLP-2 overexpression and the presence of BRAF mutation (p = 0.02) with high positive rates of lymph node metastasis (70%) and extrathyroid invasion (80%) in these cases. The significant association of SLP-2 overexpression with unfavorable clinicopathological characteristics and BRAFV600E mutation indicates that SLP-2 may have a role in aggressiveness of BRAF-mutated PTC and that SLP-2 evaluation could be clinically useful in identification of high-risk PTC patients. PMID:26750533

  6. Incidence of and significant risk factors for aminoglycoside-associated nephrotoxicity in patients dosed by using individualized pharmacokinetic monitoring.

    PubMed

    Bertino, J S; Booker, L A; Franck, P A; Jenkins, P L; Franck, K R; Nafziger, A N

    1993-01-01

    Incidence of and risk factors for aminoglycoside-associated nephrotoxicity (AAN) were evaluated in 1489 patients prospectively monitored with individualized pharmacokinetic monitoring (IPM). Incidence of AAN was 7.9% with individual (univariate) risk factors including advanced age, decreased albumin, poor nutritional status, pneumonia, concurrent furosemide, amphotericin B, vancomycin, cephalosporin, or piperacillin, intensive care unit treatment, leukemia, rapidly fatal illness, liver or renal disease, reduced aminoglycoside clearance, elevated initial steady-state trough concentration (Cminss), volume of distribution or half-life, duration of therapy, total dose, fever, male gender, shock, pleural effusion, and ascites. Multiple logistic regression revealed that Cminss, concurrent clindamycin, vancomycin, piperacillin, or cephalosporin, ascites, advanced age, male gender, decreased albumin, duration of therapy, and leukemia were significant independent risk factors for AAN. Positive predictive value of the model was 30.8%; negative predictive value was 91.7%. No identifiable risk factor alone or in combination was of sufficient sensitivity to reliably predict AAN, but use of IPM may lower the incidence of AAN. PMID:8418164

  7. Significant Differences in Markers of Oxidant Injury between Idiopathic and Bronchopulmonary-Dysplasia-Associated Pulmonary Hypertension in Children

    PubMed Central

    Vera, Kimberly B.; Moore, Donald; Flack, English; Liske, Michael; Summar, Marshall

    2012-01-01

    While oxidant stress is elevated in adult forms of pulmonary hypertension (PH), levels of oxidant stress in pediatric PH are unknown. The objective of this study is to measure F2-isoprostanes, a marker of oxidant stress, in children with idiopathic pulmonary hypertension (IPH) and PH due to bronchopulmonary dysplasia (BPD). We hypothesized that F2-isoprostanes in pediatric IPH and PH associated with BPD will be higher than in controls. Plasma F2-isoprostanes were measured in pediatric PH patients during clinically indicated cardiac catheterization and compared with controls. F2-Isoprostane levels were compared between IPH, PH due to BD, and controls. Five patients with IPH, 12 with PH due to BPD, and 20 control subjects were studied. Patients with IPH had statistically higher isoprostanes than controls 62 pg/mL (37–210) versus 20 pg/mL (16–27), P < 0.01). The patients with PH and BPD had significantly lower isoprostanes than controls 15 pg/mL (8–17) versus 20 pg/ml (16–27), P < 0.02. F2-isoprostanes are elevated in children with IPH compared to both controls and patients with PH secondary to BPD. Furthermore, F2-isoprostanes in PH secondary to BPD are lower than control levels. These findings suggest that IPH and PH secondary to BPD have distinct mechanisms of disease pathogenesis. PMID:22848815

  8. Tectonic significance of lithicwacke-polymictic conglomerate petrofacies association within Upper Cretaceous torchlight sandstone, Big Horn basin, Wyoming

    SciTech Connect

    Khandaker, N.I.; Vondra, C.F.

    1987-05-01

    The Torchlight Sandstone belonging to the Upper Cretaceous Frontier Formation in the Big Horn basin, Wyoming, shows a distinctive lithicwacke-polymictic conglomerate is composed of granule-cobble-sized clasts of quartzite, chert, andesite, and argillite, and phyllite. The survival of phyllite, argillite, and neovolcanic andesite clasts indicate that the detritus underwent very little subaerial transport before it was deposited along the proximal margin of the foreland basin. A petrologically heterogeneous upland source of high to moderate relief is indicated by the clast size and composition. Hydrodynamic structures, in conjunction with textural attributes, and compositional data indicate that detritus moved southeast from its source terrane and was deposited by a high-energy distributary complex. The lithicwacke petrofacies is dominated by higher chert and quartz content with a subordinate amount of labile components including paleovolcanic clasts and fine-grained matrix. The development of phyllosilicate matrix around quartz and chert grains preserved the primary porosity and permeability of the sandstone. Absence of any noticeable quartz overgrowth apparently contributed to the preservation of good reservoir quality in this petrofacies. Considering its (Torchlight Sandstone) close proximity to the thrust belt and to the locus of andesite volcanism in the northwest and west, it is suggested that the extrabasinal detritus within the foreland basin can provide significant clues as to the timing of the thrust events and volcanicity in the adjacent region. New perspectives for hydrocarbon exploration and regional correlation may be gained by employing this petrofacies association.

  9. Expression and significance of glucose transporter-1, P-glycoprotein, multidrug resistance-associated protein and glutathione S-transferase-π in laryngeal carcinoma

    PubMed Central

    MAO, ZHONG-PING; ZHAO, LI-JUN; ZHOU, SHUI-HONG; LIU, MENG-QIN; TAN, WEI-FENG; YAO, HONG-TIAN

    2015-01-01

    Increasing glucose transporter-1 (GLUT-1) activity is one of the most important ways to increase the cellular influx of glucose. We previously demonstrated that increased GLUT-1 expression was an independent predictor of survival in patients with laryngeal carcinoma. Thus, GLUT-1 may present a novel therapeutic target in laryngeal carcinoma. In this study, the expression of GLUT-1, P-glycoprotein (P-gp), multidrug resistance-associated protein 1 (MRP1) and glutathione S-transferase-π (GST-π) in laryngeal carcinomas was investigated by immunohistochemistry. Additionally, possible correlations between GLUT-1 and P-gp, MRP1 and GST-π and various clinicopathological parameters were analyzed. In this study, 52.9% (18/34), 58.8% (20/34), 20.6% (7/34) and 58.8% (20/34) of the laryngeal carcinomas were positive for GLUT-1, P-gp, MRP1 and GST-π, respectively. The expression of GLUT-1, P-gp, MRP1 and GST-π was higher in laryngeal carcinoma specimens when compared with laryngeal precancerous lesions (P<0.05). Pearson’s correlation analysis showed correlations between GLUT-1 and P-gp (r=0.364; P=0.034), GLUT-1 and MRP1 (r=0.359; P=0.037) and P-gp and GST-π (r=0.426; P=0.012). GLUT-1 expression was found to significantly correlate with tumor-node-metastasis classification (P=0.02) and clinical stage (P=0.037). Furthermore, P-gp was found to significantly correlate with clinical stage (P=0.026). Univariate analysis showed that MRP1 expression was significantly associated with poor survival (c2=5.16; P=0.023). Multivariate analysis revealed that lymph node metastasis (P=0.009) and MRP1 overexpression (P=0.023) were significant predictors of poor survival. In the present study, the expression of GLUT-1, P-gp, MRP1 and GST-π in laryngeal carcinomas was investigated, as well as the correlations between these proteins. P-gp was found to significantly correlate with clinical stage, while MRP1 overexpression was significantly associated with poor survival. PMID:25621055

  10. Characterization of a new wheat-Aegilops biuncialis addition line conferring quality-associated HMW glutenin subunits.

    PubMed

    Zhou, J P; Yao, C H; Yang, E N; Yin, M Q; Liu, C; Ren, Z L

    2014-01-01

    In this study, a new disomic addition line, 12-5-2, with 44 chromosomes that was derived from BC3F2 descendants of the hybridization between Triticum aestivum cv. CN19 and Aegilops biuncialis was created and reported. 12-5-2 was immune to both powdery mildew and stripe rust and has stable fertility. Fluorescence in situ hybridization and C-banding revealed that 12-5-2 was a 1U(b) disomic addition line (ADL1U(b)). The seed storage protein electrophoresis showed that 12-5-2 presented all high molecular weight glutenin subunits (7 + 8 and 2 + 12) of CN19 and 2 new subunits that were designated Ux and Uy. Additionally, the flour quality parameters showed that the protein content, Zeleny sedimentation value, wet gluten content, and grain hardness of 12-5-2 were significantly higher than those of its parent CN19. Moreover, 5 pairs of the chromosome 1U(b)-specific polymerase chain reaction-based landmark unique gene markers, TNAC1021, TNAC1041, TNAC1071, TNAC1-01, and TNAC1-04, were also obtained. The new ADL1U(b) 12-5-2 could be a valuable source for wheat improvement, especially for wheat end-product quality and resistance to disease. PMID:24615031

  11. Distribution of OCA2∗481Thr and OCA2∗615Arg, associated with hypopigmentation, in several additional populations.

    PubMed

    Yuasa, Isao; Harihara, Shinji; Jin, Feng; Nishimukai, Hiroaki; Fujihara, Junko; Fukumori, Yasuo; Takeshita, Haruo; Umetsu, Kazuo; Saitou, Naruya

    2011-07-01

    Two mutants, OCA2∗481Thr (c.1441G>A, p.Ala481Thr) and OCA2∗615Arg (c.1844A>G, p.His615Arg), in the OCA2 (oculocutaneous albinism type II) gene are associated with hypopigmentation in East Asians. Here, these two alleles were studied to assess the frequencies in five different populations. In addition, the allele frequency of OCA2∗615Arg was investigated in seven populations. Among a total of 24 global populations investigated, Oroqens in Heihe showed the highest frequency for OCA2∗481Thr (0.519), and among 26 populations, Han Chinese in Changsha showed the highest frequency for OCA2∗615Arg (0.673). This study confirmed that these two East Asian-specific alleles are characteristic of northern and central-southern East Asian populations. PMID:21565543

  12. Significance of the hedgehog pathway-associated proteins Gli-1 and Gli-2 and the epithelial-mesenchymal transition-associated proteins Twist and E-cadherin in hepatocellular carcinoma

    PubMed Central

    Chun, Hyung Wook; Hong, Ran

    2016-01-01

    It has been found that abnormal activation of the hedgehog (Hh) signaling pathway is involved in the occurrence, invasion and metastasis of malignant tumors. In addition, epithelial-mesenchymal transition (EMT) also performs an important function in the invasion and metastasis of malignant tumors. However, the significance of the Hh signaling pathway and EMT in hepatocellular carcinoma (HCC) remains unknown. In the present study, the expression of Gli family zinc finger 1 (Gli-1) and Gli family zinc finger 2 (Gli-2), which are key transcriptional factors in the Hh signaling pathway, and Twist and E-cadherin, which are two factors involved in EMT, was examined in 42 patients with HCC and 20 cases of non-tumorous liver (NTL) tissue by immunohistochemistry. Clinicopathological information was collected in order to analyze the correlation of the Hh signaling pathway with EMT. The present study aimed to examine the difference in the expression of Gli-1, Gli-2, E-cadherin and Twist in HCC and NTL to assess the diagnostic value of these factors in HCC. Additionally, the present study aimed to elucidate the correlation between those proteins and other clinicopathological parameters. Whether abnormal activation of the Hh signaling pathway is closely associated with EMT was also evaluated. Gli-1 and Twist expression was found to be significantly increased and E-cadherin expression was found to be decreased in HCC in contrast to NTL (Gli-1, P=0.019; Twist, P=0.003; E-cadherin, P<0.001). Increased Twist expression was associated with the tumor size (P=0.043), and loss of or decreased E-cadherin expression was associated with the histological type of HCC (P=0.021). There was an inverse association between the expression of Twist and E-cadherin (P=0.006). These results showed that Twist overexpression by induction of EMT changes is involved in the occurrence and progression of HCC. However, the role of Hh signaling pathway-associated proteins in HCC may require elucidation by

  13. The significance of platelet microparticles in patients with chronic hepatitis C and their association with antiviral treatment and smoking

    PubMed Central

    Kanellopoulou, Theoni; Alexopoulou, Alexandra; Kontopidou, Flora N.; Konstantinides, Polydoros; Papatheodoridis, George V.

    2016-01-01

    Background Platelet microparticles (PMPs) are platelet-derived membrane vesicles involved in cardiovascular diseases and atherosclerosis. Chronic hepatitis C (CHC) is associated with increased atherosclerosis, but the effect of therapy on its atherogenic potential has not been adequately studied. Methods We evaluated PMP levels before and after treatment with pegylated-interferon-alfa and ribavirin in 28 CHC patients compared with 20 non-alcoholic fatty liver disease (NAFLD) patients and 20 healthy volunteers (HV). Results Twenty-four (86%) CHC patients achieved sustained virological response (SVR). PMP levels were determined at baseline in CHC, NAFLD patients, and HV, and at end-of-treatment (EOT) and 24 weeks post-treatment (SVR24) in CHC patients. PMP levels at baseline were higher in CHC than NAFLD patients (P<0.001) and HV (P=0.007). Higher PMPs at baseline were observed in smokers than non-smokers with CHC (P=0.006). Among smokers from all groups, PMPs at baseline were higher in CHC than NAFLD patients (P=0.001) and HV (P=0.024). In CHC patients, PMPs declined from baseline to both EOT (P=0.035) and SVR24 (P=0.006). Only CHC patients with SVR had a significant decline in PMPs from baseline to SVR24 (P=0.018). PMPs at ΕΟΤ and SVR24 in all CHC patients were similar to PMPs in NAFLD patients and HV. Conclusions PMP levels are increased in CHC patients, particularly smokers, which further supports the atherosclerotic potential of CHC and suggests a potentially synergistic effect of smoking and CHC on the atherosclerotic process. Since PMP levels in CHC patients with SVR were similar to NAFLD patients and HV, the atherosclerotic potential of CHC seems to be abolished by effective antiviral treatment. PMID:27065733

  14. Significant Association of HLA-B Alleles and Genotypes in Thai Children with Autism Spectrum Disorders: A Case-Control Study

    PubMed Central

    Puangpetch, Apichaya; Suwannarat, Pongwut; Chamnanphol, Montri; Koomdee, Napatrupron; Ngamsamut, Nattawat; Limsila, Penkhae; Sukasem, Chonlaphat

    2015-01-01

    Autism is a severe neurodevelopmental disorder. Many susceptible causative genes have been identified. Most of the previous reports showed the relationship between the Human Leukocyte Antigen (HLA) gene and etiology of autism. In order to identify HLA-B alleles associated with autism in Thai population, we compared the frequency of HLA-B allele in 364 autistic subjects with 952 normal subjects by using a two-stage sequence-specific oligonucleotide probe system (PCR-SSOP) method based on flow-cytometry technology. HLA-B⁎13:02 (P = 0.019, OR = 2.229), HLA-B⁎38:02 (P = 0.049, OR = 1.628), HLA-B⁎44:03 (P = 0.016, OR = 1.645), and HLA-B⁎56:01 (P = 1.78 × 10−4, OR = 4.927) alleles were significantly increased in autistic subjects compared with normal subjects. Moreover, we found that the HLA-B⁎18:02 (P = 0.016, OR = 0.375) and HLA-B⁎46:12 (P = 0.008, OR = 0.147) alleles were negatively associated with autism when compared to normal controls. Both alleles might have a protective role in disease development. In addition, four HLA-B genotypes of autistic patients had statistically significant relationship with control groups, consisting of HLA-B⁎3905/⁎5801 (P = 0.032, OR = 24.697), HLA-B⁎2704/⁎5801 (P = 0.022, OR = 6.872), HLA-B⁎3501/⁎4403 (P = 0.021, OR = 30.269), and HLA-B⁎1801/⁎4402 (P = 0.017, OR = 13.757). This is the first report on HLA-B associated with Thai autism and may serve as a marker for genetic susceptibility to autism in Thai population. PMID:26819491

  15. Urine phyto-oestrogen metabolites are not significantly associated with risk of type 2 diabetes: the Singapore Chinese health study.

    PubMed

    Talaei, Mohammad; Lee, Bee L; Ong, Choon N; van Dam, Rob M; Yuan, Jian M; Koh, Woon P; Pan, An

    2016-05-01

    We evaluated the relationship between urine concentrations of phyto-oestrogens (isoflavones and lignans) and risk of incident type 2 diabetes in middle-aged and elderly Chinese residing in Singapore. Urine metabolites of isoflavones and lignans were assayed by HPLC among 564 diabetes cases and 564 matched controls in a case-control study nested within the Singapore Chinese Health Study cohort. Participants were free of diagnosed diabetes, CVD and cancer at morning urine collections during 1999-2004. Cases were participants who reported to have physician-diagnosed diabetes at follow-up visits during 2006-2010, whereas controls were randomly selected among those who remained free of diabetes and were matched to the index cases by age, sex, dialect group and date of urine collection. Conditional logistic regression models were used to calculate OR and 95 % CI with adjustment for potential confounders. The mean age of the participants at the time of urine collection was 59·8 years, and the average interval between urine collection and diabetes diagnosis was 4·0 years. The multivariate-adjusted OR for diabetes were 1·00 (reference), 0·76 (95 % CI 0·52, 1·11), 0·78 (95 % CI 0·53, 1·14) and 0·79 (95 % CI 0·54, 1·15) across quartiles of urine isoflavones (P for trend=0·54), and were 1·00 (reference), 0·87 (95 % CI 0·60, 1·27), 1·10 (95 % CI 0·77, 1·56) and 0·93 (95 % CI 0·63, 1·37) for lignans (P for trend=0·93). The results were similar in men and women, as well as for individual metabolites of isoflavones (genistein, daidzein, glycitin and equol) or lignans (enterodiol and enterolactone). The present study did not find a significant association between urine phyto-oestrogen metabolites and risk of type 2 diabetes in Chinese adults. PMID:26949260

  16. Addition of Bevacizumab to Standard Radiation Therapy and Daily Temozolomide Is Associated With Minimal Toxicity in Newly Diagnosed Glioblastoma Multiforme

    SciTech Connect

    Vredenburgh, James J.; Desjardins, Annick; Kirkpatrick, John P.; Reardon, David A.; Peters, Katherine B.; Herndon, James E.; Marcello, Jennifer; Bailey, Leighann; Threatt, Stevie; Sampson, John; Friedman, Allan; Friedman, Henry S.

    2012-01-01

    Purpose: To determine the safety of the addition of bevacizumab to standard radiation therapy and daily temozolomide for newly diagnosed glioblastoma multiforme (GBM). Methods and Materials: A total of 125 patients with newly diagnosed GBM were enrolled in the study, and received standard radiation therapy and daily temozolomide. All patients underwent a craniotomy and were at least 2 weeks postoperative. Radiation therapy was administered in 1.8-Gy fractions, with the clinical target volume for the primary course treated to a dose of 45 to 50.4 Gy, followed by a boost of 9 to 14.4 Gy, to a total dose of 59.4 Gy. Patients received temozolomide at 75 mg/m{sup 2} daily throughout the course of radiation therapy. Bevacizumab was given at 10 mg/kg intravenously every 14 days, beginning a minimum of 4 weeks postoperatively. Results: Of the 125 patients, 120 (96%) completed the protocol-specified radiation therapy. Five patients had to stop the protocol therapy, 2 patients with pulmonary emboli, and 1 patient each with a Grade 2 central nervous system hemorrhage, Grade 4 pancytopenia, and wound dehiscence requiring surgical intervention. All 5 patients ultimately finished the radiation therapy. After radiation therapy, 3 patients had progressive disease, 2 had severe fatigue and decreased performance status, 1 patient had a colonic perforation, and 1 had a rectal fissure; these 7 patients therefore did not proceed with the protocol-specified adjuvant temozolomide, bevacizumab, and irinotecan. However, 113 patients (90%) were able to continue on study. Conclusions: The addition of bevacizumab to standard radiation therapy and daily temozolomide was found to be associated with minimal toxicity in patients newly diagnosed with GBM.

  17. STAT4 Associates with SLE Through Two Independent Effects that Correlate with Gene Expression and Act Additively with IRF5 to Increase Risk

    PubMed Central

    Abelson, Anna-Karin; Delgado-Vega, Angélica M.; Kozyrev, Sergey V.; Sánchez, Elena; Velázquez-Cruz, Rafael; Eriksson, Niclas; Wojcik, Jerome; Reddy, Prasad Linga; Lima, Guadalupe; D’Alfonso, Sandra; Migliaresi, Sergio; Baca, Vicente; Orozco, Lorena; Witte, Torsten; Ortego-Centeno, Norberto; Abderrahim, Hadi; Pons-Estel, Bernardo A.; Gutiérrez, Carmen; Suárez, Ana; González-Escribano, Maria Francisca; Martin, Javier; Alarcón-Riquelme, Marta E.

    2013-01-01

    Objectives To confirm and define the genetic association of STAT4 and systemic lupus erythematosus, investigate the possibility of correlations with differential splicing and/or expression levels, and genetic interaction with IRF5. Methods 30 tag SNPs were genotyped in an independent set of Spanish cases and controls. SNPs surviving correction for multiple tests were genotyped in 5 new sets of cases and controls for replication. STAT4 cDNA was analyzed by 5’-RACE PCR and sequencing. Expression levels were measured by quantitative PCR. Results In the fine-mapping, four SNPs were significant after correction for multiple testing, with rs3821236 and rs3024866 as the strongest signals, followed by the previously associated rs7574865, and by rs1467199. Association was replicated in all cohorts. After conditional regression analyses, two major independent signals represented by SNPs rs3821236 and rs7574865, remained significant across the sets. These SNPs belong to separate haplotype blocks. High levels of STAT4 expression correlated with SNPs rs3821236, rs3024866 (both in the same haplotype block) and rs7574865 but not with other SNPs. We also detected transcription of alternative tissue-specific exons 1, indicating presence of tissue-specific promoters of potential importance in the expression of STAT4. No interaction with associated SNPs of IRF5 was observed using regression analysis. Conclusions These data confirm STAT4 as a susceptibility gene for SLE and suggest the presence of at least two functional variants affecting levels of STAT4. Our results also indicate that both genes STAT4 and IRF5 act additively to increase risk for SLE. PMID:19019891

  18. Significant associations of stearoyl-CoA desaturase (SCD1) gene with fat deposition and composition in skeletal muscle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Gene expression studies in humans and animals have shown that elevated SCD1 activity is associated with increased fat accumulation and monounsaturation of lipids in skeletal muscle, both of which are pathobiological contributors to insulin resistance in patients with obesity and type 2 diabetes. How...

  19. Identification and characterization of a genome-wide significant region associated with red blood cell phenotypes in domestic sheep

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A genome wide association study (GWAS) investigating red blood cell (RBC) phenotypes was performed with over 500 domestic sheep (Ovis aries) from three economically important breeds in the US (Columbia, Polypay, and Rambouillet). A single nucleotide polymorphism (SNP, hereafter the discovery SNP) sh...

  20. Genetic Variants in SDC3 Gene are Significantly Associated with Growth Traits in Two Chinese Beef Cattle Breeds.

    PubMed

    Huang, Yong-Zhen; Wang, Qin; Zhang, Chun-Lei; Fang, Xing-Tang; Song, En-Liang; Chen, Hong

    2016-07-01

    Identification of the genes and polymorphisms underlying quantitative traits, and understanding these genes and polymorphisms affect economic growth traits, are important for successful marker-assisted selection and more efficient management strategies in commercial cattle (Bos taurus) population. Syndecan-3 (SDC3), a member of the syndecan family of type I transmembrane heparan sulfate proteoglycans is a novel regulator of feeding behavior and body weight. The aim of this study is to examine the association of the SDC3 polymorphism with growth traits in Chinese Jiaxian and Qinchuan cattle breeds (). Four single nucleotide polymorphisms (SNPs: 1-4) were detected in 555 cows from three Chinese native cattle breeds by means of sequencing pooled DNA samples and polymerase chain reaction-single stranded conformational polymorphism (PCR-SSCP) methods. We found one SNP (g.28362A > G) in intron and three SNPs (g.30742T > G, g.30821C > T and 33418 A > G) in exons. The statistical analyses indicated that these SNPs of SDC3 gene were associated with bovine body height, body length, chest circumference, and circumference of cannon bone (P < 0.05). The mutant-type variant was superior for growth traits; the heterozygote was associated with higher growth traits compared to wild-type homozygote. Our result confirms the polymorphisms in the SDC3 gene are associated with growth traits that may be used for marker-assisted selection in beef cattle breeding programs. PMID:27119984

  1. Crystallization of the Membrane-Associated Annexin B1: Roles of Additive Screen, Dynamic Light Scattering, and Bioactivity Assay

    SciTech Connect

    Ding, F.; Xu, Y; Azzi, A; Zhu, D; Rehse, D; Chen, C; Sun, S; Lin, S

    2010-01-01

    Annexin B1 (AnxB1) is a calcium-dependent phospholipid binding protein from Taenia solium cysticercus and has been reported to possess anticoagulant activity, to inhibit phospholipase A{sub 2}, and to regulate membrane transport. Native AnxB1 and its selenomethionyl derivative have been overproduced in Escherichia coli and purified. The results of dynamic light scattering analysis showed that Hepes buffer combined with low concentration salts (NaCl or CaCl{sub 2}) was beneficial for preventing aggregation and for AnxB1 stabilization in the storage. After the additive screen, crystals have been yielded in the presence of guanidine hydrochloride (Gn-HCl). We determined that a low concentration of Gn-HCl significantly delayed clotting time and increased anticoagulant activity. Analysis of the crystal showed that in the presence of Gn-HCl, AnxB1 crystallizes in orthorhombic space group, which is modified from the cubic space group for crystals grown in the absence of Gn-HCl. A high quality data set (at 1.9 {angstrom}) has been collected successfully for crystals of L-selenomethionine labeled protein in the presence of Gn-HCl, to solve the structure with the single anomalous dispersion method (SAD). The unit cell parameters are a = 102.35 {angstrom}, b = 103.59 {angstrom}, c = 114.60 {angstrom}, {alpha} = {beta} = {gamma} = 90.00{sup o}.

  2. Health Effects Associated with Inhalation Exposure to Diesel Emission Generated with and without CeO2 Nano Fuel Additive

    EPA Science Inventory

    Diesel exhaust (DE) exposure induces adverse cardiopulmonary effects. Addition of nano cerium (Ce) oxide additive to diesel fuel (DECe) increases fuel burning efficiency resulting in altered emission characteristics and potentially altered health effects. We hypothesized that inh...

  3. Meta-analysis of gene–environment-wide association scans accounting for education level identifies additional loci for refractive error

    PubMed Central

    Fan, Qiao; Verhoeven, Virginie J. M.; Wojciechowski, Robert; Barathi, Veluchamy A.; Hysi, Pirro G.; Guggenheim, Jeremy A.; Höhn, René; Vitart, Veronique; Khawaja, Anthony P.; Yamashiro, Kenji; Hosseini, S Mohsen; Lehtimäki, Terho; Lu, Yi; Haller, Toomas; Xie, Jing; Delcourt, Cécile; Pirastu, Mario; Wedenoja, Juho; Gharahkhani, Puya; Venturini, Cristina; Miyake, Masahiro; Hewitt, Alex W.; Guo, Xiaobo; Mazur, Johanna; Huffman, Jenifer E.; Williams, Katie M.; Polasek, Ozren; Campbell, Harry; Rudan, Igor; Vatavuk, Zoran; Wilson, James F.; Joshi, Peter K.; McMahon, George; St Pourcain, Beate; Evans, David M.; Simpson, Claire L.; Schwantes-An, Tae-Hwi; Igo, Robert P.; Mirshahi, Alireza; Cougnard-Gregoire, Audrey; Bellenguez, Céline; Blettner, Maria; Raitakari, Olli; Kähönen, Mika; Seppala, Ilkka; Zeller, Tanja; Meitinger, Thomas; Ried, Janina S.; Gieger, Christian; Portas, Laura; van Leeuwen, Elisabeth M.; Amin, Najaf; Uitterlinden, André G.; Rivadeneira, Fernando; Hofman, Albert; Vingerling, Johannes R.; Wang, Ya Xing; Wang, Xu; Tai-Hui Boh, Eileen; Ikram, M. Kamran; Sabanayagam, Charumathi; Gupta, Preeti; Tan, Vincent; Zhou, Lei; Ho, Candice E. H.; Lim, Wan'e; Beuerman, Roger W.; Siantar, Rosalynn; Tai, E-Shyong; Vithana, Eranga; Mihailov, Evelin; Khor, Chiea-Chuen; Hayward, Caroline; Luben, Robert N.; Foster, Paul J.; Klein, Barbara E. K.; Klein, Ronald; Wong, Hoi-Suen; Mitchell, Paul; Metspalu, Andres; Aung, Tin; Young, Terri L.; He, Mingguang; Pärssinen, Olavi; van Duijn, Cornelia M.; Jin Wang, Jie; Williams, Cathy; Jonas, Jost B.; Teo, Yik-Ying; Mackey, David A.; Oexle, Konrad; Yoshimura, Nagahisa; Paterson, Andrew D.; Pfeiffer, Norbert; Wong, Tien-Yin; Baird, Paul N.; Stambolian, Dwight; Wilson, Joan E. Bailey; Cheng, Ching-Yu; Hammond, Christopher J.; Klaver, Caroline C. W.; Saw, Seang-Mei; Rahi, Jugnoo S.; Korobelnik, Jean-François; Kemp, John P.; Timpson, Nicholas J.; Smith, George Davey; Craig, Jamie E.; Burdon, Kathryn P.; Fogarty, Rhys D.; Iyengar, Sudha K.; Chew, Emily; Janmahasatian, Sarayut; Martin, Nicholas G.; MacGregor, Stuart; Xu, Liang; Schache, Maria; Nangia, Vinay; Panda-Jonas, Songhomitra; Wright, Alan F.; Fondran, Jeremy R.; Lass, Jonathan H.; Feng, Sheng; Zhao, Jing Hua; Khaw, Kay-Tee; Wareham, Nick J.; Rantanen, Taina; Kaprio, Jaakko; Pang, Chi Pui; Chen, Li Jia; Tam, Pancy O.; Jhanji, Vishal; Young, Alvin L.; Döring, Angela; Raffel, Leslie J.; Cotch, Mary-Frances; Li, Xiaohui; Yip, Shea Ping; Yap, Maurice K.H.; Biino, Ginevra; Vaccargiu, Simona; Fossarello, Maurizio; Fleck, Brian; Yazar, Seyhan; Tideman, Jan Willem L.; Tedja, Milly; Deangelis, Margaret M.; Morrison, Margaux; Farrer, Lindsay; Zhou, Xiangtian; Chen, Wei; Mizuki, Nobuhisa; Meguro, Akira; Mäkelä, Kari Matti

    2016-01-01

    Myopia is the most common human eye disorder and it results from complex genetic and environmental causes. The rapidly increasing prevalence of myopia poses a major public health challenge. Here, the CREAM consortium performs a joint meta-analysis to test single-nucleotide polymorphism (SNP) main effects and SNP × education interaction effects on refractive error in 40,036 adults from 25 studies of European ancestry and 10,315 adults from 9 studies of Asian ancestry. In European ancestry individuals, we identify six novel loci (FAM150B-ACP1, LINC00340, FBN1, DIS3L-MAP2K1, ARID2-SNAT1 and SLC14A2) associated with refractive error. In Asian populations, three genome-wide significant loci AREG, GABRR1 and PDE10A also exhibit strong interactions with education (P<8.5 × 10−5), whereas the interactions are less evident in Europeans. The discovery of these loci represents an important advance in understanding how gene and environment interactions contribute to the heterogeneity of myopia. PMID:27020472

  4. Meta-analysis of gene-environment-wide association scans accounting for education level identifies additional loci for refractive error.

    PubMed

    Fan, Qiao; Verhoeven, Virginie J M; Wojciechowski, Robert; Barathi, Veluchamy A; Hysi, Pirro G; Guggenheim, Jeremy A; Höhn, René; Vitart, Veronique; Khawaja, Anthony P; Yamashiro, Kenji; Hosseini, S Mohsen; Lehtimäki, Terho; Lu, Yi; Haller, Toomas; Xie, Jing; Delcourt, Cécile; Pirastu, Mario; Wedenoja, Juho; Gharahkhani, Puya; Venturini, Cristina; Miyake, Masahiro; Hewitt, Alex W; Guo, Xiaobo; Mazur, Johanna; Huffman, Jenifer E; Williams, Katie M; Polasek, Ozren; Campbell, Harry; Rudan, Igor; Vatavuk, Zoran; Wilson, James F; Joshi, Peter K; McMahon, George; St Pourcain, Beate; Evans, David M; Simpson, Claire L; Schwantes-An, Tae-Hwi; Igo, Robert P; Mirshahi, Alireza; Cougnard-Gregoire, Audrey; Bellenguez, Céline; Blettner, Maria; Raitakari, Olli; Kähönen, Mika; Seppala, Ilkka; Zeller, Tanja; Meitinger, Thomas; Ried, Janina S; Gieger, Christian; Portas, Laura; van Leeuwen, Elisabeth M; Amin, Najaf; Uitterlinden, André G; Rivadeneira, Fernando; Hofman, Albert; Vingerling, Johannes R; Wang, Ya Xing; Wang, Xu; Tai-Hui Boh, Eileen; Ikram, M Kamran; Sabanayagam, Charumathi; Gupta, Preeti; Tan, Vincent; Zhou, Lei; Ho, Candice E H; Lim, Wan'e; Beuerman, Roger W; Siantar, Rosalynn; Tai, E-Shyong; Vithana, Eranga; Mihailov, Evelin; Khor, Chiea-Chuen; Hayward, Caroline; Luben, Robert N; Foster, Paul J; Klein, Barbara E K; Klein, Ronald; Wong, Hoi-Suen; Mitchell, Paul; Metspalu, Andres; Aung, Tin; Young, Terri L; He, Mingguang; Pärssinen, Olavi; van Duijn, Cornelia M; Jin Wang, Jie; Williams, Cathy; Jonas, Jost B; Teo, Yik-Ying; Mackey, David A; Oexle, Konrad; Yoshimura, Nagahisa; Paterson, Andrew D; Pfeiffer, Norbert; Wong, Tien-Yin; Baird, Paul N; Stambolian, Dwight; Wilson, Joan E Bailey; Cheng, Ching-Yu; Hammond, Christopher J; Klaver, Caroline C W; Saw, Seang-Mei; Rahi, Jugnoo S; Korobelnik, Jean-François; Kemp, John P; Timpson, Nicholas J; Smith, George Davey; Craig, Jamie E; Burdon, Kathryn P; Fogarty, Rhys D; Iyengar, Sudha K; Chew, Emily; Janmahasatian, Sarayut; Martin, Nicholas G; MacGregor, Stuart; Xu, Liang; Schache, Maria; Nangia, Vinay; Panda-Jonas, Songhomitra; Wright, Alan F; Fondran, Jeremy R; Lass, Jonathan H; Feng, Sheng; Zhao, Jing Hua; Khaw, Kay-Tee; Wareham, Nick J; Rantanen, Taina; Kaprio, Jaakko; Pang, Chi Pui; Chen, Li Jia; Tam, Pancy O; Jhanji, Vishal; Young, Alvin L; Döring, Angela; Raffel, Leslie J; Cotch, Mary-Frances; Li, Xiaohui; Yip, Shea Ping; Yap, Maurice K H; Biino, Ginevra; Vaccargiu, Simona; Fossarello, Maurizio; Fleck, Brian; Yazar, Seyhan; Tideman, Jan Willem L; Tedja, Milly; Deangelis, Margaret M; Morrison, Margaux; Farrer, Lindsay; Zhou, Xiangtian; Chen, Wei; Mizuki, Nobuhisa; Meguro, Akira; Mäkelä, Kari Matti

    2016-01-01

    Myopia is the most common human eye disorder and it results from complex genetic and environmental causes. The rapidly increasing prevalence of myopia poses a major public health challenge. Here, the CREAM consortium performs a joint meta-analysis to test single-nucleotide polymorphism (SNP) main effects and SNP × education interaction effects on refractive error in 40,036 adults from 25 studies of European ancestry and 10,315 adults from 9 studies of Asian ancestry. In European ancestry individuals, we identify six novel loci (FAM150B-ACP1, LINC00340, FBN1, DIS3L-MAP2K1, ARID2-SNAT1 and SLC14A2) associated with refractive error. In Asian populations, three genome-wide significant loci AREG, GABRR1 and PDE10A also exhibit strong interactions with education (P<8.5 × 10(-5)), whereas the interactions are less evident in Europeans. The discovery of these loci represents an important advance in understanding how gene and environment interactions contribute to the heterogeneity of myopia. PMID:27020472

  5. Yeast-containing feed additive alters gene expression profiles associated with innate immunity in whole blood of a rodent model.

    PubMed

    Branson, Jennifer A; McLean, Derek J; Forsberg, Neil E; Bobe, Gerd

    2016-05-01

    Feeding a yeast-containing additive (YCA; OmniGen-AF) improves immune responses in ruminant livestock and reduces subsequent production losses. The objective was to identify molecular pathways by which dietary YCA may modify immune responses using a rodent model. Thirty-seven healthy, unchallenged CD rats received a diet containing 0 (control; n = 5, only 28 d), 0.5% (n = 15) or 1% (n = 17) YCA for 7 (n = 4/group), 14 (n = 3 or 4/group), 21 (n = 3 or 4/group) or 28 (n = 5/group) d. At the end of the feeding periods, whole blood was collected and the isolated RNA was analyzed for the expression of 84 genes involved in innate and cell-mediated adaptive immune responses. Three bacterial pattern recognition receptors TLR1 (0.5%: + 2.01; 1%: + 2.38), TLR6 (0.5%: + 2.11; 1%: + 2.34) and NOD2 (0.5%: + 2.32; 1%: + 2.23), two APC surface receptors CD1D1 (0.5%: + 1.75; 1%: + 2.33) and CD80 (0.5%: +2.45; 1%: +3.00), and the cell signaling molecule MAPK8 (0.5%: +1.87; 1%: +2.35) were significantly up-regulated by YCA at both inclusion rates. In conclusion, feeding YCA may potentially increase recognition and responses to bacterial pathogens and T-cell activation and differentiation and thereby maintain health and prevent production losses. PMID:27033362

  6. Preintubation Application of Oral Chlorhexidine Does Not Provide Additional Benefit in Prevention of Early-Onset Ventilator-Associated Pneumonia

    PubMed Central

    Grap, Mary Jo; Sessler, Curtis N.; Elswick, Ronald K.; Mangar, Devanand; Karlnoski-Everall, Rachel; Cairns, Paula

    2015-01-01

    BACKGROUND: Daily application of oral chlorhexidine gluconate (CHX) following intubation to reduce the risk of ventilator-associated pneumonia (VAP) is now the standard of care in many ICUs. This randomized clinical trial evaluated the benefit of adding a preintubation CHX dose to the known benefit of postintubation CHX to reduce the risk of early-onset VAP. A secondary aim was to test the effect of a preintubation oral application of CHX on early endotracheal tube (ETT) colonization. METHODS: Subjects (N = 314) were recruited from two teaching hospitals and were randomly assigned to oral application of 5 mL CHX 0.12% solution before intubation (intervention group, n = 157), or to a control group (n = 157) who received no CHX before intubation. All subjects received CHX bid after intubation. Groups were compared using a repeated-measures model with Clinical Pulmonary Infection Score (CPIS) as the response variable. In a planned subset of subjects, ETTs were cultured at extubation. RESULTS: Application of a preintubation dose of CHX did not provide benefit over the intervention period beyond that afforded by daily oral CHX following intubation. ETT colonization at extubation was < 20% in both groups (no statistically significant difference). Mean CPIS remained below 6 (VAP threshold score) in both groups. CONCLUSIONS: Although it is feasible to deliver CHX prior to intubation (including emergent or urgent intubation), the results suggest that preintubation CHX may be inconsequential when the ventilator bundle, including daily oral CHX, is in place. During the preintubation period, providers should focus their attention on other critical activities. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00893763; URL: www.clinicaltrials.gov PMID:25317722

  7. Peripheral neuropathy associated with monoclonal IgG of undetermined significance: clinical, electrophysiologic, pathologic and therapeutic study of 14 cases.

    PubMed

    Hermosilla, E; Lagueny, A; Vital, C; Vital, A; Ferrer, X; Steck, A; Julien, J

    1996-01-01

    Fourteen patients with peripheral neuropathy and monoclonal IgG of undetermined significance are reported with a retrospective study of the clinical features, electrophysiologic and sural nerve biopsy findings. There were two groups. Five patients had a relapsing chronic sensorimotor polyneuropathy with clinical (5/5), electrophysiologic (4/5) and pathologic (5/5) features compatible with chronic inflammatory demyelinating polyneuropathies (CIDP). The nine others had a slowly progressive sensory (5/9) (SPNP) or sensorimotor (4/9) (SMPNP) axonal polyneuropathy. Four patients of the first group were treated with intravenous human immunoglobulin (400 mg/kg/day for five days) with significant clinical improvement. The motor conduction velocities and distal latencies of two of these patients improved following treatment, thus matching the clinical improvement. Our results on peripheral nerve biopsies confirm the differentiation of patients with CIDP from those with SMPNP and SPNP. There was no specific immunologic serologic reactivity in any of the cases. PMID:10975722

  8. Decreased expression of Beclin-1 is significantly associated with a poor prognosis in oral tongue squamous cell carcinoma

    PubMed Central

    Hu, Zedong; Zhong, Zhaoming; Huang, Shaohui; Wen, Haojie; Chen, Xue; Chu, Hongying; Li, Qiuli; Sun, Chuanzheng

    2016-01-01

    The autophagy-related gene Beclin-1 is critical in the regulation of tumourigenesis and progression, but its role in oral tongue squamous cell carcinoma (OTSCC) has not yet been reported. This study aimed to investigate Beclin-1 expression and its significance in OTSCC. Beclin-1 expression was assessed by reverse transcription-quantitative polymerase chain reaction or western blot analysis in 14 OTSCC tissues and matched adjacent noncancerous tissues as well as in 5 OTSCC cell lines and a normal tongue epithelial cell line. Beclin-1 protein expression was examined by immunohistochemistry in 133 OTSCC specimens, and the correlation between Beclin-1 expression and clinicopathological features was investigated. Furthermore, MTT and colony formation assays were performed to investigate the effect of Beclin-1 on the proliferation and clonogenicity of OTSCC cells. It was demonstrated that Beclin-1 expression was significantly decreased in the majority of the 14 OTSCC tissues and the 5 OTSCC cell lines relative to the matched non-cancerous tissues and the normal tongue epithelial cell line, respectively. Immunohistochemistry analysis revealed that decreased Beclin-1 expression was significantly correlated with poor differentiation, lymph node metastasis, advanced clinical tumour-node-metastasis stage, and a poor prognosis in patients with OTSCC. The in vitro assays indicated that the overexpression of Beclin-1 significantly inhibits the proliferation and clonogenicity of OTSCC cells. These results demonstrate that Beclin-1 acts as a tumour suppressor in the development or progression of OTSCC and that Beclin-1 may represent a novel prognostic marker for patients with OTSCC. PMID:27356955

  9. Decreased expression of Beclin‑1 is significantly associated with a poor prognosis in oral tongue squamous cell carcinoma.

    PubMed

    Hu, Zedong; Zhong, Zhaoming; Huang, Shaohui; Wen, Haojie; Chen, Xue; Chu, Hongying; Li, Qiuli; Sun, Chuanzheng

    2016-08-01

    The autophagy-related gene Beclin-1 is critical in the regulation of tumourigenesis and progression, but its role in oral tongue squamous cell carcinoma (OTSCC) has not yet been reported. This study aimed to investigate Beclin‑1 expression and its significance in OTSCC. Beclin‑1 expression was assessed by reverse transcription‑quantitative polymerase chain reaction or western blot analysis in 14 OTSCC tissues and matched adjacent noncancerous tissues as well as in 5 OTSCC cell lines and a normal tongue epithelial cell line. Beclin‑1 protein expression was examined by immunohistochemistry in 133 OTSCC specimens, and the correlation between Beclin‑1 expression and clinicopathological features was investigated. Furthermore, MTT and colony formation assays were performed to investigate the effect of Beclin‑1 on the proliferation and clonogenicity of OTSCC cells. It was demonstrated that Beclin‑1 expression was significantly decreased in the majority of the 14 OTSCC tissues and the 5 OTSCC cell lines relative to the matched non‑cancerous tissues and the normal tongue epithelial cell line, respectively. Immunohistochemistry analysis revealed that decreased Beclin‑1 expression was significantly correlated with poor differentiation, lymph node metastasis, advanced clinical tumour‑node‑metastasis stage, and a poor prognosis in patients with OTSCC. The in vitro assays indicated that the overexpression of Beclin‑1 significantly inhibits the proliferation and clonogenicity of OTSCC cells. These results demonstrate that Beclin‑1 acts as a tumour suppressor in the development or progression of OTSCC and that Beclin‑1 may represent a novel prognostic marker for patients with OTSCC. PMID:27356955

  10. The demographics of significant firearm injury in Canadian trauma centres and the associated predictors of inhospital mortality

    PubMed Central

    Finley, Christian J.; Hemenway, David; Clifton, Joanne; Brown, D. Ross; Simons, Richard K.; Hameed, S. Morad

    2008-01-01

    Objective Our primary objective was to evaluate demographic and causal factors of inhospital mortality for significant firearm-related injuries (i.e., those with an Injury Severity Score [ISS] > 12) in Canadian trauma centres. Methods We analyzed data submitted to the Canadian Institute for Health Information (CIHI) in the National Trauma Registry for all firearm-injured patients for fiscal years 1999–2003. Univariate and bivariate adjusting for ISS and multivariate logistic regression were performed. Results Men accounted for 94% of the 784 injured. In all patients, the percentages of self-inflicted, intentional, unintentional and unknown injuries were 27.8%, 60.3%, 6.1% and 5.7%, respectively. The inhospital fatality rate was 39.8%, with 83% of fatalities occurring on the first day. Two-thirds of patients were discharged home. Univariate and adjusted analysis found that ISS, first systolic blood pressure (BP), first systolic BP under 100, first Glasgow Coma Scale (GCS) score, age over 45 years, self-inflicted injury, intentional injury and injury at home significantly worsened the odds ratio of death in hospital and that police shooting was relatively beneficial. BP under 100, age over 45 years and a low GCS score had an adjusted odds ratio of death of 4.12, 1.99 and 0.64 per point increase, respectively. The multivariate model showed that ISS, BP under 100, first GCS score, sex and self-inflicted injury were significant in predicting inhospital death. Conclusion A predominance of young men are injured intentionally with handguns in Canada, whereas older patients suffer self-inflicted injuries with long guns. The significant number of firearm deaths, largely in the first day, highlights the importance of preventative strategies and the need for rapid transport of patients to trauma centres for urgent care. PMID:18682765

  11. The addition of rituximab to fludarabine and cyclophosphamide chemotherapy results in a significant improvement in overall survival in patients with newly diagnosed mantle cell lymphoma: results of a randomized UK National Cancer Research Institute trial

    PubMed Central

    Rule, Simon; Smith, Paul; Johnson, Peter W.M.; Bolam, Simon; Follows, George; Gambell, Joanne; Hillmen, Peter; Jack, Andrew; Johnson, Stephen; Kirkwood, Amy A; Kruger, Anton; Pocock, Christopher; Seymour, John F.; Toncheva, Milena; Walewski, Jan; Linch, David

    2016-01-01

    Mantle cell lymphoma is an incurable and generally aggressive lymphoma that is more common in elderly patients. Whilst a number of different chemotherapeutic regimens are active in this disease, there is no established gold standard therapy. Rituximab has been used widely to good effect in B-cell malignancies but there is no evidence that it improves outcomes when added to chemotherapy in this disease. We performed a randomized, open-label, multicenter study looking at the addition of rituximab to the standard chemotherapy regimen of fludarabine and cyclophosphamide in patients with newly diagnosed mantle cell lymphoma. A total of 370 patients were randomized. With a median follow up of six years, rituximab improved the median progression-free survival from 14.9 to 29.8 months (P<0.001) and overall survival from 37.0 to 44.5 months (P=0.005). This equates to absolute differences of 9.0% and 22.1% for overall and progression-free survival, respectively, at two years. Overall response rates were similar, but complete response rates were significantly higher in the rituximab arm: 52.7% vs. 39.9% (P=0.014). There was no clinically significant additional toxicity observed with the addition of rituximab. Overall, approximately 18% of patients died of non-lymphomatous causes, most commonly infections. The addition of rituximab to fludarabine and cyclophosphamide chemotherapy significantly improves outcomes in patients with mantle cell lymphoma. However, these regimens have significant late toxicity and should be used with caution. This trial has been registered (ISRCTN81133184 and clinicaltrials.gov:00641095) and is supported by the UK National Cancer Research Network. PMID:26611473

  12. The addition of rituximab to fludarabine and cyclophosphamide chemotherapy results in a significant improvement in overall survival in patients with newly diagnosed mantle cell lymphoma: results of a randomized UK National Cancer Research Institute trial.

    PubMed

    Rule, Simon; Smith, Paul; Johnson, Peter W M; Bolam, Simon; Follows, George; Gambell, Joanne; Hillmen, Peter; Jack, Andrew; Johnson, Stephen; Kirkwood, Amy A; Kruger, Anton; Pocock, Christopher; Seymour, John F; Toncheva, Milena; Walewski, Jan; Linch, David

    2016-02-01

    Mantle cell lymphoma is an incurable and generally aggressive lymphoma that is more common in elderly patients. Whilst a number of different chemotherapeutic regimens are active in this disease, there is no established gold standard therapy. Rituximab has been used widely to good effect in B-cell malignancies but there is no evidence that it improves outcomes when added to chemotherapy in this disease. We performed a randomized, open-label, multicenter study looking at the addition of rituximab to the standard chemotherapy regimen of fludarabine and cyclophosphamide in patients with newly diagnosed mantle cell lymphoma. A total of 370 patients were randomized. With a median follow up of six years, rituximab improved the median progression-free survival from 14.9 to 29.8 months (P<0.001) and overall survival from 37.0 to 44.5 months (P=0.005). This equates to absolute differences of 9.0% and 22.1% for overall and progression-free survival, respectively, at two years. Overall response rates were similar, but complete response rates were significantly higher in the rituximab arm: 52.7% vs. 39.9% (P=0.014). There was no clinically significant additional toxicity observed with the addition of rituximab. Overall, approximately 18% of patients died of non-lymphomatous causes, most commonly infections. The addition of rituximab to fludarabine and cyclophosphamide chemotherapy significantly improves outcomes in patients with mantle cell lymphoma. However, these regimens have significant late toxicity and should be used with caution. This trial has been registered (ISRCTN81133184 and clinicaltrials.gov:00641095) and is supported by the UK National Cancer Research Network. PMID:26611473

  13. Associations between hurtful weight-related comments by family and significant other and the development of disordered eating behaviors in young adults

    PubMed Central

    Eisenberg, Marla E.; Berge, Jerica M.; Fulkerson, Jayne A.; Neumark-Sztainer, Dianne

    2012-01-01

    Background Research has found that weight-teasing is associated with disordered eating in adolescents. This study expands on the existing research by examining associations between hurtful weight comments by family and a significant other and disordered eating in young adults. Methods Data come from 1,902 young adults (mean age 25) who completed surveys in 1998, 2003 and 2009. Correlations were examined between receiving hurtful comments from family and significant others, and four disordered eating behaviors in young adulthood, adjusting for prior disordered eating and prior teasing. Results Disordered eating behaviors were common in young adulthood, and were associated with hearing hurtful weight-related comments from family members and a significant other, for both females and males. Conclusion Disordered eating prevention activities, which include messages about the potential harm associated with hurtful weight-related comments, should be expanded to address young adults, and programs may want to target relationship partners. PMID:21898148

  14. Love is the triumph of the imagination: Daydreams about significant others are associated with increased happiness, love and connection.

    PubMed

    Poerio, Giulia L; Totterdell, Peter; Emerson, Lisa-Marie; Miles, Eleanor

    2015-05-01

    Social relationships and interactions contribute to daily emotional well-being. The emotional benefits that come from engaging with others are known to arise from real events, but do they also come from the imagination during daydreaming activity? Using experience sampling methodology with 101 participants, we obtained 371 reports of naturally occurring daydreams with social and non-social content and self-reported feelings before and after daydreaming. Social, but not non-social, daydreams were associated with increased happiness, love and connection and this effect was not solely attributable to the emotional content of the daydreams. These effects were only present when participants were lacking in these feelings before daydreaming and when the daydream involved imagining others with whom the daydreamer had a high quality relationship. Findings are consistent with the idea that social daydreams may function to regulate emotion: imagining close others may serve the current emotional needs of daydreamers by increasing positive feelings towards themselves and others. PMID:25584779

  15. The Longitudinal Transcriptomic Response of the Substantia Nigra to Intrastriatal 6-Hydroxydopamine Reveals Significant Upregulation of Regeneration-Associated Genes

    PubMed Central

    Cole-Strauss, Allyson; Grabinski, Tessa; Mattingly, Zachary R.; Winn, Mary E.; Steece-Collier, Kathy; Sortwell, Caryl E.; Manfredsson, Fredric P.; Lipton, Jack W.

    2015-01-01

    We hypothesized that the study of gene expression at 1, 2, 4, 6 and 16 weeks in the substantia nigra (SN) after intrastriatal 6-OHDA in the Sprague-Dawley rat (rattus norvegicus) would identify cellular responses during the degenerative process that could be axoprotective. Specifically, we hypothesized that genes expressed within the SN that followed a profile of being highly upregulated early after the lesion (during active axonal degeneration) and then progressively declined to baseline over 16 weeks as DA neurons died are indicative of potential protective responses to the striatal 6-OHDA insult. Utilizing a κ-means cluster analysis strategy, we demonstrated that one such cluster followed this hypothesized expression pattern over time, and that this cluster contained several interrelated transcripts that are classified as regeneration-associated genes (RAGs) including Atf3, Sprr1a, Ecel1, Gadd45a, Gpnmb, Sox11, Mmp19, Srgap1, Rab15,Lifr, Trib3, Tgfb1, and Sema3c. All exemplar transcripts tested from this cluster (Sprr1a, Ecel1, Gadd45a, Atf3 and Sox11) were validated by qPCR and a smaller subset (Sprr1a, Gadd45a and Sox11) were shown to be exclusively localized to SN DA neurons using a dual label approach with RNAScope in situ hybridization and immunohistochemistry. Upregulation of RAGs is typically associated with the response to axonal injury in the peripheral nerves and was not previously reported as part of the axodegenerative process for DA neurons of the SN. Interestingly, as part of this cluster, other transcripts were identified based on their expression pattern but without a RAG provenance in the literature. These "RAG-like" transcripts need further characterization to determine if they possess similar functions to or interact with known RAG transcripts. Ultimately, it is hoped that some of the newly identified axodegeneration-reactive transcripts could be exploited as axoprotective therapies in PD and other neurodegenerative diseases. PMID:25992874

  16. Significant differences in fecal microbiota are associated with various stages of glucose tolerance in African American male veterans.

    PubMed

    Ciubotaru, Irina; Green, Stefan J; Kukreja, Subhash; Barengolts, Elena

    2015-11-01

    The importance of gut microbiota in pathogenesis of diabetes remains unknown. This study investigated the relationship between microbiota and metabolic markers in African American men (AAM) with prediabetes and hypovitaminosis D. The study was ancillary to a randomized trial of vitamin D supplementation with weekly ergocalciferol (50,000 IU) conducted in AAM veterans over 12 months (D Intervention in Veterans Affairs). Glycemic groups (Gr) were characterized based on changes in oral glucose tolerance between baseline and exit. Subjects with stable normal glucose tolerance were assigned to Gr-1 and those with stable prediabetes (impaired glucose tolerance and impaired fasting glucose) to Gr-2. Microbiota composition was analyzed in stool collected at the exit (n = 115) and compared between Gr-1 and Gr-2, as well as between the lowest and highest quartiles of dietary intake of energy and fat, hemoglobin A1c, and serum 25-hydroxyvitamin D (25[OH]D) level. Differences between Gr-1 and Gr-2 included the Bacteroidetes/Firmicutes and Bacteroidales/Clostridia ratios and differences in genera such as Ruminococcus and Dialister. Changes in specific taxa associated with the lowest and highest quartiles of 25(OH)D (eg, Ruminococcus, Roseburia, Blautia, Dorea) were clearly distinct from those of dietary intake (eg, Bacteroides, Bacteroides/Prevotella ratio) or A1c (eg, Faecalibacterium, Catenibacterium, Streptococcus). These findings suggest a novel interaction between microbiota and vitamin D and a role for microbiota in early stages of diabetes development. Although results suggest that specific taxa are associated with glycemic stability over time, a causative relationship between microbiota makeup and dysglycemia is still to be demonstrated. PMID:26209747

  17. A longitudinal study on the significance of environmental and individual factors associated with the development of essential hypertension.

    PubMed Central

    Lindgärde, F; Furu, M; Ljung, B O

    1987-01-01

    Altogether 379 men of the same age have been followed for more than 40 years, mainly as regards socioeconomic conditions during the first 10 years as well as cognitive ability measured at the ages of 10 and 20, education, income development, and psychosocial conditions in adulthood. At the age of 48 a health investigation was performed. In order to identify possible risk factors associated with the development of raised blood pressure 38 subjects with essential hypertension were compared with 155 men without any obvious mental or somatic diseases. No differences regarding socioeconomic conditions during childhood could be observed between the two groups. However, there was a very strong difference between father's education and the son's cognitive ability in the group with hypertension. The low income development for the group with hypertension can probably be explained partly by the lower cognitive ability. In the total group there was a positive correlation between IQ at the age of 10 and income at the age of 43 (r = 0.42; p less than 0.001). The hypertensive men were psychosocially disadvantaged with respect to divorce rate and job dissatisfaction, and furthermore they reported low physical activity during leisure time. Hypertensive men were more obese and had inferior respiratory function. The observation that a lower cognitive ability seems to be related to the development of hypertension is compatible with the observation that early mortality in this investigated group has a correlation of a low IQ with poor socioeconomic conditions in childhood. PMID:3443815

  18. [Urinary tract infection associated with urinary calculi. 1. The significance of urinary tract infection in urinary calculi].

    PubMed

    Takeuchi, H; Okada, Y; Yoshida, O; Arai, Y; Tomoyoshi, T

    1989-05-01

    We investigated 158 cases of urinary stones (infection stones 56, metabolic stones 102) with special reference to pyuria, bacteriuria, stone culture and urease activities of isolated bacteria. Abacterial pyuria was noted in 9 out of 49 (18%) infection stones and in 53 of 77 (69%) metabolic stones. Bacteriuria was noted in 79% of the infection stones and 26% of the metabolic stones. Sixty-seven percent of the infection stones were infected with mainly urea splitting bacteria such as Proteus mirabilis and Staphylococcus. Twenty-three percent of metabolic stones were also infected. Though E. coli, a non-urea splitting bacteria, was isolated most frequently from metabolic stones, urease positive Staphylococcus and Pseudomonas were also isolated. Bacteria within stones could be predicted on the basis of urine culture results of only 20 of 41 infection stones and 8 of 24 metabolic stones. These facts are useful for selection of some antibiotics in the treatment of urinary tract infections associated with urinary calculi. Urinary infections of urea splitting bacteria in infection stones are thought to be initial factors of stone formation and those of non-urea splitting bacteria are to be superimposed. However, urea splitting bacteria in metabolic stones may convert them into infection stones in future. PMID:2801372

  19. Significant elevation of tumour-associated isoforms of soluble CD44 in serum of normal individuals caused by cigarette smoking.

    PubMed

    Kittl, E M; Ruckser, R; Rech-Weichselbraun, I; Hinterberger, W; Bauer, K

    1997-02-01

    While performing a prospective study on sCD44 variant isoforms as tumour markers in certain malignancies, we detected relevant differences in the control group between non-smokers and smokers. For a detailed evaluation of these findings, serum levels of sCD44 variant proteins, including sequences encoded by exon v5 and exon v6, respectively, were adjusted to sex, age and smoking habit. We were able to demonstrate a significant elevation of serum levels of sCD44v5 and sCD44v6 in normal individuals due to cigarette smoking (non-smokers to smokers: sCD44v5: 33 +/- 11 microg/l to 62 +/- 30 microg/l; sCD44v6: 142 +/- 34 microg/l to 232 +/- 86 microg/l). Stepwise multiple linear regression analysis of the concentrations of sCD44v5 and sCD44v6 on the possible influence factors sex, age and smoking habit revealed cigarette smoking as the only factor influencing these isoforms (both p < 0.001). Further investigations have to elucidate a possible clinical importance of these findings in smokers. However, in patients with suspected or proven malignancy the diagnostic specifity of sCD44v5 and sCD44v6 is diminished due to this observation. PMID:9056747

  20. A genome-wide association study of posttraumatic stress disorder identifies the retinoid-related orphan receptor alpha (RORA) gene as a significant risk locus

    PubMed Central

    Logue, Mark W.; Baldwin, Clinton; Guffanti, Guia; Melista, Efi; Wolf, Erika J.; Reardon, Annemarie F.; Uddin, Monica; Wildman, Derek; Galea, Sandro; Koenen, Karestan C.; Miller, Mark W.

    2012-01-01

    We describe the results of the first genome-wide association study of PTSD performed using trauma-exposed white non-Hispanic participants from a cohort of veterans and their intimate partners (295 cases and 196 controls). Several SNPs yielded evidence of association. One SNP (rs8042149), located in the retinoid-related orphan receptor alpha gene (RORA), reached genome-wide significance. Nominally significant associations were observed for other RORA SNPs in two African American replication samples—one from the veteran cohort (43 cases and 41 controls) and another independent cohort (100 cases and 421 controls). However, only the associated SNP from the veteran African American replication sample survived gene-level multiple testing correction. RORA has been implicated in prior GWAS studies of psychiatric disorders and is known to play an important role in neuroprotection and other behaviorally-relevant processes. This study represents an important step towards identifying the genetic underpinnings of PTSD. PMID:22869035

  1. Significant improvement of the recombinant Borrelia-specific immunoglobulin G immunoblot test by addition of VlsE and a DbpA homologue derived from Borrelia garinii for diagnosis of early neuroborreliosis.

    PubMed

    Schulte-Spechtel, Ulrike; Lehnert, Gisela; Liegl, Gaby; Fingerle, Volker; Heimerl, Christiane; Johnson, Barbara J B; Wilske, Bettina

    2003-03-01

    We investigated whether the recombinant Borrelia Western blot test previously described (B. Wilske, C. Habermann, V. Fingerle, B. Hillenbrand, S. Jauris-Heipke, G. Lehnert, I. Pradel, D. Rössler, and U. Schulte-Spechtel, Med. Microbiol. Immunol. 188:139-144, 1999) can be improved by the addition of VlsE and additional DbpA and OspC homologues. By using a panel of sera from 36 neuroborreliosis patients and 67 control patients, the diagnostic sensitivity of the recombinant immunoblot test was significantly increased (86.1% versus 52.7%) without loss of specificity and was higher (86.1% versus 63.8%) than that of the conventional whole-cell lysate immunoblot test (U. Hauser, G. Lehnert, R. Lobentanzer, and B. Wilske, J. Clin. Microbiol. 35:1433-1444, 1997). Improvement was mainly due to the presence of VlsE and DbpA. PMID:12624072

  2. Surface deformation associated with the 2013 Mw7.7 Balochistan earthquake: Geologic slip rates may significantly underestimate strain release

    NASA Astrophysics Data System (ADS)

    Gold, Ryan; Reitman, Nadine; Briggs, Richard; Barnhart, William; Hayes, Gavin

    2015-04-01

    sections with narrow deformation zones in order to capture the full deformation field. Our results imply that hazard analyses based on geologically-determined fault slip rates (e.g., near-field) should consider the significant and heterogeneous mismatch we document between on- and off-fault coseismic deformation.

  3. Serum Sialic Acid Level Is Significantly Associated with Nonalcoholic Fatty Liver Disease in a Nonobese Chinese Population: A Cross-Sectional Study

    PubMed Central

    Lu, Zhenya; Ma, Han; Xu, Chengfu; Shao, Zhou; Cen, Chao; Li, Youming

    2016-01-01

    Background/Aim. To investigate the association between serum sialic acid (SA) levels and nonalcoholic fatty liver disease (NAFLD) in a nonobese Chinese population. Methods. A cross-sectional study was performed among the 5916 adults who took their annual health examinations at International Health Care Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, from December 2013 to November 2014. Results. A total of 693 (11.71%) subjects fulfilled the diagnostic criteria of NAFLD, and NAFLD patients had significantly higher serum SA levels than controls (P < 0.001). The prevalence of NAFLD was positively associated with serum SA levels (P for trend <0.001). Serum sialic acid levels are significantly associated with features of metabolic syndrome (Ps < 0.01). Multivariate logistic regression analysis showed that serum SA level was significantly associated with risk for NAFLD (odds ratio: 1.018, 95%; confidence interval: 1.007–1.030; P = 0.002). Conclusions. Our results suggest for the first time that NAFLD patients had higher serum SA level than controls, and increased serum SA level is significantly associated with risk for NAFLD in a large nonobese Chinese population. PMID:27042666

  4. Two poplar-associated bacterial isolates induce additive favorable responses in a constructed plant-microbiome system

    DOE PAGESBeta

    Jawdy, Sara S.; Gunter, Lee E.; Engle, Nancy L.; Yang, Zamin Koo; Lu, Tse-Yuan S.; Tschaplinski, Timothy J.; Tuskan, Gerald A.; Doktycz, Mitchel John; Pelletier, Dale A.; Weston, David J.; et al

    2016-04-26

    Here, the biological function of the plant-microbiome system is the result of contributions from the host plant and microbiome members. In this work we study the function of a simplified community consisting of Pseudomonas and Burkholderia bacterial strains isolated from Populus hosts and inoculated on axenic Populus cutting in controlled laboratory conditions. Inoculation individually with either bacterial isolate increased root growth relative to uninoculated controls. Root area, photosynthetic efficiency, gene expression and metabolite expression data in individual and dual inoculated treatments indicate that the effects of these bacteria are unique and additive, suggesting that the function of a microbiome communitymore » may be predicted from the additive functions of the individual members.« less

  5. Two Poplar-Associated Bacterial Isolates Induce Additive Favorable Responses in a Constructed Plant-Microbiome System

    PubMed Central

    Timm, Collin M.; Pelletier, Dale A.; Jawdy, Sara S.; Gunter, Lee E.; Henning, Jeremiah A.; Engle, Nancy; Aufrecht, Jayde; Gee, Emily; Nookaew, Intawat; Yang, Zamin; Lu, Tse-Yuan; Tschaplinski, Timothy J.; Doktycz, Mitchel J.; Tuskan, Gerald A.; Weston, David J.

    2016-01-01

    The biological function of the plant-microbiome system is the result of contributions from the host plant and microbiome members. The Populus root microbiome is a diverse community that has high abundance of β- and γ-Proteobacteria, both classes which include multiple plant-growth promoting representatives. To understand the contribution of individual microbiome members in a community, we studied the function of a simplified community consisting of Pseudomonas and Burkholderia bacterial strains isolated from Populus hosts and inoculated on axenic Populus cutting in controlled laboratory conditions. Both strains increased lateral root formation and root hair production in Arabidopsis plate assays and are predicted to encode for different functions related to growth and plant growth promotion in Populus hosts. Inoculation individually, with either bacterial isolate, increased root growth relative to uninoculated controls, and while root area was increased in mixed inoculation, the interaction term was insignificant indicating additive effects of root phenotype. Complementary data including photosynthetic efficiency, whole-transcriptome gene expression and GC-MS metabolite expression data in individual and mixed inoculated treatments indicate that the effects of these bacterial strains are unique and additive. These results suggest that the function of a microbiome community may be predicted from the additive functions of the individual members. PMID:27200001

  6. Administrators' Perceptions of Factors Related to Student Retention at Colleges with a Significant Black Student Enrollment Affiliated with the Association for Biblical Higher Education

    ERIC Educational Resources Information Center

    Wilson, Wesley B.

    2013-01-01

    This study described and explored the factors perceived as relevant to student retention by administrators at colleges and universities with significant Black student populations. The sample was 31 institutions affiliated with the Association for Biblical Higher Education (ABHE) that had Black student enrollment of 20% or more. The study sought to…

  7. Independent and additive association of prenatal famine exposure and intermediary life conditions with adult mortality age 18–63 years

    PubMed Central

    Ekamper, P.; van Poppel, F.; Stein, A.D.; Lumey, L.H.

    2014-01-01

    Objectives To quantify the relation between prenatal famine exposure and adult mortality, taking into account mediating effects of intermediary life conditions. Design Historical follow-up study. Setting The Dutch famine (Hunger Winter) of 1944–1945 which occurred towards the end of WWII in occupied Netherlands. Study population From 408,015 Dutch male births born 1944–1947, examined for military service at age 18, we selected for follow-up all men born at the time of the famine in six affected cities in the Western Netherlands (n=25,283), and a sample of unexposed time (n=10,667) and place (n=9,087) controls. These men were traced and followed for mortality through the national population and death record systems. Outcome measure All-cause mortality between ages 18 and 63 years using Cox proportional hazards models adjusted for intermediary life conditions. Results An increase in mortality was seen after famine exposure in early gestation (HR 1.12; 95% confidence interval (CI): 1.01 to 1.24) but not late gestation (HR 1.04; 95% CI: 0.96 to 1.13). Among intermediary life conditions at age 18 years, educational level was inversely associated with mortality and mortality was elevated in men with fathers with a manual versus non-manual occupations (HR 1.08; CI: 1.02 to 1.16) and in men who were declared unfit for military service (HR 1.44; CI: 1.31 to 1.58). Associations of intermediate factors with mortality were independent of famine exposure in early life and associations between prenatal famine exposure and adult mortality were independent of social class and education at age 18. Conclusions Timing of exposure in relation to the stage of pregnancy may be of critical importance for later health outcomes independent of intermediary life conditions. PMID:24262812

  8. Additive reductions in zebrafish PRPS1 activity result in a spectrum of deficiencies modeling several human PRPS1-associated diseases

    PubMed Central

    Pei, Wuhong; Xu, Lisha; Varshney, Gaurav K.; Carrington, Blake; Bishop, Kevin; Jones, MaryPat; Huang, Sunny C.; Idol, Jennifer; Pretorius, Pamela R.; Beirl, Alisha; Schimmenti, Lisa A.; Kindt, Katie S.; Sood, Raman; Burgess, Shawn M.

    2016-01-01

    Phosphoribosyl pyrophosphate synthetase-1 (PRPS1) is a key enzyme in nucleotide biosynthesis, and mutations in PRPS1 are found in several human diseases including nonsyndromic sensorineural deafness, Charcot-Marie-Tooth disease-5, and Arts Syndrome. We utilized zebrafish as a model to confirm that mutations in PRPS1 result in phenotypic deficiencies in zebrafish similar to those in the associated human diseases. We found two paralogs in zebrafish, prps1a and prps1b and characterized each paralogous mutant individually as well as the double mutant fish. Zebrafish prps1a mutants and prps1a;prps1b double mutants showed similar morphological phenotypes with increasingly severe phenotypes as the number of mutant alleles increased. Phenotypes included smaller eyes and reduced hair cell numbers, consistent with the optic atrophy and hearing impairment observed in human patients. The double mutant also showed abnormal development of primary motor neurons, hair cell innervation, and reduced leukocytes, consistent with the neuropathy and recurrent infection of the human patients possessing the most severe reductions of PRPS1 activity. Further analyses indicated the phenotypes were associated with a prolonged cell cycle likely resulting from reduced nucleotide synthesis and energy production in the mutant embryos. We further demonstrated the phenotypes were caused by delays in the tissues most highly expressing the prps1 genes. PMID:27425195

  9. Additive reductions in zebrafish PRPS1 activity result in a spectrum of deficiencies modeling several human PRPS1-associated diseases.

    PubMed

    Pei, Wuhong; Xu, Lisha; Varshney, Gaurav K; Carrington, Blake; Bishop, Kevin; Jones, MaryPat; Huang, Sunny C; Idol, Jennifer; Pretorius, Pamela R; Beirl, Alisha; Schimmenti, Lisa A; Kindt, Katie S; Sood, Raman; Burgess, Shawn M

    2016-01-01

    Phosphoribosyl pyrophosphate synthetase-1 (PRPS1) is a key enzyme in nucleotide biosynthesis, and mutations in PRPS1 are found in several human diseases including nonsyndromic sensorineural deafness, Charcot-Marie-Tooth disease-5, and Arts Syndrome. We utilized zebrafish as a model to confirm that mutations in PRPS1 result in phenotypic deficiencies in zebrafish similar to those in the associated human diseases. We found two paralogs in zebrafish, prps1a and prps1b and characterized each paralogous mutant individually as well as the double mutant fish. Zebrafish prps1a mutants and prps1a;prps1b double mutants showed similar morphological phenotypes with increasingly severe phenotypes as the number of mutant alleles increased. Phenotypes included smaller eyes and reduced hair cell numbers, consistent with the optic atrophy and hearing impairment observed in human patients. The double mutant also showed abnormal development of primary motor neurons, hair cell innervation, and reduced leukocytes, consistent with the neuropathy and recurrent infection of the human patients possessing the most severe reductions of PRPS1 activity. Further analyses indicated the phenotypes were associated with a prolonged cell cycle likely resulting from reduced nucleotide synthesis and energy production in the mutant embryos. We further demonstrated the phenotypes were caused by delays in the tissues most highly expressing the prps1 genes. PMID:27425195

  10. Serologically silent hepatitis B virus coinfection in patients with hepatitis C virus-associated chronic liver disease: clinical and virological significance.

    PubMed

    Fukuda, R; Ishimura, N; Niigaki, M; Hamamoto, S; Satoh, S; Tanaka, S; Kushiyama, Y; Uchida, Y; Ihihara, S; Akagi, S; Watanabe, M; Kinoshita, Y

    1999-07-01

    Frequent coinfection of surface antigen-negative hepatitis B virus (silent HBV) in hepatitis C virus (HCV)-associated chronic liver disease (CLD) has been reported. The clinical and virological significance of silent HBV infection was investigated in 65 patients with HCV-associated CLD who subsequently received interferon (IFN) therapy. HBV DNA was detected in 34 (52.3%) patients by a nested polymerase chain reaction (PCR). Virologically, all of the 34 patients were found to have HBV with an eight-nucleotide deletion in the core promoter. Coinfection of silent HBV was more frequent with HCV genotype 1b than in 2a (64.3% vs. 28.6%, P<.01). With HCV genotype 1b, the serum RNA level was significantly higher (> or =10(6) copies per milliliter vs. < or =10(5) copies per milliliter) in patients with silent HBV than those without coinfection (P<.01). Clinically, silent HBV was associated with a higher level of serum alanine aminotransferase (158.5+/-104.8 vs. 121.8+/-78.6 IU/I; mean +/- SD) and a greater histological activity of hepatitis as evaluated by histological activity index score (9.4+/-3.8 vs. 8.6+/-4.5; mean +/- SD), although it was not statistically significant. Silent HBV was also associated with poor efficacy of IFN therapy (P<.01). The results suggest that silent HBV has some promoting effect for HCV replication, at least for HCV genotype 1b, and may affect the histological activity of hepatitis and IFN response in HCV-associated CLD. PMID:10447413

  11. Association analysis for detecting significant single nucleotide polymorphisms for phosphorus-deficiency tolerance at the seedling stage in soybean [Glycine max (L) Merr].

    PubMed

    Ning, Lihua; Kan, Guizhen; Du, Wenkai; Guo, Shiwei; Wang, Qing; Zhang, Guozheng; Cheng, Hao; Yu, Deyue

    2016-03-01

    Tolerance to low-phosphorus soil is a desirable trait in soybean cultivars. Previous quantitative trait locus (QTL) studies for phosphorus-deficiency tolerance were mainly derived from bi-parental segregating populations and few reports from natural population. The objective of this study was to detect QTLs that regulate phosphorus-deficiency tolerance in soybean using association mapping approach. Phosphorus-deficiency tolerance was evaluated according to five traits (plant shoot height, shoot dry weight, phosphorus concentration, phosphorus acquisition efficiency and use efficiency) comprising a conditional phenotype at the seedling stage. Association mapping of the conditional phenotype detected 19 SNPs including 13 SNPs that were significantly associated with the five traits across two years. A novel cluster of SNPs, including three SNPs that consistently showed significant effects over two years, that associated with more than one trait was detected on chromosome 3. All favorable alleles, which were determined based on the mean of conditional phenotypic values of each trait over the two years, could be pyramided into one cultivar through parental cross combination. The best three cross combinations were predicted with the aim of simultaneously improving phosphorus acquisition efficiency and use efficiency. These results will provide a thorough understanding of the genetic basis of phosphorus deficiency tolerance in soybean. PMID:27162491

  12. Association analysis for detecting significant single nucleotide polymorphisms for phosphorus-deficiency tolerance at the seedling stage in soybean [Glycine max (L) Merr.

    PubMed Central

    Ning, Lihua; Kan, Guizhen; Du, Wenkai; Guo, Shiwei; Wang, Qing; Zhang, Guozheng; Cheng, Hao; Yu, Deyue

    2016-01-01

    Tolerance to low-phosphorus soil is a desirable trait in soybean cultivars. Previous quantitative trait locus (QTL) studies for phosphorus-deficiency tolerance were mainly derived from bi-parental segregating populations and few reports from natural population. The objective of this study was to detect QTLs that regulate phosphorus-deficiency tolerance in soybean using association mapping approach. Phosphorus-deficiency tolerance was evaluated according to five traits (plant shoot height, shoot dry weight, phosphorus concentration, phosphorus acquisition efficiency and use efficiency) comprising a conditional phenotype at the seedling stage. Association mapping of the conditional phenotype detected 19 SNPs including 13 SNPs that were significantly associated with the five traits across two years. A novel cluster of SNPs, including three SNPs that consistently showed significant effects over two years, that associated with more than one trait was detected on chromosome 3. All favorable alleles, which were determined based on the mean of conditional phenotypic values of each trait over the two years, could be pyramided into one cultivar through parental cross combination. The best three cross combinations were predicted with the aim of simultaneously improving phosphorus acquisition efficiency and use efficiency. These results will provide a thorough understanding of the genetic basis of phosphorus deficiency tolerance in soybean. PMID:27162491

  13. Genome-wide Association Study and Meta-Analysis Identify ISL1 as Genome-wide Significant Susceptibility Gene for Bladder Exstrophy

    PubMed Central

    Draaken, Markus; Knapp, Michael; Pennimpede, Tracie; Schmidt, Johanna M.; Ebert, Anne-Karolin; Rösch, Wolfgang; Stein, Raimund; Utsch, Boris; Hirsch, Karin; Boemers, Thomas M.; Mangold, Elisabeth; Heilmann, Stefanie; Ludwig, Kerstin U.; Jenetzky, Ekkehart; Zwink, Nadine; Moebus, Susanne; Herrmann, Bernhard G.; Mattheisen, Manuel; Nöthen, Markus M.

    2015-01-01

    The bladder exstrophy-epispadias complex (BEEC) represents the severe end of the uro-rectal malformation spectrum, and is thought to result from aberrant embryonic morphogenesis of the cloacal membrane and the urorectal septum. The most common form of BEEC is isolated classic bladder exstrophy (CBE). To identify susceptibility loci for CBE, we performed a genome-wide association study (GWAS) of 110 CBE patients and 1,177 controls of European origin. Here, an association was found with a region of approximately 220kb on chromosome 5q11.1. This region harbors the ISL1 (ISL LIM homeobox 1) gene. Multiple markers in this region showed evidence for association with CBE, including 84 markers with genome-wide significance. We then performed a meta-analysis using data from a previous GWAS by our group of 98 CBE patients and 526 controls of European origin. This meta-analysis also implicated the 5q11.1 locus in CBE risk. A total of 138 markers at this locus reached genome-wide significance in the meta-analysis, and the most significant marker (rs9291768) achieved a P value of 2.13 × 10−12. No other locus in the meta-analysis achieved genome-wide significance. We then performed murine expression analyses to follow up this finding. Here, Isl1 expression was detected in the genital region within the critical time frame for human CBE development. Genital regions with Isl1 expression included the peri-cloacal mesenchyme and the urorectal septum. The present study identified the first genome-wide significant locus for CBE at chromosomal region 5q11.1, and provides strong evidence for the hypothesis that ISL1 is the responsible candidate gene in this region. PMID:25763902

  14. Gene Expression Analysis of the 26S Proteasome Subunit PSMB4 Reveals Significant Upregulation, Different Expression and Association with Proliferation in Human Pulmonary Neuroendocrine Tumours

    PubMed Central

    Mairinger, Fabian Dominik; Walter, Robert Fred Henry; Theegarten, Dirk; Hager, Thomas; Vollbrecht, Claudia; Christoph, Daniel Christian; Worm, Karl; Ting, Saskia; Werner, Robert; Stamatis, Georgios; Mairinger, Thomas; Baba, Hideo; Zarogoulidis, Konstantinos; Huang, Haidong; Li, Qiang; Tsakiridis, Kosmas; Zarogoulidis, Paul; Schmid, Kurt Werner; Wohlschlaeger, Jeremias

    2014-01-01

    Background: Proteasomal subunit PSMB4 was suggested to be a survival gene in an animal model of hepatocellular carcinoma and in glioblastoma cell lines. In pulmonary adenocarcinoma, a high expression of these genes was found to be associated with poor differentiation and survival. This study investigates the gene expression levels of 26S proteasome subunits in human pulmonary neuroendocrine tumours including typical (TC) and atypical (AC) carcinoid tumours as well as small cell (SCLC) and large cell (LCNEC) neuroendocrine carcinomas. Material and methods: Gene expression levels of proteasomal subunits (PSMA1, PSMA5, PSMB4, PSMB5 and PSMD1) were investigated in 80 neuroendocrine pulmonary tumours (each 20 TC, AC, LCNLC and SCLC) and compared to controls. mRNA levels were determined by using TaqMan assays. Immunohistochemistry on tissue microarrays (TMA) was performed to determine the expression of ki67, cleaved caspase 3 and PSMB4. Results: All proteasomal subunit gene expressions were significantly upregulated in TC, AC, SCLC and LCNEC compared to controls. PSMB4 mRNA is differently expressed between all neuroendocrine tumour subtypes demonstrating the highest expression and greatest range in LCNEC (p=0.043), and is significantly associated with proliferative activity (p=0.039). Conclusion: In line with other 26S proteasomal subunits PSMB4 is significantly increased, but differently expressed between pulmonary neuroendocrine tumours and is associated with the proliferative activity. Unlike in pulmonary adenocarcinomas, no association with biological behaviour was observed, suggesting that increased proteasomal subunit gene expression is a common and probably early event in the tumorigenesis of pulmonary neuroendocrine tumours regardless of their differentiation. PMID:25157275

  15. Expression of proteins associated with adipocyte lipolysis was significantly changed in the adipose tissues of the obese spontaneously hypertensive/NDmcr-cp rat

    PubMed Central

    2014-01-01

    Background The etiology of the metabolic syndrome is complex, and is determined by the interplay of both genetic and environmental factors. The present study was designed to identify genes and proteins in the adipose tissues with altered expression in the spontaneously hypertensive/NIH –corpulent rat, SHR/NDmcr-cp (CP) and to find possible molecular targets associated with the pathogenesis or progression of obesity related to the metabolic syndrome. Methods We extracted RNAs and proteins from the epididymal adipose tissues in CP, SHR/Lean (Lean), and Wistar Kyoto (WKY) rats and performed microarray analysis and two-dimensional difference in gel electrophoresis (2D-DIGE) linked to a matrix-assisted laser desorption ionization time-of-flight tandem mass spectrometry (MALDI-TOF/TOF MS). Results The results showed different mRNA and protein expression levels in the adipose tissue: oligo DNA microarray identified 33 genes that were significantly (P < 0.01) up-regulated and 17 genes significantly down-regulated in CP compared with WKY and Lean rats at both 6 and 25 weeks of age. The affected genes-proteins were associated with lipolytic enzymes stimulated by peroxisome proliferator-activated receptor (PPAR) signaling. Further analysis using the 2D-DIGE connected with MALDI-TOF/TOF analysis, the expression of monoglyceride lipase (MGLL) was significantly up-regulated and that of carboxylesterase 3 (CES3) was significantly down-regulated in 6- and 25-week-old CP compared with age-matched control (WKY and Lean rats). Conclusions Our results suggest the possible involvement of proteins associated with adipocyte lipolysis in obesity related to the metabolic syndrome. PMID:24468282

  16. The C(-1019)G 5-HT1A promoter polymorphism and personality traits: no evidence for significant association in alcoholic patients

    PubMed Central

    Koller, G; Bondy, B; Preuss, UW; Zill, P; Soyka, M

    2006-01-01

    The 5HT1A receptor is one of at least 14 different receptors for serotonin which has a role in moderating several brain functions and may be involved in the aetiology of several psychiatric disorders. The C(-1019)G 5-HT1A promoter polymorphism was reported to be associated with major depression, depression-related personality traits and suicidal behavior in various samples. The G(-1019) allele carriers are prone to depressive personality traits and suicidal behavior, because serotonergic neurotransmission is reduced. The aim of this study is to replicate previous findings in a sample of 185 Alcohol-dependent individuals. Personality traits were evaluated using the NEO FFI and TCI. History of suicidal behavior was assessed by a standardized semistructured interview (SSAGA). No significant differences across C(-1019)G 5-HT1A genotype groups were found for TCI temperament and character traits and for NEO FFI personality scales. No association was detected between this genetic variant and history of suicide attempts. These results neither support a role of C(-1019)G 5-HT1A promoter polymorphism in the disposition of personality traits like harm avoidance or neuroticism, nor confirm previous research reporting an involvement of the G allele in suicidal behavior in alcoholics. Significant associations, however, were detected between Babor's Type B with number of suicide attempts in history, high neuroticism and harm avoidance scores in alcoholics. PMID:16504134

  17. Synonymous single nucleotide polymorphisms in the MC4R gene that are significantly associated with milk production traits in water buffaloes.

    PubMed

    Deng, T X; Pang, C Y; Liu, M Q; Zhang, C; Liang, X W

    2016-01-01

    Melanocortin-4 receptor (MC4R) is associated with feed intake, growth, fatness, and carcass composition in many domestic animals. The aim of this study was to evaluate the association of single nucleotide polymorphisms (SNPs) in MC4R with milk production traits in water buffalo. Eight SNPs were identified by direct polymerase chain reaction sequencing of samples from 18 buffaloes. SNPs were then genotyped using the matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) method in 332 buffaloes. Two of eight SNPs were not in Hardy-Weinberg equilibrium. Based on the SNP data, seven haplotypes were constructed. Three SNPs H1 (AGT), H2 (GAT), and H3 (GAC) accounted for 93.0% of the total individuals. Statistical analysis indicated that the SNP g.1104C>T was significantly associated with milk yield, protein, and fat percentage (P < 0.05). In conclusion, these results provide evidence that polymorphisms in the buffalo MC4R gene are associated with milk production traits and might be potential biomarkers for water buffalo breeding. PMID:27420995

  18. Alpha2C-adrenoceptor Del322-325 polymorphism and risk of psychiatric disorders: significant association with opiate abuse and dependence.

    PubMed

    Rivero, Guadalupe; Martín-Guerrero, Idoia; de Prado, Elena; Gabilondo, Ane M; Callado, Luis F; García-Sevilla, Jesús A; García-Orad, África; Meana, J Javier

    2016-06-01

    Objectives α2C-adrenoceptors (α2C-AR) are involved in behavioural responses relevant to psychiatric disorders and suicide completion. The genetic polymorphism α2CDel322-325-AR confers a loss-of-function phenotype. Functional human studies have associated α2CDel322-325-AR polymorphism with major depression pathophysiology. The aim of this study was to analyse, for the first time, the association of α2CDel322-325-AR polymorphism with suicide completion and with related psychiatric disorders: major depression, schizophrenia, opiate and alcohol abuse and dependence. Methods Post-mortem brain DNA was extracted (n = 516) and genotyping performed by HaeIII restriction endonuclease digestion of PCR products and DNA fragment analysis on capillary sequencer. Amplified products were sequenced to confirm the presence of the polymorphism. Results The frequency of α2CDel322-325-AR in suicide (9%, n = 236) and non-suicide victims (11%, n = 280) was similar. Genotype frequencies for the α2CDel322-325-AR polymorphism in depressed (15%, n = 39) and schizophrenic subjects (18%, n = 39) were higher than in controls (7%, n = 187), but these differences did not reach statistical significance (P = 0.125 and P = 0.063, respectively). A selective and significant association of α2CDel322-325-AR polymorphism with opiate abuse and dependence was found (23%, n = 35, P = 0.011). Conclusions Our results indicate that α2CDel322-325-AR may play a role in the pathophysiology of opiate abuse and dependence and raise the interest for larger genetic associative studies. PMID:27007576

  19. Expression and splicing of the unfolded protein response gene XBP-1 are significantly associated with clinical outcome of endocrine-treated breast cancer.

    PubMed

    Davies, Michael P A; Barraclough, Dong Liu; Stewart, Ceri; Joyce, Kathryn A; Eccles, Richard M; Barraclough, Roger; Rudland, Philip S; Sibson, David Ross

    2008-07-01

    X-box binding protein 1 (XBP-1) is stimulated by endoplasmic reticulum stress as part of the unfolded protein response (UPR), which can promote apoptosis or cell survival. Non-conventional splicing, stimulated during the UPR, converts mRNA for "unspliced" XBP-1U to "spliced" XBP-1S mRNA. XBP-1 mRNA is oestrogen-responsive, but XBP-1S confers oestrogen independence and anti-oestrogen resistance to breast cancer cell lines. We therefore evaluated XBP-1 mRNA splicing as a factor in response of breast cancer patients to endocrine treatment. XBP-1 isoforms were measured by quantitative RT-PCR in 100 primary breast cancer patients treated with adjuvant tamoxifen (including 30 ER alpha-negative cases). In ER alpha-positive cases, levels of XBP-1U mRNA correlated with ER alpha mRNA levels and were lower in grade 3 tumors. Higher levels of XBP-1U mRNA were significantly associated with breast cancer survival (Log-rank p = 0.002; Cox hazard ratio (HR) 0.2, p = 0.005), independent of grade, size, nodal status and progesterone receptor status. However, in the full cohort, higher ratios of XBP-1S/XBP-1U mRNA (indicating enhanced splicing) were associated with poor survival (Log-rank p = 0.03; Cox HR 2.3, p = 0.03) and related factors: ER alpha-negative status, progesterone receptor negative status, grade 3 tumors and greater proliferation. Significant associations with poor outcome were also seen for XBP-1 splicing in ER alpha-positive cases. Our findings, that XBP-1 isoforms are differently associated with outcome of endocrine therapy for patients, can be explained by higher levels of dominant-negative XBP-1U favouring apoptosis of tumor cells and higher levels of XBP-1S increasing tumor survival. PMID:18386815

  20. Lack of significant association between type 2 diabetes mellitus with longitudinal change in diurnal salivary cortisol: the multiethnic study of atherosclerosis.

    PubMed

    Spanakis, Elias K; Wang, Xu; Sánchez, Brisa N; Diez Roux, Ana V; Needham, Belinda L; Wand, Gary S; Seeman, Teresa; Golden, Sherita Hill

    2016-07-01

    Cross-sectional association has been shown between type 2 diabetes and hypothalamic-pituitary-adrenal (HPA) axis dysregulation; however, the temporality of this association is unknown. Our aim was to determine if type 2 diabetes is associated with longitudinal change in daily cortisol curve features. We hypothesized that the presence of type 2 diabetes may lead to a more blunted and abnormal HPA axis profile over time, suggestive of increased HPA axis dysregulation. This was a longitudinal cohort study, including 580 community-dwelling individuals (mean age 63.7 ± 9.1 years; 52.8 % women) with (n = 90) and without (n = 490) type 2 diabetes who attended two MultiEthnic Study of Atherosclerosis Stress ancillary study exams separated by 6 years. Outcome measures that were collected were wake-up and bedtime cortisol, cortisol awakening response (CAR), total area under the curve (AUC), and early, late, and overall decline slopes. In univariate analyses, wake-up and AUC increased over 6 years more in persons with as compared to those without type 2 diabetes (11 vs. 7 % increase for wake-up and 17 vs. 11 % for AUC). The early decline slope became flatter over time with a greater flattening observed in diabetic compared to non-diabetic individuals (23 vs. 9 % flatter); however, the change was only statistically significant for wake-up cortisol (p-value: 0.03). Over time, while CAR was reduced more, late decline and overall decline became flatter, and bedtime cortisol increased less in those with as compared to those without type 2 diabetes, none of these changes were statistically significant in adjusted models. We did not identify any statistically significant change in cortisol curve features over 6 years by type 2 diabetes status. PMID:26895003

  1. Lack of significant association between type 2 diabetes mellitus with longitudinal change in diurnal salivary cortisol: the multiethnic study of atherosclerosis

    PubMed Central

    Spanakis, Elias K.; Wang, Xu; Sánchez, Brisa N.; Diez Roux, Ana V.; Needham, Belinda L.; Wand, Gary S.; Seeman, Teresa; Golden, Sherita Hill

    2016-01-01

    Cross-sectional association has been shown between type 2 diabetes and hypothalamic–pituitary–adrenal (HPA) axis dysregulation; however, the temporality of this association is unknown. Our aim was to determine if type 2 diabetes is associated with longitudinal change in daily cortisol curve features. We hypothesized that the presence of type 2 diabetes may lead to a more blunted and abnormal HPA axis profile over time, suggestive of increased HPA axis dysregulation. This was a longitudinal cohort study, including 580 community-dwelling individuals (mean age 63.7 ± 9.1 years; 52.8 % women) with (n = 90) and without (n = 490) type 2 diabetes who attended two MultiEthnic Study of Atherosclerosis Stress ancillary study exams separated by 6 years. Outcome measures that were collected were wake-up and bedtime cortisol, cortisol awakening response (CAR), total area under the curve (AUC), and early, late, and overall decline slopes. In univariate analyses, wake-up and AUC increased over 6 years more in persons with as compared to those without type 2 diabetes (11 vs. 7 % increase for wake-up and 17 vs. 11 % for AUC). The early decline slope became flatter over time with a greater flattening observed in diabetic compared to non-diabetic individuals (23 vs. 9 % flatter); however, the change was only statistically significant for wake-up cortisol (p-value: 0.03). Over time, while CAR was reduced more, late decline and overall decline became flatter, and bedtime cortisol increased less in those with as compared to those without type 2 diabetes, none of these changes were statistically significant in adjusted models. We did not identify any statistically significant change in cortisol curve features over 6 years by type 2 diabetes status. PMID:26895003

  2. Meta-analysis reveals significant association of 3′-UTR VNTR in SLC6A3 with smoking cessation in Caucasian populations

    PubMed Central

    Ma, Yunlong; Yuan, Wenji; Cui, Wenyan; Li, Ming D.

    2015-01-01

    Many studies have examined the association between SLC6A3 3′-UTR VNTR polymorphism and smoking cessation; however, the results are inconclusive, primarily because of the small to moderate-size samples. The primary goal of this study was to determine whether this polymorphism has any effect on smoking cessation by a meta-analysis of all reported studies. We adopted a 9-repeat dominant model that considers 9-repeat and non 9-repeat as two genotypes and compared their frequencies in former vs. current smokers. Eleven studies with 5,480 participants were included. Considering the presence of study heterogeneity and differences in the availability of information from each study, three separate meta-analyses were performed with the Comprehensive Meta-Analysis statistical software (v. 2.0). The first meta-analysis provided evidence of association between the 9-repeat genotype and smoking cessation under the fixed-effects model (pooled odds ratio [OR] 1.13; 95% confidence interval [CI] 1.01, 1.27; P = 0.037) but not in the random-effects model (pooled OR 1.11; 95% CI 0.96, 1.29; P = 0.159). Given the marginal evidence of heterogeneity among studies (P = 0.10; I2 = 35.9%), which likely was caused by inclusion of an Asian-population treatment study with an opposite effect of the polymorphism on smoking cessation, we excluded these data, revealing a significant association between the 9-repeat genotype and smoking cessation under both the fixed- and random-effects models (pooled OR 1.15; 95% CI 1.02, 1.29; P = 0.02 for both models). By analyzing adjusted and unadjusted results, we performed the third meta-analysis, which showed consistently that the 9-repeat genotype was significantly associated with smoking cessation under both the fixed- and random-effects models (pooled OR 1.17; 95% CI 1.04, 1.31; P = 0.009 for both models). We conclude that the 3′-UTR VNTR polymorphism is significantly associated with smoking cessation, and smokers with one or more 9-repeat alleles

  3. High Malnutrition Rate in Venezuelan Yanomami Compared to Warao Amerindians and Creoles: Significant Associations WITH Intestinal Parasites and Anemia

    PubMed Central

    Verhagen, Lilly M.; Incani, Renzo N.; Franco, Carolina R.; Ugarte, Alejandra; Cadenas, Yeneska; Sierra Ruiz, Carmen I.; Hermans, Peter W. M.; Hoek, Denise; Campos Ponce, Maiza; de Waard, Jacobus H.; Pinelli, Elena

    2013-01-01

    Background Children in rural areas experience the interrelated problems of poor growth, anemia and parasitic infections. We investigated the prevalence of and associations between intestinal helminth and protozoan infections, malnutrition and anemia in school-age Venezuelan children. Methods This cross-sectional study was conducted in 390 children aged 4-16 years from three rural areas of Venezuela: the Amazon Region, Orinoco Delta and Carabobo State. Stool samples were collected for direct parasitic examinations. Anthropometric indicators of chronic (height-for-age Z score) and acute (weight-for-height and Body Mass Index (BMI)-for-age Z score in respectively children under 5 years of age and children aged 5 years and above) malnutrition were calculated. Multivariate linear and logistic regression models were built to determine factors associated with nutritional status and polyparasitism. Results Hookworm and Strongyloides stercoralis prevalences were highest in children from the Amazon rainforest (respectively 72% and 18%) while children from the Orinoco Delta and Carabobo State showed higher rates of Ascaris lumbricoides (respectively 28% and 37%) and Trichuris trichiura (40% in both regions). The prevalence of Giardia lamblia infection was not significantly different between regions (average: 18%). Anemia prevalence was highest in the Amazon Region (24%). Hemoglobin levels were significantly decreased in children with a hookworm infection. Malnutrition was present in respectively 84%, 30% and 13% of children from the Amazon Region, Orinoco Delta and Carabobo State. In multivariate analysis including all regions, G. lamblia and helminth infections were significantly and negatively associated with respectively height-for-age and weight-for-height/BMI-for-age Z scores. Furthermore, hemoglobin levels were positively associated with the height-for-age Z score (0.11, 95% CI 0.02 - 0.20). Conclusions In rural populations in Venezuela helminthiasis and giardiasis were

  4. Association Analysis of Bitter Receptor Genes in Five Isolated Populations Identifies a Significant Correlation between TAS2R43 Variants and Coffee Liking

    PubMed Central

    Pirastu, Nicola; Kooyman, Maarten; Traglia, Michela; Robino, Antonietta; Willems, Sara M.; Pistis, Giorgio; d’Adamo, Pio; Amin, Najaf; d’Eustacchio, Angela; Navarini, Luciano; Sala, Cinzia; Karssen, Lennart C.; van Duijn, Cornelia; Toniolo, Daniela; Gasparini, Paolo

    2014-01-01

    Coffee, one of the most popular beverages in the world, contains many different physiologically active compounds with a potential impact on people’s health. Despite the recent attention given to the genetic basis of its consumption, very little has been done in understanding genes influencing coffee preference among different individuals. Given its markedly bitter taste, we decided to verify if bitter receptor genes (TAS2Rs) variants affect coffee liking. In this light, 4066 people from different parts of Europe and Central Asia filled in a field questionnaire on coffee liking. They have been consequently recruited and included in the study. Eighty-eight SNPs covering the 25 TAS2R genes were selected from the available imputed ones and used to run association analysis for coffee liking. A significant association was detected with three SNP: one synonymous and two functional variants (W35S and H212R) on the TAS2R43 gene. Both variants have been shown to greatly reduce in vitro protein activity. Surprisingly the wild type allele, which corresponds to the functional form of the protein, is associated to higher liking of coffee. Since the hTAS2R43 receptor is sensible to caffeine, we verified if the detected variants produced differences in caffeine bitter perception on a subsample of people coming from the FVG cohort. We found a significant association between differences in caffeine perception and the H212R variant but not with the W35S, which suggests that the effect of the TAS2R43 gene on coffee liking is mediated by caffeine and in particular by the H212R variant. No other significant association was found with other TAS2R genes. In conclusion, the present study opens new perspectives in the understanding of coffee liking. Further studies are needed to clarify the role of the TAS2R43 gene in coffee hedonics and to identify which other genes and pathways are involved in its genetics. PMID:24647340

  5. Associations of Human Leukocyte Antigen-DRB1 Alleles with Nasopharyngeal Carcinoma and Its Clinical Significance in Xinjiang Uyghur Autonomous Region of China

    PubMed Central

    Geng, Xiao-Tao; Hu, Yun-Hui; Dong, Tao; Wang, Ruo-Zheng

    2016-01-01

    Background: Genetic susceptibility is one of the major etiological factors for nasopharyngeal carcinoma (NPC). Among the genetic predisposing factors, human leukocyte antigen (HLA) genes have been reported to be associated with NPC. This study aimed to investigate the associations of HLA-DRB1 alleles with NPC and the clinical significance of HLA-DRB1 alleles in NPC. Methods: From January 2009 to December 2013, 140 NPC patients (118 Han patients and 22 Uyghur patients) and 158 healthy controls (81 Han individuals and 77 Uyghur individuals) from Xinjiang Province were genotyped for HLA-DRB1 using the polymerase chain reaction-sequence specific primer technique. Chi-square analysis was used when comparing allele frequencies between groups. The clinical outcomes were evaluated by Kaplan-Meier method and Cox regression model. Results: Compared with healthy controls, the allele frequency of HLA-DRB1*0701 was increased in the Uyghur patients (P = 0.008) but not in the Han patients (P = 0.869). HLA-DRB1*0101 allele was presented with higher frequency in clinical Stage I + II group compared with clinical Stage III + IV group in the Han patients (P = 0.015) but not in the Uyghur patients (P = 1.000). Higher frequency of HLA-DRB1*1501 allele was observed in patients aged <45 years compared with those in patients aged ≥45 years (P = 0.002). Neither HLA-DRB1*0701 nor HLA-DRB1*0101 had a statistically significant association with 3-year survival. Conclusions: This study found HLA-DRB1*0701 in Uyghur population was associated with an increased risk of developing NPC. In Han population, we found HLA-DRB1*0101 was associated with protection from disease progression, and HLA-DRB1*1501 was associated with early age of onset. HLA-DRB1 could not be identified as a prognostic indicator for NPC in either Han or Uyghur patients. PMID:27231174

  6. Genome-wide association study of alcohol dependence:significant findings in African- and European-Americans including novel risk loci.

    PubMed

    Gelernter, J; Kranzler, H R; Sherva, R; Almasy, L; Koesterer, R; Smith, A H; Anton, R; Preuss, U W; Ridinger, M; Rujescu, D; Wodarz, N; Zill, P; Zhao, H; Farrer, L A

    2014-01-01

    We report a GWAS of alcohol dependence (AD) in European-American (EA) and African-American (AA) populations, with replication in independent samples of EAs, AAs and Germans. Our sample for discovery and replication was 16 087 subjects, the largest sample for AD GWAS to date. Numerous genome-wide significant (GWS) associations were identified, many novel. Most associations were population specific, but in several cases were GWS in EAs and AAs for different SNPs at the same locus,showing biological convergence across populations. We confirmed well-known risk loci mapped to alcohol-metabolizing enzyme genes, notably ADH1B (EAs: Arg48His, P=1.17 × 10(-31); AAs: Arg369Cys, P=6.33 × 10(-17)) and ADH1C in AAs (Thr151Thr, P=4.94 × 10(-10)), and identified novel risk loci mapping to the ADH gene cluster on chromosome 4 and extending centromerically beyond it to include GWS associations at LOC100507053 in AAs (P=2.63 × 10(-11)), PDLIM5 in EAs (P=2.01 × 10(-8)), and METAP in AAs (P=3.35 × 10(-8)). We also identified a novel GWS association (1.17 × 10(-10)) mapped to chromosome 2 at rs1437396, between MTIF2 and CCDC88A, across all of the EA and AA cohorts, with supportive gene expression evidence, and population-specific GWS for markers on chromosomes 5, 9 and 19. Several of the novel associations implicate direct involvement of, or interaction with, genes previously identified as schizophrenia risk loci. Confirmation of known AD risk loci supports the overall validity of the study; the novel loci are worthy of genetic and biological follow-up. The findings support a convergence of risk genes (but not necessarily risk alleles) between populations, and, to a lesser extent, between psychiatric traits. PMID:24166409

  7. Prognostic significance of L1CAM expression and its association with mutant p53 expression in high-risk endometrial cancer.

    PubMed

    Van Gool, Inge C; Stelloo, Ellen; Nout, Remi A; Nijman, Hans W; Edmondson, Richard J; Church, David N; MacKay, Helen J; Leary, Alexandra; Powell, Melanie E; Mileshkin, Linda; Creutzberg, Carien L; Smit, Vincent T H B M; Bosse, Tjalling

    2016-02-01

    Studies in early-stage, predominantly low- and intermediate-risk endometrial cancer have demonstrated that L1 cell adhesion molecule (L1CAM) overexpression identifies patients at increased risk of recurrence, yet its prognostic significance in high-risk endometrial cancer is unclear. To evaluate this, its frequency, and the relationship of L1CAM with the established endometrial cancer biomarker p53, we analyzed the expression of both markers by immunohistochemistry in a pilot series of 116 endometrial cancers (86 endometrioid, 30 non-endometrioid subtype) with high-risk features (such as high tumor grade and deep myometrial invasion) and correlated results with clinical outcome. We used The Cancer Genome Atlas (TCGA) endometrial cancer series to validate our findings. Using the previously reported cutoff of 10% positive staining, 51/116 (44%) tumors were classified as L1CAM-positive, with no significant association between L1CAM positivity and the rate of distant metastasis (P=0.195). However, increasing the threshold for L1CAM positivity to 50% resulted in a reduction of the frequency of L1CAM-positive tumors to 24% (28/116), and a significant association with the rate of distant metastasis (P=0.018). L1CAM expression was strongly associated with mutant p53 in the high-risk and TCGA series (P<0.001), although a substantial fraction (36% of endometrioid, 10% of non-endometrioid morphology) of p53-mutant endometrial cancers displayed <10% L1CAM positivity. Moreover, 30% of p53-wild-type non-endometrioid endometrial cancers demonstrated diffuse L1CAM staining, suggesting p53-independent mechanisms of L1CAM overexpression. In conclusion, the previously proposed threshold for L1CAM positivity of >10% does not predict prognosis in high-risk endometrial cancer, whereas an alternative threshold (>50%) does. L1CAM expression is strongly, but not universally, associated with mutant p53, and may be strong enough for clinical implementation as prognostic marker in combination

  8. The association of HMGB1 expression with clinicopathological significance and prognosis in Asian patients with colorectal carcinoma: a meta-analysis and literature review

    PubMed Central

    Zhang, Xiaoli; Yu, Jinming; Li, Minghuan; Zhu, Hui; Sun, Xindong; Kong, Li

    2016-01-01

    Background The association of high mobility group box 1 (HMGB1) expression with clinicopathological significance and prognosis in Asian patients with colorectal carcinoma (CRC) remains controversial. The purpose of this study was to conduct a meta-analysis and literature review to identify the role of HMGB1 in the development and prognosis of CRC in Asians. Methods All eligible studies regarding the association between HMGB1 expression in tissue with clinicopathological significance and prognosis in Asian patients with CRC published up to January 2015 were identified by searching PubMed, Web of Science, Chinese National Knowledge Infrastructure, and WanFang database. Analysis of pooled data was performed, while odds ratio (OR) or hazard radio with 95% confidence interval (CI) was calculated and summarized to evaluate the strength of this association in fixed- or random-effects model. Results The expression level of HMGB1 in CRC tissues was much higher than normal colorectal tissues (OR =27.35, 95% CI 9.32–80.26, P<0.0001) and para-tumor colorectal tissues (OR =10.06, 95% CI 4.61–21.95, P<0.0001). There was no relation between the HMGB1 expression and sex, age, clinical T stage, tumor size, and location (colon or rectum cancer). However, a significant relation was detected between the HMGB1 expression and clinical stage (American Joint Committee on Cancer 7), lymph node metastasis, distant metastasis, tumor invasion depth, and differentiation rate (P=0.002, P≤0.0001, P<0.0001, P<0.0001, and P=0.007, respectively). Patients with higher HMGB1 expression had shorter overall survival time, whereas patients with lower level of HMGB1 had better survival (hazard ratio =1.40, 95% CI 0.98–1.82, P<0.0001). Conclusion In this meta-analysis, our results illustrated the significant relationship of HMGB1 protein overexpression in tissues with clinicopathological characteristics and prognosis of CRC. Thus, HMGB1 may be a promising marker in predicting the clinical outcome

  9. Significant Treasures.

    ERIC Educational Resources Information Center

    Andrews, Ian A.

    1999-01-01

    Provides a crossword puzzle with an answer key corresponding to the book entitled "Significant Treasures/Tresors Parlants" that is filled with color and black-and-white prints of paintings and artifacts from 131 museums and art galleries as a sampling of the 2,200 such Canadian institutions. (CMK)

  10. Clinicopathologic significance of immunostaining of α-thalassemia/mental retardation syndrome X-linked protein and death domain-associated protein in neuroendocrine tumors.

    PubMed

    Chen, Shi-Fan; Kasajima, Atsuko; Yazdani, Samaneh; Chan, Monica S M; Wang, Lin; He, Yang-Yang; Gao, Hong-Wen; Sasano, Hironobu

    2013-10-01

    α-Thalassemia/mental retardation syndrome X-linked protein (ATRX) and death domain-associated protein (DAXX) genes are tumor suppressors whose mutations have been identified in sporadic pancreatic neuroendocrine tumors as well as in patients with MEN1. However, it is unknown whether ATRX and DAXX alterations are specific for pancreatic neuroendocrine tumor. In addition, the association of ATRX/DAXX protein loss with tumor cell proliferation has not been examined. We, therefore, immunostained ATRX and DAXX in 10 gastric, 15 duodenal, 20 rectal, 70 pancreatic, and 22 pulmonary neuroendocrine tumors with 15 nonneoplastic pancreases and 27 pancreatic adenocarcinomas to elucidate the site-specific roles of ATRX/DAXX abnormalities. At least 1 loss of ATRX and DAXX immunoreactivity was detected in all neuroendocrine tumor cases but not in any of nonneoplastic pancreatic tissues or pancreatic adenocarcinomas. The loss of DAXX protein was correlated with the Ki-67 index (ATRX, P = .904; DAXX, P = .044). The status of DAXX immunoreactivity correlated positively with World Health Organization histologic grade (P = .026). These results suggest that the status of ATRX or DAXX protein loss in neuroendocrine tumor differed among the organs in which these tumors arose, and these proteins may play site-specific roles in the development of these tumors. PMID:23954140

  11. Significant Association of Interleukin4 Intron 3 VNTR Polymorphism with Susceptibility to Gastric Cancer in a South Indian Population from Telangana

    PubMed Central

    Bhayal, Amar Chand; Krishnaveni, Devulapalli; Rao, Kondadasula Pandu Ranga; Kumar, Adi Rakesh; Jyothy, Akka; Nallari, Pratibha; Venkateshwari, Ananthapur

    2015-01-01

    Background Gastric cancer (GC) is the fifth most common malignancy and remains a considerable public health burden worldwide. Genetic variations in genes encoding cytokines and their receptors influence the intensity of the Helicobacter pylori associated inflammatory response, which may contribute to individual differences in the outcome and severity of the disease. Interleukin4 is a typical pleiotropic T helper 2 (Th2) cytokine and is a critical mediator of Th1/Th2 balance. It is involved in the regulation of inflammation-mediated carcinogenesis in human organs, including gastric cancer. Objective The present retrospective case control study was undertaken to evaluate the association of IL4 intron 3 VNTR polymorphism with the susceptibility to GC in a south Indian population from Telangana state. Materials and Methods A total of 182 patients with diagnosed GC and 326 randomly selected healthy controls were enrolled in the present study. Genomic DNA was extracted from peripheral leukocytes and genotyping was determined by PCR-based assay. Association between genotypes and gastric cancer was examined by unconditional logistic regression analysis. Result The variant 3R/2R and 2R/2R genotypes of IL4 exon3 VNTR polymorphism had about 1.9 fold and 3fold increased GC risk, respectively, when compared with 3R/3R genotype [3R/2R vs. 3R/3R: adjusted odds ratio (AOR) = 1.90, 95% confidence interval (CI) = 1.23–2.95 P = 0.004 and 2R/2R vs. 3R/3R: AOR (95%CI) = 2.96 (1.29–6.82), P = 0.011]. Furthermore, a significant increased risk of GC was found for the 2R allele carriers (3R/2R + 2R/2R) compared with the 3R/3R genotype (AOR (95%CI) = 2.04 (1.35–3.10), P = <0.000). The IL4 2R allele frequency was 0.28 among the GC group and 0.18 among the controls, and the difference was statistically significant (P = <0.000). Conclusion The present study revealed an association of 2R allele and 2R carrier genotypes in the etiopathogenesis of GC in south Indian population. PMID

  12. The Functional SNPs in the 5’ Regulatory Region of the Porcine PPARD Gene Have Significant Association with Fat Deposition Traits

    PubMed Central

    Hu, Shanyao; Lin, Bin; Yan, Dechao; Xu, Zaiyan; Zhang, Zijun; Mao, Yuanliang; Mao, Huimin; Wang, Litong; Wang, Guoshui; Xiong, Yuanzhu; Zuo, Bo

    2015-01-01

    Peroxisome proliferator-activated receptor delta (PPARD) is a key regulator of lipid metabolism, insulin sensitivity, cell proliferation and differentiation. In this study, we identified two Single Nucleotide Polymorphisms (SNPs, g.1015 A>G and g.1018 T>C) constituting four haplotypes (GT, GC, AC and AT) in the 5’ regulatory region of porcine PPARD gene. Functional analysis of the four haplotypes showed that the transcriptional activity of the PPARD promoter fragment carrying haplotype AC was significantly lower than that of the other haplotypes in 3T3-L1, C2C12 and PK-15 cells, and haplotype AC had the lowest binding capacities to the nuclear extracts. Transcription factor 7-like 2 (TCF7L2) enhanced the transcription activities of promoter fragments of PPARD gene carrying haplotypes GT, GC and AT in C2C12 and 3T3-L1 cells, and increased the protein expression of PPARD gene in C2C12 myoblasts. TCF7L2 differentially bound to the four haplotypes, and the binding capacity of TCF7L2 to haplotype AC was the lowest. There were significant associations between -655A/G and fat deposition traits in three pig populations including the Large White × Meishan F2 pigs, France and American Large White pigs. Pigs with genotype GG had significantly higher expression of PPARD at both mRNA and protein level than those with genotype AG. These results strongly suggested that the SNPs in 5’ regulatory region of PPARD genes had significant impact on pig fat deposition traits. PMID:26599230

  13. A putatively functional polymorphism in the HTR2C gene is associated with depressive symptoms in white females reporting significant life stress.

    PubMed

    Brummett, Beverly H; Babyak, Michael A; Williams, Redford B; Harris, Kathleen Mullan; Jiang, Rong; Kraus, William E; Singh, Abanish; Costa, Paul T; Georgiades, Anastasia; Siegler, Ilene C

    2014-01-01

    Psychosocial stress is well known to be positively associated with subsequent depressive symptoms. Cortisol response to stress may be one of a number of biological mechanisms that links psychological stress to depressive symptoms, although the precise causal pathway remains unclear. Activity of the x-linked serotonin 5-HTR2C receptor has also been shown to be associated with depression and with clinical response to antidepressant medications. We recently demonstrated that variation in a single nucleotide polymorphism on the HTR2C gene, rs6318 (Ser23Cys), is associated with different cortisol release and short-term changes in affect in response to a series of stress tasks in the laboratory. Based on this observation, we decided to examine whether rs6318 might moderate the association between psychosocial stress and subsequent depressive symptoms. In the present study we use cross-sectional data from a large population-based sample of young adult White men (N = 2,366) and White women (N = 2,712) in the United States to test this moderation hypothesis. Specifically, we hypothesized that the association between self-reported stressful life events and depressive symptoms would be stronger among homozygous Ser23 C females and hemizygous Ser23 C males than among Cys23 G carriers. In separate within-sex analyses a genotype-by-life stress interaction was observed for women (p = .022) but not for men (p = .471). Homozygous Ser23 C women who reported high levels of life stress had depressive symptom scores that were about 0.3 standard deviations higher than female Cys23 G carriers with similarly high stress levels. In contrast, no appreciable difference in depressive symptoms was observed between genotypes at lower levels of stress. Our findings support prior work that suggests a functional SNP on the HTR2C gene may confer an increased risk for depressive symptoms in White women with a history of significant life stress. PMID:25514629

  14. Food additives

    MedlinePlus

    Food additives are substances that become part of a food product when they are added during the processing or making of that food. "Direct" food additives are often added during processing to: Add nutrients ...

  15. Significant Association Between Fc Receptor-Like 3 Polymorphisms (-1901A>G and -658C>T) and Neuromyelitis Optica (NMO) Susceptibility in the Chinese Population.

    PubMed

    Wang, Xinling; Yu, Tao; Yan, Qichang; Wang, Wei; Meng, Nan; Li, Xuejiao; Luo, Yahong

    2016-01-01

    Neuromyelitis optica (NMO) is an autoimmune disorder. In pathogenesis, NMO-immunoglobulin G (NMO-IgG) selectively binds to aquaporin-4 (AQP4) and resulted in neuritis, myelitis, and brain lesion. Fc receptor-like 3 (FCRL3) gene encodes a member of the immunoglobulin receptor superfamily, which plays an important part in regulating immune activities. This study aimed at investigating the association between FCRL3 polymorphisms and NMO susceptibility and, hopefully, to contribute to the development of novel methods for diagnosis and treatment of NMO. We selected 150 NMO patients and 300 healthy controls from the Chinese population. Tag single nucleotide polymorphisms (SNPs) were identified with reference to CBI-dbSNP and HapMap databases. DNA were extracted and amplified. Matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF-MS) was applied to determine the polymorphisms. χ (2), odds ratio (OR), and 95 % confidence interval (95 % CI) were presented to evaluate genotype distribution and association between SNPs and NMO susceptibility. Six out of 15 SNPs were selected according to the filter. No significant altered genotype distribution was observed concerning -11G>C, -166C>T, -219G>C, and -1629C>G polymorphisms. The G allele of -1901A>G variation was demonstrated to be more frequent in patients compared with controls (P < 0.001). The T allele of -658C>T polymorphism was significantly more prevalent in NMO patients than controls (P = 0.009). In summary, the study revealed that the G allele in -1901A>G polymorphism and T allele in -658C>T polymorphism are genetic risk factors for NMO in the Chinese population. Further research is needed to account for different ethnicities and clarify the mechanisms behind, which might contribute to the elucidation of novel diagnosis methods. PMID:25575677

  16. GxE interactions between FOXO genotypes and drinking tea are significantly associated with prevention of cognitive decline in advanced age in China.

    PubMed

    Zeng, Yi; Chen, Huashuai; Ni, Ting; Ruan, Rongping; Feng, Lei; Nie, Chao; Cheng, Lingguo; Li, Yang; Tao, Wei; Gu, Jun; Land, Kenneth C; Yashin, Anatoli; Tan, Qihua; Yang, Ze; Bolund, Lars; Yang, Huanming; Hauser, Elizabeth; Willcox, D Craig; Willcox, Bradley J; Tian, Xiao-Li; Vaupel, James W

    2015-04-01

    Logistic regression analysis based on data from 822 Han Chinese oldest old aged 92+ demonstrated that interactions between carrying FOXO1A-266 or FOXO3-310 or FOXO3-292 and tea drinking at around age 60 or at present time were significantly associated with lower risk of cognitive disability at advanced ages. Associations between tea drinking and reduced cognitive disability were much stronger among carriers of the genotypes of FOXO1A-266 or FOXO3-310 or FOXO3-292 compared with noncarriers, and it was reconfirmed by analysis of three-way interactions across FOXO genotypes, tea drinking at around age 60, and at present time. Based on prior findings from animal and human cell models, we postulate that intake of tea compounds may activate FOXO gene expression, which in turn may positively affect cognitive function in the oldest old population. Our empirical findings imply that the health benefits of particular nutritional interventions, including tea drinking, may, in part, depend upon individual genetic profiles. PMID:24895270

  17. Food Additives and Hyperkinesis

    ERIC Educational Resources Information Center

    Wender, Ester H.

    1977-01-01

    The hypothesis that food additives are causally associated with hyperkinesis and learning disabilities in children is reviewed, and available data are summarized. Available from: American Medical Association 535 North Dearborn Street Chicago, Illinois 60610. (JG)

  18. Food additives

    PubMed Central

    Spencer, Michael

    1974-01-01

    Food additives are discussed from the food technology point of view. The reasons for their use are summarized: (1) to protect food from chemical and microbiological attack; (2) to even out seasonal supplies; (3) to improve their eating quality; (4) to improve their nutritional value. The various types of food additives are considered, e.g. colours, flavours, emulsifiers, bread and flour additives, preservatives, and nutritional additives. The paper concludes with consideration of those circumstances in which the use of additives is (a) justified and (b) unjustified. PMID:4467857

  19. GSTPi-positive tumour microenvironment-associated fibroblasts are significantly associated with GSTPi-negative cancer cells in paired cases of primary invasive breast cancer and axillary lymph node metastases

    PubMed Central

    Chaiwun, B; Sukhamwang, N; Trakultivakorn, H; Saha, B; Young, L; Tsao-Wei, D; Naritoku, W Y; Groshen, S; Taylor, C R; Imam, S A

    2011-01-01

    Background: Glutathione S-transferase Pi (GSTPi) expression is one of the factors, which is known to be associated with development of resistance to chemotherapeutics in cancer patients, including those with breast cancer. Yet, its expression has been reported to be undetectable in cancer cells in high percent of patients with primary breast cancer. However, GSTPi expression in stromal cells in breast tumour microenvironment, namely cancer-associated fibroblast (CAF), which is recognised to have major roles in cancer progression, remains poorly reported. Methods: The aim of the study was to determine the expression of GSTPi; vimetin, a fibroblast-associated cytoskeleton protein; and α-smooth muscle actin (α-SMA), a known marker of CAF in breast cancer tissue, by immunohistochemical staining method in consecutive histologic sections of formalin-fixed and paraffin-embedded tissue biopsy specimens from a cohort of 39 paired cases of patients with invasive breast cancer and the corresponding axillary lymph nodes metastases. Results: Ductal and acinar luminal epithelial cells, myoepithelial cells and surrounding fibroblasts exhibited a homogeneous cytoplasmic reactivity with anti-GSTPi antibody in 11 of 11 cases of benign breast tissue biopsies. The vimentin-positive fibroblasts were unreactive with anti-α-SMA antibody. Loss of GSTPi expression was observed in breast cancer cells, at both the primary and metastatic sites, in 31 of 39 paired cases, as compared with benign breast epithelial cells (Fisher's exact test P<0.001). A significant association was observed between GSTPi-positive, vimentin-positive and α-SMA-positive fibroblast in tumour microenvironment at both sites. Conclusion: This is an original report of demonstration of a significance association between tumour microenvironment-associated GSTPi-positive CAF (vimentin/α-SMA-positive) and the GSTPi-negative cancer cells in paired cases of primary invasive breast cancer and the corresponding axillary

  20. Tsumoite (BiTe) and associated Ni-PGE mineralization from Gondpipri mafic-ultramafic complex, Bastar Craton, Central India: mineralogy and genetic significance

    NASA Astrophysics Data System (ADS)

    Dora, M.; Singh, H.; Kundu, A.; Shareef, M.; Randive, K.; Joshi, S.

    2014-12-01

    This paper reports the occurrence of Tsumoite (a bismuth telluride) in the Heti Cu-Ni-PGM prospect, Gondpipri mafic-ultramafic complex, Central India. The Gondpipri complex consists of several tectonically dismembered gabbronorite-gabbro-anorthositic gabbro — olivine gabbro -websterite disposed in ˜10 km long tonalite-trondhjemitegranodiorite (TTG) and charnockite-enderbite suite of rocks. The mineralization occurs in the sulphide zone hosted by gabbro variants. The host rocks have been deformed and metamorphosed to granulite grade and subjected to various degrees of hydrothermal alteration. The mineralization comprises chalcopyrite, pentlandite, pyrrhotite, cubanite, millerite, and pyrite. In addition to these, occur (1) tsumoite (2) PGM in the form of moncheite, merenskyite, Pd-mellonite, and Pt-Pd-Te-Bi-Fe-S alloy. The present study indicates that the mineralization occurs in two stages related to: (i) magmatic and (ii) hydrothermal remobilization and transport of Cu-rich sulphides, tsumoite and PGM, and their re-deposition in hydrosilicate alteration zones. It is possible that the mineralization at Heti formed at different stages of bismuth activity under variable fS2, T, and fTe2 conditions due to change in total concentration of Te and S and /or cooling. Since the role of S is limited, Te and cooling are important factor influencing mineralogy and composition of tsumoite and associated mineralization. Mineralization occurs in two different modes of occurrences. The early mineralisation occur as blebs, specks and dissemination of sulphides, viz. pyrrhotite, chalcopyrite, pentlandite and minor pyrite ± PGM, whereas later mineralisation occur as stringers, minor veins of sulphides viz. pyrite, millerite, cubanite, sijenite, tsumoite and ± PGM. Mineral assemblages and textural relationships at Heti has indicated precipitation of tsumoite and associated PGM along fractures and secondary silicates, which confirms their hydrothermal origin.

  1. The bovine fatty acid binding protein 4 gene is significantly associated with marbling and subcutaneous fat depth in Wagyu x Limousin F2 crosses.

    PubMed

    Michal, J J; Zhang, Z W; Gaskins, C T; Jiang, Z

    2006-08-01

    Fatty acid binding protein 4 (FABP4), which is expressed in adipose tissue, interacts with peroxisome proliferator-activated receptors and binds to hormone-sensitive lipase and therefore, plays an important role in lipid metabolism and homeostasis in adipocytes. The objective of this study was to investigate associations of the bovine FABP4 gene with fat deposition. Both cDNA and genomic DNA sequences of the bovine gene were retrieved from the public databases and aligned to determine its genomic organization. Primers targeting two regions of the FABP4 gene were designed: from nucleotides 5433-6106 and from nucleotides 7417-7868 (AAFC01136716). Direct sequencing of polymerase chain reaction (PCR) products on two DNA pools from high- and low-marbling animals revealed two single nucleotide polymorphisms (SNPs): AAFC01136716.1:g.7516G>C and g.7713G>C. The former SNP, detected by PCR-restriction fragment length polymorphism using restriction enzyme MspA1I, was genotyped on 246 F2 animals in a Waygu x Limousin F2 reference population. Statistical analysis showed that the FABP4 genotype significantly affected marbling score (P = 0.0398) and subcutaneous fat depth (P = 0.0246). The FABP4 gene falls into a suggestive/significant quantitative trait loci interval for beef marbling that was previously reported on bovine chromosome 14 in three other populations. PMID:16879357

  2. Long-term use of amiodarone before heart transplantation significantly reduces early post-transplant atrial fibrillation and is not associated with increased mortality after heart transplantation

    PubMed Central

    Rivinius, Rasmus; Helmschrott, Matthias; Ruhparwar, Arjang; Schmack, Bastian; Erbel, Christian; Gleissner, Christian A; Akhavanpoor, Mohammadreza; Frankenstein, Lutz; Darche, Fabrice F; Schweizer, Patrick A; Thomas, Dierk; Ehlermann, Philipp; Bruckner, Tom; Katus, Hugo A; Doesch, Andreas O

    2016-01-01

    Background Amiodarone is a frequently used antiarrhythmic drug in patients with end-stage heart failure. Given its long half-life, pre-transplant use of amiodarone has been controversially discussed, with divergent results regarding morbidity and mortality after heart transplantation (HTX). Aim The aim of this study was to investigate the effects of long-term use of amiodarone before HTX on early post-transplant atrial fibrillation (AF) and mortality after HTX. Methods Five hundred and thirty patients (age ≥18 years) receiving HTX between June 1989 and December 2012 were included in this retrospective single-center study. Patients with long-term use of amiodarone before HTX (≥1 year) were compared to those without long-term use (none or <1 year of amiodarone). Primary outcomes were early post-transplant AF and mortality after HTX. The Kaplan–Meier estimator using log-rank tests was applied for freedom from early post-transplant AF and survival. Results Of the 530 patients, 74 (14.0%) received long-term amiodarone therapy, with a mean duration of 32.3±26.3 months. Mean daily dose was 223.0±75.0 mg. Indications included AF, Wolff–Parkinson–White syndrome, ventricular tachycardia, and ventricular fibrillation. Patients with long-term use of amiodarone before HTX had significantly lower rates of early post-transplant AF (P=0.0105). Further, Kaplan–Meier analysis of freedom from early post-transplant AF showed significantly lower rates of AF in this group (P=0.0123). There was no statistically significant difference between patients with and without long-term use of amiodarone prior to HTX in 1-year (P=0.8596), 2-year (P=0.8620), 5-year (P=0.2737), or overall follow-up mortality after HTX (P=0.1049). Moreover, Kaplan–Meier survival analysis showed no statistically significant difference in overall survival (P=0.1786). Conclusion Long-term use of amiodarone in patients before HTX significantly reduces early post-transplant AF and is not associated with

  3. Association and Prognostic Significance of the Functional -1562C/T Polymorphism in the Promoter Region of MMP-9 in Turkish Patients with Gastric Cancer.

    PubMed

    Avcı, Nilufer; Ture, Mehmet; Deligonul, Adem; Cubukcu, Erdem; Olmez, Omer Fatih; Sahinturk, Serdar; Topak, Ali; Kurt, Ender; Evrensel, Turkkan; Şahin, Ahmet Bilgehan; Yakut, Tahsin

    2015-09-01

    Matrix metalloproteinases (MMPs) are a group of zinc-dependent peptidases that participate in matrix turnover in solid malignancies. The aim of this study was twofold. First, we sought to investigate under a case-control design the association between the functional -1562C/T polymorphism in the promoter region of MMP-9 and gastric cancer (GC) in a Turkish sample. Second, we examined its prognostic significance in GC patients. A total of 144 subjects were enrolled in the case-control study (79 GC cases and 65 controls). Overall survival (OS) and progression-free survival (PFS) served as the main outcome measures in the longitudinal study. The MMP-9 -1562C/T polymorphism was genotyped using a polymerase chain reaction-restriction fragment length polymorphism method. The odds ratio (OR) of GC for the CC genotype relative to the CT+TT genotypes was not significant (OR = 0.89, 95 % confidence interval [CI] = 0.44-1.82, P = 0.75). These results did not change after allowance for age and sex in multivariable regression analysis (OR = 0.81, 95 % CI = 0.40-1.94, P = 0.84). When the MMP-9 -1562C/T polymorphism was analyzed among GC patients in relation to OS and PFS, we found no significant differences between subjects with the CC and CT+TT genotypes. In conclusion, the results of our study did not point toward a major role of the MMP-9 -1562C/T polymorphism in the pathogenesis and clinical course of GC in Turkish subjects. PMID:26156886

  4. Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes

    PubMed Central

    Zeggini, Eleftheria; Scott, Laura J.; Saxena, Richa; Voight, Benjamin F.; Marchini, Jonathan L; Hu, Tainle; de Bakker, Paul IW; Abecasis, Gonçalo R; Almgren, Peter; Andersen, Gitte; Ardlie, Kristin; Boström, Kristina Bengtsson; Bergman, Richard N; Bonnycastle, Lori L; Borch-Johnsen, Knut; Burtt, Noël P; Chen, Hong; Chines, Peter S; Daly, Mark J; Deodhar, Parimal; Ding, Charles; Doney, Alex S F; Duren, William L; Elliott, Katherine S; Erdos, Michael R; Frayling, Timothy M; Freathy, Rachel M; Gianniny, Lauren; Grallert, Harald; Grarup, Niels; Groves, Christopher J; Guiducci, Candace; Hansen, Torben; Herder, Christian; Hitman, Graham A; Hughes, Thomas E; Isomaa, Bo; Jackson, Anne U; Jørgensen, Torben; Kong, Augustine; Kubalanza, Kari; Kuruvilla, Finny G; Kuusisto, Johanna; Langenberg, Claudia; Lango, Hana; Lauritzen, Torsten; Li, Yun; Lindgren, Cecilia M; Lyssenko, Valeriya; Marvelle, Amanda F; Meisinger, Christa; Midthjell, Kristian; Mohlke, Karen L; Morken, Mario A; Morris, Andrew D; Narisu, Narisu; Nilsson, Peter; Owen, Katharine R; Palmer, Colin NA; Payne, Felicity; Perry, John RB; Pettersen, Elin; Platou, Carl; Prokopenko, Inga; Qi, Lu; Qin, Li; Rayner, Nigel W; Rees, Matthew; Roix, Jeffrey J; Sandbæk, Anelli; Shields, Beverley; Sjögren, Marketa; Steinthorsdottir, Valgerdur; Stringham, Heather M; Swift, Amy J; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Timpson, Nicholas J; Tuomi, Tiinamaija; Tuomilehto, Jaakko; Walker, Mark; Watanabe, Richard M; Weedon, Michael N; Willer, Cristen J; Illig, Thomas; Hveem, Kristian; Hu, Frank B; Laakso, Markku; Stefansson, Kari; Pedersen, Oluf; Wareham, Nicholas J; Barroso, Inês; Hattersley, Andrew T; Collins, Francis S; Groop, Leif; McCarthy, Mark I; Boehnke, Michael; Altshuler, David

    2009-01-01

    Genome-wide association (GWA) studies have identified multiple new genomic loci at which common variants modestly but reproducibly influence risk of type 2 diabetes (T2D)1-11. Established associations to common and rare variants explain only a small proportion of the heritability of T2D. As previously published analyses had limited power to discover loci at which common alleles have modest effects, we performed meta-analysis of three T2D GWA scans encompassing 10,128 individuals of European-descent and ~2.2 million SNPs (directly genotyped and imputed). Replication testing was performed in an independent sample with an effective sample size of up to 53,975. At least six new loci with robust evidence for association were detected, including the JAZF1 (p=5.0×10−14), CDC123/CAMK1D (p=1.2×10−10), TSPAN8/LGR5 (p=1.1×10−9), THADA (p=1.1×10−9), ADAMTS9 (p=1.2×10−8), and NOTCH2 (p=4.1×10−8) gene regions. The large number of loci with relatively small effects indicates the value of large discovery and follow-up samples in identifying additional clues about the inherited basis of T2D. PMID:18372903

  5. The need for annual echocardiography to detect cabergoline-associated valvulopathy in patients with prolactinoma: a systematic review and additional clinical data.

    PubMed

    Caputo, Carmela; Prior, David; Inder, Warrick J

    2015-11-01

    Present recommendations by the US Food and Drug Administration advise that patients with prolactinoma treated with cabergoline should have an annual echocardiogram to screen for valvular heart disease. Here, we present new clinical data and a systematic review of the scientific literature showing that the prevalence of cabergoline-associated valvulopathy is very low. We prospectively assessed 40 patients with prolactinoma taking cabergoline. Cardiovascular examination before echocardiography detected an audible systolic murmur in 10% of cases (all were functional murmurs), and no clinically significant valvular lesion was shown on echocardiogram in the 90% of patients without a murmur. Our systematic review identified 21 studies that assessed the presence of valvular abnormalities in patients with prolactinoma treated with cabergoline. Including our new clinical data, only two (0·11%) of 1811 patients were confirmed to have cabergoline-associated valvulopathy (three [0·17%] if possible cases were included). The probability of clinically significant valvular heart disease is low in the absence of a murmur. On the basis of these findings, we challenge the present recommendations to do routine echocardiography in all patients taking cabergoline for prolactinoma every 12 months. We propose that such patients should be screened by a clinical cardiovascular examination and that echocardiogram should be reserved for those patients with an audible murmur, those treated for more than 5 years at a dose of more than 3 mg per week, or those who maintain cabergoline treatment after the age of 50 years. PMID:25466526

  6. Additive and epistatic genome-wide association for growth and ultrasound scan measures of carcass-related traits in Brahman cattle.

    PubMed

    Ali, A A; Khatkar, M S; Kadarmideen, H N; Thomson, P C

    2015-04-01

    Genome-wide association studies are routinely used to identify genomic regions associated with traits of interest. However, this ignores an important class of genomic associations, that of epistatic interactions. A genome-wide interaction analysis between single nucleotide polymorphisms (SNPs) using highly dense markers can detect epistatic interactions, but is a difficult task due to multiple testing and computational demand. However, It is important for revealing complex trait heredity. This study considers analytical methods that detect statistical interactions between pairs of loci. We investigated a three-stage modelling procedure: (i) a model without the SNP to estimate the variance components; (ii) a model with the SNP using variance component estimates from (i), thus avoiding iteration; and (iii) using the significant SNPs from (ii) for genome-wide epistasis analysis. We fitted these three-stage models to field data for growth and ultrasound measures for subcutaneous fat thickness in Brahman cattle. The study demonstrated the usefulness of modelling epistasis in the analysis of complex traits as it revealed extra sources of genetic variation and identified potential candidate genes affecting the concentration of insulin-like growth factor-1 and ultrasound scan measure of fat depth traits. Information about epistasis can add to our understanding of the complex genetic networks that form the fundamental basis of biological systems. PMID:25754883

  7. Reverse Phase Protein Array profiling of oropharyngeal cancer and significance of PIK3CA mutations in HPV-associated head and neck cancer

    PubMed Central

    Sewell, Andrew; Brown, Brandee; Biktasova, Asel; Mills, Gordon B.; Lu, Yiling; Tyson, Darren R.; Issaeva, Natalia; Yarbrough, Wendell G.

    2014-01-01

    Purpose HPV-associated (HPV+) oropharyngeal squamous cell carcinomas (OPSCC) have different molecular and biological characteristics and clinical behavior compared to HPV-negative (HPV−) OPSCC. PIK3CA mutations are more common in HPV(+)OPSCC. To define molecular differences and tumor subsets, protein expression and phosphorylation were compared between HPV(+) and HPV(−) OPSCC and between tumors with and without PIK3CA mutations. Experimental design Expression of 137 total and phosphorylated proteins was evaluated by reverse phase protein array(RPPA) in 29 HPV(+) and 13 HPV(−)prospectively collected OPSCCs. 47 OPSCCs were tested for hotspot activating mutations in PIK3CA and AKT. Activation of PIK3CA downstream targets and sensitivity to pathway inhibitors were determined in HPV(+) head and neck cancer cells overexpressing wild-type or mutant PIK3CA. Results Analyses revealed forty-one differentially expressed proteins between HPV(+) and HPV(−) OPSCC categorized into functional groups: DNA repair, cell cycle, apoptosis, PI3K/AKT/mTOR, and receptor kinase pathways. All queried DNA repair proteins were significantly upregulated in HPV(+) samples. 8 of 33 HPV(+) and 0 of 14 HPV(−) tumors contained activating PIK3CA mutations. Despite all activating PIK3CA mutations occurring in HPV(+) samples, HPV(+) tumors had lower mean levels of activated AKT and downstream AKT target phosphorylation. Ectopic expression of mutant PIK3CA in HPV(+) cells increase dmTOR, but not AKT activity. HPV E6/E7 overexpression inhibited AKT phosphorylation in HPV-negative cells. Mutant PIK3CA overexpressing cells were more sensitive to a dual PI3K/mTOR inhibitor compared to an AKT inhibitor. Conclusions Protein expression analyses suggest that HPV(+) and HPV(−) OPSCC differentially activate DNA repair, cell cycle, apoptosis, PI3K/AKT/mTOR, and receptor kinase pathways. PIK3CA mutations are more common in HPV(+) OPSCC and are associated with activation of mTOR, but not AKT. These data

  8. Food additives.

    PubMed

    Berglund, F

    1978-01-01

    The use of additives to food fulfils many purposes, as shown by the index issued by the Codex Committee on Food Additives: Acids, bases and salts; Preservatives, Antioxidants and antioxidant synergists; Anticaking agents; Colours; Emulfifiers; Thickening agents; Flour-treatment agents; Extraction solvents; Carrier solvents; Flavours (synthetic); Flavour enhancers; Non-nutritive sweeteners; Processing aids; Enzyme preparations. Many additives occur naturally in foods, but this does not exclude toxicity at higher levels. Some food additives are nutrients, or even essential nutritents, e.g. NaCl. Examples are known of food additives causing toxicity in man even when used according to regulations, e.g. cobalt in beer. In other instances, poisoning has been due to carry-over, e.g. by nitrate in cheese whey - when used for artificial feed for infants. Poisonings also occur as the result of the permitted substance being added at too high levels, by accident or carelessness, e.g. nitrite in fish. Finally, there are examples of hypersensitivity to food additives, e.g. to tartrazine and other food colours. The toxicological evaluation, based on animal feeding studies, may be complicated by impurities, e.g. orthotoluene-sulfonamide in saccharin; by transformation or disappearance of the additive in food processing in storage, e.g. bisulfite in raisins; by reaction products with food constituents, e.g. formation of ethylurethane from diethyl pyrocarbonate; by metabolic transformation products, e.g. formation in the gut of cyclohexylamine from cyclamate. Metabolic end products may differ in experimental animals and in man: guanylic acid and inosinic acid are metabolized to allantoin in the rat but to uric acid in man. The magnitude of the safety margin in man of the Acceptable Daily Intake (ADI) is not identical to the "safety factor" used when calculating the ADI. The symptoms of Chinese Restaurant Syndrome, although not hazardous, furthermore illustrate that the whole ADI

  9. Significant Association between Sulfate-Reducing Bacteria and Uranium-Reducing Microbial Communities as Revealed by a Combined Massively Parallel Sequencing-Indicator Species Approach

    SciTech Connect

    Cardenas, Erick; Leigh, Mary Beth; Marsh, Terence; Tiedje, James M.; Wu, Wei-min; Luo, Jian; Ginder-Vogel, Matthew; Kitanidis, Peter K.; Criddle, Craig; Carley, Jack M; Carroll, Sue L; Gentry, Terry J; Watson, David B; Gu, Baohua; Jardine, Philip M; Zhou, Jizhong

    2010-10-01

    Massively parallel sequencing has provided a more affordable and high-throughput method to study microbial communities, although it has mostly been used in an exploratory fashion. We combined pyrosequencing with a strict indicator species statistical analysis to test if bacteria specifically responded to ethanol injection that successfully promoted dissimilatory uranium(VI) reduction in the subsurface of a uranium contamination plume at the Oak Ridge Field Research Center in Tennessee. Remediation was achieved with a hydraulic flow control consisting of an inner loop, where ethanol was injected, and an outer loop for flow-field protection. This strategy reduced uranium concentrations in groundwater to levels below 0.126 M and created geochemical gradients in electron donors from the inner-loop injection well toward the outer loop and downgradient flow path. Our analysis with 15 sediment samples from the entire test area found significant indicator species that showed a high degree of adaptation to the three different hydrochemical-created conditions. Castellaniella and Rhodanobacter characterized areas with low pH, heavy metals, and low bioactivity, while sulfate-, Fe(III)-, and U(VI)-reducing bacteria (Desulfovibrio, Anaeromyxobacter, and Desulfosporosinus) were indicators of areas where U(VI) reduction occurred. The abundance of these bacteria, as well as the Fe(III) and U(VI) reducer Geobacter, correlated with the hydraulic connectivity to the substrate injection site, suggesting that the selected populations were a direct response to electron donor addition by the groundwater flow path. A false-discovery-rate approach was implemented to discard false-positive results by chance, given the large amount of data compared.

  10. Significant association between sulfate-reducing bacteria and uranium-reducing microbial communities as revealed by a combined massively parallel sequencing-indicator species approach.

    PubMed

    Cardenas, Erick; Wu, Wei-Min; Leigh, Mary Beth; Carley, Jack; Carroll, Sue; Gentry, Terry; Luo, Jian; Watson, David; Gu, Baohua; Ginder-Vogel, Matthew; Kitanidis, Peter K; Jardine, Philip M; Zhou, Jizhong; Criddle, Craig S; Marsh, Terence L; Tiedje, James M

    2010-10-01

    Massively parallel sequencing has provided a more affordable and high-throughput method to study microbial communities, although it has mostly been used in an exploratory fashion. We combined pyrosequencing with a strict indicator species statistical analysis to test if bacteria specifically responded to ethanol injection that successfully promoted dissimilatory uranium(VI) reduction in the subsurface of a uranium contamination plume at the Oak Ridge Field Research Center in Tennessee. Remediation was achieved with a hydraulic flow control consisting of an inner loop, where ethanol was injected, and an outer loop for flow-field protection. This strategy reduced uranium concentrations in groundwater to levels below 0.126 μM and created geochemical gradients in electron donors from the inner-loop injection well toward the outer loop and downgradient flow path. Our analysis with 15 sediment samples from the entire test area found significant indicator species that showed a high degree of adaptation to the three different hydrochemical-created conditions. Castellaniella and Rhodanobacter characterized areas with low pH, heavy metals, and low bioactivity, while sulfate-, Fe(III)-, and U(VI)-reducing bacteria (Desulfovibrio, Anaeromyxobacter, and Desulfosporosinus) were indicators of areas where U(VI) reduction occurred. The abundance of these bacteria, as well as the Fe(III) and U(VI) reducer Geobacter, correlated with the hydraulic connectivity to the substrate injection site, suggesting that the selected populations were a direct response to electron donor addition by the groundwater flow path. A false-discovery-rate approach was implemented to discard false-positive results by chance, given the large amount of data compared. PMID:20729318

  11. A combined massively parallel sequencing indicator species approach revealed significant association between sulfate-reducing bacteria and uranium-reducing microbial communities

    SciTech Connect

    Cardenas, Erick; Wu, Wei-min; Leigh, Mary Beth; Carley, Jack M; Carroll, Sue L; Gentry, Terry; Luo, Jian; Watson, David B; Gu, Baohua; Ginder-Vogel, Matthew A.; Kitanidis, Peter K.; Jardine, Philip; Kelly, Shelly D; Zhou, Jizhong; Criddle, Craig; Marsh, Terence; Tiedje, James

    2010-08-01

    Massively parallel sequencing has provided a more affordable and high throughput method to study microbial communities, although it has been mostly used in an exploratory fashion. We combined pyrosequencing with a strict indicator species statistical analysis to test if bacteria specifically responded to ethanol injection that successfully promoted dissimilatory uranium (VI) reduction in the subsurface of a uranium contamination plume at the Oak Ridge Field Research Center in Tennessee, USA. Remediation was achieved with a hydraulic flow control consisting of an inner loop, where ethanol was injected, and an outer loop for flow field protection. This strategy reduced uranium concentrations in groundwater to levels below 0.126 {micro}M, and created geochemical gradients in electron donors from the inner loop injection well towards the outer loop and down-gradient flow path. Our analysis with 15 sediment samples from the entire test area found significant indicator species that showed a high degree of adaptation to the three different hydrochemical created conditions. Castellaniella, and Rhodanobacter characterized areas with low pH, heavy metals, and low bioactivity; while sulfate-, Fe(III)-, and U(VI)-reducing bacteria (Desulfovibrio, Anaeromyxobacter, and Desulfosporosinus) were indicators of areas where U(VI) reduction occurred. Abundance of these bacteria as well as the Fe(III)- and U(VI)-reducer Geobacter correlated with the hydraulic connectivity to the substrate injection site, suggesting that the selected populations were a direct response to the electron donor addition and by the groundwater flow path. A false discovery rate approach was implemented to discard false positives by chance given the large amount of data compared.

  12. [Significant association between nonsyndromic cleft lip with or without cleft palate and IRF6rs2235371 polymorphism in Iranian familiar population].

    PubMed

    Jafary, F; Nadeali, Z; Salehi, M; Hosseinzadeh, M; Sedghi, M; Gholamrezapour, T; Nouri, N

    2015-01-01

    According to previous studies the IRF6rs2235371 polymorphism is a risk factor for NSCL/P in different populations. However our recent study revealed no correlation between IRF6rs642961 and NSCL/P in our population. In the present study we have investigated the relationship between IRF6rs2235371 and NSCL/P in same group to determine whether IRF6rs2235371 is a risk factor in our population as well. We analyzed the IRF6rs2235371 genotype in a subset of the Iranian population using the Polymerase Chain Reaction technique. The PCR products were digested with DpnII. Chi-square test was applied to analyze the obtained result. The patients were supplied by the Cleft Lip and Palate Clinic of the Isfahan University of Medical Science. A clinician ascertained the non-syndromic status of all patients and that no clefting drugs, ethanol or smoking were abused during pregnancy. The control group was selected from unaffected subjects with no history of NSCL/P in their families. 107 patients from 107 Iranian unrelated families and 100 controls were screened. There was a significant association between the IRF6rs2235371 genotype sand an increased NSCL/P risk. Our data indicates that the IRF6rs2235371 variation can increase the risk of NSCL/P in the Iranian population. This result is in contrast with the results of our recent study on the correlation between the IRF6rs642961 polymorphism and NSCL/P in the same group. PMID:26710774

  13. Are the stray 60-Hz electromagnetic fields associated with the distribution and use of electric power a significant cause of cancer?

    PubMed

    Jackson, J D

    1992-04-15

    The putative causal relation between ambient low-frequency (50 or 60 Hz) electromagnetic fields (necessarily present in living and working environments because of our ever increasing use of electrical devices) and cancer, especially leukemia, can be tested on the large scale by examining historical data on the growth of the generation and consumption of electric power since 1900 and corresponding data on cancer death and incidence rates. The United States per capita generation and residential consumption of electric power have grown roughly exponentially since 1900; total per capita generation has increased by a factor of 10 since 1940, and per capita residential consumption has increased by a factor of 20 in the same period. The ubiquitous stray fields from power distribution lines and internal and external wiring in buildings have grown in the same proportions. In contrast to the explosive increase in the generation and use of electricity, the age-adjusted cancer death rate for the population as a whole shows only a slight rise since 1900. When respiratory cancers (largely caused by tobacco use) are subtracted, the remaining death rate has actually fallen since 1940. That the death rate may have fallen because of better diagnosis and treatment, despite a rising incidence rate, is not substantiated, especially for leukemia, including childhood leukemia, where the incidence rate has been constant or declining slightly for the past 25 yr. The absence of any appreciable change in the national cancer incidence rates during a period in which residential use of electric power has increased dramatically shows that the associated stray 50- or 60-Hz electromagnetic fields pose no significant hazard to the average individual. PMID:1565645

  14. Diagnosing Clostridium difficile-associated diarrhea using enzyme immunoassay: the clinical significance of toxin negativity in glutamate dehydrogenase-positive patients

    PubMed Central

    Yuhashi, Kazuhito; Yagihara, Yuka; Misawa, Yoshiki; Sato, Tomoaki; Saito, Ryoichi; Okugawa, Shu; Moriya, Kyoji

    2016-01-01

    Purpose The enzyme immunoassay (EIA) has lower sensitivity for Clostridium difficile toxins A and B than the polymerase chain reaction in the diagnosis of C. difficile-associated diarrhea (CDAD). Furthermore, toxin positivity with EIA performed on C. difficile isolates from stool cultures may be observed even in patients with EIA glutamate dehydrogenase (GDH)-positive and toxin-negative stool specimens. It is unclear whether such patients should be treated as having CDAD. Methods The present study retrospectively compared patient characteristics, treatment, and diarrhea duration among three groups of patients who underwent stool EIA testing for CDAD diagnosis: a toxin-positive stool group (positive stool group; n=39); a toxin-negative stool/toxin-positive isolate group (discrepant negative/positive group, n=14); and a dual toxin-negative stool and isolate group (dual negative group, n=15). All cases included were confirmed to be GDH positive on EIA test. Results Patients’ backgrounds and comorbidities were not significantly different among three groups. No difference was observed among the three groups with regard to antimicrobial drug use before diarrhea onset. Treatment was received by 82.1% of the positive stool group compared to 7.1% of the discrepant positive/negative group and 0% of the dual negative group, while mean diarrhea duration was 10.6 days compared to 7.9 days (P=0.6006) and 3.4 days (P=0.0312), respectively. Conclusion Even without treatment, patients with toxin-negative stool specimens had shorter diarrhea duration than those with toxin-positive stool specimens even with toxin-positive isolates. These findings may suggest a limited need for CDAD treatment for GDH-positive patients and toxin-negative stool specimens. PMID:27313472

  15. Potlining Additives

    SciTech Connect

    Rudolf Keller

    2004-08-10

    In this project, a concept to improve the performance of aluminum production cells by introducing potlining additives was examined and tested. Boron oxide was added to cathode blocks, and titanium was dissolved in the metal pool; this resulted in the formation of titanium diboride and caused the molten aluminum to wet the carbonaceous cathode surface. Such wetting reportedly leads to operational improvements and extended cell life. In addition, boron oxide suppresses cyanide formation. This final report presents and discusses the results of this project. Substantial economic benefits for the practical implementation of the technology are projected, especially for modern cells with graphitized blocks. For example, with an energy savings of about 5% and an increase in pot life from 1500 to 2500 days, a cost savings of $ 0.023 per pound of aluminum produced is projected for a 200 kA pot.

  16. Phosphazene additives

    SciTech Connect

    Harrup, Mason K; Rollins, Harry W

    2013-11-26

    An additive comprising a phosphazene compound that has at least two reactive functional groups and at least one capping functional group bonded to phosphorus atoms of the phosphazene compound. One of the at least two reactive functional groups is configured to react with cellulose and the other of the at least two reactive functional groups is configured to react with a resin, such as an amine resin of a polycarboxylic acid resin. The at least one capping functional group is selected from the group consisting of a short chain ether group, an alkoxy group, or an aryloxy group. Also disclosed are an additive-resin admixture, a method of treating a wood product, and a wood product.

  17. Array-Based Transcript Profiling and Limiting-Dilution Reverse Transcription-PCR Analysis Identify Additional Latent Genes in Kaposi's Sarcoma-Associated Herpesvirus▿ †

    PubMed Central

    Chandriani, Sanjay; Ganem, Don

    2010-01-01

    Kaposi's sarcoma-associated herpesvirus (KSHV) is a B-lymphotropic herpesvirus strongly linked to both lymphoproliferative diseases and Kaposi's sarcoma. The viral latency program of KSHV is central to persistent infection and plays important roles in the pathogenesis of KSHV-related tumors. Up to six polypeptides and 18 microRNAs are known to be expressed in latency, but it is unclear if all major latency genes have been identified. Here, we have employed array-based transcript profiling and limiting-dilution reverse transcription-PCR (RT-PCR) methodologies to explore this issue in several KSHV-infected cell lines. Our results show that RNAs encoding the K1 protein are found at low levels in most latently infected cell lines. The gene encoding v-IL-6 is also expressed as a latent transcript in some contexts. Both genes encode powerful signaling molecules with particular relevance to B cell biology: K1 mimics signaling through the B cell receptor, and v-IL-6 promotes B cell survival. These data resolve earlier controversies about K1 and v-IL-6 expression and indicate that, in addition to core latency genes, some transcripts can be expressed in KSHV latency in a context-dependent manner. PMID:20219929

  18. Nitrate addition to groundwater impacted by ethanol-blended fuel accelerates ethanol removal and mitigates the associated metabolic flux dilution and inhibition of BTEX biodegradation

    NASA Astrophysics Data System (ADS)

    Corseuil, Henry Xavier; Gomez, Diego E.; Schambeck, Cássio Moraes; Ramos, Débora Toledo; Alvarez, Pedro J. J.

    2015-03-01

    A comparison of two controlled ethanol-blended fuel releases under monitored natural attenuation (MNA) versus nitrate biostimulation (NB) illustrates the potential benefits of augmenting the electron acceptor pool with nitrate to accelerate ethanol removal and thus mitigate its inhibitory effects on BTEX biodegradation. Groundwater concentrations of ethanol and BTEX were measured 2 m downgradient of the source zones. In both field experiments, initial source-zone BTEX concentrations represented less than 5% of the dissolved total organic carbon (TOC) associated with the release, and measurable BTEX degradation occurred only after the ethanol fraction in the multicomponent substrate mixture decreased sharply. However, ethanol removal was faster in the nitrate amended plot (1.4 years) than under natural attenuation conditions (3.0 years), which led to faster BTEX degradation. This reflects, in part, that an abundant substrate (ethanol) can dilute the metabolic flux of target pollutants (BTEX) whose biodegradation rate eventually increases with its relative abundance after ethanol is preferentially consumed. The fate and transport of ethanol and benzene were accurately simulated in both releases using RT3D with our general substrate interaction module (GSIM) that considers metabolic flux dilution. Since source zone benzene concentrations are relatively low compared to those of ethanol (or its degradation byproduct, acetate), our simulations imply that the initial focus of cleanup efforts (after free-product recovery) should be to stimulate the degradation of ethanol (e.g., by nitrate addition) to decrease its fraction in the mixture and speed up BTEX biodegradation.

  19. High frequency of additional gene mutations in acute myeloid leukemia with MLL partial tandem duplication: DNMT3A mutation is associated with poor prognosis

    PubMed Central

    Kao, Hsiao-Wen; Liang, Der-Cherng; Kuo, Ming-Chung; Wu, Jin-Hou; Dunn, Po; Wang, Po-Nan; Lin, Tung-Liang; Shih, Yu-Shu; Liang, Sung-Tzu; Lin, Tung-Huei; Lai, Chen-Yu; Lin, Chun-Hui; Shih, Lee-Yung

    2015-01-01

    The mutational profiles of acute myeloid leukemia (AML) with partial tandem duplication of mixed-lineage leukemia gene (MLL-PTD) have not been comprehensively studied. We studied 19 gene mutations for 98 patients with MLL-PTD AML to determine the mutation frequency and clinical correlations. MLL-PTD was screened by reverse-transcriptase PCR and confirmed by real-time quantitative PCR. The mutational analyses were performed with PCR-based assays followed by direct sequencing. Gene mutations of signaling pathways occurred in 63.3% of patients, with FLT3-ITD (44.9%) and FLT3-TKD (13.3%) being the most frequent. 66% of patients had gene mutations involving epigenetic regulation, and DNMT3A (32.7%), IDH2 (18.4%), TET2 (18.4%), and IDH1 (10.2%) mutations were most common. Genes of transcription pathways and tumor suppressors accounted for 23.5% and 10.2% of patients. RUNX1 mutation occurred in 23.5% of patients, while none had NPM1 or double CEBPA mutation. 90.8% of MLL-PTD AML patients had at least one additional gene mutation. Of 55 MLL-PTD AML patients who received standard chemotherapy, age older than 50 years and DNMT3A mutation were associated with inferior outcome. In conclusion, gene mutations involving DNA methylation and activated signaling pathway were common co-existed gene mutations. DNMT3A mutation was a poor prognostic factor in MLL-PTD AML. PMID:26375248

  20. "Old" tail lobes provide significant additional substorm power

    NASA Astrophysics Data System (ADS)

    Mishin, V.; Mishin, V. V.; Karavaev, Y.

    2012-12-01

    In each polar cap (PC) we mark out "old PC" observed during quiet time before the event under consideration, and "new PC" that emerges during rounding the old one and expanding the PC total area. Old and new PCs correspond in the magnetosphere to the old and new tail lobes, respectively. The new lobe variable magnetic flux Ψ1 is usually assumed to be active, i.e. it provides transport of the electromagnetic energy flux (Poynting flux) ɛ' from solar wind into the magnetosphere. The old lobe magnetic flux Ψ2 is usually supposed to be passive, i.e. it remains constant during the disturbance and does not participate in the transporting process which would mean the old PC electric field absolute screening from the convection electric field created by the magnetopause reconnection. In fact, screening is observed, but it is far from absolute. We suggest a model of screening and determine its quantitative characteristics in the selected superstorm. The coefficient of a screening is the β = Ψ2/Ψ02, where Ψ02 = const is open magnetic flux through the old PC measured prior to the substorm, and Ψ2 is variable magnetic flux during the substorm. We consider three various regimes of disturbance. In each, the coefficient β decreased during the loading phase and increased at the unloading phase, but the rates and amplitudes of variations exhibited a strong dependence on the regime. We interpreted decrease in β as a result of involving the old PC magnetic flux Ψ2, which was considered to be constant earlier, to the ' transport process of the Poynting flux from the solar wind into the magnetosphere. A weakening of the transport process at the subsequent unloading phase creates increase in β. Estimates showed that coefficient β during each regime and the computed Poynting flux varied manifolds. In general, unlike the existing substorm conception, the new scenario describes an unknown earlier tail lobe activation process during a substorm growth phase that effectively increases the accumulated tail energy for the expansion and recovery phases.

  1. PolySearch2: a significantly improved text-mining system for discovering associations between human diseases, genes, drugs, metabolites, toxins and more

    PubMed Central

    Liu, Yifeng; Liang, Yongjie; Wishart, David

    2015-01-01

    PolySearch2 (http://polysearch.ca) is an online text-mining system for identifying relationships between biomedical entities such as human diseases, genes, SNPs, proteins, drugs, metabolites, toxins, metabolic pathways, organs, tissues, subcellular organelles, positive health effects, negative health effects, drug actions, Gene Ontology terms, MeSH terms, ICD-10 medical codes, biological taxonomies and chemical taxonomies. PolySearch2 supports a generalized ‘Given X, find all associated Ys’ query, where X and Y can be selected from the aforementioned biomedical entities. An example query might be: ‘Find all diseases associated with Bisphenol A’. To find its answers, PolySearch2 searches for associations against comprehensive collections of free-text collections, including local versions of MEDLINE abstracts, PubMed Central full-text articles, Wikipedia full-text articles and US Patent application abstracts. PolySearch2 also searches 14 widely used, text-rich biological databases such as UniProt, DrugBank and Human Metabolome Database to improve its accuracy and coverage. PolySearch2 maintains an extensive thesaurus of biological terms and exploits the latest search engine technology to rapidly retrieve relevant articles and databases records. PolySearch2 also generates, ranks and annotates associative candidates and present results with relevancy statistics and highlighted key sentences to facilitate user interpretation. PMID:25925572

  2. PolySearch2: a significantly improved text-mining system for discovering associations between human diseases, genes, drugs, metabolites, toxins and more.

    PubMed

    Liu, Yifeng; Liang, Yongjie; Wishart, David

    2015-07-01

    PolySearch2 (http://polysearch.ca) is an online text-mining system for identifying relationships between biomedical entities such as human diseases, genes, SNPs, proteins, drugs, metabolites, toxins, metabolic pathways, organs, tissues, subcellular organelles, positive health effects, negative health effects, drug actions, Gene Ontology terms, MeSH terms, ICD-10 medical codes, biological taxonomies and chemical taxonomies. PolySearch2 supports a generalized 'Given X, find all associated Ys' query, where X and Y can be selected from the aforementioned biomedical entities. An example query might be: 'Find all diseases associated with Bisphenol A'. To find its answers, PolySearch2 searches for associations against comprehensive collections of free-text collections, including local versions of MEDLINE abstracts, PubMed Central full-text articles, Wikipedia full-text articles and US Patent application abstracts. PolySearch2 also searches 14 widely used, text-rich biological databases such as UniProt, DrugBank and Human Metabolome Database to improve its accuracy and coverage. PolySearch2 maintains an extensive thesaurus of biological terms and exploits the latest search engine technology to rapidly retrieve relevant articles and databases records. PolySearch2 also generates, ranks and annotates associative candidates and present results with relevancy statistics and highlighted key sentences to facilitate user interpretation. PMID:25925572

  3. Significance of Staphylococcus epidermidis in Health Care-Associated Infections, from Contaminant to Clinically Relevant Pathogen: This Is a Wake-Up Call!

    PubMed

    Widerström, Micael

    2016-07-01

    Coagulase-negative staphylococci, particularly Staphylococcus epidermidis, have been recognized as an important cause of health care-associated infections. Concurrently, S. epidermidis is a common contaminant in clinical cultures, which poses a diagnostic challenge. An article in this issue of Journal of Clinical Microbiology (I. Tolo, J. C. Thomas, R. S. B. Fischer, E. L. Brown, B. M. Gray, and D. A. Robinson, J Clin Microbiol 54:1711-1719, 2015, http://dx.doi.org/10.1128/JCM.03345-15) describes a rapid single nucleotide polymorphism-based assay for distinguishing between S. epidermidis isolates from hospital and nonhospital sources, which represents an important contribution to the characterization and understanding of S. epidermidis health care-associated infections. PMID:27170016

  4. Significant reduction in errors associated with nonbonded contacts in protein crystal structures: automated all-atom refinement with PrimeX.

    PubMed

    Bell, Jeffrey A; Ho, Kenneth L; Farid, Ramy

    2012-08-01

    All-atom models are essential for many applications in molecular modeling and computational chemistry. Nonbonded atomic contacts much closer than the sum of the van der Waals radii of the two atoms (clashes) are commonly observed in such models derived from protein crystal structures. A set of 94 recently deposited protein structures in the resolution range 1.5-2.8 Å were analyzed for clashes by the addition of all H atoms to the models followed by optimization and energy minimization of the positions of just these H atoms. The results were compared with the same set of structures after automated all-atom refinement with PrimeX and with nonbonded contacts in protein crystal structures at a resolution equal to or better than 0.9 Å. The additional PrimeX refinement produced structures with reasonable summary geometric statistics and similar R(free) values to the original structures. The frequency of clashes at less than 0.8 times the sum of van der Waals radii was reduced over fourfold compared with that found in the original structures, to a level approaching that found in the ultrahigh-resolution structures. Moreover, severe clashes at less than or equal to 0.7 times the sum of atomic radii were reduced 15-fold. All-atom refinement with PrimeX produced improved crystal structure models with respect to nonbonded contacts and yielded changes in structural details that dramatically impacted on the interpretation of some protein-ligand interactions. PMID:22868759

  5. The XRCC1 Arg194Trp polymorphism is significantly associated with lung adenocarcinoma: a case-control study in an Eastern European Caucasian group

    PubMed Central

    Cătană, Andreea; Pop, Monica; Hincu, Bianca Domokos; Pop, Ioan V; Petrişor, Felicia M; Porojan, Mihai D; Popp, Radu A

    2015-01-01

    DNA repair plays an important role in maintaining the integrity of the genome by repairing DNA damage induced by carcinogens. Certain genetic polymorphisms that occur in DNA-repair genes may affect the ability to repair DNA defects, and may represent a risk factor in carcinogenesis. The gene XRCC1 is involved in DNA repair. The purpose of our study was to investigate the association between XRCC1 Arg194Trp and Arg399Gln polymorphisms and the risk of lung cancer in a Romanian population. We recruited 222 healthy controls and 102 patients with lung cancer. Genotypes were determined by multiplex polymerase chain-reaction restriction fragment-length polymorphism. Statistical analysis (odds ratio, recessive model) revealed an increased risk for lung cancer for the homozygous 194Trp genotype (χ2=0.186, odds ratio 10.667, 95% confidence interval 1.309–86.933; P=0.007). Also, we found an association between the 194Trp allele and women with lung adenocarcinoma. In conclusion, the results of the study place the XRCC1 Arg194Trp polymorphism among independent risk factors for developing lung cancer. PMID:26664136

  6. Significant reduction in errors associated with nonbonded contacts in protein crystal structures: automated all-atom refinement with PrimeX

    SciTech Connect

    Bell, Jeffrey A.; Ho, Kenneth L.; Farid, Ramy

    2012-08-01

    All-atom models derived from moderate-resolution protein crystal structures contain a high frequency of close nonbonded contacts, independent of the major refinement program used for structure determination. All-atom refinement with PrimeX corrects many of these problematic interactions, producing models that are better suited for use in computational chemistry and related applications. All-atom models are essential for many applications in molecular modeling and computational chemistry. Nonbonded atomic contacts much closer than the sum of the van der Waals radii of the two atoms (clashes) are commonly observed in such models derived from protein crystal structures. A set of 94 recently deposited protein structures in the resolution range 1.5–2.8 Å were analyzed for clashes by the addition of all H atoms to the models followed by optimization and energy minimization of the positions of just these H atoms. The results were compared with the same set of structures after automated all-atom refinement with PrimeX and with nonbonded contacts in protein crystal structures at a resolution equal to or better than 0.9 Å. The additional PrimeX refinement produced structures with reasonable summary geometric statistics and similar R{sub free} values to the original structures. The frequency of clashes at less than 0.8 times the sum of van der Waals radii was reduced over fourfold compared with that found in the original structures, to a level approaching that found in the ultrahigh-resolution structures. Moreover, severe clashes at less than or equal to 0.7 times the sum of atomic radii were reduced 15-fold. All-atom refinement with PrimeX produced improved crystal structure models with respect to nonbonded contacts and yielded changes in structural details that dramatically impacted on the interpretation of some protein–ligand interactions.

  7. Human Tubal-Derived Mesenchymal Stromal Cells Associated with Low Level Laser Therapy Significantly Reduces Cigarette Smoke–Induced COPD in C57BL/6 mice

    PubMed Central

    Peron, Jean Pierre Schatzmann; de Brito, Auriléia Aparecida; Pelatti, Mayra; Brandão, Wesley Nogueira; Vitoretti, Luana Beatriz; Greiffo, Flávia Regina; da Silveira, Elaine Cristina; Oliveira-Junior, Manuel Carneiro; Maluf, Mariangela; Evangelista, Lucila; Halpern, Silvio; Nisenbaum, Marcelo Gil; Perin, Paulo; Czeresnia, Carlos Eduardo; Câmara, Niels Olsen Saraiva; Aimbire, Flávio; Vieira, Rodolfo de Paula; Zatz, Mayana; Ligeiro de Oliveira, Ana Paula

    2015-01-01

    Cigarette smoke-induced chronic obstructive pulmonary disease is a very debilitating disease, with a very high prevalence worldwide, which results in a expressive economic and social burden. Therefore, new therapeutic approaches to treat these patients are of unquestionable relevance. The use of mesenchymal stromal cells (MSCs) is an innovative and yet accessible approach for pulmonary acute and chronic diseases, mainly due to its important immunoregulatory, anti-fibrogenic, anti-apoptotic and pro-angiogenic. Besides, the use of adjuvant therapies, whose aim is to boost or synergize with their function should be tested. Low level laser (LLL) therapy is a relatively new and promising approach, with very low cost, no invasiveness and no side effects. Here, we aimed to study the effectiveness of human tube derived MSCs (htMSCs) cell therapy associated with a 30mW/3J—660 nm LLL irradiation in experimental cigarette smoke-induced chronic obstructive pulmonary disease. Thus, C57BL/6 mice were exposed to cigarette smoke for 75 days (twice a day) and all experiments were performed on day 76. Experimental groups receive htMSCS either intraperitoneally or intranasally and/or LLL irradiation either alone or in association. We show that co-therapy greatly reduces lung inflammation, lowering the cellular infiltrate and pro-inflammatory cytokine secretion (IL-1β, IL-6, TNF-α and KC), which were followed by decreased mucus production, collagen accumulation and tissue damage. These findings seemed to be secondary to the reduction of both NF-κB and NF-AT activation in lung tissues with a concomitant increase in IL-10. In summary, our data suggests that the concomitant use of MSCs + LLLT may be a promising therapeutic approach for lung inflammatory diseases as COPD. PMID:26322981

  8. Human Tubal-Derived Mesenchymal Stromal Cells Associated with Low Level Laser Therapy Significantly Reduces Cigarette Smoke-Induced COPD in C57BL/6 mice.

    PubMed

    Peron, Jean Pierre Schatzmann; de Brito, Auriléia Aparecida; Pelatti, Mayra; Brandão, Wesley Nogueira; Vitoretti, Luana Beatriz; Greiffo, Flávia Regina; da Silveira, Elaine Cristina; Oliveira-Junior, Manuel Carneiro; Maluf, Mariangela; Evangelista, Lucila; Halpern, Silvio; Nisenbaum, Marcelo Gil; Perin, Paulo; Czeresnia, Carlos Eduardo; Câmara, Niels Olsen Saraiva; Aimbire, Flávio; Vieira, Rodolfo de Paula; Zatz, Mayana; de Oliveira, Ana Paula Ligeiro

    2015-01-01

    Cigarette smoke-induced chronic obstructive pulmonary disease is a very debilitating disease, with a very high prevalence worldwide, which results in a expressive economic and social burden. Therefore, new therapeutic approaches to treat these patients are of unquestionable relevance. The use of mesenchymal stromal cells (MSCs) is an innovative and yet accessible approach for pulmonary acute and chronic diseases, mainly due to its important immunoregulatory, anti-fibrogenic, anti-apoptotic and pro-angiogenic. Besides, the use of adjuvant therapies, whose aim is to boost or synergize with their function should be tested. Low level laser (LLL) therapy is a relatively new and promising approach, with very low cost, no invasiveness and no side effects. Here, we aimed to study the effectiveness of human tube derived MSCs (htMSCs) cell therapy associated with a 30mW/3J-660 nm LLL irradiation in experimental cigarette smoke-induced chronic obstructive pulmonary disease. Thus, C57BL/6 mice were exposed to cigarette smoke for 75 days (twice a day) and all experiments were performed on day 76. Experimental groups receive htMSCS either intraperitoneally or intranasally and/or LLL irradiation either alone or in association. We show that co-therapy greatly reduces lung inflammation, lowering the cellular infiltrate and pro-inflammatory cytokine secretion (IL-1β, IL-6, TNF-α and KC), which were followed by decreased mucus production, collagen accumulation and tissue damage. These findings seemed to be secondary to the reduction of both NF-κB and NF-AT activation in lung tissues with a concomitant increase in IL-10. In summary, our data suggests that the concomitant use of MSCs + LLLT may be a promising therapeutic approach for lung inflammatory diseases as COPD. PMID:26322981

  9. Significant associations of the mitochondrial transcription factor A promoter polymorphisms with marbling and subcutaneous fat depth in Wagyu x Limousin F2 crosses.

    PubMed

    Jiang, Zhihua; Kunej, Tanja; Michal, Jennifer J; Gaskins, Charles T; Reeves, Jerry J; Busboom, Jan R; Dovc, Peter; Wright, Raymond W

    2005-08-26

    Mitochondrial transcription factor A (TFAM), a nucleus-encoded protein, regulates the initiation of transcription and replication of mitochondrial DNA (mtDNA). Decreased expression of nuclear-encoded mitochondrial genes has been associated with onset of obesity in mice. Therefore, we hypothesized genetic variants in TFAM gene influence mitochondrial biogenesis consequently affecting body fat deposition and energy metabolism. In the present study, both cDNA (2259 bp) and genomic DNA (16,666 bp) sequences were generated for the bovine TFAM gene using a combination of in silico cloning with targeted region PCR amplification. Alignment of both cDNA and genomic sequences led to the determination of genomic organization and characterization of the promoter region of the bovine TFAM gene. Two closely linked A/C and C/T single nucleotide polymorphisms (SNPs) were found in the bovine TFAM promoter and then genotyped on 237 Wagyu x Limousin F(2) animals with recorded phenotypes for marbling and subcutaneous fat depth (SFD). Statistical analysis demonstrated that both SNPs and their haplotypes were associated with marbling (P=0.0153 for A/C, P=0.0026 for C/T, and P=0.0004 for haplotype) and SFD (P=0.0200 for A/C, P=0.0039 for C/T, and P=0.0029 for haplotype), respectively. A search for transcriptional regulatory elements using MatInspector indicated that both SNPs lead to a gain/loss of six putative-binding sites for transcription factors relevant to fat deposition and energy metabolism. Our results suggest for the first time that TFAM gene plays an important role in lipid metabolism and may be a strong candidate gene for obesity in mammals. PMID:16005429

  10. Permo-Triassic hypabyssal mafic intrusions and associated tholeiitic basalts of the Kolyuchinskaya Guba, Chukotka (NE Russia): Significance for interregional correlations

    NASA Astrophysics Data System (ADS)

    Ledneva, G. V.; Pease, V. L.; Sokolov, S. D.

    2008-12-01

    In order to test tectonic hypotheses regarding the evolution of the Arctic Alaska-Chukotka microplate prior to the opening of the Amerasian basin, we investigated rocks exposed near Kolyuchinskaya Guba, eastern Chukotka. Hypabyssal mafic rocks and associated basaltic flows enclose terrigenous sediments, minor cherts and limestones in pillow interstices. The hypabyssal mafic rock yields a U-Pb zircon age of 252+/-4 Ma and indicates intrusion of basic magma at the Permo-Triassic boundary, contemporaneous with voluminous magmatism of the Siberian large igneous province (LIP). The lava flows and hypabyssal mafic rocks of the Kolyuchinskaya Guba region have major and trace element compositions identical the tholeiitic flood basalts of the main plateau stage of the Siberian LIP. They are strongly differentiated, the result of high-pressure equilibrium crystallization of a low-Ti/Y tholeiitic melt, and contaminated. The compositional variations in these rocks, however, neither proves nor disproves a correlation between the Permo-Triassic tholeiitic flood basalts of eastern Chukotka and the Siberian LIP. Thus, two alternative geodynamic interpretations are possible: 1) The hypabyssal mafic rocks and associated tholeiitic flows crystallized from a plume-derived melt; 2) The rocks are not related to plume activity, consequently eastern Chukotka was probably part of a passive rifted or extensional continental margin in the Permo-Triassic. Nonetheless, we prefer the first of these two possibilities. Funding for this work is gratefully acknowledged from the Swedish Polar Research Secretariat ("Beringia-2005"), the Swedish Research Council, the Russian Foundation for Basic Research (grant No 08-05-00547), Leading Scientific School (NSH-3172.2008.5) and ONZ RAS. Thanks are also extended to M.J. Whitehouse and the Nordsim facility - the Nordsim facility is funded by the research councils of Denmark, Norway, Sweden, the Geological Survey of Finland, and the Swedish Museum of

  11. Frequent inactivation of MCC/CTNNBIP1 and overexpression of phospho-beta-catenin(Y654) are associated with breast carcinoma: Clinical and prognostic significance.

    PubMed

    Mukherjee, Nupur; Dasgupta, Hemantika; Bhattacharya, Rittwika; Pal, Debolina; Roy, Rituparna; Islam, Saimul; Alam, Neyaz; Biswas, Jaydip; Roy, Anup; Roychoudhury, Susanta; Panda, Chinmay Kumar

    2016-09-01

    Transcriptional activation of β-catenin is a hallmark of Wnt/β-catenin pathway activation. The MCC (Mutated in colorectal cancers) and CTNNBIP1 (catenin, beta interacting protein 1) are two candidate genes which inhibit the transcriptional activity of nuclear β-catenin. The importance of MCC and CTNNBIP1 in breast cancer (BC) development has not yet been studied in detail. For this reason, in present study, the alterations (deletion/methylation/mutation/expression) of MCC and CTNNBIP1 were analyzed in BC of Indian patients (N=120) followed by expression/mutation analysis of β-catenin. Then transcriptional activity of β-catenin was checked by expression analysis of its target genes (EGFR, C-MYC and CCND1) in the same set of samples. Frequent methylation (44-45%) than deletion (20-32%) with overall alterations of 52-55% was observed in MCC/CTNNBIP1 in the BC samples. The alterations of MCC/CTNNBIP1 showed significant correlation with increased nuclear β-catenin/p-β-catenin(Y654) expression. Also, a significant correlation was seen between nuclear β-catenin expression and overexpression of its target genes like EGFR, MYC and CCND1 in the BC samples (P<0.0001). An upregulation of MCC and CTNNBIP1 expression by 5-Aza-2'-deoxycytidine treatment of MCF7 and MDA-MB-231 cell lines lead to downregulation of β-catenin and its target genes. The expression of nuclear p-β-catenin(Y654), EGFR, MYC and CCND1 were significantly high in TNBC (Triple negative BC) and Her2+ compared to Luminal A/B+ subtypes. The TNBC patients in stage III/IV having reduced expression of MCC in the tumors showed poor prognosis. Thus, our data suggests that inactivation of MCC/CTNNBIP1 could be an important event in activation of β-catenin mediated transcription of target genes in BC. PMID:27208794

  12. Temporal Variability of Zooplankton (2000-2013) in the Levantine Sea: Significant Changes Associated to the 2005-2010 EMT-like Event?

    PubMed Central

    Ouba, Anthony; Abboud-Abi Saab, Marie; Stemmann, Lars

    2016-01-01

    In this study, we investigated, for the first time, the potential impact of environmental changes on zooplankton abundance over a fourteen year period (2000–2013) at an offshore station in the Eastern Mediterranean Sea (the Levantine basin, offshore Lebanon). Samples were collected monthly and analyzed using the semi-automated system ZooScan. Salinity, temperature and phytoplankton abundance (nano and microphytoplankton) were also measured. Results show no significant temporal trend in sea surface temperature over the years. Between 2005–2010, salinity in the upper layer (0–80 m) of the Levantine basin increased (~0.3°C). During this 5 year period, total zooplankton abundance significantly increased. These modifications were concomitant to the activation of Aegean Sea as a source of dense water formation as part of the “Eastern Mediterranean Transient-like” event. The results of the present study suggested that zooplankton benefited from enhanced phytoplankton production during the mixing years of the event. Changes in the phenology of some taxa were observed accordingly with a predominantly advanced peak of zooplankton abundance. In conclusion, long-term changes in zooplankton abundance were related to the Levantine thermohaline circulation rather than sea surface warming. Sampling must be maintained to assess the impact of long-term climate change on zooplankton communities. PMID:27459093

  13. Temporal Variability of Zooplankton (2000-2013) in the Levantine Sea: Significant Changes Associated to the 2005-2010 EMT-like Event?

    PubMed

    Ouba, Anthony; Abboud-Abi Saab, Marie; Stemmann, Lars

    2016-01-01

    In this study, we investigated, for the first time, the potential impact of environmental changes on zooplankton abundance over a fourteen year period (2000-2013) at an offshore station in the Eastern Mediterranean Sea (the Levantine basin, offshore Lebanon). Samples were collected monthly and analyzed using the semi-automated system ZooScan. Salinity, temperature and phytoplankton abundance (nano and microphytoplankton) were also measured. Results show no significant temporal trend in sea surface temperature over the years. Between 2005-2010, salinity in the upper layer (0-80 m) of the Levantine basin increased (~0.3°C). During this 5 year period, total zooplankton abundance significantly increased. These modifications were concomitant to the activation of Aegean Sea as a source of dense water formation as part of the "Eastern Mediterranean Transient-like" event. The results of the present study suggested that zooplankton benefited from enhanced phytoplankton production during the mixing years of the event. Changes in the phenology of some taxa were observed accordingly with a predominantly advanced peak of zooplankton abundance. In conclusion, long-term changes in zooplankton abundance were related to the Levantine thermohaline circulation rather than sea surface warming. Sampling must be maintained to assess the impact of long-term climate change on zooplankton communities. PMID:27459093

  14. Metallogenetic systems associated with granitoid magmatism in the Amazonian Craton: An overview of the present level of understanding and exploration significance

    NASA Astrophysics Data System (ADS)

    Bettencourt, Jorge Silva; Juliani, Caetano; Xavier, Roberto P.; Monteiro, Lena V. S.; Bastos Neto, Artur C.; Klein, Evandro L.; Assis, Rafael R.; Leite, Washington Barbosa, Jr.; Moreto, Carolina P. N.; Fernandes, Carlos Marcello Dias; Pereira, Vitor Paulo

    2016-07-01

    The Amazonian Craton hosts world-class metallogenic provinces with a wide range of styles of primary precious, rare, base metal, and placer deposits. This paper provides a synthesis of the geological database with regard to granitoid magmatic suites, spatio temporal distribution, tectonic settings, and the nature of selected mineral deposits. The Archean Carajás Mineral Province comprises greenstone belts (3.04-2.97 Ga), metavolcanic-sedimentary units (2.76-2.74 Ga), granitoids (3.07-2.84 Ga) formed in a magmatic arc and syn-collisional setting, post-orogenic A2-type granites as well as gabbros (ca. 2.74 Ga), and anorogenic granites (1.88 Ga). Archean iron oxide-Cu-Au (IOCG) deposits were synchronous or later than bimodal magmatism (2.74-2.70 Ga). Paleoproterozoic IOCG deposits, emplaced at shallow-crustal levels, are enriched with Nb-Y-Sn-Be-U. The latter, as well as Sn-W and Au-EGP deposits are coeval with ca. 1.88 Ga A2-type granites. The Tapajós Mineral Province includes a low-grade meta-volcano-sedimentary sequence (2.01 Ga), tonalites to granites (2.0-1.87 Ga), two calc-alkaline volcanic sequences (2.0-1.95 Ga to 1.89-1.87 Ga) and A-type rhyolites and granites (1.88 Ga). The calc-alkaline volcanic rocks host epithermal Au and base metal mineralization, whereas Cu-Au and Cu-Mo ± Au porphyry-type mineralization is associated with sub-volcanic felsic rocks, formed in two continental magmatic arcs related to an accretionary event, resulting from an Andean-type northwards subduction. The Alta Floresta Gold Province consists of Paleoproterozoic plutono-volcanic sequences (1.98-1.75 Ga), generated in ocean-ocean orogenies. Disseminated and vein-type Au ± Cu and Au + base metal deposits are hosted by calc-alkaline I-type granitic intrusions (1.98 Ga, 1.90 Ga, and 1.87 Ga) and quartz-feldspar porphyries (ca. 1.77 Ga). Timing of the gold deposits has been constrained between 1.78 Ga and 1.77 Ga and linked to post-collisional Juruena arc felsic magmatism (e.g., Col

  15. Very early posttraumatic serum alterations are significantly associated to initial massive RBC substitution, injury severity, multiple organ failure and adverse clinical outcome in multiple injured patients

    PubMed Central

    2009-01-01

    Background Multiple severe trauma frequently leads to massive dysbalances of the human immune system. This phenomenon is known as "Systemic Inflammatory Response Syndrome (SIRS)". SIRS is connected to multiple organ failure and thereby entails higher morbidity and mortality in trauma patients. Pro-and anti-inflammatory cytokines such as Il-6, Il-8 and Il-10 seem to play a superior role in the development of SIRS. Several studies support the hypothesis that the very early cytokine release pattern determines the patients' subsequent clinical course. Most data about interleukins in trauma patients however refer to serum concentrations assessed sometime in the first 24 h, but there is only little information about release dynamics in a small-meshed time frame in the very initial post-trauma period. Patients and methods 58 multiple injured patients (Injury Severity Score > 16 points) were included. Blood samples were drawn on patient admission (not later then 90 minutes after trauma) and at 6 h, 12 h, 24 h, 48 h and 72 h. Il-6, Il-8 and Il-10 were measured using an automated chemiluminescence assay (IMMULITE, Siemens Healthcare Diagnostics GmbH). Interleukin levels were correlated to distinct epidemiological and clinical parameters. Results Interleukin serum concentrations are thoroughly elevated after trauma. Patients with haemorrhagic shock and consecutive massive RBC substitution (n = 27) exhibit higher Il-6, Il-8 and Il-10 levels as compared to patients with minor RBC transfusion extent (n = 31). Interleukin levels also differentiate patients with MOF (n = 43) from such without MOF (n = 15) already at the earliest post trauma time (90 minutes). Il-6, Il-8 and Il-10 concentrations also significantly distinguish patients with adverse outcome (n = 11) from such with favourable outcome (n = 47). Exclusively Il-10 has significant correlation to injury severity (ISS > 35). Conclusion The current study presents an image of the serum Il-6, 8 and 10 releases in multiple

  16. Patterns of coral-dinoflagellate associations in Acropora: significance of local availability and physiology of Symbiodinium strains and host-symbiont selectivity.

    PubMed

    van Oppen, M J; Palstra, F P; Piquet, A M; Miller, D J

    2001-09-01

    Like other reef-building corals, members of the genus Acropora form obligate endosymbioses with dinoflagellates (zooxanthellae) belonging to the genus Symbiodinium. Both Symbiodinium and its hosts are diverse assemblages, and the relationships between host and algal genotypes are unclear. In this study, we determined phylogenetic relationships between Symbiodinium isolates from a wide range of Acropora species and plotted the algal genotypes onto a molecular phylogeny of 28 Acropora species, using the same samples for the host and symbiont genotyping. In addition, we performed a preliminary survey of zooxanthella distribution in Acropora species from the central Great Barrier Reef. Three of the four known major zooxanthellae clades were represented in the 168 samples examined, and within the major clade C, three distinct subclades were identified. No evidence was found for coevolution, but several clear patterns of specificity were identified. Moreover, composition of the zooxanthella pool varied among locales and in one host species we found light-related patterns of zooxanthella distribution. PMID:11522193

  17. Significance of host cell kinases in herpes simplex virus type 1 egress and lamin-associated protein disassembly from the nuclear lamina

    SciTech Connect

    Leach, Natalie R.; Roller, Richard J.

    2010-10-10

    The nuclear lamina is thought to be a steric barrier to the herpesvirus capsid. Disruption of the lamina accompanied by phosphorylation of lamina proteins is a conserved feature of herpesvirus infection. In HSV-1-infected cells, protein kinase C (PKC) alpha and delta isoforms are recruited to the nuclear membrane and PKC delta has been implicated in phosphorylation of emerin and lamin B. We tested two critical hypotheses about the mechanism and significance of lamina disruption. First, we show that chemical inhibition of all PKC isoforms reduced viral growth five-fold and inhibited capsid egress from the nucleus. However, specific inhibition of either conventional PKCs or PKC delta does not inhibit viral growth. Second, we show hyperphosphorylation of emerin by viral and cellular kinases is required for its disassociation from the lamina. These data support hypothesis that phosphorylation of lamina components mediates lamina disruption during HSV nuclear egress.

  18. The discovery and significance of the northeastern Jiangxi Province ophiolite (NEJXO), its metamorphic peridotite and associated high temperature-high pressure metamorphic rocks

    NASA Astrophysics Data System (ADS)

    Guoqing, Zhou

    The NEJXO with a N.E.-S.W. elongation occurs in the mid-Lower Qigong Group, under which lies the Jiuling Group (1401 Ma) and above which lies the Shangshu Group (817 ± 87 Ma), so that the age of NEJXO is defined to be Proterozoic between 1401 Ma and 817 ± 87 Ma. The sediments of the Jiuling Group show evidence of continental derivation, but the Qigong Group and Shangshu Group are characterised by CA volcanic rocks and probably represent a gradually growing island-arc. Thus, we regard the NEJXO as occurring in a back-island-arc basin between the ancient continent and the island-arc. On the whole, the main members of dismembered ophiolite are all present. The metamorphic periodotite present in them, is considered to be especially important, because it may be the sole representative of the older mantle present and it differs from those younger. The high-T metamorphic rocks associated with the NEJXO are various hornstones and melilite marble, whereas the high-P metamorphic rocks are aragonite-jadeite-glaucophane schist and schistose lawsonite marble. From the fact that high-P metamorphism was superimposed on the high-T metamorphic rocks, it may be suggested that early tension (at opening stage) and late compression (at closing stage) occurred during the development of the basin.

  19. Drug Resistance in Cortical and Hippocampal Slices from Resected Tissue of Epilepsy Patients: No Significant Impact of P-Glycoprotein and Multidrug Resistance-Associated Proteins

    PubMed Central

    Sandow, Nora; Kim, Simon; Raue, Claudia; Päsler, Dennis; Klaft, Zin-Juan; Antonio, Leandro Leite; Hollnagel, Jan Oliver; Kovacs, Richard; Kann, Oliver; Horn, Peter; Vajkoczy, Peter; Holtkamp, Martin; Meencke, Heinz-Joachim; Cavalheiro, Esper A.; Pragst, Fritz; Gabriel, Siegrun; Lehmann, Thomas-Nicolas; Heinemann, Uwe

    2015-01-01

    Drug resistant patients undergoing epilepsy surgery have a good chance to become sensitive to anticonvulsant medication, suggesting that the resected brain tissue is responsible for drug resistance. Here, we address the question whether P-glycoprotein (Pgp) and multidrug resistance-associated proteins (MRPs) expressed in the resected tissue contribute to drug resistance in vitro. Effects of anti-epileptic drugs [carbamazepine (CBZ), sodium valproate, phenytoin] and two unspecific inhibitors of Pgp and MRPs [verapamil (VPM) and probenecid (PBN)] on seizure-like events (SLEs) induced in slices from 35 hippocampal and 35 temporal cortex specimens of altogether 51 patients (161 slices) were studied. Although in slice preparations the blood brain barrier is not functional, we found that SLEs predominantly persisted in the presence of anticonvulsant drugs (90%) and also in the presence of VPM and PBN (86%). Following subsequent co-administration of anti-epileptic drugs and drug transport inhibitors, SLEs continued in 63% of 143 slices. Drug sensitivity in slices was recognized either as transition to recurrent epileptiform transients (30%) or as suppression (7%), particularly by perfusion with CBZ in PBN containing solutions (43, 9%). Summarizing responses to co-administration from more than one slice per patient revealed that suppression of seizure-like activity in all slices was only observed in 7% of patients. Patients whose tissue was completely or partially sensitive (65%) presented with higher seizure frequencies than those with resistant tissue (35%). However, corresponding subgroups of patients do not differ with respect to expression rates of drug transporters. Our results imply that parenchymal MRPs and Pgp are not responsible for drug resistance in resected tissue. PMID:25741317

  20. The significance of diagnosing associated clonal mast cell diseases in patients with venom-induced anaphylaxis and the role of bone marrow investigation

    PubMed Central

    2013-01-01

    Hymenoptera venom allergy (HVA) represents a particular risk for exceptionally severe anaphylactic sting reactions in patients with clonal mast cell disorders (CMD). Nevertheless, conventional investigations are not sufficient to do accurate risk assessments. Increased levels of baseline serum tryptase (sBT) (>11.4 μg/L) is highly associated with severe anaphylactic reactions and with a possible underlying CMD. The measurement of baseline serum tryptase, thus, has opened the possibility to screen for CMD. In the present study, we sought to investigate whether bone marrow evaluation provides more accurate diagnosis in patients with HVA. Three patients of the same sex and similar age with HVA were enrolled in this clinical study. The patients underwent comprehensive allergy work-up including skin prick testing, measurements of serum total IgE concentrations and baseline serum tryptase. Bone-marrow biopsies were also performed in all three patients to assess underlying CMD. We evaluated characteristics of the bone marrow mast cells by pathology, flow cytometry and detection of D816V mutation by using current WHO-criteria, which led to changes in the final diagnosis compared to the assessments done by classical allergy work-up and measurements of sBT. Three distinct diagnostic outcomes including systemic mastocytosis, monoclonal mast cell activation syndrome and non-clonal HVA were revealed. We conclude that a bone marrow investigation is required for the correct diagnosis of hymenoptera venom-induced anaphylactic reactions in patients with elevated baseline tryptase levels (>11.4 μg/L), and this has important implications for management strategies. PMID:23826821

  1. The significance of diagnosing associated clonal mast cell diseases in patients with venom-induced anaphylaxis and the role of bone marrow investigation.

    PubMed

    Gülen, Theo; Dahlén, Barbro; Sander, Birgitta; Hägglund, Hans; Nilsson, Gunnar

    2013-01-01

    Hymenoptera venom allergy (HVA) represents a particular risk for exceptionally severe anaphylactic sting reactions in patients with clonal mast cell disorders (CMD). Nevertheless, conventional investigations are not sufficient to do accurate risk assessments. Increased levels of baseline serum tryptase (sBT) (>11.4 μg/L) is highly associated with severe anaphylactic reactions and with a possible underlying CMD. The measurement of baseline serum tryptase, thus, has opened the possibility to screen for CMD. In the present study, we sought to investigate whether bone marrow evaluation provides more accurate diagnosis in patients with HVA.Three patients of the same sex and similar age with HVA were enrolled in this clinical study. The patients underwent comprehensive allergy work-up including skin prick testing, measurements of serum total IgE concentrations and baseline serum tryptase. Bone-marrow biopsies were also performed in all three patients to assess underlying CMD.We evaluated characteristics of the bone marrow mast cells by pathology, flow cytometry and detection of D816V mutation by using current WHO-criteria, which led to changes in the final diagnosis compared to the assessments done by classical allergy work-up and measurements of sBT. Three distinct diagnostic outcomes including systemic mastocytosis, monoclonal mast cell activation syndrome and non-clonal HVA were revealed.We conclude that a bone marrow investigation is required for the correct diagnosis of hymenoptera venom-induced anaphylactic reactions in patients with elevated baseline tryptase levels (>11.4 μg/L), and this has important implications for management strategies. PMID:23826821

  2. Understanding significant processes during work environment interventions to alleviate time pressure and associated sick leave of home care workers – a case study

    PubMed Central

    2013-01-01

    Background Ergonomic and work stress interventions rarely show long-term positive effect. The municipality participating in this study received orders from the Norwegian Labour Inspectorate due to an identified unhealthy level of time pressure, and responded by effectuating several work environment interventions. The study aim is to identify critical factors in the interaction between work environment interventions and independent rationalization measures in order to understand a potential negative interfering effect from concurrent rationalizations on a comprehensive work environment intervention. Methods The study, using a historic prospective mixed-method design, comprised 6 home care units in a municipality in Norway (138 respondents, response rate 76.2%; 17 informants). The study included quantitative estimations, register data of sick leave, a time line of significant events and changes, and qualitative descriptions of employee appraisals of their work situation gathered through semi-structured interviews and open survey responses. Results The work environment interventions were in general regarded as positive by the home care workers. However, all units were simultaneously subjected to substantial contextual instability, involving new work programs, new technology, restructurings, unit mergers, and management replacements, perceived by the home care workers to be major sources of stress. Findings suggest that concurrent changes induced through rationalization resulted in negative exposure effects that negated positive work environment intervention effects, causing an overall deteriorated work situation for the home care workers. Conclusions Establishment and active utilization of communication channels from workers to managers are recommended in order to increase awareness of putative harmful and interruptive effects of rationalization measures. PMID:24238560

  3. Total Arterial Revascularization with Radial Artery T-grafts in Patients with Significant Left Main Stem Stenosis Is Not Associated with Higher Perioperative Risk.

    PubMed

    Fleissner, Felix; Reitz, Michael; Cebotari, Serghei; Kaufeld, Tim; Haverich, Axel; Shrestha, Malakh; Ismail, Issam; Martens, Andreas

    2016-04-01

    Background Total arterial revascularization (TAR) has become a standard procedure for the treatment of coronary multivessel disease, due to the superior long-term patency rates of arterial grafts as compared with saphenous vein graft material. Controversies about the use of TAR in patients with left main coronary artery disease exist. Hence, we ought to determine whether left main coronary artery disease is a risk factor for early postoperative mortality and morbidity after TAR using the in situ left internal thoracic artery (LITA) and radial artery as composite T-graft. Methods A total of 904 consecutive patients were included in this retrospective study. They underwent first-time coronary artery bypass grafting surgery in our institution, receiving TAR using the in situ LITA and RA T-graft. Of these patients, 247 (27%) had left main coronary artery disease (Group LMSS) and 657 (73%) had no significant left main coronary artery stenosis (Group nLMSS). Results Results were comparable. Mortality and perioperative myocardial infarction rates were 0.4% LMSS versus 0.3% nLMSS, p = 1, and 2% LMSS versus 2% nLMSS, p = 0.81, respectively. Stroke rate, acute renal failure rate, and reoperation rates were 2% LMSS versus 1% nLMSS, p = 0.36, 7% LMSS versus 8% nLMSS, p = 0.41, and 2% LMSS versus 3% nLMSS, p = 0.5, respectively. Postoperative stay was shorter in the LMSS group (8.1 ± 4.3 days vs. 8.9 ± 6.1 days nLMSS, p = 0.048). Conclusion Our perioperative results indicate that TAR in patients with left main stenosis is safe and feasible. Long-term results will have to be awaited to further evaluate prognostic outcome. PMID:26334240

  4. Including xpc® feed additive in the diet of inoculated broilers during grow-out helps control salmonella associated with their carcasses after processing

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this study was to test XPC® feed additive for control of Salmonella in poultry meat products. Day of hatch broiler chicks were gavaged with 106 cells of a nalidixic acid resistant marker strain of Salmonella Typhimurium and placed on clean pine shavings in 9 separate floor pens (25 ...

  5. High-pressure metamorphic age and significance of eclogite-facies continental fragments associated with oceanic lithosphere in the Western Alps (Etirol-Levaz Slice, Valtournenche, Italy)

    NASA Astrophysics Data System (ADS)

    Fassmer, Kathrin; Obermüller, Gerrit; Nagel, Thorsten J.; Kirst, Frederik; Froitzheim, Nikolaus; Sandmann, Sascha; Miladinova, Irena; Fonseca, Raúl O. C.; Münker, Carsten

    2016-05-01

    The Etirol-Levaz Slice in the Penninic Alps (Valtournenche, Italy) is a piece of eclogite-facies continental basement sandwiched between two oceanic units, the blueschist-facies Combin Zone in the hanging wall and the eclogite-facies Zermatt-Saas Zone in the footwall. It has been interpreted as an extensional allochthon from the continental margin of Adria, emplaced onto ultramafic and mafic basement of the future Zermatt-Saas Zone by Jurassic, rifting-related detachment faulting, and later subducted together with the future Zermatt-Saas Zone. Alternatively, the Etirol-Levaz Slice could be derived from a different paleogeographic domain and be separated from the Zermatt-Saas Zone by an Alpine shear zone. We present Lu-Hf whole rock-garnet ages of two eclogite samples, one from the center of the unit and one from the border to the Zermatt-Saas Zone below. These data are accompanied by a new geological map of the Etirol-Levaz Slice and the surrounding area, as well as detailed petrology of these two samples. Assemblages, mineral compositions and garnet zoning in both samples indicate a clockwise PT-path and peak-metamorphic conditions of about 550-600 °C/20-25 kbar, similar to conditions proposed for the underlying Zermatt-Saas Zone. Prograde garnet ages of the two samples are 61.8 ± 1.8 Ma and 52.4 ± 2.1 Ma and reflect different timing of subduction. One of these is significantly older than published ages of eclogite-facies metamorphism in the Zermatt-Saas Zone and thus contradicts the hypothesis of Mesozoic emplacement. The occurrence of serpentinite and metagabbro bodies possibly derived from the Zermatt-Saas Zone inside the Etirol-Levaz Slice suggests that the latter is a tectonic composite. The basement slivers forming the Etirol-Levaz Slice and other continental fragments were subducted earlier than the Zermatt-Saas Zone, but nonetheless experienced similar pressure-temperature histories. Our results support the hypothesis that the Zermatt-Saas Zone and the

  6. Two cases of food additive-induced severe liver damage associated with positive results on lymphocyte stimulation test and for antinuclear antibodies.

    PubMed

    Kaneko, Rena; Ohishi, Chitose; Kim, Miniru; Shiina, Masaaki; Kusayanagi, Satoshi; Ogawa, Masazumi; Munakata, Kazuo; Mizuno, Kyoichi; Sato, Yuzuru

    2012-08-01

    Two cases of severe liver injury and positive result for antinuclear antibodies induced by food additives are reported. The first patient reported long-term intake of Mabo Ramen(®) noodle soup, nutritional supplements, and over-the-counter drugs. Total bilirubin, aspartate aminotransferase, and alanine aminotransferase were 9.6 mg/dL, 1,048, and 1,574 IU/L, respectively. Antinuclear antibody was 80×. The drug-induced lymphocyte stimulation test (DLST) was positive for Mabo Ramen(®) and its additives such as Xanthan gum, guar gum, and Doubanjiang. Histologic examination of a liver biopsy specimen showed lymphocyte infiltration and necrosis. The autoimmune hepatitis score was 3. The second patient reported intake of dietary supplements, including Bimore C(®) and Chokora BB(®). Laboratory tests revealed that total bilirubin was 9.8 mg/dL, aspartate aminotransferase was 1,130 IU/L, and alanine aminotransferase was 1,094 IU/L. Antinuclear antibody was 320×. Co-existing pancreatic damage was confirmed by the findings on abdominal CT and elevation of serum lipase, span-1, and DUPAN-2. DLSTs were positive for both supplements. These two supplements contained additives such as titanium oxide, magnesium stearate, and hydroxypropylcellulose. DLSTs for all three additives were positive. Histologic examination revealed periportal necrosis and lymphocyte infiltration of lobular and portal areas. These two cases demonstrate that repeating DLSTs is useful for identifying causative constituents in foods and supplements. PMID:26182392

  7. Combined action of time-delay and colored cross-associated multiplicative and additive noises on stability and stochastic resonance for a stochastic metapopulation system

    NASA Astrophysics Data System (ADS)

    Wang, Kang-Kang; Zong, De-Cai; Wang, Ya-Jun; Li, Sheng-Hong

    2016-05-01

    In this paper, the transition between the stable state of a big density and the extinction state and stochastic resonance (SR) for a time-delayed metapopulation system disturbed by colored cross-correlated noises are investigated. By applying the fast descent method, the small time-delay approximation and McNamara and Wiesenfeld's SR theory, we investigate the impacts of time-delay, the multiplicative, additive noises and colored cross-correlated noise on the SNR and the shift between the two states of the system. Numerical results show that the multiplicative, additive noises and time-delay can all speed up the transition from the stable state to the extinction state, while the correlation noise and its correlation time can slow down the extinction process of the population system. With respect to SNR, the multiplicative noise always weakens the SR effect, while noise correlation time plays a dual role in motivating the SR phenomenon. Meanwhile, time-delay mainly plays a negative role in stimulating the SR phenomenon. Conversely, it could motivate the SR effect to increase the strength of the cross-correlation noise in the SNR-β plot, while the increase of additive noise intensity will firstly excite SR, and then suppress the SR effect.

  8. Additional Burden of Diseases Associated with Cadmium Exposure: A Case Study of Cadmium Contaminated Rice Fields in Mae Sot District, Tak Province, Thailand

    PubMed Central

    Songprasert, Nisarat; Sukaew, Thitiporn; Kusreesakul, Khanitta; Swaddiwudhipong, Witaya; Padungtod, Chantana; Bundhamcharoen, Kanitta

    2015-01-01

    The cadmium (Cd) contaminated rice fields in Mae Sot District, Tak Province, Thailand has been one of the major environmental problems in Thailand for the last 10 years. We used disability adjusted life years (DALYs) to estimate the burden of disease attributable to Cd in terms of additional DALYs of Mae Sot residents. Cd exposure data included Cd and β2–microglobulin (β2-MG) in urine (as an internal exposure dose) and estimated cadmium daily intake (as an external exposure dose). Compared to the general Thai population, Mae Sot residents gained 10%–86% DALYs from nephrosis/nephritis, heart diseases, osteoporosis and cancer depending on their Cd exposure type and exposure level. The results for urinary Cd and dietary Cd intake varied according to the studies used for risk estimation. The ceiling effect was observed in results using dietary Cd intake because of the high Cd content in rice grown in the Mae Sot area. The results from β2-MG were more robust with additional DALYs ranging from 36%–86% for heart failure, cerebral infarction, and nephrosis/nephritis. Additional DALYs is a useful approach for assessing the magnitude of environmental Cd exposure. The Mae Sot population lost more healthy life compared to populations living in a non- or less Cd polluted area. This method should be applicable to various types of environmental contamination problems if exposure assessment information is available. PMID:26262629

  9. Variation in prescribing of lipid-lowering medication in primary care is associated with incidence of cardiovascular disease and all-cause mortality in people with screen-detected diabetes: findings from the ADDITION-Denmark trial

    PubMed Central

    Simmons, R K; Carlsen, A H; Griffin, S J; Charles, M; Christiansen, J S; Borch-Johnsen, K; Sandbæk, A; Lauritzen, T

    2014-01-01

    Aims To examine variation between general practices in the prescription of lipid-lowering treatment to people with screen-detected Type 2 diabetes, and associations with practice and participant characteristics and risk of cardiovascular events and all-cause mortality. Methods Observational cohort analysis of data from 1533 people with screen-detected Type 2 diabetes aged 40–69 years from the ADDITION-Denmark study. One hundred and seventy-four general practices were cluster randomized to receive: (1) routine diabetes care according to national guidelines (623 individuals), or (2) intensive multifactorial target-driven management (910 individuals). Multivariable logistic regression was used to quantify the association between the proportion of individuals in each practice who redeemed prescriptions for lipid-lowering medication in the two years following diabetes diagnosis and a composite cardiovascular disease (CVD) outcome, adjusting for age, sex, prevalent chronic disease, baseline CVD risk factors, smoking and lipid-lowering medication, and follow-up time. Results The proportion of individuals treated with lipid-lowering medication varied widely between practices (0–100%). There were 118 CVD events over 9431 person-years of follow-up. For the whole trial cohort, the risk of CVD was significantly higher in practices in the lowest compared with the highest quartile for prescribing lipid-lowering medication [adjusted odds ratio (OR) 3.4, 95% confidence interval (CI) 1.6–7.3]. Similar trends were found for all-cause mortality. Conclusions More frequent prescription of lipid-lowering treatment was associated with a lower incidence of CVD and all-cause mortality. Improved understanding of factors underlying practice variation in prescribing may enable more frequent use of lipid-lowering treatment. The results highlight the benefits of intensive treatment of people with screen-detected diabetes (Clinical Trials Registry No; NCT 00237549). What's new Despite

  10. EpCAM expression varies significantly and is differentially associated with prognosis in the luminal B HER2+, basal-like, and HER2 intrinsic subtypes of breast cancer

    PubMed Central

    Soysal, S D; Muenst, S; Barbie, T; Fleming, T; Gao, F; Spizzo, G; Oertli, D; Viehl, C T; Obermann, E C; Gillanders, W E

    2013-01-01

    Background: Epithelial cell adhesion molecule (EpCAM) is frequently expressed in breast cancer, and its expression has been associated with poor prognosis. Breast cancer can be subdivided into intrinsic subtypes, differing in prognosis and response to therapy. Methods: To investigate the association between EpCAM expression and prognosis in the intrinsic subtypes of breast cancer, we performed immunohistochemical studies on a tissue microarray encompassing a total of 1365 breast cancers with detailed clinicopathological annotation and outcomes data. Results: We observed EpCAM expression in 660 out of 1365 (48%) cases. EpCAM expression varied significantly in the different intrinsic subtypes. In univariate analyses of all cases, EpCAM expression was associated with a significantly worse overall survival. In the intrinsic subtypes, EpCAM expression was associated with an unfavourable prognosis in the basal-like and luminal B HER2+ subtypes but associated with a favourable prognosis in the HER2 subtype. Consistently, specific ablation of EpCAM resulted in increased cell viability in the breast cancer cell line SKBR3 (ER−, PR−, and HER2+) but decreased viability in the breast cancer cell line MDA-MB-231 (ER−, PR−, and HER2− ). Conclusion: The differential association of EpCAM expression with prognosis in intrinsic subtypes has important implications for the development of EpCAM-targeted therapies in breast cancer. PMID:23519058

  11. Association of Common Variants in the Human Eyes Shut Ortholog, EYS, with Statin-Induced Myopathy: Evidence for Additional Functions of EYS

    PubMed Central

    Isackson, Paul J.; Ochs-Balcom, Heather M.; Ma, Changxing; Harley, John B.; Peltier, Wendy; Tarnopolsky, Mark; Sripathi, Naganand; Wortmann, Robert L.; Simmons, Zachary; Wilson, Jon D.; Smith, Stephen A.; Barboi, Alexandru; Fine, Edward; Baer, Alan; Baker, Steven; Kaufman, Kenneth; Cobb, Beth; Kilpatrick, Jeffrey R.; Vladutiu, Georgirene D.

    2011-01-01

    Introduction Of nearly 38 million people in the U.S. receiving statin therapy, 0.1–0.5% experience severe or life-threatening myopathic side effects. Methods We performed a genome-wide association study (GWAS) in patients with severe statin myopathy versus a statin-tolerant group to identify genetic susceptibility loci. Results Replication studies in independent groups of severe statin myopathy (n=190) and statintolerant controls (n=130) resulted in the identification of three SNPs, rs9342288, rs1337512 and rs3857532, in the eyes shut homolog (EYS) on chromosome 6 suggestive of an association with risk for severe statin myopathy (p=0.0003–0.0008). Analysis of EYS cDNA demonstrated that EYS gene products are complex and expressed with relative abundance in the spinal cord as well as in the retina. Discussion Structural similarities of these EYS gene products to members of the Notch signaling pathway and to agrin suggest a possible functional role in the maintenance and regeneration of the structural integrity of skeletal muscle. PMID:21826682

  12. Additive Manufacturing Infrared Inspection

    NASA Technical Reports Server (NTRS)

    Gaddy, Darrell

    2014-01-01

    Additive manufacturing is a rapid prototyping technology that allows parts to be built in a series of thin layers from plastic, ceramics, and metallics. Metallic additive manufacturing is an emerging form of rapid prototyping that allows complex structures to be built using various metallic powders. Significant time and cost savings have also been observed using the metallic additive manufacturing compared with traditional techniques. Development of the metallic additive manufacturing technology has advanced significantly over the last decade, although many of the techniques to inspect parts made from these processes have not advanced significantly or have limitations. Several external geometry inspection techniques exist such as Coordinate Measurement Machines (CMM), Laser Scanners, Structured Light Scanning Systems, or even traditional calipers and gages. All of the aforementioned techniques are limited to external geometry and contours or must use a contact probe to inspect limited internal dimensions. This presentation will document the development of a process for real-time dimensional inspection technique and digital quality record of the additive manufacturing process using Infrared camera imaging and processing techniques.

  13. Social and Demographic Factors Associated with Morbidities in Young Children in Egypt: A Bayesian Geo-Additive Semi-Parametric Multinomial Model

    PubMed Central

    Khatab, Khaled; Adegboye, Oyelola; Mohammed, Taofeeq Ibn

    2016-01-01

    Background Globally, the burden of mortality in children, especially in poor developing countries, is alarming and has precipitated concern and calls for concerted efforts in combating such health problems. Examples of diseases that contribute to this burden of mortality include diarrhoea, cough, fever, and the overlap between these illnesses, causing childhood morbidity and mortality. Methods To gain insight into these health issues, we employed the 2008 Demographic and Health Survey Data of Egypt, which recorded details from 10,872 children under five. This data focused on the demographic and socio-economic characteristics of household members. We applied a Bayesian multinomial model to assess the area-specific spatial effects and risk factors of co-morbidity of fever, diarrhoea and cough for children under the age of five. Results The results showed that children under 20 months of age were more likely to have the three diseases (OR: 6.8; 95% CI: 4.6–10.2) than children between 20 and 40 months (OR: 2.14; 95% CI: 1.38–3.3). In multivariate Bayesian geo-additive models, the children of mothers who were over 20 years of age were more likely to have only cough (OR: 1.2; 95% CI: 0.9–1.5) and only fever (OR: 1.2; 95% CI: 0.91–1.51) compared with their counterparts. Spatial results showed that the North-eastern region of Egypt has a higher incidence than most of other regions. Conclusions This study showed geographic patterns of Egyptian governorates in the combined prevalence of morbidity among Egyptian children. It is obvious that the Nile Delta, Upper Egypt, and south-eastern Egypt have high rates of diseases and are more affected. Therefore, more attention is needed in these areas. PMID:27442018

  14. Guanosine 5'-triphosphate binding protein (G/sub i/) and two additional pertussis toxin substrates associated with muscarinic receptors in rat heart myocytes: characterization and age dependency

    SciTech Connect

    Moscona-Amir, E.; Henis, Y.I.; Sokolovsky, M.

    1988-07-12

    The coupling of muscarinic receptors with G-proteins was investigated in cultured myocytes prepared from the hearts of newborn rats. The coupling was investigated in both young (5 days after plating) and aged (14 days after plating) cultures, in view of the completely different effects of 5'-guanylyl imidodiphosphate (Gpp(NH)p) on muscarinic agonist binding to homogenates from young vs aged cultures. Pretreatment of cultures from both ages by Bordetella pertussis toxin (IAP) was found to eliminate any Gpp(NH)p effect on carbamylcholine binding. IAP by itself induced a rightward shift in the carbamylcholine competition curve in homogenates from aged cultures, but no such effect was observed in homogenates from young cultures. IAP-catalyzed (/sup 32/P)ADP-ribosylation of membrane preparations from young and aged cultures revealed major differences between them. Young cultures exhibited a major IAP substrate at 40 kDa, which was also recognized by anti-..cap alpha../sub i/ antibodies, and two novel IAP substrates at 28 and 42 kDa, which were weakly ADP-ribosylated by the toxin and were not recognized with either anti-..cap alpha../sub i/ or anti-..cap alpha../sub 0/ antibodies. In aged cultures, only the 40-kDa band (ribosylated to a lower degree) was detected. The parallel age-dependent changes in the three IAP substrates (28, 40, and 42 kDa) and in the interactions of the G-protein(s) with the muscarinic receptors strongly suggest close association between the two phenomena. All of these age-dependent changes in the G-protein related parameters were prevented by phosphatidylcholine-liposome treatment of the aged cultures. The role of the membrane lipid composition in these phenomena is discussed.

  15. Addition of 10-Day Decitabine to Fludarabine/Total Body Irradiation Conditioning is Feasible and Induces Tumor-Associated Antigen-Specific T Cell Responses.

    PubMed

    Cruijsen, Marjan; Hobo, Willemijn; van der Velden, Walter J F M; Bremmers, Manita E J; Woestenenk, Rob; Bär, Brigitte; Falkenburg, J H Frederik; Kester, Michel; Schaap, Nicolaas P M; Jansen, Joop; Blijlevens, Nicole N M; Dolstra, Harry; Huls, Gerwin

    2016-06-01

    Allogeneic hematopoietic cell transplantation (HCT) offers the possibility of curative therapy for patients with myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), and acute myelogenous leukemia (AML). However, post-HCT relapse remains a major problem, particularly in patients with high-risk cytogenetics and in patients who cannot tolerate consolidation chemotherapy (eg, due to previous toxicity). We assessed the toxicity and efficacy of 10-day decitabine (Dec), fludarabine (Flu), and 2 Gy total body irradiation (TBI) as a new conditioning regimen for allogeneic HCT in patients with MDS, CMML, or AML. Thirty patients were enrolled, including 11 with MDS, 2 with CMML, and 17 with AML. Patients received 20 mg/m(2)/day Dec on days -11 to -2, 30 mg/m(2)/day Flu on days -4 to -2, and 2 Gy TBI on day -1, followed by infusion of a donor stem cell graft on day 0. Postgrafting immunosuppression consisted of cyclosporin A and mycophenolate mofetil. At a median follow-up of 443 days, the overall survival was 53%, relapse incidence was 27%, and nonrelapse mortality was 27%. The incidence of severe acute (grade III/IV) graft-versus-host disease (GVHD) was 27%, and that of (predominantly mild) chronic GVHD was 60%. Immunomonitoring studies revealed that specific CD8(+) T cell responses against epigenetically silenced tumor-associated antigens (TAAs), including cancer-testis antigens (MAGE-A1/A2/A3 and PRAME) and RHAMM, occurred more frequently in patients who had received Dec/Flu/TBI conditioning (8 of 11 patients) compared with a control group of patients who had received only Flu/TBI conditioning (2 of 9 patients). In summary, Dec/Flu/TBI conditioning proved feasible and effective and enhanced the induction of TAA-reactive CD8(+) T cell responses in vivo, which may contribute to disease control post-transplantation. PMID:26860635

  16. HIF-1α 1772 C/T and 1790 G/A Polymorphisms Are Significantly Associated with Higher Cancer Risk: An Updated Meta-Analysis from 34 Case-Control Studies

    PubMed Central

    Zhang, Chi; Qin, Qin; Liu, Jia; Xu, Li-Ping; Zhao, Lian-Jun; Zhang, Qu; Cai, Jing; Ma, Jian-Xin; Cheng, Hong-Yan; Sun, Xin-Chen

    2013-01-01

    Background HIF-1 activates various genes in cancer progression and metastasis. HIF-1α 1772 C/T and 1790 G/A polymorphisms are reportedly associated with cancer risk; however, the results are inconclusive. Methodology/Principal Findings A meta-analysis of 34 studies that involved 7522 cases and 9847 controls for 1772 C/T and 24 studies that involved 4884 cases and 8154 controls for 1790 G/A was conducted to identify the association of C/T and G/A polymorphisms with cancer risk. Odds ratio (OR) and 95% confidence intervals (95% CI) were used to assess the strength of association. HIF-1α 1772 C/T and 1790 G/A polymorphisms were associated with higher cancer risk in homozygote comparison (1772C/T: TT vs. CC: OR = 2.45, 95% CI: 1.52, 3.96; Pheterogeneity = 0.028; 1790G/A: AA vs. GG: OR=4.74, 95% CI: 1.78, 12.6; Pheterogeneity < 0.01), dominant model (1772C/T: TT/CT vs. CC: OR = 1.27, 95% CI: 1.04, 1.55; Pheterogeneity < 0.01, 1790G/A: AA/GA vs. GG: OR = 1.65, 95% CI: 1.05, 2.60; Pheterogeneity < 0.01), T allele versus C allele (T vs. C: OR = 1.42, 95% CI: 1.18, 1.70; Pheterogeneity < 0.01), and A allele versus G allele (A vs. G: OR = 1.83, 95% CI: 1.13, 2.96; Pheterogeneity < 0.01). On a subgroup analysis, the 1772 C/T polymorphism was significantly linked to higher risks for breast cancer, lung cancer, prostate cancer, and cervical cancer, whereas the 1790 G/A polymorphism was significantly linked to higher risks for lung cancer and prostate cancer. A significantly increased cancer risk was found in both Asians and Caucasians for 1772C/T polymorphism, whereas a significantly increased cancer risk was found in Caucasians in the heterozygote comparison and recessive model for 1790G/A polymorphism. Conclusions HIF-1α 1772 C/T and 1790 G/A polymorphisms are significantly associated with higher cancer risk. PMID:24260383

  17. Significant Tsunami Events

    NASA Astrophysics Data System (ADS)

    Dunbar, P. K.; Furtney, M.; McLean, S. J.; Sweeney, A. D.

    2014-12-01

    Tsunamis have inflicted death and destruction on the coastlines of the world throughout history. The occurrence of tsunamis and the resulting effects have been collected and studied as far back as the second millennium B.C. The knowledge gained from cataloging and examining these events has led to significant changes in our understanding of tsunamis, tsunami sources, and methods to mitigate the effects of tsunamis. The most significant, not surprisingly, are often the most devastating, such as the 2011 Tohoku, Japan earthquake and tsunami. The goal of this poster is to give a brief overview of the occurrence of tsunamis and then focus specifically on several significant tsunamis. There are various criteria to determine the most significant tsunamis: the number of deaths, amount of damage, maximum runup height, had a major impact on tsunami science or policy, etc. As a result, descriptions will include some of the most costly (2011 Tohoku, Japan), the most deadly (2004 Sumatra, 1883 Krakatau), and the highest runup ever observed (1958 Lituya Bay, Alaska). The discovery of the Cascadia subduction zone as the source of the 1700 Japanese "Orphan" tsunami and a future tsunami threat to the U.S. northwest coast, contributed to the decision to form the U.S. National Tsunami Hazard Mitigation Program. The great Lisbon earthquake of 1755 marked the beginning of the modern era of seismology. Knowledge gained from the 1964 Alaska earthquake and tsunami helped confirm the theory of plate tectonics. The 1946 Alaska, 1952 Kuril Islands, 1960 Chile, 1964 Alaska, and the 2004 Banda Aceh, tsunamis all resulted in warning centers or systems being established.The data descriptions on this poster were extracted from NOAA's National Geophysical Data Center (NGDC) global historical tsunami database. Additional information about these tsunamis, as well as water level data can be found by accessing the NGDC website www.ngdc.noaa.gov/hazard/

  18. ENIGMA--evidence-based network for the interpretation of germline mutant alleles: an international initiative to evaluate risk and clinical significance associated with sequence variation in BRCA1 and BRCA2 genes.

    PubMed

    Spurdle, Amanda B; Healey, Sue; Devereau, Andrew; Hogervorst, Frans B L; Monteiro, Alvaro N A; Nathanson, Katherine L; Radice, Paolo; Stoppa-Lyonnet, Dominique; Tavtigian, Sean; Wappenschmidt, Barbara; Couch, Fergus J; Goldgar, David E

    2012-01-01

    As genetic testing for predisposition to human diseases has become an increasingly common practice in medicine, the need for clear interpretation of the test results is apparent. However, for many disease genes, including the breast cancer susceptibility genes BRCA1 and BRCA2, a significant fraction of tests results in the detection of a genetic variant for which disease association is not known. The finding of an "unclassified" variant (UV)/variant of uncertain significance (VUS) complicates genetic test reporting and counseling. As these variants are individually rare, a large collaboration of researchers and clinicians will facilitate studies to assess their association with cancer predisposition. It was with this in mind that the ENIGMA consortium (www.enigmaconsortium.org) was initiated in 2009. The membership is both international and interdisciplinary, and currently includes more than 100 research scientists and clinicians from 19 countries. Within ENIGMA, there are presently six working groups focused on the following topics: analysis, clinical, database, functional, tumor histopathology, and mRNA splicing. ENIGMA provides a mechanism to pool resources, exchange methods and data, and coordinately develop and apply algorithms for classification of variants in BRCA1 and BRCA2. It is envisaged that the research and clinical application of models developed by ENIGMA will be relevant to the interpretation of sequence variants in other disease genes. PMID:21990146

  19. Microbial biosurfactants as additives for food industries.

    PubMed

    Campos, Jenyffer Medeiros; Stamford, Tânia Lúcia Montenegro; Sarubbo, Leonie Asfora; de Luna, Juliana Moura; Rufino, Raquel Diniz; Banat, Ibrahim M

    2013-01-01

    Microbial biosurfactants with high ability to reduce surface and interfacial surface tension and conferring important properties such as emulsification, detergency, solubilization, lubrication and phase dispersion have a wide range of potential applications in many industries. Significant interest in these compounds has been demonstrated by environmental, bioremediation, oil, petroleum, food, beverage, cosmetic and pharmaceutical industries attracted by their low toxicity, biodegradability and sustainable production technologies. Despite having significant potentials associated with emulsion formation, stabilization, antiadhesive and antimicrobial activities, significantly less output and applications have been reported in food industry. This has been exacerbated by uneconomical or uncompetitive costing issues for their production when compared to plant or chemical counterparts. In this review, biosurfactants properties, present uses and potential future applications as food additives acting as thickening, emulsifying, dispersing or stabilising agents in addition to the use of sustainable economic processes utilising agro-industrial wastes as alternative substrates for their production are discussed. PMID:23956227

  20. Prevalence of defined ultrasound findings of unknown significance at the second trimester fetal anomaly scan and their association with adverse pregnancy outcomes: the Welsh study of mothers and babies population‐based cohort

    PubMed Central

    Hurt, Lisa; Wright, Melissa; Dunstan, Frank; Thomas, Susan; Brook, Fiona; Morris, Susan; Tucker, David; Wills, Marilyn Ann; Davies, Colin; John, Gareth; Fone, David

    2015-01-01

    Abstract Objective The aim of this article was to estimate the population prevalence of seven defined ultrasound findings of uncertain significance (‘markers’) in the second trimester and the associated risk of adverse pregnancy outcomes. Method A prospective record‐linked cohort study of 30 078 pregnant women who had second trimester anomaly scans between July 2008 and March 2011 in Wales was conducted. Results The prevalence of markers ranged from 43.7 per 1000 singleton pregnancies for cardiac echogenic foci [95% confidence interval (CI): 38.8, 51.1] to 0.6 for mild‐to‐moderate ventriculomegaly (95% CI: 0.3, 1.0). Isolated echogenic bowel was associated with an increased risk of congenital anomalies [risk ratio (RR) 4.54, 95% CI: 2.12, 9.73] and preterm birth (RR 2.30, 95% CI: 1.08, 4.90). Isolated pelvicalyceal dilatation was associated with an increased risk of congenital anomalies (RR 3.82, 95% CI: 2.16, 6.77). Multiple markers were associated with an increased risk of congenital anomalies (RR 5.00, 95% CI: 1.35, 18.40) and preterm birth (RR 3.38, 95% CI 1.20, 9.53). Conclusions These data are useful for counselling families and developing clinical guidance and care pathways following the detection of markers in clinical practice, particularly the need for follow‐up scans to monitor placental function and growth in pregnancies with isolated echogenic bowel, and further investigation for multiple markers. © 2015 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd. PMID:26475362

  1. Functional Generalized Additive Models.

    PubMed

    McLean, Mathew W; Hooker, Giles; Staicu, Ana-Maria; Scheipl, Fabian; Ruppert, David

    2014-01-01

    We introduce the functional generalized additive model (FGAM), a novel regression model for association studies between a scalar response and a functional predictor. We model the link-transformed mean response as the integral with respect to t of F{X(t), t} where F(·,·) is an unknown regression function and X(t) is a functional covariate. Rather than having an additive model in a finite number of principal components as in Müller and Yao (2008), our model incorporates the functional predictor directly and thus our model can be viewed as the natural functional extension of generalized additive models. We estimate F(·,·) using tensor-product B-splines with roughness penalties. A pointwise quantile transformation of the functional predictor is also considered to ensure each tensor-product B-spline has observed data on its support. The methods are evaluated using simulated data and their predictive performance is compared with other competing scalar-on-function regression alternatives. We illustrate the usefulness of our approach through an application to brain tractography, where X(t) is a signal from diffusion tensor imaging at position, t, along a tract in the brain. In one example, the response is disease-status (case or control) and in a second example, it is the score on a cognitive test. R code for performing the simulations and fitting the FGAM can be found in supplemental materials available online. PMID:24729671

  2. Addition of Rice Bran Arabinoxylan to Curcumin Therapy May Be of Benefit to Patients With Early-Stage B-Cell Lymphoid Malignancies (Monoclonal Gammopathy of Undetermined Significance, Smoldering Multiple Myeloma, or Stage 0/1 Chronic Lymphocytic Leukemia): A Preliminary Clinical Study.

    PubMed

    Golombick, Terry; Diamond, Terrence H; Manoharan, Arumugam; Ramakrishna, Rajeev

    2016-06-01

    Hypothesis Prior studies on patients with early B-cell lymphoid malignancies suggest that early intervention with curcumin may lead to delay in progressive disease and prolonged survival. These patients are characterized by increased susceptibility to infections. Rice bran arabinoxylan (Ribraxx) has been shown to have immunostimulatory, anti-inflammatory, and proapoptotic effects. We postulated that addition of Ribraxx to curcumin therapy may be of benefit. Study design Monoclonal gammopathy of undetermined significance (MGUS)/smoldering multiple myeloma (SMM) or stage 0/1 chronic lymphocytic leukemia (CLL) patients who had been on oral curcumin therapy for a period of 6 months or more were administered both curcumin (as Curcuforte) and Ribraxx. Methods Ten MGUS/SMM patients and 10 patients with stage 0/1 CLL were administered 6 g of curcumin and 2 g Ribraxx daily. Blood samples were collected at baseline and at 2-month intervals for a period of 6 months, and various markers were monitored. MGUS/SMM patients included full blood count (FBC); paraprotein; free light chains/ratio; C-reactive protein (CRP)and erythrocyte sedimentation rate (ESR); B2 microglobulin and immunological markers. Markers monitored for stage 0/1 CLL were FBC, CRP and ESR, and immunological markers. Results Of 10 MGUS/SMM patients,5 (50%) were neutropenic at baseline, and the Curcuforte/Ribraxx combination therapy showed an increased neutrophil count, varying between 10% and 90% among 8 of the 10 (80%) MGUS/SMM patients. An additional benefit of the combination therapy was the potent effect in reducing the raised ESR in 4 (44%) of the MGUS/SMM patients. Conclusion Addition of Ribraxx to curcumin therapy may be of benefit to patients with early-stage B-cell lymphoid malignancies. PMID:27154182

  3. Association and prognostic significance of BRCA1/2-mutation status with neoantigen load, number of tumor-infiltrating lymphocytes and expression of PD-1/PD-L1 in high grade serous ovarian cancer

    PubMed Central

    Strickland, Kyle C.; Howitt, Brooke E.; Shukla, Sachet A.; Rodig, Scott; Ritterhouse, Lauren L.; Liu, Joyce F.; Garber, Judy E.; Chowdhury, Dipanjan; Wu, Catherine J.; D'Andrea, Alan D.; Matulonis, Ursula A.; Konstantinopoulos, Panagiotis A.

    2016-01-01

    Immune checkpoint inhibitors (e.g., anti-PD-1 and anti-PD-L1 antibodies) have demonstrated remarkable efficacy against hypermutated cancers such as melanomas and lung carcinomas. One explanation for this effect is that hypermutated lesions harbor more tumor-specific neoantigens that stimulate recruitment of an increased number of tumor-infiltrating lymphocytes (TILs), which is counterbalanced by overexpression of immune checkpoints such as PD-1 or PD-L1. Given that BRCA1/2-mutated high grade serous ovarian cancers (HGSOCs) exhibit a higher mutational load and a unique mutational signature with an elevated number of larger indels up to 50 bp, we hypothesized that they may also harbor more tumor-specific neoantigens, and, therefore, exhibit increased TILs and PD-1/PD-L1 expression. Here, we report significantly higher predicted neoantigens in BRCA1/2-mutated tumors compared to tumors without alterations in homologous recombination (HR) genes (HR-proficient tumors). Tumors with higher neoantigen load were associated with improved overall survival and higher expression of immune genes associated with tumor cytotoxicity such as genes of the TCR, the IFN-gamma and the TNFR pathways. Furthermore, immunohistochemistry studies demonstrated that BRCA1/2-mutated tumors exhibited significantly increased CD3+ and CD8+ TILs, as well as elevated expression of PD-1 and PD-L1 in tumor-associated immune cells compared to HR-proficient tumors. Survival analysis showed that both BRCA1/2-mutation status and number of TILs were independently associated with outcome. Of note, two distinct groups of HGSOCs, one with very poor prognosis (HR proficient with low number of TILs) and one with very good prognosis (BRCA1/2-mutated tumors with high number of TILs) were defined. These findings support a link between BRCA1/2-mutation status, immunogenicity and survival, and suggesting that BRCA1/2-mutated HGSOCs may be more sensitive to PD-1/PD-L1 inhibitors compared to HR-proficient HGSOCs. PMID

  4. Work organization is significantly associated with upper extremities musculoskeletal disorders among employees engaged in interactive computer-telephone tasks of an international bank subsidiary in São Paulo, Brazil.

    PubMed

    Ferreira Júnior, M; Conceição, G M; Saldiva, P H

    1997-04-01

    This study was designed to verify the risk factors for developing upper extremities musculoskeletal disorders (UEMD) among workers engaged in customer service tasks performed by telephone at a private banking corporation in São Paulo, Brazil. The monthly incidence of UEMD in hands and/or wrists in this group was studied retrospectively from January 1993 to June 1995. The statistical analysis was done by using multiple linear regression with the monthly incidence of UEMD considered as dependent variable in models controlled for age, seniority, mean daily regular worktime and overtime per operator, time pressure at work, rest/work schedule, management status, personnel training on postural and muscle stretching, and ergonomic hazards. The variables associated with UEMD were the following: time pressure at work (coefficient = 0.049; p = 0.008) and rest/work schedule (coefficient = -0.047; p = 0.02). The results indicate that working conditions are significantly associated with UEMD, and changes in the working schedule may decrease the incidence of this problem in workers assigned to tasks related to the interactive use of computer-accessible databases during telephone contacts. PMID:9093663

  5. Metformin may function as anti-cancer agent via targeting cancer stem cells: the potential biological significance of tumor-associated miRNAs in breast and pancreatic cancers

    PubMed Central

    Bao, Bin; Azmi, Asfar S.; Ali, Shadan; Zaiem, Feras

    2014-01-01

    Metformin is one of the most used diabetic drugs for the management of type II diabetes mellitus (DM) in the world. Increased numbers of epidemiological and clinical studies have provided convincing evidence supporting the role of metformin in the development and progression of a variety of human tumors including breast and pancreatic cancer. Substantial pre-clinical evidence from in vitro and in vivo experimental studies strongly suggests that metformin has an anti-cancer activity mediated through the regulation of several cell signaling pathways including activation of AMP kinase (AMPK), and other direct and indirect mechanisms; however, the detailed mechanism(s) has not yet been fully understood. The concept of cancer stem cells (CSCs) has gained significant attention in recent years due its identification and defining its clinical implications in many different tumors including breast cancer and pancreatic cancer. In this review, we will discuss the protective role of metformin in the development of breast and pancreatic cancers. We will further discuss the role of metformin as an anti-cancer agent, which is in part mediated through targeting CSCs. Finally, we will discuss the potential role of metformin in the modulation of tumor-associated or CSC-associated microRNAs (miRNAs) as part of the novel mechanism of action of metformin in the development and progression of breast and pancreatic cancers. PMID:25333034

  6. Metformin may function as anti-cancer agent via targeting cancer stem cells: the potential biological significance of tumor-associated miRNAs in breast and pancreatic cancers.

    PubMed

    Bao, Bin; Azmi, Asfar S; Ali, Shadan; Zaiem, Feras; Sarkar, Fazlul H

    2014-06-01

    Metformin is one of the most used diabetic drugs for the management of type II diabetes mellitus (DM) in the world. Increased numbers of epidemiological and clinical studies have provided convincing evidence supporting the role of metformin in the development and progression of a variety of human tumors including breast and pancreatic cancer. Substantial pre-clinical evidence from in vitro and in vivo experimental studies strongly suggests that metformin has an anti-cancer activity mediated through the regulation of several cell signaling pathways including activation of AMP kinase (AMPK), and other direct and indirect mechanisms; however, the detailed mechanism(s) has not yet been fully understood. The concept of cancer stem cells (CSCs) has gained significant attention in recent years due its identification and defining its clinical implications in many different tumors including breast cancer and pancreatic cancer. In this review, we will discuss the protective role of metformin in the development of breast and pancreatic cancers. We will further discuss the role of metformin as an anti-cancer agent, which is in part mediated through targeting CSCs. Finally, we will discuss the potential role of metformin in the modulation of tumor-associated or CSC-associated microRNAs (miRNAs) as part of the novel mechanism of action of metformin in the development and progression of breast and pancreatic cancers. PMID:25333034

  7. AB161. High resolution melting analysis of buccal DNA revealed a significant association between UGT1A1 c.211G>A and neonatal hyperbilirubinemia development in Malay population

    PubMed Central

    Cheung, Tian Pei; Van Rostenberghe, Hans; Ismail, Rosliza; Nawawi, Noor Namirah; Abdullah, Nurul Amierah; Ramli, Noraida; Ibrahim, Nor Rosidah; Hj Abd Majid, Noorizan; Mohd Yusoff, Narazah; Nishio, Hisahide; Yusoff, Surini

    2015-01-01

    Background Severe neonatal hyperbilirubinemia or neonatal jaundice (NNJ) characterised by an elevated total serum bilirubin (TSB) level may result in kernicterus or even death. Uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) is the key enzyme which conjugates bilirubin with glucuronic acid for the subsequent bilirubin excretion. Conversely, constitutive androstane receptor (CAR), encoded by nuclear receptor subfamily 1, group I, member 3 (NR1I3) gene, regulates bilirubin excretion by activating the components of the bilirubin clearance pathway. Thus, genetic variants in UGT1A1 and NR1I3 genes may modulate bilirubin excretion and lead to NNJ. This study aimed to determine the association between UGT1A1 and NR1I3 genetic variants and NNJ development in Malay population by genotyping the DNA isolated from buccal swabs. The accuracy and reliability of the genotyping results produced by buccal DNA was also compared with that of the whole blood DNA. Methods Buccal swabs were collected from 232 hyperbilirubinemia and 232 non-hyperbilirubinemia newborns admitted to and/or born in Hospital Universiti Sains Malaysia (HUSM). Hyperbilirubinemia subjects were those with TSB levels ≥250 µmol/L within the first week after birth while non-hyperbilirubinemia subjects were newborns without significant hyperbilirubinemia. The UGT1A1 (c.211G>A) and NR1I3 [MPJ6_1I3008 (G>A), IVS8+116T>G and 540A>G] variants were genotyped by using high resolution melting (HRM) analysis. Binary logistic regression was used to assess the association between variant genotypes and risk of NNJ. Whole blood samples were also collected from 60 subjects and genotyped to compare the HRM genotyping results with that of the buccal swabs. Results When compared with wild-type genotype, both heterozygous and homozygous variant genotypes of MPJ6_1I3008 (G>A), IVS8+116T>G and 540A>G were not significantly associated with NNJ. However, the heterozygous genotype (GA) of c.211G>A was found to increase the

  8. Significant Scales in Community Structure

    PubMed Central

    Traag, V. A.; Krings, G.; Van Dooren, P.

    2013-01-01

    Many complex networks show signs of modular structure, uncovered by community detection. Although many methods succeed in revealing various partitions, it remains difficult to detect at what scale some partition is significant. This problem shows foremost in multi-resolution methods. We here introduce an efficient method for scanning for resolutions in one such method. Additionally, we introduce the notion of “significance” of a partition, based on subgraph probabilities. Significance is independent of the exact method used, so could also be applied in other methods, and can be interpreted as the gain in encoding a graph by making use of a partition. Using significance, we can determine “good” resolution parameters, which we demonstrate on benchmark networks. Moreover, optimizing significance itself also shows excellent performance. We demonstrate our method on voting data from the European Parliament. Our analysis suggests the European Parliament has become increasingly ideologically divided and that nationality plays no role. PMID:24121597

  9. Are changes in glycaemic control associated with diabetes-specific quality of life and health status in screen-detected type 2 diabetes patients? Four-year follow up of the ADDITION-Cambridge cohort

    PubMed Central

    Kuznetsov, L; Long, G H; Griffin, S J; Simmons, R K

    2015-01-01

    Background Interventions that improve HbA1c levels do not necessarily improve health-related quality of life (QoL). This issue may be particularly relevant in asymptomatic diabetes patients detected earlier in the course of the disease. Methods HbA1c, diabetes-specific QoL (ADDQoL) and health status were measured in 510 screen-detected diabetes patients from the ADDITION-Cambridge trial at 1 and 5 years post diagnosis. Multivariable logistic/linear regression was used to quantify the longitudinal association between change in HbA1c from 1 to 5 years and ADDQoL and health status at 5 years, adjusting for age, sex, education and trial group; alcohol consumption, smoking, physical activity, plasma vitamin C, HbA1c, ADDQoL or health status at 1 year, and glucose-lowering medication at 5 years. Results From 1 to 5 years, median HbA1c interquartile range increased from 6.3% (5.9–6.8) to 6.8% (6.4–7.4); the median ADDQoL score and mean health status physical health summary score decreased from -0.4 (-1 to -0.08) to -0.5 (-1.08 to -0.09) (suggesting an adverse impact of diabetes on QoL) and by -0.79 (8.94) points, respectively. Increases in HbA1c were independently associated with reporting a negative impact of diabetes on QoL (OR = 1.38, 95% CI: 1.03 to 1.85) but not with the health status summary scores. Conclusions Increases in HbA1c from 1 to 5 years post-diagnosis were independently associated with increased odds of reporting a negative impact of diabetes on QoL. While our results suggest that efforts to reduce HbA1c do not adversely affect health-related QoL, large numbers of participants still report a negative impact of diabetes on their QoL 5 years post-diagnosis. © 2014 The Authors. Diabetes/Metabolism Research and Reviews published by John Wiley & Sons, Ltd. PMID:24817063

  10. Significant lexical relationships

    SciTech Connect

    Pedersen, T.; Kayaalp, M.; Bruce, R.

    1996-12-31

    Statistical NLP inevitably deals with a large number of rare events. As a consequence, NLP data often violates the assumptions implicit in traditional statistical procedures such as significance testing. We describe a significance test, an exact conditional test, that is appropriate for NLP data and can be performed using freely available software. We apply this test to the study of lexical relationships and demonstrate that the results obtained using this test are both theoretically more reliable and different from the results obtained using previously applied tests.

  11. Elevation of neuron specific enolase and brain iron deposition on susceptibility-weighted imaging as diagnostic clues for beta-propeller protein-associated neurodegeneration in early childhood: Additional case report and review of the literature.

    PubMed

    Takano, Kyoko; Shiba, Naoko; Wakui, Keiko; Yamaguchi, Tomomi; Aida, Noriko; Inaba, Yuji; Fukushima, Yoshimitsu; Kosho, Tomoki

    2016-02-01

    Beta-propeller protein-associated neurodegeneration (BPAN), also known as static encephalopathy of childhood with neurodegeneration in adulthood (SENDA), is a subtype of neurodegeneration with brain iron accumulation (NBIA). BPAN is caused by mutations in an X-linked gene WDR45 that is involved in autophagy. BPAN is characterized by developmental delay or intellectual disability until adolescence or early adulthood, followed by severe dystonia, parkinsonism, and progressive dementia. Brain magnetic resonance imaging (MRI) shows iron deposition in the bilateral globus pallidus (GP) and substantia nigra (SN). Clinical manifestations and laboratory findings in early childhood are limited. We report a 3-year-old girl with BPAN who presented with severe developmental delay and characteristic facial features. In addition to chronic elevation of serum aspartate transaminase, lactate dehydrogenase, creatine kinase, and soluble interleukin-2 receptor, she had persistent elevation of neuron specific enolase (NSE) in serum and cerebrospinal fluid. MRI using susceptibility-weighted imaging (SWI) demonstrated iron accumulation in the GP and SN bilaterally. Targeted next-generation sequencing identified a de novo splice-site mutation, c.831-1G>C in WDR45, which resulted in aberrant splicing evidenced by reverse transcriptase-PCR. Persistent elevation of NSE and iron deposition on SWI may provide clues for diagnosis of BPAN in early childhood. PMID:26481852

  12. Statistical Significance Testing.

    ERIC Educational Resources Information Center

    McLean, James E., Ed.; Kaufman, Alan S., Ed.

    1998-01-01

    The controversy about the use or misuse of statistical significance testing has become the major methodological issue in educational research. This special issue contains three articles that explore the controversy, three commentaries on these articles, an overall response, and three rejoinders by the first three authors. They are: (1)…

  13. Lack of Statistical Significance

    ERIC Educational Resources Information Center

    Kehle, Thomas J.; Bray, Melissa A.; Chafouleas, Sandra M.; Kawano, Takuji

    2007-01-01

    Criticism has been leveled against the use of statistical significance testing (SST) in many disciplines. However, the field of school psychology has been largely devoid of critiques of SST. Inspection of the primary journals in school psychology indicated numerous examples of SST with nonrandom samples and/or samples of convenience. In this…

  14. [Food additives and healthiness].

    PubMed

    Heinonen, Marina

    2014-01-01

    Additives are used for improving food structure or preventing its spoilage, for example. Many substances used as additives are also naturally present in food. The safety of additives is evaluated according to commonly agreed principles. If high concentrations of an additive cause adverse health effects for humans, a limit of acceptable daily intake (ADI) is set for it. An additive is a risk only when ADI is exceeded. The healthiness of food is measured on the basis of nutrient density and scientifically proven effects. PMID:24772784

  15. Polyimide processing additives

    NASA Technical Reports Server (NTRS)

    Pratt, J. R.; St. Clair, T. L.; Burks, H. D.; Stoakley, D. M.

    1987-01-01

    A method has been found for enhancing the melt flow of thermoplastic polyimides during processing. A high molecular weight 422 copoly(amic acid) or copolyimide was fused with approximately 0.05 to 5 pct by weight of a low molecular weight amic acid or imide additive, and this melt was studied by capillary rheometry. Excellent flow and improved composite properties on graphite resulted from the addition of a PMDA-aniline additive to LARC-TPI. Solution viscosity studies imply that amic acid additives temporarily lower molecular weight and, hence, enlarge the processing window. Thus, compositions containing the additive have a lower melt viscosity for a longer time than those unmodified.

  16. TBX21-1993T/C (rs4794067) polymorphism is associated with increased risk of chronic periodontitis and increased T-bet expression in periodontal lesions, but does not significantly impact the IFN-g transcriptional level or the pattern of periodontophatic bacterial infection

    PubMed Central

    Cavalla, Franco; Biguetti, Claudia Cristina; Colavite, Priscila Maria; Silveira, Elcia Varise; Martins, Walter; Letra, Ariadne; Trombone, Ana Paula Favaro; Silva, Renato Menezes; Garlet, Gustavo Pompermaier

    2015-01-01

    Th1-polarized host response, mediated by IFN-γ, has been associated with increased severity of periodontal disease as well as control of periodontal infection. The functional polymorphism TBX21-1993T/C (rs4794067) increases the transcriptional activity of the TBX21 gene (essential for Th1 polarization) resulting in a predisposition to a Th-1 biased immune response. Thus, we conducted a case-control study, including a population of healthy controls (H, n = 218), chronic periodontitis (CP, n = 197), and chronic gingivitis patients (CG, n = 193), to investigate if genetic variations in TBX21 could impact the development of Th1 responses, and consequently influence the pattern of bacterial infection and periodontitis outcome. We observed that the polymorphic allele T was significantly enriched in the CP patients compared to CG subjects, while the H controls demonstrated and intermediate genotype. Also, investigating the putative functionality TBX21-1993T/C in the modulation of local response, we observed that the transcripts levels of T-bet, but not of IFN-γ, were upregulated in homozygote and heterozygote polymorphic subjects. In addition, TBX21-1993T/C did not influence the pattern of bacterial infection or the clinical parameters of disease severity, being the presence/absence of red complex bacteria the main factor associated with the disease status and the subrogate variable probing depth (PD) in the logistic regression analysis. PMID:25832120

  17. Tectonic significance of serpentinites

    NASA Astrophysics Data System (ADS)

    Guillot, Stéphane; Schwartz, Stéphane; Reynard, Bruno; Agard, Philippe; Prigent, Cécile

    2015-04-01

    At plate boundaries, where deformation is localized along centimetre- to kilometre-scale shear zones, the influence of serpentinite on tectonic processes is linked to its unique rheological properties. In this paper we review the physical properties of serpentinites and their role in tectonic processes. At the ocean-continent transition, serpentinization weakens the upper mantle layer, promoting strain localization and allowing the normal faults in the distal margin to root at low angle. Similarly, at slow to ultra-slow spreading ridges, serpentinite is potentially very abundant at the seafloor and locally associated with domal structures. Extensional deformation is localized in a ~ 100 m thick shear zone at the footwall of detachment zones dominated by serpentine derived minerals. Within subduction zone, the depth of decoupling between the mantle wedge and the subducting slab corresponds to the stability depth of serpentine weak mineral. Dehydration of serpentine has also been hypothesized to play an important role in the origin of double seismic zones, however the exact mechanism through which dehydration promotes seismicity remains a matter of debate. During exhumation of high-pressure or ultrahigh-pressure rocks, the opposite trajectories of exhumation and subduction require a decoupling zone within the subducting slab. A serpentinized layer has the potential to become a decoupling zone between the oceanic crust and underlying lithosphere. The buoyancy of serpentinite also likely contributes to eclogite exhumation. Finally, along major strike-slip faults, serpentinites have been associated with fault creep, as well as low fault strength. The presence of serpentinite blocks along creeping segments of active faults worldwide is therefore likely to originate from fluids deriving from the progressive dehydration of the mantle wedge that move such bodies upward.

  18. Additive usage levels.

    PubMed

    Langlais, R

    1996-01-01

    With the adoption of the European Parliament and Council Directives on sweeteners, colours and miscellaneous additives the Commission is now embarking on the project of coordinating the activities of the European Union Member States in the collection of the data that are to make up the report on food additive intake requested by the European Parliament. This presentation looks at the inventory of available sources on additive use levels and concludes that for the time being national legislation is still the best source of information considering that the directives have yet to be transposed into national legislation. Furthermore, this presentation covers the correlation of the food categories as found in the additives directives with those used by national consumption surveys and finds that in a number of instances this correlation still leaves a lot to be desired. The intake of additives via food ingestion and the intake of substances which are chemically identical to additives but which occur naturally in fruits and vegetables is found in a number of cases to be higher than the intake of additives added during the manufacture of foodstuffs. While the difficulties are recognized in contributing to the compilation of food additive intake data, industry as a whole, i.e. the food manufacturing and food additive manufacturing industries, are confident that in a concerted effort, use data on food additives by industry can be made available. Lastly, the paper points out that with the transportation of the additives directives into national legislation and the time by which the food industry will be able to make use of the new food legislative environment several years will still go by; food additives use data by the food industry will thus have to be reviewed at the beginning of the next century. PMID:8792135

  19. An additional middle cuneiform?

    PubMed Central

    Brookes-Fazakerley, S.D.; Jackson, G.E.; Platt, S.R.

    2015-01-01

    Additional cuneiform bones of the foot have been described in reference to the medial bipartite cuneiform or as small accessory ossicles. An additional middle cuneiform has not been previously documented. We present the case of a patient with an additional ossicle that has the appearance and location of an additional middle cuneiform. Recognizing such an anatomical anomaly is essential for ruling out second metatarsal base or middle cuneiform fractures and for the preoperative planning of arthrodesis or open reduction and internal fixation procedures in this anatomical location. PMID:26224890

  20. Statistical or biological significance?

    PubMed

    Saxon, Emma

    2015-01-01

    Oat plants grown at an agricultural research facility produce higher yields in Field 1 than in Field 2, under well fertilised conditions and with similar weather exposure; all oat plants in both fields are healthy and show no sign of disease. In this study, the authors hypothesised that the soil microbial community might be different in each field, and these differences might explain the difference in oat plant growth. They carried out a metagenomic analysis of the 16 s ribosomal 'signature' sequences from bacteria in 50 randomly located soil samples in each field to determine the composition of the bacterial community. The study identified >1000 species, most of which were present in both fields. The authors identified two plant growth-promoting species that were significantly reduced in soil from Field 2 (Student's t-test P < 0.05), and concluded that these species might have contributed to reduced yield. PMID:26541972

  1. The significance of sex.

    PubMed

    Annila, Arto; Annila, Erkki

    2012-12-01

    Sexual and asexual modes of proliferation are associated with advantages and disadvantages, yet a profound percept that would account for both ways of reproduction is missing. On the basis of the 2nd law of thermodynamics we find that both sexual and asexual reproduction can be regarded as a means to consume free energy in least time. Parthenogenesis is a fast way to consume a rich repository of free energy, e.g., an ample stock of food with a large number of individuals, whereas sexual reproduction is a fast way to consume diverse and dispersed resources with a large variety of individuals. Most organisms have adapted to their surroundings accordingly and some organisms switch from one mode of reproduction to the other depending on the amount and dispersion of free-energy sources. We conclude that the least-time free energy consumption in respective surroundings, as the general criterion of natural selection, determines also sexual and asexual modes of reproduction. PMID:23063598

  2. Anthropological significance of phenylketonuria.

    PubMed

    Saugstad, L F

    1975-01-01

    The highest incidence rates of phenylketonuria (PKU) have been observed in Ireland and Scotlant. Parents heterozygous for PKU in Norway differ significantly from the general population in the Rhesus, Kell and PGM systems. The parents investigated showed an excess of Rh negative, Kell plus and PGM type 1 individuals, which makes them similar to the present populations in Ireland and Scotlant. It is postulated that the heterozygotes for PKU in Norway are descended from a completely assimilated sub-population of Celtic origin, who came or were brought here, 1ooo years ago. Bronze objects of Western European (Scottish, Irish) origin, found in Viking graves widely distributed in Norway, have been taken as evidence of Vikings returning with loot (including a number of Celts) from Western Viking settlements. The continuity of residence since the Viking age in most habitable parts of Norway, and what seems to be a nearly complete regional relationship between the sites where Viking graves contain western imported objects and the birthplaces of grandparents of PKUs identified in Norway, lend further support to the hypothesis that the heterozygotes for PKU in Norway are descended from a completely assimilated subpopulation. The remarkable resemblance between Iceland and Ireland, in respect of several genetic markers (including the Rhesus, PGM and Kell systems), is considered to be an expression of a similar proportion of people of Celtic origin in each of the two countries. Their identical, high incidence rates of PKU are regarded as further evidence of this. The significant decline in the incidence of PKU when one passes from Ireland, Scotland and Iceland, to Denmark and on to Norway and Sweden, is therefore explained as being related to a reduction in the proportion of inhabitants of Celtic extraction in the respective populations. PMID:803884

  3. Carbamate deposit control additives

    SciTech Connect

    Honnen, L.R.; Lewis, R.A.

    1980-11-25

    Deposit control additives for internal combustion engines are provided which maintain cleanliness of intake systems without contributing to combustion chamber deposits. The additives are poly(oxyalkylene) carbamates comprising a hydrocarbyloxyterminated poly(Oxyalkylene) chain of 2-5 carbon oxyalkylene units bonded through an oxycarbonyl group to a nitrogen atom of ethylenediamine.

  4. Yawning and its physiological significance.

    PubMed

    Gupta, Sharat; Mittal, Shallu

    2013-01-01

    Although yawning is a commonly witnessed human behavior, yet it has not been taught in much detail in medical schools because, until the date, no particular physiological significance has been associated with it. It is characterized by opening up of mouth which is accompanied by a long inspiration, with a brief interruption of ventilation and followed by a short expiration. Since time immemorial, yawning has been associated with drowsiness and boredom. However, this age old belief is all set to change as the results of some newer studies have pointed out that yawning might be a way by which our body is trying to accomplish some more meaningful goals. In this review, we have tried to put together some of the important functions that have been proposed by a few authors, with the hope that this article will stimulate the interest of newer researchers in this hitherto unexplored field. PMID:23776833

  5. 24 CFR 1710.216 - Additional information.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 24 Housing and Urban Development 5 2014-04-01 2014-04-01 false Additional information. 1710.216... § 1710.216 Additional information. (a) Property Owners' Association. (1) If the association has been..., information on such matters as to: (i) Whether the developer will employ his own sales force or will...

  6. Polyimide processing additives

    NASA Technical Reports Server (NTRS)

    Fletcher, James C. (Inventor); Pratt, J. Richard (Inventor); St.clair, Terry L. (Inventor); Stoakley, Diane M. (Inventor); Burks, Harold D. (Inventor)

    1992-01-01

    A process for preparing polyimides having enhanced melt flow properties is described. The process consists of heating a mixture of a high molecular weight poly-(amic acid) or polyimide with a low molecular weight amic acid or imide additive in the range of 0.05 to 15 percent by weight of additive. The polyimide powders so obtained show improved processability, as evidenced by lower melt viscosity by capillary rheometry. Likewise, films prepared from mixtures of polymers with additives show improved processability with earlier onset of stretching by TMA.

  7. Polyimide processing additives

    NASA Technical Reports Server (NTRS)

    Pratt, J. Richard (Inventor); St.clair, Terry L. (Inventor); Stoakley, Diane M. (Inventor); Burks, Harold D. (Inventor)

    1993-01-01

    A process for preparing polyimides having enhanced melt flow properties is described. The process consists of heating a mixture of a high molecular weight poly-(amic acid) or polyimide with a low molecular weight amic acid or imide additive in the range of 0.05 to 15 percent by weight of the additive. The polyimide powders so obtained show improved processability, as evidenced by lower melt viscosity by capillary rheometry. Likewise, films prepared from mixtures of polymers with additives show improved processability with earlier onset of stretching by TMA.

  8. Genome‐wide significant schizophrenia risk variation on chromosome 10q24 is associated with altered cis‐regulation of BORCS7, AS3MT, and NT5C2 in the human brain

    PubMed Central

    Duarte, Rodrigo R. R.; Troakes, Claire; Nolan, Matthew; Srivastava, Deepak P.; Murray, Robin M.

    2016-01-01

    Chromosome 10q24.32‐q24.33 is one of the most robustly supported risk loci to emerge from genome‐wide association studies (GWAS) of schizophrenia. However, extensive linkage disequilibrium makes it difficult to distinguish the actual susceptibility gene(s) at the locus, limiting its value for improving biological understanding of the condition. In the absence of coding changes that can account for the association, risk is likely conferred by altered regulation of one or more genes in the region. We, therefore, used highly sensitive measures of allele‐specific expression to assess cis‐regulatory effects associated with the two best‐supported schizophrenia risk variants (SNP rs11191419 and indel ch10_104957618_I/rs202213518) on the primary positional candidates BORCS7, AS3MT, CNNM2, and NT5C2 in the human brain. Heterozygosity at rs11191419 was associated with increased allelic expression of BORCS7 and AS3MT in the fetal and adult brain, and with reduced allelic expression of NT5C2 in the adult brain. Heterozygosity at ch10_104957618_I was associated with reduced allelic expression of NT5C2 in both the fetal and adult brain. Comparisons between cDNA ratios in heterozygotes and homozygotes for the risk alleles indicated that cis‐effects on NT5C2 expression in the adult dorsolateral prefrontal cortex could be largely accounted for by genotype at these two risk variants. While not excluding effects on other genes in the region, this study implicates altered neural expression of BORCS7, AS3MT, and NT5C2 in susceptibility to schizophrenia arising from genetic variation at the chromosome 10q24 locus. © 2016 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc. PMID:27004590

  9. Genome-wide significant schizophrenia risk variation on chromosome 10q24 is associated with altered cis-regulation of BORCS7, AS3MT, and NT5C2 in the human brain.

    PubMed

    Duarte, Rodrigo R R; Troakes, Claire; Nolan, Matthew; Srivastava, Deepak P; Murray, Robin M; Bray, Nicholas J

    2016-09-01

    Chromosome 10q24.32-q24.33 is one of the most robustly supported risk loci to emerge from genome-wide association studies (GWAS) of schizophrenia. However, extensive linkage disequilibrium makes it difficult to distinguish the actual susceptibility gene(s) at the locus, limiting its value for improving biological understanding of the condition. In the absence of coding changes that can account for the association, risk is likely conferred by altered regulation of one or more genes in the region. We, therefore, used highly sensitive measures of allele-specific expression to assess cis-regulatory effects associated with the two best-supported schizophrenia risk variants (SNP rs11191419 and indel ch10_104957618_I/rs202213518) on the primary positional candidates BORCS7, AS3MT, CNNM2, and NT5C2 in the human brain. Heterozygosity at rs11191419 was associated with increased allelic expression of BORCS7 and AS3MT in the fetal and adult brain, and with reduced allelic expression of NT5C2 in the adult brain. Heterozygosity at ch10_104957618_I was associated with reduced allelic expression of NT5C2 in both the fetal and adult brain. Comparisons between cDNA ratios in heterozygotes and homozygotes for the risk alleles indicated that cis-effects on NT5C2 expression in the adult dorsolateral prefrontal cortex could be largely accounted for by genotype at these two risk variants. While not excluding effects on other genes in the region, this study implicates altered neural expression of BORCS7, AS3MT, and NT5C2 in susceptibility to schizophrenia arising from genetic variation at the chromosome 10q24 locus. © 2016 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc. PMID:27004590

  10. [Submitting studies without significant results].

    PubMed

    Texier, Gaëtan; Meynard, Jean-Baptiste; Michel, Rémy; Migliani, René; Boutin, Jean-Paul

    2007-03-01

    When a study finds that no exposure factor or therapy is significantly related to a given effect, researchers legitimately wonder if the results should be submitted for publication and to what journal. Clinical trials that report significant associations have a higher probability of publication, a phenomenon known as selective publication. The principal reasons of this selective publication include author self-censorship, peer-reviewing, trials not intended for publication, interpretation of the p value, cost of journal subscriptions, and policies. Subsequent reviews and meta-analyses are biased by the unavailability of nonsignificant results. Suggestions for preventing this risk include university training, trial registries, an international standard randomised controlled trial number (ISRCTN), Cochrane collaboration, and the gray literature. Journals (including electronic journals) interested in studies with nonsignificant results are listed. New technologies are changing the relations between publishers, libraries, authors and readers. PMID:17287106

  11. Significant Radionuclides Determination

    SciTech Connect

    Jo A. Ziegler

    2001-07-31

    The purpose of this calculation is to identify radionuclides that are significant to offsite doses from potential preclosure events for spent nuclear fuel (SNF) and high-level radioactive waste expected to be received at the potential Monitored Geologic Repository (MGR). In this calculation, high-level radioactive waste is included in references to DOE SNF. A previous document, ''DOE SNF DBE Offsite Dose Calculations'' (CRWMS M&O 1999b), calculated the source terms and offsite doses for Department of Energy (DOE) and Naval SNF for use in design basis event analyses. This calculation reproduces only DOE SNF work (i.e., no naval SNF work is included in this calculation) created in ''DOE SNF DBE Offsite Dose Calculations'' and expands the calculation to include DOE SNF expected to produce a high dose consequence (even though the quantity of the SNF is expected to be small) and SNF owned by commercial nuclear power producers. The calculation does not address any specific off-normal/DBE event scenarios for receiving, handling, or packaging of SNF. The results of this calculation are developed for comparative analysis to establish the important radionuclides and do not represent the final source terms to be used for license application. This calculation will be used as input to preclosure safety analyses and is performed in accordance with procedure AP-3.12Q, ''Calculations'', and is subject to the requirements of DOE/RW-0333P, ''Quality Assurance Requirements and Description'' (DOE 2000) as determined by the activity evaluation contained in ''Technical Work Plan for: Preclosure Safety Analysis, TWP-MGR-SE-000010'' (CRWMS M&O 2000b) in accordance with procedure AP-2.21Q, ''Quality Determinations and Planning for Scientific, Engineering, and Regulatory Compliance Activities''.

  12. Fungi producing significant mycotoxins.

    PubMed

    2012-01-01

    Mycotoxins are secondary metabolites of microfungi that are known to cause sickness or death in humans or animals. Although many such toxic metabolites are known, it is generally agreed that only a few are significant in causing disease: aflatoxins, fumonisins, ochratoxin A, deoxynivalenol, zearalenone, and ergot alkaloids. These toxins are produced by just a few species from the common genera Aspergillus, Penicillium, Fusarium, and Claviceps. All Aspergillus and Penicillium species either are commensals, growing in crops without obvious signs of pathogenicity, or invade crops after harvest and produce toxins during drying and storage. In contrast, the important Fusarium and Claviceps species infect crops before harvest. The most important Aspergillus species, occurring in warmer climates, are A. flavus and A. parasiticus, which produce aflatoxins in maize, groundnuts, tree nuts, and, less frequently, other commodities. The main ochratoxin A producers, A. ochraceus and A. carbonarius, commonly occur in grapes, dried vine fruits, wine, and coffee. Penicillium verrucosum also produces ochratoxin A but occurs only in cool temperate climates, where it infects small grains. F. verticillioides is ubiquitous in maize, with an endophytic nature, and produces fumonisins, which are generally more prevalent when crops are under drought stress or suffer excessive insect damage. It has recently been shown that Aspergillus niger also produces fumonisins, and several commodities may be affected. F. graminearum, which is the major producer of deoxynivalenol and zearalenone, is pathogenic on maize, wheat, and barley and produces these toxins whenever it infects these grains before harvest. Also included is a short section on Claviceps purpurea, which produces sclerotia among the seeds in grasses, including wheat, barley, and triticale. The main thrust of the chapter contains information on the identification of these fungi and their morphological characteristics, as well as factors

  13. Smog control fuel additives

    SciTech Connect

    Lundby, W.

    1993-06-29

    A method is described of controlling, reducing or eliminating, ozone and related smog resulting from photochemical reactions between ozone and automotive or industrial gases comprising the addition of iodine or compounds of iodine to hydrocarbon-base fuels prior to or during combustion in an amount of about 1 part iodine per 240 to 10,000,000 parts fuel, by weight, to be accomplished by: (a) the addition of these inhibitors during or after the refining or manufacturing process of liquid fuels; (b) the production of these inhibitors for addition into fuel tanks, such as automotive or industrial tanks; or (c) the addition of these inhibitors into combustion chambers of equipment utilizing solid fuels for the purpose of reducing ozone.

  14. Additional Types of Neuropathy

    MedlinePlus

    ... A A Listen En Español Additional Types of Neuropathy Charcot's Joint Charcot's Joint, also called neuropathic arthropathy, ... can stop bone destruction and aid healing. Cranial Neuropathy Cranial neuropathy affects the 12 pairs of nerves ...

  15. Tougher Addition Polyimides Containing Siloxane

    NASA Technical Reports Server (NTRS)

    St. Clair, T. L.; Maudgal, S.

    1986-01-01

    Laminates show increased impact resistances and other desirable mechanical properties. Bismaleamic acid extended by reaction of diaminosiloxane with maleic anhydride in 1:1 molar ratio, followed by reaction with half this molar ratio of aromatic dianhydride. Bismaleamic acid also extended by reaction of diaminosiloxane with maleic anhydride in 1:2 molar ratio, followed by reaction with half this molar ratio of aromatic diamine (Michael-addition reaction). Impact resistances improved over those of unmodified bismaleimide, showing significant increase in toughness. Aromatic addition polyimides developed as both matrix and adhesive resins for applications on future aircraft and spacecraft.

  16. Phenylethynyl Containing Reactive Additives

    NASA Technical Reports Server (NTRS)

    Connell, John W. (Inventor); Smith, Joseph G., Jr. (Inventor); Hergenrother, Paul M. (Inventor)

    2002-01-01

    Phenylethynyl containing reactive additives were prepared from aromatic diamine, containing phenylethvnvl groups and various ratios of phthalic anhydride and 4-phenylethynviphthalic anhydride in glacial acetic acid to form the imide in one step or in N-methyl-2-pvrrolidinone to form the amide acid intermediate. The reactive additives were mixed in various amounts (10% to 90%) with oligomers containing either terminal or pendent phenylethynyl groups (or both) to reduce the melt viscosity and thereby enhance processability. Upon thermal cure, the additives react and become chemically incorporated into the matrix and effect an increase in crosslink density relative to that of the host resin. This resultant increase in crosslink density has advantageous consequences on the cured resin properties such as higher glass transition temperature and higher modulus as compared to that of the host resin.

  17. Additives in plastics.

    PubMed Central

    Deanin, R D

    1975-01-01

    The polymers used in plastics are generally harmless. However, they are rarely used in pure form. In almost all commercial plastics, they are "compounded" with monomeric ingredients to improve their processing and end-use performance. In order of total volume used, these monomeric additives may be classified as follows: reinforcing fibers, fillers, and coupling agents; plasticizers; colorants; stabilizers (halogen stabilizers, antioxidants, ultraviolet absorbers, and biological preservatives); processing aids (lubricants, others, and flow controls); flame retardants, peroxides; and antistats. Some information is already available, and much more is needed, on potential toxicity and safe handling of these additives during processing and manufacture of plastics products. PMID:1175566

  18. The detection of clinically significant erythrocyte alloantibodies using a human mononuclear phagocyte assay

    SciTech Connect

    Schanfield, M.S.; Stevens, J.O.; Bauman, D.

    1981-01-01

    Red blood cell (RBC) allo- or autoantibodies, which markedly reduce the survival of transfused or autologous RBC, are considered to be clinically significant antibodies. The occurrence of antibodies against high-incidence antigens, which are occasionally associated with clinically significant RBC destruction or are of unknown clinical significance, often creates delays in providing blood to patients. In the majority of cases these antibodies are benign; however, clinically significant examples of these antibodies have been reported. An in vitro homologous human mononuclear phagocyte assay (MPA) was used to study antibodies directed against specificities associated with variable clinical significance. Two antibodies reported to be clinically significant and 25 antibodies known to be clinically insignificant were tested by MPA. The results indicate that clinically significant antibodies have a significantly higher score than do clinically insignificant antibodies, with no overlap observed between the two groups. An additional eight antibodies with unknown clinical significance were tested. None of these antibodies had scores in the clinically significant range.

  19. Impact significance determination-Back to basics

    SciTech Connect

    Lawrence, David P.

    2007-11-15

    Impact significance determination is widely recognized as a vital and critical EIA activity. But impact significance related concepts are poorly understood. And the quality of approaches for impact significance determination in EIA practice remains highly variable. This article seeks to help establish a sound and practical conceptual foundation for formulating and evaluating impact significance determination approaches. It addresses the nature (what is impact significance?), the core characteristics (what are the major properties of significance determination?), the rationale (why are impact significance determinations necessary?), the procedural and substantive objectives (what do impact significance determinations seek to achieve?), and the process for making impact significance judgments (how is impact significance determination conducted?). By identifying fundamental attributes and key distinctions associated with impact significance determinations, a basis is provided for designing and evaluating impact significance determination procedures at both the regulatory and applied levels.

  20. Obesity and Metabolic Phenotypes (Metabolically Healthy and Unhealthy Variants) Are Significantly Associated with Prevalence of Elevated C-Reactive Protein and Hepatic Steatosis in a Large Healthy Brazilian Population

    PubMed Central

    Shaharyar, Sameer; Roberson, Lara L.; Jamal, Omar; Younus, Adnan; Blaha, Michael J.; Ali, Shozab S.; Zide, Kenneth; Agatston, Arthur A.; Blumenthal, Roger S.; Conceição, Raquel D.; Santos, Raul D.; Nasir, Khurram

    2015-01-01

    Background. Among the obese, the so-called metabolically healthy obese (MHO) phenotype is thought to confer a lower CVD risk as compared to obesity with typical associated metabolic changes. The present study aims to determine the relationship of different subtypes of obesity with inflammatory-cardiometabolic abnormalities. Methods. We evaluated 5,519 healthy, Brazilian subjects (43 ± 10 years, 78% males), free of known cardiovascular disease. Those with <2 metabolic risk factors (MRF) were considered metabolically healthy, and those with BMI ≥ 25 kg/m2 and/or waist circumference meeting NCEP criteria for metabolic syndrome as overweight/obese (OW). High sensitivity C reactive protein (hsCRP) was measured to assess underlying inflammation and hepatic steatosis (HS) was determined via abdominal ultrasound. Results. Overall, 40% of OW individuals were metabolically healthy, and 12% normal-weight had ≥2 MRF. The prevalence of elevated CRP (≥3 mg/dL) and HS in MHO versus normal weight metabolically healthy group was 22% versus 12%, and 40% versus 8% respectively (P < 0.001). Both MHO individuals and metabolically unhealthy normal weight (MUNW) phenotypes were associated with elevated hsCRP and HS. Conclusion. Our study suggests that MHO and MUNW phenotypes may not be benign and physicians should strive to treat individuals in these subgroups to reverse these conditions. PMID:25838943

  1. A Retrospective Analysis of Incidence and Its Associated Risk Factors of Upper Urinary Tract Recurrence following Radical Cystectomy for Bladder Cancer with Transitional Cell Carcinoma: The Significance of Local Pelvic Recurrence and Positive Lymph Node

    PubMed Central

    Kim, Sung Han; Yang, Hyung-Kook; Lee, Jung Hoon; Lee, Eun-Sik

    2014-01-01

    Objective The aim of this study is to examine the incidence and risk factors of upper urinary tract recurrence (UUTR) following radical cystectomy (RC) in bladder cancer and to evaluate its relationship with neobladder (Neo) or ileal conduit (IC). Materials and Methods All clinicopathologic parameters and perioperative parameters of 311 patients who underwent RC with either Neo or IC by a single surgeon from 1999 to 2012 were retrospectively included in this study. Patients with a history of renal surgery, concomitant UUTR, or a histopathology of non-transitional cell carcinoma were excluded. For statistical analyses of predictive risk factors of UUTR, a multivariate analysis was performed with known risk factors of UUTR, including type of urinary diversion with significance defined as P < 0.05. Results During the median follow-up period of 53 months, 143 (46.0%) IC and 168 (54.0%) Neo were performed, resulting in 11 (3.5%) cases of UUTR (Neo 7 and IC 4) after RC and all patients then underwent nephroureterectomy. No significant differences in incidence and overall survival in UUTR were observed according different types of urinary diversion (p = 483), and the prognosis for survival of Neo was insignificantly better than that of IC (5-year overall survival 78% vs 74%, respectively, p>0.05). Higher number of positive lymph nodes (HR 9.03) and the presence of pelvic local recurrence (HR 7286.08) were significant predictive factors of UUTR (p<0.05). Conclusion This study reports a UUTR rate of 3.5%, and positive lymph nodes and presence of local recurrence at the pelvis as important risk factors. No significant differences in incidence and survival were observed between Neo and IC. PMID:24798444

  2. Biobased lubricant additives

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fully biobased lubricants are those formulated using all biobased ingredients, i.e. biobased base oils and biobased additives. Such formulations provide the maximum environmental, safety, and economic benefits expected from a biobased product. Currently, there are a number of biobased base oils that...

  3. Multifunctional fuel additives

    SciTech Connect

    Baillargeon, D.J.; Cardis, A.B.; Heck, D.B.

    1991-03-26

    This paper discusses a composition comprising a major amount of a liquid hydrocarbyl fuel and a minor low-temperature flow properties improving amount of an additive product of the reaction of a suitable diol and product of a benzophenone tetracarboxylic dianhydride and a long-chain hydrocarbyl aminoalcohol.

  4. The assisted self-association of ATP4- by a poly(amino acid) [poly(Lys)] and its significance for cell organelles that contain high concentrations of nucleotides.

    PubMed

    Sigel, H; Corfù, N A

    1996-09-15

    The occurrence of high concentrations of ATP in certain cell organelles prompted us to study the self-association of ATP via the concentration dependence of the 1H-NMR chemical shifts for H2, H8 and H1' in D2O at pD 8.4 (25 degrees C) in the range 0.0025-0.4 M in the presence and absence of poly(alpha, L-lysine), where [Lys units] was 0.4 M. The experiment in the presence of poly(Lys) was repeated at pD 12.1. At pD 8.4, the poly(amino acid) is protonated, i.e. poly(H.Lys)n+, whereas at pD 12.1 only approximately 10% of the epsilon-amino groups are positively charged. The results in all three systems are consistent with the isodesmic model of indefinite non-cooperative stacking. The stacking tendency follows the series: ATP4- (K = 1.3 M-1; pD 8.4) < ATP4-/poly(H.Lys)n+ (K = 11.5 M-1; pD 8.4) > ATP4-/90% poly(Lys)/10% poly(H.Lys)n+ (K = 3.1 M-1; pD 12.1). It is evident that poly(H.Lys)n+ assists the association of ATP by a factor of approximately 10, and it is suggested that, via its positively charged epsilon-ammonium groups, poly(H.Lys)n+ acts as a matrix by aligning ATP4- ions via ionic interactions with the negatively charged phosphate residues. The intragranular concentrations of various constituents of several storage or secretory cell organelles, as reported in the literature, are tabulated. The chromaffin granules of the adrenal medulla and the dense granules of blood platelets contain particularly high concentrations of nucleotides ([ATP] is approximately 0.14 M in the chromaffin granules and 0.5 M in the dense granules of rabbit blood platelets) and amines, such as epinephrine or 5-hydroxytryptamine. These granules, and probably also the storage vesicles of certain neurons (which seem to have a similar composition), appear, if the total concentrations of the various solutes are considered, to be osmotically unstable, which means that the intragranular solutes must be associated. This aggregation is discussed, especially with regard to the nucleotides. PMID

  5. The oxidation capacity of Mn3O4 nanoparticles is significantly enhanced by anchoring them onto reduced graphene oxide to facilitate regeneration of surface-associated Mn(III).

    PubMed

    Duan, Lin; Wang, Zhongyuan; Hou, Yan; Wang, Zepeng; Gao, Guandao; Chen, Wei; Alvarez, Pedro J J

    2016-10-15

    Metal oxides are often anchored to graphene materials to achieve greater contaminant removal efficiency. To date, the enhanced performance has mainly been attributed to the role of graphene materials as a conductor for electron transfer. Herein, we report a new mechanism via which graphene materials enhance oxidation of organic contaminants by metal oxides. Specifically, Mn3O4-rGO nanocomposites (Mn3O4 nanoparticles anchored to reduced graphene oxide (rGO) nanosheets) enhanced oxidation of 1-naphthylamine (used here as a reaction probe) compared to bare Mn3O4. Spectroscopic analyses (X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy) show that the rGO component of Mn3O4-rGO was further reduced during the oxidation of 1-naphthylamine, although rGO reduction was not the result of direct interaction with 1-naphthylamine. We postulate that rGO improved the oxidation efficiency of anchored Mn3O4 by re-oxidizing Mn(II) formed from the reaction between Mn3O4 and 1-naphthylamine, thereby regenerating the surface-associated oxidant Mn(III). The proposed role of rGO was verified by separate experiments demonstrating its ability to oxidize dissolved Mn(II) to Mn(III), which subsequently can oxidize 1-naphthylamine. The role of dissolved oxygen in re-oxidizing Mn(II) was ruled out by anoxic (N2-purged) control experiments showing similar results as O2-sparged tests. Opposite pH effects on the oxidation efficiency of Mn3O4-rGO versus bare Mn3O4 were also observed, corroborating the proposed mechanism because higher pH facilitates oxidation of surface-associated Mn(II) even though it lowers the oxidation potential of Mn3O4. Overall, these findings may guide the development of novel metal oxide-graphene nanocomposites for contaminant removal. PMID:27448035

  6. Boron addition to alloys

    SciTech Connect

    Coad, B. C.

    1985-08-20

    A process for addition of boron to an alloy which involves forming a melt of the alloy and a reactive metal, selected from the group consisting of aluminum, titanium, zirconium and mixtures thereof to the melt, maintaining the resulting reactive mixture in the molten state and reacting the boric oxide with the reactive metal to convert at least a portion of the boric oxide to boron which dissolves in the resulting melt, and to convert at least portion of the reactive metal to the reactive metal oxide, which oxide remains with the resulting melt, and pouring the resulting melt into a gas stream to form a first atomized powder which is subsequently remelted with further addition of boric oxide, re-atomized, and thus reprocessed to convert essentially all the reactive metal to metal oxide to produce a powdered alloy containing specified amounts of boron.

  7. Tackifier for addition polyimides

    NASA Technical Reports Server (NTRS)

    Butler, J. M.; St.clair, T. L.

    1980-01-01

    A modification to the addition polyimide, LaRC-160, was prepared to improve tack and drape and increase prepeg out-time. The essentially solventless, high viscosity laminating resin is synthesized from low cost liquid monomers. The modified version takes advantage of a reactive, liquid plasticizer which is used in place of solvent and helps solve a major problem of maintaining good prepeg tack and drape, or the ability of the prepeg to adhere to adjacent plies and conform to a desired shape during the lay up process. This alternate solventless approach allows both longer life of the polymer prepeg and the processing of low void laminates. This approach appears to be applicable to all addition polyimide systems.

  8. Vinyl capped addition polyimides

    NASA Technical Reports Server (NTRS)

    Vannucci, Raymond D. (Inventor); Malarik, Diane C. (Inventor); Delvigs, Peter (Inventor)

    1991-01-01

    Polyimide resins (PMR) are generally useful where high strength and temperature capabilities are required (at temperatures up to about 700 F). Polyimide resins are particularly useful in applications such as jet engine compressor components, for example, blades, vanes, air seals, air splitters, and engine casing parts. Aromatic vinyl capped addition polyimides are obtained by reacting a diamine, an ester of tetracarboxylic acid, and an aromatic vinyl compound. Low void materials with improved oxidative stability when exposed to 700 F air may be fabricated as fiber reinforced high molecular weight capped polyimide composites. The aromatic vinyl capped polyimides are provided with a more aromatic nature and are more thermally stable than highly aliphatic, norbornenyl-type end-capped polyimides employed in PMR resins. The substitution of aromatic vinyl end-caps for norbornenyl end-caps in addition polyimides results in polymers with improved oxidative stability.

  9. [Biologically active food additives].

    PubMed

    Velichko, M A; Shevchenko, V P

    1998-07-01

    More than half out of 40 projects for the medical science development by the year of 2000 have been connected with the bio-active edible additives that are called "the food of XXI century", non-pharmacological means for many diseases. Most of these additives--nutricevtics and parapharmacevtics--are intended for the enrichment of food rations for the sick or healthy people. The ecologicaly safest and most effective are combined domestic adaptogens with immuno-modulating and antioxidating action that give anabolic and stimulating effect,--"leveton", "phytoton" and "adapton". The MKTs-229 tablets are residue discharge means. For atherosclerosis and general adiposis they recommend "tsar tablets" and "aiconol (ikhtien)"--on the base of cod-liver oil or "splat" made out of seaweed (algae). All these preparations have been clinically tested and received hygiene certificates from the Institute of Dietology of the Russian Academy of Medical Science. PMID:9752776

  10. Electrophilic addition of astatine

    SciTech Connect

    Norseev, Yu.V.; Vasaros, L.; Nhan, D.D.; Huan, N.K.

    1988-03-01

    It has been shown for the first time that astatine is capable of undergoing addition reactions to unsaturated hydrocarbons. A new compound of astatine, viz., ethylene astatohydrin, has been obtained, and its retention numbers of squalane, Apiezon, and tricresyl phosphate have been found. The influence of various factors on the formation of ethylene astatohydrin has been studied. It has been concluded on the basis of the results obtained that the univalent cations of astatine in an acidic medium is protonated hypoastatous acid.

  11. Hydrocarbon fuel additive

    SciTech Connect

    Ambrogio, S.

    1989-02-28

    This patent describes the method of fuel storage or combustion, wherein the fuel supply contains small amounts of water, the step of adding to the fuel supply an additive comprising a blend of a hydrophilic agent chosen from the group of ethylene glycol, n-butyl alcohol, and cellosolve in the range of 22-37% by weight; ethoxylated nonylphenol in the range of 26-35% by weight; nonylphenol polyethylene glycol ether in the range of 32-43% by weight.

  12. Metal Additive Manufacturing: A Review

    NASA Astrophysics Data System (ADS)

    Frazier, William E.

    2014-06-01

    This paper reviews the state-of-the-art of an important, rapidly emerging, manufacturing technology that is alternatively called additive manufacturing (AM), direct digital manufacturing, free form fabrication, or 3D printing, etc. A broad contextual overview of metallic AM is provided. AM has the potential to revolutionize the global parts manufacturing and logistics landscape. It enables distributed manufacturing and the productions of parts-on-demand while offering the potential to reduce cost, energy consumption, and carbon footprint. This paper explores the material science, processes, and business consideration associated with achieving these performance gains. It is concluded that a paradigm shift is required in order to fully exploit AM potential.

  13. Uniform: an evidence review of the microbiological significance of uniforms and uniform policy in the prevention and control of healthcare-associated infections. Report to the Department of Health (England).

    PubMed

    Wilson, J A; Loveday, H P; Hoffman, P N; Pratt, R J

    2007-08-01

    A systematic search and quality assessment of published literature was conducted to establish current knowledge on the role of healthcare workers uniforms' as vehicles for the transfer of healthcare-associated infections. This review comprised a systematic search of national and international guidance, published literature and data on recent advances in laundry technology and processes. We found only a small number of relevant studies that provided limited evidence directly related to the decontamination of uniforms. Studies concerning domestic laundry processes are small scale and largely observational. Current practice and guidance for laundering uniforms is extrapolated from studies of industrial hospital linen processing. Healthcare workers' uniforms, including white coats, become progressively contaminated in use with bacteria of low pathogenicity from the wearer and of mixed pathogenicity from the clinical environment and patients. The hypothesis that uniforms/clothing could be a vehicle for the transmission of infections is not supported by existing evidence. All components of the laundering process contribute to the removal or killing of micro-organisms on fabric. There is no robust evidence of a difference in efficacy of decontamination of uniforms/clothing between industrial and domestic laundry processes, or that the home laundering of uniforms provides inadequate decontamination. PMID:17602793

  14. A Proposed Fourth Measure of Significance: The Role of Economic Significance in Educational Research

    ERIC Educational Resources Information Center

    Leech, Nancy L.; Onwuegbuzie, Anthony J.

    2004-01-01

    The purpose of this paper is to examine economic significance as a fourth measure of significance. In addition to describing and operationalising the concept of economic significance, a typology of economic significance indices is presented, including an example of how to compute these measures, as well as how to utilise them in applied research.…

  15. Adverse reactions to food additives.

    PubMed

    Simon, R A

    1986-01-01

    There are thousands of agents that are intentionally added to the food that we consume. These include preservatives, stabilizers, conditioners, thickeners, colorings, flavorings, sweeteners, antioxidants, etc. etc. Yet only a surprisingly small number have been associated with hypersensitivity reactions. Amongst all the additives, FD&C dyes have been most frequently associated with adverse reactions. Tartrazine is the most notorious of them all; however, critical review of the medical literature and current Scripps Clinic studies would indicate that tartrazine has been confirmed to be at best only occasionally associated with flares of urticaria or asthma. There is no convincing evidence in the literature of reactivity to the other azo or nonazo dyes. This can also be said of BHA/BHT, nitrites/nitrates and sorbates. Parabens have been shown to elicit IgE mediated hypersensitivity reactions when used as pharmaceutical preservatives; however, as with the other additives noted above, ingested parabens have only occasionally been associated with adverse reactions. MSG, the cause of the 'Chinese restaurant syndrome' has only been linked to asthma in one report. Sulfiting agents used primarily as food fresheners and to control microbial growth in fermented beverages have been established as the cause of any where from mild to severe and even fatal reactions in at least 5% of the asthmatic population. Other reactions reported to follow sulfite ingestion include anaphylaxis, gastro intestinal complaints and dermatological eruptions. The prevalence of these non asthmatic reactions is unknown. The mechanism of sulfite sensitive asthma is also unknown but most likely involves hyperreactivity to inhale SO2 in the great majority of cases; however, there are reports of IgE mediated reactions and other sulfite sensitive asthmatics have been found with low levels of sulfite oxidase; necessary to oxidize endogenous sulfite to sulfate. PMID:3302664

  16. Significance of hypoburrow nodule formation associated with large biogenic sedimentary structures in open-marine bay siliciclastics of the Upper Eocene Birket Qarun Formation, Wadi El-Hitan, Fayum, Egypt

    NASA Astrophysics Data System (ADS)

    Abdel-Fattah, Zaki A.; Gingras, Murray K.; Pemberton, S. George

    Unusually large biogenic sedimentary structures from the shallow quiescent-marine siliciclastics of the Upper Eocene Birket Qarun Formation in the Fayum area of Egypt display pronounced concretion formation around the trace fossils. The structures are massive, and vary morphologically, forming branched pillars (up to dm-scale), vertical (up to 180 cm height) amphora-like masses, and 3-D box-work "maze". Bioturbation, mainly Thalassinoides attributable to the Glossifungites ichnofacies, mediated and modified the physical and chemical microenvironments influencing early diagenesis; i.e., burrows promote the precipitation of pervasive calcite-dominated cement. The inferred paragenesis, combined with the negative (light) carbon and oxygen stable-isotopic values of the bulk calcite (δ 13C PDB from -0.94 to -4.98‰ and δ 18O PDB from -4.63 to -7.22‰) and bulk dolomite (δ 13C PDB from -2.05 to -8.23‰ and δ 18O PDB from -1.41 to -11.20‰), imply that the pore-water carbon was derived directly from seawater and dissolution of metastable carbonate, which was mediated by bacterial decomposition of organic matter and mixing of meteoric ground water. Thereby, the carbonate cement precipitated mostly under eodiagenetic conditions near the sediment/water interface (<~3 m in depth). The distribution of these structures is confined to parasequence-bounding flooding surfaces (generally expressed as transgressive surfaces of erosion). Notably, sedimentological, ichnological and paragenetic data can be related to stratigraphic evolution such that geochemical and textural evidence is distinctly associated with (1) early cementation of the host sandstone during highstands of relative sea level, (2) the formation of firmgrounds during low relative sea level, (3) the development of a Glossifungites-demarcated discontinuity during initial relative sea-level rise, and (4) continued cementation with rising relative sea level. This was followed by burial diagenesis, evidence for

  17. Siloxane containing addition polyimides

    NASA Technical Reports Server (NTRS)

    Maudgal, S.; St. Clair, T. L.

    1984-01-01

    Addition polyimide oligomers have been synthesized from bis(gamma-aminopropyl) tetramethyldisiloxane and 3, 3', 4, 4'-benzophenonetetracarboxylic dianhydride using a variety of latent crosslinking groups as endcappers. The prepolymers were isolated and characterized for solubility (in amide, chlorinated and ether solvents), melt flow and cure properties. The most promising systems, maleimide and acetylene terminated prepolymers, were selected for detailed study. Graphite cloth reinforced composites were prepared and properties compared with those of graphite/Kerimid 601, a commercially available bismaleimide. Mixtures of the maleimide terminated system with Kerimid 601, in varying proportions, were also studied.

  18. Oil additive process

    SciTech Connect

    Bishop, H.

    1988-10-18

    This patent describes a method of making an additive comprising: (a) adding 2 parts by volume of 3% sodium hypochlorite to 45 parts by volume of diesel oil fuel to form a sulphur free fuel, (b) removing all water and foreign matter formed by the sodium hypochlorite, (c) blending 30 parts by volume of 24% lead naphthanate with 15 parts by volume of the sulphur free fuel, 15 parts by volume of light-weight material oil to form a blended mixture, and (d) heating the blended mixture slowly and uniformly to 152F.

  19. PARTICLE-ASSOCIATED MICROORGANISMS IN STORMWATER RUNOFF

    EPA Science Inventory

    This research investigated the effects of blending and chemical addition before analysis of the concentration of microorganisms in stormwater runoff to determine whether clumped or particle-associated organisms play a significant role. All organisms, except for Escherichia coli, ...

  20. Kinetic studies and structural models of the association of E. coli sigma(70) RNA polymerase with the lambdaP(R) promoter: large scale conformational changes in forming the kinetically significant intermediates.

    PubMed

    Saecker, Ruth M; Tsodikov, Oleg V; McQuade, Kristi L; Schlax, Peter E; Capp, Michael W; Record, M Thomas

    2002-06-01

    The kinetics of interaction of Esigma(70) RNA polymerase (R) with the lambdaP(R) promoter (P) were investigated by filter binding over a broad range of temperatures (7.3-42 degrees C) and concentrations of RNA polymerase (1-123 nM) in large excess over promoter DNA. Under all conditions examined, the kinetics of formation of competitor-resistant complexes (I(2), RP(o)) are single-exponential with first order rate constant beta(CR). Interpretation of the polymerase concentration dependence of beta(CR) in terms of the three step mechanism of open complex formation yields the equilibrium constant K(1) for formation of the first kinetically significant intermediate (I(1)) and the forward rate constant (k(2)) for the conformational change converting I(1) to the second kinetically significant intermediate I(2): R + P-->(K(1))<--I(1)(k(2))-->I(2). Use of rapid quench mixing allows K(1) and k(2) to be individually determined over the entire temperature range investigated, previously not possible at this promoter using manual mixing. Given the large (>60 bp) interface formed in I(1), its relatively small binding constant K(1) at 37 degrees C at this [salt] (approximately 6 x 10(6) M(-1)) strongly argues that binding free energy is used to drive large-scale structural changes in polymerase and/or promoter DNA or other coupled processes. Evidence for coupling of protein folding is provided by the large and negative activation heat capacity of k(a)[DeltaC(o,++)(a)= -1.5(+/-0.2)kcal K(-1)], now shown to originate directly from formation of I(1) [DeltaC(o)(1)= -1.4(+/-0.3)kcal K(-1)] rather than from the formation of I(2) as previously proposed. The isomerization I(1)-->I(2) exhibits relatively slow kinetics and has a very large temperature-independent Arrhenius activation energy [E(act)(2)= 34(+/-2)kcal]. This kinetic signature suggests that formation of the transition state (I(1)-I(2)++ involves large conformational changes dominated by changes in the exposure of polar and

  1. Supplier Selection Using Weighted Utility Additive Method

    NASA Astrophysics Data System (ADS)

    Karande, Prasad; Chakraborty, Shankar

    2015-10-01

    Supplier selection is a multi-criteria decision-making (MCDM) problem which mainly involves evaluating a number of available suppliers according to a set of common criteria for choosing the best one to meet the organizational needs. For any manufacturing or service organization, selecting the right upstream suppliers is a key success factor that will significantly reduce purchasing cost, increase downstream customer satisfaction and improve competitive ability. The past researchers have attempted to solve the supplier selection problem employing different MCDM techniques which involve active participation of the decision makers in the decision-making process. This paper deals with the application of weighted utility additive (WUTA) method for solving supplier selection problems. The WUTA method, an extension of utility additive approach, is based on ordinal regression and consists of building a piece-wise linear additive decision model from a preference structure using linear programming (LP). It adopts preference disaggregation principle and addresses the decision-making activities through operational models which need implicit preferences in the form of a preorder of reference alternatives or a subset of these alternatives present in the process. The preferential preorder provided by the decision maker is used as a restriction of a LP problem, which has its own objective function, minimization of the sum of the errors associated with the ranking of each alternative. Based on a given reference ranking of alternatives, one or more additive utility functions are derived. Using these utility functions, the weighted utilities for individual criterion values are combined into an overall weighted utility for a given alternative. It is observed that WUTA method, having a sound mathematical background, can provide accurate ranking to the candidate suppliers and choose the best one to fulfill the organizational requirements. Two real time examples are illustrated to prove

  2. Performance Boosting Additive

    NASA Technical Reports Server (NTRS)

    1999-01-01

    Mainstream Engineering Corporation was awarded Phase I and Phase II contracts from Goddard Space Flight Center's Small Business Innovation Research (SBIR) program in early 1990. With support from the SBIR program, Mainstream Engineering Corporation has developed a unique low cost additive, QwikBoost (TM), that increases the performance of air conditioners, heat pumps, refrigerators, and freezers. Because of the energy and environmental benefits of QwikBoost, Mainstream received the Tibbetts Award at a White House Ceremony on October 16, 1997. QwikBoost was introduced at the 1998 International Air Conditioning, Heating, and Refrigeration Exposition. QwikBoost is packaged in a handy 3-ounce can (pressurized with R-134a) and will be available for automotive air conditioning systems in summer 1998.

  3. Sewage sludge additive

    NASA Technical Reports Server (NTRS)

    Kalvinskas, J. J.; Mueller, W. A.; Ingham, J. D. (Inventor)

    1980-01-01

    The additive is for a raw sewage treatment process of the type where settling tanks are used for the purpose of permitting the suspended matter in the raw sewage to be settled as well as to permit adsorption of the dissolved contaminants in the water of the sewage. The sludge, which settles down to the bottom of the settling tank is extracted, pyrolyzed and activated to form activated carbon and ash which is mixed with the sewage prior to its introduction into the settling tank. The sludge does not provide all of the activated carbon and ash required for adequate treatment of the raw sewage. It is necessary to add carbon to the process and instead of expensive commercial carbon, coal is used to provide the carbon supplement.

  4. Perspectives on Additive Manufacturing

    NASA Astrophysics Data System (ADS)

    Bourell, David L.

    2016-07-01

    Additive manufacturing (AM) has skyrocketed in visibility commercially and in the public sector. This article describes the development of this field from early layered manufacturing approaches of photosculpture, topography, and material deposition. Certain precursors to modern AM processes are also briefly described. The growth of the field over the last 30 years is presented. Included is the standard delineation of AM technologies into seven broad categories. The economics of AM part generation is considered, and the impacts of the economics on application sectors are described. On the basis of current trends, the future outlook will include a convergence of AM fabricators, mass-produced AM fabricators, enabling of topology optimization designs, and specialization in the AM legal arena. Long-term developments with huge impact are organ printing and volume-based printing.

  5. New addition curing polyimides

    NASA Technical Reports Server (NTRS)

    Frimer, Aryeh A.; Cavano, Paul

    1991-01-01

    In an attempt to improve the thermal-oxidative stability (TOS) of PMR-type polymers, the use of 1,4-phenylenebis (phenylmaleic anhydride) PPMA, was evaluated. Two series of nadic end-capped addition curing polyimides were prepared by imidizing PPMA with either 4,4'-methylene dianiline or p-phenylenediamine. The first resulted in improved solubility and increased resin flow while the latter yielded a compression molded neat resin sample with a T(sub g) of 408 C, close to 70 C higher than PME-15. The performance of these materials in long term weight loss studies was below that of PMR-15, independent of post-cure conditions. These results can be rationalized in terms of the thermal lability of the pendant phenyl groups and the incomplete imidization of the sterically congested PPMA. The preparation of model compounds as well as future research directions are discussed.

  6. Individualized additional instruction for calculus

    NASA Astrophysics Data System (ADS)

    Takata, Ken

    2010-10-01

    College students enrolling in the calculus sequence have a wide variance in their preparation and abilities, yet they are usually taught from the same lecture. We describe another pedagogical model of Individualized Additional Instruction (IAI) that assesses each student frequently and prescribes further instruction and homework based on the student's performance. Our study compares two calculus classes, one taught with mandatory remedial IAI and the other without. The class with mandatory remedial IAI did significantly better on comprehensive multiple-choice exams, participated more frequently in classroom discussion and showed greater interest in theorem-proving and other advanced topics.

  7. 12 CFR 1010.116 - Additional information.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 8 2014-01-01 2014-01-01 false Additional information. 1010.116 Section 1010...) Reporting Requirements § 1010.116 Additional information. (a) Property Owners' Association. (1) Will there... obligation to retire the debt. (c) Violations and litigations. This information need appear only if any...

  8. 12 CFR 1010.116 - Additional information.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 12 Banks and Banking 8 2012-01-01 2012-01-01 false Additional information. 1010.116 Section 1010...) Reporting Requirements § 1010.116 Additional information. (a) Property Owners' Association. (1) Will there... obligation to retire the debt. (c) Violations and litigations. This information need appear only if any...

  9. 12 CFR 1010.216 - Additional information.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 12 Banks and Banking 8 2012-01-01 2012-01-01 false Additional information. 1010.216 Section 1010...) Reporting Requirements § 1010.216 Additional information. (a) Property Owners' Association. (1) If the..., information on such matters as to: (i) Whether the developer will employ his own sales force or will...

  10. 12 CFR 1010.216 - Additional information.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 8 2014-01-01 2014-01-01 false Additional information. 1010.216 Section 1010...) Reporting Requirements § 1010.216 Additional information. (a) Property Owners' Association. (1) If the..., information on such matters as to: (i) Whether the developer will employ his own sales force or will...

  11. Some additional considerations in modelling the dynamic traits and genome-wide association studies. Comments on "Mapping complex traits as a dynamic system" by L. Sun and R. Wu

    NASA Astrophysics Data System (ADS)

    Das, Kiranmoy

    2015-06-01

    The revolution in the genetic research in our time is mainly due to (i) the successful completion of human genome project (2003) and its derivative hapmap project (2005), (ii) advanced statistical methodologies for analyzing ultrahigh dimensional data and (iii) the availability of statistical softwares (R, SAS etc.) to analyze large datasets. When complex traits are to be modeled as dynamic systems, the statistical issues regarding the complexity in the model, predictive power of the model, computational cost etc. are to be addressed adequately for powerful inferences. I will mention two additional considerations (statistical) which make dynamic models more meaningful and the results from GWAS more reliable.

  12. MAGNETOMETRY, SELF-POTENTIAL, AND SEISMIC - ADDITIONAL GEOPHYSICAL METHODS HAVING POTENTIALLY SIGNIFICANT FUTURE UTILIZATION IN AGRICULTURE

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Geophysical methods can provide important information in agricultural settings, and the use of these techniques are becoming more and more widespread. Magnetrometry, self-potential, and seismic are three geophysical methods, all of which have the potential for substantial future use in agriculture, ...

  13. Astrobiological Significance of Chemolithoautotrophic Acidophiles

    NASA Technical Reports Server (NTRS)

    Pikuta, Elena V.; Hoover, Richard B.

    2003-01-01

    For more than a century (since Winogradsky discovered lithoautotrophic bacteria) a dilemma in microbiology has concerned life that first inhabited the Earth. Which types of life forms first appeared in the primordial oceans during the earliest geological period on Earth as the primary ancestors of modem biological diversity? How did a metabolism of ancestors evolve: from lithoautotrophic to lithohetherotrophic and organoheterotrophic or from organoheterotrophic to organoautotrophic and lithomixotrophic types? At the present time, it is known that chemolithoheterotrophic and chemolithoautotrophic metabolizing bacteria are wide spread in different ecosystems. On Earth the acidic ecosystems are associated with geysers, volcanic fumaroles, hot springs, deep sea hydrothermal vents, caves, acid mine drainage and other technogenic ecosystems. Bioleaching played a significant role on a global geological scale during the Earth's formation. This important feature of bacteria has been successfully applied in industry. The lithoautotrophs include Bacteria and Archaea belonging to diverse genera containing thermophilic and mesophilic species. In this paper we discuss the lithotrophic microbial acidophiles and present some data with a description of new acidophilic iron- and sulfur- oxidizing bacterium isolated from the Chena Hot Springs in Alaska. We also consider the possible relevance of microbial acidophiles to Venus, Io, and acidic inclusions in glaciers and icy moons.

  14. Astrobiological significance of chemolithoautotrophic acidophiles

    NASA Astrophysics Data System (ADS)

    Pikuta, Elena V.; Hoover, Richard B.

    2004-02-01

    For more than a century (since Winogradsky discovered lithautotrophic bacteria) there has been a dilemma in microbiology about life that first inhabited the Earth. Which types of life forms first appeared in the primordial oceans during the earliest geological period on Earth as the primary ancestors of modern biological diversity? How did a metabolism of ancestors evolve: from lithoautotrophic to lithoheterotrophic and organoheterotrophic or from organoheterotrophic to organautotrophic and lithomixotrophic types? At the present time, it is known that chemolithoheterotrophic and chemolithoautotrophic metabolizing bacteria are wide spread in different ecosystems. On Earth the acidic ecosystems are associated with geysers, volcanic fumaroles, hot springs, deep sea hydrothermal vents, caves, acid mine drainage and other technogenic ecosystems. Bioleaching played a significant roel on a global geological scale during the Earth's formation. This important feature of bacteria has been successfully applied in industry. The lithoautotrophs include Bacteria and Archaea belonging to diverse genera containing thermophilic and mesophilic species. In this paper we discuss the lithotrophic microbial acidophiles and present some data with a description of new acidophilic iron- and sulfur-oxidizing bacterium isolated from the Chena Hot Springs in Alaska. We also consider the possible relevance of microbial acidophiles to Venus, Io, and acidic inclusions in glaciers and icy moons.

  15. Precancerous esophageal epithelia are associated with significantly increased scattering coefficients

    PubMed Central

    Su, Jing-Wei; Lin, Yang-Hsien; Chiang, Chun-Ping; Lee, Jang-Ming; Hsieh, Chao-Mao; Hsieh, Min-Shu; Yang, Pei-Wen; Wang, Chen-Ping; Tseng, Ping-Huei; Lee, Yi-Chia; Sung, Kung-Bin

    2015-01-01

    The progression of epithelial precancers into cancer is accompanied by changes of tissue and cellular structures in the epithelium. Correlations between the structural changes and scattering coefficients of esophageal epithelia were investigated using quantitative phase images and the scattering-phase theorem. An ex vivo study of 14 patients demonstrated that the average scattering coefficient of precancerous epithelia was 37.8% higher than that of normal epithelia from the same patient. The scattering coefficients were highly correlated with morphological features including the cell density and the nuclear-to-cytoplasmic ratio. A high interpatient variability in scattering coefficients was observed and suggests identifying precancerous lesions based on the relative change in scattering coefficients. PMID:26504630

  16. Precancerous esophageal epithelia are associated with significantly increased scattering coefficients.

    PubMed

    Su, Jing-Wei; Lin, Yang-Hsien; Chiang, Chun-Ping; Lee, Jang-Ming; Hsieh, Chao-Mao; Hsieh, Min-Shu; Yang, Pei-Wen; Wang, Chen-Ping; Tseng, Ping-Huei; Lee, Yi-Chia; Sung, Kung-Bin

    2015-10-01

    The progression of epithelial precancers into cancer is accompanied by changes of tissue and cellular structures in the epithelium. Correlations between the structural changes and scattering coefficients of esophageal epithelia were investigated using quantitative phase images and the scattering-phase theorem. An ex vivo study of 14 patients demonstrated that the average scattering coefficient of precancerous epithelia was 37.8% higher than that of normal epithelia from the same patient. The scattering coefficients were highly correlated with morphological features including the cell density and the nuclear-to-cytoplasmic ratio. A high interpatient variability in scattering coefficients was observed and suggests identifying precancerous lesions based on the relative change in scattering coefficients. PMID:26504630

  17. Prognostic significance of minichromosome maintenance proteins in breast cancer

    PubMed Central

    Kwok, Hang Fai; Zhang, Shu-Dong; McCrudden, Cian M; Yuen, Hiu-Fung; Ting, Kam-Po; Wen, Qing; Khoo, Ui-Soon; Chan, Kelvin Yuen-Kwong

    2015-01-01

    A role for the minichromosome maintenance (MCM) proteins in cancer initiation and progression is slowly emerging. Functioning as a complex to ensure a single chromosomal replication per cell cycle, the six family members have been implicated in several neoplastic disease states, including breast cancer. Our study aim to investigate the prognostic significance of these proteins in breast cancer. We studied the expression of MCMs in various datasets and the associations of the expression with clinicopathological parameters. When considered alone, high level MCM4 overexpression was only weakly associated with shorter survival in the combined breast cancer patient cohort (n = 1441, Hazard Ratio = 1.31; 95% Confidence Interval = 1.11-1.55; p = 0.001). On the other hand, when we studied all six components of the MCM complex, we found that overexpression of all MCMs was strongly associated with shorter survival in the same cohort (n = 1441, Hazard Ratio = 1.75; 95% Confidence Interval = 1.31-2.34; p < 0.001), suggesting these MCM proteins may cooperate to promote breast cancer progression. Indeed, their expressions were significantly correlated with each other in these cohorts. In addition, we found that increasing number of overexpressed MCMs was associated with negative ER status as well as treatment response. Together, our findings are reproducible in seven independent breast cancer cohorts, with 1441 patients, and suggest that MCM profiling could potentially be used to predict response to treatment and prognosis in breast cancer patients. PMID:25628920

  18. 31 CFR 561.328 - Reduce significantly, significantly reduced, and significant reduction.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 3 2013-07-01 2013-07-01 false Reduce significantly, significantly reduced, and significant reduction. 561.328 Section 561.328 Money and Finance: Treasury Regulations... IRANIAN FINANCIAL SANCTIONS REGULATIONS General Definitions § 561.328 Reduce significantly,...

  19. 31 CFR 561.328 - Reduce significantly, significantly reduced, and significant reduction.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance:Treasury 3 2014-07-01 2014-07-01 false Reduce significantly, significantly reduced, and significant reduction. 561.328 Section 561.328 Money and Finance: Treasury Regulations... IRANIAN FINANCIAL SANCTIONS REGULATIONS General Definitions § 561.328 Reduce significantly,...

  20. "Clinical" Significance: "Clinical" Significance and "Practical" Significance are NOT the Same Things

    ERIC Educational Resources Information Center

    Peterson, Lisa S.

    2008-01-01

    Clinical significance is an important concept in research, particularly in education and the social sciences. The present article first compares clinical significance to other measures of "significance" in statistics. The major methods used to determine clinical significance are explained and the strengths and weaknesses of clinical significance…

  1. Neutron Characterization for Additive Manufacturing

    NASA Technical Reports Server (NTRS)

    Watkins, Thomas; Bilheux, Hassina; An, Ke; Payzant, Andrew; DeHoff, Ryan; Duty, Chad; Peter, William; Blue, Craig; Brice, Craig A.

    2013-01-01

    Oak Ridge National Laboratory (ORNL) is leveraging decades of experience in neutron characterization of advanced materials together with resources such as the Spallation Neutron Source (SNS) and the High Flux Isotope Reactor (HFIR) shown in Fig. 1 to solve challenging problems in additive manufacturing (AM). Additive manufacturing, or three-dimensional (3-D) printing, is a rapidly maturing technology wherein components are built by selectively adding feedstock material at locations specified by a computer model. The majority of these technologies use thermally driven phase change mechanisms to convert the feedstock into functioning material. As the molten material cools and solidifies, the component is subjected to significant thermal gradients, generating significant internal stresses throughout the part (Fig. 2). As layers are added, inherent residual stresses cause warping and distortions that lead to geometrical differences between the final part and the original computer generated design. This effect also limits geometries that can be fabricated using AM, such as thin-walled, high-aspect- ratio, and overhanging structures. Distortion may be minimized by intelligent toolpath planning or strategic placement of support structures, but these approaches are not well understood and often "Edisonian" in nature. Residual stresses can also impact component performance during operation. For example, in a thermally cycled environment such as a high-pressure turbine engine, residual stresses can cause components to distort unpredictably. Different thermal treatments on as-fabricated AM components have been used to minimize residual stress, but components still retain a nonhomogeneous stress state and/or demonstrate a relaxation-derived geometric distortion. Industry, federal laboratory, and university collaboration is needed to address these challenges and enable the U.S. to compete in the global market. Work is currently being conducted on AM technologies at the ORNL

  2. Mycotoxins: significance to global economics and health

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mycotoxins are fungal metabolites produced my micro-fungi (molds and mildews) that have significant impacts on global economics and health. Some of these metabolites are beneficial, but most are harmful and have been associated with well-known epidemics dating back to medieval times. The terms ‘myco...

  3. Scope and Significance of Eating Disorders.

    ERIC Educational Resources Information Center

    Mitchell, James E.; Eckert, Elke D.

    1987-01-01

    Describes the increasing prevalence of anorexia nervosa and bulimia in many industrialized societies, and their association with significant morbidity and mortality. Discusses the genetic risks for the development of anorexia nervosa, and treatment strategies. Of these, pharmacotherapy and psychotherapy, particularly those incorporating…

  4. 31 CFR 561.404 - Significant transaction or transactions; significant financial services; significant financial...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 3 2013-07-01 2013-07-01 false Significant transaction or transactions; significant financial services; significant financial transaction. 561.404 Section 561.404 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY...

  5. Sustainability Characterization for Additive Manufacturing

    PubMed Central

    Mani, Mahesh; Lyons, Kevin W; Gupta, SK

    2014-01-01

    Additive manufacturing (AM) has the potential to create geometrically complex parts that require a high degree of customization, using less material and producing less waste. Recent studies have shown that AM can be an economically viable option for use by the industry, yet there are some inherent challenges associated with AM for wider acceptance. The lack of standards in AM impedes its use for parts production since industries primarily depend on established standards in processes and material selection to ensure the consistency and quality. Inability to compare AM performance against traditional manufacturing methods can be a barrier for implementing AM processes. AM process sustainability has become a driver due to growing environmental concerns for manufacturing. This has reinforced the importance to understand and characterize AM processes for sustainability. Process characterization for sustainability will help close the gaps for comparing AM performance to traditional manufacturing methods. Based on a literature review, this paper first examines the potential environmental impacts of AM. A methodology for sustainability characterization of AM is then proposed to serve as a resource for the community to benchmark AM processes for sustainability. Next, research perspectives are discussed along with relevant standardization efforts. PMID:26601038

  6. Sustainability Characterization for Additive Manufacturing.

    PubMed

    Mani, Mahesh; Lyons, Kevin W; Gupta, S K

    2014-01-01

    Additive manufacturing (AM) has the potential to create geometrically complex parts that require a high degree of customization, using less material and producing less waste. Recent studies have shown that AM can be an economically viable option for use by the industry, yet there are some inherent challenges associated with AM for wider acceptance. The lack of standards in AM impedes its use for parts production since industries primarily depend on established standards in processes and material selection to ensure the consistency and quality. Inability to compare AM performance against traditional manufacturing methods can be a barrier for implementing AM processes. AM process sustainability has become a driver due to growing environmental concerns for manufacturing. This has reinforced the importance to understand and characterize AM processes for sustainability. Process characterization for sustainability will help close the gaps for comparing AM performance to traditional manufacturing methods. Based on a literature review, this paper first examines the potential environmental impacts of AM. A methodology for sustainability characterization of AM is then proposed to serve as a resource for the community to benchmark AM processes for sustainability. Next, research perspectives are discussed along with relevant standardization efforts. PMID:26601038

  7. Pharmacological and Chemical Effects of Cigarette Additives

    PubMed Central

    Rabinoff, Michael; Caskey, Nicholas; Rissling, Anthony; Park, Candice

    2007-01-01

    We investigated tobacco industry documents and other sources for evidence of possible pharmacological and chemical effects of tobacco additives. Our findings indicated that more than 100 of 599 documented cigarette additives have pharmacological actions that camouflage the odor of environmental tobacco smoke emitted from cigarettes, enhance or maintain nicotine delivery, could increase the addictiveness of cigarettes, and mask symptoms and illnesses associated with smoking behaviors. Whether such uses were specifically intended for these agents is unknown. Our results provide a clear rationale for regulatory control of tobacco additives. PMID:17666709

  8. Nitrogen as a friendly addition to steel

    SciTech Connect

    Rawers, J.C.

    2006-01-01

    Interstitial alloying with nitrogen or carbon is a common means of enhancing properties of iron-based alloys. Interstitial nitrogen addition to fcc-phase Fe-Cr-Mn/Ni alloys results in improved mechanical properties, whereas addition of carbon can result in the formation of unwanted carbides. Carbon addition to low alloy, bcc-phase iron alloys significantly improves strength through the formation of carbides, whereas addition of nitrogen in bcc-phase iron alloys can result in porous casting and reduced mechanical properties. This study will show that alloying iron-based alloys with both nitrogen and carbon can produce positive results. Nitrogen addition to Fe-C and Fe-Cr-C alloys, and both nitrogen and nitrogen-carbon additions to Fe-Cr-Mn/Ni alloys altered the microstructure, improved mechanical properties, increased hardness, and reduced wear by stabilizing the fcc-phase and altering (possibly eliminating) precipitate formation.

  9. Astrobiological Significance of Microbial Extremophiles

    NASA Technical Reports Server (NTRS)

    Pikuta, Elena V.; Hoover, Richard B.

    2007-01-01

    The microflora of the cryosphere of planet Earth provides the best analogs for life forms that might be found in the permafrost or polar ice caps of Mars, near the surface of the cometary nuclei, or in the liquid water beneath and the ice crusts of icy moons of Jupiter and Saturn. The importance of study alkaliphilic microorganisms for astrobiology was enhanced by the findings of abundant carbonates and carbonate globules rimmed with possibly biogenic magnetites in association with the putative microfossils in the ALH84001 meteorite. Although the ALH84001 "nanofossils" were to small and simple to be unambiguously recognized as biogenic, they stimulated Astrobiology research and studies of microbial extremophiles and biomarkers in ancient rocks and meteorites. Recent studies of CI and CM carbonaceous meteorites have resulted in the detection of the well-preserved mineralized remains of coccoidal and filamentous microorganisms in cyanobacterial mats. Energy Dispersive X-ray Analysis has shown anomalous biogenic element ratios clearly indicating they are not recent biological contaminants. This paper reviews microbial extremophiles in context of their significance to Astrobiology. The study of halophilic microorganisms was started from work with saline soils and lakes, and one of the record of good growth for Haloferax mediterranei was shown at 30 percent NaC1. Although alkali-tolerant nitrifying bacteria had previously been reported, the first described alkaliphilic microorganism was the bacterium Streptococcus faecalis. Halophilic and alkaliphilic forms are relevant to conditions that might be found in closed impact basins and craters on Mars filled with evaporite deposits. The first obligately acidophilic bacterium described was Acidithiobacillus ferrooxydans (formally Thiobacillus ferrooxidans). Later thermophilic lithotrophic acidophiles were found, and the hyperacidophilic moderately thermophilic species of the genus Picrophilus were found to grow at negative p

  10. The impact of additional malignancies in patients diagnosed with gastrointestinal stromal tumors.

    PubMed

    Smith, Myles J; Smith, Henry G; Mahar, Alyson L; Law, Calvin; Ko, Yoo-Joung

    2016-10-15

    A higher incidence of additional malignancies has been described in patients diagnosed with gastrointestinal stromal tumors (GIST). This study aimed to identify risk factors for developing additional malignancies in patients diagnosed with GIST and evaluate the impact on survival. Individuals diagnosed with GIST from 2001 to2009 were identified from the SEER database. Logistic regression was used to identify predictors of additional malignancies and Cox-proportional hazards regression used to identify predictors of survival. In the study period, 1705 cases of GIST were identified, with 181 (10.6%) patients developing additional malignancies. Colorectal cancer was the most common cancer developing within 6 months of GIST diagnosis (30%). The median time to diagnosis of a malignancy after 6 months of GIST diagnosis was 21.9 months. Older age (p < 0.0001) and extraoesophagogastric GIST (p = 0.0027) were significant prognostic factors associated with additional malignancies. The overall 5-year survival was 65%, with the presence of additional malignancies within 6 months of GIST diagnosis associated with poor overall survival (54%, HR 1.55 1.05-2.3 95% CI, p = 0.04). Predictive factors of additional malignancies in patients diagnosed with GIST are increasing age and the primary disease site. Developing additional malignancies within 6 months of GIST diagnosis is associated with poorer overall survival. Targeted surveillance may be warranted in patients diagnosed with GIST that are at high risk of developing additional malignancies. PMID:27299364

  11. 76 FR 55882 - Procurement List; Addition

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-09

    ... INFORMATION: Additions On 6/17/2011 (76 FR 35415-35417), the Committee for Purchase From People Who Are Blind... detergent to the Government. The incumbent contractor indicated that it has a long established policy of... provide the labor associated with filling the detergent containers, as well as packaging the product...

  12. SIGNIFICANT NATURAL HERITAGE AREAS (NC)

    EPA Science Inventory

    The North Carolina Department of Environment and Natural Resources, Division of Parks and Recreation, Natural Heritage Program in cooperation with the NC Center for Geographic Information & Analysis, developed the Significant Natural Heritage Areas digital data to determine the a...

  13. Significant Decisions in Labor Cases.

    ERIC Educational Resources Information Center

    Monthly Labor Review, 1979

    1979-01-01

    Several significant court decisions involving labor cases are discussed including a series of decisions concerning constitutional protections afforded aliens; the First Amendment and national labor relations laws; and the bifurcated backpay rule. (BM)

  14. Astronomical Significance of Ancient Monuments

    NASA Astrophysics Data System (ADS)

    Simonia, I.

    2011-06-01

    Astronomical significance of Gokhnari megalithic monument (eastern Georgia) is considered. Possible connection of Amirani ancient legend with Gokhnari monument is discussed. Concepts of starry practicality and solar stations are proposed.

  15. Statistical Significance vs. Practical Significance: An Exploration through Health Education

    ERIC Educational Resources Information Center

    Rosen, Brittany L.; DeMaria, Andrea L.

    2012-01-01

    The purpose of this paper is to examine the differences between statistical and practical significance, including strengths and criticisms of both methods, as well as provide information surrounding the application of various effect sizes and confidence intervals within health education research. Provided are recommendations, explanations and…

  16. Capturing significant events with neural networks.

    PubMed

    Szu, Harold; Hsu, Charles; Jenkins, Jeffrey; Willey, Jefferson; Landa, Joseph

    2012-05-01

    Smartphone video capture and transmission to the Web contributes to data pollution. In contrast, mammalian eyes sense all, capture only significant events, allowing us vividly recall the causalities. Likewise in our videos, we wish to skip redundancies and keep only significantly differences, as determined by real-time local medium filters. We construct a Picture Index (PI) of one's (center of gravity changes) among zeros (no changes) as Motion Organized Sparseness (MOS). Only non-overlapping time-ordered PI pair is admitted in the outer-product Associative Memory (AM). Another outer product between PI and its image builds Hetero-AM (HAM) for fault tolerant retrievals. PMID:22402410

  17. Incorporation of additives into polymers

    DOEpatents

    McCleskey, T. Mark; Yates, Matthew Z.

    2003-07-29

    There has been invented a method for incorporating additives into polymers comprising: (a) forming an aqueous or alcohol-based colloidal system of the polymer; (b) emulsifying the colloidal system with a compressed fluid; and (c) contacting the colloidal polymer with the additive in the presence of the compressed fluid. The colloidal polymer can be contacted with the additive by having the additive in the compressed fluid used for emulsification or by adding the additive to the colloidal system before or after emulsification with the compressed fluid. The invention process can be carried out either as a batch process or as a continuous on-line process.

  18. Deciphering the roles of multiple additives in organocatalyzed Michael additions.

    PubMed

    Günler, Z Inci; Companyó, Xavier; Alfonso, Ignacio; Burés, Jordi; Jimeno, Ciril; Pericàs, Miquel A

    2016-05-21

    The synergistic effects of multiple additives (water and acetic acid) on the asymmetric Michael addition of acetone to nitrostyrene catalyzed by primary amine-thioureas (PAT) were precisely determined. Acetic acid facilitates hydrolysis of the imine intermediates, thus leading to catalytic behavior, and minimizes the formation of the double addition side product. In contrast, water slows down the reaction but minimizes catalyst deactivation, eventually leading to higher final yields. PMID:27128165

  19. Effect of glutathione addition in sparkling wine.

    PubMed

    Webber, Vanessa; Dutra, Sandra Valduga; Spinelli, Fernanda Rodrigues; Marcon, Ângela Rossi; Carnieli, Gilberto João; Vanderlinde, Regina

    2014-09-15

    This study aims to evaluate the effect of the addition of glutathione (GSH) on secondary aromas and on the phenolic compounds of sparkling wine elaborated by traditional method. It was added 10 and 20 mg L(-1) of GSH to must and to base wine. The determination of aroma compounds was performed by gas chromatography. Phenolic compounds and glutathione content were analyzed by high performance liquid chromatography. Sparkling wines with addition of GSH to must showed lower levels of total phenolic compounds and hydroxycinnamic acids. Furthermore, the sparkling wine with addition of GSH to must showed higher levels of 2-phenylethanol, 3-methyl-1-butanol and diethyl succinate, and lower concentrations of ethyl decanoate, octanoic and decanoic acids. The GSH addition to the must show a greater influence on sparkling wine than to base wine, however GSH addition to base wine seems retain higher SO2 free levels. The concentration of GSH added showed no significant difference. PMID:24767072

  20. Clinical significance of serum adipokines levels in lung cancer.

    PubMed

    Kerenidi, Theodora; Lada, Martha; Tsaroucha, Agori; Georgoulias, Panagiotis; Mystridou, Parthena; Gourgoulianis, Konstantinos I

    2013-06-01

    Adipokines have a significant effect on metabolism, immunoinflammatory responses as well as on carcinogenesis; therefore, we aimed at evaluating their potential predictive and prognostic significance in lung cancer. Eighty patients--mean age 62.9 ± 9.2 years--with previously untreated lung cancer (61 NSCLC and 19 SCLC) of all stages and 40 healthy individuals were enrolled in this study. Serum levels of leptin, adiponectin and ghrelin were measured using human Radioimmunoassay kits. Serum leptin levels in lung cancer patients were lower compared to control (p < 0.0001), while adiponectin and ghrelin levels were significantly increased in patients (p = 0.0003 and p = 0.0043, respectively). Additionally, the leptin/adiponectin ratio was significantly lower in the patients group compared to controls (p < 0.0001]. There was no association between serum levels of adipokines and any of the patient clinicopathological characteristics or response to therapy. Nevertheless, patients with lower values of serum leptin had shorter overall survival (p = 0.014), whereas multivariate analysis revealed leptin levels as an independent prognostic factor for survival (p = 0.024, HR 0.452, CI 95 % 0.232-0.899). These results suggest that adipokines may play a role in the pathogenesis of lung cancer, while leptin serum levels might provide useful prognostic information. PMID:23430445

  1. Adiposity significantly modifies genetic risk for dyslipidemia.

    PubMed

    Cole, Christopher B; Nikpay, Majid; Lau, Paulina; Stewart, Alexandre F R; Davies, Robert W; Wells, George A; Dent, Robert; McPherson, Ruth

    2014-11-01

    Recent genome-wide association studies have identified multiple loci robustly associated with plasma lipids, which also contribute to extreme lipid phenotypes. However, these common genetic variants explain <12% of variation in lipid traits. Adiposity is also an important determinant of plasma lipoproteins, particularly plasma TGs and HDL cholesterol (HDLc) concentrations. Thus, interactions between genes and clinical phenotypes may contribute to this unexplained heritability. We have applied a weighted genetic risk score (GRS) for both plasma TGs and HDLc in two large cohorts at the extremes of BMI. Both BMI and GRS were strongly associated with these lipid traits. A significant interaction between obese/lean status and GRS was noted for each of TG (P(Interaction) = 2.87 × 10(-4)) and HDLc (P(Interaction) = 1.05 × 10(-3)). These interactions were largely driven by SNPs tagging APOA5, glucokinase receptor (GCKR), and LPL for TG, and cholesteryl ester transfer protein (CETP), GalNAc-transferase (GALNT2), endothelial lipase (LIPG), and phospholipid transfer protein (PLTP) for HDLc. In contrast, the GRSLDL cholesterol × adiposity interaction was not significant. Sexual dimorphism was evident for the GRSHDL on HDLc in obese (P(Interaction) = 0.016) but not lean subjects. SNP by BMI interactions may provide biological insight into specific genetic associations and missing heritability. PMID:25225679

  2. Significant results: statistical or clinical?

    PubMed Central

    2016-01-01

    The null hypothesis significance test method is popular in biological and medical research. Many researchers have used this method for their research without exact knowledge, though it has both merits and shortcomings. Readers will know its shortcomings, as well as several complementary or alternative methods, as such the estimated effect size and the confidence interval. PMID:27066201

  3. The Most Significant Educational Research

    ERIC Educational Resources Information Center

    Griffiths, Daniel E.

    1972-01-01

    A reexamination of the significant research done in the decade from 1956-1966 and a revision of this list to include work up to 1971. Human characteristics, equality of educational opportunity, development of the individual, nature of intelligence, methodology of educational research, and principles of learning are some of the areas covered. (RB)

  4. Obstructive Sleep Apnea, Hypertension, and Their Additive Effects on Atherosclerosis

    PubMed Central

    Damiani, Mario Francesco; Zito, Annapaola; Carratù, Pierluigi; Falcone, Vito Antonio; Bega, Elioda; Scicchitano, Pietro; Ciccone, Marco Matteo; Resta, Onofrio

    2015-01-01

    Background and Aims. It is widely accepted that obstructive sleep apnea (OSA) is independently associated with atherosclerosis. Similar to OSA, hypertension (HTN) is a condition associated with atherosclerosis. However, to date, the impact of the simultaneous presence of OSA and HTN on the risk of atherosclerosis has not been extensively studied. The aim of this study was to evaluate the consequences of the coexistence of OSA and HTN on carotid intima-media thickness (IMT) and on inflammatory markers of atherosclerosis (such as interleukin- [IL-] 6 and pentraxin- [PTX-] 3). Methods. The study design allowed us to define 4 groups: (1) controls (n = 30); (2) OSA patients without HTN (n = 30); (3) HTN patients without OSA (n = 30); (4) patients with OSA and HTN (n = 30). In the morning after portable monitoring (between 7 am and 8 am), blood samples were collected, and carotid IMT was measured. Results. Carotid IMT, IL-6, and PTX-3 in OSA normotensive patients and in non-OSA HTN subjects were significantly higher compared to control subjects; in addition, in OSA hypertensive patients they were significantly increased compared to OSA normotensive, non-OSA HTN, or control subjects. Conclusions. OSA and HTN have an additive role in the progression of carotid atherosclerosis and in blood levels of inflammatory markers for atherosclerosis, such as interleukin-6 and pentraxin-3. PMID:26697221

  5. Prognostic significance of Tspan9 in gastric cancer

    PubMed Central

    Feng, Tongtong; Sun, Libin; Qi, Weiwei; Pan, Fei; Lv, Jing; Guo, Jing; Zhao, Shufen; Ding, Aiping; Qiu, Wensheng

    2016-01-01

    Tetraspanins are a large superfamily of glycoproteins, which are engaged in a wide range of specific molecular interactions by forming tetraspanin-enriched microdomains. Tetraspanin 9 (Tspan9) is a previously poorly studied tetraspanin gene, which was predominantly identified as an amplified gene in serous Fallopian tube carcinoma. However, the expression and role of Tspan9 in gastric cancer have yet to be fully elucidated. The aim of the present study was to evaluate the expression and clinical significance of Tspan9 in gastric cancer. In the present study, 105 gastric cancer tissue samples and corresponding adjacent normal samples were detected for Tspan9 expression using immunohistochemistry; furthermore, the association between clinical characteristics and Tspan9 expression was also analyzed. Tspan9 expression was determined to be significantly lower in cancer samples compared with those in corresponding adjacent normal samples (P<0.001). However, its increased levels of expression in cancer samples appeared to demonstrate a poorer prognostic tendency, which is associated with deeper tumor depth (P=0.025), more nodal involvement (P=0.01), more advanced tumor/lymph node/metastasis (TNM) stages (P=0.017) and a larger tumor size (P=0.026). Additionally, multivariate analysis demonstrated that high expression of Tspan9 was an independent prognostic factor for poor overall survival (P<0.01). These results suggested that Tspan9 may be used as a potential prognostic factor in gastric cancer.

  6. Enantioselective Michael Addition of Water

    PubMed Central

    Chen, Bi-Shuang; Resch, Verena; Otten, Linda G; Hanefeld, Ulf

    2015-01-01

    The enantioselective Michael addition using water as both nucleophile and solvent has to date proved beyond the ability of synthetic chemists. Herein, the direct, enantioselective Michael addition of water in water to prepare important β-hydroxy carbonyl compounds using whole cells of Rhodococcus strains is described. Good yields and excellent enantioselectivities were achieved with this method. Deuterium labeling studies demonstrate that a Michael hydratase catalyzes the water addition exclusively with anti-stereochemistry. PMID:25529526

  7. Gasoline additives, emissions, and performance

    SciTech Connect

    1995-12-31

    The papers included in this publication deal with the influence of fuel, additive, and hardware changes on a variety of vehicle performance characteristics. Advanced techniques for measuring these performance parameters are also described. Contents include: Fleet test evaluation of gasoline additives for intake valve and combustion chamber deposit clean up; A technique for evaluating octane requirement additives in modern engines on dynamometer test stands; A fleet test of two additive technologies comparing their effects on tailpipe emissions; Investigation into the vehicle exhaust emissions of high percentage ethanol blends; Variability in hydrocarbon speciation measurements at low emission (ULEV) levels; and more.

  8. 77 FR 71400 - Procurement List, Additions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-30

    ... . SUPPLEMENTARY INFORMATION: Additions On 8/24/2012 (77 FR 51522-51523) and 10/5/2012 (77 FR 60969), the Committee.... Regulatory Flexibility Act Certification I certify that the following action will not have a significant impact on a substantial number of small entities. The major factors considered for this...

  9. 31 CFR 561.404 - Significant transaction or transactions; significant financial services; significant financial...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... a business development strategy. (d) Nexus. The proximity between the foreign financial institution... (b)(3) of that section. For example, a transaction or financial service in which a foreign financial... significance than a transaction or financial service a foreign financial institution conducts for or...

  10. 31 CFR 561.404 - Significant transaction or transactions; significant financial services; significant financial...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... part of a pattern of conduct or the result of a business development strategy. (d) Nexus. The proximity... service in which a foreign financial institution provides brokerage or clearing services to, or maintains... generally would be of greater significance than a transaction or financial service a foreign...

  11. Fibromyalgia syndrome. New associations.

    PubMed

    Waylonis, G W; Heck, W

    1992-12-01

    Previous research has demonstrated a number of conditions, such as sleep disturbance, fatigue, depression, spastic colon and mitral valve prolapse, associated with fibromyalgia. The present report describes additional symptoms and medical conditions that appear to be associated with the syndrome based on a survey of 554 individuals with fibromyalgia compared with a group of 169 controls. Individuals with fibromyalgia self report a greater incidence of bursitis, chondromalacia, constipation, diarrhea, temporomandibular joint dysfunction, vertigo, sinus and thyroid problems. Symptomatic complaints found statistically more prevalent in fibromyalgia patients included concentration problems, sensory symptoms, swollen glands and tinnitus. Other associations occurring with significant increased frequency were chronic cough, coccygeal and pelvic pain, tachycardia and weakness. Our previous report on inheritance patterns in fibromyalgia was reaffirmed with 12% reporting symptomatic children and 25% reporting symptomatic parents. Of the respondents, 70% noted that their symptoms were aggravated by noise, lights, stress, posture and weather. PMID:1466872

  12. Toxicological significance of dihydrodiol metabolites

    SciTech Connect

    Hsia, M.T.

    1982-01-01

    Dihydrodiols are often found as the major organic-extractable metabolites of various olefinic or aromatic xenobiotics in many biological samples. Studies on the chemistry of dihydrodiol metabolites have provided insight into the pharmacokinetic behavior and the mode of action of the parent compound. The toxicology of dihydrodiol is more complex than what can be deduced solely on the basis of diminished bioavailability of the epoxide precursor, and the increased hydrophilicity associated with the dihydrodiol moiety. Dihydrodiols can be intrinsically toxic and may even represent metabolically activated species. Some of the dihydrodiol metabolites may still retain sufficient lipophilic character to serve again as substrates for microsomal oxygenases. Because of the tremendous chemical and biological diversity that existed among the various dihydrodiols, more mechanistic studies are needed to examine the toxicological properties of these compounds. It may be premature to conclude dihydrodiol formation as purely a detoxification route for xenobioties.

  13. Color Addition and Subtraction Apps

    ERIC Educational Resources Information Center

    Ruiz, Frances; Ruiz, Michael J.

    2015-01-01

    Color addition and subtraction apps in HTML5 have been developed for students as an online hands-on experience so that they can more easily master principles introduced through traditional classroom demonstrations. The evolution of the additive RGB color model is traced through the early IBM color adapters so that students can proceed step by step…

  14. 75 FR 27313 - Proposed Additions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-14

    ... FROM PEOPLE WHO ARE BLIND OR SEVERELY DISABLED PROCUREMENT LIST Proposed Additions AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION: Proposed additions to the... or Severely Disabled, Jefferson Plaza 2, Suite 10800, 1421 Jefferson Davis Highway,...

  15. Where boosted significances come from

    NASA Astrophysics Data System (ADS)

    Plehn, Tilman; Schichtel, Peter; Wiegand, Daniel

    2014-03-01

    In an era of increasingly advanced experimental analysis techniques it is crucial to understand which phase space regions contribute a signal extraction from backgrounds. Based on the Neyman-Pearson lemma we compute the maximum significance for a signal extraction as an integral over phase space regions. We then study to what degree boosted Higgs strategies benefit ZH and tt¯H searches and which transverse momenta of the Higgs are most promising. We find that Higgs and top taggers are the appropriate tools, but would profit from a targeted optimization towards smaller transverse momenta. MadMax is available as an add-on to MadGraph 5.

  16. Significances of Multimedia Technologies Training

    NASA Astrophysics Data System (ADS)

    Zhang, Fulei

    The use of multimedia technologies in education has enabled teachers to simulate final outcomes and assist s-tudents in applying knowledge learned from textbooks, thereby compensating for the deficiency of traditional teach- ing methods. It is important to examine how effective these technologies are in practical use. This study developed online learning-teaching resource platforms using Flash multimedia, providing interactive and integrated features in an easy-to-use user interface, in order to discuss Computer-Aided Drawing (CAD). The study utilized a teaching experiment with a non-equivalent pretest-posttest control group design to test and discuss students' professional cognition, operating skill cognition, and level of learning satisfaction during the learning process. No significant differences emerged between the groups in regards to professional cognition or operation skills cognition. However, a significant difference in learning satisfaction was noted, indicating that the coursework with multimedia Flash produced greater satisfaction than with traditional learning methods. Results are explained in detail and recommendations for further research provided.

  17. Public Health Significance of Neuroticism

    PubMed Central

    Lahey, Benjamin B.

    2009-01-01

    The personality trait of neuroticism refers to relatively stable tendencies to respond with negative emotions to threat, frustration, or loss. Individuals in the population vary markedly on this trait, ranging from frequent and intense emotional reactions to minor challenges to little emotional reaction even in the face of significant difficulties. Although not widely appreciated, there is growing evidence that neuroticism is a psychological trait of profound public health significance. Neuroticism is a robust correlate and predictor of many different mental and physical disorders, comorbidity among them, and the frequency of mental and general health service use. Indeed, neuroticism apparently is a predictor of the quality and longevity of our lives. Achieving a full understanding of the nature and origins of neuroticism, and the mechanisms through which neuroticism is linked to mental and physical disorders, should be a top priority for research. Knowing why neuroticism predicts such a wide variety of seemingly diverse outcomes should lead to improved understanding of commonalities among those outcomes and improved strategies for preventing them. PMID:19449983

  18. Significance of biofilms in dentistry.

    PubMed

    Wróblewska, Marta; Strużycka, Izabela; Mierzwińska-Nastalska, Elżbieta

    2015-01-01

    In the past decades significant scientific progress has taken place in the knowledge about biofilms. They constitute multilayer conglomerates of bacteria and fungi, surrounded by carbohydrates which they produce, as well as substances derived from saliva and gingival fluid. Modern techniques showed significant diversity of the biofilm environment and a system of microbial communication (quorum sensing), enhancing their survival. At present it is believed that the majority of infections, particularly chronic with exacerbations, are a result of biofilm formation, particularly in the presence of biomaterials. It should be emphasised that penetration of antibiotics and other antimicrobial agents into deeper layers of a biofilm is poor, causing therapeutic problems and necessitating sometimes removal of the implant or prosthesis. Biofilms play an increasing role in dentistry as a result of more and more broad use in dental practice of plastic and implantable materials. Biofilms are produced on the surfaces of teeth as dental plaque, in the para-nasal sinuses, on prostheses, dental implants, as well as in waterlines of a dental unit, constituting a particular risk for severely immunocompromised patients. New methods of therapy and prevention of infections linked to biofilms are under development. PMID:27139354

  19. Food Additives Permitted for Direct Addition to Food for Human Consumption; Folic Acid. Final rule.

    PubMed

    2016-04-15

    The Food and Drug Administration (FDA or we) is amending the food additive regulations to provide for the safe use of folic acid in corn masa flour. We are taking this action in response to a food additive petition filed jointly by Gruma Corporation, Spina Bifida Association, March of Dimes Foundation, American Academy of Pediatrics, Royal DSM N.V., and National Council of La Raza. PMID:27101640

  20. Pathological Significance of Mitochondrial Glycation

    PubMed Central

    Pun, Pamela Boon Li; Murphy, Michael P.

    2012-01-01

    Glycation, the nonenzymatic glycosylation of biomolecules, is commonly observed in diabetes and ageing. Reactive dicarbonyl species such as methylglyoxal and glyoxal are thought to be major physiological precursors of glycation. Because these dicarbonyls tend to be formed intracellularly, the levels of advanced glycation end products on cellular proteins are higher than on extracellular ones. The formation of glycation adducts within cells can have severe functional consequences such as inhibition of protein activity and promotion of DNA mutations. Although several lines of evidence suggest that there are specific mitochondrial targets of glycation, and mitochondrial dysfunction itself has been implicated in disease and ageing, it is unclear if glycation of biomolecules specifically within mitochondria induces dysfunction and contributes to disease pathology. We discuss here the possibility that mitochondrial glycation contributes to disease, focussing on diabetes, ageing, cancer, and neurodegeneration, and highlight the current limitations in our understanding of the pathological significance of mitochondrial glycation. PMID:22778743

  1. Clinical significance of complement deficiencies.

    PubMed

    Pettigrew, H David; Teuber, Suzanne S; Gershwin, M Eric

    2009-09-01

    The complement system is composed of more than 30 serum and membrane-bound proteins, all of which are needed for normal function of complement in innate and adaptive immunity. Historically, deficiencies within the complement system have been suspected when young children have had recurrent and difficult-to-control infections. As our understanding of the complement system has increased, many other diseases have been attributed to deficiencies within the complement system. Generally, complement deficiencies within the classical pathway lead to increased susceptibility to encapsulated bacterial infections as well as a syndrome resembling systemic lupus erythematosus. Complement deficiencies within the mannose-binding lectin pathway generally lead to increased bacterial infections, and deficiencies within the alternative pathway usually lead to an increased frequency of Neisseria infections. However, factor H deficiency can lead to membranoproliferative glomerulonephritis and hemolytic uremic syndrome. Finally, deficiencies within the terminal complement pathway lead to an increased incidence of Neisseria infections. Two other notable complement-associated deficiencies are complement receptor 3 and 4 deficiency, which result from a deficiency of CD18, a disease known as leukocyte adhesion deficiency type 1, and CD59 deficiency, which causes paroxysmal nocturnal hemoglobinuria. Most inherited deficiencies of the complement system are autosomal recessive, but properidin deficiency is X-linked recessive, deficiency of C1 inhibitor is autosomal dominant, and mannose-binding lectin and factor I deficiencies are autosomal co-dominant. The diversity of clinical manifestations of complement deficiencies reflects the complexity of the complement system. PMID:19758139

  2. The energetic significance of cooking.

    PubMed

    Carmody, Rachel N; Wrangham, Richard W

    2009-10-01

    While cooking has long been argued to improve the diet, the nature of the improvement has not been well defined. As a result, the evolutionary significance of cooking has variously been proposed as being substantial or relatively trivial. In this paper, we evaluate the hypothesis that an important and consistent effect of cooking food is a rise in its net energy value. The pathways by which cooking influences net energy value differ for starch, protein, and lipid, and we therefore consider plant and animal foods separately. Evidence of compromised physiological performance among individuals on raw diets supports the hypothesis that cooked diets tend to provide energy. Mechanisms contributing to energy being gained from cooking include increased digestibility of starch and protein, reduced costs of digestion for cooked versus raw meat, and reduced energetic costs of detoxification and defence against pathogens. If cooking consistently improves the energetic value of foods through such mechanisms, its evolutionary impact depends partly on the relative energetic benefits of non-thermal processing methods used prior to cooking. We suggest that if non-thermal processing methods such as pounding were used by Lower Palaeolithic Homo, they likely provided an important increase in energy gain over unprocessed raw diets. However, cooking has critical effects not easily achievable by non-thermal processing, including the relatively complete gelatinisation of starch, efficient denaturing of proteins, and killing of food borne pathogens. This means that however sophisticated the non-thermal processing methods were, cooking would have conferred incremental energetic benefits. While much remains to be discovered, we conclude that the adoption of cooking would have led to an important rise in energy availability. For this reason, we predict that cooking had substantial evolutionary significance. PMID:19732938

  3. The functional significance of stereopsis.

    PubMed

    O'Connor, Anna R; Birch, Eileen E; Anderson, Susan; Draper, Hayley

    2010-04-01

    Purpose. Development or restoration of binocular vision is one of the key goals of strabismus management; however, the functional impact of stereoacuity has largely been neglected. Methods. Subjects aged 10 to 30 years with normal, reduced, or nil stereoacuity performed three tasks: Purdue pegboard (measured how many pegs placed in 30 seconds), bead threading (with two sizes of bead, to increase the difficulty; measured time taken to thread a number of beads), and water pouring (measured both accuracy and time). All tests were undertaken both with and without occlusion of one eye. Results. One hundred forty-three subjects were recruited, 32.9% (n = 47) with a manifest deviation. Performances on the pegboard and bead tasks were significantly worse in the nil stereoacuity group when compared with that of the normal stereoacuity group. On the large and small bead tasks, those with reduced stereoacuity were better than those with nil stereoacuity (when the Preschool Randot Stereoacuity Test [Stereo Optical Co, Inc., Chicago, IL] results were used to determine stereoacuity levels). Comparison of the short-term monocular conditions (those with normal stereoacuity but occluded) with nil stereoacuity showed that, on all measures, the performance was best in the nil stereoacuity group and was statistically significant for the large and small beads task, irrespective of which test result was used to define the stereoacuity levels. Conclusions. Performance on motor skills tasks was related to stereoacuity, with subjects with normal stereoacuity performing best on all tests. This quantifiable degradation in performance on some motor skill tasks supports the need to implement management strategies to maximize development of high-grade stereoacuity. PMID:19933184

  4. Color Addition and Subtraction Apps

    NASA Astrophysics Data System (ADS)

    Ruiz, Frances; Ruiz, Michael J.

    2015-10-01

    Color addition and subtraction apps in HTML5 have been developed for students as an online hands-on experience so that they can more easily master principles introduced through traditional classroom demonstrations. The evolution of the additive RGB color model is traced through the early IBM color adapters so that students can proceed step by step in understanding mathematical representations of RGB color. Finally, color addition and subtraction are presented for the X11 colors from web design to illustrate yet another real-life application of color mixing.

  5. Orbital Fracture: Significance of lateral wall

    PubMed Central

    Alsuhaibani, Adel H.

    2010-01-01

    The lateral orbital wall is the strongest among other orbital walls. However, it is commonly fractured in the setting of severe facial trauma. The fracture usually occurs at the sphenozygomatic suture line. In general, patients with lateral wall fractures are commonly young male who may present with mid facial swelling and some degree of deformity. In some cases, lateral orbital wall fracture may be associated with visual loss or change in mental status due to associated intracranial injury. Imaging studies with computed tomography is important in the proper diagnosis and planning of the surgical intervention. Management of intracranial or eye injuries should be undertaken on emergent basis. Thereafter, significantly displaced lateral wall fractures need to be repaired on timely basis. Proper realignment of the plane of the lateral orbital wall at the sphenozygomatic suture along with the other complex articulations of the zygomatic bone is necessary for proper functional and aesthetic outcome. PMID:23960875

  6. Packaging and Transportation of Additional Neptunium Oxide

    SciTech Connect

    Watkins, R.; Jordan, J.; Hensel, S.

    2010-05-05

    The Savannah River Site's HB-Line Facility completed a second neptunium oxide production campaign in which nine (9) additional cans of neptunium oxide were produced and shipped to the Idaho National Laboratory and Oak Ridge National Laboratory in the 9975 shipping container. These additional cans were from a different feed solution than the first fifty (50) cans of neptunium oxide that were previously produced and shipped via a Letter of Amendment to the 9975 Safety Analysis Report for Packaging (SARP) content table. This paper will address the challenges associated with demonstrating the neptunium oxide produced from the additional feed solution was equivalent to the original neptunium oxide and within the content description of the Letter of Amendment.

  7. Calculators and Computers: Graphical Addition.

    ERIC Educational Resources Information Center

    Spero, Samuel W.

    1978-01-01

    A computer program is presented that generates problem sets involving sketching graphs of trigonometric functions using graphical addition. The students use calculators to sketch the graphs and a computer solution is used to check it. (MP)

  8. Discovery of medically significant lantibiotics.

    PubMed

    Piper, Clare; Cotter, Paul D; Ross, R Paul; Hill, Colin

    2009-03-01

    The emergence of drug-resistant pathogens such as staphylococci and enterococci in the hospital setting has long being recognized as a serious clinical problem. Staphylococcus aureus is the causative agent of many nosocomial infections from minor skin abscesses to serious, potentially life threatening diseases such as bone and soft tissue intra-surgical infections, sepsis and invasive endocarditis, while enterococci are responsible for nosocomial bacteraemia, surgical wound infections and endocarditis. The most infamous drug-resistant forms of these include MRSA (methicillin resistant S. aureus), VISA (vancomycin insensitive S. aureus), hVISA (heterogenous vancomycin insensitive S. aureus) and VRE (vancomycin resistant S. aureus). While enhanced hygiene awareness is essential to any solution, the identification of effective novel antimicrobial compounds remains a major goal in eradicating these and other infections caused by multi-drug resistant pathogens. In recent years a class of antimicrobial peptides, the Lantibiotics, have been the focus of an ever increasing level of attention. This interest has been prompted by an enhanced appreciation of the mode of action of these peptides (including, in many cases, the ability to bind lipid II) and their frequently high levels of antimicrobial activity. Here we review lantibiotic-related issues in drug discovery, outline the strategies that have been employed to identify these peptides and summarize the use of bioengineering to generate enhanced forms of these peptides as well as the application of the associated biological machinery to generate novel forms of existing pharmaceutical compounds. In so doing we highlight how some, or all, of these approaches have the potential to result in the development of clinically important drugs. PMID:19275538

  9. Are Carotid Stent Fractures Clinically Significant?

    SciTech Connect

    Garcia-Toca, Manuel; Rodriguez, Heron E.; Naughton, Peter A.; Keeling, Aiofee; Phade, Sachin V.; Morasch, Mark D.; Kibbe, Melina R.; Eskandari, Mark K.

    2012-04-15

    Purpose: Late stent fatigue is a known complication after carotid artery stenting (CAS) for cervical carotid occlusive disease. The purpose of this study was to determine the prevalence and clinical significance of carotid stent fractures. Materials and Methods: A single-center retrospective review of 253 carotid bifurcation lesions treated with CAS and mechanical embolic protection from April 2001 to December 2009 was performed. Stent integrity was analyzed by two independent observers using multiplanar cervical plain radiographs with fractures classified into the following types: type I = single strut fracture; type II = multiple strut fractures; type III = transverse fracture; and type IV = transverse fracture with dislocation. Mean follow-up was 32 months. Results: Follow-up imaging was completed on 106 self-expanding nitinol stents (26 closed-cell and 80 open-cell stents). Eight fractures (7.5%) were detected (type I n = 1, type II n = 6, and type III n = 1). Seven fractures were found in open-cell stents (Precise n = 3, ViVEXX n = 2, and Acculink n = 2), and 1 fracture was found in a closed-cell stent (Xact n = 1) (p = 0.67). Only a previous history of external beam neck irradiation was associated with fractures (p = 0.048). No associated clinical sequelae were observed among the patients with fractures, and only 1 patient had an associated significant restenosis ({>=}80%) requiring reintervention. Conclusions: Late stent fatigue after CAS is an uncommon event and rarely clinically relevant. Although cell design does not appear to influence the occurrence of fractures, lesion characteristics may be associated risk factors.

  10. Polyolefins as additives in plastics

    SciTech Connect

    Deanin, R.D.

    1993-12-31

    Polyolefins are not only major commodity plastics - they are also very useful as additives, both in other polyolefins and also in other types of plastics. This review covers ethylene, propylene, butylene and isobutylene polymers, in blends with each other, and as additives to natural rubber, styrene/butadiene rubber, polystyrene, polyvinyl chloride, polymethyl methacrylate, polyphenylene oxide, polycarbonate, thermoplastic polyesters, polyurethanes, polyamides, and mixed automotive plastics recycling.

  11. Reappraisal of risk factors for monoclonal gammopathy of undetermined significance.

    PubMed

    Boursi, Ben; Weiss, Brendan M; Haynes, Kevin; Mamtani, Ronac; Yang, Yu-Xiao

    2016-06-01

    A number of epidemiologic studies have demonstrated associations between obesity and diabetes and the risk of monoclonal gammopathy of undetermined significance (MGUS). However, since MGUS is an asymptomatic condition we evaluated whether these are true associations or the result of detection-bias. We conducted a nested case-control study using a large primary-care database. Cases were defined as those with incident diagnosis of MGUS. For every case, four eligible controls matched on age, sex, practice site, and duration of follow-up were selected. Exposure variables included obesity and diabetes (including antidiabetic therapies) as well as other metabolic risk factors. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression. The study included 2363 MGUS patients and 9193 matched controls. In the primary analysis, obesity and diabetes were associated with higher MGUS risk with an adjusted ORs of 1.15 (95% CI 1.02-1.29) and 1.30 (95% CI 1.13-1.50), respectively. However, after adjustment to the number of laboratory tests prior to the MGUS diagnosis, there was no association between obesity and diabetes and MGUS risk (ORs of 1.08, 95% CI 0.96-1.22 and 1.08, 95% CI 0.93-1.25, respectively). In an additional analysis of antidiabetic therapies and MGUS risk, there was a nonsignificant decrease in MGUS risk among diabetes patients treated with metformin alone compared to subjects without diabetes (OR 0.77, 95% CI 0.56-1.05). In summary, while previously described risk factors for MGUS might be the result of detection bias, metformin should be further evaluated as a possible chemoprevention modality. Am. J. Hematol. 91:581-584, 2016. © 2016 Wiley Periodicals, Inc. PMID:26953904

  12. Statistically significant relational data mining :

    SciTech Connect

    Berry, Jonathan W.; Leung, Vitus Joseph; Phillips, Cynthia Ann; Pinar, Ali; Robinson, David Gerald; Berger-Wolf, Tanya; Bhowmick, Sanjukta; Casleton, Emily; Kaiser, Mark; Nordman, Daniel J.; Wilson, Alyson G.

    2014-02-01

    This report summarizes the work performed under the project (3z(BStatitically significant relational data mining.(3y (BThe goal of the project was to add more statistical rigor to the fairly ad hoc area of data mining on graphs. Our goal was to develop better algorithms and better ways to evaluate algorithm quality. We concetrated on algorithms for community detection, approximate pattern matching, and graph similarity measures. Approximate pattern matching involves finding an instance of a relatively small pattern, expressed with tolerance, in a large graph of data observed with uncertainty. This report gathers the abstracts and references for the eight refereed publications that have appeared as part of this work. We then archive three pieces of research that have not yet been published. The first is theoretical and experimental evidence that a popular statistical measure for comparison of community assignments favors over-resolved communities over approximations to a ground truth. The second are statistically motivated methods for measuring the quality of an approximate match of a small pattern in a large graph. The third is a new probabilistic random graph model. Statisticians favor these models for graph analysis. The new local structure graph model overcomes some of the issues with popular models such as exponential random graph models and latent variable models.

  13. Determining Semantically Related Significant Genes.

    PubMed

    Taha, Kamal

    2014-01-01

    GO relation embodies some aspects of existence dependency. If GO term xis existence-dependent on GO term y, the presence of y implies the presence of x. Therefore, the genes annotated with the function of the GO term y are usually functionally and semantically related to the genes annotated with the function of the GO term x. A large number of gene set enrichment analysis methods have been developed in recent years for analyzing gene sets enrichment. However, most of these methods overlook the structural dependencies between GO terms in GO graph by not considering the concept of existence dependency. We propose in this paper a biological search engine called RSGSearch that identifies enriched sets of genes annotated with different functions using the concept of existence dependency. We observe that GO term xcannot be existence-dependent on GO term y, if x- and y- have the same specificity (biological characteristics). After encoding into a numeric format the contributions of GO terms annotating target genes to the semantics of their lowest common ancestors (LCAs), RSGSearch uses microarray experiment to identify the most significant LCA that annotates the result genes. We evaluated RSGSearch experimentally and compared it with five gene set enrichment systems. Results showed marked improvement. PMID:26357049

  14. Significant biases affecting abundance determinations

    NASA Astrophysics Data System (ADS)

    Wesson, Roger

    2015-08-01

    I have developed two highly efficient codes to automate analyses of emission line nebulae. The tools place particular emphasis on the propagation of uncertainties. The first tool, ALFA, uses a genetic algorithm to rapidly optimise the parameters of gaussian fits to line profiles. It can fit emission line spectra of arbitrary resolution, wavelength range and depth, with no user input at all. It is well suited to highly multiplexed spectroscopy such as that now being carried out with instruments such as MUSE at the VLT. The second tool, NEAT, carries out a full analysis of emission line fluxes, robustly propagating uncertainties using a Monte Carlo technique.Using these tools, I have found that considerable biases can be introduced into abundance determinations if the uncertainty distribution of emission lines is not well characterised. For weak lines, normally distributed uncertainties are generally assumed, though it is incorrect to do so, and significant biases can result. I discuss observational evidence of these biases. The two new codes contain routines to correctly characterise the probability distributions, giving more reliable results in analyses of emission line nebulae.

  15. Clinical significance of monocyte heterogeneity.

    PubMed

    Stansfield, Brian K; Ingram, David A

    2015-01-01

    Monocytes are primitive hematopoietic cells that primarily arise from the bone marrow, circulate in the peripheral blood and give rise to differentiated macrophages. Over the past two decades, considerable attention to monocyte diversity and macrophage polarization has provided contextual clues into the role of myelomonocytic derivatives in human disease. Until recently, human monocytes were subdivided based on expression of the surface marker CD16. "Classical" monocytes express surface markers denoted as CD14(++)CD16(-) and account for greater than 70% of total monocyte count, while "non-classical" monocytes express the CD16 antigen with low CD14 expression (CD14(+)CD16(++)). However, recognition of an intermediate population identified as CD14(++)CD16(+) supports the new paradigm that monocytes are a true heterogeneous population and careful identification of specific subpopulations is necessary for understanding monocyte function in human disease. Comparative studies of monocytes in mice have yielded more dichotomous results based on expression of the Ly6C antigen. In this review, we will discuss the use of monocyte subpopulations as biomarkers of human disease and summarize correlative studies in mice that may yield significant insight into the contribution of each subset to disease pathogenesis. PMID:25852821

  16. [The significance of antiphospholipid antibodies].

    PubMed

    Fojtík, Z

    2004-04-01

    Antiphospholipid antibodies (APLA) present very heterogeneous groups of antibodies which can significantly influence processes on different levels of coagulation cascade depending on effects of phospholipid surfaces on blood coagulation. This usually leads to a particular level of thrombophylia. Clinical syndrome accompanying positive APLA, such as antiphospholipid syndrome, was defined by clinical and laboratory symptoms. This clinical syndrome can be a primary syndrome, if other disorders with ability to induce generation of antibodies can be excluded, or a secondary syndrome. The most often in cases of systemic tissue disease. APLA can be divided according to the presence of lupus anticoagulant and anticardiolipin antibodies. According to a definition lupus anticoagulants are antibodies able to inhibit and prolong in vitro one or more blood clotting processes dependent on phospholipid surfaces. Anticardiolipin antibodies are antibodies measured by ELISA method with cardiolipin used as an antibody. Findings show that some APLA are directed against proteins bound to phospholipid surfaces. Main cofactor proteins include beta 2-GPI and prothrombin. Because of their heterogeneous specificity, APLA are directed against negative phospholipids or proteins bound to phospholipid surfaces and have important pathophysiology role in development of antiphospholipid syndrome. PMID:15214303

  17. ADDITIVITY ASSESSMENT OF TRIHALOMETHANE MIXTURES BY PROPORTIONAL RESPONSE ADDITION

    EPA Science Inventory

    If additivity is known or assumed, the toxicity of a chemical mixture may be predicted from the dose response curves of the individual chemicals comprising the mixture. As single chemical data are abundant and mixture data sparse, mixture risk methods that utilize single chemical...

  18. [INVITED] Lasers in additive manufacturing

    NASA Astrophysics Data System (ADS)

    Pinkerton, Andrew J.

    2016-04-01

    Additive manufacturing is a topic of considerable ongoing interest, with forecasts predicting it to have major impact on industry in the future. This paper focusses on the current status and potential future development of the technology, with particular reference to the role of lasers within it. It begins by making clear the types and roles of lasers in the different categories of additive manufacturing. This is followed by concise reviews of the economic benefits and disadvantages of the technology, current state of the market and use of additive manufacturing in different industries. Details of these fields are referenced rather than expanded in detail. The paper continues, focusing on current indicators to the future of additive manufacturing. Barriers to its development, trends and opportunities in major industrial sectors, and wider opportunities for its development are covered. Evidence indicates that additive manufacturing may not become the dominant manufacturing technology in all industries, but represents an excellent opportunity for lasers to increase their influence in manufacturing as a whole.

  19. Evaluation of certain food additives.

    PubMed

    2015-01-01

    This report represents the conclusions of a Joint FAO/WHO Expert Committee convened to evaluate the safety of various food additives, including flavouring agents, and to prepare specifications for identity and purity. The first part of the report contains a general discussion of the principles governing the toxicological evaluation of and assessment of dietary exposure to food additives, including flavouring agents. A summary follows of the Committee's evaluations of technical, toxicological and dietary exposure data for eight food additives (Benzoe tonkinensis; carrageenan; citric and fatty acid esters of glycerol; gardenia yellow; lutein esters from Tagetes erecta; octenyl succinic acid-modified gum arabic; octenyl succinic acid-modified starch; paprika extract; and pectin) and eight groups of flavouring agents (aliphatic and alicyclic hydrocarbons; aliphatic and aromatic ethers; ionones and structurally related substances; miscellaneous nitrogen-containing substances; monocyclic and bicyclic secondary alcohols, ketones and related esters; phenol and phenol derivatives; phenyl-substituted aliphatic alcohols and related aldehydes and esters; and sulfur-containing heterocyclic compounds). Specifications for the following food additives were revised: citric acid; gellan gum; polyoxyethylene (20) sorbitan monostearate; potassium aluminium silicate; and Quillaia extract (Type 2). Annexed to the report are tables summarizing the Committee's recommendations for dietary exposures to and toxicological evaluations of all of the food additives and flavouring agents considered at this meeting. PMID:26118220

  20. Manipulating crystallization with molecular additives.

    PubMed

    Shtukenberg, Alexander G; Lee, Stephanie S; Kahr, Bart; Ward, Michael D

    2014-01-01

    Given the importance of organic crystals in a wide range of industrial applications, the chemistry, biology, materials science, and chemical engineering communities have focused considerable attention on developing methods to control crystal structure, size, shape, and orientation. Tailored additives have been used to control crystallization to great effect, presumably by selectively binding to particular crystallographic surfaces and sites. However, substantial knowledge gaps still exist in the fundamental mechanisms that govern the formation and growth of organic crystals in both the absence and presence of additives. In this review, we highlight research discoveries that reveal the role of additives, either introduced by design or present adventitiously, on various stages of formation and growth of organic crystals, including nucleation, dislocation spiral growth mechanisms, growth inhibition, and nonclassical crystal morphologies. The insights from these investigations and others of their kind are likely to guide the development of innovative methods to manipulate crystallization for a wide range of materials and applications. PMID:24579880

  1. Additive Manufacturing of Hybrid Circuits

    NASA Astrophysics Data System (ADS)

    Sarobol, Pylin; Cook, Adam; Clem, Paul G.; Keicher, David; Hirschfeld, Deidre; Hall, Aaron C.; Bell, Nelson S.

    2016-07-01

    There is a rising interest in developing functional electronics using additively manufactured components. Considerations in materials selection and pathways to forming hybrid circuits and devices must demonstrate useful electronic function; must enable integration; and must complement the complex shape, low cost, high volume, and high functionality of structural but generally electronically passive additively manufactured components. This article reviews several emerging technologies being used in industry and research/development to provide integration advantages of fabricating multilayer hybrid circuits or devices. First, we review a maskless, noncontact, direct write (DW) technology that excels in the deposition of metallic colloid inks for electrical interconnects. Second, we review a complementary technology, aerosol deposition (AD), which excels in the deposition of metallic and ceramic powder as consolidated, thick conformal coatings and is additionally patternable through masking. Finally, we show examples of hybrid circuits/devices integrated beyond 2-D planes, using combinations of DW or AD processes and conventional, established processes.

  2. Prognostic significance of Dicer expression in hepatocellular carcinoma

    PubMed Central

    ZHANG, LI; WANG, CUIJU; LIU, SHUFENG; ZHAO, YUFEI; LIU, CHAO; GUO, ZHANJUN

    2016-01-01

    Dicer is a RNaseIII endonuclease of the microRNA processing pathway, which is implicated in carcinogenesis of various types of human cancer. The present study assessed the expression level of Dicer in hepatocellular carcinoma (HCC) tissue to evaluate its association with HCC tumorigenesis. A low expression of Dicer was significantly associated with a shorter postoperative survival time of patients with HCC, which was assessed using the log-rank test with Kaplan-Meier survival analysis. Multivariate analysis identified that Dicer expression was an independent predictor for HCC outcome (relative risk, 0.660; 95% confidence interval, 0.506–0.861; P=0.002). A functional assay demonstrated that Dicer overexpression inhibited the proliferation and promoted the apoptosis of HCC cells. In addition, a Transwell assay revealed that Dicer markedly inhibited the migration and invasion of HCC cells. The present findings indicate that Dicer expression modified the outcomes of HCC patients by inhibiting proliferation, promoting apoptosis and inhibiting metastasis of HCC cells. PMID:27313724

  3. Clinical significance of midkine expression in sporadic desmoid tumors

    PubMed Central

    KIM, HEE SUNG; KIM, JIN; NAM, KYUNG HAN; KIM, WOO HO

    2016-01-01

    The aim of the present study was to identify the prognostic factors for the propensity for recurrence in sporadic desmoid tumors. The catenin (cadherin-associated protein) β1 (CTNNB1) genotypes and expression of Wnt pathway proteins and midkine (also termed neurite growth-promoting factor 2) were investigated in 159 patients with sporadic desmoid tumors. Formalin-fixed paraffin-embedded tissues of the surgically resected desmoid tumors were examined by direct sequencing of CTNNB1 exon 3, and immunostained for the expression of β-catenin, T-cell factor 4 (TCF-4), phosphorylated protein kinase B (pAkt), midkine and menin using a tissue microarray method. Among the samples, 70% (111/159) exhibited point mutations of the CTNNB1 gene, including T41A (56%), S45F (8%), S45P (2%), S45N (2%) and T42A (1%). In addition, 100, 57, 24, 15 and 92% of the tumors expressed β-catenin, TCF-4, midkine, pAkt and menin, respectively. Positive midkine expression was significantly associated with the recurrence of tumors (P=0.001). The multivariate analysis of recurrence demonstrated that an extra-abdominal tumor site [hazard ratio (HR), 2.625; P=0.001] and midkine expression (HR, 2.077; P<0.009) were independent prognostic factors of tumor recurrence. In conclusion, the present results suggest that the tumor site and midkine expression may be predictive markers for the recurrence of sporadic desmoid tumors. PMID:26998061

  4. Prognostic significance of QRS duration and morphology.

    PubMed

    Brenyo, Andrew; Zaręba, Wojciech

    2011-01-01

    QRS duration and morphology, evaluated via a standard 12-lead electrocardiogram (ECG), represent an opportunity to derive useful prognostic information regarding the risk of subsequent cardiac events or therapeutic outcomes. Prolonged QRS duration, and the presence of intraventricular conduction abnormalities, usually indicate the presence of changes in the myocardium due to underlying heart disease. Prolonged QRS duration is often associated with depressed ejection fraction or enlarged left ventricular volumes, but several studies have demonstrated that this simple ECG measure provides independent prognostic value, after adjusting for relevant clinical covariates. Post-infarction patients with prolonged QRS duration have a significantly increased risk of mortality, although data associating QRS prolongation specifically with sudden death is less supportive. In non-ischemic cardiomyopathy, there is no evidence that QRS duration has prognostic significance in predicting mortality or sudden death. Prolonged QRS duration, and especially presence of left bundle branch block, seems to predict a benefit from cardiac resynchronization therapy in both ischemic and non-ischemic cardiomyopathy patients. Therefore, QRS duration and morphology should not only be considered a predictor of death or sudden death in patients after myocardial infarction, and in those suspected of coronary artery disease, but also as a predictor of benefit from cardiac resynchronization therapy in patients with heart failure, whether of an ischemic or non-ischemic origin. PMID:21305480

  5. 7 CFR 1469.4 - Significant resource concerns.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Provisions § 1469.4 Significant resource concerns. (a) Soil quality and water quality are nationally significant resource concerns for all land uses. (b) For each sign-up, the Chief may determine additional... 7 Agriculture 10 2010-01-01 2010-01-01 false Significant resource concerns. 1469.4 Section...

  6. Promoting Additive Acculturation in Schools.

    ERIC Educational Resources Information Center

    Gibson, Margaret A.

    1995-01-01

    A study focusing on 113 ninth graders of Mexican descent indicates that most students and their parents adhere to a strategy of additive acculturation (incorporating skills of the new culture and language), but that the school curriculum and general school climate devalue Mexican culture. (SLD)

  7. Individualized Additional Instruction for Calculus

    ERIC Educational Resources Information Center

    Takata, Ken

    2010-01-01

    College students enrolling in the calculus sequence have a wide variance in their preparation and abilities, yet they are usually taught from the same lecture. We describe another pedagogical model of Individualized Additional Instruction (IAI) that assesses each student frequently and prescribes further instruction and homework based on the…

  8. Out of bounds additive manufacturing

    SciTech Connect

    Holshouser, Chris; Newell, Clint; Palas, Sid; Love, Lonnie J.; Kunc, Vlastimil; Lind, Randall F.; Lloyd, Peter D.; Rowe, John C.; Blue, Craig A.; Duty, Chad E.; Peter, William H.; Dehoff, Ryan R.

    2013-03-01

    Lockheed Martin and Oak Ridge National Laboratory are working on an additive manufacturing system capable of manufacturing components measured not in terms of inches or feet, but multiple yards in all dimensions with the potential to manufacture parts that are completely unbounded in size.

  9. The Additive Property of Energy.

    ERIC Educational Resources Information Center

    Tsaoussis, Dimitris S.

    1995-01-01

    Presents exercises that analyze the additive property of energy. Concludes that if a body has more than one component of energy depending on the same physical quantity, the body's total energy will be the algebraic sum of the components if a linear relationship exists between the energy components and that physical quantity. (JRH)

  10. Tinkertoy Color-Addition Device.

    ERIC Educational Resources Information Center

    Ferguson, Joe L.

    1995-01-01

    Describes construction and use of a simple home-built device, using an overhead projector, for use in demonstrations of the addition of various combinations of red, green, and blue light. Useful in connection with discussions of color, color vision, or color television. (JRH)

  11. Silage Additives and Management Issues

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Inoculants are the most common silage additives in the United States. These products contain lactic acid bacteria to supplement the lactic acid bacteria naturally on the crop and help insure a consistent fermentation in the silo. There are three types of inoculants: homofermentative lactic acid bact...

  12. Tetrasulfide extreme pressure lubricant additives

    SciTech Connect

    Gast, L.E.; Kenney, H.E.; Schwab, A.W.

    1980-08-19

    A novel class of compounds has been prepared comprising the tetrasulfides of /sup 18/C hydrocarbons, /sup 18/C fatty acids, and /sup 18/C fatty and alkyl and triglyceride esters. These tetrasulfides are useful as extreme pressure lubricant additives and show potential as replacements for sulfurized sperm whale oil.

  13. Estimating soil water retention using soil component additivity model

    NASA Astrophysics Data System (ADS)

    Zeiliger, A.; Ermolaeva, O.; Semenov, V.

    2009-04-01

    Soil water retention is a major soil hydraulic property that governs soil functioning in ecosystems and greatly affects soil management. Data on soil water retention are used in research and applications in hydrology, agronomy, meteorology, ecology, environmental protection, and many other soil-related fields. Soil organic matter content and composition affect both soil structure and adsorption properties; therefore water retention may be affected by changes in soil organic matter that occur because of both climate change and modifications of management practices. Thus, effects of organic matter on soil water retention should be understood and quantified. Measurement of soil water retention is relatively time-consuming, and become impractical when soil hydrologic estimates are needed for large areas. One approach to soil water retention estimation from readily available data is based on the hypothesis that soil water retention may be estimated as an additive function obtained by summing up water retention of pore subspaces associated with soil textural and/or structural components and organic matter. The additivity model and was tested with 550 soil samples from the international database UNSODA and 2667 soil samples from the European database HYPRES containing all textural soil classes after USDA soil texture classification. The root mean square errors (RMSEs) of the volumetric water content estimates for UNSODA vary from 0.021 m3m-3 for coarse sandy loam to 0.075 m3m-3 for sandy clay. Obtained RMSEs are at the lower end of the RMSE range for regression-based water retention estimates found in literature. Including retention estimates of organic matter significantly improved RMSEs. The attained accuracy warrants testing the 'additivity' model with additional soil data and improving this model to accommodate various types of soil structure. Keywords: soil water retention, soil components, additive model, soil texture, organic matter.

  14. The Clinicopathologic Significance of BAF250a (ARID1A) Expression in Hepatocellular Carcinoma.

    PubMed

    Zhao, Jie; Chen, Jiang; Lin, Hui; Jin, Renan; Liu, Jinghua; Liu, Xiaolong; Meng, Ning; Cai, Xiujun

    2016-07-01

    Hepatocellular carcinoma (HCC) is one of the most common and lethal human cancers. Recently, exome sequencing has revealed that mutation of ARID1A is frequent in HCC. Herein, we determined the clinicopathologic significance of ARID1A expression in HCC. We detected the level of mRNA and protein expression of ARID1A in 12 paired HCC tumors and adjacent non-cancerous tissues by quantitative real-time PCR and immunohistochemistry (IHC). In addition, we determined the expression of BAF250a on 121 HCC tumors by IHC and assessed the association between BAF250a expression and clinicopathologic and prognostic features. The levels of ARID1A mRNA were significantly elevated in 10 of 12 HCC tumors compared with adjacent non-cancerous tissues. The level of BAF250a protein expression was higher in 10 of 12 HCC tumors compared with adjacent liver tissues. IHC indicated that 12.17 % of HCC tumors (14/115) were BAF250a-negative. Loss of BAF250a was significantly associated with larger tumor size, but not associated with other clinicopathologic features. There was no significant difference in disease-free or overall survival between BAF250a-positive and BAF250a-negative patients. Most HCCs had an increased level of ARID1A mRNA and BAF250a expression. Loss of BAF250a was significantly more frequent in larger HCC tumors, but had no prognostic significance. PMID:26589513

  15. Dissociation between exact and approximate addition in developmental dyslexia.

    PubMed

    Yang, Xiujie; Meng, Xiangzhi

    2016-09-01

    Previous research has suggested that number sense and language are involved in number representation and calculation, in which number sense supports approximate arithmetic, and language permits exact enumeration and calculation. Meanwhile, individuals with dyslexia have a core deficit in phonological processing. Based on these findings, we thus hypothesized that children with dyslexia may exhibit exact calculation impairment while doing mental arithmetic. The reaction time and accuracy while doing exact and approximate addition with symbolic Arabic digits and non-symbolic visual arrays of dots were compared between typically developing children and children with dyslexia. Reaction time analyses did not reveal any differences across two groups of children, the accuracies, interestingly, revealed a distinction of approximation and exact addition across two groups of children. Specifically, two groups of children had no differences in approximation. Children with dyslexia, however, had significantly lower accuracy in exact addition in both symbolic and non-symbolic tasks than that of typically developing children. Moreover, linguistic performances were selectively associated with exact calculation across individuals. These results suggested that children with dyslexia have a mental arithmetic deficit specifically in the realm of exact calculation, while their approximation ability is relatively intact. PMID:27310366

  16. Diesel fuel detergent additive performance and assessment

    SciTech Connect

    Vincent, M.W.; Papachristos, M.J.; Williams, D.; Burton, J.

    1994-10-01

    Diesel fuel detergent additives are increasingly linked with high quality automotive diesel fuels. Both in Europe and in the USA, field problems associated with fuel injector coking or fouling have been experienced. In Europe indirect injection (IDI) light duty engines used in passenger cars were affected, while in the USA, a direct injection (DI) engine in heavy duty truck applications experienced field problems. In both cases, a fuel additive detergent performance test has evolved using an engine linked with the original field problem, although engine design modifications employed by the manufacturers have ensured improved operation in service. Increasing awareness of the potential for injector nozzle coking to cause deterioration in engine performance is coupled with a need to meet ever more stringent exhaust emissions legislation. These two requirements indicate that the use of detergency additives will continue to be associated with high quality diesel fuels. The paper examines detergency performance evaluated in a range of IDI and DI engines and correlates performance in the two most widely recognised test engines, namely the Peugeot 1.9 litre IDI, and Cummins L10 DI engines. 17 refs., 18 figs., 5 tabs.

  17. Sibling Competition & Growth Tradeoffs. Biological vs. Statistical Significance

    PubMed Central

    Kramer, Karen L.; Veile, Amanda; Otárola-Castillo, Erik

    2016-01-01

    Early childhood growth has many downstream effects on future health and reproduction and is an important measure of offspring quality. While a tradeoff between family size and child growth outcomes is theoretically predicted in high-fertility societies, empirical evidence is mixed. This is often attributed to phenotypic variation in parental condition. However, inconsistent study results may also arise because family size confounds the potentially differential effects that older and younger siblings can have on young children’s growth. Additionally, inconsistent results might reflect that the biological significance associated with different growth trajectories is poorly understood. This paper addresses these concerns by tracking children’s monthly gains in height and weight from weaning to age five