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Sample records for increased mi risk

  1. MiR-146a rs2910164 polymorphism increases the risk of digestive system cancer: A meta-analysis.

    Xie, Wen Qun; Wang, Xiao Fan

    2017-02-01

    There is merging evidence suggesting that the miR-146a polymorphism might be associated with susceptibility to digestive system cancer. However, previous published studies have failed to achieve a definitive conclusion. To address this issue, an updated meta-analysis was performed. A comprehensive electronic search was conducted using the following source to identify the eligible studies: PubMed, Embase, China BioMedicine, the Cochrane Library, and Google Scholar. Odds ratios and its corresponding 95% confidence interval (CI) was used in the quantitative synthesis. The database search identified 1344 eligible studies, of which 32 (comprising 12,541 cases and 15,925 controls) were included. The results indicate that the miR-146a rs2910164 polymorphism was significantly associated with increased risk of digestive system cancer in heterozygote comparison (GC vs. CC: OR=1.15, 95% CI: 1.02-1.30, P=0.02), and recessive model (GG vs. GC+CC: OR=1.11, 95% CI: 1.04-1.17, P=0.006). Subgroup analysis by cancer site revealed increased risk in gastric cancer above heterozygote comparison (GG vs. GC: OR=1.13, 95% CI: 1.02-1.25, P=0.02), and recessive model (GG vs. GC+CC: OR=1.15, 95% CI: 1.04-1.26, P=0.006). Similarly, increased cancer risk was observed in hepatocellular carcinoma when compared with homozygote comparison (GG vs. CC: OR=1.21, 95% CI: 1.04-1.42, P=0.02), heterozygote comparison (GC vs. CC: OR=1.15, 95% CI: 1.02-1.29, P=0.02), and dominant model (GG+GC vs. CC: OR=1.16, 95% CI: 1.04-1.29, P=0.009). When stratified by ethnicity and quality score, increased cancer risks were also observed among Asians, Caucasians and high quality studies subgroup. The current study revealed that miR-146a G/C genetic polymorphism was more likely to be associated with digestive system cancer risk. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  2. Increased risk of polycystic ovary syndrome (PCOS) associated with CC genotype of miR-146a gene variation.

    Ebrahimi, Seyed Omar; Reiisi, Somayeh; Parchami Barjui, Shahrbanou

    2018-04-11

    Polycystic ovary syndrome (PCOS) is an endocrinopathy in reproductive-age women believed to be affected by several genetics and environmental factors or both. Different miRNAs are one of such genetic factors that their associations with PCOS have been implicated. For instance, miR-146a that is well known for strongly regulating the immune response and inflammation was upregulated in serum plasma, follicular fluid and granulosa cells of PCOS patients. Different studies have shown that genetic changes in pre-miRNA can cause change in the expression or biological function of mature miRNA. Therefore, the main aim of this study was to investigate the association of miR-146a gene variation (rs2910164) with the susceptibility to PCOS. This study consists of 180 patients with PCOS and 192 healthy women matched by age and geographical region. Genotyping were determined by using PCR-RFLP in all subjects. The genotype frequency and allele distributions of all subjects were evaluated using Fisher's exact test directed by SPSS v.20. The genotype and allele frequencies of the miR-146a polymorphism (rs2910164) significantly differ between PCOS and healthy controls. The frequencies of CC genotype (p = .054) and 'C' allele (p = .0001) of the miR-146a variant indicated a significant incidence in cases compared to controls. Such association was obtained in co-dominant (OR = 3.16) and dominant (OR = 2.29) models. Result of this study can be proposed that women with miR-146a variation are at a higher risk for developing PCOS, which can be due to up-regulation of miR-146a.

  3. miR-146a C/G polymorphism increased the risk of head and neck cancer, but overall cancer risk: an analysis of 89 studies.

    Sun, Dezhong; Zhang, Xiaoyan; Zhang, Xiaolei

    2018-02-28

    Several studies have evaluated the association of miR-146a C/G with head and neck cancer (HNC) susceptibility, and overall cancer risk, but with inconclusive outcomes. To drive a more precise estimation, we carried out this meta-analysis. The literature was searched from MEDLINE (mainly PubMed), Embase, the Cochrane Library, and Google Scholar databases to identify eligible studies. A total of 89 studies were included. The results showed that miR-146a C/G was significantly associated with increased HNC risk in dominant model ( I 2 =15.6%, P heterogeneity =0.282, odds ratio (OR) =1.088, 95% confidence interval (CI) =1.002-1.182, P =0.044). However, no cancer risk was detected under all genetic models. By further stratified analysis, we found that rs4919510 mutation contributed to the risk of HNC amongst Asians under homozygote model ( I 2 =0, P heterogeneity =0.541, OR =1.189, 95% CI =1.025-1.378, P =0.022), and dominant model ( I 2 =0, P heterogeneity =0.959, OR =1.155, 95% CI =1.016-1.312, P =0.028). Simultaneously, in the stratified analysis by source of controls, a significantly increased cancer risk amongst population-based studies was found under homozygote model, dominant model, recessive model, and allele comparison model. However, no significant association was found in the stratified analysis by ethnicity and source of control. The results indicated that miR-146a C/G polymorphism may contribute to the increased HNC susceptibility and could be a promising target to forecast cancer risk for clinical practice. However, no significant association was found in subgroup analysis by ethnicity and source of control. To further confirm these results, well-designed large-scale case-control studies are needed in the future. © 2018 The Author(s).

  4. MiR-27a rs895819 is involved in increased atrophic gastritis risk, improved gastric cancer prognosis and negative interaction with Helicobacter pylori

    Xu, Qian; Chen, Tie-jun; He, Cai-yun; Sun, Li-ping; Liu, Jing-wei; Yuan, Yuan

    2017-01-01

    MiR-27a rs895819 is a loop-stem structure single nucleotide polymorphism affecting mature miR-27a function. In this study, we performed a comprehensive analysis about the association of rs895819 with gastric cancer risk and prognosis, atrophic gastritis risk, as well as the interactions with environmental factors. A total of 939 gastric cancer patients, 1,067 atrophic gastritis patients and 1,166 healthy controls were screened by direct sequencing and MALDI-TOF-MS. The association of rs895819 with clinical pathological parameters and prognostic survival in 357 gastric cancer patients was also been analyzed. The rs895819 variant genotype increased the risk for atrophic gastritis (1.58-fold) and gastric cancer (1.24-fold). While in stratified analysis, the risk effect was demonstrated more significantly in the female, age >60y, Helicobacter pylori (H. pylori) negative and non-drinker subgroups. Rs895819 and H. pylori showed an interaction effect for atrophic gastritis risk. In the survival analysis, the rs895819 AG heterozygosis was associated with better survival than the AA wild-type in the TNM stage I–II subgroup. In vitro study by overexpressing miR-27a, cells carrying polymorphic-type G allele expressed lower miR-27a than wild-type A allele. In conclusion, miR-27a rs895819 is implicated as a biomarker for gastric cancer and atrophic gastritis risk, and interacts with H. pylori in gastric carcinogenesis. PMID:28150722

  5. A genetic variant in miR-196a2 increased digestive system cancer risks: a meta-analysis of 15 case-control studies.

    Jing Guo

    Full Text Available BACKGROUND: MicroRNAs (miRNAs negatively regulate the gene expression and act as tumor suppressors or oncogenes in oncogenesis. The association between single nucleotide polymorphism (SNP in miR-196a2 rs11614913 and the susceptibility of digestive system cancers was inconsistent in previous studies. METHODOLOGY/PRINCIPAL FINDINGS: An updated meta-analysis based on 15 independent case-control studies consisting of 4999 cancer patients and 7606 controls was performed to address this association. It was found that miR-196a2 polymorphism significantly elevated the risks of digestive system cancers (CT vs. TT, OR = 1.25, 95% CI = 1.07-1.45; CC vs. TT, OR = 1.38, 95% CI = 1.13-1.67; CC/CT vs. TT, OR = 1.29, 95% CI = 1.10-1.50; CC vs. CT/TT, OR = 1.14, 95% CI = 1.01-1.30; C vs. T, OR = 1.15, 95% CI = 1.05-1.26. We also found that variant in miR-196a2 increased the susceptibility of colorectal cancer (CRC (CT vs. TT, OR = 1.23, 95% CI = 1.04-1.44; CC vs. TT, OR = 1.32, 95% CI = 1.08-1.61; CC/CT vs. TT, OR = 1.25, 95% CI = 1.07-1.46; C vs. T, OR = 1.15, 95% CI = 1.05-1.28, while the association in recessive model (CC vs. CT/TT, OR = 1.16, 95% CI = 0.98-1.38 showed a marginal significance. Additionally, significant association between miR-196a2 polymorphism and increased risk of hepatocellular cancer (HCC was detected. By stratifying tumors on the basis of site of origin, source of controls, ethnicity and allele frequency in controls, elevated cancer risks were observed. CONCLUSION/SIGNIFICANCE: Our findings suggest the significant association between miR-196a2 polymorphism and increased susceptibility of digestive system cancers, especially of CRC, HCC and Asians. Besides, C allele may contribute to increased digestive cancer risks.

  6. Decreased miR-128 and increased miR-21 synergistically cause podocyte injury in sepsis.

    Wang, Shanshan; Wang, Jun; Zhang, Zengdi; Miao, Hongjun

    2017-08-01

    Glomerular podocytes are injured in sepsis. We studied, in a sepsis patient, whether microRNAs (miRNAs) play a role in the podocyte injury. Podocytes were cultured and treated with lipopolysaccharide (LPS). Filtration barrier function of podocyte was analyzed with albumin influx assay. Nephrin level was analyzed with reverse transcription polymerase chain reaction (RT-PCR) and western blot. MiRNAs were detected using miRNAs PCR Array and in situ hybridization. MiRNA target sites were evaluated with luciferase reporter assays. LPS impaired the filtration barrier function of podocytes. MiR-128 level was decreased and miR-21 level was increased in podocytes in vitro and in the sepsis patient. The decrease in miR-128 was sufficient to induce the loss of nephrin and the impairment of filtration barrier function, while the increase of miR-21 exacerbated the process. Snail and phosphatase and tensin homolog (PTEN) were identified as the targets of miR-128 and miR-21. Decreased miR-128 induced Snail expression, and the increased miR-21 stabilized Snail by regulating the PTEN/Akt/GSK3β pathway. Supplementation of miR-128 and inhibition of miR-21 suppressed Snail expression and prevented the podocyte injury induced by LPS. Our study suggests that decreased miR-128 and increased miR-21 synergistically cause podocyte injury and are the potential therapeutic targets in sepsis.

  7. A New Polymorphism Biomarker rs629367 Associated with Increased Risk and Poor Survival of Gastric Cancer in Chinese by Up-Regulated miRNA-let-7a Expression

    Xu, Qian; Dong, Qiguan; He, Caiyun; Liu, Wenjing; Sun, Liping; Liu, Jingwei; Xing, Chengzhong; Li, Xiaohang; Wang, Bengang; Yuan, Yuan

    2014-01-01

    Background Variant in pri-miRNA could affect miRNA expression and mature process or splicing efficiency, thus altering the hereditary susceptibility and prognosis of cancer. We aimed to assess miRNA-let-7 single nucleotide polymorphisms (SNP) associated with the risk and prognosis of gastric cancer (GC) as predicting biomarkers, and furthermore, its possible mechanisms. Methods A two-stage case-control study was designed to screen four miRNA SNPs (pri-let-7a-2 rs629367 and rs1143770, pri-let-7a-1 rs10739971, pri-let-7f-2 rs17276588) in 107 GC patients, 107 atrophic gastritis (AG), and matched 124 controls using PCR-RFLP. Two promising SNPs were validated in another independent 1949 samples (including 579 gastric cancer patients, 649 atrophic gastritis and 721 controls) using Sequenom MassARRAY platform and sequencing. Results We found that pri-let-7a-2 rs629367 CC variant genotype was associated with increased risks of gastric cancer and atrophic gastritis by 1.83-fold and 1.86-fold, respectively. For gastric cancer prognosis, patients with rs629367 CC genotype had significantly poorer survival than patients with AA genotype (log-rank P = 0.004). We further investigated the let-7a expression levels in serum and found that let-7a expression elevated gradually for rs629367 AA, CA, CC genotype in the atrophic gastritis group (P = 0.043). Furthermore, we confirmed these findings in vitro study by overexpressing let-7a carrying pri-let-7a-2 wild-type A or polymorphic-type C allele (Pcancer as well as atrophic gastritis and was also associated with poor survival of gastric cancer, which possibly by affecting the mature let-7a expression, and could serve as a predicting biomarker for high-risk and poor prognosis of gastric cancer. PMID:24760009

  8. Circulating miR-1, miR-133a, and miR-206 levels are increased after a half-marathon run.

    Gomes, Clarissa P C; Oliveira, Getúlio P; Madrid, Bibiano; Almeida, Jeeser A; Franco, Octávio L; Pereira, Rinaldo W

    2014-11-01

    Circulating miRNAs are potential biomarkers that can be important molecules driving cell-to-cell communication. To investigate circulating muscle-specific miRNAs in recreational athletes. Three miRNAs from whole plasma before and after a half-marathon were analyzed by qPCR. MiR-1, -133a, and -206 significantly increased after the race. Increased levels of miRNAs after exercise point to potential biomarkers and to the possibility of being functional players following endurance training. These miRNAs are potential biomarkers of muscle damage or adaptation to exercise.

  9. A new polymorphism biomarker rs629367 associated with increased risk and poor survival of gastric cancer in chinese by up-regulated miRNA-let-7a expression.

    Qian Xu

    Full Text Available BACKGROUND: Variant in pri-miRNA could affect miRNA expression and mature process or splicing efficiency, thus altering the hereditary susceptibility and prognosis of cancer. We aimed to assess miRNA-let-7 single nucleotide polymorphisms (SNP associated with the risk and prognosis of gastric cancer (GC as predicting biomarkers, and furthermore, its possible mechanisms. METHODS: A two-stage case-control study was designed to screen four miRNA SNPs (pri-let-7a-2 rs629367 and rs1143770, pri-let-7a-1 rs10739971, pri-let-7f-2 rs17276588 in 107 GC patients, 107 atrophic gastritis (AG, and matched 124 controls using PCR-RFLP. Two promising SNPs were validated in another independent 1949 samples (including 579 gastric cancer patients, 649 atrophic gastritis and 721 controls using Sequenom MassARRAY platform and sequencing. RESULTS: We found that pri-let-7a-2 rs629367 CC variant genotype was associated with increased risks of gastric cancer and atrophic gastritis by 1.83-fold and 1.86-fold, respectively. For gastric cancer prognosis, patients with rs629367 CC genotype had significantly poorer survival than patients with AA genotype (log-rank P = 0.004. We further investigated the let-7a expression levels in serum and found that let-7a expression elevated gradually for rs629367 AA, CA, CC genotype in the atrophic gastritis group (P = 0.043. Furthermore, we confirmed these findings in vitro study by overexpressing let-7a carrying pri-let-7a-2 wild-type A or polymorphic-type C allele (P<0.001. CONCLUSIONS: pri-let-7a-2 rs629367 CC genotype could increase the risks of gastric cancer as well as atrophic gastritis and was also associated with poor survival of gastric cancer, which possibly by affecting the mature let-7a expression, and could serve as a predicting biomarker for high-risk and poor prognosis of gastric cancer.

  10. miR-132 and miR-212 are increased in pancreatic cancer and target the retinoblastoma tumor suppressor

    Park, Jong-Kook [College of Pharmacy, Ohio State University, Columbus, OH 43210 (United States); Henry, Jon C. [Department of Surgery, Ohio State University, Columbus, OH 43210 (United States); Jiang, Jinmai [College of Pharmacy, Ohio State University, Columbus, OH 43210 (United States); Esau, Christine [Regulus Therapeutics, Carlsbad, CA (United States); Gusev, Yuriy [Lombardi Cancer Center, Georgetown University, Washington, DC (United States); Lerner, Megan R. [Veterans Affairs Medical Center, Oklahoma City, OK (United States); Postier, Russell G. [Department of Surgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States); Brackett, Daniel J. [Veterans Affairs Medical Center, Oklahoma City, OK (United States); Schmittgen, Thomas D., E-mail: Schmittgen.2@osu.edu [College of Pharmacy, Ohio State University, Columbus, OH 43210 (United States)

    2011-03-25

    Research highlights: {yields} The expression of miR-132 and miR-212 are significantly increased in pancreatic cancer. {yields} miR-132 and miR-212 target the tumor suppressor pRb, resulting in enhanced proliferation. {yields} miR-132 and miR-212 expression is increased by a {beta}2 adrenergic receptor agonist, suggesting a novel mechanism for pancreatic cancer progression. -- Abstract: Numerous microRNAs (miRNAs) are reported as differentially expressed in cancer, however the consequence of miRNA deregulation in cancer is unknown for many miRNAs. We report that two miRNAs located on chromosome 17p13, miR-132 and miR-212, are over-expressed in pancreatic adenocarcinoma (PDAC) tissues. Both miRNAs are predicted to target the retinoblastoma tumor suppressor, Rb1. Validation of this interaction was confirmed by luciferase reporter assay and western blot in a pancreatic cancer cell line transfected with pre-miR-212 and pre-miR-132 oligos. Cell proliferation was enhanced in Panc-1 cells transfected with pre-miR-132/-212 oligos. Conversely, antisense oligos to miR-132/-212 reduced cell proliferation and caused a G{sub 2}/M cell cycle arrest. The mRNA of a number of E2F transcriptional targets were increased in cells over expressing miR-132/-212. Exposing Panc-1 cells to the {beta}2 adrenergic receptor agonist, terbutaline, increased the miR-132 and miR-212 expression by 2- to 4-fold. We report that over-expression of miR-132 and miR-212 result in reduced pRb protein in pancreatic cancer cells and that the increase in cell proliferation from over-expression of these miRNAs is likely due to increased expression of several E2F target genes. The {beta}2 adrenergic pathway may play an important role in this novel mechanism.

  11. miR-132 and miR-212 are increased in pancreatic cancer and target the retinoblastoma tumor suppressor

    Park, Jong-Kook; Henry, Jon C.; Jiang, Jinmai; Esau, Christine; Gusev, Yuriy; Lerner, Megan R.; Postier, Russell G.; Brackett, Daniel J.; Schmittgen, Thomas D.

    2011-01-01

    Research highlights: → The expression of miR-132 and miR-212 are significantly increased in pancreatic cancer. → miR-132 and miR-212 target the tumor suppressor pRb, resulting in enhanced proliferation. → miR-132 and miR-212 expression is increased by a β2 adrenergic receptor agonist, suggesting a novel mechanism for pancreatic cancer progression. -- Abstract: Numerous microRNAs (miRNAs) are reported as differentially expressed in cancer, however the consequence of miRNA deregulation in cancer is unknown for many miRNAs. We report that two miRNAs located on chromosome 17p13, miR-132 and miR-212, are over-expressed in pancreatic adenocarcinoma (PDAC) tissues. Both miRNAs are predicted to target the retinoblastoma tumor suppressor, Rb1. Validation of this interaction was confirmed by luciferase reporter assay and western blot in a pancreatic cancer cell line transfected with pre-miR-212 and pre-miR-132 oligos. Cell proliferation was enhanced in Panc-1 cells transfected with pre-miR-132/-212 oligos. Conversely, antisense oligos to miR-132/-212 reduced cell proliferation and caused a G 2 /M cell cycle arrest. The mRNA of a number of E2F transcriptional targets were increased in cells over expressing miR-132/-212. Exposing Panc-1 cells to the β2 adrenergic receptor agonist, terbutaline, increased the miR-132 and miR-212 expression by 2- to 4-fold. We report that over-expression of miR-132 and miR-212 result in reduced pRb protein in pancreatic cancer cells and that the increase in cell proliferation from over-expression of these miRNAs is likely due to increased expression of several E2F target genes. The β2 adrenergic pathway may play an important role in this novel mechanism.

  12. miRNA-Processing Gene Methylation and Cancer Risk.

    Joyce, Brian T; Zheng, Yinan; Zhang, Zhou; Liu, Lei; Kocherginsky, Masha; Murphy, Robert; Achenbach, Chad J; Musa, Jonah; Wehbe, Firas; Just, Allan; Shen, Jincheng; Vokonas, Pantel; Schwartz, Joel; Baccarelli, Andrea A; Hou, Lifang

    2018-05-01

    Background: Dysregulation of miRNA and methylation levels are epigenetic hallmarks of cancer, potentially linked via miRNA-processing genes. Studies have found genetic alterations to miRNA-processing genes in cancer cells and human population studies. Our objective was to prospectively examine changes in DNA methylation of miRNA-processing genes and their associations with cancer risk. Methods: We examined cohort data from the Department of Veterans' Affairs Normative Aging Study. Participants were assessed every 3 to 5 years starting in 1999 through 2013 including questionnaires, medical record review, and blood collection. Blood from 686 consenting participants was analyzed using the Illumina 450K BeadChip array to measure methylation at CpG sites throughout the genome. We selected 19 genes based on a literature review, with 519 corresponding CpG sites. We then used Cox proportional hazards models to examine associations with cancer incidence, and generalized estimating equations to examine associations with cancer prevalence. Associations at false discovery rate time to cancer development (positively for cg06751583, inversely for cg23230564 and cg21034183), whereas methylation of one CpG site ( DROSHA : cg16131300) was positively associated with cancer prevalence. Conclusions: DNA methylation of DROSHA , a key miRNA-processing gene, and TNRC6B may play a role in early carcinogenesis. Impact: Changes in miRNA processing may exert multiple effects on cancer development, including protecting against it via altered global miRNAs, and may be a useful early detection biomarker of cancer. Cancer Epidemiol Biomarkers Prev; 27(5); 550-7. ©2018 AACR . ©2018 American Association for Cancer Research.

  13. Celecoxib increases miR-222 while deterring aromatase-expressing breast tumor growth in mice

    Wong, Tsz Yan; Li, Fengjuan; Lin, Shu-mei; Chan, Franky L; Chen, Shiuan; Leung, Lai K

    2014-01-01

    Breast cancer is one of the most deadly diseases in women. Inhibiting the synthesis of estrogen is effective in treating patients with estrogen-responsive breast cancer. Previous studies have demonstrated that use of cyclooxygenase (COX) inhibitors is associated with reduced breast cancer risk. In the present study, we employed an established mouse model for postmenopausal breast cancer to evaluate the potential mechanisms of the COX-2 inhibitor celecoxib. Aromatase-expressing MCF-7 cells were transplanted into ovariectomized athymic mice. The animals were given celecoxib at 1500 ppm or aspirin at 200 ppm by oral administration with androstenedione injection. Our results showed that both COX inhibitors could suppress the cancer xenograft growth without changing the plasma estrogen level. Protein expression of ERα, COX-2, Cyclin A, and Bcl-xL were reduced in celecoxib-treated tumor samples, whereas only Bcl-xL expression was suppressed in those treated with aspirin. Among the breast cancer-related miRNAs, miR-222 expression was elevated in samples treated with celecoxib. Further studies in culture cells verified that the increase in miR-222 expression might contribute to ERα downregulation but not the growth deterrence of cells. Overall, this study suggested that both celecoxib and aspirin could prevent breast cancer growth by regulating proteins in the cell cycle and apoptosis without blocking estrogen synthesis. Besides, celecoxib might affect miR expression in an undesirable fashion

  14. Decreased neutrophil-associated miRNA and increased B-cell associated miRNA expression during tuberculosis.

    van Rensburg, I C; du Toit, L; Walzl, G; du Plessis, N; Loxton, A G

    2018-05-20

    MicroRNAs are short non-coding RNAs that regulate gene expression by binding to, and suppressing the expression of genes. Research show that microRNAs have potential to be used as biomarkers for diagnosis, treatment response and can be used for therapeutic interventions. Furthermore, microRNA expression has effects on immune cell functions, which may lead to disease. Considering the important protective role of neutrophils and B-cells during M.tb infection, we evaluated the expression of microRNAs, known to alter function of these cells, in the context of human TB. We utilised real-time PCR to evaluate the levels of microRNA transcripts in the peripheral blood of TB cases and healthy controls. We found that neutrophil-associated miR-197-3p, miR-99b-5p and miR-191-5p transcript levels were significantly lower in TB cases. Additionally, B-cell-associated miR-320a, miR-204-5p, miR331-3p and other transcript levels were higher in TB cases. The miRNAs differentially expressed in neutrophils are predominantly implicated in signalling pathways leading to cytokine productions. Here, the decreased expression in TB cases may imply a lack of suppression on signalling pathways, which may lead to increased production of pro-inflammatory cytokines such as interferon-gamma. Furthermore, the miRNAs differentially expressed in B-cells are mostly involved in the induction/suppression of apoptosis. Further functional studies are however required to elucidate the significance and functional effects of changes in the expression of these microRNAs. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. The adipokine leptin increases skeletal muscle mass and significantly alters skeletal muscle miRNA expression profile in aged mice

    Hamrick, Mark W.; Herberg, Samuel; Arounleut, Phonepasong; He, Hong-Zhi; Shiver, Austin; Qi, Rui-Qun; Zhou, Li; Isales, Carlos M.

    2010-01-01

    Research highlights: → Aging is associated with muscle atrophy and loss of muscle mass, known as the sarcopenia of aging. → We demonstrate that age-related muscle atrophy is associated with marked changes in miRNA expression in muscle. → Treating aged mice with the adipokine leptin significantly increased muscle mass and the expression of miRNAs involved in muscle repair. → Recombinant leptin therapy may therefore be a novel approach for treating age-related muscle atrophy. -- Abstract: Age-associated loss of muscle mass, or sarcopenia, contributes directly to frailty and an increased risk of falls and fractures among the elderly. Aged mice and elderly adults both show decreased muscle mass as well as relatively low levels of the fat-derived hormone leptin. Here we demonstrate that loss of muscle mass and myofiber size with aging in mice is associated with significant changes in the expression of specific miRNAs. Aging altered the expression of 57 miRNAs in mouse skeletal muscle, and many of these miRNAs are now reported to be associated specifically with age-related muscle atrophy. These include miR-221, previously identified in studies of myogenesis and muscle development as playing a role in the proliferation and terminal differentiation of myogenic precursors. We also treated aged mice with recombinant leptin, to determine whether leptin therapy could improve muscle mass and alter the miRNA expression profile of aging skeletal muscle. Leptin treatment significantly increased hindlimb muscle mass and extensor digitorum longus fiber size in aged mice. Furthermore, the expression of 37 miRNAs was altered in muscles of leptin-treated mice. In particular, leptin treatment increased the expression of miR-31 and miR-223, miRNAs known to be elevated during muscle regeneration and repair. These findings suggest that aging in skeletal muscle is associated with marked changes in the expression of specific miRNAs, and that nutrient-related hormones such as leptin

  16. The adipokine leptin increases skeletal muscle mass and significantly alters skeletal muscle miRNA expression profile in aged mice

    Hamrick, Mark W., E-mail: mhamrick@mail.mcg.edu [Department of Cellular Biology and Anatomy, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Department of Orthopaedic Surgery, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Herberg, Samuel; Arounleut, Phonepasong [Department of Cellular Biology and Anatomy, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Department of Orthopaedic Surgery, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); He, Hong-Zhi [Henry Ford Immunology Program, Henry Ford Health System, Detroit, MI (United States); Department of Dermatology, Henry Ford Health System, Detroit, MI (United States); Shiver, Austin [Department of Cellular Biology and Anatomy, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Department of Orthopaedic Surgery, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Qi, Rui-Qun [Henry Ford Immunology Program, Henry Ford Health System, Detroit, MI (United States); Department of Dermatology, Henry Ford Health System, Detroit, MI (United States); Zhou, Li [Henry Ford Immunology Program, Henry Ford Health System, Detroit, MI (United States); Department of Dermatology, Henry Ford Health System, Detroit, MI (United States); Department of Internal Medicine, Henry Ford Health System, Detroit, MI (United States); Isales, Carlos M. [Department of Cellular Biology and Anatomy, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Department of Orthopaedic Surgery, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); others, and

    2010-09-24

    Research highlights: {yields} Aging is associated with muscle atrophy and loss of muscle mass, known as the sarcopenia of aging. {yields} We demonstrate that age-related muscle atrophy is associated with marked changes in miRNA expression in muscle. {yields} Treating aged mice with the adipokine leptin significantly increased muscle mass and the expression of miRNAs involved in muscle repair. {yields} Recombinant leptin therapy may therefore be a novel approach for treating age-related muscle atrophy. -- Abstract: Age-associated loss of muscle mass, or sarcopenia, contributes directly to frailty and an increased risk of falls and fractures among the elderly. Aged mice and elderly adults both show decreased muscle mass as well as relatively low levels of the fat-derived hormone leptin. Here we demonstrate that loss of muscle mass and myofiber size with aging in mice is associated with significant changes in the expression of specific miRNAs. Aging altered the expression of 57 miRNAs in mouse skeletal muscle, and many of these miRNAs are now reported to be associated specifically with age-related muscle atrophy. These include miR-221, previously identified in studies of myogenesis and muscle development as playing a role in the proliferation and terminal differentiation of myogenic precursors. We also treated aged mice with recombinant leptin, to determine whether leptin therapy could improve muscle mass and alter the miRNA expression profile of aging skeletal muscle. Leptin treatment significantly increased hindlimb muscle mass and extensor digitorum longus fiber size in aged mice. Furthermore, the expression of 37 miRNAs was altered in muscles of leptin-treated mice. In particular, leptin treatment increased the expression of miR-31 and miR-223, miRNAs known to be elevated during muscle regeneration and repair. These findings suggest that aging in skeletal muscle is associated with marked changes in the expression of specific miRNAs, and that nutrient

  17. Inhibition of 14q32 MicroRNAs miR-329, miR-487b, miR-494, and miR-495 Increases Neovascularization and Blood Flow Recovery After Ischemia

    Welten, S. M. J.; Bastiaansen, Ajnm; de Jong, R. C. M.

    2014-01-01

    in mice after single femoral artery ligation. Methods and Results: Gene silencing oligonucleotides (GSOs) were used to inhibit 4 14q32 microRNAs, miR-329, miR-487b, miR-494, and miR-495, 1 day before double femoral artery ligation. Blood flow recovery was followed by laser Doppler perfusion imaging. All 4...... GSOs clearly improved blood flow recovery after ischemia. Mice treated with GSO-495 or GSO-329 showed increased perfusion already after 3 days (30% perfusion versus 15% in control), and those treated with GSO-329 showed a full recovery of perfusion after 7 days (versus 60% in control). Increased...

  18. Genetic polymorphisms of miR-146a and miR-27a, H. pylori infection, and risk of gastric lesions in a Chinese population.

    Ming-yang Song

    Full Text Available BACKGROUND: MicroRNAs (miRNAs have been implicated in various human diseases. Single nucleotide polymorphisms (SNPs in inflammation-related miRNA may play an important role in Helicobacter pylori (H. pylori-induced gastric lesions. To evaluate the associations between miRNA SNPs, H. pylori and gastric lesions, a population-based study was conducted in Linqu County, China. METHODOLOGY/PRINCIPAL FINDINGS: Based on serum miRNA array conducted in this population, two SNP loci (miR-146a rs2910164: G>C and miR-27a rs895819: T>C were determined by polymerase chain reaction-restriction fragment length polymorphism in 2,380 participants with diverse gastric lesions. Using participants with superficial gastritis and mild chronic atrophic gastritis as the reference group, we found that rs2910164 CC carriers had a significantly increased risk of intestinal metaplasia [adjusted odds ratio (OR, 1.42; 95% confidence interval (CI, 1.03-1.97] and dysplasia (OR, 1.54; 95% CI, 1.05-2.25 compared to GG carriers, whereas no significant association was observed for rs895819. Stratified analysis by H. pylori infection indicated that rs2910164 C allele was associated with an increased risk of intestinal metaplasia and dysplasia only among individuals infected with H. pylori (CC vs. GG: OR, 1.53; 95% CI, 1.12-2.08, P for trend = 0.004. Participants who simultaneously carried variant alleles and H. pylori infection were more likely to develop intestinal metaplasia and dysplasia, although the interaction between genetic variants and H. pylori infection was not significant (P for interaction = 0.35 for rs2910164 and 0.92 for rs895819. CONCLUSIONS/SIGNIFICANCE: These findings suggest that miR-146a rs2910164 polymorphism may contribute to the evolution of H. pylori-associated gastric lesions in this high-risk population.

  19. Cardiovascular Risk and Statin Eligibility of Young Adults After an MI: Partners YOUNG-MI Registry.

    Singh, Avinainder; Collins, Bradley L; Gupta, Ankur; Fatima, Amber; Qamar, Arman; Biery, David; Baez, Julio; Cawley, Mary; Klein, Josh; Hainer, Jon; Plutzky, Jorge; Cannon, Christopher P; Nasir, Khurram; Di Carli, Marcelo F; Bhatt, Deepak L; Blankstein, Ron

    2018-01-23

    Despite significant progress in primary prevention, the rate of MI has not declined in young adults. The purpose of this study was to evaluate statin eligibility based on the 2013 American College of Cardiology/American Heart Association guidelines for treatment of blood cholesterol and 2016 U.S. Preventive Services Task Force recommendations for statin use in primary prevention in a cohort of adults who experienced a first-time myocardial infarction (MI) at a young age. The YOUNG-MI registry is a retrospective cohort from 2 large academic centers, which includes patients who experienced an MI at age ≤50 years. Diagnosis of type 1 MI was adjudicated by study physicians. Pooled cohort risk equations were used to estimate atherosclerotic cardiovascular disease risk score based on data available prior to MI or at the time of presentation. Of 1,685 patients meeting inclusion criteria, 210 (12.5%) were on statin therapy prior to MI and were excluded. Among the remaining 1,475 individuals, the median age was 45 years, there were 294 (20%) women, and 846 (57%) had ST-segment elevation MI. At least 1 cardiovascular risk factor was present in 1,225 (83%) patients. The median 10-year atherosclerotic cardiovascular disease risk score of the cohort was 4.8% (interquartile range: 2.8% to 8.0%). Only 724 (49%) and 430 (29%) would have met criteria for statin eligibility per the 2013 American College of Cardiology/American Heart Association guidelines and 2016 U.S. Preventive Services Task Force recommendations, respectively. This finding was even more pronounced in women, in whom 184 (63%) were not eligible for statins by either guideline, compared with 549 (46%) men (p adults who present with an MI at a young age would not have met current guideline-based treatment thresholds for statin therapy prior to their MI. These findings highlight the need for better risk assessment tools among young adults. Copyright © 2018 American College of Cardiology Foundation. Published by

  20. Association between polymorphisms in pre-miRNA genes and risk of oral squamous cell cancer in a Chinese population.

    Enjiao Zhang

    Full Text Available MicroRNAs play important roles in the development of human cancers. This case-control study is to evaluate the roles of the polymorphisms in pre-miRNAs on risk of oral cancer in a Chinese population.The genotypes of three polymorphisms were determined in 340 patients with oral squamous cell cancer and 340 healthy controls who were frequency matched for age and sex. Odds ratios (ORs and 95% confidence intervals (95%CIs were calculated to assess the association. All analyses were performed using the SPSS software. 3.154( 0.001.For miR-499 rs3746444, individuals carrying homozygous CC genotype had increased risks of oral cancer compared with the homozygous wild TT genotype (adjusted OR was 3.154, 95%CI was 1.555-6.397, P value was 0.001. The C allele of miR-499 rs3746444 was associated with a higher risk of oral cancer with significant odds ratio of 1.453. In the stratified analyses by sex, the associations between miR-499 rs3746444 and miR-146a rs2910164 polymorphisms with the susceptibility of oral squamous cell cancer were significant in males. However, with 1/4 as many subjects there were no significant associations between the three polymorphisms and oral cancer risks in females. The joint effects of miRNA polymorphisms and smoking on the risk of OSCC were analyzed and the results suggested that the association between microRNA genetic variants and OSCC risk was modified by smoking.These findings suggest that miR-499 rs3746444 and miR-146a rs2910164 polymorphisms may contribute to genetic susceptibility to oral squamous cell cancer.

  1. Deregulation of miR-100, miR-99a and miR-199b in tissues and plasma coexists with increased expression of mTOR kinase in endometrioid endometrial carcinoma

    Torres, Anna; Torres, Kamil; Pesci, Anna; Ceccaroni, Marcello; Paszkowski, Tomasz; Cassandrini, Paola; Zamboni, Giuseppe; Maciejewski, Ryszard

    2012-01-01

    Alterations of mTOR gene expression have been implicated in the pathogenesis of endometrioid endometrial cancer however only few studies explored the cause of increased mTOR activation in this malignancy. miRNAs are small, noncoding RNAs, which were proven to regulated gene expression at the posttranscriptional level. The study aimed to explore deregulation of miRNAs targeting mTOR kinase (miR-99a, miR-100 and miR-199b) as a possible cause of its altered expression in EEC tissues. In addition expression of the three miRNAs was investigated in plasma of EEC patients and was assessed in terms of diagnostic and prognostic utility. We investigated expression of mTOR kinase transcripts in 46 fresh tissue samples. Expression of miR-99a, miR-100 and miR-199b was investigated in the same group of fresh samples, and in additional 58 FFPE sections as well as in 48 plasma samples using qPCR. Relative quantification was performed using experimentally validated endogenous controls. mTOR kinase expression was increased in EEC tissues and was accompanied by decreased expression of all three miRNAs. Down-regulation of the investigated miRNAs was discovered in plasma of EEC patients and miRNA signatures classified EEC tissues (miR-99a/miR-100/miR-199b) and plasma (miR-99a/miR-199b) samples with higher accuracy in comparison to single miRNAs. We also revealed that miR-100 was an independent prognostic marker of overall survival. We conclude that increased expression of mTOR kinase coexists with down-regulation of its targeting miRNAs, which could suggest a new mechanism of mTOR pathway alterations in EEC. In addition, our findings implicate that miRNA signatures can be considered promising biomarkers for early detection and prognosis of endometrioid endometrial carcinoma

  2. Increased circulating miR-21 levels are associated with kidney fibrosis.

    François Glowacki

    Full Text Available MicroRNAs (miRNAs are a class of noncoding RNA acting at a post-transcriptional level to control the expression of large sets of target mRNAs. While there is evidence that miRNAs deregulation plays a causative role in various complex disorders, their role in fibrotic kidney diseases is largely unexplored. Here, we found a strong up-regulation of miR-21 in the kidneys of mice with unilateral ureteral obstruction and also in the kidneys of patients with severe kidney fibrosis. In addition, mouse primary fibroblasts derived from fibrotic kidneys exhibited higher miR-21 expression level compared to those derived from normal kidneys. Expression of miR-21 in normal primary kidney fibroblasts was induced upon TGFβ exposure, a key growth factor involved in fibrogenesis. Finally, ectopic expression of miR-21 in primary kidney fibroblasts was sufficient to promote myofibroblast differentiation. As circulating miRNAs have been suggested as promising non-invasive biomarkers, we further assess whether circulating miR-21 levels are associated with renal fibrosis using sera from 42 renal transplant recipients, categorized according to their renal fibrosis severity, evaluated on allograft biopsies (Interstitial Fibrosis/Tubular Atrophy (IF/TA. Circulating miR-21 levels are significantly increased in patients with severe IF/TA grade (IF/TA grade 3: 3.0±1.0 vs lower grade of fibrosis: 1.5±1.2; p = 0.001. By contrast, circulating miR-21 levels were not correlated with other renal histological lesions. In a multivariate linear regression model including IF/TA grade and estimated GFR, independent associations were found between circulating miR-21 levels and IF/TA score (ß = 0.307, p = 0.03, and between miR-21 levels and aMDRD (ß = -0.398, p = 0.006. Altogether, these data suggest miR-21 has a key pathogenic role in kidney fibrosis and may represent a novel, predictive and reliable blood marker of kidney fibrosis.

  3. Hsa-miR-34b/c rs4938723 T>C and hsa-miR-423 rs6505162 C>A polymorphisms are associated with the risk of esophageal cancer in a Chinese population.

    Jun Yin

    Full Text Available Esophageal cancer is the eighth most common cancer and sixth leading cause of cancer associated death worldwide. Besides environmental risk factors, genetic factors might play an important role in the esophageal cancer carcinogenesis. We conducted a hospital based case-control study to evaluate the genetic susceptibility of functional single nucleotide polymorphisms (SNPs in the microRNAs on the development of esophageal cancer. A total of 629 esophageal squamous cell carcinoma (ESCC cases and 686 controls were recruited for this study. The hsa-miR-34b/c rs4938723 T>C, pri-miR-124-1 rs531564 C>G, pre-miR-125a rs12975333 G>T and hsa-miR-423 rs6505162 C>A genotypes were determined using Ligation Detection Reaction (LDR method. Our results demonstrated that hsa-miR-34b/c rs4938723 CC genotype had a decreased risk of ESCC. The association was evident among patients who never drinking. Hsa-miR-423 rs6505162 C>A might associated with a significantly increased risk of ESCC in patients who smoking. These findings indicated that functional polymorphisms hsa-miR-34b/c rs4938723 T>C and hsa-miR-423 rs6505162 C>A might alter individual susceptibility to ESCC. However, our results were obtained with a limited sample size. Future larger studies with other ethnic populations are required to confirm current findings.

  4. Reduced miR-659-3p levels correlate with progranulin increase in hypoxic conditions: implications for frontotemporal dementia.

    Paola ePiscopo

    2016-05-01

    Full Text Available Progranulin (PGRN is a secreted protein expressed ubiquitously throughout the body, including the brain, where it localizes in neurons and activated microglia. Loss-of-function mutations in the GRN gene are an important cause of familial Frontotemporal Lobar Degeneration (FTLD. PGRN has a neurotrophic and anti-inflammatory activity, and it is neuroprotective in several injury conditions, such as oxygen or glucose deprivation, oxidative injury, and hypoxic stress. Indeed, we have previously demonstrated that hypoxia induces the up-regulation of GRN transcripts. Several studies have shown microRNAs involvement in hypoxia. Moreover, in FTLD patients with a genetic variant of GRN (rs5848, the reinforcement of miR-659-3p binding site has been suggested to be a risk factor. Here, we report that miR-659-3p interacts directly with GRN 3’UTR as shown by luciferase assay in HeLa cells and ELISA and Western Blot analysis in HeLa and Kelly cells. Moreover, we demonstrate the physical binding between GRN mRNA and miR-659-3p employing a miRNA capture-affinity technology in SK-N-BE and Kelly cells. In order to study miRNAs involvement in hypoxia-mediated up-regulation of GRN, we evaluated miR-659-3p levels in SK-N-BE cells after 24h of hypoxic treatment, finding them inversely correlated to GRN transcripts. Furthermore, we analyzed an animal model of asphyxia, finding that GRN mRNA levels increased at post-natal day (pnd 1 and pnd 4 in rat cortices subjected to asphyxia in comparison to control rats and miR-659-3p decreased at pnd 4 just when GRN reached the highest levels. Our results demonstrate the interaction between miR-659-3p and GRN transcript and the involvement of miR-659-3p in GRN up-regulation mediated by hypoxic/ischemic insults.

  5. A pri-miR-218 variant and risk of cervical carcinoma in Chinese women

    Shi, Ting-Yan; Cheng, Xi; Wu, Xiaohua; Wei, Qingyi; Chen, Xiao-Jun; Zhu, Mei-Ling; Wang, Meng-Yun; He, Jing; Yu, Ke-Da; Shao, Zhi-Ming; Sun, Meng-Hong; Zhou, Xiao-Yan

    2013-01-01

    MicroRNA (miRNA)-related single nucleotide polymorphisms (SNPs) may compromise miRNA binding affinity and modify mRNA expression levels of the target genes, thus leading to cancer susceptibility. However, few studies have investigated roles of miRNA-related SNPs in the etiology of cervical carcinoma. In this case–control study of 1,584 cervical cancer cases and 1,394 cancer-free female controls, we investigated associations between two miR-218-related SNPs involved in the LAMB3-miR-218 pathway and the risk of cervical carcinoma in Eastern Chinese women. We found that the pri-miR-218 rs11134527 variant GG genotype was significantly associated with a decreased risk of cervical carcinoma compared with AA/AG genotypes (adjusted OR=0.77, 95% CI=0.63-0.95, P=0.015). However, this association was not observed for the miR-218 binding site SNP (rs2566) on LAMB3. Using the multifactor dimensionality reduction analysis, we observed some evidence of interactions of these two SNPs with other risk factors, especially age at primiparity and menopausal status, in the risk of cervical carcinoma. The pri-miR-218 rs11134527 SNP was significantly associated with the risk of cervical carcinoma in Eastern Chinese women. Larger, independent studies are warranted to validate our findings

  6. Increasing of miR-148a 0061nd Decreasing of miR-146a Gene Expression in the Stomach with Ageing in Men

    Shirin Abdolvand

    2017-06-01

    Full Text Available Abstract Background: The incidence of gastric cancer is different in two sexes with ratio 2 to 1 that it is more common in men. The most important biologically reason is sexual hormones between two sexes that lead to sexual dimorphism and in turn can cause a sex bias in incidence of disease between two sexes. Recently, studies have shown that microRNA is involved in sexual dimorphism in gene expression. Given the sexual dimorphism in the incidence of gastric cancer and sex hormones response elements in the regulatory regions of miR-146a and miR-148a genes, in this study, the expression of these two genes in the stomach of healthy men and women at different age groups were compared. Materials and Methods: Using endoscopy, gastric antrum tissues of 35 healthy women and 35 healthy men were collected. After RNA extraction and synthesis of cDNA, the expression of miR-146a and miR-148a genes were compared between sexes by Real time RT-PCR and data were analyzed using independent sample t and ANOVA tests. Results: There was no difference between men and women in genes expression of miR-146a and miR-148a. However, expression of miR-146a gene was significantly more in men under 45 years than men over 45 years (p= 0.017, df= 14, t= 1.47. Also, expression of miR-148a gene was significantly more in men over 45 years than men under 45 years (p=0.001, df= 12, t= 1.28. But the expression of both genes had no significant difference between women under 45 years and women over 45 years. Conclusion: Expression of miR-146a and miR-148a genes in the stomach is increased and decreased with aging in men, respectively.

  7. High expression of miR-21 in tumor stroma correlates with increased cancer cell proliferation in human breast cancer

    Rask, Lene; Balslev, Eva; Jørgensen, Stine

    2011-01-01

    features, we performed in situ hybridization and semi-quantitative assessment of the miR-21 signal on 12 LN negative grade I (assumed low risk), and 12 LN positive grade II (high risk) breast cancers. miR-21 was predominantly seen in cancer associated fibroblast-like cells, with no difference in expression......Low-risk and high-risk breast cancer patients are stratified primarily according to their lymph node (LN) status and grading. However, some low-risk patients relapse, and some high-risk patients have a favorable clinical outcome, implying a need for better prognostic and predictive tests. Micro...... RNAs are often aberrantly expressed in cancer and microRNA-21 is upregulated in a variety of cancers, including breast cancer. High miR-21 levels have been associated with poor prognosis. To determine the cellular localization of miR-21 and to compare its expression levels with histopathological...

  8. Identification of miRSNPs associated with the risk of multiple myeloma

    Macauda, Angelica; Calvetti, Diego; Maccari, Giuseppe

    2017-01-01

    to be associated with risk of various types of cancer, but they have never been investigated in MM. We performed an in silico genome-wide search for miRSNPs predicted to alter binding of miRNAs to their target sequences. We selected 12 miRSNPs and tested their association with MM risk. Our study population...... TCF19). Results from IMMEnSE were meta-analyzed with data from a previously published genome-wide association study (GWAS). The SNPs rs13409 (located in the 3'UTR of the POU5F1 gene), rs1419881 (TCF19), rs1049633, rs1049623 (both in DDR1) showed significant associations with MM risk. In conclusion, we...... pathogenesis, and several studies have identified single nucleotide polymorphisms (SNPs) associated with the susceptibility to the disease. SNPs within miRNA-binding sites in target genes (miRSNPs) may alter the strength of miRNA-mRNA interactions, thus deregulating protein expression. MiRSNPs are known...

  9. Genetic Ablation of miR-33 Increases Food Intake, Enhances Adipose Tissue Expansion, and Promotes Obesity and Insulin Resistance

    Nathan L. Price

    2018-02-01

    Full Text Available While therapeutic modulation of miRNAs provides a promising approach for numerous diseases, the promiscuous nature of miRNAs raises concern over detrimental off-target effects. miR-33 has emerged as a likely target for treatment of cardiovascular diseases. However, the deleterious effects of long-term anti-miR-33 therapies and predisposition of miR-33−/− mice to obesity and metabolic dysfunction exemplify the possible pitfalls of miRNA-based therapies. Our work provides an in-depth characterization of miR-33−/− mice and explores the mechanisms by which loss of miR-33 promotes insulin resistance in key metabolic tissues. Contrary to previous reports, our data do not support a direct role for SREBP-1-mediated lipid synthesis in promoting these effects. Alternatively, in adipose tissue of miR-33−/− mice, we observe increased pre-adipocyte proliferation, enhanced lipid uptake, and impaired lipolysis. Moreover, we demonstrate that the driving force behind these abnormalities is increased food intake, which can be prevented by pair feeding with wild-type animals.

  10. Economic inequality increases risk taking.

    Payne, B Keith; Brown-Iannuzzi, Jazmin L; Hannay, Jason W

    2017-05-02

    Rising income inequality is a global trend. Increased income inequality has been associated with higher rates of crime, greater consumer debt, and poorer health outcomes. The mechanisms linking inequality to poor outcomes among individuals are poorly understood. This research tested a behavioral account linking inequality to individual decision making. In three experiments ( n = 811), we found that higher inequality in the outcomes of an economic game led participants to take greater risks to try to achieve higher outcomes. This effect of unequal distributions on risk taking was driven by upward social comparisons. Next, we estimated economic risk taking in daily life using large-scale data from internet searches. Risk taking was higher in states with greater income inequality, an effect driven by inequality at the upper end of the income distribution. Results suggest that inequality may promote poor outcomes, in part, by increasing risky behavior.

  11. Big endothelin changes the cellular miRNA environment in TMOb osteoblasts and increases mineralization.

    Johnson, Michael G; Kristianto, Jasmin; Yuan, Baozhi; Konicke, Kathryn; Blank, Robert

    2014-08-01

    Endothelin (ET1) promotes the growth of osteoblastic breast and prostate cancer metastases. Conversion of big ET1 to mature ET1, catalyzed primarily by endothelin converting enzyme 1 (ECE1), is necessary for ET1's biological activity. We previously identified the Ece1, locus as a positional candidate gene for a pleiotropic quantitative trait locus affecting femoral size, shape, mineralization, and biomechanical performance. We exposed TMOb osteoblasts continuously to 25 ng/ml big ET1. Cells were grown for 6 days in growth medium and then switched to mineralization medium for an additional 15 days with or without big ET1, by which time the TMOb cells form mineralized nodules. We quantified mineralization by alizarin red staining and analyzed levels of miRNAs known to affect osteogenesis. Micro RNA 126-3p was identified by search as a potential regulator of sclerostin (SOST) translation. TMOb cells exposed to big ET1 showed greater mineralization than control cells. Big ET1 repressed miRNAs targeting transcripts of osteogenic proteins. Big ET1 increased expression of miRNAs that target transcripts of proteins that inhibit osteogenesis. Big ET1 increased expression of 126-3p 121-fold versus control. To begin to assess the effect of big ET1 on SOST production we analyzed both SOST transcription and protein production with and without the presence of big ET1 demonstrating that transcription and translation were uncoupled. Our data show that big ET1 signaling promotes mineralization. Moreover, the results suggest that big ET1's osteogenic effects are potentially mediated through changes in miRNA expression, a previously unrecognized big ET1 osteogenic mechanism.

  12. MiRNA-Related SNPs and Risk of Esophageal Adenocarcinoma and Barrett's Esophagus: Post Genome-Wide Association Analysis in the BEACON Consortium.

    Matthew F Buas

    Full Text Available Incidence of esophageal adenocarcinoma (EA has increased substantially in recent decades. Multiple risk factors have been identified for EA and its precursor, Barrett's esophagus (BE, such as reflux, European ancestry, male sex, obesity, and tobacco smoking, and several germline genetic variants were recently associated with disease risk. Using data from the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON genome-wide association study (GWAS of 2,515 EA cases, 3,295 BE cases, and 3,207 controls, we examined single nucleotide polymorphisms (SNPs that potentially affect the biogenesis or biological activity of microRNAs (miRNAs, small non-coding RNAs implicated in post-transcriptional gene regulation, and deregulated in many cancers, including EA. Polymorphisms in three classes of genes were examined for association with risk of EA or BE: miRNA biogenesis genes (157 SNPs, 21 genes; miRNA gene loci (234 SNPs, 210 genes; and miRNA-targeted mRNAs (177 SNPs, 158 genes. Nominal associations (P0.50, and we did not find evidence for interactions between variants analyzed and two risk factors for EA/BE (smoking and obesity. This analysis provides the most extensive assessment to date of miRNA-related SNPs in relation to risk of EA and BE. While common genetic variants within components of the miRNA biogenesis core pathway appear unlikely to modulate susceptibility to EA or BE, further studies may be warranted to examine potential associations between unassessed variants in miRNA genes and targets with disease risk.

  13. Comparison of risk factors of CHD in the men and women with MI.

    Ilali, E; Taraghi, Z

    2010-04-01

    The purpose of this study is comparison of risk factors of MI in hospitalized men and women patients in CCU. The CHD is the most important cause of mortality in the industry countries. Different environmental and race in each location can affect on frequency of risk factors of MI. In this cross sectional study, comparison was done between men and women who have involved in MI. The random sampling method was used Blood sugar, cholesterol and homocystein, LPa, BMI, family history, skin color, smoking and the amount of activity were assessed with variables such as age. The data was collected via questionnaire from September until March 2004-2005. Finally the data were analyzed with using t-test, Chi square and pearson correlation. In this research 169 patients who involved in MI (114 men and 55 women) have participated. The mean of age in the men was 55.4 and in the women was 61.02. All patients had risk factors. In the men, smoking (52.6%) and family history (41.1%) were the most common risk factors of MI. In the women, hyperlipidemia (66.4%), diabetes (62%) and hypertension (58.2%) were the most common risk factors of MI. The mean of BMI in the men was 25.9 +/- 4.25 and in the women was 27.6 +/- 4.71. The mean of LPa in the men was 59.2 +/- 4.21 and in the women was 50.9 +/- 4.25. the mean of homocystein in the men was 10.7 +/- 7.67 and in the women was 8.9 +/- 14.45. Diabetes, hyperlipidemia, hypertension and smoking had significant relationship with age and sex (p homocystein, LPa, job, personality type and mobility didn't have significant relationship with age and sex. In this study the most common risk factors of MI in the men were smoking and positive family history and in the women were known hyperlipidemia and diabetes.

  14. SNP-SNP interactions of three new pri-miRNAs with the target gene PGC and multidimensional analysis of H. pylori in the gastric cancer/atrophic gastritis risk in a Chinese population.

    Xu, Qian; Wu, Ye-Feng; Li, Ying; He, Cai-Yun; Sun, Li-Ping; Liu, Jing-Wei; Yuan, Yuan

    2016-04-26

    Gastric cancer (GC) is a multistep complex disease involving multiple genes, and gene-gene interactions have a greater effect than a single gene in determining cancer susceptibility. This study aimed to explore the interaction of the let-7e rs8111742, miR-365b rs121224, and miR-4795 rs1002765 single nucleotide polymorphisms (SNPs) with SNPs of the predicted target gene PGC and Helicobacter pylori status in GC and atrophic gastritis (AG) risk. Three miRNA SNPs and seven PGC SNPs were detected in 2448 cases using the Sequenom MassArray platform. Two pairwise combinations of miRNA and PGC SNPs were associated with increased AG risk (let-7e rs8111742 - PGC rs6458238 and miR-4795 rs1002765 - PGC rs9471643). Singly, miR-365b rs121224 and PGC rs6912200 had no effect individually but in combination they demonstrated an epistatic interaction associated with AG risk. Similarly, let-7e rs8111742 and miR-4795 rs1002765 SNPs interacted with H. pylori infection to increase GC risk (rs8111742: Pinteraction = 0.024; rs1002765: Pinteraction = 0.031, respectively). A three-dimensional interaction analysis found miR-4795 rs1002765, PGC rs9471643, and H. pylori infection positively interacted to increase AG risk (Pinteraction = 0.027). Also, let-7e rs8111742, PGC rs6458238, and H. pylori infection positively interacted to increase GC risk (Pinteraction = 0.036). Furthermore, both of these three-dimensional interactions had a dosage-effect correspondence (Ptrend < 0.001) and were verified by MDR. In conclusion, the miRNAs SNPs (let-7e rs8111742 and miR-4795 rs1002765) might have more superior efficiency when combined with PGC SNPs and/or H. pylori for GC or AG risk than a single SNP on its own.

  15. miR-1 is increased in pulmonary hypertension and downregulates Kv1.5 channels in rat pulmonary arteries.

    Mondejar-Parreño, Gema; Callejo, María; Barreira, Bianca; Morales-Cano, Daniel; Esquivel-Ruiz, Sergio; Moreno, Laura; Cogolludo, Angel; Perez-Vizcaino, Francisco

    2018-05-02

    ■The expression of miR-1 is increased in lungs from the Hyp/Su5416 PAH rat model. ■PASMC from this animal model are more depolarised and show decreased expression and activity of Kv1.5. ■miR-1 directly targets Kv1.5 channels, reduces Kv1.5 activity and induces membrane depolarization. ■Antagomir-1 prevents Kv1.5 channel downregulation and the depolarization induced by hypoxia/Su5416 exposition. Impairment of voltage-dependent potassium channel (Kv) plays a central role in the development of cardiovascular diseases, including pulmonary arterial hypertension (PAH). MicroRNAs (miRNAs) are non-coding RNAs that regulate gene expression by binding to the 3'-UTR region of specific mRNAs. The aim of this study was to analyze the effects of miR-1 on Kv channel function in pulmonary arteries (PA). Kv channel activity was studied in PA from healthy animals transfected with miR-1 or scrambled-miR. Kv currents were studied using the whole-cell configuration of patch-clamp technique. The characterization of the Kv1.5 currents was performed with the selective inhibitor DPO-1. miR-1 expression was increased and Kv1.5 channels were decreased in lungs from a rat model of PAH induced by hypoxia and Su5416. miR-1 transfection increased cell capacitance, reduced Kv1.5 currents and induced membrane depolarization in isolated pulmonary artery smooth muscle cells (PASMCs). Luciferase reporter assay indicated that KCNA5, which encodes Kv1.5 channels, is a direct target gene of miR-1. Incubation of PA with Su5416 and hypoxia (3% O 2 ) increased miR-1 and induced a decline in Kv1.5 currents, which was prevented by antagomiR-1. In conclusion, these data indicate that miR-1 induces PASMC hypertrophy and reduces the activity and expression of Kv channels, suggesting a pathophysiological role in PAH. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  16. A polymorphism in miR-1262 regulatory region confers the risk of lung cancer in Chinese population.

    Xie, Kaipeng; Chen, Mengxi; Zhu, Meng; Wang, Cheng; Qin, Na; Liang, Cheng; Song, Ci; Dai, Juncheng; Jin, Guangfu; Shen, Hongbing; Lin, Dongxin; Ma, Hongxia; Hu, Zhibin

    2017-09-01

    It has been proposed that the majority of disease-associated loci identified by genome-wide association studies (GWAS) are enriched in non-coding regions, such as the promoter, enhancer or non-coding RNA genes. Thus, we performed a two-stage case-control study to systematically evaluate the association of genetic variants in miRNA regulatory regions (promoter and enhancer) with lung cancer risk in 7,763 subjects (discovery stage: 2,331 cases and 3,077 controls; validation stage: 1,065 cases and 1,290 controls). As a result, we identified that rs12740674 (C > T) in miR-1262 enhancer was significantly associated with the increased risk of lung cancer (additive model in discovery stage: adjusted OR = 1.31, 95%CI = 1.13-1.53, p = 3.846 × 10 -4 in Nanjing GWAS; adjusted OR = 1.20, 95%CI = 1.00-1.44, p = 0.041 in Beijing GWAS; validation stage: adjusted OR = 1.20, 95%CI = 1.03-1.41, p = 0.024). In meta-analysis, the p value for the association between rs12740674 and lung cancer risk reached 6.204 × 10 -6 (adjusted OR = 1.24, 95%CI = 1.13-1.36). Using 3DSNP database, The Cancer Genome Atlas (TCGA) data and functional assays, we observed that the risk T allele of rs12740674 reduced the expression level of miR-1262 in lung tissue through chromosomal looping, and overexpression of miR-1262 inhibited lung cancer cell proliferation probably through targeting the expression levels of ULK1 and RAB3D. Our findings confirmed the important role that genetic variants of noncoding sequence play in lung cancer susceptibility and indicated that rs12740674 in miR-1262 may be biologically relevant to lung carcinogenesis. © 2017 UICC.

  17. Adrenaline promotes cell proliferation and increases chemoresistance in colon cancer HT29 cells through induction of miR-155

    Pu, Jun; Bai, Danna; Yang, Xia; Lu, Xiaozhao; Xu, Lijuan; Lu, Jianguo

    2012-01-01

    Highlights: ► Adrenaline increases colon cancer cell proliferation and its resistance to cisplatin. ► Adrenaline activates NFκB in a dose dependent manner. ► NFκB–miR-155 pathway contributes to cell proliferation and resistance to cisplatin. -- Abstract: Recently, catecholamines have been described as being involved in the regulation of cancer genesis and progression. Here, we reported that adrenaline increased the cell proliferation and decreased the cisplatin induced apoptosis in HT29 cells. Further study found that adrenaline increased miR-155 expression in an NFκB dependent manner. HT29 cells overexpressing miR-155 had a higher cell growth rate and more resistance to cisplatin induced apoptosis. In contrast, HT29 cells overexpressing miR-155 inhibitor displayed decreased cell proliferation and sensitivity to cisplatin induced cell death. In summary, our study here revealed that adrenaline–NFκB–miR-155 pathway at least partially contributes to the psychological stress induced proliferation and chemoresistance in HT29 cells, shedding light on increasing the therapeutic strategies of cancer chemotherapy.

  18. Adrenaline promotes cell proliferation and increases chemoresistance in colon cancer HT29 cells through induction of miR-155

    Pu, Jun [Department of General Surgery, Tangdu Hospital of the Fourth Military Medical University, Xi' an 710038 (China); Bai, Danna [Department of Cardiology, 323 Hospital of PLA, Xi' an 710054 (China); Yang, Xia [Department of Teaching and Medical Administration, Tangdu Hospital of the Fourth Military Medical University, Xi' an 710038 (China); Lu, Xiaozhao [Department of Nephrology, The 323 Hospital of PLA, Xi' an 710054 (China); Xu, Lijuan, E-mail: 13609296272@163.com [Department of Nephrology, The 323 Hospital of PLA, Xi' an 710054 (China); Lu, Jianguo, E-mail: lujianguo029@yahoo.com.cn [Department of General Surgery, Tangdu Hospital of the Fourth Military Medical University, Xi' an 710038 (China)

    2012-11-16

    Highlights: Black-Right-Pointing-Pointer Adrenaline increases colon cancer cell proliferation and its resistance to cisplatin. Black-Right-Pointing-Pointer Adrenaline activates NF{kappa}B in a dose dependent manner. Black-Right-Pointing-Pointer NF{kappa}B-miR-155 pathway contributes to cell proliferation and resistance to cisplatin. -- Abstract: Recently, catecholamines have been described as being involved in the regulation of cancer genesis and progression. Here, we reported that adrenaline increased the cell proliferation and decreased the cisplatin induced apoptosis in HT29 cells. Further study found that adrenaline increased miR-155 expression in an NF{kappa}B dependent manner. HT29 cells overexpressing miR-155 had a higher cell growth rate and more resistance to cisplatin induced apoptosis. In contrast, HT29 cells overexpressing miR-155 inhibitor displayed decreased cell proliferation and sensitivity to cisplatin induced cell death. In summary, our study here revealed that adrenaline-NF{kappa}B-miR-155 pathway at least partially contributes to the psychological stress induced proliferation and chemoresistance in HT29 cells, shedding light on increasing the therapeutic strategies of cancer chemotherapy.

  19. Increased Expression of Herpes Virus-Encoded hsv1-miR-H18 and hsv2-miR-H9-5p in Cancer-Containing Prostate Tissue Compared to That in Benign Prostate Hyperplasia Tissue

    Seok Joong Yun

    2016-06-01

    Full Text Available Purpose: Previously, we reported the presence of virus-encoded microRNAs (miRNAs in the urine of prostate cancer (CaP patients. In this study, we investigated the expression of two herpes virus-encoded miRNAs in prostate tissue. Methods: A total of 175 tissue samples from noncancerous benign prostatic hyperplasia (BPH, 248 tissue samples from patients with CaP and BPH, and 50 samples from noncancerous surrounding tissues from these same patients were analyzed for the expression of two herpes virus-encoded miRNAs by real-time polymerase chain reaction (PCR and immunocytochemistry using nanoparticles as molecular beacons. Results: Real-time reverse transcription-PCR results revealed significantly higher expression of hsv1-miR-H18 and hsv2-miRH9- 5p in surrounding noncancerous and CaP tissues than that in BPH tissue (each comparison, P<0.001. Of note, these miRNA were expressed equivalently in the CaP tissues and surrounding noncancerous tissues. Moreover, immunocytochemistry clearly demonstrated a significant enrichment of both hsv1-miR-H18 and hsv2-miR-H9 beacon-labeled cells in CaP and surrounding noncancerous tissue compared to that in BPH tissue (each comparison, P<0.05 for hsv1-miR-H18 and hsv2- miR-H9. Conclusions: These results suggest that increased expression of hsv1-miR-H18 and hsv2-miR-H95p might be associated with tumorigenesis in the prostate. Further studies will be required to elucidate the role of these miRNAs with respect to CaP and herpes viral infections.

  20. Differential expression of miRNAs in the serum of patients with high-risk oral lesions

    MacLellan, Sara Ann; Lawson, James; Baik, Jonathan; Guillaud, Martial; Poh, Catherine Fang-Yeu; Garnis, Cathie

    2012-01-01

    Oral cancer is one of the most commonly diagnosed cancers worldwide. Disease is often diagnosed at later stages, which is associated with a poor 5-year survival rate and a high rate of local recurrence. MicroRNAs (miRNAs), a group of small, noncoding RNAs, can be isolated from blood serum samples and have demonstrated utility as biomarkers in multiple cancer types. The aim of this study was to examine the expression profiles of circulating miRNAs in the serum of patients with high-risk oral lesions (HRLs; oral cancer or carcinoma in situ) and to explore their utility as potential oral cancer biomarkers. Global serum miRNA profiles were generated using quantitative PCR method from 1) patients diagnosed with HRLs and undergoing intent-to-cure surgical treatment (N = 30) and 2) a demographically matched, noncancer control group (N = 26). We next honed our list of serum miRNAs associated with disease by reducing the effects of interpatient variability; we compared serum miRNA profiles from samples taken both before and after tumor resections (N = 10). Based on these analyses, fifteen miRNAs were significantly upregulated and five were significantly downregulated based on presence of disease (minimum fold-change >2 in at least 50% of samples, P < 0.05, permutation). Five of these miRNAs (miR-16, let-7b, miR-338-3p, miR-223, and miR-29a) yielded an area under the ROC curve (AUC) >0.8, suggesting utility as noninvasive biomarkers for detection of oral cancer or high-grade lesions. Combining these serum miRNA profiles with other screening techniques could greatly improve the sensitivity in oral cancer detection

  1. Disruption of the Cx43/miR21 pathway leads to osteocyte apoptosis and increased osteoclastogenesis with aging.

    Davis, Hannah M; Pacheco-Costa, Rafael; Atkinson, Emily G; Brun, Lucas R; Gortazar, Arancha R; Harris, Julia; Hiasa, Masahiro; Bolarinwa, Surajudeen A; Yoneda, Toshiyuki; Ivan, Mircea; Bruzzaniti, Angela; Bellido, Teresita; Plotkin, Lilian I

    2017-06-01

    Skeletal aging results in apoptosis of osteocytes, cells embedded in bone that control the generation/function of bone forming and resorbing cells. Aging also decreases connexin43 (Cx43) expression in bone; and osteocytic Cx43 deletion partially mimics the skeletal phenotype of old mice. Particularly, aging and Cx43 deletion increase osteocyte apoptosis, and osteoclast number and bone resorption on endocortical bone surfaces. We examined herein the molecular signaling events responsible for osteocyte apoptosis and osteoclast recruitment triggered by aging and Cx43 deficiency. Cx43-silenced MLO-Y4 osteocytic (Cx43 def ) cells undergo spontaneous cell death in culture through caspase-3 activation and exhibit increased levels of apoptosis-related genes, and only transfection of Cx43 constructs able to form gap junction channels reverses Cx43 def cell death. Cx43 def cells and bones from old mice exhibit reduced levels of the pro-survival microRNA miR21 and, consistently, increased levels of the miR21 target phosphatase and tensin homolog (PTEN) and reduced phosphorylated Akt, whereas PTEN inhibition reduces Cx43 def cell apoptosis. miR21 reduction is sufficient to induce apoptosis of Cx43-expressing cells and miR21 deletion in miR21 fl/fl bones increases apoptosis-related gene expression, whereas a miR21 mimic prevents Cx43 def cell apoptosis, demonstrating that miR21 lies downstream of Cx43. Cx43 def cells release more osteoclastogenic cytokines [receptor activator of NFκB ligand (RANKL)/high-mobility group box-1 (HMGB1)], and caspase-3 inhibition prevents RANKL/HMGB1 release and the increased osteoclastogenesis induced by conditioned media from Cx43 def cells, which is blocked by antagonizing HMGB1-RAGE interaction. These findings identify a novel Cx43/miR21/HMGB1/RANKL pathway involved in preventing osteocyte apoptosis that also controls osteoclast formation/recruitment and is impaired with aging. © 2017 The Authors. Aging Cell published by the Anatomical Society

  2. Increased MiR-221 expression in hepatocellular carcinoma tissues and its role in enhancing cell growth and inhibiting apoptosis in vitro

    Rong, Minhua; Chen, Gang; Dang, Yiwu

    2013-01-01

    MiR-221 is over-expressed in human hepatocellular carcinoma (HCC), but its clinical significance and function in HCC remains uncertain. The aim of the study was to investigate the relationship between miR-221 overexpression and clinicopathological parameters in HCC formalin-fixed paraffin-embedded (FFPE) tissues, and the effect of miR-221 inhibitor and mimic on different HCC cell lines in vitro. MiR-221 expression was detected using real time RT-qPCR in FFPE HCC and the adjacent noncancerous liver tissues. The relationship between miR-221 level and clinicopathological features was also analyzed. Furthermore, miR-221 inhibitor and mimic were transfected into HCC cell lines HepB3, HepG2 and SNU449. The effects of miR-221 on cell growth, cell cycle, caspase activity and apoptosis were also investigated by spectrophotometry, fluorimetry, fluorescence microscopy and flow cytometry, respectively. The relative expression of miR-221 in clinical TNM stages III and IV was significantly higher than that in the stages I and II. The miR-221 level was also upregulated in the metastatic group compared to the nonmetastatic group. Furthermore, miR-221 over-expression was related to the status of tumor capsular infiltration in HCC clinical samples. Functionally, cell growth was inhibited, cell cycle was arrested in G1/S-phase and apoptosis was increased by miR-221 inhibitor in vitro. Likewise, miR-221 mimic accelerated the cell growth. Expression of miR-221 in FFPE tissues could provide predictive significance for prognosis of HCC patients. Moreover, miR-221 inhibitor could be useful to suppress proliferation and induce apoptosis in HCC cells. Thus miR-221 might be a critical targeted therapy strategy for HCC

  3. Increased Brain-Specific MiR-9 and MiR-124 in the Serum Exosomes of Acute Ischemic Stroke Patients.

    Qiuhong Ji

    Full Text Available The aims of this study were to examine the alternation in serum exosome concentrations and the levels of serum exosomal miR-9 and miR-124, two brain-specific miRNAs, in acute ischemic stroke (AIS patients and to explore the predictive values of these miRNAs for AIS diagnosis and damage evaluation. Sixty-five patients with AIS at the acute stage were enrolled and 66 non-stroke volunteers served as controls. Serum exosomes isolated by ExoQuick precipitations were characterized by transmission electron microscopy, nanoparticle-tracking analysis and western blotting. The levels of exosomal miR-9 and miR-124 were determined by real-time quantitative PCR. Compared with controls, the concentration of serum exosomes and the median levels of serum exosomal miR-9 and miR-124 were significantly higher in AIS patients (p<0.01. The levels of both miR-9 and miR-124 were positively correlated with National Institutes of Health Stroke Scale (NIHSS scores, infarct volumes and serum concentrations of IL-6. The areas under the curve for exosomal miR-9 and miR-124 were 0.8026 and 0.6976, respectively. This proof of concept study suggests that serum exosomal miR-9 and miR-124 are promising biomarkers for diagnosing AIS and evaluating the degree of damage caused by ischemic injury. However, further studies are needed to explore the potential roles of the exosomes released from brain tissues in post stroke complications.

  4. Progress risk assessment of oral premalignant lesions with saliva miRNA analysis

    Yang, Ya; Li, Yue-xiu; Yang, Xi; Jiang, Long; Zhou, Zuo-jun; Zhu, Ya-qin

    2013-01-01

    Oral cancer develops through multi-stages: from normal to mild (low grade) dysplasia (LGD), moderate dysplasia, and severe (high grade) dysplasia (HGD), to carcinoma in situ (CIS) and finally invasive oral squamous cell carcinomas (OSCC). Clinical and histological assessments are not reliable in predicting which precursor lesions will progress. The aim of this study was to assess the potential of a noninvasive approach to assess progress risk of oral precancerous lesions. We first used microRNA microarray to profile progressing LGD oral premaligant lesions (OPLs) from non-progressing LGD OPLs in order to explore the possible microRNAs deregulated in low grade OPLs which later progressed to HGD or OSCC. We then used RT-qPCR to detect miRNA targets from the microarray results in saliva samples of these patients. We identified a specific miRNA signature that is aberrantly expressed in progressing oral LGD leukoplakias. Similar expression patterns were detected in saliva samples from these patients. These results show promise for using saliva miRNA signature for monitoring of cancer precursor lesions and early detection of disease progression

  5. Increased Expression of miR-146a in Children With Allergic Rhinitis After Allergen-Specific Immunotherapy.

    Luo, Xi; Hong, Haiyu; Tang, Jun; Wu, Xingmei; Lin, Zhibin; Ma, Renqiang; Fan, Yunping; Xu, Geng; Liu, Dabo; Li, Huabin

    2016-03-01

    MicroRNAs (miRs) were recently recognized to be important for immune cell differentiation and immune regulation. However, whether miRs were involved in allergen-specific immunotherapy (SIT) remains largely unknown. This study sought to examine changes in miR-146a and T regulatory cells in children with persistent allergic rhinitis (AR) after 3 months of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT). Twenty-four HDM-sensitized children with persistent AR were enrolled and treated with SCIT (n=13) or SLIT (n=11) for 3 months. Relative miR-146a and Foxp3 mRNA expression, the TRAF6 protein level, and the ratio of post-treatment to baseline IL-10+CD4+ T cells between the SCIT and SLIT groups were examined in the peripheral blood mononuclear cells (PBMCs) of AR patients using quantitative reverse transcription polymerase chain reaction (qRT-PCR), flow cytometry, and Western blot analysis, respectively. Serum levels of IL-5 and IL-10 were determined using ELISA. After 3 months of SIT, both the TNSS and INSS scores were significantly decreased compared to the baseline value (P<0.01). The relative expression of miR-146a and Foxp3 mRNA was significantly increased after both SCIT and SLIT (P<0.01). The ratio of post-treatment to baseline IL-10⁺CD4⁺ T cells and the serum IL-10 level were significantly increased in both the SCIT and SLIT groups (P<0.01), whereas the TRAF6 protein level and serum IL-5 level were significantly decreased (P<0.01). No significant differences in these biomarkers were observed between the SCIT and SLIT groups. Our findings suggest that miR-146a and its related biomarkers may be comparably modulated after both SCIT and SLIT, highlighting miR-146a as a potential therapeutic target for the improved management of AR.

  6. Increased risk of cardiovascular disease (CVD) with age in HIV-positive men

    Petoumenos, K; Reiss, P; Ryom, L

    2014-01-01

    equations. METHODS: We analysed three endpoints: myocardial infarction (MI), coronary heart disease (CHD: MI or invasive coronary procedure) and CVD (CHD or stroke). We fitted a number of parametric age effects, adjusting for known risk factors and antiretroviral therapy (ART) use. The best-fitting age...... rates per 1000 person-years increased from 2.29, 3.11 and 3.65 in those aged 40-45 years to 6.53, 11.91 and 15.89 in those aged 60-65 years, respectively. The best-fitting models included inverse age for MI and age + age(2) for CHD and CVD. In D:A:D there was a slowly accelerating increased risk of CHD...... and CVD per year older, which appeared to be only modest yet was consistently raised compared with the risk in the general population. The relative risk of MI with age was not different between D:A:D and the general population. CONCLUSIONS: We found only limited evidence of accelerating increased risk...

  7. Application of TRiMiCri for the evaluation of risk based microbiological criteria for Campylobacter on broiler meat

    Seliwiorstow, Tomasz; Uyttendaele, Mieke; De Zutter, Lieven

    2016-01-01

    A potential solution for the reduction of consumer exposure to Campylobacter is establishing a microbiological criterion (MC) for Campylobacter on broiler meat. In the present study the freely available software tool TRiMiCri was applied to evaluate risk-based microbiological criteria by two appr...... of microbiological criteria for Campylobacter in the EU is discussed. TRiMiCri provides user friendly software to evaluate the available data and can help risk managers in establishing risk based microbiological criteria for Campylobacter in broiler meat.......A potential solution for the reduction of consumer exposure to Campylobacter is establishing a microbiological criterion (MC) for Campylobacter on broiler meat. In the present study the freely available software tool TRiMiCri was applied to evaluate risk-based microbiological criteria by two...

  8. miR-214-Dependent Increase of PHLPP2 Levels Mediates the Impairment of Insulin-Stimulated Akt Activation in Mouse Aortic Endothelial Cells Exposed to Methylglyoxal

    Cecilia Nigro

    2018-02-01

    Full Text Available Evidence has been provided linking microRNAs (miRNAs and diabetic complications, by the regulation of molecular pathways, including insulin-signaling, involved in the pathophysiology of vascular dysfunction. Methylglyoxal (MGO accumulates in diabetes and is associated with cardiovascular complications. This study aims to analyze the contribution of miRNAs in the MGO-induced damaging effect on insulin responsiveness in mouse aortic endothelial cells (MAECs. miRNA modulation was performed by transfection of specific miRNA mimics and inhibitors in MAECs, treated or not with MGO. miRNA-target protein levels were evaluated by Western blot. PH domain leucine-rich repeat protein phosphatase 2 (PHLPP2 regulation by miR-214 was tested by luciferase assays and by the use of a target protector specific for miR-214 on PHLPP2-3′UTR. This study reveals a 4-fold increase of PHLPP2 in MGO-treated MAECs. PHLPP2 levels inversely correlate with miR-214 modulation. Moreover, miR-214 overexpression is able to reduce PHLPP2 levels in MGO-treated MAECs. Interestingly, a direct regulation of PHLPP2 is proved to be dependent by miR-214. Finally, the inhibition of miR-214 impairs the insulin-dependent Akt activation, while its overexpression rescues the insulin effect on Akt activation in MGO-treated MAECs. In conclusion, this study shows that PHLPP2 is a target of miR-214 in MAECs, and identifies miR-214 downregulation as a contributing factor to MGO-induced endothelial insulin-resistance.

  9. Differential expression of miR-139, miR-486 and miR-21 in breast cancer patients sub-classified according to lymph node status

    Rask, Lene; Balslev, Eva; Søkilde, Rolf

    2014-01-01

    PURPOSE: Therapeutic decisions in breast cancer are increasingly guided by prognostic and predictive biomarkers. Non-protein-coding microRNAs (miRNAs) have recently been found to be deregulated in breast cancers and, in addition, to be correlated with several clinico-pathological features. One...... of the most consistently up-regulated miRNAs is miR-21. Here, we specifically searched for differentially expressed miRNAs in high-risk breast cancer patients as compared to low-risk breast cancer patients. In the same patients, we also compared miR-21 expression with the expression of its presumed target...... PTEN. METHODS: Both microarray and RT-qPCR techniques were used to assess miRNA expression levels in lymph node-positive and -negative human invasive ductal carcinoma tissues. Simultaneously, PTEN protein expression levels were assessed using immunohistochemistry. RESULTS: miR-486-5p and miR-139-5p...

  10. Circulating and Urinary miR-210 and miR-16 Increase during Cardiac Surgery Using Cardiopulmonary Bypass - A Pilot Study.

    Mazzone, Annette L; Baker, Robert A; McNicholas, Kym; Woodman, Richard J; Michael, Michael Z; Gleadle, Jonathan M

    2018-03-01

    A pilot study to measure and compare blood and urine microRNAs miR-210 and miR-16 in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) and off-pump coronary artery bypass grafting surgery. Frequent serial blood and urine samples were taken from patients undergoing cardiac surgery with CPB (n = 10) and undergoing off-pump cardiac surgery (n = 5) before, during, and after surgery. Circulating miR-210 and miR-16 levels were determined by relative quantification real-time polymerase chain reaction. Levels of plasma-free haemoglobin (fHb), troponin-T, creatine kinase, and creatinine were measured. Perioperative serum miR-210 and miR-16 were elevated significantly compared to preoperative levels in patients undergoing cardiac surgery with CPB (CPB vs. Pre Op and Rewarm vs. Pre Op; p Octopus on vs. Pre Op); however, the release was less marked when compared to cardiac surgery with CPB. A significant association was observed between both miR-16 and miR-210 and plasma fHb when CPB was used ( r = -.549, p red cell, and renal injury during cardiac surgery.

  11. A Serum Circulating miRNA Signature for Short-Term Risk of Progression to Active Tuberculosis Among Household Contacts

    Fergal J. Duffy

    2018-04-01

    Full Text Available Biomarkers that predict who among recently Mycobacterium tuberculosis (MTB-exposed individuals will progress to active tuberculosis are urgently needed. Intracellular microRNAs (miRNAs regulate the host response to MTB and circulating miRNAs (c-miRNAs have been developed as biomarkers for other diseases. We performed machine-learning analysis of c-miRNA measurements in the serum of adult household contacts (HHCs of TB index cases from South Africa and Uganda and developed a c-miRNA-based signature of risk for progression to active TB. This c-miRNA-based signature significantly discriminated HHCs within 6 months of progression to active disease from HHCs that remained healthy in an independent test set [ROC area under the ROC curve (AUC 0.74, progressors < 6 Mo to active TB and ROC AUC 0.66, up to 24 Mo to active TB], and complements the predictions of a previous cellular mRNA-based signature of TB risk.

  12. A Serum Circulating miRNA Signature for Short-Term Risk of Progression to Active Tuberculosis Among Household Contacts.

    Duffy, Fergal J; Thompson, Ethan; Downing, Katrina; Suliman, Sara; Mayanja-Kizza, Harriet; Boom, W Henry; Thiel, Bonnie; Weiner Iii, January; Kaufmann, Stefan H E; Dover, Drew; Tabb, David L; Dockrell, Hazel M; Ottenhoff, Tom H M; Tromp, Gerard; Scriba, Thomas J; Zak, Daniel E; Walzl, Gerhard

    2018-01-01

    Biomarkers that predict who among recently Mycobacterium tuberculosis (MTB)-exposed individuals will progress to active tuberculosis are urgently needed. Intracellular microRNAs (miRNAs) regulate the host response to MTB and circulating miRNAs (c-miRNAs) have been developed as biomarkers for other diseases. We performed machine-learning analysis of c-miRNA measurements in the serum of adult household contacts (HHCs) of TB index cases from South Africa and Uganda and developed a c-miRNA-based signature of risk for progression to active TB. This c-miRNA-based signature significantly discriminated HHCs within 6 months of progression to active disease from HHCs that remained healthy in an independent test set [ROC area under the ROC curve (AUC) 0.74, progressors < 6 Mo to active TB and ROC AUC 0.66, up to 24 Mo to active TB], and complements the predictions of a previous cellular mRNA-based signature of TB risk.

  13. Association Between Functional PSMD10 Rs111638916 Variant Regulated by MiR-505 and Gastric Cancer Risk in a Chinese Population

    Yong Liu

    2015-09-01

    Full Text Available Background/Aims: Gankyrin is an oncoprotein involved in regulating the cell cycle through protein-protein interactions with cyclin-dependent kinase 4 and p53. However, its association with gastric cancer (GC risk has not yet been determined. In this study, we investigated micro RNA (miRNA-associated single nucleotide polymorphisms (SNPs in the 3′-untranslated region (UTR of the gankyrin gene PSMD10 to clarify the relationship between these SNPs and miRNAs in Chinese patients with GC. Methods: We performed a case-control study including 857 GC patients and 748 cancer-free controls. PSMD10 expression was investigated using genotyping, real-time polymerase chain reaction, cell transfection, and dual luciferase reporter assays. Results: Patients with histories of smoking, alcohol consumption, and cancer were more susceptible to GC than controls. The SNP rs111638916 in the PSMD10 3′-UTR was identified as a risk factor for GC and acted as a tumor promoting factor. SNP rs111638916 was also regulated by miR-505, resulting in up-regulation of gankyrin expression in patients with GA and AA genotypes. Carriers of the GA and AA genotypes also presented with larger tumors and had a higher risk of metastasis. Conclusion: The PSMD10 rs111638916 SNP is highly associated with an increased risk of GC in Chinese patients, and could serve as a novel biomarker for this disease.

  14. Cisplatin-induced downregulation of miR-199a-5p increases drug resistance by activating autophagy in HCC cell

    Xu, Ning; Zhang, Jianjun; Shen, Conghuan; Luo, Yi; Xia, Lei; Xue, Feng; Xia, Qiang

    2012-01-01

    Highlights: ► miR-199a-5p levels were significantly decreased after cisplatin treatment. ► Cisplatin treatment induced autophagy activation. ► Cisplatin-induced downregulation of miR-199a-5p increases drug resistance by activating autophagy in HCC cell. -- Abstract: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Systemic chemotherapy plays an important role in the treatment of patients with advanced liver cancer. However, chemoresistance to cisplatin is a major limitation of cisplatin-based chemotherapy in the clinic, and the underlying mechanism of such resistance is not fully understood. In the study, we found that miR-199a-5p levels were significantly reduced in HCC patients treated with cisplatin-based chemotherapy. Cisplatin treatment also resulted in decreased miR-199a-5p levels in human HCC cell lines. Forced expression of miR-199a-5p promoted cisplatin-induced inhibition of cell proliferation. Cisplatin treatment activated autophagy in Huh7 and HepG2 cells, which increased cell proliferation. We further demonstrated that downregulated miR-199a-5p enhanced autophagy activation by targeting autophagy-associated gene 7 (ATG7). More important, autophagy inhibition abrogated miR-199a-5p downregulation-induced cell proliferation. These data demonstrated that miR-199a-5p/autophagy signaling represents a novel pathway regulating chemoresistance, thus offering a new target for chemotherapy of HCC.

  15. miRNA engineering of CHO cells facilitates production of difficult-to-express proteins and increases success in cell line development.

    Fischer, Simon; Marquart, Kim F; Pieper, Lisa A; Fieder, Juergen; Gamer, Martin; Gorr, Ingo; Schulz, Patrick; Bradl, Harald

    2017-07-01

    In recent years, coherent with growing biologics portfolios also the number of complex and thus difficult-to-express (DTE) therapeutic proteins has increased considerably. DTE proteins challenge bioprocess development and can include various therapeutic protein formats such as monoclonal antibodies (mAbs), multi-specific affinity scaffolds (e.g., bispecific antibodies), cytokines, or fusion proteins. Hence, the availability of robust and versatile Chinese hamster ovary (CHO) host cell factories is fundamental for high-yielding bioprocesses. MicroRNAs (miRNAs) have emerged as potent cell engineering tools to improve process performance of CHO manufacturing cell lines. However, there has not been any report demonstrating the impact of beneficial miRNAs on industrial cell line development (CLD) yet. To address this question, we established novel CHO host cells constitutively expressing a pro-productive miRNA: miR-557. Novel host cells were tested in two independent CLD campaigns using two different mAb candidates including a normal as well as a DTE antibody. Presence of miR-557 significantly enhanced each process step during CLD in a product independent manner. Stable expression of miR-557 increased the probability to identify high-producing cell clones. Furthermore, production cell lines derived from miR-557 expressing host cells exhibited significantly increased final product yields in fed-batch cultivation processes without compromising product quality. Strikingly, cells co-expressing miR-557 and a DTE antibody achieved a twofold increase in product titer compared to clones co-expressing a negative control miRNA. Thus, host cell engineering using miRNAs represents a promising tool to overcome limitations in industrial CLD especially with regard to DTE proteins. Biotechnol. Bioeng. 2017;114: 1495-1510. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  16. Red meat consumption and risk of cardiovascular diseases-is increased iron load a possible link?

    Quintana Pacheco, Daniel A; Sookthai, Disorn; Wittenbecher, Clemens; Graf, Mirja E; Schübel, Ruth; Johnson, Theron; Katzke, Verena; Jakszyn, Paula; Kaaks, Rudolf; Kühn, Tilman

    2018-01-01

    High iron load and red meat consumption could increase the risk of cardiovascular diseases (CVDs). As red meat is the main source of heme iron, which is in turn a major determinant of increased iron load, adverse cardiometabolic effects of meat consumption could be mediated by increased iron load. The object of the study was to assess whether associations between red meat consumption and CVD risk are mediated by iron load in a population-based human study. We evaluated relations between red meat consumption, iron load (plasma ferritin), and risk of CVD in the prospective EPIC-Heidelberg Study using a case-cohort sample including a random subcohort (n = 2738) and incident cases of myocardial infarction (MI, n = 555), stroke (n = 513), and CVD mortality (n = 381). Following a 4-step mediation analysis, associations between red meat consumption and iron load, red meat consumption and CVD risk, and iron load and CVD risk were assessed by multivariable regression models before finally testing to which degree associations between red meat consumption and CVD risk were attenuated by adjustment for iron status. Red meat consumption was significantly positively associated with ferritin concentrations and MI risk [HR per 50 g daily intake: 1.18 (95% CI: 1.05, 1.33)], but no significant associations with stroke risk and CVD mortality were observed. While direct associations between ferritin concentrations and MI risk as well as CVD mortality were significant in age- and sex-adjusted Cox regression models, these associations were substantially attenuated and no longer significant after multivariable adjustment for classical CVD risk factors. Strikingly, ferritin concentrations were positively associated with a majority of classical CVD risk factors (age, male sex, alcohol intake, obesity, inflammation, and lower education). Increased ferritin concentrations may be a marker of an overall unfavorable risk factor profile rather than a mediator of greater CVD risk due to meat

  17. Colombia Mi Pronostico Flood Application: Updating and Improving the Mi Pronostico Flood Web Application to Include an Assessment of Flood Risk

    Rushley, Stephanie; Carter, Matthew; Chiou, Charles; Farmer, Richard; Haywood, Kevin; Pototzky, Anthony, Jr.; White, Adam; Winker, Daniel

    2014-01-01

    Colombia is a country with highly variable terrain, from the Andes Mountains to plains and coastal areas, many of these areas are prone to flooding disasters. To identify these risk areas NASA's Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) was used to construct a digital elevation model (DEM) for the study region. The preliminary risk assessment was applied to a pilot study area, the La Mosca River basin. Precipitation data from the National Aeronautics and Space Administration (NASA) Tropical Rainfall Measuring Mission (TRMM)'s near-real-time rainfall products as well as precipitation data from the Instituto de Hidrologia, Meteorologia y Estudios Ambientales (the Institute of Hydrology, Meteorology and Environmental Studies, IDEAM) and stations in the La Mosca River Basin were used to create rainfall distribution maps for the region. Using the precipitation data and the ASTER DEM, the web application, Mi Pronóstico, run by IDEAM, was updated to include an interactive map which currently allows users to search for a location and view the vulnerability and current weather and flooding conditions. The geospatial information was linked to an early warning system in Mi Pronóstico that can alert the public of flood warnings and identify locations of nearby shelters.

  18. Comprehensive review of genetic association studies and meta-analyses on miRNA polymorphisms and cancer risk.

    Kshitij Srivastava

    Full Text Available MicroRNAs (miRNAs are small RNA molecules that regulate the expression of corresponding messenger RNAs (mRNAs. Variations in the level of expression of distinct miRNAs have been observed in the genesis, progression and prognosis of multiple human malignancies. The present study was aimed to investigate the association between four highly studied miRNA polymorphisms (mir-146a rs2910164, mir-196a2 rs11614913, mir-149 rs2292832 and mir-499 rs3746444 and cancer risk by using a two-sided meta-analytic approach.An updated meta-analysis based on 53 independent case-control studies consisting of 27573 cancer cases and 34791 controls was performed. Odds ratio (OR and 95% confidence interval (95% CI were used to investigate the strength of the association.Overall, the pooled analysis showed that mir-196a2 rs11614913 was associated with a decreased cancer risk (OR = 0.846, P = 0.004, TT vs. CC while other miRNA SNPs showed no association with overall cancer risk. Subgroup analyses based on type of cancer and ethnicity were also performed, and results indicated that there was a strong association between miR-146a rs2910164 and overall cancer risk in Caucasian population under recessive model (OR = 1.274, 95%CI = 1.096-1.481, P = 0.002. Stratified analysis by cancer type also associated mir-196a2 rs11614913 with lung and colorectal cancer at allelic and genotypic level.The present meta-analysis suggests an important role of mir-196a2 rs11614913 polymorphism with overall cancer risk especially in Asian population. Further studies with large sample size are needed to evaluate and confirm this association.

  19. Increased risk of arterial thromboembolic events after Staphylococcus aureus bacteremia

    Mejer, N; Gotland, N; Uhre, M L

    2015-01-01

    OBJECTIVES: An association between infection and arterial thromboembolic events (ATE) has been suggested. Here we examined the risk of myocardial infarction (MI), stroke and other ATE after Staphylococcus aureus bacteremia (SAB). METHODS: Danish register-based nation-wide observational cohort study...

  20. BAG3 increases the invasiveness of uterine corpus carcinoma cells by suppressing miR-29b and enhancing MMP2 expression.

    Habata, Shutaro; Iwasaki, Masahiro; Sugio, Asuka; Suzuki, Miwa; Tamate, Masato; Satohisa, Seiro; Tanaka, Ryoichi; Saito, Tsuyoshi

    2015-05-01

    Approximately 30% of uterine corpus carcinomas are diagnosed at an advanced stage and have a poor prognosis. Our previous study indicated that BCL2-associated athanogene 3 (BAG3) enhances matrix metalloproteinase-2 (MMP2) expression and binds to MMP2 to positively regulate the process of cell invasion in ovarian cancer cells. Recently, altered miRNA expression patterns were observed in several groups of patients with endometrial cancers. One of the altered miRNAs, miR-29b, reportedly reduces tumor invasiveness by suppressing MMP2 expression. Our aim in the present study was to examine the relationships among BAG3, miR-29b and MMP2 in endometrioid adenocarcinoma cells. We found that BAG3 suppresses miR-29b expression and enhances MMP2 expression, which in turn increases cell motility and invasiveness. Moreover, restoration of miR-29b through BAG3 knockdown reduced MMP2 expression, as well as cell motility and invasiveness. Collectively, our findings indicate that BAG3 enhances MMP2 expression by suppressing miR-29b, thereby increasing the metastatic potential of endometrioid adenocarcinomas.

  1. Keystone Symposia "ncRNAs in Development and Cancer", Vancouver, Canada: Increased release of exosomes and export of invasion-modulating miRNAs miR921, -23b, -and -224 from metastatic urothelial carcinoma cells

    Ostenfeld, Marie Stampe; Jeppesen, Dennis Kjølhede; Laurberg, Jens Reumert

    2013-01-01

    Cancer cells secrete soluble factors and various extracellular vesicles, including exosomes, into their tissue microenvironment. The secretion of exosomes is speculated to facilitate local invasion and increase the propensity of tumors to form distant metastases. Here we present a characterization...... of exosome vesicles from isogenic urothelial carcinoma cell lines, with different metastatic propensity by western blotting, electron microscopy, nanoparticle tracking analysis, dynamic light scattering, and profiling of 671 miRNAs by qRT-PCR. An increase in the number of multivesicular bodies and exosomes...... was observed for metastatic FL3 cells compared to isogenic non-metastatic T24 cells. The release was significantly inhibited by knockdown of Rab27b and pharmacological inhibition of nsmase2 by GW4869. miRNA profiling was conducted on parental cells and their secreted exosomes. Here, selective export of miR921...

  2. The increased risk of predation enhances cooperation

    Krams, Indrikis; Bērziņš, Arnis; Krama, Tatjana; Wheatcroft, David; Igaune, Kristīne; Rantala, Markus J.

    2010-01-01

    Theory predicts that animals in adverse conditions can decrease individual risks and increase long-term benefits by cooperating with neighbours. However, some empirical studies suggest that animals often focus on short-term benefits, which can reduce the likelihood that they will cooperate with others. In this experimental study, we tested between these two alternatives by evaluating whether increased predation risk (as a correlate of environmental adversity) enhances or diminishes the occurrence of cooperation in mobbing, a common anti-predator behaviour, among breeding pied flycatchers Ficedula hypoleuca. We tested whether birds would join their mobbing neighbours more often and harass a stuffed predator placed near their neighbours' nests more intensely in areas with a higher perceived risk of predation. Our results show that birds attended mobs initiated by their neighbours more often, approached the stuffed predator significantly more closely, and mobbed it at a higher intensity in areas where the perceived risk of predation was experimentally increased. In such high-risk areas, birds also were more often involved in between-pair cooperation. This study demonstrates the positive impact of predation risk on cooperation in breeding songbirds, which might help in explaining the emergence and evolution of cooperation. PMID:19846454

  3. rno-miR-665 targets BCL2L1 (Bcl-xl) and increases vulnerability to propofol in developing astrocytes.

    Sun, Wen-Chong; Pei, Ling

    2016-07-01

    anaesthesia and risk for impairment. Here, it revealed that propofol-related neurotoxicity of neonatal astrocytes was under rno-miR-665 regulation during the brain growth spurt. Rno-miR-665 might act as a clinically alternative therapeutic target for treatment of neurological disorders in peadiatric anesthesia or sedation with propofol in future. © 2016 International Society for Neurochemistry.

  4. Increased cancer risk in patients with periodontitis.

    Dizdar, Omer; Hayran, Mutlu; Guven, Deniz Can; Yılmaz, Tolga Birtan; Taheri, Sahand; Akman, Abdullah C; Bilgin, Emre; Hüseyin, Beril; Berker, Ezel

    2017-12-01

    Previous studies have noted a possible association between periodontal diseases and the risk of various cancers. We assessed cancer risk in a cohort of patients with moderate to severe periodontitis. Patients diagnosed with moderate to severe periodontitis by a periodontist between 2001 and 2010 were identified from the hospital registry. Patients younger than 35 years of age or with a prior cancer diagnosis were excluded. The age- and gender-standardized incidence rates (SIR) were calculated by dividing the number of observed cases by the number of expected cases from Turkish National Cancer Registry 2013 data. A total of 280 patients were included (median age 49.6, 54% female). Median follow-up was 12 years. Twenty-five new cancer cases were observed. Patients with periodontitis had 77% increased risk of cancer (SIR 1.77, 95% CI 1.17-2.58, p = .004). Women with periodontitis had significantly higher risk of breast cancer (SIR 2.40, 95% CI 0.88-5.33) and men with periodontitis had significantly higher risk of prostate cancer (SIR 3.75, 95% CI 0.95-10.21) and hematological cancers (SIR 6.97, 95% CI 1.77-18.98). Although showing a causal association necessitates further investigation, our results support the idea that periodontitis might be associated with increased cancer risk, particularly with hematological, breast and prostate cancers.

  5. A genetic risk score of 45 coronary artery disease risk variants associates with increased risk of myocardial infarction in 6041 Danish individuals

    Krarup, N T; Borglykke, A; Allin, K H

    2015-01-01

    with age as time scale was adjusted for sex, BMI, type 2 diabetes mellitus and smoking status. Analyses were also stratified either by sex or median age (below or above 45 years of age). We estimated GRS contribution to MI prediction by assessing net reclassification index (NRI) and integrated...... discrimination improvement (IDI) added to the European SCORE for 10-year MI risk prediction. RESULTS: The GRS associated significantly with risk of incident MI (allele-dependent hazard ratio (95%CI): 1.06 (1.02-1.11), p = 0.01) but not with CAD (p = 0.39). Stratification revealed association of GRS with MI...... in men (1.06 (1.01-1.12), p = 0.02) and in individuals above the median of 45.11 years of age (1.06 (1.00-1.12), p = 0.03). There was no interaction between GRS and gender (p = 0.90) or age (p = 0.83). The GRS improved neither NRI nor IDI. CONCLUSION: The GRS of 45 GWAS identified risk variants increase...

  6. Association of the miR-196a2 C>T and miR-499 A>G polymorphisms with hepatitis B virus-related hepatocellular carcinoma risk: an updated meta-analysis

    Zhu SL

    2016-04-01

    Full Text Available Shao-Liang Zhu,1,* Jian-Hong Zhong,1,* Wen-Feng Gong,1,* Hang Li,2 Le-Qun Li11Department of Hepatobiliary Surgery, 2Department of Ultrasound, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, People’s Republic of China*These authors contributed equally to this workBackground: This study meta-analyzed data on the possible association of the miR-196a2 C>T (rs11614913 and miR-499 A>G (rs3746444 polymorphisms with risk of hepatitis B virus (HBV-related hepatocellular carcinoma (HCC.Methods: Databases in PubMed, EMBASE, Web of Science, China BioMedicine, and Google Scholar were systematically searched to identify relevant studies. Meta-analyses were performed to examine the association of the miR-196a2 C>T and miR-499 A>G polymorphisms with HBV-related HCC risk. Odds ratios (ORs and 95% confidence intervals (95% CIs were calculated.Results: A total of 13 studies involving 3,964 cases and 5,875 healthy controls were included. Random-effect meta-analysis showed that the T allele and TT genotype of miR-196a2 C>T were associated with significantly lower HBV-related HCC risk (allelic model, OR =0.84, 95% CI =0.71–0.99, P=0.04; homozygous model, OR =0.68, 95% CI =0.47–0.98, P=0.04. In contrast, miR-499 A>G showed no significant association with HBV-related HCC risk in either overall pooled analysis or ethnic subgroup analysis according to any of the four genetic models. Based on analysis of ethnic subgroups, neither miR-196a2 C>T nor miR-499 A>G was significantly associated with risk of HBV-related HCC in Chinese population.Conclusion: The polymorphism miR-196a2 C>T, but not miR-499 A>G, may be associated with decreased HBV-related HCC risk. These conclusions should be verified in large, well-designed studies.Keywords: microRNA, single nucleotide polymorphisms, hepatitis B virus related, meta-analysis, hepatocellular carcinoma

  7. A Serum miR Signature Specific to Low-Risk Prostate Cancer

    2017-09-01

    clear threshold and a negative predictive value of 0.9 to predict the absence of highgrade PCa among the patients. A unique feature of our discovery...miRs we created a combined “miR Score” which had clear threshold and a negative predictive value of 0.9 to predict the absence of high-grade PCa among...analysis 24 Major Task 2: Measure miR panel in PCa patient sera Subtask 1: Isolate RNA (ongoing through this time frame ) 6-24 Dr. Nonn 0

  8. Increased suicidal risk among smoking schizophrenia patients.

    Iancu, Iulian; Sapir, Anna Piccone; Shaked, Ginette; Poreh, Amir; Dannon, Pinhas Nadim; Chelben, Joseph; Kotler, Moshe

    2006-01-01

    Schizophrenia patients display a high suicidal risk, although this risk is difficult to predict. One of the variables associated with increased suicide risk is smoking. In the present study, we assessed the suicidal risk in schizophrenia patients, smokers and nonsmokers. We also evaluated the impact of various variables such as psychotic symptoms, impulsivity, and extra-pyramidal side effects on suicidal risk. Sixty-one schizophrenia patients responded to a battery of measures, including the suicidal risk scale (SRS), the positive and negative syndrome scale (PANSS), the impulsivity control scale, and the Simpson Angus Scale for extrapyramidal side effects. The effect of smoking on the various measures, especially suicidal risk, was examined. Schizophrenia patients who smoke obtained higher PANSS scores (both total score and positive and negative subscales), but did not differ on the Simpson Angus scale of extrapyramidal side effects. They also exhibited higher suicide risk as reflected by higher scores on the SRS, and a trend for higher impulsivity as measured by the impulsivity control scale. Women that smoked had higher SRS scores as compared with female nonsmokers, and also higher than in males, smokers and nonsmokers. Smoking and a history of suicide attempt predicted in our regression analysis a higher SRS score. When conducting separate analyses for the male and female patients, the significant contributors were the PANSS total score among the males and the number of pack-years among the female patients. Despite hints toward the role of smoking in suicidal behavior in Schizophrenia, especially among female patients, more studies are needed to elucidate the association between smoking and suicidality in schizophrenia patients.

  9. Identification of an enhancer that increases miR-200b~200a~429 gene expression in breast cancer cells.

    Joanne L Attema

    Full Text Available The miR-200b~200a~429 gene cluster is a key regulator of EMT and cancer metastasis, however the transcription-based mechanisms controlling its expression during this process are not well understood. We have analyzed the miR-200b~200a~429 locus for epigenetic modifications in breast epithelial and mesenchymal cell lines using chromatin immunoprecipitation assays and DNA methylation analysis. We discovered a novel enhancer located approximately 5.1kb upstream of the miR-200b~200a~429 transcriptional start site. This region was associated with the active enhancer chromatin signature comprising H3K4me1, H3K27ac, RNA polymerase II and CpG dinucleotide hypomethylation. Luciferase reporter assays revealed the upstream enhancer stimulated the transcription of the miR-200b~200a~429 minimal promoter region approximately 27-fold in breast epithelial cells. Furthermore, we found that a region of the enhancer was transcribed, producing a short, GC-rich, mainly nuclear, non-polyadenylated RNA transcript designated miR-200b eRNA. Over-expression of miR-200b eRNA had little effect on miR-200b~200a~429 promoter activity and its production did not correlate with miR-200b~200a~429 gene expression. While additional investigations of miR-200b eRNA function will be necessary, it is possible that miR-200b eRNA may be involved in the regulation of miR-200b~200a~429 gene expression and silencing. Taken together, these findings reveal the presence of a novel enhancer, which contributes to miR-200b~200a~429 transcriptional regulation in epithelial cells.

  10. Cisplatin-induced downregulation of miR-199a-5p increases drug resistance by activating autophagy in HCC cell

    Xu, Ning; Zhang, Jianjun; Shen, Conghuan; Luo, Yi; Xia, Lei; Xue, Feng [Department of Transplantation and Hepatic Surgery, Renji Hospital, Shanghai Jiaotong University School of Medicine, 1630 Dongfang Road, Shanghai 200127, People' s Republic of China (China); Xia, Qiang, E-mail: xiaqiang1@yahoo.com.cn [Department of Transplantation and Hepatic Surgery, Renji Hospital, Shanghai Jiaotong University School of Medicine, 1630 Dongfang Road, Shanghai 200127, People' s Republic of China (China)

    2012-07-13

    Highlights: Black-Right-Pointing-Pointer miR-199a-5p levels were significantly decreased after cisplatin treatment. Black-Right-Pointing-Pointer Cisplatin treatment induced autophagy activation. Black-Right-Pointing-Pointer Cisplatin-induced downregulation of miR-199a-5p increases drug resistance by activating autophagy in HCC cell. -- Abstract: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Systemic chemotherapy plays an important role in the treatment of patients with advanced liver cancer. However, chemoresistance to cisplatin is a major limitation of cisplatin-based chemotherapy in the clinic, and the underlying mechanism of such resistance is not fully understood. In the study, we found that miR-199a-5p levels were significantly reduced in HCC patients treated with cisplatin-based chemotherapy. Cisplatin treatment also resulted in decreased miR-199a-5p levels in human HCC cell lines. Forced expression of miR-199a-5p promoted cisplatin-induced inhibition of cell proliferation. Cisplatin treatment activated autophagy in Huh7 and HepG2 cells, which increased cell proliferation. We further demonstrated that downregulated miR-199a-5p enhanced autophagy activation by targeting autophagy-associated gene 7 (ATG7). More important, autophagy inhibition abrogated miR-199a-5p downregulation-induced cell proliferation. These data demonstrated that miR-199a-5p/autophagy signaling represents a novel pathway regulating chemoresistance, thus offering a new target for chemotherapy of HCC.

  11. miR-34 increases in vitro PANC-1 cell sensitivity to gemcitabine via targeting Slug/PUMA.

    Zhang, Qing-An; Yang, Xu-Hai; Chen, Dong; Yan, Xiang; Jing, Fu-Chun; Liu, Hong-Qian; Zhang, Ronghua

    2018-01-01

    miR-34 was deregulated in tumor tissues compared with corresponding noncancerous tissue samples. Furthermore, miR-34 may contribute to cancer-stromal interaction associated with cancer progression. However, whether miR-34 could decrease chemoresistance of cancer cells to chemotherapeutic agent remains unclear. In our study, we examined whether overexpression of miR-34 could sensitize gemcitabine -mediated apoptosis in human pancreatic cancer PANC-1 cells. We found that miR-34 markedly induced gemcitabine -mediated apoptosis in PANC-1 cells. miR-34 induced down-regulation of Slug expression and upregulation of p53 up-regulated modulator of apoptosis (PUMA) expression. The over-expression of Slug or downregulation of PUMA by Slug cDNA or PUMA siRNA transfection markedly blocked miR-34-induced gemcitabine sensitization. Furthermore, miR-34 induced PUMA expression by downregulation of Slug. Taken together, our study demonstrates that miR-34 enhances sensitization against gemcitabine-mediated apoptosis through the down-regulation of Slug expression, and up-regulation of Slug-dependent PUMA expression.

  12. Fractures and the increased risk of suicide.

    Chang, C-F; Lai, E C-C; Yeh, M-K

    2018-06-01

    Aims A high rate of suicide has been reported in patients who sustain fractures, but the association remains uncertain in the context of other factors. The aim of this study was to examine the association between fractures and the risk of suicide in this contextual setting. Patients and Methods We performed a case-control study of patients aged 40 years or older who died by suicide between 2000 and 2011. We included patients' demographics, physical and mental health problems, and socioeconomic factors. We performed conditional logistic regression to evaluate the associations between fractures and the risk of suicide. Results We included a total of 34 794 patients who died by suicide and 139 176 control patients. We found that fractures as a homogenous group (adjusted odds ratios (aOR), 1.48; 95% confidence interval (CI) 1.43 to 1.53), and specifically pelvic (aOR 2.04; 95% CI 1.68 to 2.47) and spinal fractures (aOR 1.53; 95% CI 1.43 to 1.64), were associated with a higher risk of suicide. In addition, we found that patients who had a lower income, had never married, had lower levels of educational attainment, or had coexistent physical and mental conditions such as anxiety, mood disorders, and psychosis-related disorders had a higher risk of suicide. Conclusion Fractures, specifically those of the hip and spine, were associated with an increased risk of suicide. The findings suggest that greater clinical attention should be given to this risk in patients with fractures, especially for those with additional risk factors. Cite this article: Bone Joint J 2018;100-B:780-6.

  13. Cryptorchidism and increased risk of neurodevelopmental disorders.

    Chen, Jianping; Sørensen, Henrik Toft; Miao, Maohua; Liang, Hong; Ehrenstein, Vera; Wang, Ziliang; Yuan, Wei; Li, Jiong

    2018-01-01

    Male congenital malformations as cryptorchidism may contribute to the development of neurodevelopmental disorders directly or via shared familial genetic and/or environmental factors, but the evidence is sparse. Using population-based health registries, we conducted a cohort study of all liveborn singleton boys in Denmark during 1979-2008. Boys with a diagnosis of cryptorchidism were categorized into the exposed cohort and the other boys into the unexposed comparison cohort. The outcomes were diagnoses of any neurodevelopmental disorders and their subtypes. We used Cox proportional hazards regression to compute hazard ratios (HRs), taking into consideration several potential confounders. Among 884,083 male infants, 27,505 received a diagnosis of cryptorchidism during follow-up. Boys with cryptorchidism were more likely to be diagnosed with intellectual disability (HR = 1.77; 95%confidence interval [CI]:1.59,1.97), autism spectrum disorders (ASD) (HR = 1.24; 95% CI:1.13,1.35), attention-deficit hyperactivity disorder (ADHD) (HR = 1.17; 95% CI: 1.08,1.26), anxiety (HR = 1.09; 95% CI: 1.01,1.17), and other behavioral/emotional disorders (HR = 1.16; 95% CI: 1.08,1.26) compared to boys without cryptorchidism. The observed risks of intellectual disability, ASD, and ADHD were increased further in boys with bilateral cryptorchidism. Except for anxiety, cryptorchid boys had higher risks of neurodevelopmental disorders than their non-cryptorchid full brothers. The observed increased risks were similar among boys who underwent orchiopexy, as well as among those with shorter waiting times for this surgery. Cryptorchidism may be associated with increased risks of intellectual disability, ASD, ADHD, and other behavioral/emotional disorders. Cryptorchidism and neurodevelopmental disorders may have shared genetic or in-utero/early postnatal risk factors, which need to be further investigated. Copyright © 2017. Published by Elsevier Ltd.

  14. Communicating Zika Risk: Using Metaphor to Increase Perceived Risk Susceptibility.

    Lu, Hang; Schuldt, Jonathon P

    2018-02-27

    Effectively communicating the risks associated with emerging zoonotic diseases remains an important challenge. Drawing on research into the psychological effects of metaphoric framing, we explore the conditions under which exposure to the "nation as a body" metaphor influences perceived risk susceptibility, behavioral intentions, and policy support in the context of Zika virus. In a between-subjects experiment, 354 U.S. adults were randomly assigned to one of four experimental conditions as part of a 2 (severity message: high vs. low) × 2 (U.S. framing: metaphoric vs. literal) design. Results revealed an interaction effect such that metaphoric (vs. literal) framing increased perceived risk susceptibility in the high-severity condition only. Further analyses revealed that perceived risk susceptibility and negative affect mediated the path between the two-way interaction and policy support and behavioral intentions regarding Zika prevention. Overall, these findings complement prior work on the influence of metaphoric framing on risk perceptions, while offering practical insights for risk communicators seeking to communicate about Zika and other zoonotic diseases. © 2018 Society for Risk Analysis.

  15. Increasing tsunami risk awareness via mobile application

    Leelawat, N.; Suppasri, A.; Latcharote, P.; Imamura, F.; Abe, Y.; Sugiyasu, K.

    2017-02-01

    In the information and communication technology era, smartphones have become a necessity. With the capacity and availability of smart technologies, a number of benefits are possible. As a result, designing a mobile application to increase tsunami awareness has been proposed, and a prototype has been designed and developed. The application uses data from the 2011 Great East Japan Tsunami. Based on the current location determined by a GPS function matched with the nearest point extracted from the detailed mesh data of that earlier disaster, the application generates the inundation depth at the user’s location. Thus, not only local people but also tourists visiting the affected areas can understand the risks involved. Application testing has been conducted in an evacuation experiment involving both Japanese and foreign students. The proposed application can be used as a supplementary information tool in tsunami evacuation drills. It also supports the idea of smart tourism: when people realize their risks, they possess risk awareness and hence can reduce their risks. This application can also be considered a contribution to disaster knowledge and technology, as well as to the lessons learned from the practical outcome.

  16. MiR-144 Increases Intestinal Permeability in IBS-D Rats by Targeting OCLN and ZO1

    Qiuke Hou

    2017-12-01

    Full Text Available Background/Aims: Irritable bowel syndrome with diarrhoea (IBS-D is a chronic, functional bowel disorder characterized by abdominal pain or diarrhoea and altered bowel habits, which correlate with intestinal hyperpermeability. MicroRNAs (miRNAs are involved in regulating intestinal permeability in IBS-D. However, the role of miRNAs in regulating intestinal permeability and protecting the epithelial barrier remains unclear. Our goals were to (i identify differential expression of miRNAs and their targets in the distal colon of IBS-D rats; (ii verify in vitro whether occludin (OCLN and zonula occludens 1 (ZO1/TJP1 were direct targets of miR-144 and were down-regulated in IBS-D rats; and (iii determine whether down-regulation of miR-144 in vitro could reverse the pathological hallmarks of intestinal hyperpermeability via targeting OCLN and ZO1. Methods: The IBS-D rat model was established using 4% acetic acid and evaluated by haematoxylin-eosin (HE staining. The distal colon was obtained in order to perform miRNA microarray analysis and to isolate and culture colonic epithelial cells. When differential expression of miRNA was found, the results were verified by qRT-PCR, and the target genes were further explored by bioinformatics analysis. Correlation analyses were carried out to compare the expression of miRNA and target genes. Then, mutants, miRNA mimics and inhibitors of the target genes were constructed and transfected to colonic epithelial cells. qRT-PCR, western blotting, enzyme-linked immunosorbent assays (ELISAs and dual-luciferase assays were used to investigate the expression of miR-144 and OCLN, ZO1 in IBS-D rats. Results: There were 8 up-regulated and 18 down-regulated miRNAs identified in the IBS-D rat model. Of these, miR-144 was markedly up-regulated and resulted in the down-regulation of OCLN and ZO1 expression. Overexpression of miR-144 by transfection of miR-144 precursor markedly inhibited the expression of OCLN and ZO1. Further

  17. Low Adiponectin Levels and Increased Risk of Type 2 Diabetes in Patients With Myocardial Infarction

    Lindberg, Søren; Jensen, Jan S; Pedersen, Sune H

    2014-01-01

    OBJECTIVE: Patients with acute myocardial infarction (MI) have increased risk of developing type 2 diabetes mellitus (T2DM). Adiponectin is an insulin-sensitizing hormone produced in adipose tissue, directly suppressing hepatic gluconeogenesis, stimulating fatty acid oxidation and glucose uptake...... 5.3-6.1]) 6% (n = 38) developed T2DM. Risk of T2DM was analyzed using a competing risk analysis. RESULTS: Low adiponectin levels were associated with increased risk of T2DM (P age, sex, hypertension, hypercholesterolemia, current smoking.......001). Importantly, plasma adiponectin added to the predictive value of blood glucose, with the combination of high blood glucose and low plasma adiponectin, vastly increasing the risk of developing T2DM (HR 9.6 [3.7-25.3]; P

  18. Has risk associated with smoking increased?

    Prescott, E; Osler, M; Andersen, P K

    1997-01-01

    BACKGROUND: Two recent much cited publications have raised the concern that risk associated with cigarette smoking has so far been underestimated. In this study we wish to determine whether excess all-cause mortality associated with smoking has increased during the last 20-30 years in a study...... population representative of the general Danish population and whether any such changes relate to changes in smoking behaviour. METHODS: Pooled data from three prospective population studies conducted in Copenhagen with detailed information on smoking habits. A total of 31,194 subjects, 17,669 males and 13......,525 females, initially examined between 1964 and 1992 with examinations repeated at intervals from 1-10 years, were followed until 1995 for all-cause mortality. Relative mortality risk in smokers versus never-smokers was calculated within periods of five calendar years and compared throughout the study period...

  19. Exosome-mediated transfer of miR-222 is sufficient to increase tumor malignancy in melanoma.

    Felicetti, Federica; De Feo, Alessandra; Coscia, Carolina; Puglisi, Rossella; Pedini, Francesca; Pasquini, Luca; Bellenghi, Maria; Errico, Maria Cristina; Pagani, Elena; Carè, Alessandra

    2016-02-24

    Growing evidence is showing that metastatic cell populations are able to transfer their characteristics to less malignant cells. Exosomes (EXOs) are membrane vesicles of endocytic origin able to convey their cargo of mRNAs, microRNAs (miRs), proteins and lipids from donors to proximal as well as distant acceptor cells. Our previous results indicated that miR-221&222 are key factors for melanoma development and dissemination. The aim of this study was to verify whether the tumorigenic properties associated with miR-222 overexpression can be also propagated by miR-222-containing EXOs. EXOs were isolated by UltraCentrifugation or Exoquick-TC(®) methods. Preparations of melanoma-derived vesicles were characterized by using the Nanosight™ technology and the expression of exosome markers analyzed by western blot. The expression levels of endogenous and exosomal miRNAs were examined by real time PCR. Confocal microscopy was used to evaluate transfer and uptake of microvesicles from donor to recipient cells. The functional significance of exosomal miR-222 was estimated by analyzing the vessel-like process formation, as well as cell cycle rates, invasive and chemotactic capabilities. Besides microvesicle marker characterization, we evidenced that miR-222 exosomal expression mostly reflected its abundance in the cells of origin, correctly paralleled by repression of its target genes, such as p27Kip1, and induction of the PI3K/AKT pathway, thus confirming its functional implication in cancer. The possible differential significance of PI3K/AKT blockade was assessed by using the BKM120 inhibitor in miR-222-transduced cell lines. In addition, in vitro cultures showed that vesicles released by miR-222-overexpressing cells were able to transfer miR-222-dependent malignancy when taken-up by recipient primary melanomas. Results were confirmed by antagomiR-221&222 treatments and by functional observations after internalization of EXOs devoid of these miRs. All together these data

  20. Increased level of miRNA 30b-3p in patients with prostatic hyperplasia and testosterone with high-level of prostate-specific antigen

    Wasnaa Jumaa Mohammad

    2018-01-01

    Full Text Available Background: Prostate cancer (PCa is the most common causing cancer-related in death in men and lack of reliable diagnostic tool. MicroRNAs are small molecules single-stranded RNA that affecting protein expression at the level of translation and dysregulation can dramatically affect cell metabolism. However, the using of circulating miRNAs as diagnostic biomarkers for diagnosis of PCa is still unknown. Methods: Ten patients with prostatic hyperplasia with high-level of PSA and 10 healthy controls were conducted in this study. The reverse transcription of miRNA based on quantitative polymerase chain reaction (qPCR were used for evaluating the dysregulation of miRNA 30b-3p and using of ELISA to evaluate the level of prostate-specific antigen (PSA and testosterone hormone. Results: Circulating miRNA 30b-3p level was increased in patients with prostatic hyperplasia with higher level of PSA as compared with healthy controls. Also, the testosterone hormone was increased in those patients as compared with normal level of testosterone in healthy individuals. Conclusion: The serum miRNA 30b-3p level increased in patients with hyperplasia in prostate and may be one of potential biomarker for diagnosis of PCa.

  1. Alcoholic Cirrhosis Increases Risk for Autoimmune Diseases

    Grønbæk, Lisbet; Vilstrup, Hendrik; Deleuran, Bent

    2015-01-01

    IRR, 1.56; 95% CI, 1.26-1.92), celiac disease (aIRR, 5.12; 95% CI, 2.58-10.16), pernicious anemia (aIRR, 2.35; 95% CI, 1.50-3.68), and psoriasis (aIRR, 4.06; 95% CI, 3.32-4.97). There was no increase in the incidence rate for rheumatoid arthritis (aIRR, 0.89; 95% CI, 0.69-1.15); the incidence rate......BACKGROUND & AIMS: Alcoholic cirrhosis is associated with hyperactivation and dysregulation of the immune system. In addition to its ability to increase risk for infections, it also may increase the risk for autoimmune diseases. We studied the incidence of autoimmune diseases among patients...... (controls) of the same sex and age. The incidence rates of various autoimmune diseases were compared between patients with cirrhosis and controls and adjusted for the number of hospitalizations in the previous year (a marker for the frequency of clinical examination). RESULTS: Of the 24,679 patients...

  2. Homocysteine increases the risk associated with hyperlipidaemia.

    Daly, Caroline

    2009-04-01

    The European Concerted Action Project \\'Homocysteine and Vascular Disease\\' showed that an elevated homocysteine is associated with a substantially increased risk of cardiovascular disease, and particularly when combined with other factors such as smoking, hypertension and hypercholesterolaemia. The purpose of this study was to examine the potential interactions between homocysteine and individual lipid subfractions. In addition, it was hypothesized that HDL cholesterol may protect against hyperhomocysteinaemia because HDL cholesterol is associated with the enzyme paroxonase, which reduces oxidization of homocysteine to the harmful metabolite, homocysteine thiolactonase.

  3. Hypospadias and increased risk for neurodevelopmental disorders.

    Butwicka, Agnieszka; Lichtenstein, Paul; Landén, Mikael; Nordenvall, Anna S; Nordenström, Anna; Nordenskjöld, Agneta; Frisén, Louise

    2015-02-01

    Hypospadias (aberrant opening of the urethra on the underside of the penis) occurs in 1 per 300 newborn boys. It has been previously unknown whether this common malformation is associated with increased psychiatric morbidity later in life. Studies of individuals with hypospadias also provide an opportunity to examine whether difference in androgen signaling is related to neurodevelopmental disorders. To elucidate the mechanisms behind a possible association, we also studied psychiatric outcomes among brothers of the hypospadias patients. Registry study within a national cohort of all 9,262 males with hypospadias and their 4,936 healthy brothers born in Sweden between 1973 and 2009. Patients with hypospadias and their brothers were matched with controls by year of birth and county. The following outcomes were evaluated (1) any psychiatric (2) psychotic, (3) mood, (4) anxiety, (5) eating, and (6) personality disorders, (7) substance misuse, (8) attention-deficit hyperactivity disorder (ADHD), (9) autism spectrum disorders (ASD), (10) intellectual disability, and (11) other behavioral/emotional disorders with onset in childhood. Patients with hypospadias were more likely to be diagnosed with intellectual disability (OR 3.2; 95% CI 2.8-3.8), ASD (1.4; 1.2-1.7), ADHD (1.5; 1.3-1.9), and behavioral/emotional disorders (1.4; 1.2-1.6) compared with the controls. Brothers of patients with hypospadias had an increased risk of ASD (1.6; 1.3-2.1) and other behavioral/emotional disorders with onset in childhood (1.2; 0.9-1.5) in comparison to siblings of healthy individuals. A slightly higher, although not statistically significant, risk was found for intellectual disability (1.3; 1.0-1.9). No relation between other psychiatric diagnosis and hypospadias was found. This is the first study to identify an increased risk for neurodevelopmental disorders in patients with hypospadias, as well as an increased risk for ASD in their brothers, suggesting a common familial (genetic and

  4. BDNF VAL66MET Polymorphism Elevates the Risk of Bladder Cancer via MiRNA-146b in Micro-Vehicles

    Cong Li

    2018-01-01

    Full Text Available Background/Aims: Emerging studies on brain-derived neurotrophic factor (BDNF have shown that might be novel biomarkers and therapeutic targets for cancer. We explore the role of BDNF in the tumorigenesis of bladder cancer and the underlying molecular mechanism. Methods: 368 patients with diagnosed bladder cancer and 352 healthy controls were enrolled to evaluate the association of BDNF and the miR-146b. Bioinformatics algorithm analysis and luciferase assay were performed to identify the target genes of miR-146b. Real-time PCR and western-blot were carried out to validate the relationship between miR-146b and CRK. MTT assay and FACS were used to evaluated the proliferation and apoptosis of cancer cells. MVs were isolated and transfect into the culture cells to confirm the above observation. Results: The clinical study shows that BDNF Met/Met was significantly associated with the risk of bladder cancer. In addition, comparing with Val/Val and Val/Met, Met/Met has lower miR-146b level. Luciferase assay shows that BDNF Val/Val is apparently enhanced miR-146b promoter-luciferase, but not BDNF Met/Met. Based on luciferase assay, CRK is a direct target gene of miR-146b. MiR-146b mimics significantly inhibited the expression of CRK and activation of AKT level. The expression of CRK and the activation of AKT (p-AKT were significantly inhibited by MV-BDNF Val/Val-miR-146b or MV-BDNF Val/Met-miR-146b, but not MV-BDNF Met/Met-miR-146b. MV-BDNF Val/Val-miR-146b or Val/Met-miR-146b obviously inhibited cell proliferation, which eliminated by CRK. Meanwhile, with MV-BDNF Met/Met-miR-146b or Met/Met-miR-146b+CRK did not affect the proliferation. MV-BDNF Val/Val-miR-146b or Val/Met-miR-146b enhanced cell apoptosis, which could be eliminated by CRK. Meanwhile, MV-BDNF Met/Met-miR-146b or Met/Met-miR-146b+CRK did not promote apoptosis. Conclusion: BDNF VAL66MET polymorphism is associated with miR-146b and its target gene CRK. MiR-146b and CRK mediated BDNF VAL66

  5. The interaction of miR-34b/c polymorphisms and negative life events increases susceptibility to major depressive disorder in Han Chinese population.

    Xu, Cheng; Yang, Chunxia; Zhang, Aixia; Xu, Yong; Li, Xinrong; Liu, Zhifen; Liu, Sha; Sun, Ning; Zhang, Kerang

    2017-06-09

    Previous studies have shown that microRNAs(miRNAs) are involved in the pathogenesis of MDD; in particular, miR-34b/c has been implicated in MDD risk and found to exert antidepressant effects. However, the effects of miR-34b/c polymorphisms on MDD risk have not been investigated. In this study, we evaluated the effect of miR-34b/c gene polymorphisms and their interaction with negative life events in relation to MDD, using data from 381 Han Chinese patients with MDD and 291 healthy volunteers. Allelic, genotypic, haplotypic, and gene-environment associations were analyzed using UNPHASED and SPSS software. After discarding data with extremely severe negative life events in our study population, we found an association between rs4938723, rs2187473 polymorphisms and MDD in the dominant models (TC/CC vs. TT, OR=1.45, P=0.027; TC/CC vs. TT, OR=3.32, P=0.030). In haplotype analysis, the C-G haplotype (rs4938723/rs28757623) showed the strongest association with MDD (OR=1.95, P=0.026). Additionally, we found significant gene-environment combination rs4938723 C allele, rs28757623 G allele and high level of negative life events (C-G-HN) was significantly associated with MDD (OR, 3.85; 95% CI, 1.62-9.13). In addition, the combination of (C-C-HN) is of significance (OR, 2.99; 95% CI, 1.36-6.60), indicating that the rs28757623 C allele may contribute to the risk of MDD as well. The sample size was small and the role of miR-34b/c polymorphisms for MDD should be assessed using independent samples from other ethnic populations. Our results suggest that miR-34b/c is a susceptibility factor for MDD stratified by negative life events and that rs4938723 is a significant association locus for gene-environment interaction in relation to MDD risk. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Polymorphisms in miRNA binding sites of nucleotide excision repair genes and colorectal cancer risk

    Naccarati, Alessio; Pardini, Barbara; Landi, S.; Landi, D.; Slyšková, Jana; Novotný, J.; Levý, M.; Poláková, Veronika; Lipská, L.; Vodička, Pavel

    2012-01-01

    Roč. 33, č. 7 (2012), s. 1346-1351 ISSN 0143-3334 R&D Projects: GA ČR GAP304/10/1286; GA ČR GP305/09/P194 Institutional research plan: CEZ:AV0Z50390703 Keywords : DNA repair * polymorphisms * miRNA binding sites Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.635, year: 2012

  7. miR-18a promotes cell proliferation of esophageal squamous cell carcinoma cells by increasing cylin D1 via regulating PTEN-PI3K-AKT-mTOR signaling axis

    Zhang, Weiguo, E-mail: weiguozhangHU@gmail.com; Lei, Caipeng; Fan, Junli; Wang, Jing

    2016-08-12

    Esophageal squamous cell carcinoma (ESCC) is one of the lethal cancers with a high incidence rate in Asia. Cyclin D1 is overexpressed and plays an important role in the carcinogenesis of ESCC; however the mechanism of the deregulation of Cyclin D1 in ESCC remains to be determined. In the study, we found that miR-18a promotes the expression Cyclin D1 by targeting PTEN in eophageal squamous cell carcinoma TE13 and Eca109 cells. Transfection of miR-18a mimetics increased cyclin D1, while transfection of miR-18a antagomir decreased D1. Moreover, miR-18a-mediated upregulation of cyclin D1 was accompanied with downregulation of PTEN, which is a direct target of miR-18a, and increase of the phosphorylation of AKT and S6K1. In addition, pharmacologic inhibition of AKT or mTOR kinases abolished the increase of cyclinD1 by miR-18a, which was accompanied with decreased phosphorylation of Rb−S780 and inhibition of cell proliferation. Our results demonstrated the upregulation of miR-18a promoted cell proliferation by increasing cylin D1 via regulating PTEN-PI3K-AKT-mTOR signaling axis, suggesting that small molecule inhibitors of AKT-mTOR signaling are potential agents for the treatment of ESCC patients with upregulation of miR-17-92 cluster. - Highlights: • miR-18a promotes the proliferation of ESCC cells. • miR-18a increase cyclin D1 expression in ESCC cells. • miR-18a directly targets PTEN in ESCC cells. • Inhibition of AKT-mTOR prevents miR-18a-induced cyclin D1 in ESCC cells. • miR-18a antagomir sensitizes ESCC cells to cisplatin.

  8. MiR-2964a-5p binding site SNP regulates ATM expression contributing to age-related cataract risk.

    Rong, Han; Gu, Shanshan; Zhang, Guowei; Kang, Lihua; Yang, Mei; Zhang, Junfang; Shen, Xinyue; Guan, Huaijin

    2017-10-17

    This study was to explore the involvement of DNA repair genes in the pathogenesis of age-related cataract (ARC). We genotyped nine single nucleotide polymorphisms (SNPs) of genes responsible to DNA double strand breaks (DSBs) in 804 ARC cases and 804 controls in a cohort of eye diseases in Chinese population and found that the ataxia telangiectasia mutated ( ATM ) gene-rs4585:G>T was significantly associated with ARC risk. An in vitro functional test found that miR-2964a-5p specifically down-regulated luciferase reporter expression and ATM expression in the cell lines transfected with rs4585 T allele compared to rs4585 G allele. The molecular assay on human tissue samples discovered that ATM expression was down-regulated in majority of ARC tissues and correlated with ATM genotypes. In addition, the Comet assay of cellular DNA damage of peripheral lymphocytes indicated that individuals carrying the G allele (GG/GT) of ATM -rs4585 had lower DNA breaks compared to individuals with TT genotype. These findings suggested that the SNP rs4585 in ATM might affect ARC risk through modulating the regulatory affinity of miR-2964a-5p. The reduced DSBs repair might be involved in ARC pathogenesis.

  9. Increased leukemia risk in Chernobyl cleanup workers

    A new study found a significantly elevated risk for chronic lymphocytic leukemia among workers who were engaged in recovery and clean-up activities following the Chernobyl power plant accident in 1986.

  10. Improved cardiovascular risk among Hispanic border participants of the HEART II Mi Corazón Mi Comunidad Promotores de Salud Model: the cohort intervention study 2009-2013

    Hendrik Dirk ede Heer

    2015-06-01

    Full Text Available AbstractBackgroundCommunity resources (parks, recreational facilities provide opportunities for health promotion, but little is known about how to promote utilization of these resources and their impact on cardiovascular disease risk (CVD. MethodsThis cohort study evaluated the impact of an intervention called Mi Corazon Mi Comunidad (MiCMiC, which consisted of promoting use of community physical activity and nutrition resources by Promotoras de Salud/Community Health Workers. Participants were assessed at baseline and following the 4-month intervention. Attendance records were objectively collected to assess utilization of intervention programming. ResultsA total of 5 consecutive cohorts were recruited between 2009 and 2013. Participants were mostly females (86.0%, on average 46.6 years old, and 81% were low in acculturation. Participants who completed follow-up (n=413 showed significant improvements in reported health behaviors and body composition. Higher attendance significantly predicted greater improvements. The baseline to 4-month change for the highest versus the lowest attendance quartiles were (-5.2 lbs vs. +0.01 lbs, p<.001, waist circumference (-1.20 inches vs. -0.56 inches, p=.047, hip circumference (-1.13 inches vs. -0.41 inches, p<.001; hours of exercise/week (+3.87 hours vs. +0.81 hrs, p<.001, proportion of participants eating 5 servings of fruits and vegetables/day (+54.7% vs. 14.7%, p<.001.ConclusionsFollowing the Promotora-led MiCMiC intervention, substantial improvements in health behaviors and modest improvements in cardiovascular risk factors were found. Greater utilization of community resources was associated with more favorable changes. This study provided preliminary evidence for the effectiveness of Promotora-led interventions for promoting use of existing community resources in CVD risk reduction. Key Words: Community resources, community health workers, U.S.- Mexico border, Hispanic, cardiovascular disease, cohort

  11. Improved Cardiovascular Risk among Hispanic Border Participants of the Mi Corazón Mi Comunidad Promotores De Salud Model: The HEART II Cohort Intervention Study 2009-2013.

    de Heer, Hendrik Dirk; Balcazar, Hector G; Wise, Sherrie; Redelfs, Alisha H; Rosenthal, E Lee; Duarte, Maria O

    2015-01-01

    Community resources (parks, recreational facilities) provide opportunities for health promotion, but little is known about how to promote utilization of these resources and their impact on cardiovascular disease risk (CVD). This cohort study evaluated the impact of an intervention called Mi Corazon Mi Comunidad (MiCMiC), which consisted of promoting use of community physical activity and nutrition resources by Promotoras de Salud/Community Health Workers. Participants were assessed at baseline and following the 4-month intervention. Attendance records were objectively collected to assess utilization of intervention programing. A total of five consecutive cohorts were recruited between 2009 and 2013. Participants were mostly females (86.0%), on average 46.6 years old, and 81% were low in acculturation. Participants who completed follow-up (n = 413) showed significant improvements in reported health behaviors and body composition. Higher attendance significantly predicted greater improvements. The baseline to 4-month change for the highest vs. the lowest attendance quartiles were for weight (-5.2 vs. +0.01 lbs, p < 0.001), waist circumference (-1.20 vs. -0.56 inches, p = 0.047), hip circumference (-1.13 vs. -0.41 inches, p < 0.001); hours of exercise/week (+3.87 vs. +0.81 hours, p < 0.001), proportion of participants eating five servings of fruits and vegetables/day (+54.7 vs. 14.7%, p < 0.001). Following the Promotora-led MiCMiC intervention, substantial improvements in health behaviors and modest improvements in cardiovascular risk factors were found. Greater utilization of community resources was associated with more favorable changes. This study provided preliminary evidence for the effectiveness of Promotora-led interventions for promoting use of existing community resources in CVD risk reduction.

  12. Protamine reduces bleeding complications associated with carotid endarterectomy without increasing the risk of stroke.

    Stone, David H; Nolan, Brian W; Schanzer, Andres; Goodney, Philip P; Cambria, Robert A; Likosky, Donald S; Walsh, Daniel B; Cronenwett, Jack L

    2010-03-01

    Controversy persists regarding the use of protamine during carotid endarterectomy (CEA) based on prior conflicting reports documenting both reduced bleeding as well as increased stroke risk. The purpose of this study was to determine the effect of protamine reversal of heparin anticoagulation on the outcome of CEA in a contemporary multistate registry. We reviewed a prospective regional registry of 4587 CEAs in 4311 patients performed by 66 surgeons from 11 centers in Northern New England from 2003-2008. Protamine use varied by surgeon (38% routine use, 44% rare use, 18% selective use). Endpoints were postoperative bleeding requiring reoperation as well as potential thrombotic complications, including stroke, death, and myocardial infarction (MI). Predictors of endpoints were determined by multivariate logistic regression after associated variables were identified by univariate analysis. Of the 4587 CEAs performed, 46% utilized protamine, while 54% did not. Fourteen patients (0.64%) in the protamine-treated group required reoperation for bleeding compared with 42 patients (1.66%) in the untreated cohort (P = .001). Protamine use did not affect the rate of MI (1.1% vs 0.91%, P = .51), stroke (0.78% vs 1.15%, P = .2), or death (0.23% vs 0.32%, P = .57) between treated and untreated patients, respectively. By multivariate analysis, protamine (odds ratio [OR] 0.32, 95% confidence interval [CI], 0.17-0.63; P = .001) and patch angioplasty (OR 0.46, 95% CI, 0.26-0.81; P = .007) were independently associated with diminished reoperation for bleeding. A single center was associated with a significantly higher rate of reoperation for bleeding (OR 6.47, 95% CI, 3.02-13.9; P < .001). Independent of protamine use, consequences of reoperation for bleeding were significant, with a four-fold increase in MI, a seven-fold increase in stroke, and a 30-fold increase in death. Protamine reduced serious bleeding requiring reoperation during CEA without increasing the risk of MI, stroke

  13. Increased risk for depression after breast cancer

    Suppli, Nis P; Johansen, Christoffer; Christensen, Jane

    2014-01-01

    PURPOSE: To investigate the risk for first depression, assessed as incident hospital contacts for depression and incident use of antidepressants, among women with breast cancer. PATIENTS AND METHODS: Danish national registries were used to identify 1,997,669 women with no diagnosis of cancer...... or a major psychiatric disorder. This cohort was followed from 1998 to 2011 for a diagnosis of breast cancer and for the two outcomes, hospital contact for depression and redeemed prescriptions for antidepressants. Rate ratios for incident hospital contacts for depression and incident use of antidepressants...... were estimated with Poisson regression models. Multivariable Cox regression was used to evaluate factors associated with the two outcomes among patients with breast cancer. RESULTS: We identified 44,494 women with breast cancer. In the first year after diagnosis, the rate ratio for a hospital contact...

  14. Hypospadias and increased risk for neurodevelopmental disorders

    Butwicka, Agnieszka; Lichtenstein, Paul; Landén, Mikael; Nordenvall, Anna; Nordenström, Anna; Nordenskjöld, Agneta; Frisén, Louise

    2014-01-01

    BACKGROUND: Hypospadias (aberrant opening of the urethra on the underside of the penis) occurs in 1 per 300 newborn boys. It has been previously unknown whether this common malformation is associated with increased psychiatric morbidity later in life. Studies of individuals with hypospadias also provide an opportunity to examine whether difference in androgen signaling is related to neurodevelopmental disorders. To elucidate the mechanisms behind ...

  15. Cardiovascular Risk is not Increased in Patients with Chronic Urticaria

    Egeberg, Alexander; Gislason, Gunnar H; Vestergaard, Christian

    2016-01-01

    in an Italian cohort as between 0.02% and 0.38%, whereas a German study showed a lifetime prevalence of CU at 1.8% (2, 3). While an association between CU and certain autoimmune diseases is well-established (3), CSU was surprisingly associated with obesity in a recent Italian study (4). Moreover, in a South...... was significantly associated with having received a prior diagnosis of hyperlipidaemia (6). Despite the above observations, no study has examined a possible association between CU and cardiovascular (CV) disease. We therefore investigated the risk of myocardial infarction (MI), ischaemic stroke, CV death, and major...... Korean cohort of 131 patients with CU, metabolic syndrome was present in 30% of patients, and these individuals had particularly poor clinical outcomes and a more severe disease course (5). Finally, a population-based Taiwanese study of 9798 adults with CU recently showed that the condition...

  16. DoReMi workshop on multidisciplinary approaches to evaluating cancer risks associated with low-dose internal contamination

    Laurier, D.; Guseva Canu, I.; Bertho, J.M.; Blanchardon, E.; Rage, E.; Baatout, S.; Bouffler, S.; Cardis, E.; Gomolka, M.; Kreuzer, M.; Hall, J.; Kesminiene, A.

    2012-01-01

    A workshop dedicated to cancer risks associated with low-dose internal contamination was organised in March 2011, in Paris, in the framework of the DoReMi (Low Dose Research towards Multidisciplinary Integration) European Network of Excellence. The aim was to identify the best epidemiological studies that provide an opportunity to develop a multidisciplinary approach to improve the evaluation of the cancer risk associated with internal contamination. This workshop provided an opportunity for in-depth discussions between researchers working in different fields including (but not limited to) epidemiology, dosimetry, biology and toxicology. Discussions confirmed the importance of research on the health effects of internal contamination. Several existing epidemiological studies provide a real possibility to improve the quantification of cancer risk associated with internal emitters. Areas for future multidisciplinary collaborations were identified, that should allow feasibility studies to be carried out in the near future. The goal of this paper is to present an overview of the presentations and discussions that took place during this workshop. (authors)

  17. The interaction between coagulation factor 2 receptor and interleukin 6 haplotypes increases the risk of myocardial infarction in men.

    Bruna Gigante

    Full Text Available The aim of the study was to investigate if the interaction between the coagulation factor 2 receptor (F2R and the interleukin 6 (IL6 haplotypes modulates the risk of myocardial infarction (MI in the Stockholm Heart Epidemiology Program (SHEEP. Seven SNPs at the F2R locus and three SNPs at the IL6 locus were genotyped. Haplotypes and haplotype pairs (IL6*F2R were generated. A logistic regression analysis was performed to analyze the association of the haplotypes and haplotype pairs with the MI risk. Presence of an interaction between the two haplotypes in each haplotype pair was calculated using two different methods: the statistical, on a multiplicative scale, which includes the cross product of the two factors into the logistic regression model; the biological, on an additive scale, which evaluates the relative risk associated with the joint presence of both factors. The ratio between the observed and the predicted effect of the joint exposure, the synergy index (S, indicates the presence of a synergy (S>1 or of an antagonism (S<1. None of the haplotypes within the two loci was associated with the risk of MI. Out of 22 different haplotype pairs, the haplotype pair 17 GGG*ADGTCCT was associated with an increased risk of MI with an OR (95%CI of 1.58 (1.05-2.41 (p = 0.02 in the crude and an OR of 1.72 (1.11-2.67 (p = 0.01 in the adjusted analysis. We observed the presence of an interaction on a multiplicative scale with an OR (95%CI of 2.24 (1.27-3.95 (p = 0.005 and a slight interactive effect between the two haplotypes on an additive scale with an OR (95%CI of 1.56 (1.02-2.37 (p = 0.03 and S of 1.66 (0.89-31. In conclusion, our results support the hypothesis that the interaction between these two functionally related genes may influence the risk of MI and suggest new mechanisms involved in the genetic susceptibility to MI.

  18. Placental Chorangiosis: Increased Risk for Cesarean Section

    Shariska S. Petersen

    2017-01-01

    Full Text Available We describe a patient with Class C diabetes who presented for nonstress testing at 36 weeks and 4 days of gestation with nonreassuring fetal heart tones (NRFHT and oligohydramnios. Upon delivery, thrombosis of the umbilical cord was grossly noted. Pathological analysis of the placenta revealed chorangiosis, vascular congestion, and 40% occlusion of the umbilical vein. Chorangiosis is a vascular change of the placenta that involves the terminal chorionic villi. It has been proposed to result from longstanding, low-grade hypoxia in the placental tissue and has been associated with such conditions such as diabetes, intrauterine growth restriction (IUGR, and hypertensive conditions in pregnancy. To characterize chorangiosis and its associated obstetric outcomes we identified 61 cases of “chorangiosis” on placental pathology at Henry Ford Hospital from 2010 to 2015. Five of these cases were omitted due to lack of complete records. Among the 56 cases, the cesarean section rate was 51%, indicated in most cases for nonreassuring fetal status. Thus, we suggest that chorangiosis, a marker of chronic hypoxia, is associated with increased rates of cesarean sections for nonreassuring fetal status because of long standing hypoxia coupled with the stress of labor.

  19. Diagnostic and prognostic potential of serum miR-7, miR-16, miR-25, miR-93, miR-182, miR-376a and miR-429 in ovarian cancer patients.

    Meng, Xiaodan; Joosse, Simon A; Müller, Volkmar; Trillsch, Fabian; Milde-Langosch, Karin; Mahner, Sven; Geffken, Maria; Pantel, Klaus; Schwarzenbach, Heidi

    2015-11-03

    Owing to late diagnosis in advanced disease stages, prognosis of patients with epithelial ovarian cancer (EOC) is poor. The quantification of deregulated levels of microRNAs could facilitate earlier diagnosis and improve prognosis of EOC. Seven microRNAs (miR-7, miR-16, miR-25, miR-93, miR-182, miR-376a and miR-429) were quantified in the serum of 180 EOC patients and 66 healthy women by TaqMan PCR microRNA assays. Median follow-up time was 21 months. The effects of miR-7 and miR-429 on apoptosis, cell proliferation, migration and invasion were investigated in two (EOC) cell lines. Serum levels of miR-25 (P=0.0001) and miR-93 (P=0.0001) were downregulated, whereas those of miR-7 (P=0.001) and miR-429 (P=0.0001) were upregulated in EOC patients compared with healthy women. The four microRNAs discriminated EOC patients from healthy women with a sensitivity of 93% and a specificity of 92%. The levels of miR-429 positively correlated with CA125 values (P=0.0001) and differed between FIGO I-II and III-IV stages (P=0.001). MiR-429 was an independent predictor of overall survival (P=0.011). Overexpressed miR-429 in SKOV3 cells led to suppression of cell migration (P=0.037) and invasion (P=0.011). Increased levels of miR-7 were associated with lymph node metastases (P=0.0001) and FIGO stages III-IV (P=0.0001). Overexpressed miR-7 in SKOV3 cells resulted in increased cell migration (P=0.001) and invasion (P=0.011). Additionally, the increased levels of miR-376a correlated with FIGO stages III-IV (P=0.02). Our data indicate the diagnostic potential of miR-7, miR-25, miR-93 and miR-429 in EOC and the prognostic potential of miR-429. This microRNA panel may be promising molecules to be targeted in the treatment of EOC.

  20. Multiple Sclerosis Increases Fracture Risk: A Meta-Analysis

    Guixian Dong

    2015-01-01

    Full Text Available Purpose. The association between multiple sclerosis (MS and fracture risk has been reported, but results of previous studies remain controversial and ambiguous. To assess the association between MS and fracture risk, a meta-analysis was performed. Method. Based on comprehensive searches of the PubMed, Embase, and Web of Science, we identified outcome data from all articles estimating the association between MS and fracture risk. The pooled risk ratios (RRs with 95% confidence intervals (CIs were calculated. Results. A significant association between MS and fracture risk was found. This result remained statistically significant when the adjusted RRs were combined. Subgroup analysis stratified by the site of fracture suggested significant associations between MS and tibia fracture risk, femur fracture risk, hip fracture risk, pelvis fracture risk, vertebrae fracture risk, and humerus fracture risk. In the subgroup analysis by gender, female MS patients had increased fracture risk. When stratified by history of drug use, use of antidepressants, hypnotics/anxiolytics, anticonvulsants, and glucocorticoids increased the risk of fracture risk in MS patients. Conclusions. This meta-analysis demonstrated that MS was significantly associated with fracture risk.

  1. Inhibition of miR-146b expression increases radioiodine-sensitivity in poorly differential thyroid carcinoma via positively regulating NIS expression

    Li, Luchuan; Lv, Bin; Chen, Bo [Department of General Surgery, Shandong University Qilu Hospital, Jinan, Shandong 250012 (China); Guan, Ming [Department of General Surgery, Qihe People' s Hospital, Qihe, Shandong 251100 (China); Sun, Yongfeng [Department of General Surgery, Licheng District People' s Hospital, Jinan, Shandong 250115 (China); Li, Haipeng [Department of General Surgery, Caoxian People' s Hospital, Caoxian, Shandong 274400 (China); Zhang, Binbin; Ding, Changyuan; He, Shan [Department of General Surgery, Shandong University Qilu Hospital, Jinan, Shandong 250012 (China); Zeng, Qingdong, E-mail: qingdz0201@163.com [Department of General Surgery, Shandong University Qilu Hospital, Jinan, Shandong 250012 (China)

    2015-07-10

    Dedifferentiated thyroid carcinoma (DTC) with the loss of radioiodine uptake (RAIU) is often observed in clinical practice under radioiodine therapy, indicating the challenge for poor prognosis. MicroRNA (miRNA) has emerged as a promising therapeutic target in many diseases; yet, the role of miRNAs in RAIU has not been generally investigated. Based on recent studies about miRNA expression in papillary or follicular thyroid carcinomas, the expression profiles of several thyroid relative miRNAs were investigated in one DTC cell line, derived from normal DTC cells by radioiodine treatment. The top candidate miR-146b, with the most significant overexpression profiles in dedifferentiated cells, was picked up. Further research found that miR-146b could be negatively regulated by histone deacetylase 3 (HDAC3) in normal cells, indicating the correlation between miR-146b and Na{sup +}/I{sup −} symporter (NIS)-mediated RAIU. Fortunately, it was confirmed that miR-146b could regulate NIS expression/activity; what is more important, miR-146b interference would contribute to the recovery of radioiodine-sensitivity in dedifferentiated cells via positively regulating NIS. In the present study, it was concluded that NIS-mediated RAIU could be modulated by miR-146b; accordingly, miR-146b might serve as one of targets to enhance efficacy of radioactive therapy against poorly differential thyroid carcinoma (PDTC). - Highlights: • Significant upregulated miR-146b was picked up from thyroid relative miRNAs in DTC. • MiR-146b was negatively regulated by HDAC3 in normal thyroid carcinoma cells. • NIS activity and expression could be regulated by miR-146b in thyroid carcinoma. • MiR-146b inhibition could recover the decreased radioiodine-sensitivity of DTC cells.

  2. Early second-trimester serum miRNA profiling predicts gestational diabetes mellitus.

    Chun Zhao

    Full Text Available BACKGROUND: Gestational diabetes mellitus (GDM is one type of diabetes that presents during pregnancy and significantly increases the risk of a number of adverse consequences for the fetus and mother. The microRNAs (miRNA have recently been demonstrated to abundantly and stably exist in serum and to be potentially disease-specific. However, no reported study investigates the associations between serum miRNA and GDM. METHODOLOGY/PRINCIPAL FINDINGS: We systematically used the TaqMan Low Density Array followed by individual quantitative reverse transcription polymerase chain reaction assays to screen miRNAs in serum collected at 16-19 gestational weeks. The expression levels of three miRNAs (miR-132, miR-29a and miR-222 were significantly decreased in GDM women with respect to the controls in similar gestational weeks in our discovery evaluation and internal validation, and two miRNAs (miR-29a and miR-222 were also consistently validated in two-centric external validation sample sets. In addition, the knockdown of miR-29a could increase Insulin-induced gene 1 (Insig1 expression level and subsequently the level of Phosphoenolpyruvate Carboxy Kinase2 (PCK2 in HepG2 cell lines. CONCLUSIONS/SIGNIFICANCE: Serum miRNAs are differentially expressed between GDM women and controls and could be candidate biomarkers for predicting GDM. The utility of miR-29a, miR-222 and miR-132 as serum-based non-invasive biomarkers warrants further evaluation and optimization.

  3. Increased risk of sudden cardiac arrest in obstructive pulmonary disease

    Warnier, Miriam Jacoba; Blom, Marieke Tabo; Bardai, Abdennasser

    2013-01-01

    BACKGROUND: We aimed to determine whether (1) patients with obstructive pulmonary disease (OPD) have an increased risk of sudden cardiac arrest (SCA) due to ventricular tachycardia or fibrillation (VT/VF), and (2) the SCA risk is mediated by cardiovascular risk-profile and/or respiratory drug use...... with electrocardiographic documentation of VT/VF were included. Conditional logistic regression analysis was used to assess the association between SCA and OPD. Pre-specified subgroup analyses were performed regarding age, sex, cardiovascular risk-profile, disease severity, and current use of respiratory drugs. RESULTS...... is associated with an increased observed risk of SCA. The most increased risk was observed in patients with a high cardiovascular risk-profile, and in those who received SABA and, possibly, those who received AC at the time of SCA....

  4. Relationship Between Maternal Obesity And Increased Risk Of ...

    Introduction: The incidence of obesity has risen over the past several decades and in spite of advancement in modern medicine, it remains a risk factor for maternal morbidity and mortality. Objective: To determine the association between obesity (increased body mass index) and increased risk of preeclampsia. The possible ...

  5. MiRNA-513a-5p inhibits progesterone receptor expression and constitutes a risk factor for breast cancer: the hOrmone and Diet in the ETiology of breast cancer prospective study.

    Muti, Paola; Donzelli, Sara; Sacconi, Andrea; Hossain, Ahmed; Ganci, Federica; Frixa, Tania; Sieri, Sabina; Krogh, Vittorio; Berrino, Franco; Biagioni, Francesca; Strano, Sabrina; Beyene, Joseph; Yarden, Yosef; Blandino, Giovanni

    2018-02-09

    MicroRNAs (miRNAs) might be considered both predictors and players of cancer development. The aim of the present report was to investigate whether many years before the diagnosis of breast cancer miRNA expression is already disregulated. In order to test this hypothesis, we compared miRNAs extracted from leukocytes in healthy women who later developed breast cancer and in women who remain healthy during the whole 15-year follow-up time. Accordantly, we used a case-control study design nested in the hOrmone and Diet in the ETiology of breast cancer (ORDET) prospective cohort study addressing the possibility that miRNAs can serve as both early biomarkers and components of the hormonal etiological pathways leading to breast cancer development in premenopausal women. We compared leukocyte miRNA profiles of 191 incident premenopausal breast cancer cases and profiles of 191 women who remained healthy over a follow-up period of 20 years. The analysis identified 20 differentially expressed miRNAs in women candidate to develop breast cancer versus control women. The upregulated miRNAs, miR-513-a-5p, miR-513b-5p and miR-513c-5p were among the most significantly deregulated miRNAs. In multivariate analysis, miR-513a-5p upregulation was directly and statistically significant associated with breast cancer risk (OR = 1.69; 95% CI 1.08-2.64; P = 0.0293). In addition, the upregulation of miR-513-a-5p displayed the strongest direct association with serum progesterone and testosterone levels. The experimental data corroborated the inhibitory function of miR-513a-5p on progesterone receptor expression confirming that progesterone receptor is a target of miR-513a-5p. The identification of upregulated miR-513a-5p with its oncogenic potential further validates the use of miRNAs as long-term biomarker of breast cancer risk. © The Author(s) 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  6. Circulating miR-29a and miR-150 correlate with delivered dose during thoracic radiation therapy for non-small cell lung cancer

    Dinh, Tru-Khang T.; Fendler, Wojciech; Chałubińska-Fendler, Justyna; Acharya, Sanket S.; O’Leary, Colin; Deraska, Peter V.; D’Andrea, Alan D.; Chowdhury, Dipanjan; Kozono, David

    2016-01-01

    Risk of normal tissue toxicity limits the amount of thoracic radiation therapy (RT) that can be routinely prescribed to treat non-small cell lung cancer (NSCLC). An early biomarker of response to thoracic RT may provide a way to predict eventual toxicities—such as radiation pneumonitis—during treatment, thereby enabling dose adjustment before the symptomatic onset of late effects. MicroRNAs (miRNAs) were studied as potential serological biomarkers for thoracic RT. As a first step, we sought to identify miRNAs that correlate with delivered dose and standard dosimetric factors. We performed miRNA profiling of plasma samples obtained from five patients with Stage IIIA NSCLC at five dose-points each during radical thoracic RT. Candidate miRNAs were then assessed in samples from a separate cohort of 21 NSCLC patients receiving radical thoracic RT. To identify a cellular source of circulating miRNAs, we quantified in vitro miRNA expression intracellularly and within secreted exosomes in five NSCLC and stromal cell lines. miRNA profiling of the discovery cohort identified ten circulating miRNAs that correlated with delivered RT dose as well as other dosimetric parameters such as lung V20. In the validation cohort, miR-29a-3p and miR-150-5p were reproducibly shown to decrease with increasing radiation dose. Expression of miR-29a-3p and miR-150-5p in secreted exosomes decreased with radiation. This was concomitant with an increase in intracellular levels, suggesting that exosomal export of these miRNAs may be downregulated in both NSCLC and stromal cells in response to radiation. miR-29a-3p and miR-150-5p were identified as circulating biomarkers that correlated with delivered RT dose. miR-150 has been reported to decrease in the circulation of mammals exposed to radiation while miR-29a has been associated with fibrosis in the human heart, lungs, and kidneys. One may therefore hypothesize that outlier levels of circulating miR-29a-3p and miR-150-5p may eventually help

  7. TMEM106B, the risk gene for frontotemporal dementia, is regulated by the miRNA-132/212 cluster and affects progranulin pathways

    Chen-Plotkin, Alice S.; Unger, Travis L.; Gallagher, Michael D.; Bill, Emily; Kwong, Linda K.; Volpicelli-Daley, Laura; Busch, Johanna I.; Akle, Sebastian; Grossman, Murray; Van Deerlin, Vivianna; Trojanowski, John Q.; Lee, Virginia M.-Y.

    2012-01-01

    Frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP) is a fatal neurodegenerative disease with no available treatments. Mutations in the progranulin gene (GRN) causing impaired production or secretion of progranulin are a common Mendelian cause of FTLD-TDP; additionally, common variants at chromosome 7p21 in the uncharacterized gene TMEM106B were recently linked by genome-wide association to FTLD-TDP with and without GRN mutations. Here we show that TMEM106B is neuronally expressed in postmortem human brain tissue, and that expression levels are increased in FTLD-TDP brain. Furthermore, using an unbiased, microarray-based screen of over 800 microRNAs, we identify microRNA-132 as the top microRNA differentiating FTLD-TDP and control brains, with progranulin in late endo-lysosomes, and TMEM106B over-expression increases intracellular levels of progranulin. Thus, TMEM106B is an FTLD-TDP risk gene, with microRNA-132/212 depression as an event which can lead to aberrant over-expression of TMEM106B, which in turn alters progranulin pathways. Evidence for this pathogenic cascade includes the striking convergence of two independent, genomic-scale screens on a microRNA:mRNA regulatory pair. Our findings open novel directions for elucidating miRNA-based therapies in FTLD-TDP. PMID:22895706

  8. The Role of miR-330-3p/PKC-α Signaling Pathway in Low-Dose Endothelial-Monocyte Activating Polypeptide-II Increasing the Permeability of Blood-Tumor Barrier

    Jiahui Liu

    2017-12-01

    Full Text Available This study was performed to determine whether EMAP II increases the permeability of the blood-tumor barrier (BTB by affecting the expression of miR-330-3p as well as its possible mechanisms. We determined the over-expression of miR-330-3p in glioma microvascular endothelial cells (GECs by Real-time PCR. Endothelial monocyte-activating polypeptide-II (EMAP-II significantly decreased the expression of miR-330-3p in GECs. Pre-miR-330-3p markedly decreased the permeability of BTB and increased the expression of tight junction (TJ related proteins ZO-1, occludin and claudin-5, however, anti-miR-330-3p had the opposite effects. Anti-miR-330-3p could enhance the effect of EMAP-II on increasing the permeability of BTB, however, pre-miR-330-3p partly reversed the effect of EMAP-II on that. Similarly, anti-miR-330-3p improved the effects of EMAP-II on increasing the expression levels of PKC-α and p-PKC-α in GECs and pre-miR-330-3p partly reversed the effects. MiR-330-3p could target bind to the 3′UTR of PKC-α. The results of in vivo experiments were similar to those of in vitro experiments. These suggested that EMAP-II could increase the permeability of BTB through inhibiting miR-330-3p which target negative regulation of PKC-α. Pre-miR-330-3p and PKC-α inhibitor decreased the BTB permeability and up-regulated the expression levels of ZO-1, occludin and claudin-5 while anti-miR-330-3p and PKC-α activator brought the reverse effects. Compared with EMAP-II, anti-miR-330-3p and PKC-α activator alone, the combination of the three combinations significantly increased the BTB permeability. EMAP-II combined with anti-miR-330-3p and PKCα activator could enhance the DOX’s effects on inhibiting the cell viabilities and increasing the apoptosis of U87 glioma cells. Our studies suggest that low-dose EMAP-II up-regulates the expression of PKC-α and increases the activity of PKC-α by inhibiting the expression of miR-330-3p, reduces the expression of ZO-1

  9. Increased risk of hyperthyroidism among patients hospitalized with bipolar disorder

    Thomsen, Anders F; Kessing, Lars V

    2005-01-01

    OBJECTIVES: Hyperthyroidism has been associated with affective disorder in many cross-sectional studies, but longitudinal studies in this connection are scarce. We assessed whether hospitalization with depressive disorder or bipolar disorder was a risk factor for development of hyperthyroidism....... METHODS: We conducted a historical cohort study using the Danish register data. The observational period was 1977--99. Three study cohorts were identified: all patients with a first hospital admission with resulting index discharge diagnoses of depression, bipolar disorder, or osteoarthritis. The risks...... with depressive disorder did not have an increased risk of hyperthyroidism, whereas patients with bipolar disorder had an increased of risk on the margin of statistical significance, when compared to patients with osteoarthritis. Patients with bipolar disorder had a significantly increased risk of hyperthyroidism...

  10. Increased Risk of Gallstone Disease Following Colectomy for Ulcerative Colitis

    Mark-Christensen, Anders; Brandsborg, Søren; Laurberg, Søren

    2017-01-01

    Objectives:Biochemical studies suggest that patients who have had a colectomy or restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) are at an increased risk of developing gallstone disease, but epidemiological studies are lacking. We evaluated the risk of gallstone disease follo...

  11. Increased Cardiometabolic Risk and Worsening Hypoxemia at High Altitude

    Miele, Catherine H.; Schwartz, Alan R.; Gilman, Robert H.; Pham, Luu; Wise, Robert A.; Davila-Roman, Victor G.; Jun, Jonathan C.; Polotsky, Vsevolod Y.; Miranda, J. Jaime; Leon-Velarde, Fabiola; Checkley, William

    2016-01-01

    Miele, Catherine H., Alan R. Schwartz, Robert H. Gilman, Luu Pham, Robert A. Wise, Victor G. Davila-Roman, Jonathan C. Jun, Vsevolod Y. Polotsky, J. Jaime Miranda, Fabiola Leon-Velarde, and William Checkley. Increased cardiometabolic risk and worsening hypoxemia at high altitude. High Alt Med Biol. 17:93���100, 2016.���Metabolic syndrome, insulin resistance, diabetes, and dyslipidemia are associated with an increased risk of cardiovascular disease. While excessive erythrocytosis is associated...

  12. Significant increase of Echinococcus multilocularis prevalencein foxes, but no increased predicted risk for humans

    Maas, M.; Dam-Deisz, W.D.C.; Roon, van A.M.; Takumi, K.; Giessen, van der J.W.B.

    2014-01-01

    The emergence of the zoonotic tapeworm Echinococcus multilocularis, causative agent ofalveolar echinococcosis (AE), poses a public health risk. A previously designed risk mapmodel predicted a spread of E. multilocularis and increasing numbers of alveolar echinococ-cosis patients in the province of

  13. Interactions of miR-323/miR-326/miR-329 and miR-130a/miR-155/miR-210 as prognostic indicators for clinical outcome of glioblastoma patients

    Qiu Shuwei

    2013-01-01

    Full Text Available Abstract Background Glioblastoma multiforme (GBM is the most common and aggressive brain tumor with poor clinical outcome. Identification and development of new markers could be beneficial for the diagnosis and prognosis of GBM patients. Deregulation of microRNAs (miRNAs or miRs is involved in GBM. Therefore, we attempted to identify and develop specific miRNAs as prognostic and predictive markers for GBM patient survival. Methods Expression profiles of miRNAs and genes and the corresponding clinical information of 480 GBM samples from The Cancer Genome Atlas (TCGA dataset were downloaded and interested miRNAs were identified. Patients’ overall survival (OS and progression-free survival (PFS associated with interested miRNAs and miRNA-interactions were performed by Kaplan-Meier survival analysis. The impacts of miRNA expressions and miRNA-interactions on survival were evaluated by Cox proportional hazard regression model. Biological processes and network of putative and validated targets of miRNAs were analyzed by bioinformatics. Results In this study, 6 interested miRNAs were identified. Survival analysis showed that high levels of miR-326/miR-130a and low levels of miR-323/miR-329/miR-155/miR-210 were significantly associated with long OS of GBM patients, and also showed that high miR-326/miR-130a and low miR-155/miR-210 were related with extended PFS. Moreover, miRNA-323 and miRNA-329 were found to be increased in patients with no-recurrence or long time to progression (TTP. More notably, our analysis revealed miRNA-interactions were more specific and accurate to discriminate and predict OS and PFS. This interaction stratified OS and PFS related with different miRNA levels more detailed, and could obtain longer span of mean survival in comparison to that of one single miRNA. Moreover, miR-326, miR-130a, miR-155, miR-210 and 4 miRNA-interactions were confirmed for the first time as independent predictors for survival by Cox regression model

  14. Mutations Inactivating Herpes Simplex Virus 1 MicroRNA miR-H2 Do Not Detectably Increase ICP0 Gene Expression in Infected Cultured Cells or Mouse Trigeminal Ganglia.

    Pan, Dongli; Pesola, Jean M; Li, Gang; McCarron, Seamus; Coen, Donald M

    2017-01-15

    Herpes simplex virus 1 (HSV-1) latency entails the repression of productive ("lytic") gene expression. An attractive hypothesis to explain some of this repression involves inhibition of the expression of ICP0, a lytic gene activator, by a viral microRNA, miR-H2, which is completely complementary to ICP0 mRNA. To test this hypothesis, we engineered mutations that disrupt miR-H2 without affecting ICP0 in HSV-1. The mutant virus exhibited drastically reduced expression of miR-H2 but showed wild-type levels of infectious virus production and no increase in ICP0 expression in lytically infected cells, which is consistent with the weak expression of miR-H2 relative to the level of ICP0 mRNA in that setting. Following corneal inoculation of mice, the mutant was not significantly different from wild-type virus in terms of infectious virus production in the trigeminal ganglia during acute infection, mouse mortality, or the rate of reactivation from explanted latently infected ganglia. Critically, the mutant was indistinguishable from wild-type virus for the expression of ICP0 and other lytic genes in acutely and latently infected mouse trigeminal ganglia. The latter result may be related to miR-H2 being less effective in inhibiting ICP0 expression in transfection assays than a host microRNA, miR-138, which has previously been shown to inhibit lytic gene expression in infected ganglia by targeting ICP0 mRNA. Additionally, transfected miR-138 reduced lytic gene expression in infected cells more effectively than miR-H2. While this study provides little support for the hypothesis that miR-H2 promotes latency by inhibiting ICP0 expression, the possibility remains that miR-H2 might target other genes during latency. Herpes simplex virus 1 (HSV-1), which causes a variety of diseases, can establish lifelong latent infections from which virus can reactivate to cause recurrent disease. Latency is the most biologically interesting and clinically vexing feature of the virus. Ever since

  15. Genetic variants in CETP increase risk of intracerebral hemorrhage

    Anderson, C.D.; Falcone, G.J.; Phuah, C.L.; Radmanesh, F.; Brouwers, H.B.; Battey, T.W.; Biffi, A.; Peloso, G.M.; Liu, D.J.; Ayres, A.M.; Goldstein, J.N.; Viswanathan, A.; Greenberg, S.M.; Selim, M.; Meschia, J.F.; Brown, D.L.; Worrall, B.B.; Silliman, S.L.; Tirschwell, D.L.; Flaherty, M.L.; Kraft, P.; Jagiella, J.M.; Schmidt, H.; Hansen, B.M.; Jimenez-Conde, J.; Giralt-Steinhauer, E.; Elosua, R.; Cuadrado-Godia, E.; Soriano, C.; Nieuwenhuizen, K.M. van; Klijn, C.J.M.; Rannikmae, K.; Samarasekera, N.; Salman, R.A.; Sudlow, C.L.; Deary, I.J.; Morotti, A.; Pezzini, A.; Pera, J.; Urbanik, A.; Pichler, A.; Enzinger, C.; Norrving, B.; Montaner, J.; Fernandez-Cadenas, I.; Delgado, P.; Roquer, J.; Lindgren, A.; Slowik, A.; Schmidt, R.; Kidwell, C.S.; Kittner, S.J.; Waddy, S.P.; Langefeld, C.D.; Abecasis, G.; Willer, C.J.; Kathiresan, S.; Woo, D.; Rosand, J.

    2016-01-01

    OBJECTIVE: In observational epidemiologic studies, higher plasma high-density lipoprotein cholesterol (HDL-C) has been associated with increased risk of intracerebral hemorrhage (ICH). DNA sequence variants that decrease cholesteryl ester transfer protein (CETP) gene activity increase plasma HDL-C;

  16. Genetic variants in CETP increase risk of intracerebral hemorrhage

    Anderson, Christopher D.; Falcone, Guido J.; Phuah, Chia Ling; Radmanesh, Farid; Brouwers, H. Bart; Battey, Thomas W K; Biffi, Alessandro; Peloso, Gina M.; Liu, Dajiang J.; Ayres, Alison M.; Goldstein, Joshua N.; Viswanathan, Anand; Greenberg, Steven M.; Selim, Magdy; Meschia, James F.; Brown, Devin L.; Worrall, Bradford B.; Silliman, Scott L.; Tirschwell, David L.; Flaherty, Matthew L.; Kraft, Peter; Jagiella, Jeremiasz M.; Schmidt, Helena; Hansen, Björn M.; Jimenez-Conde, Jordi; Giralt-Steinhauer, Eva; Elosua, Roberto; Cuadrado-Godia, Elisa; Soriano, Carolina; van Nieuwenhuizen, Koen M.; Klijn, Catharina J M; Rannikmae, Kristiina; Samarasekera, Neshika; Salman, Rustam Al Shahi; Sudlow, Catherine L.; Deary, Ian J.; Morotti, Andrea; Pezzini, Alessandro; Pera, Joanna; Urbanik, Andrzej; Pichler, Alexander; Enzinger, Christian; Norrving, Bo; Montaner, Joan; Fernandez-Cadenas, Israel; Delgado, Pilar; Roquer, Jaume; Lindgren, Arne; Slowik, Agnieszka; Schmidt, Reinhold; Kidwell, Chelsea S.; Kittner, Steven J.; Waddy, Salina P.; Langefeld, Carl D.; Abecasis, Goncalo; Willer, Cristen J.; Kathiresan, Sekar; Woo, Daniel; Rosand, Jonathan

    2016-01-01

    Objective: In observational epidemiologic studies, higher plasma high-density lipoprotein cholesterol (HDL-C) has been associated with increased risk of intracerebral hemorrhage (ICH). DNA sequence variants that decrease cholesteryl ester transfer protein (CETP) gene activity increase plasma HDL-C;

  17. On capital allocation for stochastic arrangement increasing actuarial risks

    Pan Xiaoqing

    2017-01-01

    Full Text Available This paper studies the increasing convex ordering of the optimal discounted capital allocations for stochastic arrangement increasing risks with stochastic arrangement decreasing occurrence times. The application to optimal allocation of policy limits is presented as an illustration as well.

  18. Increased stomach cancer risk following radiotherapy for testicular cancer

    Hauptmann, M; Fossa, S D; Stovall, M

    2015-01-01

    BACKGROUND: Abdominal radiotherapy for testicular cancer (TC) increases risk for second stomach cancer, although data on the radiation dose-response relationship are sparse. METHODS: In a cohort of 22,269 5-year TC survivors diagnosed during 1959-1987, doses to stomach subsites were estimated...... for 92 patients who developed stomach cancer and 180 matched controls. Chemotherapy details were recorded. Odds ratios (ORs) were estimated using logistic regression. RESULTS: Cumulative incidence of second primary stomach cancer was 1.45% at 30 years after TC diagnosis. The TC survivors who received...... radiotherapy (87 (95%) cases, 151 (84%) controls) had a 5.9-fold (95% confidence interval (CI) 1.7-20.7) increased risk of stomach cancer. Risk increased with increasing stomach dose (P-trend

  19. Vaginal dysbiosis increases risk of preterm fetal membrane rupture, neonatal sepsis and is exacerbated by erythromycin.

    Brown, Richard G; Marchesi, Julian R; Lee, Yun S; Smith, Ann; Lehne, Benjamin; Kindinger, Lindsay M; Terzidou, Vasso; Holmes, Elaine; Nicholson, Jeremy K; Bennett, Phillip R; MacIntyre, David A

    2018-01-24

    Preterm prelabour rupture of the fetal membranes (PPROM) precedes 30% of preterm births and is a risk factor for early onset neonatal sepsis. As PPROM is strongly associated with ascending vaginal infection, prophylactic antibiotics are widely used. The evolution of vaginal microbiota compositions associated with PPROM and the impact of antibiotics on bacterial compositions are unknown. We prospectively assessed vaginal microbiota prior to and following PPROM using MiSeq-based sequencing of 16S rRNA gene amplicons and examined the impact of erythromycin prophylaxis on bacterial load and community structures. In contrast to pregnancies delivering at term, vaginal dysbiosis characterised by Lactobacillus spp. depletion was present prior to the rupture of fetal membranes in approximately a third of cases (0% vs. 27%, P = 0.026) and persisted following membrane rupture (31%, P = 0.005). Vaginal dysbiosis was exacerbated by erythromycin treatment (47%, P = 0.00009) particularly in women initially colonised by Lactobacillus spp. Lactobacillus depletion and increased relative abundance of Sneathia spp. were associated with subsequent funisitis and early onset neonatal sepsis. Our data show that vaginal microbiota composition is a risk factor for subsequent PPROM and is associated with adverse short-term maternal and neonatal outcomes. This highlights vaginal microbiota as a potentially modifiable antenatal risk factor for PPROM and suggests that routine use of erythromycin for PPROM be re-examined.

  20. Polygenic risk score is associated with increased disease risk in 52 Finnish breast cancer families

    Muranen, Taru A.; Mavaddat, Nasim; Khan, Sofia; Fagerholm, Rainer; Pelttari, Liisa; Lee, Andrew; Aittom?ki, Kristiina; Blomqvist, Carl; Easton, Douglas F.; Nevanlinna, Heli

    2016-01-01

    The risk of developing breast cancer is increased in women with family history of breast cancer and particularly in families with multiple cases of breast or ovarian cancer. Nevertheless, many women with a positive family history never develop the disease. Polygenic risk scores (PRSs) based on the risk effects of multiple common genetic variants have been proposed for individual risk assessment on a population level. We investigate the applicability of the PRS for risk prediction within breas...

  1. Cisplatin-resistant lung cancer cell-derived exosomes increase cisplatin resistance of recipient cells in exosomal miR-100-5p-dependent manner.

    Qin, Xiaobing; Yu, Shaorong; Zhou, Leilei; Shi, Meiqi; Hu, Yong; Xu, Xiaoyue; Shen, Bo; Liu, Siwen; Yan, Dali; Feng, Jifeng

    2017-01-01

    Exosomes derived from lung cancer cells confer cisplatin (DDP) resistance to other cancer cells. However, the underlying mechanism is still unknown. A549 resistance to DDP (A549/DDP) was established. Microarray was used to analyze microRNA (miRNA) expression profiles of A549 cells, A549/DDP cells, A549 exosomes, and A549/DDP exosomes. There was a strong correlation of miRNA profiles between exosomes and their maternal cells. A total of 11 miRNAs were significantly upregulated both in A549/DDP cells compared with A549 cells and in exosomes derived from A549/DDP cells in contrast to exosomes from A549 cells. A total of 31 downregulated miRNAs were also observed. miR-100-5p was the most prominent decreased miRNA in DDP-resistant exosomes compared with the corresponding sensitive ones. Downregulated miR-100-5p was proved to be involved in DDP resistance in A549 cells, and mammalian target of rapamycin (mTOR) expression was reverse regulated by miR-100-5p. Exosomes confer recipient cells' resistance to DDP in an exosomal miR-100-5p-dependent manner with mTOR as its potential target both in vitro and in vivo. Exosomes from DDP-resistant lung cancer cells A549 can alter other lung cancer cells' sensitivity to DDP in exosomal miR-100-5p-dependent manner. Our study provides new insights into the molecular mechanism of DDP resistance in lung cancer.

  2. Increased Correlation in Bear markets: A Downside Risk Perspective

    Campbell, Rachel; Koedijk, Kees; Kofman, Paul

    2002-01-01

    A number of studies have provided evidence of increased correlation in global financial market returns during bear markets. Others, however, have shown that some of this evidence may have been biased. We derive an alternative estimator for implied correlation based on portfolio downside risk measures that does not suffer from this bias. These unbiased quantile correlation estimates are directly applicable to portfolio optimization and to risk management techniques in general. This simple and ...

  3. Association of Increased Prenatal Estrogen With Risk Factors for Schizophrenia

    Brown, James S.

    2010-01-01

    The author previously described a theoretical cause of schizophrenia based on the effects of estrogenic endocrine disruption. In the current review, the author describes how increased estrogen during pregnancy increases susceptibility to certain viral infections associated with increased risk for schizophrenia. The review further discusses how prenatal estrogen exposure could explain associations of schizophrenia with autoimmune diseases, urban environments, and stress. Based on the associati...

  4. Pet ownership increases human risk of encountering ticks.

    Jones, E H; Hinckley, A F; Hook, S A; Meek, J I; Backenson, B; Kugeler, K J; Feldman, K A

    2018-02-01

    We examined whether pet ownership increased the risk for tick encounters and tickborne disease among residents of three Lyme disease-endemic states as a nested cohort within a randomized controlled trial. Information about pet ownership, use of tick control for pets, property characteristics, tick encounters and human tickborne disease were captured through surveys, and associations were assessed using univariate and multivariable analyses. Pet-owning households had 1.83 times the risk (95% CI = 1.53, 2.20) of finding ticks crawling on and 1.49 times the risk (95% CI = 1.20, 1.84) of finding ticks attached to household members compared to households without pets. This large evaluation of pet ownership, human tick encounters and tickborne diseases shows that pet owners, whether of cats or dogs, are at increased risk of encountering ticks and suggests that pet owners are at an increased risk of developing tickborne disease. Pet owners should be made aware of this risk and be reminded to conduct daily tick checks of all household members, including the pets, and to consult their veterinarian regarding effective tick control products. © 2017 Blackwell Verlag GmbH.

  5. Increasing stress on disaster risk finance due to large floods

    Jongman, Brenden; Hochrainer-Stigler, Stefan; Feyen, Luc; Aerts, Jeroen; Mechler, Reinhard; Botzen, Wouter; Bouwer, Laurens; Pflug, Georg; Rojas, Rodrigo; Ward, Philip

    2014-05-01

    Recent major flood disasters have shown that single extreme events can affect multiple countries simultaneously, which puts high pressure on trans-national risk reduction and risk transfer mechanisms. To date, little is known about such flood hazard interdependencies across regions, and the corresponding joint risks at regional to continental scales. Reliable information on correlated loss probabilities is crucial for developing robust insurance schemes and public adaptation funds, and for enhancing our understanding of climate change impacts. Here we show that extreme discharges are strongly correlated across European river basins and that these correlations can, or should, be used in national to continental scale risk assessment. We present probabilistic trends in continental flood risk, and demonstrate that currently observed extreme flood losses could more than double in frequency by 2050 under future climate change and socioeconomic development. The results demonstrate that accounting for tail dependencies leads to higher estimates of extreme losses than estimates based on the traditional assumption of independence between basins. We suggest that risk management for these increasing losses is largely feasible, and we demonstrate that risk can be shared by expanding risk transfer financing, reduced by investing in flood protection, or absorbed by enhanced solidarity between countries. We conclude that these measures have vastly different efficiency, equity and acceptability implications, which need to be taken into account in broader consultation, for which our analysis provides a basis.

  6. miR-434-3p and DNA hypomethylation co-regulate eIF5A1 to increase AChRs and to improve plasticity in SCT rat skeletal muscle.

    Shang, Fei-Fei; Xia, Qing-Jie; Liu, Wei; Xia, Lei; Qian, Bao-Jiang; You, Ling; He, Mu; Yang, Jin-Liang; Wang, Ting-Hua

    2016-03-11

    Acetylcholine receptors (AChRs) serve as connections between motor neurons and skeletal muscle and are essential for recovery from spinal cord transection (SCT). Recently, microRNAs have emerged as important potential biotherapeutics for several diseases; however, whether miRNAs operate in the modulation of AChRs remains unknown. We found increased AChRs numbers and function scores in rats with SCT; these increases were reduced following the injection of a eukaryotic translation initiation factor 5A1 (eIF5A1) shRNA lentivirus into the hindlimb muscle. Then, high-throughput screening for microRNAs targeting eIF5A1 was performed, and miR-434-3p was found to be robustly depleted in SCT rat skeletal muscle. Furthermore, a highly conserved miR-434-3p binding site was identified within the mRNA encoding eIF5A1 through bioinformatics analysis and dual-luciferase assay. Overexpression or knockdown of miR-434-3p in vivo demonstrated it was a negative post-transcriptional regulator of eIF5A1 expression and influenced AChRs expression. The microarray-enriched Gene Ontology (GO) terms regulated by miR-434-3p were muscle development terms. Using a lentivirus, one functional gene (map2k6) was confirmed to have a similar function to that of miR-434-3p in GO terms. Finally, HRM and MeDIP-PCR analyses revealed that DNA demethylation also up-regulated eIF5A1 after SCT. Consequently, miR-434-3p/eIF5A1 in muscle is a promising potential biotherapy for SCI repair.

  7. Increasing resilience through participative flood risk map design

    Fuchs, Sven; Spira, Yvonne; Stickler, Therese

    2013-04-01

    In recent years, an increasing number of flood hazards has shown to the European Commission and the Member States of the European Union the importance of flood risk management strategies in order to reduce losses and to protect the environment and the citizens. Exposure to floods as well as flood vulnerability might increase across Europe due to the ongoing economic development in many EU countries. Thus even without taking climate change into account an increase of flood disasters in Europe might be foreseeable. These circumstances have produced a reaction in the European Commission, and a Directive on the Assessment and Management of Flood Risks was issued as one of the three components of the European Action Programme on Flood Risk Management. Floods have the potential to jeopardise economic development, above all due to an increase of human activities in floodplains and the reduction of natural water retention by land use activities. As a result, an increase in the likelihood and adverse impacts of flood events is expected. Therefore, concentrated action is needed at the European level to avoid severe impacts on human life and property. In order to have an effective tool available for gathering information, as well as a valuable basis for priority setting and further technical, financial and political decisions regarding flood risk mitigation and management, it is necessary to provide for the establishment of flood risk maps which show the potential adverse consequences associated with different flood scenarios. So far, hazard and risk maps are compiled in terms of a top-down linear approach: planning authorities take the responsibility to create and implement these maps on different national and local scales, and the general public will only be informed about the outcomes (EU Floods Directive, Article 10). For the flood risk management plans, however, an "active involvement of interested parties" is required, which means at least some kind of multilateral

  8. Shrimp miR-10a Is Co-opted by White Spot Syndrome Virus to Increase Viral Gene Expression and Viral Replication

    Jiun-Yan Huang

    2017-09-01

    Full Text Available Members of the microRNA miR-10 family are highly conserved and play many important roles in diverse biological mechanisms, including immune-related responses and cancer-related processes in certain types of cancer. In this study, we found the most highly upregulated shrimp microRNA from Penaeus vannamei during white spot syndrome virus (WSSV infection was miR-10a. After confirming the expression level of miR-10a by northern blot and quantitative RT-PCR, an in vivo experiment showed that the viral copy number was decreased in miR-10a-inhibited shrimp. We found that miR-10a targeted the 5′ untranslated region (UTR of at least three viral genes (vp26, vp28, and wssv102, and plasmids that were controlled by the 5′ UTR of these genes produced enhanced luciferase signals in transfected SF9 cells. These results suggest a previously unreported role for shrimp miR-10a and even a new type of host–virus interaction, whereby a co-opts the key cellular regulator miR-10a to globally enhance the translation of viral proteins.

  9. Shrimp miR-10a Is Co-opted by White Spot Syndrome Virus to Increase Viral Gene Expression and Viral Replication.

    Huang, Jiun-Yan; Kang, Shih-Ting; Chen, I-Tung; Chang, Li-Kwan; Lin, Shih-Shun; Kou, Guang-Hsiung; Chu, Chia-Ying; Lo, Chu-Fang

    2017-01-01

    Members of the microRNA miR-10 family are highly conserved and play many important roles in diverse biological mechanisms, including immune-related responses and cancer-related processes in certain types of cancer. In this study, we found the most highly upregulated shrimp microRNA from Penaeus vannamei during white spot syndrome virus (WSSV) infection was miR-10a. After confirming the expression level of miR-10a by northern blot and quantitative RT-PCR, an in vivo experiment showed that the viral copy number was decreased in miR-10a-inhibited shrimp. We found that miR-10a targeted the 5' untranslated region (UTR) of at least three viral genes ( vp26, vp28 , and wssv102 ), and plasmids that were controlled by the 5' UTR of these genes produced enhanced luciferase signals in transfected SF9 cells. These results suggest a previously unreported role for shrimp miR-10a and even a new type of host-virus interaction, whereby a co-opts the key cellular regulator miR-10a to globally enhance the translation of viral proteins.

  10. Long working hours may increase risk of coronary heart disease.

    Kang, Mo-Yeol; Cho, Soo-Hun; Yoo, Min-Sang; Kim, Taeshik; Hong, Yun-Chul

    2014-11-01

    To evaluate the association between long working hours and risk of coronary heart disease (CHD) estimated by Framingham risk score (FRS) in Korean adults. This study evaluated adult participants in Korean National Health and Nutrition Examination Survey IV (2007-2009). After inclusion and exclusion criteria were applied, the final sample size for this study model was 8,350. Subjects were asked about working hours and health status. Participants also completed physical examinations and biochemical measurement necessary for estimation of FRS. Multiple logistic regression was conducted to investigate the association between working hours and 10-year risk for CHD estimated by FRS. Compared to those who work 31-40 hr, significantly higher 10-year risk was estimated among subjects working longer hours. As working hours increased, odds ratio (OR) for upper 10 percent of estimated 10-year risk for CHD was increased up to 1.94. Long working hours are significantly related to risk of coronary heart disease. © 2014 Wiley Periodicals, Inc.

  11. Risk based maintenance to increase safety and decrease costs

    Phillips, J.H.

    2000-01-01

    Risk-Based techniques have been developed for commercial nuclear power plants for the last eight years by a team working through the ASME Center for Research and Technology Development (CRTD). System boundaries and success criteria is defined using the Probabilistic Risk Analysis or Probabilistic Safety Analysis developed to meet the Individual Plant Evaluation. Final ranking of components is by a plant expert panel similar to the one developed for the Maintenance Rule. Components are identified as being high risk-significant or low risk-significant. Maintenance and resources are focused on those components that have the highest risk-significance. The techniques have been developed and applied at a number of plants. Results from the first risk-based inspection pilot plant indicates safety due to pipe failure can be doubled while the inspection reduced to about 80% when compared with current inspection programs. Pilot studies on risk-based testing indicate that about 60% of pumps and 25 to 30% of valves in plants are high safety-significant The reduction in inspection and testing reduces the person-rem exposure and resulting in further increases in safety. These techniques have been documented in publications by the ASME CRTD which are referenced. (author)

  12. Increased risk of antidepressant use in childhood cancer survivors

    Lund, Lasse Wegener; Winther, J.F.; Cederkvist, L

    2015-01-01

    to the National Prescription Drug Database, which worldwide is the oldest nationwide registry of prescription medication. Hazard ratios (HRs) for antidepressant use were estimated in a Cox proportional hazards model stratified on sex, with population comparisons as referents. RESULTS: Overall, childhood cancer......AIM: Childhood cancer survivors are at risk of both somatic and mental late effects, but large population-based studies of depression are lacking. METHODS: Risk of antidepressant use was evaluated in a population-based cohort of 5452 Danish children treated for cancer in 1975-2009 by linkage....... Increased HRs of 30-50% were seen for survivors of cancers of all main groups (haematological malignancies, central nervous system (CNS) and solid tumors); the highest risk was among children treated with haematopoietic stem cell transplantation (HR, 1.9; 95% CI, 1.2-3.1). Our data suggested that the risk...

  13. Debunking vaccination myths: strong risk negations can increase perceived vaccination risks.

    Betsch, Cornelia; Sachse, Katharina

    2013-02-01

    Information about risks is often contradictory, especially in the health domain. A vast amount of bizarre information on vaccine-adverse events (VAE) can be found on the Internet; most are posted by antivaccination activists. Several actors in the health sector struggle against these statements by negating claimed risks with scientific explanations. The goal of the present work is to find optimal ways of negating risk to decrease risk perceptions. In two online experiments, we varied the extremity of risk negations and their source. Perception of the probability of VAE, their expected severity (both variables serve as indicators of perceived risk), and vaccination intentions. Paradoxically, messages strongly indicating that there is "no risk" led to a higher perceived vaccination risk than weak negations. This finding extends previous work on the negativity bias, which has shown that information stating the presence of risk decreases risk perceptions, while information negating the existence of risk increases such perceptions. Several moderators were also tested; however, the effect occurred independently of the number of negations, recipient involvement, and attitude. Solely the credibility of the information source interacted with the extremity of risk negation: For credible sources (governmental institutions), strong and weak risk negations lead to similar perceived risk, while for less credible sources (pharmaceutical industries) weak negations lead to less perceived risk than strong negations. Optimal risk negation may profit from moderate rather than extreme formulations as a source's trustworthiness can vary.

  14. Mobile Motion Capture--MiMiC.

    Harbert, Simeon D; Jaiswal, Tushar; Harley, Linda R; Vaughn, Tyler W; Baranak, Andrew S

    2013-01-01

    The low cost, simple, robust, mobile, and easy to use Mobile Motion Capture (MiMiC) system is presented and the constraints which guided the design of MiMiC are discussed. The MiMiC Android application allows motion data to be captured from kinematic modules such as Shimmer 2r sensors over Bluetooth. MiMiC is cost effective and can be used for an entire day in a person's daily routine without being intrusive. MiMiC is a flexible motion capture system which can be used for many applications including fall detection, detection of fatigue in industry workers, and analysis of individuals' work patterns in various environments.

  15. Does vital exhaustion increase the risk of type 2 diabetes?

    Volden, Sasia; Wimmelmann, Cathrine Lawaetz; Flensborg-Madsen, Trine

    2017-01-01

    Hospital Discharge Register to detect registrations with type 2 diabetes until 2014. Results: A high degree of VE was associated with an increased risk of developing type 2 diabetes in both substudies. In the first substudy, the OR for developing type 2 diabetes was 2.56 (95% CI, 1.53; 4,29, P ...Background: There is evidence that both stress and depression have a causal relationship with type 2 diabetes suggesting that vital exhaustion (VE) too could be a risk factor. The association between VE and type 2 diabeteshas, however, not been investigated prospectively. Aim: To prospectively...... investigate whether VE is associated with an increased risk of type 2 diabetes in a Danish population. Methods: A prospective cohort study based on the Copenhagen City Heart Study (1991–1993). The degree of VE was measured among 9075 participants without type 1 or 2 diabetes at baseline. To detect type 2...

  16. Increased pancreatic cancer risk following radiotherapy for testicular cancer.

    Hauptmann, Michael; Børge Johannesen, Tom; Gilbert, Ethel S; Stovall, Marilyn; van Leeuwen, Flora E; Rajaraman, Preetha; Smith, Susan A; Weathers, Rita E; Aleman, Berthe M P; Andersson, Michael; Curtis, Rochelle E; Dores, Graça M; Fraumeni, Joseph F; Hall, Per; Holowaty, Eric J; Joensuu, Heikki; Kaijser, Magnus; Kleinerman, Ruth A; Langmark, Frøydis; Lynch, Charles F; Pukkala, Eero; Storm, Hans H; Vaalavirta, Leila; van den Belt-Dusebout, Alexandra W; Morton, Lindsay M; Fossa, Sophie D; Travis, Lois B

    2016-09-27

    Pancreatic cancer risk is elevated among testicular cancer (TC) survivors. However, the roles of specific treatments are unclear. Among 23 982 5-year TC survivors diagnosed during 1947-1991, doses from radiotherapy to the pancreas were estimated for 80 pancreatic cancer patients and 145 matched controls. Chemotherapy details were recorded. Logistic regression was used to estimate odds ratios (ORs). Cumulative incidence of second primary pancreatic cancer was 1.1% at 30 years after TC diagnosis. Radiotherapy (72 (90%) cases and 115 (80%) controls) was associated with a 2.9-fold (95% confidence interval (CI) 1.0-7.8) increased risk. The OR increased linearly by 0.12 per Gy to the pancreas (P-trendcancer risk, and persists for over 20 years. These excesses, although small, should be considered when radiotherapy with exposure to the pancreas is considered for newly diagnosed patients. Additional data are needed on the role of chemotherapy.

  17. Increased Suicide Risk in Patients with Hidradenitis Suppurativa

    Thorlacius, Linnea; Cohen, Arnon D; Gislason, Gunnar H

    2018-01-01

    Patients with skin disorders are considered at a higher risk of depression and anxiety than the background population. Patients with hidradenitis suppurativa (HS) may be particularly affected. We explored the association between HS and depression, anxiety, and completed suicides in the Danish...... nonsignificant association with depression (odds ratio [95% confidence interval] = 1.13; 0.87-1.47]; P = 0.36 and hospitalization due to depression (1.32 [0.94-1.85]; P = 0.1083). To the best of our knowledge, no previous studies have reported on the increased risk of completed suicide among HS patients...... national registries, expanding to include data on suicidal behavior, using both a cross-sectional and a cohort study design. Both designs included 7,732 patients with HS and a background population of 4,354,137. The cohort study revealed that HS patients had an increased risk of completed suicide after...

  18. Early menarche is associated with increased risk of asthma

    Lieberoth, Sofie; Gade, Elisabeth; Kyvik, Kirsten Ohm

    2015-01-01

    in girls with early menarche compared to girls without early menarche (7.4 vs. 4.5%), OR = 1.71 (1.31-2.22), p increased by 8% (1-15%), p = 0...... in discordant monozygotic and dizygotic twins. CONCLUSION: Early menarche is associated with increased risk of asthma among Danish female twins independently of BMI, age, physical activity, educational level and smoking. Results indicate a complex relationship possibly mediated through innate and non...

  19. Rare disaster information can increase risk-taking

    Newell, Ben R.; Rakow, Tim; Yechiam, Eldad; Sambur, Michael

    2016-02-01

    The recent increase in the frequency and impact of natural disasters highlights the need to provide the public with accurate information concerning disaster prevalence. Most approaches to this problem assume that providing summaries of the nature and scale of disasters will lead people to reduce their exposure to risk. Here we present experimental evidence that such ex post `news reports’ of disaster occurrences can increase the tolerance for risk-taking (which implies that rare events are underweighted). This result is robust across several hundred rounds of choices in a simulated microworld, persists even when the long-run expected value of risky choices is substantially lower than safe choices, and is contingent on providing risk information about disasters that have been (personally) experienced and those that have been avoided (`forgone’ outcomes). The results suggest that augmenting personal experience with information summaries of the number of adverse events (for example, storms, floods) in different regions may, paradoxically, increase the appeal of a disaster-prone region. This finding implies a need to communicate long-term trends in severe climatic events, thereby reinforcing the accumulation of events, and the increase in their associated risks, across time.

  20. Type 2 Diabetes Mellitus and Increased Risk for Malaria Infection

    This podcast describes research done in Ghana examining a correlation between type 2 diabetes and a possible increased risk for malaria infection in adults. Dr. Manoj Menon, a medical officer in the Division of Parasitic Diseases and Malaria in the Center for Global Health, discusses questions the study raises.

  1. Increasing Risk Awareness: The Coastal Community Resilience Index

    Thompson, Jody A.; Sempier, Tracie; Swann, LaDon

    2012-01-01

    As the number of people moving to the Gulf Coast increases, so does the risk of exposure to floods, hurricanes, and other storm-related events. In an effort to assist communities in preparing for future storm events, the Coastal Community Resilience Index was created. The end result is for communities to take actions to address the weaknesses they…

  2. Does Childhood Disability Increase Risk for Child Abuse and Neglect?

    Leeb, Rebecca T.; Bitsko, Rebecca H.; Merrick, Melissa T.; Armour, Brian S.

    2012-01-01

    In this article we review the empirical evidence for the presumptions that children with disabilities are at increased risk for child maltreatment, and parents with disabilities are more likely to perpetrate child abuse and neglect. Challenges to the epidemiological examination of the prevalence of child maltreatment and disabilities are…

  3. Peculiarities of territorial governing in the area of increased risk

    Marchinskas, A.

    1998-01-01

    The area of Ignalina NPP can be evaluated from the standpoint of governing as the area of increased risk territory (zone), so the local administration should acquire a specific status. The results of expert examination show insufficient efficiency of the administration's activity, it's orientation to quantitative results. An objective fund is necessary for the supporting the local administration and population of this area. (author)

  4. People with Increased Risk of Eye Damage from UV Light

    ... With Increased Risk of Eye Damage from UV Light Leer en Español: Algunas Personas Están en Mayor Riesgo de Sufrir Daño Ocular por los Rayos UV Written By: Shirley Dang Apr. 30, 2014 Everyone of any age and any degree of skin pigmentation is susceptible to UV damage. Children are ...

  5. Patients with chronic pancreatitis are at increased risk for osteoporosis.

    Duggan, SN

    2012-10-01

    Patients with chronic pancreatitis may be at an increased risk of low bone density because of malabsorption of vitamin D and calcium, poor diet, pain, alcoholism, and smoking. We investigated the rates of osteoporosis in patients with chronic pancreatitis compared to matched controls.

  6. Climate change and sugarcane expansion increase Hantavirus infection risk.

    Prist, Paula Ribeiro; Uriarte, María; Fernandes, Katia; Metzger, Jean Paul

    2017-07-01

    Hantavirus Cardiopulmonary Syndrome (HCPS) is a disease caused by Hantavirus, which is highly virulent for humans. High temperatures and conversion of native vegetation to agriculture, particularly sugarcane cultivation can alter abundance of rodent generalist species that serve as the principal reservoir host for HCPS, but our understanding of the compound effects of land use and climate on HCPS incidence remains limited, particularly in tropical regions. Here we rely on a Bayesian model to fill this research gap and to predict the effects of sugarcane expansion and expected changes in temperature on Hantavirus infection risk in the state of São Paulo, Brazil. The sugarcane expansion scenario was based on historical data between 2000 and 2010 combined with an agro-environment zoning guideline for the sugar and ethanol industry. Future evolution of temperature anomalies was derived using 32 general circulation models from scenarios RCP4.5 and RCP8.5 (Representative greenhouse gases Concentration Pathways adopted by IPCC). Currently, the state of São Paulo has an average Hantavirus risk of 1.3%, with 6% of the 645 municipalities of the state being classified as high risk (HCPS risk ≥ 5%). Our results indicate that sugarcane expansion alone will increase average HCPS risk to 1.5%, placing 20% more people at HCPS risk. Temperature anomalies alone increase HCPS risk even more (1.6% for RCP4.5 and 1.7%, for RCP8.5), and place 31% and 34% more people at risk. Combined sugarcane and temperature increases led to the same predictions as scenarios that only included temperature. Our results demonstrate that climate change effects are likely to be more severe than those from sugarcane expansion. Forecasting disease is critical for the timely and efficient planning of operational control programs that can address the expected effects of sugarcane expansion and climate change on HCPS infection risk. The predicted spatial location of HCPS infection risks obtained here can be

  7. Climate change and sugarcane expansion increase Hantavirus infection risk.

    Paula Ribeiro Prist

    2017-07-01

    Full Text Available Hantavirus Cardiopulmonary Syndrome (HCPS is a disease caused by Hantavirus, which is highly virulent for humans. High temperatures and conversion of native vegetation to agriculture, particularly sugarcane cultivation can alter abundance of rodent generalist species that serve as the principal reservoir host for HCPS, but our understanding of the compound effects of land use and climate on HCPS incidence remains limited, particularly in tropical regions. Here we rely on a Bayesian model to fill this research gap and to predict the effects of sugarcane expansion and expected changes in temperature on Hantavirus infection risk in the state of São Paulo, Brazil. The sugarcane expansion scenario was based on historical data between 2000 and 2010 combined with an agro-environment zoning guideline for the sugar and ethanol industry. Future evolution of temperature anomalies was derived using 32 general circulation models from scenarios RCP4.5 and RCP8.5 (Representative greenhouse gases Concentration Pathways adopted by IPCC. Currently, the state of São Paulo has an average Hantavirus risk of 1.3%, with 6% of the 645 municipalities of the state being classified as high risk (HCPS risk ≥ 5%. Our results indicate that sugarcane expansion alone will increase average HCPS risk to 1.5%, placing 20% more people at HCPS risk. Temperature anomalies alone increase HCPS risk even more (1.6% for RCP4.5 and 1.7%, for RCP8.5, and place 31% and 34% more people at risk. Combined sugarcane and temperature increases led to the same predictions as scenarios that only included temperature. Our results demonstrate that climate change effects are likely to be more severe than those from sugarcane expansion. Forecasting disease is critical for the timely and efficient planning of operational control programs that can address the expected effects of sugarcane expansion and climate change on HCPS infection risk. The predicted spatial location of HCPS infection risks

  8. Increased colon cancer risk after severe Salmonella infection.

    Lapo Mughini-Gras

    Full Text Available Colon cancer constitutes one of the most frequent malignancies. Previous studies showed that Salmonella manipulates host cell signaling pathways and that Salmonella Typhimurium infection facilitates colon cancer development in genetically predisposed mice. This epidemiological study examined whether severe Salmonella infection, usually acquired from contaminated food, is associated with increased colon cancer risk in humans.We performed a nationwide registry-based study to assess colon cancer risk after diagnosed Salmonella infection. National infectious disease surveillance records (1999-2015 for Dutch residents aged ≥20 years when diagnosed with salmonellosis (n = 14,264 were linked to the Netherlands Cancer Registry. Salmonella-infected patients were laboratory-confirmed under medical consultation after 1-2 weeks of illness. These datasets also contained information on Salmonella serovar and type of infection. Colon cancer risk (overall and per colon subsite among patients with a diagnosed Salmonella infection was compared with expected colon cancer risk in the general population. Data from the nationwide registry of histo- and cytopathology (PALGA and Statistics Netherlands (CBS allowed assessing potential effects of age, gender, latency, socioeconomic status, genetic predisposition, inflammatory bowel disease (IBD, and tumor features. We found that compared to the general population, colon cancer risk was significantly increased (standardized incidence ratio [SIR] 1.54; 95%CI 1.09-2.10 among patients with Salmonella infection diagnosed <60 years of age. Such increased risk concerned specifically the ascending/transverse colon (SIR 2.12; 95%CI 1.38-3.09 after S. Enteritidis infection (SIR 2.97; 95%CI 1.73-4.76. Salmonellosis occurred more frequently among colon cancer patients with pre-infectious IBD, a known risk factor for colon cancer. Colon tumors of patients with a history of Salmonella infection were mostly of low grade

  9. Nutrition deficiency increases the risk of stomach cancer mortality

    Da Li Qing

    2012-07-01

    Full Text Available Abstract Background The purpose of the study is to determine whether exposure to malnutrition during early life is associated with increased risk of stomach cancer in later life. Methods The design protocol included analyzing the trend of gastric cancer mortality and nutrition and evaluating the association between nutrient deficiency in early life and the risk of gastric cancer by hierarchical age–period–birth cohort (APC analysis using general log-linear Poisson models and to compare the difference between birth cohorts who were exposed to the 1959–1961 Chinese famine and those who were not exposed to the famine. Data on stomach cancer mortality from 1970 to 2009 and the dietary patterns from 1955 to 1985 which included the 1959–1961 Chinese famine period in the Zhaoyuan County population were obtained. The nutrition information was collected 15 years prior to the mortality data as based on the latest reference of disease incubation. Results APC analysis revealed that severe nutrition deficiency during early life may increase the risk of stomach cancer. Compared with the 1960–1964 birth cohort, the risk for stomach cancer in all birth cohorts from 1900 to 1959 significantly increased; compared with the 1970–1974 cohort, the risk for stomach cancer in the 1975–1979 cohort significantly increased, whereas the others had a steadily decreased risk; compared with 85–89 age group in the 2005–2009 death survey, the ORs decreased with younger age and reached significant levels for the 50–54 age group after adjusting the confounding factors. The 1930 to 1964 group (exposed to famine had a higher mortality rate than the 1965 to 1999 group (not exposed to famine. For males, the relative risk (RR was 2.39 and the 95% confidence interval (CI was 1.51 to 3.77. For females, RR was 1.64 and 95% CI was 1.02 to 2.62. Conclusion The results of the present study suggested that prolonged malnutrition during early life may increase the risk of

  10. Excess fertilizer responsive miRNAs revealed in Linum usitatissimum L.

    Melnikova, Nataliya V; Dmitriev, Alexey A; Belenikin, Maxim S; Speranskaya, Anna S; Krinitsina, Anastasia A; Rachinskaia, Olga A; Lakunina, Valentina A; Krasnov, George S; Snezhkina, Anastasiya V; Sadritdinova, Asiya F; Uroshlev, Leonid A; Koroban, Nadezda V; Samatadze, Tatiana E; Amosova, Alexandra V; Zelenin, Alexander V; Muravenko, Olga V; Bolsheva, Nadezhda L; Kudryavtseva, Anna V

    2015-02-01

    Effective fertilizer application is necessary to increase crop yields and reduce risk of plant overdosing. It is known that expression level of microRNAs (miRNAs) alters in plants under different nutrient concentrations in soil. The aim of our study was to identify and characterize miRNAs with expression alterations under excessive fertilizer in agriculturally important crop - flax (Linum usitatissimum L.). We have sequenced small RNAs in flax grown under normal and excessive fertilizer using Illumina GAIIx. Over 14 million raw reads was obtained for two small RNA libraries. 84 conserved miRNAs from 20 families were identified. Differential expression was revealed for several flax miRNAs under excessive fertilizer according to high-throughput sequencing data. For 6 miRNA families (miR395, miR169, miR408, miR399, miR398 and miR168) expression level alterations were evaluated on the extended sampling using qPCR. Statistically significant up-regulation was revealed for miR395 under excessive fertilizer. It is known that target genes of miR395 are involved in sulfate uptake and assimilation. However, according to our data alterations of the expression level of miR395 could be associated not only with excess sulfur application, but also with redundancy of other macro- and micronutrients. Furthermore expression level was evaluated for miRNAs and their predicted targets. The negative correlation between miR399 expression and expression of its predicted target ubiquitin-conjugating enzyme E2 gene was shown in flax for the first time. So we suggested miR399 involvement in phosphate regulation in L. usitatissimum. Revealed in our study expression alterations contribute to miRNA role in flax response to excessive fertilizer. Copyright © 2014 Elsevier B.V. and Société française de biochimie et biologie Moléculaire (SFBBM). All rights reserved.

  11. miR-210 inhibits trophoblast invasion and is a serum biomarker for preeclampsia.

    Anton, Lauren; Olarerin-George, Anthony O; Schwartz, Nadav; Srinivas, Sindhu; Bastek, Jamie; Hogenesch, John B; Elovitz, Michal A

    2013-11-01

    Preeclampsia is characterized by hypertension and proteinuria in pregnant women. Its exact cause is unknown. Preeclampsia increases the risk of maternal and fetal morbidity and mortality. Although delivery, often premature, is the only known cure, early targeted interventions may improve maternal and fetal outcomes. Successful intervention requires a better understanding of the molecular etiology of preeclampsia and the development of accurate methods to predict women at risk. To this end, we tested the role of miR-210, a miRNA up-regulated in preeclamptic placentas, in first-trimester extravillous trophoblasts. miR-210 overexpression reduced trophoblast invasion, a process necessary for uteroplacental perfusion, in an extracellular signal-regulated kinase/mitogen-activated protein kinase-dependent manner. Conversely, miR-210 inhibition promoted invasion. Furthermore, given that the placenta secretes miRNAs into the maternal circulation, we tested if serum expression of miR-210 was associated with the disease. We measured miR-210 expression in two clinical studies: a case-control study and a prospective cohort study. Serum miR-210 expression was significantly associated with a diagnosis of preeclampsia (P = 0.007, area under the receiver operator curves = 0.81) and was predictive of the disease, even months before clinical diagnosis (P preeclampsia that can help in identifying at-risk women for monitoring and treatment. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  12. Cisplatin-resistant lung cancer cell–derived exosomes increase cisplatin resistance of recipient cells in exosomal miR-100–5p-dependent manner

    Qin X

    2017-05-01

    Full Text Available Xiaobing Qin,1,2,* Shaorong Yu,1,3,* Leilei Zhou,1,4 Meiqi Shi,3 Yong Hu,1 Xiaoyue Xu,1 Bo Shen,1 Siwen Liu,1 Dali Yan,1 Jifeng Feng1,3 1Research Center for Clinical Oncology, Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research, Nanjing, 2Department of Oncology, Xuzhou First People’s Hospital, Xuzhou, 3Department of Oncology, Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research, Nanjing, 4Department of Oncology, Affiliated Huai’an Hospital of Nanjing Medical University, Huai’an, Jiangsu, China *These authors have contributed equally to this work Abstract: Exosomes derived from lung cancer cells confer cisplatin (DDP resistance to other cancer cells. However, the underlying mechanism is still unknown. A549 resistance to DDP (A549/DDP was established. Microarray was used to analyze microRNA (miRNA expression profiles of A549 cells, A549/DDP cells, A549 exosomes, and A549/DDP exosomes. There was a strong correlation of miRNA profiles between exosomes and their maternal cells. A total of 11 miRNAs were significantly upregulated both in A549/DDP cells compared with A549 cells and in exosomes derived from A549/DDP cells in contrast to exosomes from A549 cells. A total of 31 downregulated miRNAs were also observed. miR-100–5p was the most prominent decreased miRNA in DDP-resistant exosomes compared with the corresponding sensitive ones. Downregulated miR-100–5p was proved to be involved in DDP resistance in A549 cells, and mammalian target of rapamycin (mTOR expression was reverse regulated by miR-100–5p. Exosomes confer recipient cells’ resistance to DDP in an exosomal miR-100–5p-dependent manner with mTOR as its potential target both in vitro and in vivo. Exosomes from DDP-resistant lung cancer cells A549 can alter other lung cancer cells’ sensitivity to DDP in exosomal miR-100–5p

  13. Characterization of susceptible chiasma configurations that increase the risk for maternal nondisjunction of chromosome 21.

    Lamb, N E; Feingold, E; Savage, A; Avramopoulos, D; Freeman, S; Gu, Y; Hallberg, A; Hersey, J; Karadima, G; Pettay, D; Saker, D; Shen, J; Taft, L; Mikkelsen, M; Petersen, M B; Hassold, T; Sherman, S L

    1997-09-01

    Recent studies of trisomy 21 have shown that altered levels of recombination are associated with maternal non-disjunction occurring at both meiosis I (MI) and meiosis II (MII). To comprehend better the association of recombination with nondisjunction, an understanding of the pattern of meiotic exchange, i.e. the exchange of genetic material at the four-strand stage during prophase, is required. We examined this underlying exchange pattern to determine if specific meiotic configurations are associated with a higher risk of non-disjunction than others. We examined the crossover frequencies of chromosome 21 for three populations: (i) normal female meiotic events; (ii) meiotic events leading to MI non-disjunction; and (iii) those leading to MII non-disjunction. From these crossover frequencies, we estimated the array of meiotic tetrads that produced the observed crossovers. Using this approach, we found that nearly one-half of MI errors were estimated to be achiasmate. The majority of the remaining MI bivalents had exchanges that clustered at the telomere. In contrast, exchanges occurring among MII cases clustered at the pericentromeric region of the chromosome. Unlike the single exchange distributions, double exchanges from the non-disjoined populations seemed to approximate the distribution in the normal population. These data suggest that the location of certain exchanges makes a tetrad susceptible to non-disjunction. Specifically, this susceptibility is associated with the distance between the centromere and closest exchange. This result challenges the widely held concept that events occurring at MII are largely independent of events occurring at MI, and suggests that all non-disjunction events may be initiated during MI and simply resolved at either of the two meiotic stages.

  14. Smoking increases the risk of early meniscus repair failure.

    Blackwell, Ryan; Schmitt, Laura C; Flanigan, David C; Magnussen, Robert A

    2016-05-01

    The goal of this study is to determine whether patients who smoke cigarettes at the time of surgery are at significantly increased risk of early meniscus repair failure relative to non-smokers. Retrospective chart review identified 64 current smokers within a series of 444 consecutive patients who underwent meniscus repair during a 7 years period. Fifty-two of these 64 smokers were available for follow-up and were matched by age, sex, and ACL status with non-smokers from the same cohort. Records of these 104 patients with a total of 120 meniscus repairs were reviewed to identify meniscus repair failure (defined as repeat surgery on the index meniscus) during the median 13-month (range: 3-79 months) follow-up period. The smoking and non-smoking groups were similar in age, sex, ACL status, BMI, meniscus repair technique, and meniscus involved. Meniscus repair failure occurred in 19 of the 112 menisci in 104 patients, for an overall failure risk of 17 %. Of the 19 failures, 14 occurred in 79 repaired medial menisci (18 % failure risk) and 5 occurred in 33 repaired lateral menisci (15 % failure risk). Meniscus repair failure occurred in significantly more smokers (15 failures in 56 menisci in 52 patients -27 % failure risk) than non-smokers (4 failures in 56 menisci in 52 patients -7 % failure risk) (p = 0.0076). Smoking is associated with significantly increased risk of early meniscus repair failure as defined by the incidence of repeat surgery on the index meniscus. III.

  15. Increased risk of oesophageal adenocarcinoma among upstream petroleum workers

    Kirkeleit, Jorunn; Riise, Trond; Bjørge, Tone; Moen, Bente E; Bråtveit, Magne; Christiani, David C

    2013-01-01

    Objectives To investigate cancer risk, particularly oesophageal cancer, among male upstream petroleum workers offshore potentially exposed to various carcinogenic agents. Methods Using the Norwegian Registry of Employers and Employees, 24 765 male offshore workers registered from 1981 to 2003 was compared with 283 002 male referents from the general working population matched by age and community of residence. The historical cohort was linked to the Cancer Registry of Norway and the Norwegian Cause of Death Registry. Results Male offshore workers had excess risk of oesophageal cancer (RR 2.6, 95% CI 1.4 to 4.8) compared with the reference population. Only the adenocarcinoma type had a significantly increased risk (RR 2.7, 95% CI 1.0 to 7.0), mainly because of an increased risk among upstream operators (RR 4.3, 95% CI 1.3 to 14.5). Upstream operators did not have significant excess of respiratory system or colon cancer or mortality from any other lifestyle-related diseases investigated. Conclusion We found a fourfold excess risk of oesophageal adenocarcinoma among male workers assumed to have had the most extensive contact with crude oil. Due to the small number of cases, and a lack of detailed data on occupational exposure and lifestyle factors associated with oesophageal adenocarcinoma, the results must be interpreted with caution. Nevertheless, given the low risk of lifestyle-related cancers and causes of death in this working group, the results add to the observations in other low-powered studies on oesophageal cancer, further suggesting that factors related to the petroleum stream or carcinogenic agents used in the production process might be associated with risk of oesophageal adenocarcinoma. PMID:19858535

  16. Recognising and managing increased HIV transmission risk in newborns

    Max Kroon

    2015-05-01

    Full Text Available Prevention of mother-to-child transmission (PMTCT programmes have improved maternalhealth outcomes and reduced the incidence of paediatric HIV, resulting in improved childhealth and survival. Nevertheless, high-risk vertical exposures remain common and areresponsible for a high proportion of transmissions. In the absence of antiretrovirals (ARVs,an 8- to 12-hour labour has approximately the same 15% risk of transmission as 18 monthsof mixed feeding. The intensity of transmission risk is highest during labour and delivery;however, the brevity of this intra-partum period lends itself to post-exposure interventions toreduce such risk. There is good evidence that infant post-exposure prophylaxis (PEP reducesintra-partum transmission even in the absence of maternal prophylaxis. Recent reports suggestthat infant combination ARV prophylaxis (cARP is more efficient at reducing intra-partumtransmission than a single agent in situations of minimal pre-labour prophylaxis. Guidelinesfrom the developed world have incorporated infant cARP for increased-risk scenarios. Incontrast, recent guidelines for low-resource settings have rightfully focused on reducingpostnatal transmission to preserve the benefits of breastfeeding, but have largely ignored thepotential of augmented infant PEP for reducing intra-partum transmissions. Minimal prelabourprophylaxis, poor adherence in the month prior to delivery, elevated maternal viralload at delivery, spontaneous preterm labour with prolonged rupture of membranes andchorioamnionitis are simple clinical criteria that identify increased intra-partum transmissionrisk. In these increased-risk scenarios, transmission frequency may be halved by combiningnevirapine and zidovudine as a form of boosted infant PEP. This strategy may be important toreduce intra-partum transmissions when PMTCT is suboptimal.

  17. Risk of falls after withdrawal of fall-risk-increasing drugs: a prospective cohort study

    van der Velde, Nathalie; Stricker, Bruno H. Ch; Pols, Huib A. P.; van der Cammen, Tischa J. M.

    2007-01-01

    AIMS: Falling in older persons is a frequent and serious clinical problem. Several drugs have been associated with increased fall risk. The objective of this study was to identify differences in the incidence of falls after withdrawal (discontinuation or dose reduction) of fall-risk-increasing drugs

  18. Female gonadal shielding with automatic exposure control increases radiation risks

    Kaplan, Summer L.; Zhu, Xiaowei [Children' s Hospital of Philadelphia, Department of Radiology, Philadelphia, PA (United States); University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA (United States); Magill, Dennise; Felice, Marc A. [University of Pennsylvania, Environmental Health and Radiation Safety, Philadelphia, PA (United States); Xiao, Rui [University of Pennsylvania, Department of Biostatistics and Epidemiology, Philadelphia, PA (United States); Ali, Sayed [Temple University Hospital, Department of Radiology, Philadelphia, PA (United States)

    2018-02-15

    Gonadal shielding remains common, but current estimates of gonadal radiation risk are lower than estimated risks to colon and stomach. A female gonadal shield may attenuate active automatic exposure control (AEC) sensors, resulting in increased dose to colon and stomach as well as to ovaries outside the shielded area. We assess changes in dose-area product (DAP) and absorbed organ dose when female gonadal shielding is used with AEC for pelvis radiography. We imaged adult and 5-year-old equivalent dosimetry phantoms using pelvis radiograph technique with AEC in the presence and absence of a female gonadal shield. We recorded DAP and mAs and measured organ absorbed dose at six internal sites using film dosimetry. Female gonadal shielding with AEC increased DAP 63% for the 5-year-old phantom and 147% for the adult phantom. Absorbed organ dose at unshielded locations of colon, stomach and ovaries increased 21-51% in the 5-year-old phantom and 17-100% in the adult phantom. Absorbed organ dose sampled under the shield decreased 67% in the 5-year-old phantom and 16% in the adult phantom. Female gonadal shielding combined with AEC during pelvic radiography increases absorbed dose to organs with greater radiation sensitivity and to unshielded ovaries. Difficulty in proper use of gonadal shields has been well described, and use of female gonadal shielding may be inadvisable given the risks of increasing radiation. (orig.)

  19. Female gonadal shielding with automatic exposure control increases radiation risks

    Kaplan, Summer L.; Zhu, Xiaowei; Magill, Dennise; Felice, Marc A.; Xiao, Rui; Ali, Sayed

    2018-01-01

    Gonadal shielding remains common, but current estimates of gonadal radiation risk are lower than estimated risks to colon and stomach. A female gonadal shield may attenuate active automatic exposure control (AEC) sensors, resulting in increased dose to colon and stomach as well as to ovaries outside the shielded area. We assess changes in dose-area product (DAP) and absorbed organ dose when female gonadal shielding is used with AEC for pelvis radiography. We imaged adult and 5-year-old equivalent dosimetry phantoms using pelvis radiograph technique with AEC in the presence and absence of a female gonadal shield. We recorded DAP and mAs and measured organ absorbed dose at six internal sites using film dosimetry. Female gonadal shielding with AEC increased DAP 63% for the 5-year-old phantom and 147% for the adult phantom. Absorbed organ dose at unshielded locations of colon, stomach and ovaries increased 21-51% in the 5-year-old phantom and 17-100% in the adult phantom. Absorbed organ dose sampled under the shield decreased 67% in the 5-year-old phantom and 16% in the adult phantom. Female gonadal shielding combined with AEC during pelvic radiography increases absorbed dose to organs with greater radiation sensitivity and to unshielded ovaries. Difficulty in proper use of gonadal shields has been well described, and use of female gonadal shielding may be inadvisable given the risks of increasing radiation. (orig.)

  20. Female gonadal shielding with automatic exposure control increases radiation risks.

    Kaplan, Summer L; Magill, Dennise; Felice, Marc A; Xiao, Rui; Ali, Sayed; Zhu, Xiaowei

    2018-02-01

    Gonadal shielding remains common, but current estimates of gonadal radiation risk are lower than estimated risks to colon and stomach. A female gonadal shield may attenuate active automatic exposure control (AEC) sensors, resulting in increased dose to colon and stomach as well as to ovaries outside the shielded area. We assess changes in dose-area product (DAP) and absorbed organ dose when female gonadal shielding is used with AEC for pelvis radiography. We imaged adult and 5-year-old equivalent dosimetry phantoms using pelvis radiograph technique with AEC in the presence and absence of a female gonadal shield. We recorded DAP and mAs and measured organ absorbed dose at six internal sites using film dosimetry. Female gonadal shielding with AEC increased DAP 63% for the 5-year-old phantom and 147% for the adult phantom. Absorbed organ dose at unshielded locations of colon, stomach and ovaries increased 21-51% in the 5-year-old phantom and 17-100% in the adult phantom. Absorbed organ dose sampled under the shield decreased 67% in the 5-year-old phantom and 16% in the adult phantom. Female gonadal shielding combined with AEC during pelvic radiography increases absorbed dose to organs with greater radiation sensitivity and to unshielded ovaries. Difficulty in proper use of gonadal shields has been well described, and use of female gonadal shielding may be inadvisable given the risks of increasing radiation.

  1. Financing increasing flood risk: evidence from millions of buildings

    Jongman, B.; Koks, E. E.; Husby, T. G.; Ward, P. J.

    2014-01-01

    The effectiveness of disaster risk management and financing mechanisms depends on the accurate assessment of current and future hazard exposure. The increasing availability of detailed data offers policy makers and the insurance sector new opportunities to understand trends in risk, and to make informed decisions on the ways to deal with these trends. In this paper we show how comprehensive property level information can be used for the assessment of exposure to flooding on a national scale, and how this information can contribute to discussions on possible risk financing practices. The case-study used is the Netherlands, which is one of the countries most exposed to flooding globally, and which is currently undergoing a debate on strategies for the compensation of potential losses. Our results show that flood exposure has increased rapidly between 1960 and 2012, and that the growth of the building stock and its economic value in flood prone areas has been higher than in not flood prone areas. We also find that property values in flood prone areas are lower than those in not flood prone areas. We argue that the increase in the share of economic value located in potential flood prone areas can have a negative effect on the feasibility of private insurance schemes in the Netherlands. The methodologies and results presented in this study are relevant for many regions around the world where the effects of rising flood exposure create a challenge for risk financing.

  2. Increasing flood exposure in the Netherlands: implications for risk financing

    Jongman, B.; Koks, E. E.; Husby, T. G.; Ward, P. J.

    2014-05-01

    The effectiveness of disaster risk management and financing mechanisms depends on an accurate assessment of current and future hazard exposure. The increasing availability of detailed data offers policy makers and the insurance sector new opportunities to understand trends in risk, and to make informed decisions on ways to deal with these trends. In this paper we show how comprehensive property level information can be used for the assessment of exposure to flooding on a national scale, and how this information provides valuable input to discussions on possible risk financing practices. The case study used is the Netherlands, which is one of the countries most exposed to flooding globally, and which is currently undergoing a debate on strategies for the compensation of potential losses. Our results show that flood exposure has increased rapidly between 1960 and 2012, and that the growth of the building stock and its economic value in flood-prone areas has been higher than in non-flood-prone areas. We also find that property values in flood-prone areas are lower than those in non-flood-prone areas. We argue that the increase in the share of economic value located in potential flood-prone areas can have a negative effect on the feasibility of private insurance schemes in the Netherlands. The methodologies and results presented in this study are relevant for many regions around the world where the effects of rising flood exposure create a challenge for risk financing.

  3. Increased Baseline C-Reactive Protein Concentrations Are Associated with Increased Risk of Infections

    Zacho, Jeppe; Benfield, Thomas; Tybjærg-Hansen, Anne

    2016-01-01

    BACKGROUND: The acute-phase reactant C-reactive protein (CRP) increases rapidly during an infection. We tested the hypothesis that chronic low-level increases in CRP are associated with an increased risk of infectious disease. METHODS: We studied 9660 individuals from a prospective general...... population cohort, including 3592 in whom infectious disease developed, and another 60 896 individuals from a cross-sectional general population study, of whom 13 332 developed infectious disease; 55% were women, and the mean age was 57 years. Hospital diagnoses of infections in 1977-2010 were based....... RESULTS: Individuals with CRP >3 mg/L had 1.2 and 1.7 times increased risk of infectious disease, in the prospective general population cohort and the cross-sectional general population study, respectively, compared with individuals with CRP

  4. Hypoxia-induced aggressiveness of pancreatic cancer cells is due to increased expression of VEGF, IL-6 and miR-21, which can be attenuated by CDF treatment.

    Bin Bao

    Full Text Available Hypoxia is known to play critical roles in cell survival, angiogenesis, tumor invasion, and metastasis. Hypoxia mediated over-expression of hypoxia-inducible factor (HIF has been shown to be associated with therapeutic resistance, and contributes to poor prognosis of cancer patients. Emerging evidence suggest that hypoxia and HIF pathways contributes to the acquisition of epithelial-to-mesenchymal transition (EMT, maintenance of cancer stem cell (CSC functions, and also maintains the vicious cycle of inflammation-all which lead to therapeutic resistance. However, the precise molecular mechanism(s by which hypoxia/HIF drives these events are not fully understood. Here, we show, for the first time, that hypoxia leads to increased expression of VEGF, IL-6, and CSC signature genes Nanog, Oct4 and EZH2 consistent with increased cell migration/invasion and angiogenesis, and the formation of pancreatospheres, concomitant with increased expression of miR-21 and miR-210 in human pancreatic cancer (PC cells. The treatment of PC cells with CDF, a novel synthetic compound inhibited the production of VEGF and IL-6, and down-regulated the expression of Nanog, Oct4, EZH2 mRNAs, as well as miR-21 and miR-210 under hypoxia. CDF also led to decreased cell migration/invasion, angiogenesis, and formation of pancreatospheres under hypoxia. Moreover, CDF decreased gene expression of miR-21, miR-210, IL-6, HIF-1α, VEGF, and CSC signatures in vivo in a mouse orthotopic model of human PC. Collectively, these results suggest that the anti-tumor activity of CDF is in part mediated through deregulation of tumor hypoxic pathways, and thus CDF could become a novel, and effective anti-tumor agent for PC therapy.

  5. Endometriosis increases the risk of obstetrical and neonatal complications.

    Berlac, Janne Foss; Hartwell, Dorthe; Skovlund, Charlotte Wessel; Langhoff-Roos, Jens; Lidegaard, Øjvind

    2017-06-01

    The objective of this study was to assess obstetrical complications and neonatal outcomes in women with endometriosis as compared with women without endometriosis. National cohort including all delivering women and their newborns in Denmark 1997-2014. Data were extracted from the Danish Health Register and the Medical Birth Register. Logistic regression analysis provided odds ratios (OR) with 95% confidence intervals (CI). Sub-analyses were made for primiparous women with a singleton pregnancy and for women with endometriosis who underwent gynecological surgery before pregnancy. In 19 331 deliveries, women with endometriosis had a higher risk of severe preeclampsia (OR 1.7, 95% CI 1.5-2.0), hemorrhage in pregnancy (OR 2.3, 95% CI 2.0-2.5), placental abruption (OR 2.0, 95% CI 1.7-2.3), placenta previa (OR 3.9, 95% CI 3.5-4.3), premature rupture of membranes (OR 1.7, 95% CI 1.5-1.8), and retained placenta (OR 3.1, 95% CI 1.4-6.6). The neonates had increased risks of preterm birth before 28 weeks (OR 3.1, 95% CI 2.7-3.6), being small for gestational age (OR 1.5, 95% CI 1.4-1.6), being diagnosed with congenital malformations (OR 1.3, 95% CI 1.3-1.4), and neonatal death (OR 1.8, 95% CI 1.4-2.1). Results were similar in primiparous women with a singleton pregnancy. Gynecological surgery for endometriosis before pregnancy carried a further increased risk. Women with endometriosis had a significantly higher risk of several complications, such as preeclampsia and placental complications in pregnancy and at delivery. The newborns had increased risk of being delivered preterm, having congenital malformations, and having a higher neonatal death rate. Pregnant women with endometriosis require increased antenatal surveillance. © 2017 Nordic Federation of Societies of Obstetrics and Gynecology.

  6. Acrolein exposure is associated with increased cardiovascular disease risk.

    DeJarnett, Natasha; Conklin, Daniel J; Riggs, Daniel W; Myers, John A; O'Toole, Timothy E; Hamzeh, Ihab; Wagner, Stephen; Chugh, Atul; Ramos, Kenneth S; Srivastava, Sanjay; Higdon, Deirdre; Tollerud, David J; DeFilippis, Andrew; Becher, Carrie; Wyatt, Brad; McCracken, James; Abplanalp, Wes; Rai, Shesh N; Ciszewski, Tiffany; Xie, Zhengzhi; Yeager, Ray; Prabhu, Sumanth D; Bhatnagar, Aruni

    2014-08-06

    Acrolein is a reactive aldehyde present in high amounts in coal, wood, paper, and tobacco smoke. It is also generated endogenously by lipid peroxidation and the oxidation of amino acids by myeloperoxidase. In animals, acrolein exposure is associated with the suppression of circulating progenitor cells and increases in thrombosis and atherogenesis. The purpose of this study was to determine whether acrolein exposure in humans is also associated with increased cardiovascular disease (CVD) risk. Acrolein exposure was assessed in 211 participants of the Louisville Healthy Heart Study with moderate to high (CVD) risk by measuring the urinary levels of the major acrolein metabolite-3-hydroxypropylmercapturic acid (3-HPMA). Generalized linear models were used to assess the association between acrolein exposure and parameters of CVD risk, and adjusted for potential demographic confounders. Urinary 3-HPMA levels were higher in smokers than nonsmokers and were positively correlated with urinary cotinine levels. Urinary 3-HPMA levels were inversely related to levels of both early (AC133(+)) and late (AC133(-)) circulating angiogenic cells. In smokers as well as nonsmokers, 3-HPMA levels were positively associated with both increased levels of platelet-leukocyte aggregates and the Framingham Risk Score. No association was observed between 3-HPMA and plasma fibrinogen. Levels of C-reactive protein were associated with 3-HPMA levels in nonsmokers only. Regardless of its source, acrolein exposure is associated with platelet activation and suppression of circulating angiogenic cell levels, as well as increased CVD risk. © 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  7. Increased nuchal translucency thickness and the risk of neurodevelopmental disorders

    Hellmuth, Signe G; Pedersen, L H; Miltoft, Caroline B

    2016-01-01

    spectrum disorders (ASD), cerebral palsy, epilepsy and febrile seizures was obtained from national patient registries. RESULTS: There was no excess risk of neurodevelopmental disorders among euploid children with first-trimester NT 95(th) -99(th) percentile. For children with NT > 99(th) percentile...... in the risk of cerebral palsy (OR, 1.91 (95% CI, 0.61-5.95), 0.47%), epilepsy (OR, 1.51 (95% CI, 0.63-3.66), 0.78%) or febrile seizures (OR, 0.72 (95% CI, 0.44-1.16), 2.65%). CONCLUSIONS: In a large unselected cohort of euploid children, there was no increased risk of neurodevelopmental disorders among those......OBJECTIVE: To investigate the association between fetal nuchal translucency (NT) thickness and neurodevelopmental disorders in euploid children. METHODS: This study included 222 505 euploid children who had undergone routine first-trimester screening during fetal life. Children were divided...

  8. Visible Age-Related Signs and Risk of Ischemic Heart Disease in the General Population

    Christoffersen, Mette; Frikke-Schmidt, Ruth; Schnohr, Peter

    2014-01-01

    developed MI. Presence of frontoparietal baldness, crown top baldness, earlobe crease, and xanthelasmata was associated with increased risk of IHD or MI after multifactorial adjustment for chronological age and well-known cardiovascular risk factors. The risk of IHD and MI increased stepwise with increasing...... risk of IHD and MI increased with increasing number of visible age-related signs. CONCLUSIONS: Male pattern baldness, earlobe crease, and xanthelasmata-alone or in combination-associate with increased risk of ischemic heart disease and myocardial infarction independent of chronological age and other...

  9. Increased colon cancer risk after severe Salmonella infection

    Mooij, Sofie; Neefjes-Borst, E. Andra; van Pelt, Wilfrid; Neefjes, Jacques

    2018-01-01

    Background Colon cancer constitutes one of the most frequent malignancies. Previous studies showed that Salmonella manipulates host cell signaling pathways and that Salmonella Typhimurium infection facilitates colon cancer development in genetically predisposed mice. This epidemiological study examined whether severe Salmonella infection, usually acquired from contaminated food, is associated with increased colon cancer risk in humans. Methods and findings We performed a nationwide registry-based study to assess colon cancer risk after diagnosed Salmonella infection. National infectious disease surveillance records (1999–2015) for Dutch residents aged ≥20 years when diagnosed with salmonellosis (n = 14,264) were linked to the Netherlands Cancer Registry. Salmonella-infected patients were laboratory-confirmed under medical consultation after 1–2 weeks of illness. These datasets also contained information on Salmonella serovar and type of infection. Colon cancer risk (overall and per colon subsite) among patients with a diagnosed Salmonella infection was compared with expected colon cancer risk in the general population. Data from the nationwide registry of histo- and cytopathology (PALGA) and Statistics Netherlands (CBS) allowed assessing potential effects of age, gender, latency, socioeconomic status, genetic predisposition, inflammatory bowel disease (IBD), and tumor features. We found that compared to the general population, colon cancer risk was significantly increased (standardized incidence ratio [SIR] 1.54; 95%CI 1.09–2.10) among patients with Salmonella infection diagnosed transverse colon (SIR 2.12; 95%CI 1.38–3.09) after S. Enteritidis infection (SIR 2.97; 95%CI 1.73–4.76). Salmonellosis occurred more frequently among colon cancer patients with pre-infectious IBD, a known risk factor for colon cancer. Colon tumors of patients with a history of Salmonella infection were mostly of low grade. Conclusions Patients diagnosed with severe

  10. Increased risk of stroke in contact dermatitis patients

    Chang, Wei-Lun; Hsu, Min-Hsien; Lin, Cheng-Li; Chan, Po-Chi; Chang, Ko-Shih; Lee, Ching-Hsiao; Hsu, Chung-Yi; Tsai, Min-Tein; Yeh, Chung-Hsin; Sung, Fung-Chang

    2017-01-01

    Abstract Dermatologic diseases are not traditional risk factors of stroke, but recent studies show atopic dermatitis, psoriasis, and bullous skin disease may increase the risk of stroke and other cardiovascular diseases. No previous studies have focused on the association between contact dermatitis and stroke. We established a cohort comprised of 48,169 contact dermatitis patients newly diagnosed in 2000–2003 and 96,338 randomly selected subjects without the disorder, frequency matched by sex, age, and diagnosis year, as the comparison cohort. None of them had a history of stroke. Stroke incidence was assessed by the end of 2011 for both cohorts. The incidence stroke was 1.1-fold higher in the contact dermatitis cohort than in the comparison cohort (5.93 vs 5.37 per 1000 person-years, P contact dermatitis cohort increased with age, from 1.14 (95% CI, 1.03–1.27) for 65 to 74 years; to 1.27 (95% CI, 1.15–1.42) for 75 years and older. The aHR of stroke were 1.16 (95% CI, 1.07–1.27) and 1.09 (95% CI, 1.00–1.18) for men and women, respectively. This study suggests that patients with contact dermatitis were at a modestly increased risk of stroke, significant for ischemic stroke but not for hemorrhagic stroke. Comorbidity, particularly hypertension, increased the hazard of stroke further. PMID:28272195

  11. Obesity increases risk of ischemic stroke in young adults.

    Mitchell, Andrew B; Cole, John W; McArdle, Patrick F; Cheng, Yu-Ching; Ryan, Kathleen A; Sparks, Mary J; Mitchell, Braxton D; Kittner, Steven J

    2015-06-01

    Body mass index has been associated with ischemic stroke in older populations, but its association with stroke in younger populations is not known. In light of the current obesity epidemic in the United States, the potential impact of obesity on stroke risk in young adults deserves attention. A population-based case-control study design with 1201 cases and 1154 controls was used to investigate the relationship of obesity and young onset ischemic stroke. Stroke cases were between the ages of 15 and 49 years. Logistic regression analysis was used to evaluate the association between body mass index and ischemic stroke with and without adjustment for comorbid conditions associated with stroke. In analyses adjusted for age, sex, and ethnicity, obesity (body mass index >30 kg/m(2)) was associated with an increased stroke risk (odds ratio, 1.57; 95% confidence interval, 1.28-1.94) although this increased risk was highly attenuated and not statistically significant after adjustment for smoking, hypertension, and diabetes mellitus. These results indicate that obesity is a risk factor for young onset ischemic stroke and suggest that this association may be partially mediated through hypertension, diabetes mellitus, or other variables associated with these conditions. © 2015 American Heart Association, Inc.

  12. The increased risk of joint venture promotes social cooperation.

    Te Wu

    Full Text Available The joint venture of many members is common both in animal world and human society. In these public enterprizes, highly cooperative groups are more likely to while low cooperative groups are still possible but not probable to succeed. Existent literature mostly focuses on the traditional public goods game, in which cooperators create public wealth unconditionally and benefit all group members unbiasedly. We here institute a model addressing this public goods dilemma with incorporating the public resource foraging failure risk. Risk-averse individuals tend to lead a autarkic life, while risk-preferential ones tend to participate in the risky public goods game. For participants, group's success relies on its cooperativeness, with increasing contribution leading to increasing success likelihood. We introduce a function with one tunable parameter to describe the risk removal pattern and study in detail three representative classes. Analytical results show that the widely replicated population dynamics of cyclical dominance of loner, cooperator and defector disappear, while most of the time loners act as savors while eventually they also disappear. Depending on the way that group's success relies on its cooperativeness, either cooperators pervade the entire population or they coexist with defectors. Even in the later case, cooperators still hold salient superiority in number as some defectors also survive by parasitizing. The harder the joint venture succeeds, the higher level of cooperation once cooperators can win the evolutionary race. Our work may enrich the literature concerning the risky public goods games.

  13. The increased risk of joint venture promotes social cooperation.

    Wu, Te; Fu, Feng; Zhang, Yanling; Wang, Long

    2013-01-01

    The joint venture of many members is common both in animal world and human society. In these public enterprizes, highly cooperative groups are more likely to while low cooperative groups are still possible but not probable to succeed. Existent literature mostly focuses on the traditional public goods game, in which cooperators create public wealth unconditionally and benefit all group members unbiasedly. We here institute a model addressing this public goods dilemma with incorporating the public resource foraging failure risk. Risk-averse individuals tend to lead a autarkic life, while risk-preferential ones tend to participate in the risky public goods game. For participants, group's success relies on its cooperativeness, with increasing contribution leading to increasing success likelihood. We introduce a function with one tunable parameter to describe the risk removal pattern and study in detail three representative classes. Analytical results show that the widely replicated population dynamics of cyclical dominance of loner, cooperator and defector disappear, while most of the time loners act as savors while eventually they also disappear. Depending on the way that group's success relies on its cooperativeness, either cooperators pervade the entire population or they coexist with defectors. Even in the later case, cooperators still hold salient superiority in number as some defectors also survive by parasitizing. The harder the joint venture succeeds, the higher level of cooperation once cooperators can win the evolutionary race. Our work may enrich the literature concerning the risky public goods games.

  14. Extreme Geohazards: Reducing the Disaster Risk and Increasing Resilience

    Plag, Hans-Peter; Stein, Seth; Brocklebank, Sean; Jules-Plag, Shelley; Marsh, Stuart; Campus, Paola

    2013-04-01

    Extreme geohazards have the potential to escalate the global sustainability crisis and put us close to the boundaries of the safe operating space for humanity. Exposure of human assets to geohazards has increased dramatically in recent decades, and the sensitivity of the built environment and the embedded socio-economic fabric have changed. We are putting the urban environment, including megacities, in harm's way. Paradoxically, innovation during recent decades, in particular, urban innovation, has increased the disaster risk and coupled this risk to the sustainability crisis. Only more innovation can reduce disaster risk and lead us out of the sustainability crisis. Extreme geohazards (volcanic eruptions, earthquakes, tsunamis) that occurred regularly throughout the last few millennia mostly did not cause major disasters because population density was low and the built environment was not sprawling into hazardous areas to the same extent as today. Similar extreme events today would cause unparalleled damage on a global scale and could worsen the sustainability crisis. Simulation of these extreme hazards under present conditions can help to assess the disaster risk. The Geohazards Community of Practice of the Group on Earth Observations (GEO) with support from the European Science Foundation is preparing a white paper assessing the contemporary disaster risks associated with extreme geohazards and developing a vision for science and society to engage in deliberations addressing this risk (see http://www.geohazcop.org/projects/extgeowp). Risk awareness and monitoring is highly uneven across the world, and this creates two kinds of problems. Firstly, potential hazards are much more closely monitored in wealthy countries than in the developing world. But the largest hazards are global in nature, and it is critical to get as much forewarning as possible to develop an effective response. The disasters and near-misses of the past show that adherence to scientific

  15. Increasing risk of prosthetic joint infection after total hip arthroplasty

    Dale, Håvard; Fenstad, Anne M; Hallan, Geir

    2012-01-01

    Background and purpose The risk of revision due to infection after primary total hip arthroplasty (THA) has been reported to be increasing in Norway. We investigated whether this increase is a common feature in the Nordic countries (Denmark, Finland, Norway, and Sweden). Materials and methods The...... explain this increase. We believe that there has been an actual increase in the incidence of prosthetic joint infections after THA.......Background and purpose The risk of revision due to infection after primary total hip arthroplasty (THA) has been reported to be increasing in Norway. We investigated whether this increase is a common feature in the Nordic countries (Denmark, Finland, Norway, and Sweden). Materials and methods...... The study was based on the Nordic Arthroplasty Register Association (NARA) dataset. 432,168 primary THAs from 1995 to 2009 were included (Denmark: 83,853, Finland 78,106, Norway 88,455, and Sweden 181,754). Adjusted survival analyses were performed using Cox regression models with revision due to infection...

  16. Increased risk of migraine in patients with psoriasis

    Egeberg, A.; Mallbris, L.; Gislason, G. H.

    2015-01-01

    Background: Psoriasis and migraine are common conditions with potential overlap of pathophysiological mechanisms. Both these diseases have been associated with increased cardiovascular risk but little is known about their interplay. Objective: We sought to investigate the link between psoriasis...... and adjusted incidence rate ratios were estimated by Poisson regression models. Results: The study comprised a total of 5,379,859 individuals, including 53,006 and 6831 patients with mild and severe psoriasis, respectively, and 6243 patients with psoriatic arthritis. Fully adjusted incidence rate ratios...... for migraine were 1.37 (95% confidence interval 1.30-1.45), 1.55 (95% confidence interval 1.29-1.86), and 1.92 (95% confidence interval 1.65-2.22) for mild psoriasis, severe psoriasis, and psoriatic arthritis, respectively. Stratification for sex revealed increased risk of migraine in both male and female...

  17. Micronutrient-fortified rice can increase hookworm infection risk

    de Gier, Brechje; Campos Ponce, Maiza; Perignon, Marlene

    2016-01-01

    or inflammation after iron supplementation. OBJECTIVE: To study effects of micronutrient-fortified rice on hookworm infection in Cambodian schoolchildren. METHODS: A double-blinded, cluster-randomized trial was conducted in 16 Cambodian primary schools partaking in the World Food Program school meal program....... Three types of multi-micronutrient fortified rice were tested against placebo rice within the school meal program: UltraRice_original, UltraRice_improved and NutriRice. Four schools were randomly assigned to each study group (placebo n = 492, UltraRice_original n = 479, UltraRice_improved n = 500, NutriRice.......6%, but differed considerably among schools (range 0%- 48.1%).Micronutrient-fortified rice significantly increased risk of new hookworm infection. This effect was modified by baseline hookworm prevalence at the school; hookworm infection risk was increased by all three types of fortified rice in schools where...

  18. Preoperative dehydration increases risk of postoperative acute renal failure in colon and rectal surgery.

    Moghadamyeghaneh, Zhobin; Phelan, Michael J; Carmichael, Joseph C; Mills, Steven D; Pigazzi, Alessio; Nguyen, Ninh T; Stamos, Michael J

    2014-12-01

    There is limited data regarding the effects of preoperative dehydration on postoperative renal function. We sought to identify associations between hydration status before operation and postoperative acute renal failure (ARF) in patients undergoing colorectal resection. The NSQIP database was used to examine the data of patients undergoing colorectal resection from 2005 to 2011. We used preoperative blood urea nitrogen (BUN)/creatinine ratio >20 as a marker of relative dehydration. Multivariate analysis using logistic regression was performed to quantify the association of BUN/Cr ratio with ARF. We sampled 27,860 patients who underwent colorectal resection. Patients with dehydration had higher risk of ARF compared to patients with BUN/Cr Dehydration was associated with an increase in mortality of the affected patients (AOR, 2.19; P dehydrated patients. Open colorectal procedures (AOR, 2.67; P = 0.01) and total colectomy procedure (AOR, 1.62; P Dehydration before operation is a common condition in colorectal surgery (incidence of 27.7 %). Preoperative dehydration is associated with increased rates of postoperative ARF, MI, and cardiac arrest. Hydrotherapy of patients with dehydration may decrease postoperative complications in colorectal surgery.

  19. Increased colon cancer risk after severe Salmonella infection

    Mughini-Gras, Lapo; Schaapveld, Michael; Kramers, Jolanda; Mooij, Sofie; Neefjes-Borst, E. Andra; van Pelt, Wilfrid; Neefjes, Jacques

    2018-01-01

    Background Colon cancer constitutes one of the most frequent malignancies. Previous studies showed that Salmonella manipulates host cell signaling pathways and that Salmonella Typhimurium infection facilitates colon cancer development in genetically predisposed mice. This epidemiological study examined whether severe Salmonella infection, usually acquired from contaminated food, is associated with increased colon cancer risk in humans. Methods and findings We performed a nationwide registry-b...

  20. Betel nut chewing associated with increased risk of arterial stiffness.

    Wei, Yu-Ting; Chou, Yu-Tsung; Yang, Yi-Ching; Chou, Chieh-Ying; Lu, Feng-Hwa; Chang, Chih-Jen; Wu, Jin-Shang

    2017-11-01

    Betel nut chewing is associated with certain cardiovascular outcomes. Subclinical atherosclerosis may be one link between betel nut chewing and cardiovascular risk. Few studies have examined the association between chewing betel nut and arterial stiffness. The aim of this study was thus to determine the relationship between betel nut chewing and arterial stiffness in a Taiwanese population. We enrolled 7540 eligible subjects in National Cheng Kung University Hospital from October 2006 to August 2009. The exclusion criteria included history of cerebrovascular events, coronary artery disease, and taking lipid-lowering drugs, antihypertensives, and hypoglycemic agents. Increased arterial stiffness was defined as brachial-ankle pulse wave velocity (baPWV) ≥1400cm/s. According to their habit of betel nut use, the subjects were categorized into non-, ex-, and current chewers. The prevalence of increased arterial stiffness was 32.7, 43.3, and 43.2% in non-, ex- and current chewers, respectively (p=0.011). Multiple logistic regression analysis revealed that ex-chewers (odds ratio [OR] 1.69, 95% confidence interval (CI)=1.08-2.65) and current chewers (OR 2.29, 95% CI=1.05-4.99) had elevated risks of increased arterial stiffness after adjustment for co-variables. Both ex- and current betel nut chewing were associated with a higher risk of increased arterial stiffness. Stopping betel nut chewing may thus potentially be beneficial to reduce cardiovascular risk, based on the principals of preventive medicine. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Type 2 Diabetes Mellitus and Increased Risk for Malaria Infection

    2010-09-23

    This podcast describes research done in Ghana examining a correlation between type 2 diabetes and a possible increased risk for malaria infection in adults. Dr. Manoj Menon, a medical officer in the Division of Parasitic Diseases and Malaria in the Center for Global Health, discusses questions the study raises.  Created: 9/23/2010 by National Center for Emerging and Zoonotic Infectious Diseases; Center for Global Health.   Date Released: 9/23/2010.

  2. Increased mortality risk in women with depression and diabetes mellitus

    Pan, An; Lucas, Michel; Sun, Qi; van Dam, Rob M.; Franco, Oscar H.; Willett, Walter C.; Manson, JoAnn E.; Rexrode, Kathryn M.; Ascherio, Alberto; Hu, Frank B.

    2011-01-01

    Context Both depression and diabetes have been associated with an increased risk of all-cause and cardiovascular diseases (CVD) mortality. However, data evaluating the joint effects of these two conditions on mortality are sparse. Objectives To evaluate the individual and joint effects of depression and diabetes on all-cause and CVD mortality in a prospective cohort study. Design, Settings and Participants A total of 78282 female participants in the Nurses' Health Study aged 54-79 years at baseline in 2000 were followed until 2006. Depression was defined as having self-reported diagnosed depression, treatment with antidepressant medications, or a score indicating severe depressive symptomatology, i.e., a five-item Mental Health Index score ≤52. Self-reported type 2 diabetes was confirmed using a supplementary questionnaire. Main outcome measures All-cause and CVD-specific mortality. Results During 6 years of follow-up (433066 person-years), 4654 deaths were documented, including 979 deaths from CVD. Compared to participants without either condition, the age-adjusted relative risks (95% confidence interval, CI) for all-cause mortality were 1.76 (1.64-1.89) for women with depression only, 1.71 (1.54-1.89) for individuals with diabetes only, and 3.11 (2.70-3.58) for those with both conditions. The corresponding age-adjusted relative risks of CVD mortality were 1.81 (1.54-2.13), 2.67 (2.20-3.23), and 5.38 (4.19-6.91), respectively. These associations were attenuated after multivariate adjustment for other demographic variables, body mass index, smoking status, alcohol intake, physical activity, and major comorbidities (including hypertension, hypercholesterolemia, heart diseases, stroke and cancer) but remained significant, with the highest relative risks for all-cause and CVD mortality found in those with both conditions (2.07 [95% CI, 1.79-2.40] and 2.72 [95% CI, 2.09-3.54], respectively). Furthermore, the combination of depression with a long duration of diabetes

  3. An Increase in the Omega-6/Omega-3 Fatty Acid Ratio Increases the Risk for Obesity

    Simopoulos, Artemis P.

    2016-01-01

    In the past three decades, total fat and saturated fat intake as a percentage of total calories has continuously decreased in Western diets, while the intake of omega-6 fatty acid increased and the omega-3 fatty acid decreased, resulting in a large increase in the omega-6/omega-3 ratio from 1:1 during evolution to 20:1 today or even higher. This change in the composition of fatty acids parallels a significant increase in the prevalence of overweight and obesity. Experimental studies have suggested that omega-6 and omega-3 fatty acids elicit divergent effects on body fat gain through mechanisms of adipogenesis, browning of adipose tissue, lipid homeostasis, brain-gut-adipose tissue axis, and most importantly systemic inflammation. Prospective studies clearly show an increase in the risk of obesity as the level of omega-6 fatty acids and the omega-6/omega-3 ratio increase in red blood cell (RBC) membrane phospholipids, whereas high omega-3 RBC membrane phospholipids decrease the risk of obesity. Recent studies in humans show that in addition to absolute amounts of omega-6 and omega-3 fatty acid intake, the omega-6/omega-3 ratio plays an important role in increasing the development of obesity via both AA eicosanoid metabolites and hyperactivity of the cannabinoid system, which can be reversed with increased intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). A balanced omega-6/omega-3 ratio is important for health and in the prevention and management of obesity. PMID:26950145

  4. An Increase in the Omega-6/Omega-3 Fatty Acid Ratio Increases the Risk for Obesity

    Artemis P. Simopoulos

    2016-03-01

    Full Text Available In the past three decades, total fat and saturated fat intake as a percentage of total calories has continuously decreased in Western diets, while the intake of omega-6 fatty acid increased and the omega-3 fatty acid decreased, resulting in a large increase in the omega-6/omega-3 ratio from 1:1 during evolution to 20:1 today or even higher. This change in the composition of fatty acids parallels a significant increase in the prevalence of overweight and obesity. Experimental studies have suggested that omega-6 and omega-3 fatty acids elicit divergent effects on body fat gain through mechanisms of adipogenesis, browning of adipose tissue, lipid homeostasis, brain-gut-adipose tissue axis, and most importantly systemic inflammation. Prospective studies clearly show an increase in the risk of obesity as the level of omega-6 fatty acids and the omega-6/omega-3 ratio increase in red blood cell (RBC membrane phospholipids, whereas high omega-3 RBC membrane phospholipids decrease the risk of obesity. Recent studies in humans show that in addition to absolute amounts of omega-6 and omega-3 fatty acid intake, the omega-6/omega-3 ratio plays an important role in increasing the development of obesity via both AA eicosanoid metabolites and hyperactivity of the cannabinoid system, which can be reversed with increased intake of eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA. A balanced omega-6/omega-3 ratio is important for health and in the prevention and management of obesity.

  5. miRNA-497 Negatively Regulates the Growth and Motility of Chondrosarcoma Cells by Targeting Cdc25A.

    Lu, Yandong; Li, Fangguo; Xu, Tao; Sun, Jie

    2016-01-01

    Chondrosarcoma (CHS) is the second most common malignant bone sarcoma with increased risk of invasion and metastasis. However, the regulatory mechanisms of CHS tumorigenesis remain unknown. Here we investigated the novel role of miR-497 in regulating chondrosarcoma cell growth and cell cycle arrest. RT-PCR analysis showed that the expression of miR-497 is aberrantly downregulated in human chondrosarcoma samples and cells. After transfection with miR-497 mimic or antagomir, the proliferation and apoptosis of JJ012 and OUMS-27 chondrosarcoma cells were determined by CCK-8 assay and flow cytometric analysis, respectively. Results showed that the proliferation capacity of JJ012 and OUMS-27 cells was significantly decreased by miR-497 overexpression but increased by miR-497 repression. Apoptosis in both cell types was remarkably enhanced by miR-497 mimic but inhibited by miR-497 antagomir. By bioinformatics and luciferase reporter analysis, Cdc25A was proven to be a direct target of miR-497 in chondrosarcoma cells. Further studies indicated that miR-497 modulates the growth of chondrosarcoma cells by targeting Cdc25A, in which the cell cycle inhibitor p21 is involved through a p53-independent pathway. In conclusion, we demonstrated that miR-497 represents a potential tumor suppressor in human chondrosarcoma that regulates the growth of chondrosarcoma cells by targeting Cdc25A. This may provide a novel therapeutic target for chondrosarcoma.

  6. Implementing the number needed to harm in clinical practice: risk of myocardial infarction in HIV-1-infected patients treated with abacavir

    Kowalska, J D; Kirk, O; Mocroft, A

    2010-01-01

    OBJECTIVES: The D:A:D study group reported a 1.9-fold increased relative risk (RR) of myocardial infarction (MI) associated with current or recent use of abacavir. The number needed to harm (NNH) incorporates information about the underlying risk of MI and the increased RR of MI in patients taking...

  7. Increased bleeding risk during percutaneous coronary interventions by arterial hypertension.

    Ndrepepa, Gjin; Groha, Philipp; Lahmann, Anna L; Lohaus, Raphaela; Cassese, Salvatore; Schulz-Schüpke, Stefanie; Kufner, Sebastian; Mayer, Katharina; Bernlochner, Isabell; Byrne, Robert A; Fusaro, Massimiliano; Laugwitz, Karl-Ludwig; Schunkert, Heribert; Kastrati, Adnan

    2016-08-01

    We aimed to assess the association between arterial hypertension and bleeding in patients undergoing percutaneous coronary intervention (PCI). The impact of arterial hypertension on bleeding risk of patients with coronary artery disease undergoing PCI is unknown. This study included 14,180 patients who underwent PCI. Bleeding was defined using the Bleeding Academic Research Consortium (BARC) criteria. Arterial hypertension was defined as treatment with antihypertensive drugs or a systolic blood pressure >140 mm Hg and/or diastolic blood pressure value >90 mm Hg documented on at least 2 occasions. The primary outcome was bleeding rate within 30 days of PCI. Overall, 11,066 patients (78.0%) had arterial hypertension. Bleeding events occurred in 1,232 patients with arterial hypertension and 278 patients without arterial hypertension (11.1% vs 8.9%; odds ratio [OR] = 1.28, 95% confidence interval [CI] 1.11-1.46, P arterial hypertension and 175 patients without arterial hypertension (6.6% vs 5.6%: OR = 1.19 [1.01-1.41], P = 0.049). Non-access-site bleeding occurred in 502 patients with and 103 patients without arterial hypertension (4.5% vs 3.3%; OR = 1.39 [1.12-1.72], P = 0.003). After adjustment, arterial hypertension was significantly associated with any bleeding (adjusted OR = 1.41 [1.19-1.67], P arterial hypertension increased the risk of non-access-site bleeding (P = 0.002), whereas systolic blood pressure at the time of PCI increased the risk of access site bleeding (P = 0.018). Arterial hypertension is associated with increased risk of bleeding during PCI procedures. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  8. Increased Cardiometabolic Risk and Worsening Hypoxemia at High Altitude.

    Miele, Catherine H; Schwartz, Alan R; Gilman, Robert H; Pham, Luu; Wise, Robert A; Davila-Roman, Victor G; Jun, Jonathan C; Polotsky, Vsevolod Y; Miranda, J Jaime; Leon-Velarde, Fabiola; Checkley, William

    2016-06-01

    Miele, Catherine H., Alan R. Schwartz, Robert H. Gilman, Luu Pham, Robert A. Wise, Victor G. Davila-Roman, Jonathan C. Jun, Vsevolod Y. Polotsky, J. Jaime Miranda, Fabiola Leon-Velarde, and William Checkley. Increased cardiometabolic risk and worsening hypoxemia at high altitude. High Alt Med Biol. 17:93-100, 2016.-Metabolic syndrome, insulin resistance, diabetes, and dyslipidemia are associated with an increased risk of cardiovascular disease. While excessive erythrocytosis is associated with cardiovascular complications, it is unclear how worsening hypoxemia of any degree affects cardiometabolic risk factors in high-altitude populations. We studied the relationship between daytime resting oxyhemoglobin saturation and cardiometabolic risk factors in adult participants living in Puno, Peru (3825 m above sea level). We used multivariable logistic regression models to study the relationship between having a lower oxyhemoglobin saturation and markers of cardiometabolic risk. Nine hundred and fifty-four participants (mean age 55 years, 52% male) had information available on pulse oximetry and markers of cardiometabolic risk. Average oxyhemoglobin saturation was 90% (interquartile range 88%-92%) and 43 (4.5%) had excessive erythrocytosis. Older age, decreased height-adjusted lung function, and higher body mass index (BMI) were associated with having an oxyhemoglobin saturation ≤85%. When adjusting for age, sex, socioeconomic status, having excessive erythrocytosis, and site, we found that each 5% decrease in oxyhemoglobin saturation was associated with a higher adjusted odds of metabolic syndrome (OR = 1.35, 95% CI: 1.07-1.72, p 2 mass units (OR = 1.29, 95% CI: 1.00-1.67, p < 0.05), hemoglobin A1c ≥6.5% (OR = 1.66, 95% CI: 1.09-2.51, p < 0.04), and high sensitivity C-reactive protein (hs-CRP) ≥3 mg/L (OR = 1.46, 95% CI: 1.09-1.96, p < 0.01). In high-altitude populations in Puno, Peru, a higher BMI and lower pulmonary function were

  9. Bidi smokers at increased risk of oral cancer.

    Warnakulasuriya, Saman

    2005-01-01

    Source articles were searched for using Medline, the Cochrane Library and within the references lists of identified articles. Articles were selected that included data enabling construction of 2 x 2 tables to estimate odds ratios (OR) and 95% confidence intervals (CI). For each study, two-way contingency tables were constructed, based on exposure frequency distributions, for cases and controls. Unadjusted OR and 95% CI were recalculated based on the reported data using standard procedures. Separate contingency tables were made for bidi smoking, cigarette smoking and both types of smoking if the data were available in the same article. The overall OR combined across all studies, and its 95% CI, was calculated using a random-effects model for bidi and cigarette smoking. Tests for publication bias and heterogeneity were conducted. Confounding factors, for example, betel quid chewing or alcohol use, were not included in the meta-regression model. An increased risk of oral cancer was found for bidi smokers compared with people who had never smoked (OR, 3.1; 95% CI, 2.0-5.0) whereas no significant pattern of risk was found for cigarette smokers (OR, 1.1; 95% CI, 0.7-1.8). There was substantial heterogeneity in the pooled OR estimate. The results clearly indicate that bidi smokers are at increased risk of oral cancer. It is important that this information be incorporated into smoking prevention and cessation efforts, particularly in the urban poor and rural mass in south Asian countries where bidi smoking is widespread.

  10. Splenectomy increases the subsequent risk of systemic lupus erythematosus.

    Hsu, Chao-Yu; Chen, Hsuan-Ju; Hsu, Chung Y; Kao, Chia-Hung

    2016-02-01

    Splenectomy may be necessary to treat systemic lupus erythematosus (SLE) patients with thrombocytopenia; however, whether performing a splenectomy on patients without SLE increases the subsequent risk of SLE remains unknown. Therefore, this study was conducted to determine the association between splenectomy and SLE. We conducted a cohort study by using data from the Taiwan National Health Institute Research Database to identify 10,298 patients with received a splenectomy between 2000 and 2006 and 41,192 participants without received a splenectomy who were selected by frequency matched based on sex, age, and the index year. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95 % confidence intervals (CIs) of developing SLE associated with splenectomy compared with patients who did not receive a splenectomy. During the study period, the overall incidence density rate of SLE was higher in the splenectomy cohort than in the non-splenectomy cohort (adjusted HR 10.55; 95 % CI 50.55-20.05). The incidence density rates of SLE in women and men who received a splenectomy were higher than those of patients who did not receive a splenectomy. Non-traumatic splenectomy increases the subsequent risk of SLE. The risk of SLE should be considered before performing a splenectomy, particularly in women and younger patients.

  11. miRSeqNovel

    Qian, Kui; Auvinen, Eeva; Greco, Dario

    2012-01-01

    We present miRSeqNovel, an R based workflow for miRNA sequencing data analysis. miRSeqNovel can process both colorspace (SOLiD) and basespace (Illumina/Solexa) data by different mapping algorithms. It finds differentially expressed miRNAs and gives conservative prediction of novel miRNA candidates...... with customized parameters. miRSeqNovel is freely available at http://sourceforge.net/projects/mirseq/files....

  12. Increased relative risk of myelodysplastic syndrome in atomic bomb survivors

    Oda, Kenji; Kimura, Akiro; Matsuo, Tatsuki; Tomonaga, Masao; Kodama, Kazunori; Mabuchi, Kiyohiko

    1998-01-01

    It was investigated what blood disorders except leukemia increased the relative risk with dose dependency in atomic bomb survivors. Subjects were 217 patients of atomic bomb survivors in Hiroshima and Nagasaki, who had blood disorders except leukemia and died between 1950 and 1990. Their medical records were analyzed and their diagnoses were reevaluated. Sixteen cases were diagnosed as the aplastic anemia and 12 as the myelodysplastic syndrome (MDS). In the aplastic anemia, there was no correlation between the exposure dose and the mortality. In MDS, the excess relative risk (ERR)/bone marrow exposure dose of 1 Sv was very high (13.0). These results supports the hypothesis that MDS would be broken out by the clonal abnormality of the hematopoietic stem cell and radiation exposure could cause the appearance of the abnormal stem cell clone. (K.H.)

  13. Increased relative risk of myelodysplastic syndrome in atomic bomb survivors

    Oda, Kenji [Hiroshima City Hospital (Japan); Kimura, Akiro; Matsuo, Tatsuki; Tomonaga, Masao; Kodama, Kazunori; Mabuchi, Kiyohiko

    1998-12-01

    It was investigated what blood disorders except leukemia increased the relative risk with dose dependency in atomic bomb survivors. Subjects were 217 patients of atomic bomb survivors in Hiroshima and Nagasaki, who had blood disorders except leukemia and died between 1950 and 1990. Their medical records were analyzed and their diagnoses were reevaluated. Sixteen cases were diagnosed as the aplastic anemia and 12 as the myelodysplastic syndrome (MDS). In the aplastic anemia, there was no correlation between the exposure dose and the mortality. In MDS, the excess relative risk (ERR)/bone marrow exposure dose of 1 Sv was very high (13.0). These results supports the hypothesis that MDS would be broken out by the clonal abnormality of the hematopoietic stem cell and radiation exposure could cause the appearance of the abnormal stem cell clone. (K.H.)

  14. Schooling increases risk exposure for fish navigating past artificial barriers.

    Bertrand H Lemasson

    Full Text Available Artificial barriers have become ubiquitous features in freshwater ecosystems and they can significantly impact a region's biodiversity. Assessing the risk faced by fish forced to navigate their way around artificial barriers is largely based on assays of individual swimming behavior. However, social interactions can significantly influence fish movement patterns and alter their risk exposure. Using an experimental flume, we assessed the effects of social interactions on the amount of time required for juvenile palmetto bass (Morone chrysops × M. saxatilis to navigate downstream past an artificial barrier. Fish were released either individually or in groups into the flume using flow conditions that approached the limit of their expected swimming stamina. We compared fish swimming behaviors under solitary and schooling conditions and measured risk as the time individuals spent exposed to the barrier. Solitary fish generally turned with the current and moved quickly downstream past the barrier, while fish in groups swam against the current and displayed a 23-fold increase in exposure time. Solitary individuals also showed greater signs of skittish behavior than those released in groups, which was reflected by larger changes in their accelerations and turning profiles. While groups displayed fission-fusion dynamics, inter-individual positions were highly structured and remained steady over time. These spatial patterns align with theoretical positions necessary to reduce swimming exertion through either wake capturing or velocity sheltering, but diverge from any potential gains from channeling effects between adjacent neighbors. We conclude that isolated performance trials and projections based on individual behaviors can lead to erroneous predictions of risk exposure along engineered structures. Our results also suggest that risk perception and behavior may be more important than a fish's swimming stamina in artificially modified systems.

  15. Schooling increases risk exposure for fish navigating past artificial barriers.

    Lemasson, Bertrand H; Haefner, James W; Bowen, Mark D

    2014-01-01

    Artificial barriers have become ubiquitous features in freshwater ecosystems and they can significantly impact a region's biodiversity. Assessing the risk faced by fish forced to navigate their way around artificial barriers is largely based on assays of individual swimming behavior. However, social interactions can significantly influence fish movement patterns and alter their risk exposure. Using an experimental flume, we assessed the effects of social interactions on the amount of time required for juvenile palmetto bass (Morone chrysops × M. saxatilis) to navigate downstream past an artificial barrier. Fish were released either individually or in groups into the flume using flow conditions that approached the limit of their expected swimming stamina. We compared fish swimming behaviors under solitary and schooling conditions and measured risk as the time individuals spent exposed to the barrier. Solitary fish generally turned with the current and moved quickly downstream past the barrier, while fish in groups swam against the current and displayed a 23-fold increase in exposure time. Solitary individuals also showed greater signs of skittish behavior than those released in groups, which was reflected by larger changes in their accelerations and turning profiles. While groups displayed fission-fusion dynamics, inter-individual positions were highly structured and remained steady over time. These spatial patterns align with theoretical positions necessary to reduce swimming exertion through either wake capturing or velocity sheltering, but diverge from any potential gains from channeling effects between adjacent neighbors. We conclude that isolated performance trials and projections based on individual behaviors can lead to erroneous predictions of risk exposure along engineered structures. Our results also suggest that risk perception and behavior may be more important than a fish's swimming stamina in artificially modified systems.

  16. Is white-coat hypertension a harbinger of increased risk?

    Kollias, Anastasios; Ntineri, Angeliki; Stergiou, George S

    2014-09-01

    White-coat hypertension is defined by elevated office and normal out-of-office blood pressure (home or ambulatory) in untreated subjects. This condition is common in clinical practice and requires appropriate work-up for detection and management. Many studies have examined the relationship between white-coat hypertension and cardiovascular risk but with marked heterogeneity in the definitions and methodology applied. Thus, the results have been inconsistent leading to confusion in scientific research and clinical practice. Some but not all the relevant studies suggested that white-coat hypertension is associated with subclinical target-organ damage, yet the cross-sectional design of these studies and the fact that these indices are only surrogate end points do not allow firm conclusions to be drawn. In recent years, longitudinal studies have examined the prognostic significance of white-coat hypertension in terms of cardiovascular morbidity and mortality. Most of them indicate that white-coat hypertensive compared with normotensive subjects present a moderate-in most cases not significant-increase in risk. Meta-analyses of raw data from large databases, such as the International Database on Ambulatory blood pressure and Cardiovascular Outcomes (IDACO) and the International Database on HOme blood pressure in relation to Cardiovascular Outcomes (IDHOCO) allowed separate powered analyses in untreated subjects and provided a clearer picture regarding the modest risk associated with white-coat hypertension, especially in the long term. White-coat hypertension is regarded as an intermediate phenotype between normotension and hypertension associated with increased risk of developing sustained hypertension, and therefore requires regular follow-up using nonpharmacological measures.

  17. Organ utilization from increased infectious risk donors: An observational study.

    L'Huillier, Arnaud G; Humar, Atul; Payne, Clare; Kumar, Deepali

    2017-12-01

    Donors with an increased risk of transmitting human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) (increased risk donors [IRDs]) are a potential source of organs for transplant. Organs from IRDs can be utilized with appropriate recipient consent and post-transplant follow-up. We reviewed the characteristics and utilization of IRDs in our Organ Procurement Organization (OPO) over a 2-year period. Donor information from April 1, 2013 to March 31, 2015 was obtained through the OPO database. Only consented donors were included. Donors were categorized as IRDs according to Health Canada/Canadian Standards Association (CSA) criteria. A total of 494 potential donors were identified, of which 92 (18.6%) were IRDs. Of these, at least one organ was transplanted from 76 (82.6%). Risk factors for IRDs included injection drug user (IDU) (12%), men having sex with men (MSM) (7%), commercial sex worker (CSW) (4%), and incarceration (24%). Fifty-nine percent (253/429) of IRD organs were utilized. The most frequently used organ was kidney, followed by liver. Median number of organs recovered per IRD was 3 (interquartile range: 2-5). Nucleic acid testing (NAT) was performed in 18.5% (17/92) of IRDs. Reasons for NAT were IDU (n = 2), MSM (n = 2), CSW (n = 2), and previous incarceration (n = 7). Organ utilization from donors that had NAT was similar to donors who did not (94% vs 80%, P = .29). Follow-up NAT was done in multiple factors contribute to the perception of infectious risk from such organs. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Topiramate increases the risk of valproic acid-induced encephalopathy.

    Noh, Young; Kim, Dong Wook; Chu, Kon; Lee, Soon-Tae; Jung, Keun-Hwa; Moon, Hye-Jin; Lee, Sang Kun

    2013-01-01

    Metabolic encephalopathy is a rare but serious complication of valproic acid (VPA) therapy that usually presents with impaired consciousness or increased seizure frequency. Although it has been suggested that topiramate (TPM) increases the risk of VPA-induced encephalopathy, the additional risk in patients receiving TPM therapy has not been evaluated. We reviewed all adult patients who took VPA between January 2005 and February 2009 at the Seoul National University Hospital and identified patients with VPA-induced encephalopathy based on clinical and electroencephalography (EEG) data. Information on sex, age, serum ammonia level, serum VPA level, liver function test, and EEG was collected from patient registry and medical data. We enrolled 8,372 patients who received VPA therapy and 1,236 patients who received VPA/TPM combination therapy. We identified 11 patients with VPA-induced encephalopathy (0.13%), 7 of whom received a combination therapy of VPA and TPM. The odds ratio of VPA-induced encephalopathy with TPM over that without TPM was 10.16. There were no significant differences in sex distribution, number of antiepileptic agents, ammonia level, VPA serum level, underlying diseases, dosage of VPA, duration of VPA treatment, treatment of encephalopathy, and outcomes between the two groups. Our study showed that the prevalence of VPA-induced encephalopathy is approximately 0.1% among patients treated with VPA and that the risk of this condition, although still low, can increase by approximately 10 times in the presence of TPM therapy. Based on these results, we suggest that TPM should be carefully used in patients receiving VPA treatment. Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.

  19. Risk of myocardial infarction in parents of HIV-infected Individuals: a population-based Cohort Study

    Rasmussen, Line D; Omland, Lars H; Pedersen, Court

    2010-01-01

    with the HIV disease and HAART or whether life-style related or genetic factors also increase the risk in this population. To establish whether the increased risk of myocardial infarction in HIV patients partly reflects an increased risk of MI in their families, we estimated the relative risk of MI in parents...

  20. Possible risk factors for increased suicide following bariatric surgery.

    Mitchell, James E; Crosby, Ross; de Zwaan, Martina; Engel, Scott; Roerig, James; Steffen, Kristine; Gordon, Kathryn H; Karr, Trisha; Lavender, Jason; Wonderlich, Steve

    2013-04-01

    There is a growing research literature suggesting that there may be elevated risk of suicide following bariatric surgery. Most of the data reported thus far has been cross-sectional and observational, and very little is known about the possible specific causal variables involved. The purpose of this report is to review this literature and to review possible risk factors for increased suicidal risk following bariatric surgery, to delineate future research directions. First a variety of medical, biological, and genetic factors, including the persistence or recurrence of medical comorbidities after bariatric surgery, the disinhibition and impulsivity secondary to changes in the absorption of alcohol, hypoglycemia, as well as pharmacokinetic changes that may affect the absorption of various medications including antidepressant medications are reviewed. Also reviewed are possible mediating factors involving changes in various peptidergic systems such as GLP-1 and Ghrelin. A number of psychosocial issues that might be involved are discussed, including lack of improvement in quality of life after surgery, continued or recurrent physical mobility restrictions, persistence or recurrence of sexual dysfunction and relationship problems, low self-esteem, and a history of child maltreatment. Inadequate weight loss or weight regain are also discussed. A number of possible contributing factors have been identified. Possible theoretical models involved and directions for research are suggested. Copyright © 2012 The Obesity Society.

  1. A detailed family history of myocardial infarction and risk of myocardial infarction

    Ranthe, Mattis Flyvholm; Petersen, Jonathan Aavang; Bundgård, Henning

    2015-01-01

    of cardiovascular medications. CONCLUSION: A detailed family history, particularly number of affected first- and second-degree relatives, contributes meaningfully to risk assessment, especially in middle-aged persons. Future studies should test for potential improvement of risk algorithm prediction using detailed......BACKGROUND: Family history of myocardial infarction (MI) is an independent risk factor for MI. Several genetic variants are associated with increased risk of MI and family history of MI in a first-degree relative doubles MI risk. However, although family history of MI is not a simple dichotomous...... risk factor, the impact of specific, detailed family histories has not received much attention, despite its high clinical relevance. We examined risk of MI by MIs in first- and second-degree relatives and by number and age of affected relatives. METHODS AND FINDINGS: Using Danish national registers, we...

  2. Energy drink consumption and increased risk for alcohol dependence.

    Arria, Amelia M; Caldeira, Kimberly M; Kasperski, Sarah J; Vincent, Kathryn B; Griffiths, Roland R; O'Grady, Kevin E

    2011-02-01

    Energy drinks are highly caffeinated beverages that are increasingly consumed by young adults. Prior research has established associations between energy drink use and heavier drinking and alcohol-related problems among college students. This study investigated the extent to which energy drink use might pose additional risk for alcohol dependence over and above that from known risk factors. Data were collected via personal interview from 1,097 fourth-year college students sampled from 1 large public university as part of an ongoing longitudinal study. Alcohol dependence was assessed according to DSM-IV criteria. After adjustment for the sampling design, 51.3%(wt) of students were classified as "low-frequency" energy drink users (1 to 51 days in the past year) and 10.1%(wt) as "high-frequency" users (≥52 days). Typical caffeine consumption varied widely depending on the brand consumed. Compared to the low-frequency group, high-frequency users drank alcohol more frequently (141.6 vs. 103.1 days) and in higher quantities (6.15 vs. 4.64 drinks/typical drinking day). High-frequency users were at significantly greater risk for alcohol dependence relative to both nonusers (AOR = 2.40, 95% CI = 1.27 to 4.56, p = 0.007) and low-frequency users (AOR = 1.86, 95% CI = 1.10, 3.14, p = 0.020), even after holding constant demographics, typical alcohol consumption, fraternity/sorority involvement, depressive symptoms, parental history of alcohol/drug problems, and childhood conduct problems. Low-frequency energy drink users did not differ from nonusers on their risk for alcohol dependence. Weekly or daily energy drink consumption is strongly associated with alcohol dependence. Further research is warranted to understand the possible mechanisms underlying this association. College students who frequently consume energy drinks represent an important target population for alcohol prevention. Copyright © 2010 by the Research Society on Alcoholism.

  3. Knockdown of long non-coding RNA HOTAIR increases miR-454-3p by targeting Stat3 and Atg12 to inhibit chondrosarcoma growth.

    Bao, Xing; Ren, Tingting; Huang, Yi; Sun, Kunkun; Wang, Shidong; Liu, Kuisheng; Zheng, Bingxin; Guo, Wei

    2017-02-09

    Current practices for the therapy of chondrosarcoma, including wide-margin surgical resection and chemotherapy, are less than satisfactory. Recently, emerging evidence has demonstrated that long non-coding RNAs (lncRNAs) have an essential role in the initiation and progression of tumors. As a typical lncRNA, HOTAIR is significantly overexpressed in various tumors. However, the function and potential biological mechanisms of HOTAIR in human chondrosarcoma remain unknown. Quantitative RT-PCR demonstrated that HOTAIR expression was upregulated in chondrosarcoma tissues and cell lines. High HOTAIR expression is correlated with tumor stage and poor prognosis. Functional experiments reveal that HOTAIR knockdown leads to growth inhibition of human chondrosarcoma cells in vitro and in vivo. In addition to cycle arrest and apoptosis, knockdown of HOTAIR inhibits autophagy, which favors cell death. Mechanistically, we demonstrated that HOTAIR induced DNA methylation of miR-454-3p by recruiting EZH2 and DNMT1 to the miR-454-3p promoter regions, which markedly silences miR-454-3p expression. Further analysis revealed that STAT3 and ATG12 are targets of miR-454-3p, initiate HOTAIR deficiency-induced apoptosis and reduce autophagy. Collectively, our data reveal the roles and functional mechanisms of HOTAIR in human chondrosarcoma and suggest that HOTAIR may act as a prognostic biomarker and potential therapeutic target for chondrosarcoma.

  4. Heightened fire risk in Indonesia in response to increasing temperature

    Fernandes, K.; Baethgen, W.; Verchot, L. V.; Gutierrez-Velez, V.; Pinedo-Vasquez, M.

    2016-12-01

    In Indonesia, drought driven fires occur typically during the warm phase of the El Niño Southern Oscillation (ENSO), such as those of 1997 and 2015 that resulted in months-long hazardous atmospheric pollution levels in Equatorial Asia and record greenhouse gas emissions. Nonetheless, anomalously active fire seasons have also been observed in non-drought years. In this work, we investigated whether fires are impacted by temperature anomalies and if so, if the responses differ under contrasting precipitation regimes. Our findings show that when the July-October dry-season is anomalously dry, the sensitivity of fires to temperature anomalies is similar regardless of the sign of the anomalies. In contrast, in wet condition, fire risk increases sharply when the dry season is anomalously warm. We also present a characterization of near-term regional climate projections over the next few decades and the implications of continuing global temperature increase in future fire probability in Indonesia.

  5. Modifiable risk factors for increased arterial stiffness in outpatient nephrology.

    Usama Elewa

    Full Text Available Arterial stiffness, as measured by pulse wave velocity (PWV, is an independent predictor of cardiovascular events and mortality. Arterial stiffness increases with age. However, modifiable risk factors such as smoking, BP and salt intake also impact on PWV. The finding of modifiable risk factors may lead to the identification of treatable factors, and, thus, is of interest to practicing nephrologist. We have now studied the prevalence and correlates of arterial stiffness, assessed by PWV, in 191 patients from nephrology outpatient clinics in order to identify modifiable risk factors for arterial stiffness that may in the future guide therapeutic decision-making. PWV was above normal levels for age in 85/191 (44.5% patients. Multivariate analysis showed that advanced age, systolic BP, diabetes mellitus, serum uric acid and calcium polystyrene sulfonate therapy or calcium-containing medication were independent predictors of PWV. A new parameter, Delta above upper limit of normal PWV (Delta PWV was defined to decrease the weight of age on PWV values. Delta PWV was calculated as (measured PWV - (upper limit of the age-adjusted PWV values for the general population. Mean±SD Delta PWV was 0.76±1.60 m/sec. In multivariate analysis, systolic blood pressure, active smoking and calcium polystyrene sulfonate therapy remained independent predictors of higher delta PWV, while age, urinary potassium and beta blocker therapy were independent predictors of lower delta PWV. In conclusion, arterial stiffness was frequent in nephrology outpatients. Systolic blood pressure, smoking, serum uric acid, calcium-containing medications, potassium metabolism and non-use of beta blockers are modifiable factors associated with increased arterial stiffness in Nephrology outpatients.

  6. Increased physical activity decreases periodontitis risk in men

    Merchant, Anwar T.; Pitiphat, Waranuch; Rimm, Eric B.; Joshipura, Kaumudi

    2003-01-01

    Background: Increased physical activity improves insulin sensitivity and glucose metabolism, and may therefore affect incidence of periodontitis. Methods: We studied the association of physical activity, walking and periodontitis in 39,461 male, US based, health professionals, 40-75 years old at baseline, more than half of whom were dentists, being followed up continuously since 1986. Participants were free of periodontitis, coronary heart disease and stroke at the start of follow-up. Physical activity and periodontitis were measured by validated questionnaires (expressed in metabolic equivalents - METs); the first report of professionally diagnosed periodontitis was considered a case. Results: Periodontitis risk decreased by 3% for every 10-MET increase in average physical activity after adjustment for age, smoking, diabetes, BMI, alcohol consumption and total calories (RR = 0.97; 95% CI: 0.95-0.99). The inverse trend remained significant in the categorical analysis. Compared to men in the lowest quintile of physical activity, those in the highest quintile had a 13% lower risk of periodontitis (RR = 0.87; 95% CI: 0.76-1.01, p-value, test for trend = 0.02). In a sub-sample of men with radiographs (n = 137) the physically active had less average bone loss (β = -0.29, p-value = 0.03) after multivariate adjustment compared to those inactive. Conclusions: In this large-scale prospective study, we found an inverse, linear association between sustained physical activity and periodontitis independent of known risk factors. The benefits of a physically active lifestyle may extend to periodontal health

  7. Are recreational SCUBA divers with asthma at increased risk?

    Ustrup, Amalie S; Ulrik, Charlotte S

    2017-10-01

    Asthma has traditionally been regarded as a contraindication to self-contained underwater breathing apparatus (SCUBA) diving, although large numbers of patients with asthma dive. The aim of the review is to provide an update on current knowledge on potential disease-related hazards in SCUBA divers with asthma. Systematic literature review based on the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Seven studies met the criteria for inclusion in the review (comprising a total of 560 subjects). Five studies reported an increased risk for developing diving-related injuries in divers with asthma, based on case reports (n = 1), case history combined with objective assessment (n = 1), and dives and/or simulated dives (n = 3). The remaining studies (n = 2) were based on self-reported diving habits in divers suffering from asthma, obtained from anonymous questionnaires in diving magazines, reported no diving-related injuries among respondents. Due to limited evidence it is difficult to draw valid conclusions, but there are indications that recreational divers with asthma may be at increased risk for diving-related injuries compared to non-asthmatic divers. However, it is of at most importance to obtain further evidence from large-scale, well-designed studies.

  8. miRNAs in brain development

    Petri, Rebecca; Malmevik, Josephine; Fasching, Liana; Åkerblom, Malin; Jakobsson, Johan

    2014-01-01

    MicroRNAs (miRNAs) are small, non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. In the brain, a large number of miRNAs are expressed and there is a growing body of evidence demonstrating that miRNAs are essential for brain development and neuronal function. Conditional knockout studies of the core components in the miRNA biogenesis pathway, such as Dicer and DGCR8, have demonstrated a crucial role for miRNAs during the development of the central nervous system. Furthermore, mice deleted for specific miRNAs and miRNA-clusters demonstrate diverse functional roles for different miRNAs during the development of different brain structures. miRNAs have been proposed to regulate cellular functions such as differentiation, proliferation and fate-determination of neural progenitors. In this review we summarise the findings from recent studies that highlight the importance of miRNAs in brain development with a focus on the mouse model. We also discuss the technical limitations of current miRNA studies that still limit our understanding of this family of non-coding RNAs and propose the use of novel and refined technologies that are needed in order to fully determine the impact of specific miRNAs in brain development. - Highlights: • miRNAs are essential for brain development and neuronal function. • KO of Dicer is embryonically lethal. • Conditional Dicer KO results in defective proliferation or increased apoptosis. • KO of individual miRNAs or miRNA families is necessary to determine function

  9. Increased risk of coronary heart disease among individuals reporting adverse impact of stress on their health: the Whitehall II prospective cohort study.

    Nabi, Hermann; Kivimäki, Mika; Batty, G David; Shipley, Martin J; Britton, Annie; Brunner, Eric J; Vahtera, Jussi; Lemogne, Cédric; Elbaz, Alexis; Singh-Manoux, Archana

    2013-09-01

    Response to stress can vary greatly between individuals. However, it remains unknown whether perceived impact of stress on health is associated with adverse health outcomes. We examined whether individuals who report that stress adversely affects their health are at increased risk of coronary heart disease (CHD) compared with those who report that stress has no adverse health impact. Analyses are based on 7268 men and women (mean age: 49.5 years, interquartile range: 11 years) from the British Whitehall II cohort study. Over 18 years of follow-up, there were 352 coronary deaths or first non-fatal myocardial infarction (MI) events. After adjustment for sociodemographic characteristics, participants who reported at baseline that stress has affected their health 'a lot or extremely' had a 2.12 times higher (95% CI 1.52-2.98) risk of coronary death or incident non-fatal MI when compared with those who reported no effect of stress on their health. This association was attenuated but remained statistically significant after adjustment for biological, behavioural, and other psychological risk factors including perceived stress levels, and measures of social support; fully adjusted hazard ratio: 1.49 (95% CI 1.01-2.22). In this prospective cohort study, the perception that stress affects health, different from perceived stress levels, was associated with an increased risk of coronary heart disease. Randomized controlled trials are needed to determine whether disease risk can be reduced by increasing clinical attention to those who complain that stress greatly affects their health.

  10. Lifestyle Risk Factors Increase the Risk of Hospitalization for Sciatica: Findings of Four Prospective Cohort Studies.

    Shiri, Rahman; Euro, Ulla; Heliövaara, Markku; Hirvensalo, Mirja; Husgafvel-Pursiainen, Kirsti; Karppinen, Jaro; Lahti, Jouni; Rahkonen, Ossi; Raitakari, Olli T; Solovieva, Svetlana; Yang, Xiaolin; Viikari-Juntura, Eira; Lallukka, Tea

    2017-12-01

    The purpose of this study is to assess the effects of lifestyle risk factors on the risk of hospitalization for sciatica and to determine whether overweight or obesity modifies the effect of leisure-time physical activity on hospitalization for sciatica. We included 4 Finnish prospective cohort studies (Health 2000 Survey, Mobile Clinic Survey, Helsinki Health Study, and Young Finns Study) consisting of 34,589 participants and 1259 hospitalizations for sciatica during 12 to 30 years of follow-up. Sciatica was based on hospital discharge register data. We conducted a random-effects individual participant data meta-analysis. After adjustment for confounding factors, current smoking at baseline increased the risk of subsequent hospitalization for sciatica by 33% (95% confidence interval [CI], 13%-56%), whereas past smokers were no longer at increased risk. Obesity defined by body mass index increased the risk of hospitalization for sciatica by 36% (95% CI 7%-74%), and abdominal obesity defined by waist circumference increased the risk by 41% (95% CI 3%-93%). Walking or cycling to work reduced the risk of hospitalization for sciatica by 33% (95% CI 4%-53%), and the effect was independent of body weight and other leisure activities, while other types of leisure activities did not have a statistically significant effect. Smoking and obesity increase the risk of hospitalization for sciatica, whereas walking or cycling to work protects against hospitalization for sciatica. Walking and cycling can be recommended for the prevention of sciatica in the general population. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Increased sexually transmitted infection incidence in a low risk population: identifying the risk factors.

    Shiely, Frances

    2010-04-01

    Between 1994 and 2006, the incidence of sexually transmitted infections (STIs) in Ireland has increased by over 300%. Recent literature would suggest that this figure is an underestimation of the true scale of infection. Our objective was to determine the risk factors associated with STI diagnosis in a population with a rapidly increasing STI incidence.

  12. Thyroid cancer risk is not increased in diabetic patients.

    Chin-Hsiao Tseng

    -inflammatory drugs might be associated with a significantly lower risk. CONCLUSIONS: There is a lack of an overall association between diabetes and thyroid cancer, but patients with diabetes duration <5 years have a significantly lower risk. Sulfonylurea may increase the risk of thyroid cancer.

  13. Women referred for occupational risk assessment in pregnancy have no increased risk of adverse obstetric outcomes

    Bidstrup, Signe Brøker; Kaerlev, Linda; Thulstrup, Ane Marie

    2015-01-01

    INTRODUCTION: Our aim was to study the association between pregnant women's referral status for occupational risk assessment, and their risk of preterm delivery (METHODS: In a cohort study, 1,202 deliveries among....../or that the occupational risk assessment and counselling of pregnant women are preventing these selected adverse pregnancy outcomes. FUNDING: The Research Unit at Department of Occupational and Environmental Medicine at Bispebjerg Hospital supported the study financially. TRIAL REGISTRATION: not relevant. The study.......72-1.17). CONCLUSION: The women who are referred for occupational risk assessment at two large occupational university departments are not at an increased risk of preterm birth or of delivering low birth weight children. This may reflect that reproductive hazards in Danish workplaces are limited and...

  14. Women referred for occupational risk assessment in pregnancy have no increased risk of adverse obstetric outcomes

    Bidstrup, Signe Brøker; Kaerlev, Linda; Thulstrup, Ane Marie

    2015-01-01

    .72-1.17). CONCLUSION: The women who are referred for occupational risk assessment at two large occupational university departments are not at an increased risk of preterm birth or of delivering low birth weight children. This may reflect that reproductive hazards in Danish workplaces are limited and....../or that the occupational risk assessment and counselling of pregnant women are preventing these selected adverse pregnancy outcomes. FUNDING: The Research Unit at Department of Occupational and Environmental Medicine at Bispebjerg Hospital supported the study financially. TRIAL REGISTRATION: not relevant. The study......INTRODUCTION: Our aim was to study the association between pregnant women's referral status for occupational risk assessment, and their risk of preterm delivery (

  15. Increased risk of hydrocephalus in long-term dialysis patients.

    Wang, I-Kuan; Lin, Cheng-Li; Cheng, Yu-Kai; Chou, Che-Yi; Liang, Chih-Chia; Yen, Tzung-Hai; Sung, Fung-Chang

    2016-05-01

    The risk of hydrocephalus in end-stage renal disease (ESRD) patients on dialysis has not been studied in depth. Using Taiwan National Health Insurance claims data, we identified 29 684 incident ESRD patients from 2000 to 2010, including 10 030 peritoneal dialysis (PD) patients and 19 654 hemodialysis (HD) patients. The control cohort consisted of 118 736 people randomly selected from those without kidney disease, frequency matched with ESRD patients by age, sex and index year. We also established propensity score-matched cohorts with 10 014 PD and 10 014 HD patients. The incidence rates and hazard ratios (HRs) of hydrocephalus were calculated until the end of 2011. Incidence rates of hydrocephalus were greater in HD and PD patients than in controls (8.44 and 11.0 versus 4.11 per 10 000 person-years, respectively), with an adjusted HR of 1.86 [95% confidence interval (CI) 1.43-2.41] for all ESRD patients compared with controls. A higher proportion of hydrocephalus patients underwent surgical bypass to relieve hydrocephalus in ESRD patients than controls, 40.7% (46/113) versus 24.5% (67/273), with an adjusted odds ratio of 2.11 (95% CI 1.33-3.36). Compared with controls, the adjusted HRs of communicating hydrocephalus for HD and PD patients were 1.77 (95% CI 1.22-2.55) and 2.51 (95% CI 1.61-3.89), respectively. The propensity score-matched analysis showed an HR of 0.72 (95% CI 0.42-1.23) for hydrocephalus in HD patients compared with PD patients. Patients with ESRD are at an increased risk of hydrocephalus. The risk difference between HD and PD patients is not significant. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  16. Regulation of cardiac expression of the diabetic marker microRNA miR-29.

    Nicholas Arnold

    Full Text Available Diabetes mellitus (DM is an independent risk factor for heart disease and its underlying mechanisms are unclear. Increased expression of diabetic marker miR-29 family miRNAs (miR-29a, b and c that suppress the pro-survival protein Myeloid Cell Leukemia 1(MCL-1 is reported in pancreatic β-cells in Type 1 DM. Whether an up-regulation of miR-29 family miRNAs and suppression of MCL-1 (dysregulation of miR-29-MCL-1 axis occurs in diabetic heart is not known. This study tested the hypothesis that insulin regulates cardiac miR-29-MCL-1 axis and its dysregulation correlates with DM progression. In vitro studies with mouse cardiomyocyte HL-1 cells showed that insulin suppressed the expression of miR-29a, b and c and increased MCL-1 mRNA. Conversely, Rapamycin (Rap, a drug implicated in the new onset DM, increased the expression of miR-29a, b and c and suppressed MCL-1 and this effect was reversed by transfection with miR-29 inhibitors. Rap inhibited mammalian target of rapamycin complex 1 (mTORC1 signaling in HL-1 cells. Moreover, inhibition of either mTORC1 substrate S6K1 by PF-4708671, or eIF4E-induced translation by 4E1RCat suppressed MCL-1. We used Zucker diabetic fatty (ZDF rat, a rodent model for DM, to test whether dysregulation of cardiac miR-29-MCL-1 axis correlates with DM progression. 11-week old ZDF rats exhibited significantly increased body weight, plasma glucose, insulin, cholesterol, triglycerides, body fat, heart weight, and decreased lean muscle mass compared to age-matched lean rats. Rap treatment (1.2 mg/kg/day, from 9-weeks to 15-weeks significantly reduced plasma insulin, body weight and heart weight, and severely dysregulated cardiac miR-29-MCL1 axis in ZDF rats. Importantly, dysregulation of cardiac miR-29-MCL-1 axis in ZDF rat heart correlated with cardiac structural damage (disorganization or loss of myofibril bundles. We conclude that insulin and mTORC1 regulate cardiac miR-29-MCL-1 axis and its dysregulation caused by reduced

  17. Caesarean section greatly increases risk of scar endometriosis.

    Nominato, Nilo Sérgio; Prates, Luis Felipe Victor Spyer; Lauar, Isabela; Morais, Jaqueline; Maia, Laura; Geber, Selmo

    2010-09-01

    To estimate the incidence of scar endometriosis after different surgical procedures. A retrospective study of 72 patients diagnosed with scar endometriosis between 1978 and 2003 was performed. Patient age, site of endometriosis, previous operations, time-gap between last surgery and onset of symptoms, nodule characteristics, and recurrence were evaluated. Age ranged from 16 to 48 years. Location varied according to the previous surgery: 46 caesarean section, one hysterectomy, one in abdominal surgery, 19 episiotomy, one was a relapse and two pelvic floor procedures, two women with no previous surgery. The incidence of scar endometriosis after caesarean section was significantly higher than after episiotomy (0.2 and 0.06%, respectively: p<0.00001) with a relative risk of 3.3. Pain was the most frequent symptom. The mean time between surgery and onset of symptoms was 3.7 years. Our findings confirm that scar endometriosis is a rare condition and indicate, probably for the first time, that caesarean section greatly increases the risk of developing scar endometriosis. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

  18. Risk Factors Associated with Increased Morbidity in Living Liver Donation

    Helry L. Candido

    2015-01-01

    Full Text Available Living donor liver donation (LDLD is an alternative to cadaveric liver donation. We aimed at identifying risk factors and developing a score for prediction of postoperative complications (POCs after LDLD in donors. This is a retrospective cohort study in 688 donors between June 1995 and February 2014 at Hospital Sírio-Libanês and A.C. Camargo Cancer Center, in São Paulo, Brazil. Primary outcome was POC graded ≥III according to the Clavien-Dindo classification. Left lateral segment (LLS, left lobe (LL, and right lobe resections (RL were conducted in 492 (71.4%, 109 (15.8%, and 87 (12.6% donors, respectively. In total, 43 (6.2% developed POCs, which were more common after RL than LLS and LL (14/87 (16.1% versus 23/492 (4.5% and 6/109 (5.5%, resp., p<0.001. Multivariate analysis showed that RL resection (OR: 2.81, 95% CI: 1.32 to 3.01; p=0.008, smoking status (OR: 3.2, 95% CI: 1.35 to 7.56; p=0.012, and blood transfusion (OR: 3.15, 95% CI: 1.45 to 6.84; p=0.004 were independently associated with POCs. RL resection, intraoperative blood transfusion, and smoking were associated with increased risk for POCs in donors.

  19. Increased risk of abortion after genetic amniocentesis in twin pregnancies

    Palle, C; Andersen, J W; Tabor, A

    1983-01-01

    Forty-seven twin pregnancies among 3676 patients who had a genetic amniocentesis between 1973 and 1979, are reported. The detection rate of twins at the time of amniocentesis was 62 per cent. Five (17 per cent) of the 29 women with detected twin pregnancy aborted spontaneously, these are compared...... in at least one sac aborted, while 3 of 20 twin pregnancies with one puncture in each sac aborted (15 per cent). One of 18 (6 per cent) twin pregnancies, where only one sac was punctured, because the twin pregnancies were undetected, aborted. Amniocentesis of both sacs in twin pregnancies seems associated...... with an increased risk of spontaneous abortion. The indications for amniocentesis in twin pregnancies should be critically evaluated....

  20. Drugs of abuse and increased risk of psychosis development.

    Gururajan, Anand; Manning, Elizabeth E; Klug, Maren; van den Buuse, Maarten

    2012-12-01

    There is considerable evidence to suggest that the abuse of illicit drugs, particularly cannabis and methamphetamine, has aetiological roles in the pathogenesis of psychosis and schizophrenia. Factors that may increase susceptibility to the propsychotic effects of these drugs include the age at which the abuse starts as well as family history of genetic polymorphisms relevant to the pathophysiology of this disorder. However, the neurobiological mechanisms involved in drug abuse-associated psychosis remain largely unclear. This paper presents an overview of the available evidence, including clinical, animal model, and molecular studies, with a focus on brain regions and neurotransmitters systems, such as dopamine and glutamate, previously implicated in psychosis. It is clear that further studies are urgently needed to provide a greater insight into the mechanisms that mediate the long-term and neurodevelopmental effects of cannabis and methamphetamine. A dialogue between basic science and clinical research may help to identify at-risk individuals and novel pathways for treatment and prevention.

  1. Can stress in farm animals increase food safety risk?

    Rostagno, Marcos H

    2009-09-01

    All farm animals will experience some level of stress during their lives. Stress reduces the fitness of an animal, which can be expressed through failure to achieve production performance standards, or through disease and death. Stress in farm animals can also have detrimental effects on the quality of food products. However, although a common assumption of a potential effect of stress on food safety exists, little is actually known about how this interaction may occur. The aim of this review was to examine the current knowledge of the potential impact of stress in farm animals on food safety risk. Colonization of farm animals by enteric pathogens such as Escherichia coli O157:H7, Salmonella, and Campylobacter, and their subsequent dissemination into the human food chain are a major public health and economic concern for the food industries. This review shows that there is increasing evidence to demonstrate that stress can have a significant deleterious effect on food safety through a variety of potential mechanisms. However, as the impact of stress is difficult to precisely determine, it is imperative that the issue receives more research attention in the interests of optimizing animal welfare and minimizing losses in product yield and quality, as well as to food safety risks to consumers. While there is some evidence linking stress with pathogen carriage and shedding in farm animals, the mechanisms underlying this effect have not been fully elucidated. Understanding when pathogen loads on the farm are the highest or when animals are most susceptible to infection will help identifying times when intervention strategies for pathogen control may be most effective, and consequently, increase the safety of food of animal origin.

  2. Preoperative weight gain might increase risk of gastric bypass surgery.

    Istfan, Nawfal W; Anderson, Wendy A; Apovian, Caroline M; Hess, Donald T; Forse, R Armour

    2011-01-01

    Weight loss improves the cardiovascular and metabolic risk associated with obesity. However, insufficient data are available about the health effects of weight gain, separate from the obesity itself. We sought to determine whether the changes in body weight before open gastric bypass surgery (OGB) would have a significant effect on the immediate perioperative hospital course. A retrospective chart review of 100 consecutive patients was performed to examine the effects of co-morbidities and body weight changes in the immediate preoperative period on the hospital length of stay and the rate of admission to the surgical intensive care unit (SICU). Of our class III obese patients undergoing OGB, 95% had ≥1 co-morbid condition and an overall SICU admission rate of 18%. Compared with the patients with no perioperative SICU admission, the patients admitted to the SICU had a greater degree of insulin resistance (homeostatic model analysis-insulin resistance 10.8 ± 1.3 versus 5.9 ± 0.5, P = .001), greater serum triglyceride levels (225 ± 47 versus 143 ± 8 mg/dL, P = .003), and had gained more weight preoperatively (.52 ± .13 versus .06 ± .06 lb/wk, P = .003). The multivariate analyses showed that preoperative weight gain was a risk factor for a longer length of stay and more SICU admissions lasting ≥3 days, as were a diagnosis of sleep apnea and an elevated serum triglyceride concentration. The results of the present retrospective study suggest that weight gain increases the risk of perioperative SICU admission associated with OGB, independent of the body mass index. Sleep apnea and elevated serum triglyceride levels were also important determinants of perioperative morbidity. In view of the increasing epidemic of obesity and the popularity of bariatric surgical procedures, we propose that additional clinical and metabolic research focusing on the understanding of the complex relationship among obesity, positive energy balance, weight gain, and perioperative

  3. Increased Flooding Risk - Accelerating Threat and Stakeholder Response

    Atkinson, L. P.; Ezer, T.; De Young, R.; McShane, M. K.; McFarlane, B.

    2012-12-01

    projects, and "…subsidence …. is not well-documented". Studies sponsored by the City of Norfolk for example suggest massive tidal barriers. Flood insurance - Flood insurance is available only from the National Flood Insurance Program (NFIP), not from private insurers. NFIP has a current deficit of about 18B, which is estimated to increase by about 2B annually. The rates are subsidized and do not reflect the true risk of coastal flooding and do not incorporate the likelihood of future sea-level rise. In effect, the subsidy promotes increased building on the coast, leading to increased deficits in the tax-payer financed program. Risk-based flood insurance pricing would lead to less coastal development, therefore decreasing the tax base of the community. Stakeholder needs - Planning for increased flooding due to sea level rise extends 50 to 100 years given the lifetime of infrastructure. Planners need guidance and error estimates. To make adequate predictions for users we must understand the various components of sea level rise including subsidence, global sea level rise and regional and local dynamic sea level rise. Predictions of regional sea level rise will be presented in the context of existing infrastructure such as NASA research facilities and the city of Norfolk, Virginia.

  4. Increased Risk of Drug-Induced Hyponatremia during High Temperatures

    Anna K Jönsson

    2017-07-01

    Full Text Available Purpose: To investigate the relationship between outdoor temperature in Sweden and the reporting of drug-induced hyponatremia to the Medical Products Agency (MPA. Methods: All individual adverse drug reactions (ADR reported to MPA from 1 January 2010 to 31 October 2013 of suspected drug-induced hyponatremia and random controls were identified. Reports where the ADR had been assessed as having at least a possible relation to the suspected drug were included. Information on administered drugs, onset date, causality assessment, sodium levels, and the geographical origin of the reports was extracted. A case-crossover design was used to ascertain the association between heat exposure and drug-induced hyponatremia at the individual level, while linear regression was used to study its relationship to sodium concentration in blood. Temperature exposure data were obtained from the nearest observation station to the reported cases. Results: During the study period, 280 reports of hyponatremia were identified. More cases of drug-induced hyponatremia were reported in the warmer season, with a peak in June, while other ADRs showed an opposite annual pattern. The distributed lag non-linear model indicated an increasing odds ratio (OR with increasing temperature in the warm season with a highest odds ratio, with delays of 1–5 days after heat exposure. A cumulative OR for a lag time of 1 to 3 days was estimated at 2.21 at an average daily temperature of 20 °C. The change in sodium per 1 °C increase in temperature was estimated to be −0.37 mmol/L (95% CI: −0.02, −0.72. Conclusions: Warm weather appears to increase the risk of drug-induced hyponatremia

  5. Increased Risk of Metabolic Syndrome in Patients with Vitiligo.

    Ataş, Hatice; Gönül, Müzeyyen

    2017-05-05

    Inflammatory and immune processes can be triggered in vitiligo due to a decreased number of melanocytes and their anti-inflammatory effects. Because of the systemic nature of vitiligo, metabolic abnormalities such as insulin resistance and lipid profile disturbances as well as skin involvement may be observed in vitiligo. To investigate the association between metabolic syndrome and vitiligo. Case-control study. The demographic, clinical and laboratory features in the subjects were compared according to presence of vitiligo and metabolic syndrome [patients (n=63) vs. gender-age matched controls (n=65) and metabolic syndrome positive (n=38) vs. negative (n=90)]. A logistic regression analysis was also used. We identified metabolic syndrome in 24 (38.1%) subjects with vitiligo and 14 (21.5%) subjects without vitiligo (p=0.04). Active vitiligo, segmental vitiligo, an increased duration of vitiligo and an increased percentage in the affected body surface area were determined to be independent predictors of metabolic syndrome [activity of vitiligo: p=0.012, OR (95% CI)=64.4 (2.5-1672); type of vitiligo: p=0.007, OR (95% CI)=215.1 (4.3-10725.8); duration of vitiligo: p=0.03, OR (95% CI)=1.4 (1.1-2.0); percentage of affected body surface area: p=0.07, OR (95% CI)=1.2 (0.98-1.5)]. The risk of developing metabolic syndrome is increased in patients with vitiligo. The poor clinical features of vitiligo, such as active, extended and segmental vitiligo with an increased duration of time, are independent predictors for developing metabolic syndrome.

  6. Balancing Life with an Increased Risk of Cancer

    Petersen, Helle Vendel; Nilbert, Mef; Bernstein, Inge

    2014-01-01

    led us to explore lived experiences in healthy mutation carriers with Lynch syndrome. Individual interviews were subjected to descriptive phenomenological analysis. Four constitutions, namely, family context, interpretation and transformation, approach to risk and balancing life at risk were...

  7. Women referred for occupational risk assessment in pregnancy have no increased risk of adverse obstetric outcomes

    Bidstrup, Signe Brøker; Kaerlev, Linda; Thulstrup, Ane Marie

    2015-01-01

    .72-1.17). CONCLUSION: The women who are referred for occupational risk assessment at two large occupational university departments are not at an increased risk of preterm birth or of delivering low birth weight children. This may reflect that reproductive hazards in Danish workplaces are limited and......INTRODUCTION: Our aim was to study the association between pregnant women's referral status for occupational risk assessment, and their risk of preterm delivery (... pregnant women referred to two Danish clinics of occupational medicine (Copenhagen and Aarhus) from 1984 to 2010 were compared with the referred women's 1,077 non-referred pregnancy outcomes and with the pregnancy outcomes of 345,467 gainfully employed women from the same geographical areas and time period...

  8. Traumatic Stress Interacts With Bipolar Disorder Genetic Risk to Increase Risk for Suicide Attempts.

    Wilcox, Holly C; Fullerton, Janice M; Glowinski, Anne L; Benke, Kelly; Kamali, Masoud; Hulvershorn, Leslie A; Stapp, Emma K; Edenberg, Howard J; Roberts, Gloria M P; Ghaziuddin, Neera; Fisher, Carrie; Brucksch, Christine; Frankland, Andrew; Toma, Claudio; Shaw, Alex D; Kastelic, Elizabeth; Miller, Leslie; McInnis, Melvin G; Mitchell, Philip B; Nurnberger, John I

    2017-12-01

    Bipolar disorder (BD) is one of the most heritable psychiatric conditions and is associated with high suicide risk. To explore the reasons for this link, this study examined the interaction between traumatic stress and BD polygenic risk score in relation to suicidal ideation, suicide attempt, and nonsuicidal self-injury (NSSI) in adolescent and young adult offspring and relatives of persons with BD (BD-relatives) compared with adolescent and young adult offspring of individuals without psychiatric disorders (controls). Data were collected from 4 sites in the United States and 1 site in Australia from 2006 through 2012. Generalized estimating equation models were used to compare rates of ideation, attempts, and NSSI between BD-relatives (n = 307) and controls (n = 166) and to determine the contribution of demographic factors, traumatic stress exposure, lifetime mood or substance (alcohol/drug) use disorders, and BD polygenic risk score. After adjusting for demographic characteristics and mood and substance use disorders, BD-relatives were at increased risk for suicidal ideation and attempts but not for NSSI. Independent of BD-relative versus control status, demographic factors, or mood and substance use disorders, exposure to trauma within the past year (including bullying, sexual abuse, and domestic violence) was associated with suicide attempts (p = .014), and BD polygenic risk score was marginally associated with attempts (p = .061). Importantly, the interaction between BD polygenic risk score and traumatic event exposures was significantly associated with attempts, independent of demographics, relative versus control status, and mood and substance use disorders (p = .041). BD-relatives are at increased risk for suicide attempts and ideation, especially if they are exposed to trauma and have evidence of increased genetic vulnerability. Copyright © 2017 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

  9. Does physical activity increase the risk of unsafe sun exposure?

    Jardine, Andrew; Bright, Margaret; Knight, Libby; Perina, Heather; Vardon, Paul; Harper, Catherine

    2012-04-01

    Recent increases in the prevalence of self-reported participation in physical activity are encouraging and beneficial for health overall. However, the implications for sun safety need to be considered, particularly in Australia, which has the highest incidence of skin cancer in the world. This study investigated the relationship between physical activity and sunburn to determine if there is a need for integration of sun safety in physical activity promotion. During the 2009/10 southern hemisphere summer, 7802 adults aged 18 to 74 years participated in a computer-assisted telephone interview survey which included a range of self-reported health measures including physical activity, sunburn, skin type, sun protection behaviour and demographic questions. Multivariate logistic regression modelling was undertaken to estimate the association between physical activity and sunburn. Those who reported doing any level of physical activity were significantly more likely to report having experienced sunburn in the past 12 months and on the last weekend, compared with those who did none, with the strongest association among those who undertook 7 hours or more. Each hour of physical activity was associated with a modest increase in the odds of experiencing sunburn in the previous 12 months (OR 1.02, 95% CI 1.010-1.037) and weekend (OR 1.04, 95% CI: 1.023-1.065), after adjusting for potential confounding variables. This study highlights the need for sun protection to be given more prominence in physical activity promotion in order to optimise health benefits without increasing the prevalence of sunburn and associated skin cancer risk.

  10. Does Operational Risk Disclosure Quality Increase Operating Cash Flows?

    Haitham Nobanee

    2017-12-01

    Full Text Available This study aims to measure the degree of operational risk disclosure and examine its impact on operating cash flow of banks listed on the UAE Abu Dhabi Stock Exchange (ADX and Dubai Financial Market (DFM during the period 2003-2016. The authors conducted content analysis of the annual reports to measure the degree of operational risk disclosure. In addition, they used dynamic panel data regressions to analyze the impact of operational risk disclosure on the operating cash flow generated by the banks. The results show a low degree of operational risk disclosure for all UAE banks, both Islamic and conventional. In addition, the results show no association between the levels of disclosure of operational risk and cash flow for all banks, conventional and Islamic. Operational risk disclosure of Islamic banks has not been examined by any prior researchers. In addition, this paper examines the potential impact of operational risk disclosure on the operating cash flow generated by the banks.

  11. Pharmaco-miR

    Rukov, Jakob Lewin; Wilentzik, Roni; Jaffe, Ishai

    2014-01-01

    MicroRNAs (miRNAs) are short regulatory RNAs that down-regulate gene expression. They are essential for cell homeostasis and active in many disease states. A major discovery is the ability of miRNAs to determine the efficacy of drugs, which has given rise to the field of 'miRNA pharmacogenomics......' through 'Pharmaco-miRs'. miRNAs play a significant role in pharmacogenomics by down-regulating genes that are important for drug function. These interactions can be described as triplet sets consisting of a miRNA, a target gene and a drug associated with the gene. We have developed a web server which...... links miRNA expression and drug function by combining data on miRNA targeting and protein-drug interactions. miRNA targeting information derive from both experimental data and computational predictions, and protein-drug interactions are annotated by the Pharmacogenomics Knowledge base (Pharm...

  12. Human Adenovirus 36 Infection Increased the Risk of Obesity

    Xu, Mei-Yan; Cao, Bing; Wang, Dong-Fang; Guo, Jing-Hui; Chen, Kai-Li; Shi, Mai; Yin, Jian; Lu, Qing-Bin

    2015-01-01

    Abstract Human adenovirus 36 (HAdV-36), as the key pathogen, was supposed and discussed to be associated with obesity. We searched the references on the association between HAdV-36 infection and obesity with the different epidemiological methods, to explore the relationship with a larger sample size by meta-analysis and compare the differences of epidemiological methods and population subsets by the subgroup analyses. We conducted literature search on the association between HAdV-36 infections and obesity in English or Chinese published up to July 1, 2015. The primary outcome was the HAdV-36 infection rate in the obese and lean groups; the secondary outcomes were the BMI level and BMI z-score in the HAdV-36 positive and negative groups. The pooled odds ratio (OR) was calculated for the primary outcome; the standardized mean differences (SMDs) were calculated for the secondary and third outcomes. Prediction interval (PI) was graphically presented in the forest plot of the random effect meta-analyses. Metaregression analysis and subgroup analysis were performed. Finally 24 references with 10,191 study subjects were included in the meta-analysis. The obesity subjects were more likely to be infected with HAdV-36 compared to the lean controls (OR = 2.00; 95%CI: 1.46, 2.74; PI: 0.59, 6.76; P infection for obesity were 1.77 (95%CI: 1.19, 2.63; PI: 0.44, 7.03; P = 0.005) and 2.26 (95%CI: 1.67, 3.07; PI: 1.45, 3.54; P SMD of BMI was 0.28 (95% CI: 0.08, 0.47; PI: −0.53, 1.08; P = 0.006) in the HAdV-36 positive subjects with a high heterogeneity (I2 = 86.5%; P infection was higher than those without HAdV-36 infection (SMD = 0.19; 95%CI: −0.31, 0.70; PI: −2.10, 2.49), which had no significantly statistical difference (P = 0.453). HAdV-36 infection increased the risk of obesity. HAdV-36 also increased the risk of weight gain in adults, which was not observed in children. PMID:26705235

  13. Evaluation of miR-182/miR-100 Ratio for Diagnosis and Survival Prediction in Bladder Cancer.

    Chen, Zhanguo; Wu, Lili; Lin, Qi; Shi, Jing; Lin, Xiangyang; Shi, Liang

    2016-09-01

    Abnormal expression of microRNAs (miRNAs) plays an important role in development of several cancer types, including bladder cancer (BCa). However, the relationship between the ratio of miR-181/miR-100 and the prognosis of BCa has not been studied yet. The aim of this study was to evaluate the expression of miR-182, miR-100 and their clinical significance in BCa. Upregulation of miR-182 and down-regulation of miR-100 were validated in tissue specimens of 134 BCa cases compared with 148 normal bladder epithelia (NBE) specimens  using TaqMan-based real-time reverse transcription quantitative PCR (RT-qPCR). The diagnostic and prognostic evaluation of miR-182, miR-100, and miR-182/miR-100 ratio was also performed. miR-182 was upregulated in BCa and miR-100 was down-regulated in BCa compared with NBE (P ratio increased the diagnostic performance, yielding an AUC of 0.981 (97.01% sensitivity and 90.54% specificity). Moreover, miR-182/miR-100 ratio was associated with pT-stage, histological grade, BCa recurrence and carcinoma in situ (P analysis indicated that miR-182/miR-100 ratio was an independent prognostic factor for overall survival (Hazard ratio: 7.142; 95% CI: 2.106 - 9.891; P analysis revealed that high-level of miR-182/miR-100 ratio was significantly correlated with shortened survival time for BCa patients (P ratio may serve as a novel promising biomarker for diagnosis and survival prediction in BCa. Further studies are needed to elucidate the role of miR-182/miR-100 ratio as a non‑invasive diagnostic tool for BCa.

  14. Daytime napping and increased risk of incident respiratory diseases: symptom, marker, or risk factor?

    Leng, Yue; Wainwright, Nick W J; Cappuccio, Francesco P; Surtees, Paul G; Hayat, Shabina; Luben, Robert; Brayne, Carol; Khaw, Kay-Tee

    2016-07-01

    We have identified a strong association between daytime napping and increased mortality risk from respiratory diseases, but little is known about the relationship between daytime napping and respiratory morbidity. Data were drawn from the European Prospective Investigation into Cancer and Nutrition-Norfolk cohort. Participants reported napping habits during 1998-2000 and were followed up for respiratory disease hospital admissions until March 2009. Cox proportional hazards regression was used to examine the association between daytime napping and respiratory disease incidence risk. The study sample included 10,978 men and women with a mean age of 61.9 years, and a total of 946 incident respiratory disease cases were recorded. After adjustment for age, sex, social class, education, marital status, employment status, nightshift work, body mass index, physical activity, smoking, alcohol intake, self-reported general health, hypnotic drug use, habitual sleep duration, and preexisting health conditions, daytime napping was associated with an increase in the overall respiratory disease incidence risk (hazard ratio (HR) = 1.32, 95% confidence interval (CI) 1.15, 1.52 for napping respiratory diseases, especially for the risk of chronic lower respiratory diseases (HR = 1.52, 95% CI: 1.18, 1.96 for napping respiratory disease incidence risk. Further studies are required to confirm these findings and help understand potential mechanisms. Copyright © 2016 The Author(s). Published by Elsevier B.V. All rights reserved.

  15. Global risk of big earthquakes has not recently increased.

    Shearer, Peter M; Stark, Philip B

    2012-01-17

    The recent elevated rate of large earthquakes has fueled concern that the underlying global rate of earthquake activity has increased, which would have important implications for assessments of seismic hazard and our understanding of how faults interact. We examine the timing of large (magnitude M≥7) earthquakes from 1900 to the present, after removing local clustering related to aftershocks. The global rate of M≥8 earthquakes has been at a record high roughly since 2004, but rates have been almost as high before, and the rate of smaller earthquakes is close to its historical average. Some features of the global catalog are improbable in retrospect, but so are some features of most random sequences--if the features are selected after looking at the data. For a variety of magnitude cutoffs and three statistical tests, the global catalog, with local clusters removed, is not distinguishable from a homogeneous Poisson process. Moreover, no plausible physical mechanism predicts real changes in the underlying global rate of large events. Together these facts suggest that the global risk of large earthquakes is no higher today than it has been in the past.

  16. Patients with psoriasis have an increased risk of cardiovascular diseases

    Ahlehoff, Ole; Gislason, Gunnar; Lindhardsen, Jesper

    2012-01-01

    Psoriasis is a chronic immunoinflammatory disease that affects 2-3% of the population and shares pathophysiologic mechanisms and risk factors with cardiovascular diseases. Studies have suggested psoriasis as an independent risk factor for cardiovascular disease and Danish guidelines...... on cardiovascular risk factor modification in patients with psoriasis and psoriatic arthritis have recently been published. We provide a short review of the current evidence and the Danish guidelines....

  17. Care for patients with an increased risk for cardiovascular diseases.

    Boheemen, C. van; Geffen, K. van; Philbert, D.; Bos, M.; Dis, I. van; Strijbis, A.; Bouvy, M.; Dijk, L. van

    2010-01-01

    Background: In 2009, a national standard of care for vascular risk management (VRM) was developed. This standard, which was sent to all general practitioners (GPs), contains requirements for optimal care. One requirement is the formulation of a written individual-care plan which contains an extended description of the patient’s cardiovascular risk factors and a plan to reduce the risk. The aim of our study is to describe to what extent current care meets the requirement posed in the care stan...

  18. HUD INFORMATION SYSTEMS: Immature Software Acquisition Capability Increases Project Risks

    2001-01-01

    .... GAO has designated HUD's major program areas as high risk, in part because the department's information and financial management systems were poorly integrated, ineffective, and generally unreliable...

  19. Increase of Meningitis Risk in Stroke Patients in Taiwan

    Chie-Hong Wang

    2018-03-01

    Full Text Available Background and purposeThe blood–brain barrier (BBB not only provides a physical obstruction but also recruits and activates neutrophils in cases of infection. Hemorrhagic or ischemic stroke reportedly induces the disruption of the BBB. However, few studies have reported a correlation between the incidence of meningitis in patients with a history of stroke. This study tested the hypothesis that patients with a history of stroke may be more vulnerable to meningitis.MethodsStroke and age-matched comparison (n = 29,436 and 87,951, respectively cohorts were recruited from the Taiwan National Health Insurance database (2000–2011. Correlations between the two cohorts were evaluated by Cox proportional hazard regression model, Kaplan–Meier curve, and log-rank tests.ResultsThe incidence of meningitis was higher in the stroke cohort compared to that in the comparison cohort [hazard ratio (HR, 2.89; 95% confidence interval (CI, 2.23–3.74, p < 0.001]. After adjusting for age, sex, and comorbidities, the estimated HR in the stroke cohort was 2.55-fold higher than that in the comparison cohort (CI, 1.94–3.37; p < 0.001. Notably, patients who had experienced hemorrhagic stroke had a higher incidence rate of meningitis than those with a history of ischemic stroke, except for patients older than 75 years (incidence rates in hemorrhagic/ischemic stroke patients, 3.14/1.48 in patients younger than 45 years, 1.52/0.41 in 45- to 64-year group, 1.15/0.90 in 65- to 74-year group, 0.74/0.93 in patients older than 75 years. Moreover, stroke patients who had undergone head surgery had the highest meningitis risk (adjusted HR, 8.66; 95% CI, 5.55–13.5; p < 0.001 followed by stroke patients who had not undergone head surgery (adjusted HR, 2.11; 95% CI, 1.57–2.82; p < 0.001.ConclusionOur results indicated that stroke patients have higher risks of meningitis. Compromised BBB integrity in stroke patients may lead to increased

  20. Women referred for occupational risk assessment in pregnancy have no increased risk of adverse obstetric outcomes

    Bidstrup, Signe Brøker; Kaerlev, Linda; Thulstrup, Ane Marie

    2015-01-01

    pregnant women referred to two Danish clinics of occupational medicine (Copenhagen and Aarhus) from 1984 to 2010 were compared with the referred women's 1,077 non-referred pregnancy outcomes and with the pregnancy outcomes of 345,467 gainfully employed women from the same geographical areas and time period.......72-1.17). CONCLUSION: The women who are referred for occupational risk assessment at two large occupational university departments are not at an increased risk of preterm birth or of delivering low birth weight children. This may reflect that reproductive hazards in Danish workplaces are limited and....../or that the occupational risk assessment and counselling of pregnant women are preventing these selected adverse pregnancy outcomes. FUNDING: The Research Unit at Department of Occupational and Environmental Medicine at Bispebjerg Hospital supported the study financially. TRIAL REGISTRATION: not relevant. The study...

  1. Hormone replacement therapy increases the risk of cranial meningioma

    Andersen, Lene; Friis, Søren; Hallas, Jesper

    2013-01-01

    We investigated the influence of hormone replacement therapy (HRT) use on the risk of meningioma in a population-based setting.......We investigated the influence of hormone replacement therapy (HRT) use on the risk of meningioma in a population-based setting....

  2. The miRNome of bipolar disorder.

    Fries, Gabriel R; Carvalho, Andre F; Quevedo, Joao

    2018-06-01

    Epigenetic mechanisms have been suggested to play a key role in the pathophysiology of bipolar disorder (BD), among which microRNAs (miRNAs) may be of particular significance according to recent studies. We aimed to summarize miRNA studies in BD to identify consistent findings, limitations, and future directions of this emerging field. We performed a comprehensive search on PUBMED and Medline for studies investigating an association between BD and miRNAs. The included studies report miRNA alterations in postmortem brain tissues and in the periphery, cell culture and preclinical findings, genetic associations, and the effects of medications. Several studies report changes in miRNA expression levels in postmortem brain and in the periphery of patients, although most of the results so far have not been replicated and are not concordant between different populations. Genetic studies also suggest that miRNA genes are located within susceptibility loci of BD, and also a putative role of miRNAs in modulating genes previously shown to confer risk of BD. We did not perform a systematic review of the literature, and miRNAs represent only one facet of the plethora of epigenetic mechanisms that might be involved in BD's pathophysiology. miRNA findings in BD significantly vary between studies, but are consistent to suggest a key role for these molecules in BD's pathophysiology and treatment, particularly miR-34a and miR-137. Accordingly, miRNA might represent important biomarkers of illness to be used in the clinical settings, and potentially also for the development of novel therapeutics for BD in the near future. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Risk factor management in a contemporary Australian population at increased cardiovascular disease risk.

    Campbell, D J; Coller, J M; Gong, F F; McGrady, M; Prior, D L; Boffa, U; Shiel, L; Liew, D; Wolfe, R; Owen, A J; Krum, H; Reid, C M

    2017-11-14

    Effective management of cardiovascular and chronic kidney disease risk factors offers longer, healthier lives and savings in health care. We examined risk factor management in participants of the SCReening Evaluation of the Evolution of New Heart Failure (SCREEN-HF) study, a self-selected population at increased cardiovascular disease risk recruited from members of a health insurance fund in Melbourne and Shepparton, Australia. Inclusion criteria were age ≥60 years with one or more of self-reported ischaemic or other heart disease, irregular or rapid heart rhythm, cerebrovascular disease, renal impairment, or treatment for hypertension or diabetes for ≥2 years. Exclusion criteria were known heart failure or cardiac abnormality on echocardiography or other imaging. Medical history, clinical examination, full blood examination and biochemistry (without lipids and HbA1c) were performed for 3847 participants on enrolment, and blood pressure, lipids and HbA1c were measured 1-2 years after enrolment for 3202 participants. Despite 99% of 3294 participants with hypertension receiving antihypertensive medication, half had blood pressures >140/90 mmHg. Approximately 77% of participants were overweight or obese, with one third obese. Additionally, 74% of participants at high cardiovascular disease risk had low density lipoprotein cholesterol levels ≥2 mmol/l, one third of diabetic participants had HbA1c >7%, 22% had estimated glomerular filtration rate management of modifiable risk factors. This article is protected by copyright. All rights reserved.

  4. Design and baseline characteristics of the PerfectFit study: a multicenter cluster-randomized trial of a lifestyle intervention in employees with increased cardiovascular risk.

    Kouwenhoven-Pasmooij, Tessa A; Djikanovic, Bosiljka; Robroek, Suzan J W; Helmhout, Pieter; Burdorf, Alex; Hunink, M G Myriam

    2015-07-28

    , physical activity, stress management) and body mass index. Furthermore, a process evaluation and an economic analysis will be performed. Additional coaching using MI is expected to be a key factor for success of the web-based HRA in employees with increased cardiovascular risk. This "blended care"-approach may be an essential strategy for effective health promotion activities. Dutch Trial Register by registration number NTR4894 , 14/11/2014.

  5. Is use of fall risk-increasing drugs in an elderly population associated with an increased risk of hip fracture, after adjustment for multimorbidity level

    Thorell, Kristine; Ranstad, Karin; Midlöv, Patrik

    2014-01-01

    BACKGROUND: Risk factors for hip fracture are well studied because of the negative impact on patients and the community, with mortality in the first year being almost 30% in the elderly. Age, gender and fall risk-increasing drugs, identified by the National Board of Health and Welfare in Sweden......, are well known risk factors for hip fracture, but how multimorbidity level affects the risk of hip fracture during use of fall risk-increasing drugs is to our knowledge not as well studied. This study explored the relationship between use of fall risk-increasing drugs in combination with multimorbidity...... level and risk of hip fracture in an elderly population. METHODS: Data were from Östergötland County, Sweden, and comprised the total population in the county aged 75 years and older during 2006. The odds ratio (OR) for hip fracture during use of fall risk-increasing drugs was calculated by multivariate...

  6. IκK-16 decreases miRNA-155 expression and attenuates the human monocyte inflammatory response.

    Norman James Galbraith

    Full Text Available Excessive inflammatory responses in the surgical patient may result in cellular hypo-responsiveness, which is associated with an increased risk of secondary infection and death. microRNAs (miRNAs, such as miR-155, are powerful regulators of inflammatory signalling pathways including nuclear factor κB (NFκB. Our objective was to determine the effect of IκK-16, a selective blocker of inhibitor of kappa-B kinase (IκK, on miRNA expression and the monocyte inflammatory response. In a model of endotoxin tolerance using primary human monocytes, impaired monocytes had decreased p65 expression with suppressed TNF-α and IL-10 production (P < 0.05. miR-155 and miR-138 levels were significantly upregulated at 17 h in the impaired monocyte (P < 0.05. Notably, IκK-16 decreased miR-155 expression with a corresponding dose-dependent decrease in TNF-α and IL-10 production (P < 0.05, and impaired monocyte function was associated with increased miR-155 and miR-138 expression. In the context of IκK-16 inhibition, miR-155 mimics increased TNF-α production, while miR-155 antagomirs decreased both TNF-α and IL-10 production. These data demonstrate that IκK-16 treatment attenuates the monocyte inflammatory response, which may occur through a miR-155-mediated mechanism, and that IκK-16 is a promising approach to limit the magnitude of an excessive innate inflammatory response to LPS.

  7. Reducing Risk and Increasing Exploration Payoff with Symbiotic Rover Pairs

    National Aeronautics and Space Administration — Planetary explorations missions avoid the destinations that offer the greatest scientific payout because these destinations come with a risk too great for a primary...

  8. Change in circulating microRNA profile of obese children indicates future risk of adult diabetes.

    Cui, Xianwei; You, Lianghui; Zhu, Lijun; Wang, Xing; Zhou, Yahui; Li, Yun; Wen, Juan; Xia, Yankai; Wang, Xinru; Ji, Chenbo; Guo, Xirong

    2018-01-01

    Childhood obesity increases susceptibility to type 2 diabetes (T2D) in adults. Circulating microRNAs (miRNAs) in serum have been proposed as potential diagnostic biomarkers, and they may contribute to the progression toward T2D. Here, we investigated the possibility of predicting the future risk of adult T2D in obese children by using circulating miRNAs. We performed miRNA high-throughput sequencing to screen relevant circulating miRNAs in obese children. The expression patterns of targeted miRNAs were further explored in obese children and adults with T2D. To investigate the underlying contributions of these miRNAs to the development of T2D, we detected the impacts of the candidate miRNAs on preadipocyte proliferation, insulin secretion by pancreatic β-cell, and glucose uptake by skeletal muscle cells. Three miRNAs (miR-486, miR-146b and miR-15b), whose expression in the circulation was most dramatically augmented in obese children and adult T2D patients, were selected for further investigation. Of these 3 miRNAs, miR-486 was implicated in accelerating preadipocyte proliferation and myotube glucose intolerance, miR-146b and miR-15b were engaged in the suppression of high concentration glucose-induced pancreatic insulin secretion, and they all contributed to the pathological processes of obesity and T2D. Our results provide a better understanding of the role of circulating miRNAs, particularly miR-486, miR-146b and miR-15b, in predicting the future risk of T2D in obese children. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  9. Chronic Pancreatitis Correlates With Increased Risk of Cerebrovascular Disease

    Wong, Tuck-Siu; Liao, Kuan-Fu; Lin, Chi-Ming; Lin, Cheng-Li; Chen, Wen-Chi; Lai, Shih-Wei

    2016-01-01

    Abstract The aim of this study is to explore whether there is a relationship between chronic pancreatitis and cerebrovascular disease in Taiwan. Using the claims data of the Taiwan National Health Insurance Program, we identified 16,672 subjects aged 20 to 84 years with a new diagnosis of chronic pancreatitis from 2000 to 2010 as the chronic pancreatitis group. We randomly selected 65,877 subjects aged 20 to 84 years without chronic pancreatitis as the nonchronic pancreatitis group. Both groups were matched by sex, age, comorbidities, and the index year of diagnosing chronic pancreatitis. The incidence of cerebrovascular disease at the end of 2011 was measured. The multivariable Cox proportional hazards regression model was used to measure the hazard ratio (HR) and 95% confidence interval (CI) for cerebrovascular disease risk associated with chronic pancreatitis and other comorbidities. The overall incidence of cerebrovascular disease was 1.24-fold greater in the chronic pancreatitis group than that in the nonchronic pancreatitis group (14.2 vs. 11.5 per 1000 person-years, 95% CI = 1.19–1.30). After controlling for confounding factors, the adjusted HR of cerebrovascular disease was 1.27 (95% CI = 1.19–1.36) for the chronic pancreatitis group as compared with the nonchronic pancreatitis group. Woman (adjusted HR = 1.41, 95% CI = 1.31–1.51), age (every 1 year, HR = 1.04, 95% CI = 1.04–1.05), atrial fibrillation (adjusted HR = 1.23, 95% CI = 1.02–1.48), chronic kidney disease (adjusted HR = 1.48, 95% CI = 1.31–1.67), chronic obstructive pulmonary disease (adjusted HR = 1.27, 95% CI = 1.16–1.40), diabetes mellitus (adjusted HR = 1.82, 95% CI = 1.72–1.92), hypertension (adjusted HR = 1.66, 95% CI = 1.56–1.76), and peripheral atherosclerosis (adjusted HR = 1.26, 95% CI = 1.06–1.51) were other factors significantly associated with cerebrovascular disease. Chronic pancreatitis is

  10. Increased genetic risk for obesity in premature coronary artery disease.

    Cole, Christopher B; Nikpay, Majid; Stewart, Alexandre F R; McPherson, Ruth

    2016-04-01

    There is ongoing controversy as to whether obesity confers risk for CAD independently of associated risk factors including diabetes mellitus. We have carried out a Mendelian randomization study using a genetic risk score (GRS) for body mass index (BMI) based on 35 risk alleles to investigate this question in a population of 5831 early onset CAD cases without diabetes mellitus and 3832 elderly healthy control subjects, all of strictly European ancestry, with adjustment for traditional risk factors (TRFs). We then estimated the genetic correlation between these BMI and CAD (rg) by relating the pairwise genetic similarity matrix to a phenotypic covariance matrix between these two traits. GRSBMI significantly (P=2.12 × 10(-12)) associated with CAD status in a multivariate model adjusted for TRFs, with a per allele odds ratio (OR) of 1.06 (95% CI 1.042-1.076). The addition of GRSBMI to TRFs explained 0.75% of CAD variance and yielded a continuous net recombination index of 16.54% (95% CI=11.82-21.26%, P<0.0001). To test whether GRSBMI explained CAD status when adjusted for measured BMI, separate models were constructed in which the score and BMI were either included as covariates or not. The addition of BMI explained ~1.9% of CAD variance and GRSBMI plus BMI explained 2.65% of CAD variance. Finally, using bivariate restricted maximum likelihood analysis, we provide strong evidence of genome-wide pleiotropy between obesity and CAD. This analysis supports the hypothesis that obesity is a causal risk factor for CAD.

  11. Single-living is associated with increased risk of long-term mortality among employed patients with acute myocardial infarction

    Finn Erl

    2010-05-01

    Full Text Available Finn Erland Nielsen, Shan MardDepartment of Cardiology S, Herlev University Hospital, DenmarkObjective: There is conflicting evidence about the impact of social support on adverse outcome after acute myocardial infarction (MI. We examined the relation between single-living and long-term all-cause mortality after MI.Design: A prospective cohort study of 242 employed patients with MI followed up to 16 years after MI.Results: A total of 106 (43.8% patients died during the follow-up. Single-living nearly doubled the risk of death; after adjusting for potential confounding factors, single-living was an independent predictor of death, with a hazard ratio of 2.55 (95% confidence interval: 1.52–4.30. Other predictors of death were diabetes mellitus, atrial fibrillation, age, and ejection fraction less than 35%.Conclusion: Single-living is a prognostic determinant of long-term all-cause mortality after MI.Keywords: acute myocardial infarction, social support, single-living, prognosis.

  12. Does alcohol increase the risk of preterm delivery?

    Kesmodel, Ulrik; Olsen, Sjúrður Fróði; Secher, Niels Jørgen

    2000-01-01

    We evaluated the association between alcohol intake during pregnancy and preterm delivery. Women attending routine antenatal care at Aarhus University Hospital, Denmark, from 1989–1991 and 1992–1996 were eligible. We included 18,228 singleton pregnancies in the analyses. We obtained prospective...... information on alcohol intake at 16 and 30 weeks of gestation, other lifestyle factors, maternal characteristics, and obstetrical risk factors from self-administered questionnaires and hospital files. For women with alcohol intake of 1–2, 3–4, 5–9, and >=10 drinks/week the risk ratio (RR) of preterm delivery...

  13. Identifying potential functional impact of mutations and polymorphisms: Linking heart failure, increased risk of arrhythmias and sudden cardiac death.

    BENOIT eJAGU

    2013-09-01

    Full Text Available Researchers and clinicians have discovered several important concepts regarding the mechanisms responsible for increased risk of arrhythmias, heart failure and sudden cardiac death. One major step in defining the molecular basis of normal and abnormal cardiac electrical behaviour has been the identification of single mutations that greatly increase the risk for arrhythmias and sudden cardiac death by changing channel-gating characteristics. Indeed, mutations in several genes encoding ion channels, such as SCN5A, which encodes the major cardiac Na+ channel, have emerged as the basis for a variety of inherited cardiac arrhythmias such as long QT syndrome, Brugada syndrome, progressive cardiac conduction disorder, sinus node dysfunction or sudden infant death syndrome. In addition, genes encoding ion channel accessory proteins, like anchoring or chaperone proteins, which modify the expression, the regulation of endocytosis and the degradation of ion channel α-subunits have also been reported as susceptibility genes for arrhythmic syndromes. The regulation of ion channel protein expression also depends on a fine-tuned balance among different other mechanisms, such as gene transcription, RNA processing, post-transcriptional control of gene expression by miRNA, protein synthesis, assembly and post-translational modification and trafficking.

  14. Maternal SSRI exposure increases the risk of autistic offspring

    Andalib, S; Emamhadi, M R; Yousefzadeh-Chabok, S

    2017-01-01

    , childhood, children, neurodevelopment were identified using databases PubMed and PMC, MEDLINE, EMBASE, SCOPUS, and Google Scholar. Cochran's Q statistic-value (Q), degree of freedom (df), and I(2) indices (variation in odds ratio [OR] attributable to heterogeneity) were calculated to analyze the risk...

  15. Increased pancreatic cancer risk following radiotherapy for testicular cancer

    Hauptmann, Michael; Børge Johannesen, Tom; Gilbert, Ethel S

    2016-01-01

    with the number of cycles of chemotherapy with alkylating or platinum agents (P=0.057), although only one case was exposed to platinum. CONCLUSIONS: A dose-response relationship exists between radiation to the pancreas and subsequent cancer risk, and persists for over 20 years. These excesses, although small...

  16. Subjective expected utility with non-increasing risk aversion

    Wakker, P.P.

    1989-01-01

    It is shown that assumptions about risk aversion, usually studied under the presupposition of expected utility maximization, have a surprising extra merit at an earlier stage of the measurement work: together with the sure-thing principle, these assumptions imply subjective expected utility

  17. Drugged Driving: Increased Traffic Risks Involving Licit and Illicit Substances

    Pilkinton, Melinda W.; Robertson, Angela; McCluskey, D. Lee

    2013-01-01

    Driving under the influence of drugs poses risks for traffic safety. Most research attention has been focused on the most prevalent drugs of abuse, such as alcohol, illegal drugs, and prescription drugs with high abuse potential. The objectives of this study were to determine the types of drugs used by convicted DUI offenders on the day of their…

  18. Starting Hormone Therapy at Menopause Increases Breast Cancer Risk

    According to a January 28, 2011 article in the Journal of the National Cancer Institute, women who start taking menopausal hormone therapy around the time of menopause have a higher risk of breast cancer than women who begin taking hormones a few years later.

  19. Care for patients with an increased risk for cardiovascular diseases.

    Boheemen, C. van; Geffen, K. van; Philbert, D.; Bos, M.; Dis, I. van; Strijbis, A.; Bouvy, M.; Dijk, L. van

    2010-01-01

    Background: In 2009, a national standard of care for vascular risk management (VRM) was developed. This standard, which was sent to all general practitioners (GPs), contains requirements for optimal care. One requirement is the formulation of a written individual-care plan which contains an extended

  20. CIA increases cybersecurity Integrated approach to digital risks

    2015-01-01

    The article gives an overview of activities of the cybersecurity group, which was set up in order to go a step further. They have launched a project to manage cybersecurity. The underlying principle is a general pattern that determines policies and the responsibilities for risk management.

  1. Increased Risk of Ischemic Stroke in Young Nasopharyngeal Carcinoma Patients

    Lee, Ching-Chih; Su, Yu-Chieh; Ho, Hsu-Chueh; Hung, Shih-Kai; Lee, Moon-Sing; Chiou, Wen-Yen; Chou, Pesus; Huang, Yung-Sung

    2011-01-01

    Purpose: Radiation/chemoradiotherapy-induced carotid stenosis and cerebrovascular events in patients with nasopharyngeal carcinoma (NPC) can cause severe disability and even death. This study aimed to estimate the risk of ischemic stroke in this patient population over more than 10 years of follow-up. Methods and Materials: The study cohorts consisted of all patients hospitalized with a principal diagnosis of NPC (n = 1094), whereas patients hospitalized for an appendectomy during 1997 and 1998 (n = 4376) acted as the control group and surrogate for the general population. Cox proportional hazard model was performed as a means of comparing the stroke-free survival rate between the two cohorts after adjusting for possible confounding and risk factors. Results: Of the 292 patients with ischemic strokes, 62 (5.7%) were from the NPC cohort and 230 (5.3%) were from the control group. NPC patients ages 35–54 had a 1.66 times (95% CI, 1.16–2.86; p = 0.009) higher risk of ischemic stroke after adjusting for patient characteristics, comorbidities, geographic region, urbanization level of residence, and socioeconomic status. There was no statistical difference in ischemic stroke risk between the NPC patients and appendectomy patients ages 55–64 years (hazard ratio = 0.87; 95% CI, 0.56–1.33; p = 0.524) after adjusting for other factors. Conclusions: Young NPC patients carry a higher risk for ischemic stroke than the general population. Besides regular examinations of carotid duplex, different irradiation strategies or using new technique of radiotherapy, such as intensity modulated radiation therapy or volumetric modulated arc therapy, should be considered in young NPC patients.

  2. miR482 and Its Isoforms in Plants

    Abdil Hakan EREN

    2016-09-01

    Full Text Available In plants, miR482 family members are generally 22-nucleotide long, distinguishing from other microRNA (miRNA families by their extraordinary and diverse sequence structures. Studies showed that miRNA482 is related to NBLRR (Nucleotide binding-site leucine-rich repeat genes conferring resistance to disease in plants. There are different coded NB-LRR genes which are considered as the part immune response assisting the recognition of pathogens in plant genomes. NB-LRR proteins are mostly related to effector – triggering immune system against pathogens. The main immune receptors in plants are PRR (Pattern recoginition receptor and R (Resistance proteins. R proteins code for immune system proteins by NB-LRR activity. miR482, miR1448, slmiR2118 and ath-miR472 are disease resistance related miRNAs. In several studies, miR482 was found to be a homolog of miR1448 and phylogenetic analyses showed that miR1448 is formed by tandem duplication of miR482. While suppression of miR482 results in plant susceptibility to pathogens, miR482 was considered to play role in nodulation and mycorrhizal processes of soya roots. Increasing evidences exhibit that miR482 is critical in disease resistance against pathogen attacks.

  3. Potential impact of miR-137 and its targets in schizophrenia

    Carrie eWright

    2013-04-01

    Full Text Available The significant impact of microRNAs (miRNAs on disease pathology is becoming increasingly evident. These small non-coding RNAs have the ability to post-transcriptionally silence the expression of thousands of genes. Therefore, dysregulation of even a single miRNA could confer a large polygenic effect. Schizophrenia is a genetically complex illness thought to involve multiple genes each contributing a small risk. Large genome-wide association studies identified miR-137, a miRNA shown to be involved in neuronal maturation, as one of the top risk genes. To assess the potential mechanism of impact of miR-137 in this disorder and identify its targets, we used a combination of literature searches, Ingenuity Pathway Analysis (IPA, and freely accessible bioinformatics resources. Using TargetScan and the Schizophrenia Gene Resource (SZGR database, we found that in addition to CSMD1, C10orf26, CACNA1C, TCF4, and ZNF804A, five schizophrenia risk genes whose transcripts are also validated miR-137 targets, there are other schizophrenia-associated genes that may be targets of miR-137, including ERBB4, GABRA1, GRIN2A, GRM5, GSK3B, NRG2 and HTR2C. IPA analyses of all the potential targets identified several nervous system functions as the top canonical pathways including synaptic long-term potentiation, a process implicated in learning and memory mechanisms and recently shown to be altered in patients with schizophrenia. Among the subset of targets involved in nervous system development and function, the top scoring pathways were ephrin receptor signaling and axonal guidance, processes that are critical for proper circuitry formation and were shown to be disrupted in schizophrenia. These results suggest that miR-137 may indeed play a substantial role in the genetic etiology of schizophrenia by regulating networks involved in neural development and brain function.

  4. Can stress increase Alzheimer's disease risk in women?

    Johansson, Lena

    2014-02-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of β-amyloid peptides and neurofibrilllary tangles in brain, resulting in neuronal death and loss of cognitive abilities. It has been hypothesized that longstanding psychological stress can result in neural degeneration and AD due to pathological alterations in the hypothalamic-pituitary-adrenal axis. In recent years several epidemiological studies been published on stress as a risk factor for AD. As women are more likely to suffer from stress-related psychiatric disorders, such as post-traumatic stress disorder and clinical burnout syndrome, special effort has been made according to the gender differences in risk of AD. However, few studies have stratified for gender, due to small sample sizes and limited statistic power, and no reliable findings have been found. Additional longitudinal studies are therefore needed for studying gender differences and for determining what mediates the stress and AD association, in both genders.

  5. Type 2 diabetes: postprandial hyperglycemia and increased cardiovascular risk

    Aryangat, Ajikumar V; Gerich, John E

    2010-01-01

    Ajikumar V Aryangat, John E GerichUniversity of Rochester, Rochester, New York, USAAbstract: Hyperglycemia is a major risk factor for both the microvascular and macrovascular complications in  patients with type 2 diabetes. This review summarizes the cardiovascular results of large outcomes trials in diabetes and presents new evidence on the role of hyperglycemia, with particular emphasis on postprandial hyperglycemia, in adverse cardiovascular outcomes in patients with type 2 diabet...

  6. Increasing Effectiveness and Efficiency Through Risk-Based Deployments

    2015-12-01

    Shaw and Henry McKay, both University of Chicago professors, began using maps to understand juvenile delinquency better in Chicago, IL.36 In the...André-Michel Guerry’s Ordonnateur Statistique: The First Statistical Calculator?,” The American Statistician 66, no. 3 (August 1, 2012): 195–200...micro or macro levels using basic inferential statistics .”91 5. Protecting Civil Rights and Liberties It is also important to note that a risk

  7. An Increased Risk of Osteoporosis during Acquired Immunodeficiency Syndrome.

    Annapoorna, N; Rao, G Venkateswara; Reddy, N S; Rambabu, P; Rao, K R S Samabasiva

    2004-01-01

    Osteoporosis is characterized by decreased bone mineral density and mechanistic imbalances of bone tissue that may result in reduced skeletal strength and an enhanced susceptibility to fractures. Osteoporosis in its most common form affects the elderly (both sexes) and all racial groups of human beings. Multiple environmental risk factors like acquired immune deficiency syndrome (AIDS) are believed to be one of the causes of osteoporosis. Recently a high incidence of osteoporosis has been observed in human immunodeficiency virus (HIV) infected individuals. The etiology of this occurrence in HIV infections is controversial. This problem seems to be more frequent in patients receiving potent antiretroviral therapy. In AIDS, the main suggested risk factors for the development of osteoporosis are use of protease inhibitors, longer duration of HIV infection, lower body weight before antiretroviral therapy, high viral load. Variations in serum parameters like osteocalcin, c-telopeptide, levels of elements like Calcium, Magnesium, Phosphorus, concentration of vitamin-D metabolites, lactate levels, bicarbonate concentrations, amount of alkaline phosphatase are demonstrated in the course of development of osteoporosis. OPG/RANKL/RANK system is final mediator of bone remodeling. Bone mineral density (BMD) test is of added value to assess the risk of osteoporosis in patients infected with AIDS. The biochemical markers also aid in this assessment. Clinical management mostly follows the lines of treatment of osteoporosis and osteopenia.

  8. Virtual driving and risk taking: do racing games increase risk-taking cognitions, affect, and behaviors?

    Fischer, Peter; Kubitzki, Jörg; Guter, Stephanie; Frey, Dieter

    2007-03-01

    Research has consistently shown that aggressive video console and PC games elicit aggressive cognitions, affect, and behaviors. Despite the increasing popularity of racing (driving) games, nothing is known about the psychological impact of this genre. This study investigated whether playing racing games affects cognitions, affect, and behaviors that can promote risk taking in actual road traffic situations. In Study 1, the authors found that the frequency of playing racing games was positively associated with competitive driving, obtrusive driving, and car accidents; a negative association with cautious driving was observed. To determine cause and effect, in Study 2, the authors manipulated whether participants played 1 of 3 racing games or 1 of 3 neutral games. Participants who played a racing game subsequently reported a higher accessibility of cognitions and affect positively associated with risk taking than did participants who played a neutral game. Finally, on a more behavioral level, in Study 3, the authors found that men who played a racing game subsequently took higher risks in computer-simulated critical road traffic situations than did men who played a neutral game. Theoretical and practical implications are discussed. ((c) 2007 APA, all rights reserved).

  9. Psycho Educational Group Intervention for Women at Increased Risk for Breast Cancer

    Kash, Kathryn

    1998-01-01

    ... in women at increased risk for breast cancer; (2) examine the impact of a psychoeducational intervention on the endpoint variables of quality of life and adherence to screening in women at increased risk for breast cancer; and (3...

  10. Psycho Educational Group Intervention for Women at Increased Risk for Breast Cancer

    Kash, Kathryn

    1997-01-01

    ... skills in women at increased risk for breast cancer; (2) to examine the impact of a psychoeducational intervention on the endpoint variables of quality of life and adherence to screening in women at increased risk for breast cancer; and (3...

  11. Does Aggregated Returns Disclosure Increase Portfolio Risk Taking?

    Beshears, John; Choi, James J.; Laibson, David; Madrian, Brigitte C.

    2016-01-01

    Many experiments have found that participants take more investment risk if they see returns less frequently, see portfolio-level returns (rather than each individual asset’s returns), or see long-horizon (rather than one-year) historical return distributions. In contrast, we find that such information aggregation treatments do not affect total equity investment when we make the investment environment more realistic than in prior experiments. Previously documented aggregation effects are not robust to changes in the risky asset’s return distribution or the introduction of a multi-day delay between portfolio choice and return realizations. PMID:28553012

  12. Does Aggregated Returns Disclosure Increase Portfolio Risk Taking?

    Beshears, John; Choi, James J; Laibson, David; Madrian, Brigitte C

    2017-06-01

    Many experiments have found that participants take more investment risk if they see returns less frequently, see portfolio-level returns (rather than each individual asset's returns), or see long-horizon (rather than one-year) historical return distributions. In contrast, we find that such information aggregation treatments do not affect total equity investment when we make the investment environment more realistic than in prior experiments. Previously documented aggregation effects are not robust to changes in the risky asset's return distribution or the introduction of a multi-day delay between portfolio choice and return realizations.

  13. Inflammatory bowel disease increases the risk of Parkinson's disease

    Villumsen, Marie; Aznar, Susana; Pakkenberg, Bente

    2018-01-01

    OBJECTIVE: Intestinal inflammation has been suggested to play a role in development of Parkinson's disease (PD) and multiple system atrophy (MSA). To test the hypothesis that IBD is associated with risk of PD and MSA, we performed a nationwide population-based cohort study. DESIGN: The cohort...... patients with UC (HR=1.35; 95% CI 1.20 to 1.52) and not significantly different among patients with Crohn's disease (HR=1.12; 95% CI 0.89 to 1.40). CONCLUSIONS: This nationwide, unselected, cohort study shows a significant association between IBD and later occurrence of PD, which is consistent with recent...

  14. Bacterial infection increases risk of carcinogenesis by targeting mitochondria

    Strickertsson, Jesper A.B.; Desler, Claus; Rasmussen, Lene Juel

    2017-01-01

    pathways, and compares the impact of the bacterial alteration of mitochondrial function to that of cancer. Bacterial virulence factors have been demonstrated to induce mutations of mitochondrial DNA (mtDNA) and to modulate DNA repair pathways of the mitochondria. Furthermore, virulence factors can induce...... or impair the intrinsic apoptotic pathway. The effect of bacterial targeting of mitochondria is analogous to behavior of mitochondria in a wide array of tumours, and this strongly suggests that mitochondrial targeting of bacteria is a risk factor for carcinogenesis....

  15. Increased risk of type 2 diabetes in elderly twins

    Poulsen, Pernille; Grunnet, Louise G; Pilgaard, Kasper

    2009-01-01

    OBJECTIVE: Genetic susceptibility, low birth weight (LBW), and aging are key etiological factors in the development of type 2 diabetes. LBW is common among twins. It is unknown whether twin status per se is associated with risk of type 2 diabetes, and valid concordance rates of type 2 diabetes...... in twins on a lifetime perspective are lacking. RESEARCH DESIGN AND METHODS: A clinical study was done on a population-based cohort of same-sex elderly monozygotic (MZ) and dizygotic (DZ) twins (n = 297) and singleton control subjects (C) (n = 71) including measures of anthropometry and glucose tolerance...

  16. Role of serum miRNAs in the prediction of ovarian hyperstimulation syndrome in polycystic ovarian syndrome patients.

    Zhao, Chun; Liu, Xiaoguang; Shi, Zhonghua; Zhang, Jing; Zhang, Junqiang; Jia, Xuemei; Ling, Xiufeng

    2015-01-01

    Polycystic ovarian syndrome (PCOS) causes a significantly increased risk of ovarian hyperstimulation syndrome (OHSS). Here, we focused on the altered expression of serum miRNAs and their predictive value for OHSS in PCOS patients. We used the TaqMan low density array followed by individual quantitative reverse transcription-polymerase chain reaction to identify and validate the expression of serum miRNAs in PCOS patients likely to develop severe OHSS. The miR-16 and miR-223 expression levels were significantly reduced in the patients who were likely to develop severe OHSS than in the control subjects who were likely to develop mild or no OHSS. The sensitivity and specificity of the basal LH, basal LH/FSH, and body mass index (BMI) as OHSS predictors were also evaluated. miR-16 was the most efficient for OHSS prediction as it yielded the highest AUC. Logistic binary regression analyses revealed a positive association of miR-223 and BMI. Serum miRNAs are differentially expressed in PCOS patients likely to suffer from severe OHSS. We identified and validated two serum miRNAs that have potential for use as novel noninvasive biomarkers to accurately predict OHSS before controlled ovarian hyperstimulation (COH) for PCOS patients. © 2015 S. Karger AG, Basel.

  17. Increased risk for ovarian cancer and borderline ovarian tumours in subfertile women with endometriosis

    Buis, C. C. M.; van Leeuwen, F. E.; Mooij, T. M.; Burger, C. W.; Lambalk, Cornelis B.; Kortman, Marian; Laven, Joop S. E.; Jansen, Cees A. M.; Helmerhorst, Frans M.; Cohlen, Ben J.; Willemsen, Wim N. P.; Smeenk, Jesper M. J.; Simons, Arnold H. M.; van der Veen, Fulco; Evers, Johannes L. H.; van Dop, Peter A.; Macklon, Nicholas S.

    2013-01-01

    Is ovarian or extra-ovarian endometriosis associated with an increased risk of ovarian cancer and borderline ovarian tumours (BOT)? We found a 3- to 8-fold increased risk of ovarian tumours associated with endometriosis: the magnitude of the risk increase depended on the definition of endometriosis.

  18. A path-based measurement for human miRNA functional similarities using miRNA-disease associations

    Ding, Pingjian; Luo, Jiawei; Xiao, Qiu; Chen, Xiangtao

    2016-09-01

    Compared with the sequence and expression similarity, miRNA functional similarity is so important for biology researches and many applications such as miRNA clustering, miRNA function prediction, miRNA synergism identification and disease miRNA prioritization. However, the existing methods always utilized the predicted miRNA target which has high false positive and false negative to calculate the miRNA functional similarity. Meanwhile, it is difficult to achieve high reliability of miRNA functional similarity with miRNA-disease associations. Therefore, it is increasingly needed to improve the measurement of miRNA functional similarity. In this study, we develop a novel path-based calculation method of miRNA functional similarity based on miRNA-disease associations, called MFSP. Compared with other methods, our method obtains higher average functional similarity of intra-family and intra-cluster selected groups. Meanwhile, the lower average functional similarity of inter-family and inter-cluster miRNA pair is obtained. In addition, the smaller p-value is achieved, while applying Wilcoxon rank-sum test and Kruskal-Wallis test to different miRNA groups. The relationship between miRNA functional similarity and other information sources is exhibited. Furthermore, the constructed miRNA functional network based on MFSP is a scale-free and small-world network. Moreover, the higher AUC for miRNA-disease prediction indicates the ability of MFSP uncovering miRNA functional similarity.

  19. Overexpression of microRNAs from the miR-17-92 paralog clusters in AIDS-related non-Hodgkin's lymphomas.

    Dharma R Thapa

    Full Text Available Individuals infected by HIV are at an increased risk for developing non-Hodgkin's lymphomas (AIDS-NHL. In the highly active antiretroviral therapy (HAART era, there has been a significant decline in the incidence of AIDS-associated primary central nervous system lymphoma (PCNSL. However, only a modest decrease in incidence has been reported for other AIDS-NHL subtypes. Thus, AIDS-NHLs remain a significant cause of morbidity and mortality in HIV infected individuals. Recently, much attention has been directed toward the role of miRNAs in cancer, including NHL. Several miRNAs, including those encoded by the miR-17-92 polycistron, have been shown to play significant roles in B cell tumorigenesis. However, the role of miRNAs in NHL in the setting of HIV infection has not been defined.We used quantitative realtime PCR to assess the expression of miRNAs from three different paralog clusters, miR-17-92, miR-106a-363, and miR-106b-25 in 24 cases of AIDS-NHLs representing four tumor types, Burkitt's lymphoma (BL, n = 6, diffuse large B-cell lymphoma (DLBCL, n = 8, primary central nervous system lymphoma (PCNSL, n = 5, and primary effusion lymphoma (PEL, n = 5. We also used microarray analysis to identify a differentiation specific miRNA signature of naïve, germinal center, and memory B cell subsets from tonsils (n = 4. miRNAs from the miR-17-92 paralog clusters were upregulated by B cells, specifically during the GC differentiation stage. We also found overexpression of these miRNA clusters in all four AIDS-NHL subtypes. Finally, we also show that select miRNAs from these clusters (miR-17, miR-106a, and miR-106b inhibited p21 in AIDS-BL and DLBCL cases, thus providing a mechanistic role for these miRNAs in AIDS-NHL pathogenesis.Dysregulation of miR-17-92 paralog clusters is a common feature of AIDS-associated NHLs.

  20. Increased risk of hepatitis E in sewage workers from India.

    Vaidya, Sunil R; Tilekar, Bipin N; Walimbe, Atul M; Arankalle, Vidya A

    2003-11-01

    Considering feco-oral transmission of hepatitis E virus (HEV), the risk of the infection was assessed among sewage workers. On the basis of the close contact with sewage, the participants (n = 147) were divided into sewage workers (n = 92) and others (n = 55); none used personal protective equipment (eg, coveralls, boots, gloves) Age-matched individuals from lower socioeconomic status and without any exposure to sewage were used as controls. IgG-anti-HEV positivity in enzyme-linked immunosorbent assay was significantly higher (P 5 years. Multivariate regression analysis identified contact with sewage as the independent variable associated with anti-HEV positivity. Strict adherence to good working practices must take top priority for protection of these workers from sewage pathogens.

  1. Dysfunctional nitric oxide signalling increases risk of myocardial infarction.

    Erdmann, Jeanette; Stark, Klaus; Esslinger, Ulrike B; Rumpf, Philipp Moritz; Koesling, Doris; de Wit, Cor; Kaiser, Frank J; Braunholz, Diana; Medack, Anja; Fischer, Marcus; Zimmermann, Martina E; Tennstedt, Stephanie; Graf, Elisabeth; Eck, Sebastian; Aherrahrou, Zouhair; Nahrstaedt, Janja; Willenborg, Christina; Bruse, Petra; Brænne, Ingrid; Nöthen, Markus M; Hofmann, Per; Braund, Peter S; Mergia, Evanthia; Reinhard, Wibke; Burgdorf, Christof; Schreiber, Stefan; Balmforth, Anthony J; Hall, Alistair S; Bertram, Lars; Steinhagen-Thiessen, Elisabeth; Li, Shu-Chen; März, Winfried; Reilly, Muredach; Kathiresan, Sekar; McPherson, Ruth; Walter, Ulrich; Ott, Jurg; Samani, Nilesh J; Strom, Tim M; Meitinger, Thomas; Hengstenberg, Christian; Schunkert, Heribert

    2013-12-19

    Myocardial infarction, a leading cause of death in the Western world, usually occurs when the fibrous cap overlying an atherosclerotic plaque in a coronary artery ruptures. The resulting exposure of blood to the atherosclerotic material then triggers thrombus formation, which occludes the artery. The importance of genetic predisposition to coronary artery disease and myocardial infarction is best documented by the predictive value of a positive family history. Next-generation sequencing in families with several affected individuals has revolutionized mutation identification. Here we report the segregation of two private, heterozygous mutations in two functionally related genes, GUCY1A3 (p.Leu163Phefs*24) and CCT7 (p.Ser525Leu), in an extended myocardial infarction family. GUCY1A3 encodes the α1 subunit of soluble guanylyl cyclase (α1-sGC), and CCT7 encodes CCTη, a member of the tailless complex polypeptide 1 ring complex, which, among other functions, stabilizes soluble guanylyl cyclase. After stimulation with nitric oxide, soluble guanylyl cyclase generates cGMP, which induces vasodilation and inhibits platelet activation. We demonstrate in vitro that mutations in both GUCY1A3 and CCT7 severely reduce α1-sGC as well as β1-sGC protein content, and impair soluble guanylyl cyclase activity. Moreover, platelets from digenic mutation carriers contained less soluble guanylyl cyclase protein and consequently displayed reduced nitric-oxide-induced cGMP formation. Mice deficient in α1-sGC protein displayed accelerated thrombus formation in the microcirculation after local trauma. Starting with a severely affected family, we have identified a link between impaired soluble-guanylyl-cyclase-dependent nitric oxide signalling and myocardial infarction risk, possibly through accelerated thrombus formation. Reversing this defect may provide a new therapeutic target for reducing the risk of myocardial infarction.

  2. Lithium-induced neuroprotection in stroke involves increased miR-124 expression, reduced RE1-silencing transcription factor abundance and decreased protein deubiquitination by GSK3β inhibition-independent pathways.

    Doeppner, Thorsten R; Kaltwasser, Britta; Sanchez-Mendoza, Eduardo H; Caglayan, Ahmet B; Bähr, Mathias; Hermann, Dirk M

    2017-03-01

    Lithium promotes acute poststroke neuronal survival, which includes mechanisms that are not limited to GSK3β inhibition. However, whether lithium induces long-term neuroprotection and enhanced brain remodeling is unclear. Therefore, mice were exposed to transient middle cerebral artery occlusion and lithium (1 mg/kg bolus followed by 2 mg/kg/day over up to 7 days) was intraperitoneally administered starting 0-9 h after reperfusion onset. Delivery of lithium no later than 6 h reduced infarct volume on day 2 and decreased brain edema, leukocyte infiltration, and microglial activation, as shown by histochemistry and flow cytometry. Lithium-induced neuroprotection persisted throughout the observation period of 56 days and was associated with enhanced neurological recovery. Poststroke angioneurogenesis and axonal plasticity were also enhanced by lithium. On the molecular level, lithium increased miR-124 expression, reduced RE1-silencing transcription factor abundance, and decreased protein deubiquitination in cultivated cortical neurons exposed to oxygen-glucose deprivation and in brains of mice exposed to cerebral ischemia. Notably, this effect was not mimicked by pharmacological GSK3β inhibition. This study for the first time provides efficacy data for lithium in the postacute ischemic phase, reporting a novel mechanism of action, i.e. increased miR-124 expression facilitating REST degradation by which lithium promotes postischemic neuroplasticity and angiogenesis.

  3. Increase of baclofen intoxications : risks involved and management

    Arbouw, M E L; Hoge, H L; Meulenbelt, J; Jansman, F G A

    2014-01-01

    Baclofen has been increasingly used in the treatment of alcohol withdrawal syndrome (AWS). We present a patient with AWS and psychiatric comorbidity who ingested 700 mg of baclofen. ICU admission was necessary for ventilatory support and symptomatic treatment. The patient was dismissed without

  4. Uric acid stones increase the risk of chronic kidney disease.

    Li, Ching-Chia; Chien, Tsu-Ming; Wu, Wen-Jeng; Huang, Chun-Nung; Chou, Yii-Her

    2018-02-28

    The aim of this study was to compare the clinical characteristics of uric acid stones and their potential risk for chronic kidney disease (CKD). A total of 401 patients (196 with uric acid stone and 205 without) were enrolled from our database of patients with urolithiasis. We analyzed the clinical demographic features, stone location, urine chemistries, and renal function. There was a significant difference (p uric acid group. Patients with uric acid stones had much lower pH of urine (p uric acid level (p = 0.002). Notably, those with uric acid stones had worse eGFR than those with non-uric acid stones. Multivariate analysis confirmed that age over 60 years (ORs = 9.19; 95% CI 3.5-24.3), female sex (ORs = 4.01; 95% CI 1.8-9.0), hyperuricemia (ORs = 8.47; 95% CI 1.6-43.5), and uric acid stone (OR = 2.86; 95% CI 1.2-6.7) were the independent predictors of poor prognoses in CKD. Therefore, an association exists between uric acid stones and higher prevalence of CKD. Patients with uric acid stones may need close monitoring of renal function during follow-up.

  5. Endometriosis increases the risk of obstetrical and neonatal complications

    Berlac, Janne Foss; Hartwell, Dorthe; Skovlund, Charlotte Wessel

    2017-01-01

    Introduction: The objective of this study was to assess obstetrical complications and neonatal outcomes in women with endometriosis as compared with women without endometriosis. Material and methods: National cohort including all delivering women and their newborns in Denmark 1997–2014. Data were...... extracted from the Danish Health Register and the Medical Birth Register. Logistic regression analysis provided odds ratios (OR) with 95% confidence intervals (CI). Sub-analyses were made for primiparous women with a singleton pregnancy and for women with endometriosis who underwent gynecological surgery...... before pregnancy. Results: In 19 331 deliveries, women with endometriosis had a higher risk of severe preeclampsia (OR 1.7, 95% CI 1.5–2.0), hemorrhage in pregnancy (OR 2.3, 95% CI 2.0–2.5), placental abruption (OR 2.0, 95% CI 1.7–2.3), placenta previa (OR 3.9, 95% CI 3.5–4.3), premature rupture...

  6. Restaurant Cooking Trends and Increased Risk for Campylobacter Infection.

    Jones, Anna K; Rigby, Dan; Burton, Michael; Millman, Caroline; Williams, Nicola J; Jones, Trevor R; Wigley, Paul; O'Brien, Sarah J; Cross, Paul

    2016-07-01

    In the United Kingdom, outbreaks of Campylobacter infection are increasingly attributed to undercooked chicken livers, yet many recipes, including those of top chefs, advocate short cooking times and serving livers pink. During 2015, we studied preferences of chefs and the public in the United Kingdom and investigated the link between liver rareness and survival of Campylobacter. We used photographs to assess chefs' ability to identify chicken livers meeting safe cooking guidelines. To investigate the microbiological safety of livers chefs preferred to serve, we modeled Campylobacter survival in infected chicken livers cooked to various temperatures. Most chefs correctly identified safely cooked livers but overestimated the public's preference for rareness and thus preferred to serve them more rare. We estimated that 19%-52% of livers served commercially in the United Kingdom fail to reach 70°C and that predicted Campylobacter survival rates are 48%-98%. These findings indicate that cooking trends are linked to increasing Campylobacter infections.

  7. Warming increases the risk of civil war in Africa.

    Burke, Marshall B; Miguel, Edward; Satyanath, Shanker; Dykema, John A; Lobell, David B

    2009-12-08

    Armed conflict within nations has had disastrous humanitarian consequences throughout much of the world. Here we undertake the first comprehensive examination of the potential impact of global climate change on armed conflict in sub-Saharan Africa. We find strong historical linkages between civil war and temperature in Africa, with warmer years leading to significant increases in the likelihood of war. When combined with climate model projections of future temperature trends, this historical response to temperature suggests a roughly 54% increase in armed conflict incidence by 2030, or an additional 393,000 battle deaths if future wars are as deadly as recent wars. Our results suggest an urgent need to reform African governments' and foreign aid donors' policies to deal with rising temperatures.

  8. Risks of increased UV-B radiation for humans

    Przybilla, B.; Eberlein-Koenig, B.; Bergner, T.

    1994-01-01

    If not compensated in any way, depletion of the stratospheric ozone layer leads to an increase of UV-B radiation at the earth's surface, especially towards the short-wave range, which is biologically the more active. The most concerning effect here is that of UV-B induced skin reactions, in particular malignant skintumors (malignant melanoma, spinocellular carcinoma, basalioma), whose incidence is expected to increase in future. As some photoreactions can be inhibited or enhanced also by radiation outside their action spectrum, it is possible for changes in solar spectral radiation flux density to influence photo-induced reactions that are driven at wavelengths outside the UV-B range. The authors have performed studies for developing methods of quantifying individual UV sensitivity. In vitro studies have shown that UV-A dependent photoreactions can be partly inhibited by UV-B. A number of drugs, as well as sulphites, which are used as preservatives amongst other things, have been shown to have phototoxic properties that may be relevant to photocarcinogenesis. Irradiation tests on cell cultures for different UV-B ranges have shown that irradiation at shorter wavelengths leads to a stronger release of proinflammatory cytokines that ar longer wavelengths with the same dose. Altogether it can be said that despite compelling theoretical evidence it is not easily possible to predict the actual consequences of an increase in particular of short-wave UV-B radiation at the earth's surface. The assumed effects must be examined individually by appropriate methods. (orig.) [de

  9. Circular RNA and miR-7 in Cancer

    Hansen, Thomas Birkballe; Kjems, Jørgen; Damgaard, Christian Kroun

    2013-01-01

    MicroRNAs (miRNA) play important roles in fine-tuning gene expression and are often deregulated in cancer. The identification of competing endogenous RNA and circular RNA (circRNA) as important regulators of miRNA activity underscores the increasing complexity of ncRNA-mediated regulatory networks....... Particularly, the recently identified circular RNA, ciRS-7, which acts as a designated miR-7 inhibitor/sponge, has conceptually changed the mechanistic understanding of miRNA networks. As miR-7 modulates the expression of several oncogenes, disclosing the regulation of miR-7 activity will likely advance...... the understanding of various cancer etiologies. Here, we review the current knowledge about the ciRS-7/miR-7 axis in cancer-related pathways and discuss possible models explaining the relevance of coexpressing miR-7 along with a circRNA inhibitor....

  10. Stochastic arrangement increasing risks in financial engineering andactuarial science – a review

    Chen Li

    2018-03-01

    Full Text Available We review recent research results on stochastic arrangement increasing risks in financialand actuarial risk management, including allocation of deductibles and coverage limits concerned withmultiple dependent risks in an insurance policy, the independence model and the threshold models fora portfolio of defaults risks with dependence, and the optimal capital allocation for a financial institutewith multiple line of business.

  11. Programming of adipose tissue miR-483-3p and GDF-3 expression by maternal diet in type 2 diabetes

    Ferland-McCollough, D; Fernandez-Twinn, D S; Cannell, I G

    2012-01-01

    substantially modulates the capacity of adipocytes to differentiate and store lipids. We show that some of these effects are mediated by translational repression of growth/differentiation factor-3, a target of miR-483-3p. We propose that increased miR-483-3p expression in vivo, programmed by early......Nutrition during early mammalian development permanently influences health of the adult, including increasing the risk of type 2 diabetes and coronary heart disease. However, the molecular mechanisms underlying such programming are poorly defined. Here we demonstrate that programmed changes in mi......RNA expression link early-life nutrition to long-term health. Specifically, we show that miR-483-3p is upregulated in adipose tissue from low-birth-weight adult humans and prediabetic adult rats exposed to suboptimal nutrition in early life. We demonstrate that manipulation of miR-483-3p levels in vitro...

  12. Risk perception after genetic counseling in patients with increased risk of cancer

    Rantala Johanna

    2009-08-01

    Full Text Available Abstract Background Counselees are more aware of genetics and seek information, reassurance, screening and genetic testing. Risk counseling is a key component of genetic counseling process helping patients to achieve a realistic view for their own personal risk and therefore adapt to the medical, psychological and familial implications of disease and to encourage the patient to make informed choices 12. The aim of this study was to conceptualize risk perception and anxiety about cancer in individuals attending to genetic counseling. Methods The questionnaire study measured risk perception and anxiety about cancer at three time points: before and one week after initial genetic counseling and one year after completed genetic investigations. Eligibility criteria were designed to include only index patients without a previous genetic consultation in the family. A total of 215 individuals were included. Data was collected during three years period. Results Before genetic counseling all of the unaffected participants subjectively estimated their risk as higher than their objective risk. Participants with a similar risk as the population overestimated their risk most. All risk groups estimated the risk for children's/siblings to be lower than their own. The benefits of preventive surveillance program were well understood among unaffected participants. The difference in subjective risk perception before and directly after genetic counseling was statistically significantly lower in all risk groups. Difference in risk perception for children as well as for population was also statistically significant. Experienced anxiety about developing cancer in the unaffected subjects was lower after genetic counseling compared to baseline in all groups. Anxiety about cancer had clear correlation to perceived risk of cancer before and one year after genetic investigations. The affected participants overestimated their children's risk as well as risk for anyone in

  13. Risks of increased UV-B radiation: higher plants

    Rau, W.; Hofmann, H.

    1994-01-01

    The question pursued within the Bavarian climate research programme (BayFORKLIM) in the present context was as follows: Does the fact that UV-B radiation increases with growing site elevation mean that the low sensitivity of predominantly alpine plants compared with that of lowland plants is attributable to their different genetic constitution, possibly as a result of selective pressure and/or de alpine species have a greater capacity to develop protective mechanisms? Pairs and triplets of species belonging to the same genus but occuring at different site elevations were grown from seeds in a greenhouse that is, without UV-B. In order to determine their capacity to adapt to UV-B radiation, some of the plants were additionally exposed to UV-B for 5-6 weeks prior to sensitivity testing. Sensitivity was tested by exposing the plants to additional UV-B of different intensities in test chambers. Visible damage, ranging from light bronzing or yellowing to withering, served as an assessment criterion. Levels of UV-B absorbing substances (phenylpropane species, usually flavonoids) were also measured in these plants. The results obtained permit the following conclusions: The greater UV-B resistance of alpine species compared with that of lowland species of the same genus is not attributable to their genetic constitution but rather to their superior adaptability. Superior resistance is in part due to a greater accumulation of UV-B absorbing substances. Distinct differences in sensitivity between different genera could lead to population shifts within ecosystems as a result of increased UV-B radiation. (orig./KW) [de

  14. Geographical variance in the risk of gastric stump cancer: no increased risk in Japan?

    Tersmette, A. C.; Giardiello, F. M.; Offerhaus, G. J.; Tersmette, K. W.; Ohara, K.; Vandenbroucke, J. P.; Tytgat, G. N.

    1991-01-01

    Geographical differences may exist in the risk of gastric stump cancer. Therefore, we performed meta-analysis of literature reports in Japan (n = 3), the USA (n = 4), and Europe (n = 20) on the risk of postgastrectomy cancer. The weighted mean relative risk of stump cancer in Japan was 0.28, 95%

  15. The Racing-Game Effect : Why Do Video Racing Games Increase Risk-Taking Inclinations?

    Fischer, Peter; Greitemeyer, Tobias; Morton, Thomas; Kastenmueller, Andreas; Postmes, Tom; Frey, Dieter; Kubitzki, Joerg; Odenwaelder, Joerg; Kastenmüller, A.; Odenwälder, J.

    2009-01-01

    The present studies investigated why video racing games increase players' risk-taking inclinations. Four studies reveal that playing video racing games increases risk taking in a subsequent simulated road traffic situation, as well as risk-promoting cognitions and emotions, blood pressure, sensation

  16. Cannabis use and childhood trauma interact additively to increase the risk of psychotic symptoms in adolescence.

    Harley, M

    2010-10-01

    Adolescent cannabis use has been shown in many studies to increase the risk of later psychosis. Childhood trauma is associated with both substance misuse and risk for psychosis. In this study our aim was to investigate whether there is a significant interaction between cannabis use and childhood trauma in increasing the risk for experiencing psychotic symptoms during adolescence.

  17. Selenium deficiency risk predicted to increase under future climate change.

    Jones, Gerrad D; Droz, Boris; Greve, Peter; Gottschalk, Pia; Poffet, Deyan; McGrath, Steve P; Seneviratne, Sonia I; Smith, Pete; Winkel, Lenny H E

    2017-03-14

    Deficiencies of micronutrients, including essential trace elements, affect up to 3 billion people worldwide. The dietary availability of trace elements is determined largely by their soil concentrations. Until now, the mechanisms governing soil concentrations have been evaluated in small-scale studies, which identify soil physicochemical properties as governing variables. However, global concentrations of trace elements and the factors controlling their distributions are virtually unknown. We used 33,241 soil data points to model recent (1980-1999) global distributions of Selenium (Se), an essential trace element that is required for humans. Worldwide, up to one in seven people have been estimated to have low dietary Se intake. Contrary to small-scale studies, soil Se concentrations were dominated by climate-soil interactions. Using moderate climate-change scenarios for 2080-2099, we predicted that changes in climate and soil organic carbon content will lead to overall decreased soil Se concentrations, particularly in agricultural areas; these decreases could increase the prevalence of Se deficiency. The importance of climate-soil interactions to Se distributions suggests that other trace elements with similar retention mechanisms will be similarly affected by climate change.

  18. Decreased expression of miR-21, miR-26a, miR-29a, and miR-142-3p in CD4⁺ T cells and peripheral blood from tuberculosis patients.

    Kleinsteuber, Katja; Heesch, Kerrin; Schattling, Stefanie; Kohns, Malte; Sander-Jülch, Claudia; Walzl, Gerhard; Hesseling, Anneke; Mayatepek, Ertan; Fleischer, Bernhard; Marx, Florian M; Jacobsen, Marc

    2013-01-01

    The vast majority of Mycobacterium tuberculosis (M. tuberculosis) infected individuals are protected from developing tuberculosis and T cells are centrally involved in this process. MicroRNAs (miRNA) regulate T-cell functions and are biomarker candidates of disease susceptibility and treatment efficacy in M. tuberculosis infection. We determined the expression profile of 29 selected miRNAs in CD4(+) T cells from tuberculosis patients and contacts with latent M. tuberculosis infection (LTBI). These analyses showed lower expression of miR-21, miR-26a, miR-29a, and miR-142-3p in CD4(+) T cells from tuberculosis patients. Whole blood miRNA candidate analyses verified decreased expression of miR-26a, miR-29a, and miR-142-3p in children with tuberculosis as compared to healthy children with LTBI. Despite marked variances between individual donor samples, trends of increased miRNA candidate expression during treatment and recovery were observed. Functional in vitro analysis identified increased miR-21 and decreased miR-26a expression after re-stimulation of T cells. In vitro polarized Interleukin-17 positive T-cell clones showed activation-dependent miR-29a up-regulation. In order to characterize the role of miR-29a (a described suppressor of Interferon-γ in tuberculosis), we analyzed M. tuberculosis specific Interferon-γ expressing T cells in children with tuberculosis and healthy contacts but detected no correlation between miR-29a and Interferon-γ expression. Suppression of miR-29a in primary human T cells by antagomirs indicated no effect on Interferon-γ expression after in vitro activation. Finally, classification of miRNA targets revealed only a moderate overlap between the candidates. This may reflect differential roles of miR-21, miR-26a, miR-29a, and miR-142-3p in T-cell immunity against M. tuberculosis infection and disease.

  19. Decreased Expression of miR-21, miR-26a, miR-29a, and miR-142-3p in CD4+ T Cells and Peripheral Blood from Tuberculosis Patients

    Schattling, Stefanie; Kohns, Malte; Sander-Jülch, Claudia; Walzl, Gerhard; Hesseling, Anneke; Mayatepek, Ertan; Fleischer, Bernhard; Marx, Florian M.; Jacobsen, Marc

    2013-01-01

    The vast majority of Mycobacterium tuberculosis (M. tuberculosis) infected individuals are protected from developing tuberculosis and T cells are centrally involved in this process. MicroRNAs (miRNA) regulate T-cell functions and are biomarker candidates of disease susceptibility and treatment efficacy in M. tuberculosis infection. We determined the expression profile of 29 selected miRNAs in CD4+ T cells from tuberculosis patients and contacts with latent M. tuberculosis infection (LTBI). These analyses showed lower expression of miR-21, miR-26a, miR-29a, and miR-142-3p in CD4+ T cells from tuberculosis patients. Whole blood miRNA candidate analyses verified decreased expression of miR-26a, miR-29a, and miR-142-3p in children with tuberculosis as compared to healthy children with LTBI. Despite marked variances between individual donor samples, trends of increased miRNA candidate expression during treatment and recovery were observed. Functional in vitro analysis identified increased miR-21 and decreased miR-26a expression after re-stimulation of T cells. In vitro polarized Interleukin-17 positive T-cell clones showed activation-dependent miR-29a up-regulation. In order to characterize the role of miR-29a (a described suppressor of Interferon-γ in tuberculosis), we analyzed M. tuberculosis specific Interferon-γ expressing T cells in children with tuberculosis and healthy contacts but detected no correlation between miR-29a and Interferon-γ expression. Suppression of miR-29a in primary human T cells by antagomirs indicated no effect on Interferon-γ expression after in vitro activation. Finally, classification of miRNA targets revealed only a moderate overlap between the candidates. This may reflect differential roles of miR-21, miR-26a, miR-29a, and miR-142-3p in T-cell immunity against M. tuberculosis infection and disease. PMID:23613882

  20. Motion sickness increases the risk of accidental hypothermia.

    Nobel, Gerard; Eiken, Ola; Tribukait, Arne; Kölegård, Roger; Mekjavic, Igor B

    2006-09-01

    Motion sickness (MS) has been found to increase body-core cooling during immersion in 28 degrees C water, an effect ascribed to attenuation of the cold-induced peripheral vasoconstriction (Mekjavic et al. in J Physiol 535(2):619-623, 2001). The present study tested the hypothesis that a more profound cold stimulus would override the MS effect on peripheral vasoconstriction and hence on the core cooling rate. Eleven healthy subjects underwent two separate head-out immersions in 15 degrees C water. In the control trial (CN), subjects were immersed after baseline measurements. In the MS-trial, subjects were rendered motion sick prior to immersion, by using a rotating chair in combination with a regimen of standardized head movements. During immersion in the MS-trial, subjects were exposed to an optokinetic stimulus (rotating drum). At 5-min intervals subjects rated their temperature perception, thermal comfort and MS discomfort. During immersion mean skin temperature, rectal temperature, the difference in temperature between the non-immersed right forearm and 3rd finger of the right hand (DeltaTff), oxygen uptake and heart rate were recorded. In the MS-trial, rectal temperature decreased substantially faster (33%, P < 0.01). Also, the DeltaTff response, an index of peripheral vasomotor tone, as well as the oxygen uptake, indicative of the shivering response, were significantly attenuated (P < 0.01 and P < 0.001, respectively) by MS. Thus, MS may predispose individuals to hypothermia by enhancing heat loss and attenuating heat production. This might have significant implications for survival in maritime accidents.

  1. Micromanagement of Immune System: Role of miRNAs in Helminthic Infections.

    Arora, Naina; Tripathi, Shweta; Singh, Aloukick K; Mondal, Prosenjit; Mishra, Amit; Prasad, Amit

    2017-01-01

    Helminthic infections fall under neglected tropical diseases, although they inflict severe morbidity to human and causes major economic burden on health care system in many developing countries. There is increased effort to understand their immunopathology in recent days due to their immuno-modulatory capabilities. Immune response is primarily controlled at the transcriptional level, however, microRNA-mediated RNA interference is emerging as important regulatory machinery that works at the translation level. In the past decade, microRNA (miRNA/miR) research has advanced with significant momentum. The result is ever increasing list of curated sequences from a broad panel of organisms including helminths. Several miRNAs had been discovered from trematodes, nematodes and cestodes like let-7, miR155, miR-199, miR-134, miR-223, miR-146, and fhe-mir-125a etc., with potential role in immune modulation. These miRs had been associated with TGF-β, MAPK, Toll-like receptor, PI3K/AKT signaling pathways and insulin growth factor regulation. Thus, controlling the immune cells development, survival, proliferation and death. Apart from micromanagement of immune system, they also express certain unique miRNA also like cis- miR-001, cis- miR-2, cis- miR-6, cis- miR-10, cis- miR-18, cis- miR-19, trs-mir-0001, fhe-miR-01, fhe-miR-07, fhe-miR-08, egr-miR-4988, egr-miR-4989 etc. The specific role played by most of these species specific unique miRs are yet to be discovered. However, these newly discovered miRNAs might serve as novel targets for therapeutic intervention or biomarkers for parasitic infections.

  2. Increasing fall risk awareness using wearables: A fall risk awareness protocol.

    Danielsen, Asbjørn; Olofsen, Hans; Bremdal, Bernt Arild

    2016-10-01

    Each year about a third of elderly aged 65 or older experience a fall. Many of these falls may have been avoided if fall risk assessment and prevention tools where available in a daily living situation. We identify what kind of information is relevant for doing fall risk assessment and prevention using wearable sensors in a daily living environment by investigating current research, distinguishing between prospective and context-aware fall risk assessment and prevention. Based on our findings, we propose a fall risk awareness protocol as a fall prevention tool integrating both wearables and ambient sensing technology into a single platform. Copyright © 2016. Published by Elsevier Inc.

  3. Risk of anxiety and depressive disorders in patients with myocardial infarction

    Feng, Hsin-Pei; Chien, Wu-Chien; Cheng, Wei-Tung; Chung, Chi-Hsiang; Cheng, Shu-Meng; Tzeng, Wen-Chii

    2016-01-01

    Abstract Anxiety and depressive symptoms are associated with adverse cardiovascular events after an acute myocardial infarction (MI). However, most studies focusing on anxiety or depression have used rating scales or self-report methods rather than clinical diagnosis. This study aimed to investigate the association between psychiatrist-diagnosed psychiatric disorders and cardiovascular prognosis. We sampled data from the National Health Insurance Research Database; 1396 patients with MI were recruited as the study cohort and 13,960 patients without MI were recruited as the comparison cohort. Cox proportional hazard regression models were used to examine the effect of MI on the risk of anxiety and depressive disorders. During the first 2 years of follow-up, patients with MI exhibited a significantly higher risk of anxiety disorders (adjusted hazard ratio [HR] = 5.06, 95% confidence interval [CI]: 4.61–5.54) and depressive disorders (adjusted HR = 7.23, 95% CI: 4.88–10.88) than those without MI did. Greater risk for anxiety and depressive disorders was observed among women and patients aged 45 to 64 years following an acute MI. Patients with post-MI anxiety had a 9.37-fold (95% CI: 4.45–19.70) higher risk of recurrent MI than those without MI did after adjustment for age, sex, socioeconomic status, and comorbidities. This nationwide population-based cohort study provides evidence that MI increases the risk of anxiety and depressive disorders during the first 2 years post-MI, and post-MI anxiety disorders are associated with a higher risk of recurrent MI. PMID:27559951

  4. Infradiaphragmatic irradiation and high procarbazine doses increase colorectal cancer risk in Hodgkin lymphoma survivors

    van Eggermond, Anna M.; Schaapveld, Michael; Janus, Cécile Pm; de Boer, Jan Paul; Krol, Augustinus Dg; Zijlstra, Josée M.; van der Maazen, Richard Wm; Kremer, Leontien C.; van Leerdam, Monique E.; Louwman, Marieke Wj; Visser, Otto; de Bruin, Marie L.; Aleman, Berthe Mp; van Leeuwen, Flora E.

    2017-01-01

    Hodgkin lymphoma (HL) survivors are at increased risk of second malignancies, but few studies have assessed colorectal cancer (CRC) risk after HL treatment. We assessed long-term, subsite-specific CRC risk associated with specific radiation fields and chemotherapy regimens. In a Dutch cohort of 3121

  5. Infradiaphragmatic irradiation and high procarbazine doses increase colorectal cancer risk in Hodgkin lymphoma survivors

    Eggermond, A.M. van; Schaapveld, M.; Janus, C.P.; Boer, J.P. de; Krol, A.D.; Zijlstra, J.M.; Maazen, R.W.M. van der; Kremer, L.C.; Leerdam, M.E. van; Louwman, M.W.; Visser, O; Bruin, M.L. De; Aleman, B.M.; Leeuwen, F.E. van

    2017-01-01

    BACKGROUND: Hodgkin lymphoma (HL) survivors are at increased risk of second malignancies, but few studies have assessed colorectal cancer (CRC) risk after HL treatment. We assessed long-term, subsite-specific CRC risk associated with specific radiation fields and chemotherapy regimens. METHODS: In a

  6. Valproate attenuates the risk of myocardial infarction in patients with epilepsy: a nationwide cohort study

    Olesen, J. B.; Hansen, P. R.; Abildstrom, S. Z.

    2011-01-01

    Purpose Patients with epilepsy have increased risk of myocardial infarction (MI). Valproate can exert anti-atherosclerotic effects. We therefore examined the risk of MI in patients with epilepsy receiving valproate. Methods Two cohorts of patients with valproate-treated epilepsy and sex- and age-...

  7. Clot lysis time and the risk of myocardial infarction and ischaemic stroke in young women; results from the RATIO case-control study

    Siegerink, Bob; Meltzer, Mirjam E.; de Groot, Philip G.; Algra, Ale; Lisman, Ton; Rosendaal, Frits R.

    Reduced overall fibrinolytic capacity increases the risk of myocardial infarction (MI), as demonstrated in studies with predominantly male participants. We determined the influence of altered fibrinolysis on the risk of MI and ischaemic stroke (IS) in young women. The RATIO (Risk of Arterial

  8. Circulating miR-126 and miR-499 reflect progression of cardiovascular disease; correlations with uric acid and ejection fraction

    Masoud Khanaghaei

    2016-04-01

    Full Text Available BackgroundThe aim of this study was to assess plasma levels of endothelium- and heart-associated microRNAs (miRNAs miR-126 and miR-499, respectively, using quantitative reverse transcriptase polymerase chain reaction.MethodsA two-step analysis was conducted on 75 patients undergoing off-pomp coronary artery bypass graft (CABG surgery. Five biomarkers of inflammation and cardiac injury were assessed in addition to the above-mentioned miRNAs.ResultsPlasma concentrations of miRNAs were found to be significantly correlated with plasma levels of cardiac troponin I (cTnI (miR-499, r 0.49, p~0.002; miR-126, r = 0.30, p~0.001, indicating cardiac damage. Data analysis revealed that miR-499 had higher sensitivity and specificity for cardiac injury than miR-126, which reflects more endothelial activation. Interestingly, a strong correlation was observed between both miRNAs and uric acid (UA levels with ventricular contractility measured as ejection fraction (EF (miR-499/EF%, r = 0.58, p~0.004; UA/EF%, r = -0.6, p~0.006; UA/miR-499, r = -0.34; UA/miR-126, r = 0.5, p~0.01.ConclusionsIn patients undergoing CABG, circulating miR-126/499 is associated with presentation of traditional risk factors and reflects post-operative response to injury. Plasma pool of miRNAs likely reflects extracellular miRNAs which are proportional to intracellular miRNA levels. Therefore, circulating levels of these miRNAs have prognostic implications in detection of higher risk of future cardiovascular events.

  9. The prognostic importance of miR-21 in stage II colon cancer: a population-based study

    Kjaer-Frifeldt, S.; Hansen, T. F.; Nielsen, B. S.

    2012-01-01

    that increasing miR-21 expression levels were significantly correlated to decreasing RF-CSS. Further investigations of the clinical importance of miR-21 in the selection of high-risk stage II colon cancer patients are merited. British Journal of Cancer (2012) 107, 1169-1174. doi:10.1038/bjc.2012.365 www......BACKGROUND: Despite several years of research and attempts to develop prognostic models a considerable fraction of stage II colon cancer patients will experience relapse within few years from their operation. The aim of the present study was to investigate the prognostic importance of miRNA-21 (mi......-free cancer-specific survival (RF-CSS): HR = 1.26; 95% CI: 1.15-1.60; P importance and was found to be significantly related to poor RF-CSS: HR 1.41; 95% CI: 1.19-1.67; P

  10. The Racing-Game Effect: Why Do Video Racing Games Increase Risk-Taking Inclinations?

    Fischer, Peter; Greitemeyer, Tobias; Morton, Thomas; Kastenmüller, Andreas; Postmes, Tom; Frey, Dieter; Kubitzki, Jörg; Odenwälder, Jörg

    2009-01-01

    The present studies investigated why video racing games increase players’ risk-taking inclinations. Four studies reveal that playing video racing games increases risk taking in a subsequent simulated road traffic situation, as well as risk-promoting cognitions and emotions, blood pressure,sensation seeking, and attitudes toward reckless driving. Study 1 ruled out the role of experimental demand in creating such effects. Studies 2 and 3 showed that the effect of playing video racing games on r...

  11. Increased Bleeding Risk With Concurrent Use of Selective Serotonin Reuptake inhibitors and Coumarins

    Schalekamp, Tom; Klungel, Olaf H; Souverein, Patrick C; de Boer, Anthonius

    2008-01-01

    BACKGROUND: Treatment with vitamin K antagonists (coumarins) is associated with an increased risk of bleeding. Because use of selective serotonin reuptake inhibitors (SSRIs) is also associated with an increased risk of bleeding, we assessed the odds ratio (OR) of abnormal bleeding associated with

  12. Breast cancer patients with dense breasts do not have increased death risk

    High mammographic breast density, which is a marker of increased risk of developing breast cancer, does not seem to increase the risk of death among breast cancer patients, according to a study led by Gretchen L. Gierach, Ph.D., NCI. Image shows physician

  13. Different risk-increasing drugs in recurrent versus single fallers: are recurrent fallers a distinct population?

    Askari, Marjan; Eslami, Saied; Scheffer, Alice C.; Medlock, Stephanie; de Rooij, Sophia E.; van der Velde, Nathalie; Abu-Hanna, Ameen

    2013-01-01

    Polypharmacy, and specifically the use of multiple fall-risk-increasing drugs (FRID), have been associated with increased risk of falling in older age. However, it is not yet clear whether the known set of FRIDs can be extrapolated to recurrent fallers, since they form a distinct group of more

  14. How do women at increased breast cancer risk perceive and decide between risks of cancer and risk-reducing treatments? A synthesis of qualitative research.

    Fielden, Hannah G; Brown, Stephen L; Saini, Pooja; Beesley, Helen; Salmon, Peter

    2017-09-01

    Risk-reducing procedures can be offered to people at increased cancer risk, but many procedures can have iatrogenic effects. People therefore need to weigh risks associated with both cancer and the risk-reduction procedure in their decisions. By reviewing relevant literature on breast cancer (BC) risk reduction, we aimed to understand how women at relatively high risk of BC perceive their risk and how their risk perceptions influence their decisions about risk reduction. Synthesis of 15 qualitative studies obtained from systematic searches of SCOPUS, Web of Knowledge, PsychINFO, and Medline electronic databases (inception-June 2015). Women did not think about risk probabilistically. Instead, they allocated themselves to broad risk categories, typically influenced by their own or familial experiences of BC. In deciding about risk-reduction procedures, some women reported weighing the risks and benefits, but papers did not describe how they did so. For many women, however, an overriding wish to reduce intense worry about BC led them to choose aggressive risk-reducing procedures without such deliberation. Reasoning that categorisation is a fundamental aspect of risk perception, we argue that patients can be encouraged to develop more nuanced and accurate categorisations of their own risk through their interactions with clinicians. Empirically-based ethical reflection is required to determine whether and when it is appropriate to provide risk-reduction procedures to alleviate worry. © 2016 The Authors. Psycho-Oncology Published by John Wiley & Sons Ltd.

  15. Growth inhibitory effects of miR-221 and miR-222 in non-small cell lung cancer cells

    Yamashita, Ryo; Sato, Mitsuo; Kakumu, Tomohiko; Hase, Tetsunari; Yogo, Naoyuki; Maruyama, Eiichi; Sekido, Yoshitaka; Kondo, Masashi; Hasegawa, Yoshinori

    2015-01-01

    Both pro- and anti-oncogenic roles of miR-221 and miR-222 microRNAs are reported in several types of human cancers. A previous study suggested their oncogenic role in invasiveness in lung cancer, albeit only one cell line (H460) was used. To further evaluate involvement of miR-221 and miR-222 in lung cancer, we investigated the effects of miR-221 and miR-222 overexpression on six lung cancer cell lines, including H460, as well as one immortalized normal human bronchial epithelial cell line, HBEC4. miR-221 and miR-222 induced epithelial-to-mesenchymal transition (EMT)-like changes in a minority of HBEC4 cells but, unexpectedly, both the microRNAs rather suppressed their invasiveness. Consistent with the prior report, miR-221 and miR-222 promoted growth in H460; however, miR-221 suppressed growth in four other cell lines with no effects in one, and miR-222 suppressed growth in three cell lines but promoted growth in two. These are the first results to show tumor-suppressive effects of miR-221 and miR-222 in lung cancer cells, and we focused on clarifying the mechanisms. Cell cycle and apoptosis analyses revealed that growth suppression by miR-221 and miR-222 occurred through intra-S-phase arrest and/or apoptosis. Finally, lung cancer cell lines transfected with miR-221 or miR-222 became more sensitive to the S-phase targeting drugs, possibly due to an increased S-phase population. In conclusion, our data are the first to show tumor-suppressive effects of miR-221 and miR-222 on lung cancer, warranting testing their potential as therapeutics for the disease

  16. Exploration of miRNA families for hypotheses generation.

    Kamanu, T.K.

    2013-10-15

    Technological improvements have resulted in increased discovery of new microRNAs (miRNAs) and refinement and enrichment of existing miRNA families. miRNA families are important because they suggest a common sequence or structure configuration in sets of genes that hint to a shared function. Exploratory tools to enhance investigation of characteristics of miRNA families and the functions of family-specific miRNA genes are lacking. We have developed, miRNAVISA, a user-friendly web-based tool that allows customized interrogation and comparisons of miRNA families for hypotheses generation, and comparison of per-species chromosomal distribution of miRNA genes in different families. This study illustrates hypothesis generation using miRNAVISA in seven species. Our results unveil a subclass of miRNAs that may be regulated by genomic imprinting, and also suggest that some miRNA families may be species-specific, as well as chromosome- and/or strand-specific.

  17. Evolutionary relationships between miRNA genes and their activity.

    Zhu, Yan; Skogerbø, Geir; Ning, Qianqian; Wang, Zhen; Li, Biqing; Yang, Shuang; Sun, Hong; Li, Yixue

    2012-12-22

    The emergence of vertebrates is characterized by a strong increase in miRNA families. MicroRNAs interact broadly with many transcripts, and the evolution of such a system is intriguing. However, evolutionary questions concerning the origin of miRNA genes and their subsequent evolution remain unexplained. In order to systematically understand the evolutionary relationship between miRNAs gene and their function, we classified human known miRNAs into eight groups based on their evolutionary ages estimated by maximum parsimony method. New miRNA genes with new functional sequences accumulated more dynamically in vertebrates than that observed in Drosophila. Different levels of evolutionary selection were observed over miRNA gene sequences with different time of origin. Most genic miRNAs differ from their host genes in time of origin, there is no particular relationship between the age of a miRNA and the age of its host genes, genic miRNAs are mostly younger than the corresponding host genes. MicroRNAs originated over different time-scales are often predicted/verified to target the same or overlapping sets of genes, opening the possibility of substantial functional redundancy among miRNAs of different ages. Higher degree of tissue specificity and lower expression level was found in young miRNAs. Our data showed that compared with protein coding genes, miRNA genes are more dynamic in terms of emergence and decay. Evolution patterns are quite different between miRNAs of different ages. MicroRNAs activity is under tight control with well-regulated expression increased and targeting decreased over time. Our work calls attention to the study of miRNA activity with a consideration of their origin time.

  18. Increased fracture risk assessed by fracture risk assessment tool in Greek patients with Crohn's disease.

    Terzoudis, Sotirios; Zavos, Christos; Damilakis, John; Neratzoulakis, John; Dimitriadi, Daphne Anna; Roussomoustakaki, Maria; Kouroumalis, Elias A; Koutroubakis, Ioannis E

    2013-01-01

    The World Health Organization has recently developed the fracture risk assessment tool (FRAX) based on clinical risk factors and bone mineral density (BMD) for evaluation of the 10-year probability of a hip or a major osteoporotic fracture. The aim of this study was to evaluate the use of the FRAX tool in Greek patients with inflammatory bowel disease (IBD). FRAX scores were applied to 134 IBD patients [68 Crohn's disease (CD); 66 ulcerative colitis (UC)] who underwent dual-energy X-ray absorptiometry scans at the femoral neck and lumbar spine during the period 2007-2012. Calculation of the FRAX scores, with or without BMD, was made through a web-based probability model used to compute individual fracture probabilities according to specific clinical risk factors. The median 10-year probability of a major osteoporotic fracture for IBD patients based on clinical data was 7.1%, and including the BMD was 6.2%. A significant overestimation with the first method was found (P = 0.01). Both scores with and without BMD were significantly higher in CD patients compared with UC patients (P = 0.02 and P = 0.005, respectively). The median 10-year probability of hip fracture based on clinical data was 0.8%, and including the BMD was 0.9%. The score with use of BMD was significantly higher in CD compared with UC patients (P = 0.04). CD patients have significantly higher FRAX scores and possibly fracture risk compared with UC patients. The clinical FRAX score alone seems to overestimate the risk of osteoporotic fracture in Greek IBD patients.

  19. Risk of anxiety and depressive disorders in patients with myocardial infarction: A nationwide population-based cohort study.

    Feng, Hsin-Pei; Chien, Wu-Chien; Cheng, Wei-Tung; Chung, Chi-Hsiang; Cheng, Shu-Meng; Tzeng, Wen-Chii

    2016-08-01

    Anxiety and depressive symptoms are associated with adverse cardiovascular events after an acute myocardial infarction (MI). However, most studies focusing on anxiety or depression have used rating scales or self-report methods rather than clinical diagnosis. This study aimed to investigate the association between psychiatrist-diagnosed psychiatric disorders and cardiovascular prognosis.We sampled data from the National Health Insurance Research Database; 1396 patients with MI were recruited as the study cohort and 13,960 patients without MI were recruited as the comparison cohort. Cox proportional hazard regression models were used to examine the effect of MI on the risk of anxiety and depressive disorders.During the first 2 years of follow-up, patients with MI exhibited a significantly higher risk of anxiety disorders (adjusted hazard ratio [HR] = 5.06, 95% confidence interval [CI]: 4.61-5.54) and depressive disorders (adjusted HR = 7.23, 95% CI: 4.88-10.88) than those without MI did. Greater risk for anxiety and depressive disorders was observed among women and patients aged 45 to 64 years following an acute MI. Patients with post-MI anxiety had a 9.37-fold (95% CI: 4.45-19.70) higher risk of recurrent MI than those without MI did after adjustment for age, sex, socioeconomic status, and comorbidities.This nationwide population-based cohort study provides evidence that MI increases the risk of anxiety and depressive disorders during the first 2 years post-MI, and post-MI anxiety disorders are associated with a higher risk of recurrent MI.

  20. Fuel poverty increases risk of mould contamination, regardless of adult risk perception & ventilation in social housing properties.

    Sharpe, Richard A; Thornton, Christopher R; Nikolaou, Vasilis; Osborne, Nicholas J

    2015-06-01

    Fuel poverty affects 2.4 million UK homes leading to poor hygrothermal conditions and risk of mould and house dust mite contaminations, which in turn increases risk of asthma exacerbation. For the first time we assess how fuel poverty, occupants' risk perception and use of mechanical ventilation mediate the risk of mould contamination in social housing. Postal questionnaires were sent to 3867 social housing properties to collect adult risk perception, and demographic and environmental information on occupants. Participant details were linked to data pertaining to the individual properties. Multiple logistic regression was used to calculate odds ratios and confidence intervals while allowing for clustering of individuals coming from the same housing estate. We used Structured Equation Modelling and Goodness of Fit analysis in mediation analyses to examine the role of fuel poverty, risk perception, use of ventilation and energy efficiency. Eighteen percent of our target social housing populations (671 households) were included into our study. High risk perception (score of 8-10) was associated with reduced risk of mould contamination in the bedrooms of children (OR 0.5 95% CI; 0.3-0.9) and adults (OR 0.4 95% CI; 0.3-0.7). High risk perception of living with inadequate heating and ventilation reduced the risk of mould contamination (OR 0.5 95% CI; 0.3-0.8 and OR 0.5 95% CI; 0.3-0.7, respectively). Participants living with inadequate heating and not heating due to the cost of fuel had an increased risk of mould contamination (OR 3.4 95% CI; 2.0-5.8 and OR 2.2 95% CI; 1.5-3.2, respectively). Increased risk perception and use of extractor fans did not mediate the association between fuel poverty behaviours and increased risk of mould contamination. Fuel poverty behaviours increased the risk of mould contamination, which corresponds with existing literature. For the first time we used mediation analysis to assess how this association maybe modified by occupant behaviours

  1. Risk factors for myocardial infarction during vacation travel.

    Kop, Willem J; Vingerhoets, Ad; Kruithof, Gert-Jan; Gottdiener, John S

    2003-01-01

    Medical emergencies occur increasingly outside the usual health care area as a result of increased leisure and professional travel. Acute coronary syndromes are the leading cause of mortality during vacation. Vacation activities include physical and emotional triggers for myocardial infarction (MI). This study examines characteristics of vacation travel as risk factors for MI. Patients diagnosed with MI during vacation abroad (N = 92; age, 59.5 +/- 10.2; 79 men) were recruited through an emergency health insurance organization. Risk indicators for Vacation MI were examined and included: cardiovascular risk factors, psychosocial measures, and specific demands and activities related to vacation (eg, lodging accommodations, unfamiliar destination, mode of transportation, short-term planning). Vacation MI patients were compared with two reference groups: age-matched Vacation Controls with noncardiovascular medical emergencies (N = 67) and Hospital MI Controls, admitted in their usual health care area (N = 30). Vacation MI occurred disproportionately (21.1%) during the first 2 days of vacation. Cardiovascular risk factors were more prevalent among Vacation MI patients than Vacation Controls (p values traveling by car versus other modes of transportation (OR = 2.5, CI = 1.0-6.1) and among patients staying in a tent or mobile home versus hotel (OR = 9.7, CI = 2.0-47.9). Incidence of MI during vacation is highest during the first 2 days of vacation. Vacation activities such as adverse driving conditions and less luxurious accommodations may increase risk for MI. Individuals with known vulnerability for MI may therefore benefit from minimizing physical and emotional challenges specifically related to vacation travel.

  2. Risk assessment tools to identify women with increased risk of osteoporotic fracture. Complexity or simplicity?

    Rubin, Katrine Hass; Friis-Holmberg, Teresa; Hermann, Anne Pernille

    2013-01-01

    A huge number of risk assessment tools have been developed. Far from all have been validated in external studies, more of them have absence of methodological and transparent evidence and few are integrated in national guidelines. Therefore, we performed a systematic review to provide an overview...... of existing valid and reliable risk assessment tools for prediction of osteoporotic fractures. Additionally, we aimed to determine if the performance each tool was sufficient for practical use and lastly to examine whether the complexity of the tools influenced their discriminative power. We searched Pub......Med, Embase and Cochrane databases for papers and evaluated these with respect to methodological quality using the QUADAS checklist. A total of 48 tools were identified, 20 had been externally validated, however only 6 tools had been tested more than once in a population-based setting with acceptable...

  3. miRSponge: a manually curated database for experimentally supported miRNA sponges and ceRNAs.

    Wang, Peng; Zhi, Hui; Zhang, Yunpeng; Liu, Yue; Zhang, Jizhou; Gao, Yue; Guo, Maoni; Ning, Shangwei; Li, Xia

    2015-01-01

    In this study, we describe miRSponge, a manually curated database, which aims at providing an experimentally supported resource for microRNA (miRNA) sponges. Recent evidence suggests that miRNAs are themselves regulated by competing endogenous RNAs (ceRNAs) or 'miRNA sponges' that contain miRNA binding sites. These competitive molecules can sequester miRNAs to prevent them interacting with their natural targets to play critical roles in various biological and pathological processes. It has become increasingly important to develop a high quality database to record and store ceRNA data to support future studies. To this end, we have established the experimentally supported miRSponge database that contains data on 599 miRNA-sponge interactions and 463 ceRNA relationships from 11 species following manual curating from nearly 1200 published articles. Database classes include endogenously generated molecules including coding genes, pseudogenes, long non-coding RNAs and circular RNAs, along with exogenously introduced molecules including viral RNAs and artificial engineered sponges. Approximately 70% of the interactions were identified experimentally in disease states. miRSponge provides a user-friendly interface for convenient browsing, retrieval and downloading of dataset. A submission page is also included to allow researchers to submit newly validated miRNA sponge data. Database URL: http://www.bio-bigdata.net/miRSponge. © The Author(s) 2015. Published by Oxford University Press.

  4. Mycobacterium tuberculosis decreases human macrophage IFN-γ responsiveness through miR-132 and miR-26a.

    Ni, Bin; Rajaram, Murugesan V S; Lafuse, William P; Landes, Michelle B; Schlesinger, Larry S

    2014-11-01

    IFN-γ-activated macrophages play an essential role in controlling intracellular pathogens; however, macrophages also serve as the cellular home for the intracellular pathogen Mycobacterium tuberculosis. Based on previous evidence that M. tuberculosis can modulate host microRNA (miRNA) expression, we examined the miRNA expression profile of M. tuberculosis-infected primary human macrophages. We identified 31 differentially expressed miRNAs in primary human macrophages during M. tuberculosis infection by NanoString and confirmed our findings by quantitative real-time RT-PCR. In addition, we determined a role for two miRNAs upregulated upon M. tuberculosis infection, miR-132 and miR-26a, as negative regulators of transcriptional coactivator p300, a component of the IFN-γ signaling cascade. Knockdown expression of miR-132 and miR-26a increased p300 protein levels and improved transcriptional, translational, and functional responses to IFN-γ in human macrophages. Collectively, these data validate p300 as a target of miR-132 and miR-26a, and demonstrate a mechanism by which M. tuberculosis can limit macrophage responses to IFN-γ by altering host miRNA expression. Copyright © 2014 by The American Association of Immunologists, Inc.

  5. Genetic variants in regulatory regions of microRNAs are associated with lung cancer risk.

    Xie, Kaipeng; Wang, Cheng; Qin, Na; Yang, Jianshui; Zhu, Meng; Dai, Juncheng; Jin, Guangfu; Shen, Hongbing; Ma, Hongxia; Hu, Zhibin

    2016-07-26

    Genetic variants in regulatory regions of some miRNAs might be associated with lung cancer risk and survival. We performed a case-control study including 1341 non-small cell lung cancer (NSCLC) cases and 1982 controls to evaluate the associations of 7 potentially functional polymorphisms in several differently expressed miRNAs with NSCLC risk. Each SNP was also tested for the association with overall survival of 1001 NSCLC patients. We identified that rs9660710 in miR-200b/200a/429 cluster and rs763354 in miR-30a were significantly associated with NSCLC risk [odds ratio (OR) = 1.17, 95% confidence interval (CI) = 1.06-1.30, P = 0.002; OR = 0.88, 95% CI = 0.80-0.98, P = 0.017; respectively]. However, no significant association between variants and NSCLC death risk was observed in survival analysis. Functional annotation showed that both rs9660710 and rs763354 were located in regulatory elements in lung cancer cells. Compared to normal tissues, miR-200a-3p, miR-200a-5p, miR-200b-3p, miR-200b-5p and miR-429 were significantly increased in The Cancer Genome Atlas (TCGA) Lung Adenocarcinoma (LUAD) tumors, whereas miR-30a-3p and miR-30a-5p were significantly decreased in tumors (all P < 0.05). Furthermore, we observed that rs9660710 is an expression quantitative trait locus (eQTL) or methylation eQTL for miR-429 expression in TCGA normal tissues. Our results indicated that rs9660710 in miR-200b/200a/429 cluster and rs763354 in miR-30a might modify the susceptibility to NSCLC.

  6. Blocking miRNA Biogenesis in Adult Forebrain Neurons Enhances Seizure Susceptibility, Fear Memory, and Food Intake by Increasing Neuronal Responsiveness.

    Fiorenza, Anna; Lopez-Atalaya, Jose P; Rovira, Victor; Scandaglia, Marilyn; Geijo-Barrientos, Emilio; Barco, Angel

    2016-04-01

    The RNase Dicer is essential for the maturation of most microRNAs, a molecular system that plays an essential role in fine-tuning gene expression. To gain molecular insight into the role of Dicer and the microRNA system in brain function, we conducted 2 complementary RNA-seq screens in the hippocampus of inducible forebrain-restricted Dicer1 mutants aimed at identifying the microRNAs primarily affected by Dicer loss and their targets, respectively. Functional genomics analyses predicted the main biological processes and phenotypes associated with impaired microRNA maturation, including categories related to microRNA biology, signal transduction, seizures, and synaptic transmission and plasticity. Consistent with these predictions, we found that, soon after recombination, Dicer-deficient mice exhibited an exaggerated seizure response, enhanced induction of immediate early genes in response to different stimuli, stronger and more stable fear memory, hyperphagia, and increased excitability of CA1 pyramidal neurons. In the long term, we also observed slow and progressive excitotoxic neurodegeneration. Overall, our results indicate that interfering with microRNA biogenesis causes an increase in neuronal responsiveness and disrupts homeostatic mechanisms that protect the neuron against overactivation, which may explain both the initial and late phenotypes associated with the loss of Dicer in excitatory neurons. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  7. Illumina MiSeq Phylogenetic Amplicon Sequencing Shows a Large Reduction of an Uncharacterised Succinivibrionaceae and an Increase of the Methanobrevibacter gottschalkii Clade in Feed Restricted Cattle.

    Matthew Sean McCabe

    Full Text Available Periodic feed restriction is used in cattle production to reduce feed costs. When normal feed levels are resumed, cattle catch up to a normal weight by an acceleration of normal growth rate, known as compensatory growth, which is not yet fully understood. Illumina Miseq Phylogenetic marker amplicon sequencing of DNA extracted from rumen contents of 55 bulls showed that restriction of feed (70% concentrate, 30% grass silage for 125 days, to levels that caused a 60% reduction of growth rate, resulted in a large increase of relative abundance of Methanobrevibacter gottschalkii clade (designated as OTU-M7, and a large reduction of an uncharacterised Succinivibrionaceae species (designated as OTU-S3004. There was a strong negative Spearman correlation (ρ = -0.72, P = <1x10(-20 between relative abundances of OTU-3004 and OTU-M7 in the liquid rumen fraction. There was also a significant increase in acetate:propionate ratio (A:P in feed restricted animals that showed a negative Spearman correlation (ρ = -0.69, P = <1x10(-20 with the relative abundance of OTU-S3004 in the rumen liquid fraction but not the solid fraction, and a strong positive Spearman correlation with OTU-M7 in the rumen liquid (ρ = 0.74, P = <1x10(-20 and solid (ρ = 0.69, P = <1x10(-20 fractions. Reduced A:P ratios in the rumen are associated with increased feed efficiency and reduced production of methane which has a global warming potential (GWP 100 years of 28. Succinivibrionaceae growth in the rumen was previously suggested to reduce methane emissions as some members of this family utilise hydrogen, which is also utilised by methanogens for methanogenesis, to generate succinate which is converted to propionate. Relative abundance of OTU-S3004 showed a positive Spearman correlation with propionate (ρ = 0.41, P = <0.01 but not acetate in the liquid rumen fraction.

  8. Prognostic significance of miR-205 in endometrial cancer.

    Mihriban Karaayvaz

    Full Text Available microRNAs have emerged as key regulators of gene expression, and their altered expression has been associated with tumorigenesis and tumor progression. Thus, microRNAs have potential as both cancer biomarkers and/or potential novel therapeutic targets. Although accumulating evidence suggests the role of aberrant microRNA expression in endometrial carcinogenesis, there are still limited data available about the prognostic significance of microRNAs in endometrial cancer. The goal of this study is to investigate the prognostic value of selected key microRNAs in endometrial cancer by the analysis of archival formalin-fixed paraffin-embedded tissues.Total RNAs were extracted from 48 paired normal and endometrial tumor specimens using Trizol based approach. The expression of miR-26a, let-7g, miR-21, miR-181b, miR-200c, miR-192, miR-215, miR-200c, and miR-205 were quantified by real time qRT-PCR expression analysis. Targets of the differentially expressed miRNAs were quantified using immunohistochemistry. Statistical analysis was performed by GraphPad Prism 5.0.The expression levels of miR-200c (P<0.0001 and miR-205 (P<0.0001 were significantly increased in endometrial tumors compared to normal tissues. Kaplan-Meier survival analysis revealed that high levels of miR-205 expression were associated with poor patient overall survival (hazard ratio, 0.377; Logrank test, P = 0.028. Furthermore, decreased expression of a miR-205 target PTEN was detected in endometrial cancer tissues compared to normal tissues.miR-205 holds a unique potential as a prognostic biomarker in endometrial cancer.

  9. Search for <mi>CP> Violation and Measurement of the Branching Fraction in the Decay <mi>D>0<mi>KS>0<mi>KS>0

    Dash, N.; Bahinipati, S.; Bhardwaj, V.; Trabelsi, K.; Adachi, I.; Aihara, H.; Al Said, S.; Asner, D. M.; Aulchenko, V.; Aushev, T.; Ayad, R.; Babu, V.; Badhrees, I.; Bakich, A. M.; Bansal, V.; Barberio, E.; Bhuyan, B.; Biswal, J.; Bobrov, A.; Bondar, A.; Bonvicini, G.; Bozek, A.; Bračko, M.; Breibeck, F.; Browder, T. E.; Červenkov, D.; Chang, M. -C.; Chekelian, V.; Chen, A.; Cheon, B. G.; Chilikin, K.; Cho, K.; Choi, Y.; Cinabro, D.; Di Carlo, S.; Doležal, Z.; Drásal, Z.; Dutta, D.; Eidelman, S.; Epifanov, D.; Farhat, H.; Fast, J. E.; Ferber, T.; Fulsom, B. G.; Gaur, V.; Gabyshev, N.; Garmash, A.; Gillard, R.; Goldenzweig, P.; Haba, J.; Hara, T.; Hayasaka, K.; Hayashii, H.; Hedges, M. T.; Hou, W. -S.; Iijima, T.; Inami, K.; Ishikawa, A.; Itoh, R.; Iwasaki, Y.; Jacobs, W. W.; Jaegle, I.; Jeon, H. B.; Jin, Y.; Joffe, D.; Joo, K. K.; Julius, T.; Kahn, J.; Kaliyar, A. B.; Karyan, G.; Katrenko, P.; Kawasaki, T.; Kiesling, C.; Kim, D. Y.; Kim, H. J.; Kim, J. B.; Kim, K. T.; Kim, M. J.; Kim, S. H.; Kim, Y. J.; Kinoshita, K.; Kodyš, P.; Korpar, S.; Kotchetkov, D.; Križan, P.; Krokovny, P.; Kuhr, T.; Kulasiri, R.; Kumar, R.; Kumita, T.; Kuzmin, A.; Kwon, Y. -J.; Lange, J. S.; Lee, I. S.; Li, C. H.; Li, L.; Li, Y.; Li Gioi, L.; Libby, J.; Liventsev, D.; Lubej, M.; Luo, T.; Masuda, M.; Matvienko, D.; Merola, M.; Miyabayashi, K.; Miyata, H.; Mizuk, R.; Mohanty, G. B.; Mohanty, S.; Moon, H. K.; Mori, T.; Mussa, R.; Nakano, E.; Nakao, M.; Nanut, T.; Nath, K. J.; Natkaniec, Z.; Nayak, M.; Niiyama, M.; Nisar, N. K.; Nishida, S.; Ogawa, S.; Okuno, S.; Ono, H.; Pakhlov, P.; Pakhlova, G.; Pal, B.; Pardi, S.; Park, C. -S.; Park, H.; Paul, S.; Pedlar, T. K.; Pesántez, L.; Pestotnik, R.; Piilonen, L. E.; Prasanth, K.; Ritter, M.; Rostomyan, A.; Sahoo, H.; Sakai, Y.; Sandilya, S.; Santelj, L.; Sanuki, T.; Sato, Y.; Savinov, V.; Schneider, O.; Schnell, G.; Schwanda, C.; Schwartz, A. J.; Seino, Y.; Senyo, K.; Sevior, M. E.; Shebalin, V.; Shen, C. P.; Shibata, T. -A.; Shiu, J. -G.; Shwartz, B.; Simon, F.; Sokolov, A.; Solovieva, E.; Starič, M.; Strube, J. F.; Stypula, J.; Sumisawa, K.; Sumiyoshi, T.; Takizawa, M.; Tamponi, U.; Tanida, K.; Tenchini, F.; Uchida, M.; Uglov, T.; Unno, Y.; Uno, S.; Urquijo, P.; Usov, Y.; Van Hulse, C.; Varner, G.; Vorobyev, V.; Vossen, A.; Waheed, E.; Wang, C. H.; Wang, M. -Z.; Wang, P.; Watanabe, M.; Watanabe, Y.; Widmann, E.; Williams, K. M.; Won, E.; Yamashita, Y.; Ye, H.; Yelton, J.; Yook, Y.; Yuan, C. Z.; Yusa, Y.; Zhang, Z. P.; Zhilich, V.; Zhukova, V.; Zhulanov, V.; Zupanc, A.

    2017-10-01

    We report a study of the decay <mi>D>0<mi>KS>0<mi>KS>0 using 921 fb-1 of data collected at or near the Υ(4S) and Υ(5S) resonances with the Belle detector at the KEKB asymmetric energy e+e- collider. The measured time-integrated CP asymmetry is ACP(<mi>D>0<mi>KS>0<mi>KS>0) = (-0.02 ± 1.53 ± 0.02 ± 0.17)%, and the branching fraction is B(<mi>D>0<mi>KS>0<mi>KS>0) = (1.321 ± 0.023 ± 0.036 ± 0.044) × 10-4, where the first uncertainty is statistical, the second is systematic, and the third is due to the normalization mode (<mi>D>0<mi>KS>0π0). These results are significantly more precise than previous measurements available for this mode. The ACP measurement is consistent with the standard model expectation.

  10. Reducing risks and increasing safety in everyday life: the role of the public

    Enander, A.

    1998-01-01

    Full text of publication follows: in social science risk research more attention has been paid to examining how people in general perceive risks than to how they perceive possible measures to reduce risks and to increase their own safety. The latter area is, however, becoming increasingly important to understand, particularly in the light of current emphasis on individual responsibility in risk prevention and emergency preparedness. For example, in Sweden a major effort to increase safety awareness among the general public and to increase knowledge and skills in a number of safety-related areas is at present being planned. This effort is being undertaken as a cooperative effort between different authorities and institutions and is coordinated by the Swedish Rescue Services Agency. The intentions behind this and similar programmes raise a number of questions concerning how people view risks and safety measures in their own immediate environment. Knowledge of the factors affecting willingness to take precautions is important in the design of communication and information. The factors which are of significance may be risk-related and concern perceptions of personal risk, but may also be related to attitudes an beliefs concerning different precautionary measures, to perception of social norms and conventions as well as to personal experiences and values. This paper presents some data concerning views and actions among lay groups in relation to reducing risks and increasing safety. Factors affecting these views are discussed in the light of previous research and of empirical data from some recent studies. (author)

  11. Does employee resistance during a robbery increase the risk of customer injury?

    Yau, Rebecca K; Casteel, Carri; Nocera, Maryalice; Bishop, Stephanie F; Peek-Asa, Corinne

    2015-04-01

    Retail business robberies can lead to employee and customer injury. Previous work demonstrates that employee resistance increases employee injury risk; limited research has investigated customer injuries. This study examines associations between employee resistance against perpetrators and the risk of customer injury. Retail and service robbery reports were obtained from a metropolitan police department. Generalized estimating equations estimated risk ratios and 95% confidence intervals (CIs). Customers were injured in 75 out of 697 robberies. Employees resisted the perpetrator in 32 out of 697 robberies. Customers had higher injury risk when employees resisted the perpetrator, compared with robberies where employees did not resist (adjusted risk ratio [95% CI], 2.6 [1.5 to 4.5]). Employee resistance against a perpetrator during a robbery increased customer injury risk. Businesses can train employees to not resist during a robbery, providing benefits for both customers and the business itself.

  12. On the increased risk of developing late-onset epilepsy for patients with major affective disorder

    Nilsson, Flemming Mørkeberg; Kessing, Lars Vedel; Bolwig, Tom Gert

    2003-01-01

    for the control groups. However, the increased risk seemed to be due to the effect of comorbid alcohol or drug abuse and not to the effect of the affective illness itself. LIMITATIONS: The results only apply to hospitalised patients. Diagnoses are not validated for research purposes. CONCLUSION: Patients...... with a diagnosis of affective disorder have an increased risk of developing epilepsy in later life. In patients with affective disorder, comorbid alcoholism/drug abuse seriously increased the risk of a subsequent diagnosis of epilepsy....

  13. At-Risk Variant in TCF7L2 for Type II Diabetes Increases Risk of Schizophrenia

    Hansen, Thomas; Ingason, Andrés; Djurovic, Srdjan

    2011-01-01

    BACKGROUND: Schizophrenia is associated with increased risk of type II diabetes and metabolic disorders. However, it is unclear whether this comorbidity reflects shared genetic risk factors, at-risk lifestyle, or side effects of antipsychotic medication. METHODS: Eleven known risk variants of type...... (SGENE+) using Mantel-Haenszel test. RESULTS: One type II diabetes at-risk allele located in TCF7L2, rs7903146 [T], was associated with schizophrenia in the discovery sample (p = .0052) and in the replication with an odds ratio of 1.07 (95% confidence interval 1.01-1.14, p = .033). CONCLUSION...... II diabetes were genotyped in patients with schizophrenia in a sample of 410 Danish patients, each matched with two healthy control subjects on sex, birth year, and month. Replication was carried out in a large multinational European sample of 4089 patients with schizophrenia and 17,597 controls...

  14. Analysis of miRNA and mRNA Expression Profiles Highlights Alterations in Ionizing Radiation Response of Human Lymphocytes under Modeled Microgravity

    Casara, Silvia; Sales, Gabriele; Lanfranchi, Gerolamo; Celotti, Lucia; Mognato, Maddalena

    2012-01-01

    Background Ionizing radiation (IR) can be extremely harmful for human cells since an improper DNA-damage response (DDR) to IR can contribute to carcinogenesis initiation. Perturbations in DDR pathway can originate from alteration in the functionality of the microRNA-mediated gene regulation, being microRNAs (miRNAs) small noncoding RNA that act as post-transcriptional regulators of gene expression. In this study we gained insight into the role of miRNAs in the regulation of DDR to IR under microgravity, a condition of weightlessness experienced by astronauts during space missions, which could have a synergistic action on cells, increasing the risk of radiation exposure. Methodology/Principal Findings We analyzed miRNA expression profile of human peripheral blood lymphocytes (PBL) incubated for 4 and 24 h in normal gravity (1 g) and in modeled microgravity (MMG) during the repair time after irradiation with 0.2 and 2Gy of γ-rays. Our results show that MMG alters miRNA expression signature of irradiated PBL by decreasing the number of radio-responsive miRNAs. Moreover, let-7i*, miR-7, miR-7-1*, miR-27a, miR-144, miR-200a, miR-598, miR-650 are deregulated by the combined action of radiation and MMG. Integrated analyses of miRNA and mRNA expression profiles, carried out on PBL of the same donors, identified significant miRNA-mRNA anti-correlations of DDR pathway. Gene Ontology analysis reports that the biological category of “Response to DNA damage” is enriched when PBL are incubated in 1 g but not in MMG. Moreover, some anti-correlated genes of p53-pathway show a different expression level between 1 g and MMG. Functional validation assays using luciferase reporter constructs confirmed miRNA-mRNA interactions derived from target prediction analyses. Conclusions/Significance On the whole, by integrating the transcriptome and microRNome, we provide evidence that modeled microgravity can affects the DNA-damage response to IR in human PBL. PMID:22347458

  15. Leptin and insulin up-regulate miR-4443 to suppress NCOA1 and TRAF4, and decrease the invasiveness of human colon cancer cells

    Meerson, Ari; Yehuda, Hila

    2016-01-01

    Obesity is a risk factor for colorectal cancer (CRC). Normal and tumor cells respond to metabolic hormones, such as leptin and insulin. Thus, obesity-associated resistance to these hormones likely leads to changes in gene expression and behavior of tumor cells. However, the mechanisms affected by leptin and insulin signaling in CRC cells remain mostly unknown. We hypothesized that microRNAs (miRNAs) are involved in the regulation of tumorigenesis-related gene expression in CRC cells by leptin and insulin. To test this hypothesis, miRNA levels in the CRC-derived cell lines HCT-116, HT-29 and DLD-1 were profiled, following leptin and insulin treatment. Candidate miRNAs were validated by RT-qPCR. Predicted miRNA targets with known roles in cancer, were validated by immunoblots and reporter assays in HCT-116 cells. Transfection of HCT-116 cells with candidate miRNA mimic was used to test in vitro effects on proliferation and invasion. Of ~800 miRNAs profiled, miR-4443 was consistently up-regulated by leptin and insulin in HCT-116 and HT-29, but not in DLD-1, which lacked normal leptin receptor expression. Dose response experiments showed that leptin at 100 ng/ml consistently up-regulated miR-4443 in HCT-116 cells, concomitantly with a significant decrease in cell invasion ability. Transfection with miR-4443 mimic decreased invasion and proliferation of HCT-116 cells. Moreover, leptin and miR-4443 transfection significantly down-regulated endogenous NCOA1 and TRAF4, both predicted targets of miR-4443 with known roles in cancer metastasis. miR-4443 was found to directly regulate TRAF4 and NCOA1, as validated by a reporter assay. The up-regulation of miR-4443 by leptin or insulin was attenuated by the inhibition of MEK1/2. Our findings suggest that miR-4443 acts in a tumor-suppressive manner by down-regulating TRAF4 and NCOA1 downstream of MEK-C/EBP-mediated leptin and insulin signaling, and that insulin and/or leptin resistance (e.g. in obesity) may suppress this pathway

  16. Rationality on the rise: Why relative risk aversion increases with stake size

    Fehr-Duda, Helga; Bruhin, Adrian; Epper, Thomas F.; Schubert, Renate

    2008-01-01

    How does risk tolerance vary with stake size? This important question cannot be adequately answered if framing effects, nonlinear probability weighting, and heterogeneity of preference types are neglected. We show that, contrary to gains, no coherent change in relative risk aversion is observed for losses. The increase in relative risk aversion over gains cannot be captured by the curvature of the utility function. It is driven predominantly by a change in probability weighting of a majority ...

  17. What can be offered to couples at (possibly) increased genetic risk?

    Read, Andrew P.; Donnai, Dian

    2012-01-01

    We review the reasons why a couple might seek specialist genetic counselling about a possible reproductive risk and the options available to them. Most commonly, the couple will be concerned about the risk of recurrence of a medical condition that has already occurred in the family. Sometimes, the increased risk may come from their ethnicity or because of a consanguineous marriage, rather than because any problem has occurred previously. The geneticist must identify the exact nature of any pr...

  18. miR-758-3p: a blood-based biomarker that's influence on the expression of CERP/ABCA1 may contribute to the progression of obesity to metabolic syndrome.

    O'Neill, Sadhbh; Larsen, Mette Bohl; Gregersen, Søren; Hermansen, Kjeld; O'Driscoll, Lorraine

    2018-02-06

    Due to increasing prevalence of obesity, a simple method or methods for the diagnosis of metabolic syndrome are urgently required to reduce the risk of associated cardiovascular disease, diabetes and cancer. This study aimed to identify a miRNA biomarker that may distinguish metabolic syndrome from obesity and to investigate if such a miRNA may have functional relevance for metabolic syndrome. 52 adults with clinical obesity (n=26) or metabolic syndrome (n=26) were recruited. Plasma specimens were procured from all and were randomly designated to discovery and validation cohorts. miRNA discovery profiling was performed, using array technology, on plasma RNA. Validation was performed by quantitative polymerase chain reaction. The functional effect of miR-758-3p on its predicted target, cholesterol efflux regulatory protein/ATP-binding cassette transporter, was investigated using HepG2 liver cells. Custom miRNA profiling of 25 miRNAs in the discovery cohort found miR-758-3p to be detected in the obese cohort but undetected in the metabolic syndrome cohort. miR-758-3p was subsequently validated as a potential biomarker for metabolic syndrome by quantitative polymerase chain reaction. Bioinformatics analysis identified cholesterol efflux regulatory protein/ATP-binding cassette transporter as miR-758-3p's predicted target. Specifically, mimicking miR-758-3p in HepG2 cells suppressed cholesterol efflux regulatory protein/ATP-binding cassette transporter protein expression; conversely, inhibiting miR-758-3p increased cholesterol efflux regulatory protein/ATP-binding cassette transporter protein expression. miR-758-3p holds potential as a blood-based biomarker for distinguishing progression from obesity to metabolic syndrome and as a driver in controlling cholesterol efflux regulatory protein/ATP-binding cassette transporter expression, indicating it potential role in cholesterol control in metabolic syndrome.

  19. miR-758-3p: a blood-based biomarker that’s influence on the expression of CERP/ABCA1 may contribute to the progression of obesity to metabolic syndrome

    O’Neill, Sadhbh; Larsen, Mette Bohl; Gregersen, Søren; Hermansen, Kjeld; O’Driscoll, Lorraine

    2018-01-01

    Due to increasing prevalence of obesity, a simple method or methods for the diagnosis of metabolic syndrome are urgently required to reduce the risk of associated cardiovascular disease, diabetes and cancer. This study aimed to identify a miRNA biomarker that may distinguish metabolic syndrome from obesity and to investigate if such a miRNA may have functional relevance for metabolic syndrome. 52 adults with clinical obesity (n=26) or metabolic syndrome (n=26) were recruited. Plasma specimens were procured from all and were randomly designated to discovery and validation cohorts. miRNA discovery profiling was performed, using array technology, on plasma RNA. Validation was performed by quantitative polymerase chain reaction. The functional effect of miR-758-3p on its predicted target, cholesterol efflux regulatory protein/ATP-binding cassette transporter, was investigated using HepG2 liver cells. Custom miRNA profiling of 25 miRNAs in the discovery cohort found miR-758-3p to be detected in the obese cohort but undetected in the metabolic syndrome cohort. miR-758-3p was subsequently validated as a potential biomarker for metabolic syndrome by quantitative polymerase chain reaction. Bioinformatics analysis identified cholesterol efflux regulatory protein/ATP-binding cassette transporter as miR-758-3p’s predicted target. Specifically, mimicking miR-758-3p in HepG2 cells suppressed cholesterol efflux regulatory protein/ATP-binding cassette transporter protein expression; conversely, inhibiting miR-758-3p increased cholesterol efflux regulatory protein/ATP-binding cassette transporter protein expression. miR-758-3p holds potential as a blood-based biomarker for distinguishing progression from obesity to metabolic syndrome and as a driver in controlling cholesterol efflux regulatory protein/ATP-binding cassette transporter expression, indicating it potential role in cholesterol control in metabolic syndrome. PMID:29507696

  20. HIV infection is associated with an increased risk for lung cancer, independent of smoking.

    Kirk, Gregory D; Merlo, Christian; O' Driscoll, Peter; Mehta, Shruti H; Galai, Noya; Vlahov, David; Samet, Jonathan; Engels, Eric A

    2007-07-01

    Human immunodeficiency virus (HIV)-infected persons have an elevated risk for lung cancer, but whether the increase reflects solely their heavy tobacco use remains an open question. The Acquired Immunodeficiency Syndrome (AIDS) Link to the Intravenous Experience Study has prospectively observed a cohort of injection drug users in Baltimore, Maryland, since 1988, using biannual collection of clinical, laboratory, and behavioral data. Lung cancer deaths were identified through linkage with the National Death Index. Cox proportional hazards regression was used to examine the effect of HIV infection on lung cancer risk, controlling for smoking status, drug use, and clinical variables. Among 2086 AIDS Link to the Intravenous Experience Study participants observed for 19,835 person-years, 27 lung cancer deaths were identified; 14 of the deaths were among HIV-infected persons. All but 1 (96%) of the patients with lung cancer were smokers, smoking a mean of 1.2 packs per day. Lung cancer mortality increased during the highly active antiretroviral therapy era, compared with the pre-highly active antiretroviral therapy period (mortality rate ratio, 4.7; 95% confidence interval, 1.7-16). After adjusting for age, sex, smoking status, and calendar period, HIV infection was associated with increased lung cancer risk (hazard ratio, 3.6; 95% confidence interval, 1.6-7.9). Preexisting lung disease, particularly noninfectious diseases and asthma, displayed trends for increased lung cancer risk. Illicit drug use was not associated with increased lung cancer risk. Among HIV-infected persons, smoking remained the major risk factor; CD4 cell count and HIV load were not strongly associated with increased lung cancer risk, and trends for increased risk with use of highly active antiretroviral therapy were not significant. HIV infection is associated with significantly increased risk for developing lung cancer, independent of smoking status.

  1. The Environmental Neurotoxicant PCB 95 Promotes Synaptogenesis via Ryanodine Receptor-Dependent miR132 Upregulation

    Lesiak, Adam; Zhu, Mingyan; Chen, Hao; Appleyard, Suzanne M.; Impey, Soren; Wayman, Gary A.

    2014-01-01

    Non–dioxin-like (NDL) polychlorinated biphenyls (PCBs) are widespread environmental contaminants linked to neuropsychological dysfunction in children. NDL PCBs increase spontaneous Ca2+ oscillations in neurons by stabilizing ryanodine receptor (RyR) calcium release channels in the open configuration, which results in CREB-dependent dendritic outgrowth. In this study, we address the question of whether activation of CREB by NDL PCBs also triggers dendritic spine formation. Nanomolar concentrations of PCB 95, a NDL congener with potent RyR activity, significantly increased spine density and the frequency of miniature EPSCs in primary dissociated rat hippocampal cultures coincident with upregulation of miR132. Inhibition of RyR, CREB, or miR132 as well as expression of a mutant p250GAP cDNA construct that is not suppressed by miR132 blocked PCB 95 effects on spines and miniature EPSCs. PCB 95 also induced spine formation via RyR- and miR132-dependent mechanisms in hippocampal slice cultures. These data demonstrate a novel mechanism of PCB developmental neurotoxicity whereby RyR sensitization modulates spine formation and synaptogenesis via CREB-mediated miR132 upregulation, which in turn suppresses the translation of p250GAP, a negative regulator of synaptogenesis. In light of recent evidence implicating miR132 dysregulation in Rett syndrome and schizophrenia, these findings identify NDL PCBs as potential environmental risk factors for neurodevelopmental disorders. PMID:24431430

  2. Subfertility increases risk of testicular cancer: evidence from population-based semen samples.

    Hanson, Heidi A; Anderson, Ross E; Aston, Kenneth I; Carrell, Douglas T; Smith, Ken R; Hotaling, James M

    2016-02-01

    To further understand the association between semen quality and cancer risk by means of well defined semen parameters. Retrospective cohort study. Not applicable. A total of 20,433 men who underwent semen analysis (SA) and a sample of 20,433 fertile control subjects matched by age and birth year. None. Risk of all cancers as well as site-specific results for prostate cancer, testicular cancer, and melanoma. Compared with fertile men, men with SA had an increased risk of testicular cancer (hazard rate [HR] 3.3). When the characterization of infertility was refined using individual semen parameters, we found that oligozoospermic men had an increased risk of cancer compared with fertile control subjects. This association was particularly strong for testicular cancer, with increased risk in men with oligozoospermia based on concentration (HR 11.9) and on sperm count (HR 10.3). Men in the in the lowest quartile of motility (HR 4.1), viability (HR 6.6), morphology (HR 4.2), or total motile count (HR 6.9) had higher risk of testicular cancer compared with fertile men. Men with sperm concentration and count in the 90th percentiles of the distribution (≥178 and ≥579 × 10(6)/mL, respectively), as well as total motile count, had an increased risk of melanoma (HRs 2.1, 2.7, and 2.0, respectively). We found no differences in cancer risk between azoospermic and fertile men. Men with SA had an increased risk of testicular cancer which varied by semen quality. Unlike earlier work, we did not find an association between azoospermia and increased cancer risk. Published by Elsevier Inc.

  3. Atazanavir is not associated with an increased risk of cardio- or cerebrovascular disease events

    Monforte, Antonella d'Arminio; Reiss, Peter; Nielsen, Lene Ryom

    2013-01-01

    To investigate whether there is any association between exposure to atazanavir (ATV), either when boosted or unboosted by ritonavir, and myocardial infarction (MI) or stroke within the D:A:D: Study.......To investigate whether there is any association between exposure to atazanavir (ATV), either when boosted or unboosted by ritonavir, and myocardial infarction (MI) or stroke within the D:A:D: Study....

  4. No Increased Risk of Cancer after Coal Tar Treatment in Patients with Psoriasis or Eczema

    Roelofzen, Judith H. J.; Aben, Katja K. H.; Oldenhof, Ursula T. H.; Coenraads, Pieter-Jan; Alkemade, Hans A.; van de Kerkhof, Peter C. M.; van der Valk, Pieter G. M.; Kiemeney, Lambertus A. L. M.

    Coal tar is an effective treatment for psoriasis and eczema, but it contains several carcinogenic compounds. Occupational and animal studies have shown an increased risk of cancer after exposure to coal tar. Many dermatologists have abandoned this treatment for safety reasons, although the risk of

  5. Polymorphisms near TBX5 and GDF7 are associated with increased risk for Barrett's esophagus

    Palles, Claire; Chegwidden, Laura; Li, Xinzhong; Findlay, John M.; Farnham, Garry; Castro Giner, Francesc; Peppelenbosch, Maikel P.; Kovac, Michal; Adams, Claire L.; Prenen, Hans; Briggs, Sarah; Harrison, Rebecca; Sanders, Scott; MacDonald, David; Haigh, Chris; Tucker, Art; Love, Sharon; Nanji, Manoj; Decaestecker, John; Ferry, David; Rathbone, Barrie; Hapeshi, Julie; Barr, Hugh; Moayyedi, Paul; Watson, Peter; Zietek, Barbara; Maroo, Neera; Gay, Laura; Underwood, Tim; Boulter, Lisa; McMurtry, Hugh; Monk, David; Patel, Praful; Ragunath, Krish; Al Dulaimi, David; Murray, Iain; Koss, Konrad; Veitch, Andrew; Trudgill, Nigel; Nwokolo, Chuka; Rembacken, Bjorn; Atherfold, Paul; Green, Elaine; Ang, Yeng; Kuipers, Ernst J.; Chow, Wu; Paterson, Stuart; Kadri, Sudarshan; Beales, Ian; Grimley, Charles; Mullins, Paul; Beckett, Conrad; Farrant, Mark; Dixon, Andrew; Kelly, Sean; Johnson, Matthew; Wajed, Shahjehan; Dhar, Anjan; Sawyer, Elinor; Roylance, Rebecca; Onstad, Lynn; Gammon, Marilie D.; Corley, Douglas A.; Shaheen, Nicholas J.; Bird, Nigel C.; Hardie, Laura J.; Reid, Brian J.; Ye, Weimin; Liu, Geoffrey; Romero, Yvonne; Bernstein, Leslie; Wu, Anna H.; Casson, Alan G.; Fitzgerald, Rebecca; Whiteman, David C.; Risch, Harvey A.; Levine, David M.; Vaughan, Tom L.; Verhaar, Auke P.; van den Brande, Jan; Toxopeus, Eelke L.; Spaander, Manon C.; Wijnhoven, Bas P. L.; van der Laan, Luc J. W.; Krishnadath, Kausilia; Wijmenga, Cisca; Trynka, Gosia; McManus, Ross; Reynolds, John V.; O'Sullivan, Jacintha; MacMathuna, Padraic; McGarrigle, Sarah A.; Kelleher, Dermot; Vermeire, Severine; Cleynen, Isabelle; Bisschops, Raf; Tomlinson, Ian; Jankowski, Janusz

    2015-01-01

    Barrett's esophagus (BE) increases the risk of esophageal adenocarcinoma (EAC). We found the risk to be BE has been associated with single nucleotide polymorphisms (SNPs) on chromosome 6p21 (within the HLA region) and on 16q23, where the closest protein-coding gene is FOXF1. Subsequently, the

  6. Polymorphisms near TBX5 and GDF7 are associated with increased risk for Barrett's esophagus

    C. Palles (Claire); L. Chegwidden (Laura); X. Li (Xinzhong); J.M. Findlay (John M.); G. Farnham (Garry); F. Castro Giner (Francesc); M.P. Peppelenbosch (Maikel); M. Kovac (Michal); C.L. Adams (Claire); H. Prenen (Hans); S. Briggs (Sarah); R. Harrison (Rebecca); S. Sanders (Scott); D. Macdonald (David); K. Haigh (Katharina); A.T. Tucker (Art); S. Love (Sharon); M. Nanji (Manoj); J. Decaestecker (John); D.R. Ferry (David); B. Rathbone (Barrie); J. Hapeshi (Julie); H. Barr (Hugh); P. Moayyedi (Paul); P. Watson (Peter); B. Zietek (Barbara); N. Maroo (Neera); L. Gay (Laura); T. Underwood (Tim); L. Boulter (Lisa); H. McMurtry (Hugh); A.B. Monk (Alastair); P. Patel (Poulam); K. Ragunath (Krish); D. Al Dulaimi (David); I. Murray (Iain); C. Koss (Clara); A. Veitch (Andrew); N. Trudgill (Nigel); C. Nwokolo (Chuka); B. Rembacken; P. Atherfold (Paul); E.K. Green (Elaine K); Y. Ang (Yeng); E.J. Kuipers (Ernst); W. Chow (Wu); S. Paterson (Stuart); S. Kadri (Sudarshan); I. Beales (Ian); C. Grimley (Charles); P. Mullins (Paul); C. Beckett (Conrad); M. Farrant (Mark); A. Dixon (Andrew); S. Kelly (Sean); M. Johnson (Matthew); S. Wajed (Shahjehan); A. Dhar (Archana); E.J. Sawyer (Elinor); R. Roylance (Rebecca); L. Onstad (Lynn); M.D. Gammon (Marilie); D.A. Corley (Douglas); N. Shaheen (Nazima); N.C. Bird (Nigel); B.G.S. Hardie (Bruce); B.J. Reid (Brian); W. Ye (Weimin); G. Liu (Geoffrey); Y. Romero (Yvonne); L. Bernstein (Leslie); A.H. Wu (Anna H.); A.G. Casson (Alan); R.C. Fitzgerald (Rebecca); D.C. Whiteman (David C.); H. Risch (Harvey); D.M. Levine (David M.); T.L. Vaughan (Thomas); A.P. Verhaar (Auke); J. Van Den Brande (Jan); E.L.A. Toxopeus (Eelke); M.C.W. Spaander (Manon); B.P.L. Wijnhoven (Bas); L.J.W. van der Laan (Luc); K.K. Krishnadath (Kausilia); C. Wijmenga (Cisca); G. Trynka (Gosia); R. McManus (Ross); J.V. Reynolds (John V.); J. O'Sullivan (Jacintha); P. Macmathuna (Padraic); S.A. McGarrigle (Sarah A.); D. Kelleher (Dermot); S. Vermeire (Séverine); I. Cleynen (Isabelle); R. Bisschops (Raf); I.P. Tomlinson (Ian); J.A. Jankowski (Janusz Antoni)

    2015-01-01

    textabstractBackground & Aims Barrett's esophagus (BE) increases the risk of esophageal adenocarcinoma (EAC). We found the risk to be BE has been associated with single nucleotide polymorphisms (SNPs) on chromosome 6p21 (within the HLA region) and on 16q23, where the closest protein-coding gene is

  7. Polymorphisms Near TBX5 and GDF7 Are Associated With Increased Risk for Barrett's Esophagus

    Palles, Claire; Chegwidden, Laura; Li, Xinzhong; Findlay, John M.; Farnham, Garry; Giner, Francesc Castro; Peppelenbosch, Maikel P.; Kovac, Michal; Adams, Claire L.; Prenen, Hans; Briggs, Sarah; Harrison, Rebecca; Sanders, Scott; MacDonald, David; Haigh, Chris; Tucker, Art; Love, Sharon; Nanji, Manoj; Decaestecker, John; Ferry, David; Rathbone, Barrie; Hapeshi, Julie; Barr, Hugh; Moayyedi, Paul; Watson, Peter; Zietek, Barbara; Maroo, Neera; Gay, Laura; Underwood, Tim; Boulter, Lisa; McMurtry, Hugh; Monk, David; Patel, Praful; Ragunath, Krish; Al Dulaimi, David; Murray, Iain; Koss, Konrad; Veitch, Andrew; Trudgill, Nigel; Nwokolo, Chuka; Rembacken, Bjorn; Atherfold, Paul; Green, Elaine; Ang, Yeng; Kuipers, Ernst J.; Chow, Wu; Paterson, Stuart; Kadri, Sudarshan; Beales, Ian; Grimley, Charles; Mullins, Paul; Beckett, Conrad; Farrant, Mark; Dixon, Andrew; Kelly, Sean; Johnson, Matthew; Wajed, Shahjehan; Dhar, Anjan; Sawyer, Elinor; Roylance, Rebecca; Onstad, Lynn; Gammon, Marilie D.; Corley, Douglas A.; Shaheen, Nicholas J.; Bird, Nigel C.; Hardie, Laura J.; Reid, Brian J.; Ye, Weimin; Liu, Geoffrey; Romero, Yvonne; Bernstein, Leslie; Wu, Anna H.; Casson, Alan G.; Fitzgerald, Rebecca; Whiteman, David C.; Risch, Harvey A.; Levine, David M.; Vaughan, Tom L.; Verhaar, Auke P.; van den Brande, Jan; Toxopeus, Eelke L.; Spaander, Manon C.; Wijnhoven, Bas P. L.; van der Laan, Luc J. W.; Krishnadath, Kausilia; Wijmenga, Cisca; Trynka, Gosia; McManus, Ross; Reynolds, John V.; O'Sullivan, Jacintha; MacMathuna, Padraic; McGarrigle, Sarah A.; Kelleher, Dermot; Vermeire, Severine; Cleynen, Isabelle; Bisschops, Raf; Tomlinson, Ian; Jankowski, Janusz

    BACKGROUND & AIMS: Barrett's esophagus (BE) increases the risk of esophageal adenocarcinoma (EAC). We found the risk to be BE has been associated with single nucleotide polymorphisms (SNPs) on chromosome 6p21 (within the HLA region) and on 16q23, where the closest protein-coding gene is FOXF1.

  8. Increasing flood exposure in the Netherlands: implications for risk financing

    Jongman, B.; Koks, E.E.; Husby, T.G.; Ward, P.J.

    2014-01-01

    The effectiveness of disaster risk management and financing mechanisms depends on an accurate assessment of current and future hazard exposure. The increasing availability of detailed data offers policy makers and the insurance sector new opportunities to understand trends in risk, and to make

  9. Non-exposure parenting increases risk of bullying behavior in junior high school students

    Surilena Hasan

    2016-05-01

    Non-exposure parenting was the most relevant risk factor of bullying behavior. Low self-esteem increases the risk of bullying behavior. These findings suggest the need of timely bullying prevention and intervention programs that should have a special focus on families of primary high school students.

  10. Problems and fall risk determinants of quality of life in older adults with increased risk of falling.

    Lin, Sang-I; Chang, Ku-Chou; Lee, Hsuei-Chen; Yang, Yi-Ching; Tsauo, Jau-Yih

    2015-05-01

    Determine quality of life and its association with fall risk factors in older adults with increased risk of falling. A total of 597 community-dwelling Taiwanese older adults who were screened to have increased risk of falling participated in the present study. The fall risk factors included sociodemographics, physical and psychological function, Timed Up and Go, past fall/medical histories, fear of falling and medications. The Euro QOL EQ-5D was used to measure health-related quality of life. Pain/discomfort was the EQ-5D dimension most frequently reported to be impaired (35%), regardless of the level of fall risk or age groups, followed by mobility (25%). Hierarchical regression analysis showed that Geriatric Depression Scale, Mini-Mental State Examination, physiological function, up-and-go, fear of falling and psychotropic medication were independent predictors for total EQ-5D, explaining 68.37% of the variance. Logistic regression analysis showed that for the five EQ-5D dimensions, Geriatric Depression Scale and Up and Go time were the most common determinants. Pain/discomfort was the leading impairment, and greater Geriatric Depression Scale and longer up-and-go time were the main contributing factors in declines in quality of life in older adults with increased risk of falling. These factors are often modifiable, and their management might be considered a priority in falls prevention. © 2014 Japan Geriatrics Society.

  11. Delineating miRNA profile induced by chewing tobacco in oral keratinocytes

    Mohd Younis Bhat

    2017-10-01

    Full Text Available The major established etiologic risk factor for oral cancer is tobacco (chewed, smoked and snuffed forms. Chewing form of tobacco is predominantly used in India making it the leading cause of oral cancer. Despite being one of the leading causes of oral cancer, the molecular alterations induced by chewing tobacco remains largely unclear. Carcinogenic effect of chewing tobacco is through chronic and not acute exposure. To understand the molecular alterations induced by chewing tobacco, we developed a cell line model where non-neoplastic oral keratinocytes were chronically exposed to chewing tobacco for a period of 6 months. This resulted in increased cellular proliferation and invasive ability of normal oral keratinocytes. Using this cellular model we studied the differential expression of miRNAs associated with chewing tobacco and the altered signaling pathways through which the aberrantly expressed miRNAs affect tumorigenesis. miRNA sequencing  was carried out using Illumina HiSeq 2500 platform  which resulted in the identification of 427 annotated miRNAs of which 10 were significantly dysregulated (≥ 4 fold; p-value ≤ 0.05 in tobacco exposed cells compared to untreated parental cells. To study the altered signaling in oral keratinocytes chronically exposed to chewing tobacco, we employed quantitative proteomics to characterize the dysregulated proteins. Integration of miRNA sequencing data with proteomic data resulted in identification of 36 proven protein targets which (≥1.5 fold; p-value ≤ 0.05 showed expression correlation with the 10 significantly dysregulated miRNAs. Pathway analysis of the dysregulated targets revealed enrichment of interferon signaling and mRNA processing related pathways in the chewing tobacco exposed cells. In addition, we also identified 6 novel miRNA in oral keratinocytes chronically exposed to chewing tobacco extract. Our study provides a framework to understand the oncogenic transformation induced by

  12. Cigarette graphic warning labels increase both risk perceptions and smoking myth endorsement.

    Evans, Abigail T; Peters, Ellen; Shoben, Abigail B; Meilleur, Louise R; Klein, Elizabeth G; Tompkins, Mary Kate; Tusler, Martin

    2018-02-01

    Cigarette graphic warning labels elicit negative emotion, which increases risk perceptions through multiple processes. We examined whether this emotion simultaneously affects motivated cognitions like smoking myth endorsement (e.g. 'exercise can undo the negative effects of smoking') and perceptions of cigarette danger versus other products. 736 adult and 469 teen smokers/vulnerable smokers viewed one of three warning label types (text-only, low emotion graphic or high emotion graphic) four times over two weeks. Emotional reactions to the warnings were reported during the first and fourth exposures. Participants reported how often they considered the warnings, smoking myth endorsement, risk perceptions and perceptions of cigarette danger relative to smokeless tobacco and electronic cigarettes. In structural equation models, emotional reactions influenced risk perceptions and smoking myth endorsement through two processes. Emotion acted as information about risk, directly increasing smoking risk perceptions and decreasing smoking myth endorsement. Emotion also acted as a spotlight, motivating consideration of the warning information. Warning consideration increased risk perceptions, but also increased smoking myth endorsement. Emotional reactions to warnings decreased perceptions of cigarette danger relative to other products. Emotional reactions to cigarette warnings increase smoking risk perceptions, but also smoking myth endorsement and misperceptions that cigarettes are less dangerous than potentially harm-reducing tobacco products.

  13. Views of Low-Income Women of Color at Increased Risk for Breast Cancer.

    E Anderson, Emily; Tejada, Silvia; B Warnecke, Richard; Hoskins, Kent

    2018-01-01

    Individual risk assessment (IRA) for breast cancer may increase adherence to risk-appropriate screening and prevention measures. However, knowledge gaps exist regarding how best to communicate IRA results and support women at increased risk in future health care decisions, in part because patients conceptualize and make meaning of risk differently from the medical community. Better understanding the views of low-income women of color identified as being at increased risk for breast cancer can inform efforts to conduct IRA in an ethical and respectful manner. We conducted in-depth interviews with 13 low-income African American and Latina women who receive care at a federally qualified health center (FQHC) and had recently learned of their increased risk for breast cancer. These interviews explored their experience of the IRA process, their interpretation of what being at increased risk means, and their reactions to provider recommendations. Eight key themes were identified. We conclude with recommendations for the implementation of IRA for breast cancer in underserved primary care settings.

  14. The Effects of Fall-Risk-Increasing Drugs on Postural Control : A Literature Review

    de Groot, Maartje H.; van Campen, Jos P. C. M.; Moek, Marije A.; Tulner, Linda R.; Beijnen, Jos H.; Lamoth, Claudine J. C.

    Meta-analyses showed that psychotropic drugs (antidepressants, neuroleptics, benzodiazepines, antiepileptic drugs) and some cardiac drugs (digoxin, type IA anti-arrhythmics, diuretics) are associated with increased fall risk. Because balance and gait disorders are the most consistent predictors of

  15. is there an increased risk of post-operative surgical site infection

    2012-09-06

    Sep 6, 2012 ... requiring implant orthopaedic surgery are at an increased risk for post-operative surgical ... further studies should determine the effect of reduced CD4 counts, viral load .... Language not Enlish, French, Ducth or German (n=2).

  16. Increased Risks of Upper Tract Urothelial Carcinoma in Male and Female Chinese Herbalists

    Hsiao-Yu Yang

    2011-03-01

    Conclusion: The significant risk of urothelial carcinoma noted in male herbalists increases our suspicion that this is an occupational disease that renders regular health assessment of herbalists an urgent necessity.

  17. Women with minor menstrual irregularities have increased risk of preeclampsia and low birthweight in spontaneous pregnancies

    Bonnesen, Barbara; Oddgeirsdóttir, Hanna L; Naver, Klara Vinsand

    2016-01-01

    INTRODUCTION: Very few studies describe the obstetric and neonatal outcome of spontaneous pregnancies in women with irregular menstrual cycles. However, menstrual cycle irregularities are common and may be associated with increased risk, and women who develop pregnancy complications more frequent...

  18. NT-proBNP is increased in differentiated thyroid carcinoma patients and may predict cardiovascular risk

    Klein Hesselink, Esther N; Horst-Schrivers, van der Anouk; van der Horst, Iwan C C; Bakker, Stephan J L; Muller Kobold, Anneke C.; Brouwers, Adrienne H; de Bock, Geertruida H; Gietema, Jourik A; Dullaart, Robin P F; Links, Thera P; Lefrandt, Joop D

    INTRODUCTION: Chronic suppression of TSH in patients treated for differentiated thyroid carcinoma (DTC) may induce cardiac damage and increase risk for cardiovascular events and premature mortality. We aimed to compare circulating concentrations of N-terminal pro Brain Natriuretic Peptide

  19. Thyroid Dysfunction and Fibrin Network Structure: A Mechanism for Increased Thrombotic Risk in Hyperthyroid Individuals

    Hooper, J. M. W.; Stuijver, D. J. F.; Orme, S. M.; van Zaane, B.; Hess, K.; Gerdes, V. E.; Phoenix, F.; Rice, P.; Smith, K. A.; Alzahrani, S. H.; Standeven, K. F.; Ajjan, R. A.

    2012-01-01

    Context: Hyperthyroidism is associated with increased thrombosis risk, and fibrin clot structure determines susceptibility to vascular thrombotic events. Objective: Our objective was to investigate clot formation and lysis in hyperthyroidism using observational and interventional studies. Design: Ex

  20. Stratifying a Risk for an Increased Variation of Airway Caliber among the Clinically Stable Asthma

    Atsushi Hayata

    2013-01-01

    Conclusions: These results indicate that ACQ, %FEV1 and FENO can stratify the risk for increased variation in airway caliber among patients with stable asthma. This may help identify subjects in whom further monitoring of lung function fluctuations is indicated.

  1. Nine-year risk of depression diagnosis increases with increasing self-reported concussions in retired professional football players.

    Kerr, Zachary Y; Marshall, Stephen W; Harding, Herndon P; Guskiewicz, Kevin M

    2012-10-01

    Concussions may accelerate the progression to long-term mental health outcomes such as depression in athletes. To prospectively determine the effects of recurrent concussions on the clinical diagnosis of depression in a group of retired football players. Cohort study; Level of evidence, 2. Members of the National Football League Retired Players Association responded to a baseline General Health Survey (GHS) in 2001. They also completed a follow-up survey in 2010. Both surveys asked about demographic information, number of concussions sustained during their professional football career, physical/mental health, and prevalence of diagnosed medical conditions. A physical component summary (Short Form 36 Measurement Model for Functional Assessment of Health and Well-Being [SF-36 PCS]) was calculated from responses for physical health. The main exposure, the history of concussions during the professional playing career (self-report recalled in 2010), was stratified into 5 categories: 0 (referent), 1 to 2, 3 to 4, 5 to 9, and 10+ concussions. The main outcome was a clinical diagnosis of depression between the baseline and follow-up GHS. Classic tabular methods computed crude risk ratios. Binomial regression with a Poisson residual and robust variance estimation to stabilize the fitting algorithm estimated adjusted risk ratios. χ(2) analyses identified associations and trends between concussion history and the 9-year risk of a depression diagnosis. Of the 1044 respondents with complete data from the baseline and follow-up GHS, 106 (10.2%) reported being clinically diagnosed as depressed between the baseline and follow-up GHS. Approximately 65% of all respondents self-reported sustaining at least 1 concussion during their professional careers. The 9-year risk of a depression diagnosis increased with an increasing number of self-reported concussions, ranging from 3.0% in the "no concussions" group to 26.8% in the "10+" group (linear trend: P football and 2001 SF-36 PCS

  2. Changes in Adult BMI and Waist Circumference Are Associated with Increased Risk of Advanced Colorectal Neoplasia.

    Gathirua-Mwangi, Wambui G; Monahan, Patrick; Song, Yiqing; Zollinger, Terrell W; Champion, Victoria L; Stump, Timothy E; Imperiale, Thomas F

    2017-11-01

    Waist circumference (WC) is a stronger predictor of colon cancer (CRC) risk than body mass index (BMI). However, how well change in either WC or BMI predicts risk of advanced colorectal neoplasia (AN) is unclear. To determine the relationship between change in BMI and WC from early adulthood to later age and the risk of AN and which change measure is a stronger predictor. In 4500 adults, ages 50-80, with no previous neoplasia and undergoing screening colonoscopy, BMI and WC at age 21 and at time of screening were reported. Changes in BMI and WC were defined using universal risk cutoffs. Known CRC risk factors were controlled in the logistic models. Overall, model statistics showed WC change (omnibus test χ 2  = 10.15, 2 DF, p value = 0.006) was a statistically stronger predictor of AN than BMI change (omnibus test χ 2  = 5.66, 5 DF, p value = 0.34). Independent of BMI change, participants who increased WC (OR 1.44; 95% CI 1.05-1.96) or maintained a high-risk WC (OR 2.50; 95% CI 1.38-4.53) at age 21 and at screening had an increased risk of AN compared to those with a low-risk WC. Study participants who were obese at age 21 and at screening had an increased risk of AN (OR 1.87; 95% CI 1.08-3.23) compared to those who maintained a healthy BMI. Maintaining an overweight BMI or increasing BMI was not associated with AN. Maintaining an unhealthy BMI and WC throughout adult life may increase risk of AN. WC change may be a better predictor of AN than BMI change.

  3. MiDAS

    McIlroy, Simon Jon; Saunders, Aaron Marc; Albertsen, Mads

    2015-01-01

    The Microbial Database for Activated Sludge (MiDAS) field guide is a freely available online resource linking the identity of abundant and process critical microorganisms in activated sludge wastewater treatment systems to available data related to their functional importance. Phenotypic properties...... of some of these genera are described, but most are known only from sequence data. The MiDAS taxonomy is a manual curation of the SILVA taxonomy that proposes a name for all genus-level taxa observed to be abundant by large-scale 16 S rRNA gene amplicon sequencing of full-scale activated sludge...... communities. The taxonomy can be used to classify unknown sequences, and the online MiDAS field guide links the identity to the available information about their morphology, diversity, physiology and distribution. The use of a common taxonomy across the field will provide a solid foundation for the study...

  4. Increased risk of hepatocellular carcinoma in patients with chronic hepatitis C

    Hallager, Sofie; Weis, Nina

    2014-01-01

    Chronic hepatitis C (CHC) frequently leads to cirrhosis with an increased risk of hepatocellular carcinomas (HCC). CHC therapy is currently changing for the better whereas prognosis for HCC remains dismal if not detected early and thus regular screening in cirrhotic CHC patients for HCC...... is recommended. CHC is known to be underdiagnosed in Denmark where it is up to the involved physician to screen for risk factors for CHC and increase the patient's chance of a cure for CHC with therapy....

  5. Increased peripheral vascular disease risk progressively constrains perfusion adaptability in the skeletal muscle microcirculation

    Butcher, Joshua T.; Frisbee, Stephanie J.; Olfert, I. Mark; Chantler, Paul D.; Tabone, Lawrence E.; d'Audiffret, Alexandre C.; Shrader, Carl D.; Goodwill, Adam G.; Stapleton, Phoebe A.; Brooks, Steven D.; Brock, Robert W.; Lombard, Julian H.

    2015-01-01

    To determine the impact of progressive elevations in peripheral vascular disease (PVD) risk on microvascular function, we utilized eight rat models spanning “healthy” to “high PVD risk” and used a multiscale approach to interrogate microvascular function and outcomes: healthy: Sprague-Dawley rats (SDR) and lean Zucker rats (LZR); mild risk: SDR on high-salt diet (HSD) and SDR on high-fructose diet (HFD); moderate risk: reduced renal mass-hypertensive rats (RRM) and spontaneously hypertensive rats (SHR); high risk: obese Zucker rats (OZR) and Dahl salt-sensitive rats (DSS). Vascular reactivity and biochemical analyses demonstrated that even mild elevations in PVD risk severely attenuated nitric oxide (NO) bioavailability and caused progressive shifts in arachidonic acid metabolism, increasing thromboxane A2 levels. With the introduction of hypertension, arteriolar myogenic activation and adrenergic constriction were increased. However, while functional hyperemia and fatigue resistance of in situ skeletal muscle were not impacted with mild or moderate PVD risk, blood oxygen handling suggested an increasingly heterogeneous perfusion within resting and contracting skeletal muscle. Analysis of in situ networks demonstrated an increasingly stable and heterogeneous distribution of perfusion at arteriolar bifurcations with elevated PVD risk, a phenomenon that was manifested first in the distal microcirculation and evolved proximally with increasing risk. The increased perfusion distribution heterogeneity and loss of flexibility throughout the microvascular network, the result of the combined effects on NO bioavailability, arachidonic acid metabolism, myogenic activation, and adrenergic constriction, may represent the most accurate predictor of the skeletal muscle microvasculopathy and poor health outcomes associated with chronic elevations in PVD risk. PMID:26702145

  6. Small RNA sequencing reveals a comprehensive miRNA signature of BRCA1-associated high-grade serous ovarian cancer

    Brouwer, Jan; Kluiver, Joost; de Almeida, Rodrigo C.; Modderman, Rutger; Terpstra, Martijn; Kok, Klaas; Withoff, Sebo; Hollema, Harry; Reitsma, Welmoed; de Bock, Geertruida H.; Mourits, Marian J. E.; van den Berg, Anke

    2016-01-01

    AimsBRCA1 mutation carriers are at increased risk of developing high-grade serous ovarian cancer (HGSOC), a malignancy that originates from fallopian tube epithelium. We aimed to identify differentially expressed known and novel miRNAs in BRCA1-associated HGSOC. Methods Small RNA sequencing was

  7. Assessment of Credit Risk Approaches in Relation with Competitiveness Increase of the Banking Sector

    Cipovová Eva

    2012-06-01

    Full Text Available The article is focused on a presentation and analysis of selected methods of credit risk management in relation with competitiveness increase of the banking sector. The article is defined credit risk approaches under the Basel III gradually. Aim of this contribution constitutes various methods of credit risk management and effects of their usage on regulatory capital amount in respect of corporate exposures. Optimal equity amount in relation to the risk portfolio presents an essential prerequisite of performance and competitiveness growth of commercial banks. Gradually capital requirements using Standardized Approach and Internal Based Approach in a case of used and unused techniques of credit risk reduce has been quantified. We presume that sophisticated approach means significant saving for bank’s equity which increases competitiveness of banking sector also. Within the article, quantification of capital savings in case of Standardized (with and without assigned external ratings and Foundation Internal Based Approach at the selected credit portfolio has been effected.

  8. Risk management strategy to increase the safety of workers in the nanomaterials industry

    Ling, Min-Pei, E-mail: lingmp@mail.cmu.edu.tw [Department of Health Risk Management, China Medical University, Taichung 40402, Taiwan, ROC (China); Lin, Wei-Chao; Liu, Chia-Chyuan [Department of Cosmetic Science, Chia Nan University of Pharmacy and Science, Tainan 71710, Taiwan, ROC (China); Huang, Yi-Shiao; Chueh, Miao-Ju [Industrial Safety and Health Association of the ROC, Taipei 11670, Taiwan, ROC (China); Shih, Tung-Sheng [Institute of Occupational Safety and Health, Council of Labor Affairs, Taipei 22143, Taiwan, ROC (China)

    2012-08-30

    Highlights: Black-Right-Pointing-Pointer On-site assessment of nanomaterials using physiochemical and cytotoxic analysis can help identify risks for each nanomaterials manufacturing plant. Black-Right-Pointing-Pointer The risk of the nanomaterials manufacturing plants can be divided into three levels based on exposure routes (tier 1), aspect identification (tier 2), and toxicological screening (tier 3). Black-Right-Pointing-Pointer According to the different risk levels, the precautionary risk management (PRM) such as technology control, engineering control, and personal protective equipment were applied. Black-Right-Pointing-Pointer The PRM strategy can be effectively reduced workers risks for nanomaterial industries. - Abstract: In recent years, many engineered nanomaterials (NMs) have been produced, but increasing research has revealed that these may have toxicities far greater than conventional materials and cause significant adverse health effects. At present, there is insufficient data to determine the permissible concentrations of NMs in the workplace. There is also a lack of toxicity data and environmental monitoring results relating to complete health risk assessment. In view of this, we believe that workers in the NMs industry should be provided with simple and practical risk management strategy to ensure occupational health and safety. In this study, we developed a risk management strategy based on the precautionary risk management (PRM). The risk of the engineered NMs manufacturing plants can be divided into three levels based on aspect identification, solubility tests, dermal absorption, and cytotoxic analyses. The risk management strategies include aspects relating to technology control, engineering control, personal protective equipment, and monitoring of the working environment for each level. Here we report the first case in which a simple and practical risk management strategy applying in specific engineered NMs manufacturing plants. We are

  9. Risk management strategy to increase the safety of workers in the nanomaterials industry

    Ling, Min-Pei; Lin, Wei-Chao; Liu, Chia-Chyuan; Huang, Yi-Shiao; Chueh, Miao-Ju; Shih, Tung-Sheng

    2012-01-01

    Highlights: ► On-site assessment of nanomaterials using physiochemical and cytotoxic analysis can help identify risks for each nanomaterials manufacturing plant. ► The risk of the nanomaterials manufacturing plants can be divided into three levels based on exposure routes (tier 1), aspect identification (tier 2), and toxicological screening (tier 3). ► According to the different risk levels, the precautionary risk management (PRM) such as technology control, engineering control, and personal protective equipment were applied. ► The PRM strategy can be effectively reduced workers risks for nanomaterial industries. - Abstract: In recent years, many engineered nanomaterials (NMs) have been produced, but increasing research has revealed that these may have toxicities far greater than conventional materials and cause significant adverse health effects. At present, there is insufficient data to determine the permissible concentrations of NMs in the workplace. There is also a lack of toxicity data and environmental monitoring results relating to complete health risk assessment. In view of this, we believe that workers in the NMs industry should be provided with simple and practical risk management strategy to ensure occupational health and safety. In this study, we developed a risk management strategy based on the precautionary risk management (PRM). The risk of the engineered NMs manufacturing plants can be divided into three levels based on aspect identification, solubility tests, dermal absorption, and cytotoxic analyses. The risk management strategies include aspects relating to technology control, engineering control, personal protective equipment, and monitoring of the working environment for each level. Here we report the first case in which a simple and practical risk management strategy applying in specific engineered NMs manufacturing plants. We are confident that our risk management strategy can be effectively reduced engineered NM industries risks for

  10. Does red noise increase or decrease extinction risk? Single extreme events versus series of unfavorable conditions.

    Schwager, Monika; Johst, Karin; Jeltsch, Florian

    2006-06-01

    Recent theoretical studies have shown contrasting effects of temporal correlation of environmental fluctuations (red noise) on the risk of population extinction. It is still debated whether and under which conditions red noise increases or decreases extinction risk compared with uncorrelated (white) noise. Here, we explain the opposing effects by introducing two features of red noise time series. On the one hand, positive autocorrelation increases the probability of series of poor environmental conditions, implying increasing extinction risk. On the other hand, for a given time period, the probability of at least one extremely bad year ("catastrophe") is reduced compared with white noise, implying decreasing extinction risk. Which of these two features determines extinction risk depends on the strength of environmental fluctuations and the sensitivity of population dynamics to these fluctuations. If extreme (catastrophic) events can occur (strong noise) or sensitivity is high (overcompensatory density dependence), then temporal correlation decreases extinction risk; otherwise, it increases it. Thus, our results provide a simple explanation for the contrasting previous findings and are a crucial step toward a general understanding of the effect of noise color on extinction risk.

  11. Proximity to vacant buildings is associated with increased fire risk in Baltimore, Maryland, homes.

    Schachterle, Stephen E; Bishai, David; Shields, Wendy; Stepnitz, Rebecca; Gielen, Andrea C

    2012-04-01

    Fires and burns are a leading cause of unintentional injury death in the USA. Although it has been anecdotally reported that vacant dwellings are at a higher risk for fire, the association between vacancy and fire risk at the individual household level has not been empirically measured. In this cross-sectional study, geocoded residential vacant properties (VP) and fire events are analysed in Baltimore City at the census tract level and the individual household level. On average, a 10% increase in the proportion of vacancies in a census tract was associated with a 9.9% increase in fires (95% CI: 5% to 15%). Random-effects Poisson models, controlling for housing and neighbourhood conditions, found contagion effects. The risk of fire in an occupied dwelling increased by 8% (95% CI: 1% to 10%) for every vacant structure within 10 m, and the risk of fire decreased by half (95% CI: 45% to 62%) for every km between an occupied dwelling and vacant building. Close proximity to VP was associated with trash fires within dwellings (p=0.039) and structure fires (p=0.012). We believe that this is the first study to demonstrate increased risk posed by nearby VP at the household level, confirming earlier ecological analyses of the role of VP as strong correlates of home fires. Measurement of this risk can motivate property owners, policy makers and insurers to invest in risk reduction measures that include building maintenance and trash removal.

  12. The Involvement of miR-29b-3p in Arterial Calcification by Targeting Matrix Metalloproteinase-2

    Wenhong Jiang

    2017-01-01

    Full Text Available Vascular calcification is a risk predictor and common pathological change in cardiovascular diseases that are associated with elastin degradation and phenotypic transformation of vascular smooth muscle cells via gelatinase matrix metalloproteinase-2 (MMP2. However, the mechanisms involved in this process remain unclear. In this study, we investigated the relationships between miR-29b-3p and MMP2, to confirm miR-29b-3p-mediated MMP2 expression at the posttranscriptional level in arterial calcification. In male Sprague Dawley rats, arterial calcification was induced by subcutaneous injection of a toxic dose of cholecalciferol. In vivo, the quantitative real-time polymerase chain reaction (qRT-PCR showed that MMP2 expression was upregulated in calcified arterial tissues, and miR-29b-3p expression was downregulated. There was a negative correlation between MMP2 mRNA expression and miR-29b-3p levels (P=0.0014, R2=0.481. Western blotting showed that MMP2 expression was significantly increased in rats treated with cholecalciferol. In vitro, overexpression of miR-29b-3p led to decreased MMP2 expression in rat vascular smooth muscle cells, while downregulation of miR-29b-3p expression led to increased MMP2 expression. Moreover, the luciferase reporter assay confirmed that MMP2 is the direct target of miR-29b-3p. Together, our results demonstrated that a role of miR-29b-3p in vascular calcification involves targeting MMP2.

  13. Heterogeneity of miRNA expression in localized prostate cancer with clinicopathological correlations.

    Ahmed Hussein Zedan

    Full Text Available In the last decade microRNAs (miRNAs have been widely investigated in prostate cancer (PCa and have shown to be promising biomarkers in diagnostic, prognostic and predictive settings. However, tumor heterogeneity may influence miRNA expression. The aims of this study were to assess the impact of tumor heterogeneity, as demonstrated by a panel of selected miRNAs in PCa, and to correlate miRNA expression with risk profile and patient outcome.Prostatectomy specimens and matched, preoperative needle biopsies from a retrospective cohort of 49 patients, who underwent curatively intended surgery for localized PCa, were investigated with a panel of 6 miRNAs (miRNA-21, miRNA-34a, miRNA-125b, miRNA-126, miRNA-143, and miRNA-145 using tissue micro-array (TMA and in situ hybridization (ISH. Inter- and intra-patient variation was assessed using intra-class correlation (ICC.Four miRNAs (miRNA-21, miRNA-34a, miRNA-125, and miRNA-126 were significantly upregulated in PCa compared to benign prostatic hyperplasia (BPH, and except for miRNA-21 these miRNAs documented a positive correlation between the expression level in PCa cores and their matched BPH cores, (r > 0.72. The ICC varied from 0.451 to 0.764, with miRNA-34a showing an intra-tumoral heterogeneity accounting for less than 50% of the total variation. Regarding clinicopathological outcomes, only miRNA-143 showed potential as a prognostic marker with a higher expression correlating with longer relapse-free survival (p = 0.016.The present study documents significant upregulation of the expression of miRNA-21, miRNA-34a, miRNA-125, and miRNA-126 in PCa compared to BPH and suggests a possible prognostic value associated with the expression of miRNA-143. The results, however, document intra-tumoral heterogeneity in the expression of various miRNAs calling for caution when using these tumor tissue biomarkers in prognostic and predictive settings.

  14. Does retirement reduce the risk of myocardial infarction?

    Olesen, Kasper; Rugulies, Reiner; Rod, Naja Hulvej

    2014-01-01

    BACKGROUND: Recent studies have suggested that retirement may have beneficial effects on health outcomes. In this study we examined whether the risk of myocardial infarction (MI) was reduced following retirement in a Danish population sample. METHODS: Participants were 617 511 Danish workers, born...... of 1.11 (95% confidence interval: 1.06, 1.16) when comparing retirees with active workers of the same age. CONCLUSIONS: This study does not support the hypothesis that retirement reduces risk of MI. On the contrary, we find that retirement is associated with a modestly increased risk of MI....

  15. Increased risk of flooding on the coast of Alicante (Region of Valencia, Spain

    J. Olcina Cantos

    2010-11-01

    Full Text Available In the past two decades, episodes of flooding on the coast of Alicante (Spain have led to substantial losses in human life in economic terms. With increased exposure to these phenomena comes also increased vulnerability. Given the various effects of flooding in areas of similar exposure, differences in vulnerability across regions at risk need to be analysed also in terms of the socioeconomic factors of the groups of society that may be affected, and of their perception of risk. This paper studies the increased risk of flooding in three locations on the Alicante coast as a result of urban occupation of areas subject to this hazard. The consequences of the most recent episodes in this area are analysed and a risk assessment, using survey-based research in the affected areas, is performed.

  16. Identification and management of patients at increased risk of osteoporotic fracture

    Kanis, J A; Cooper, C; Rizzoli, R

    2017-01-01

    where the risk of a subsequent fracture following a first fracture is high. Consequently, there is a significant treatment gap between those who would benefit from treatment and those who receive it, which urgently needs to be addressed so that the burden of disease can be reduced. Conclusions......Summary: Osteoporosis represents a significant and increasing healthcare burden in Europe, but most patients at increased risk of fracture do not receive medication, resulting in a large treatment gap. Identification of patients who are at particularly high risk will help clinicians target...... appropriate treatment more precisely and cost-effectively, and should be the focus of future research. Introduction: The purpose of the study was to review data on the identification and treatment of patients with osteoporosis at increased risk of fracture. Methods: A working group convened by the European...

  17. Infradiaphragmatic irradiation and high procarbazine doses increase colorectal cancer risk in Hodgkin lymphoma survivors

    van Eggermond, Anna M; Schaapveld, Michael; Janus, Cécile Pm

    2017-01-01

    incidence ratios (SIR) was 2.4-fold increased (95% confidence interval (95%CI) 1.8-3.2), leading to 5.7 excess cases per 10 000 patient-years. Risk was still increased 30 years after HL treatment (SIR: 2.8; 95%CI: 1.6-4.6). The highest (SIR: 6.5, 95%CI: 3.3-11.3) was seen for transverse colon cancer (15......BACKGROUND: Hodgkin lymphoma (HL) survivors are at increased risk of second malignancies, but few studies have assessed colorectal cancer (CRC) risk after HL treatment. We assessed long-term, subsite-specific CRC risk associated with specific radiation fields and chemotherapy regimens. METHODS...... a hazard ratio of 6.8 (95%CI: 3.0-15.6) compared with patients receiving neither treatment, which is significantly higher than an additive joint effect (Padditivity=0.004). CONCLUSIONS: Colorectal cancer surveillance should be considered for HL survivors who received Infradiaphragmatic radiotherapy...

  18. Risk Factors Associated with Mortality and Increased Drug Costs in Nonvariceal Upper Gastrointestinal Bleeding.

    Lu, Mingliang; Sun, Gang; Zhang, Xiu-li; Zhang, Xiao-mei; Liu, Qing-sen; Huang, Qi-yang; Lau, James W Y; Yang, Yun-sheng

    2015-06-01

    To determine risk factors associated with mortality and increased drug costs in patients with nonvariceal upper gastrointestinal bleeding. We retrospectively analyzed data from patients hospitalized with nonvariceal upper gastrointestinal bleeding between January 2001-December 2011. Demographic and clinical characteristics and drug costs were documented. Univariate analysis determined possible risk factors for mortality. Statistically significant variables were analyzed using a logistic regression model. Multiple linear regression analyzed factors influencing drug costs. p study included data from 627 patients. Risk factors associated with increased mortality were age > 60, systolic blood pressurebleeding rate is 11.20% and mortality is 5.74%. The mortality risk in patients with comorbidities was higher than in patients without comorbidities, and was higher in patients requiring blood transfusion than in patients not requiring transfusion. Rebleeding was associ-ated with mortality. Rebleeding, blood transfusion, and prolonged hospital stay were associated with increased drug costs, whereas bleeding from lesions in the esophagus and duodenum was associated with lower drug costs.

  19. miR-184 and miR-150 promote renal glomerular mesangial cell aging by targeting Rab1a and Rab31.

    Liu, Xiujuan; Fu, Bo; Chen, Dapeng; Hong, Quan; Cui, Jing; Li, Jin; Bai, Xueyuan; Chen, Xiangmei

    2015-08-15

    The molecular mechanism of kidney aging is not well understood, but the abnormal expression of miRNAs with aging is considered to be an important contributor. miR-184 and miR-150 were screened using a miRNA microarray and qRT-PCR and found to be significantly upregulated in 24-month-old rats. Rat renal primary glomerular mesangial cells (GMCs) were isolated from 3-month and 24-month-old rats for the in vitro analysis of the roles of miR-184 and miR-150 in kidney aging. Bioinformatics analyses suggested that Rab1a and Rab31, which are associated with cell autophagy, were targeted by both miR-184 and miR-150. miR-184 and miR-150 were increased significantly in aging GMCs versus young cells, while Rab1a and Rab31 were significantly lower in aging cells. Furthermore, dual luciferase reporter assays revealed that miR-184 and miR-150 bound to the 3'-UTR of Rab1a and Rab31 mRNAs. Transfection of miR-184 and miR-150 mimics into young GMCs suppressed the expression of Rab1a and Rab31. Transfected cells showed lower autophagy activities and higher levels of cellular oxidative products, leading to the aging of young GMCs. However, miR-184 and miR-150 inhibitors promoted autophagy and reduced oxidative damage by upregulating Rab1a and Rab31 in old GMCs. In conclusion, miR-184 and miR-150 inhibited autophagy, promoting GMC aging. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Adverse life events increase risk for postpartum psychiatric episodes: A population-based epidemiologic study.

    Meltzer-Brody, S; Larsen, J T; Petersen, L; Guintivano, J; Florio, A Di; Miller, W C; Sullivan, P F; Munk-Olsen, T

    2018-02-01

    Trauma histories may increase risk of perinatal psychiatric episodes. We designed an epidemiological population-based cohort study to explore if adverse childhood experiences (ACE) in girls increases risk of later postpartum psychiatric episodes. Using Danish registers, we identified women born in Denmark between January 1980 and December 1998 (129,439 childbirths). Exposure variables were ACE between ages 0 and 15 including: (1) family disruption, (2) parental somatic illness, (3) parental labor market exclusion, (4) parental criminality, (5) parental death, (6) placement in out-of-home care, (7) parental psychopathology excluding substance use, and (8) parental substance use disorder. Primary outcome was first occurrence of in- or outpatient contact 0-6 months postpartum at a psychiatric treatment facility with any psychiatric diagnoses, ICD-10, F00-F99 (N = 651). We conducted survival analyses using Cox proportional hazard regressions of postpartum psychiatric episodes. Approximately 52% of the sample experienced ACE, significantly increasing risk of any postpartum psychiatric diagnosis. Highest risks were observed among women who experienced out-of-home placement, hazard ratio (HR) 2.57 (95% CI: 1.90-3.48). Women experiencing two adverse life events had higher risks of postpartum psychiatric diagnosis HR: 1.88 (95% CI: 1.51-2.36), compared to those with one ACE, HR: 1.24 (95% CI: 1.03-49) and no ACE, HR: 1.00 (reference group). ACE primarily due to parental psychopathology and disability contributes to increased risk of postpartum psychiatric episodes; and greater numbers of ACE increases risk for postpartum psychiatric illness with an observed dose-response effect. Future work should explore genetic and environmental factors that increase risk and/or confer resilience. © 2017 Wiley Periodicals, Inc.

  1. Diffusion-weighted MRI for detecting prostate tumour in men at increased genetic risk

    Souza, Nandita M. de; Morgan, Veronica A.; Bancroft, Elizabeth; Sohaib, S. Aslam; Giles, Sharon L.; Kote-Jarai, Zsofia; Castro, Elena; Hazell, Steven; Jafar, Maysam; Eeles, Rosalind

    2014-01-01

    •Endorectal T2W + DW-MRI is potentially useful for prostate cancer screening.•MRI is specific for detecting prostate cancer in men with increased genetic risk.•Detection of prostate cancer in men at genetically low risk with MRI is limited. Endorectal T2W + DW-MRI is potentially useful for prostate cancer screening. MRI is specific for detecting prostate cancer in men with increased genetic risk. Detection of prostate cancer in men at genetically low risk with MRI is limited. Diffusion-weighted (DW)-MRI is invaluable in detecting prostate cancer. We determined its sensitivity and specificity and established interobserver agreement for detecting tumour in men with a family history of prostate cancer stratified by genetic risk. 51 men with a family history of prostate cancer underwent T2-W + DW-endorectal MRI at 3.0 T. Presence of tumour was noted at right and left apex, mid and basal prostate sextants by 2 independent observers, 1 experienced and the other inexperienced in endorectal MRI. Sensitivity and specificity against a 10-core sampling technique (lateral and medial cores at each level considered together) in men with >2× population risk based on 71 SNP analysis versus those with lower genetic risk scores was established. Interobserver agreement was determined at a subject level. Biopsies indicated cancer in 28 sextants in 13/51 men; 32 of 51 men had twice the population risk (>0.25) based on 71 SNP profiling. Sensitivity/specificity per-subject for patients was 90.0%/86.4% (high-risk) vs. 66.7%/100% (low-risk, observer 1) and 60.0%/86.3% (high-risk) vs. 33.3%/93.8% (low-risk, observer 2) with moderate overall inter-observer agreement (kappa = 0.42). Regional sensitivities/specificities for high-risk vs. low-risk for observer 1 apex 72.2%/100% [33.3%/100%], mid 100%/93.1% [100%/97.3%], base 16.7%/98.3% [0%/100%] and for observer 2 apex 36.4%/98.1% [0%/100%], mid 28.6%/96.5% [100%/100%], base 20%/100% [0%/97.3%] were poorer as they failed to detect

  2. Treasury Offset Program (TOP) MI

    Social Security Administration — The TOP MI helps OPSOS coordinate TOP case processing in the regions. The MI also helped communicate our progress and findings to BFQM and ORDP, as well as the ACOSS.

  3. miR-181a and miR-630 regulate cisplatin-induced cancer cell death.

    Galluzzi, Lorenzo; Morselli, Eugenia; Vitale, Ilio; Kepp, Oliver; Senovilla, Laura; Criollo, Alfredo; Servant, Nicolas; Paccard, Caroline; Hupé, Philippe; Robert, Thomas; Ripoche, Hugues; Lazar, Vladimir; Harel-Bellan, Annick; Dessen, Philippe; Barillot, Emmanuel; Kroemer, Guido

    2010-03-01

    MicroRNAs (miRNA) are noncoding RNAs that regulate multiple cellular processes, including proliferation and apoptosis. We used microarray technology to identify miRNAs that were upregulated by non-small cell lung cancer (NSCLC) A549 cells in response to cisplatin (CDDP). The corresponding synthetic miRNA precursors (pre-miRNAs) per se were not lethal when transfected into A549 cells yet affected cell death induction by CDDP, C2-ceramide, cadmium, etoposide, and mitoxantrone in an inducer-specific fashion. Whereas synthetic miRNA inhibitors (anti-miRNAs) targeting miR-181a and miR-630 failed to modulate the response of A549 to CDDP, pre-miR-181a and pre-miR-630 enhanced and reduced CDDP-triggered cell death, respectively. Pre-miR-181a and pre-miR-630 consistently modulated mitochondrial/postmitochondrial steps of the intrinsic pathway of apoptosis, including Bax oligomerization, mitochondrial transmembrane potential dissipation, and the proteolytic maturation of caspase-9 and caspase-3. In addition, pre-miR-630 blocked early manifestations of the DNA damage response, including the phosphorylation of the ataxia-telangiectasia mutated (ATM) kinase and of two ATM substrates, histone H2AX and p53. Pharmacologic and genetic inhibition of p53 corroborated the hypothesis that pre-miR-630 (but not pre-miR-181a) blocks the upstream signaling pathways that are ignited by DNA damage and converge on p53 activation. Pre-miR-630 arrested A549 cells in the G0-G1 phase of the cell cycle, correlating with increased levels of the cell cycle inhibitor p27(Kip1) as well as with reduced proliferation rates and resulting in greatly diminished sensitivity of A549 cells to the late S-G2-M cell cycle arrest mediated by CDDP. Altogether, these results identify miR-181a and miR-630 as novel modulators of the CDDP response in NSCLC.

  4. Increased risk of ischemic stroke in cervical cancer patients: a nationwide population-based study

    Tsai, Shiang-Jiun; Su, Yu-Chieh; Hung, Shih-Kai; Huang, Yung-Sung; Tung, Chien-Hsueh; Lee, Ching-Chih; Lee, Moon-Sing; Chiou, Wen-Yen; Lin, Hon-Yi; Hsu, Feng-Chun; Tsai, Chih-Hsin

    2013-01-01

    Increased risk of ischemic stroke has been validated for several cancers, but limited study evaluated this risk in cervical cancer patients. Our study aimed to evaluate the risk of ischemic stroke in cervical cancer patients. The study analyzed data from the 2003 to 2008 National Health Insurance Research Database (NHIRD) provided by the National Health Research Institutes in Taiwan. Totally, 893 cervical cancer patients after radiotherapy and 1786 appendectomy patients were eligible. The Kaplan-Meier method and the Cox proportional hazards model were used to assess the risk of ischemic stroke. The 5-year cumulative risk of ischemic stroke was significantly higher for the cervical cancer group than for the control group (7.8% vs 5.1%; p <0.005). The risk of stroke was higher in younger (age <51 years) than in older (age ≥51 years) cervical cancer patients (HR = 2.73, p = 0.04; HR = 1.37, p = 0.07) and in patients with more than two comorbid risk factors (5 years cumulative stroke rate of two comorbidities: 15% compared to no comorbidities: 4%). These study demonstrated cervical cancer patients had a higher risk of ischemic stroke than the general population, especially in younger patients. Strategies to reduce this risk should be assessed

  5. Increased maternal plasma leptin in early pregnancy and risk of gestational diabetes mellitus.

    Qiu, Chunfang; Williams, Michelle A; Vadachkoria, Surab; Frederick, Ihunnaya O; Luthy, David A

    2004-03-01

    Emerging evidence suggests that leptin, an adipocyte-derived hormone, may have independent direct effects on both insulin secretion and action, in addition to its well documented effects on appetite and energy expenditure. Some, but not all, previously published studies suggest that maternal leptin concentrations may be increased in pregnancies complicated by gestational diabetes mellitus (GDM). We examined the association between plasma leptin concentration and GDM risk. Women were recruited before 16 weeks of gestation and were followed up until delivery. Maternal plasma leptin concentrations (collected at 13 weeks of gestation) were measured by using immunoassay. We used generalized linear models to estimate relative risks and 95% confidence intervals. GDM developed in 5.7% of the cohort (47 of 823). Elevated leptin concentrations were positively associated with GDM risk (P for trend risk of GDM (95% confidence interval 1.2, 18.0) as compared with women who had concentrations of 14.3 ng/mL or lower. We noted a strong linear component of trend in risk of GDM with increasing maternal plasma leptin concentration. Each 10-ng/mL increase in the leptin concentration was associated with a 20% increase in GDM risk (relative risk 1.2; 95% confidence interval 1.0, 1.3). Hyperleptinemia, independent of maternal adiposity, in early pregnancy appears to be predictive of an increased risk of GDM later in pregnancy. Additional larger prospective cohort studies are needed to confirm and more precisely assess the etiologic importance of hyperleptinemia in pregnancy. II-2

  6. Increased risk of intraoperative and early postoperative periprosthetic femoral fracture with uncemented stems

    Lindberg-Larsen, Martin; Jørgensen, Christoffer C.; Solgaard, Søren

    2017-01-01

    Background and purpose - The use of uncemented fixation in total hip arthroplasty (THA) is increasing. Registry studies have indicated an increased risk of revision of uncemented implants due to early periprosthetic femoral fracture. In this paper, we describe the incidence and predisposing facto...

  7. Hyperglycemia is associated with increased risk of patient delay in pulmonary tuberculosis in rural areas

    Wang, Qiuzhen; Ma, Aiguo; Han, Xiuxia; Zhao, Shanliang; Cai, Jing; Kok, Frans J.; Schouten, Evert G.

    2017-01-01

    Background: Excessive time between the first presentation of symptoms of pulmonary tuberculosis (PTB) and diagnosis contributes to ongoing transmission and increased risk of infection in the community, as well as to increased disease severity and higher mortality. People with type 2 diabetes

  8. miR398 and miR395 are involved in response to SO2 stress in Arabidopsis thaliana.

    Li, Lihong; Yi, Huilan; Xue, Meizhao; Yi, Min

    2017-11-01

    Sulfur dioxide (SO 2 ) is a common air pollutant that has adverse effects on plants. MicroRNAs (miRNAs) are small noncoding RNA that play critical roles in plant development and stress response. In this study, we found that two miRNAs, miR398 and miR395, were differentially expressed in Arabidopsis shoots under SO 2 stress. The expression of miR398 was down-regulated, and the transcript levels of its target genes, Cu/Zn superoxide dismutases (CSD1 and CSD2), were increased during SO 2 exposure. The activity of superoxide dismutase (SOD), one of the major antioxidant enzymes, was enhanced with the increase in the CSD transcript level, suggesting an important role of miR398 in response to SO 2 -induced oxidative stress. Meanwhile, the expression of miR395 was increased, and the transcript levels of its target genes, ATP sulfurylases (APS3 and APS4) and a low-affinity sulfate transporter (SULTR2;1), were decreased in Arabidopsis shoots, showing that miR395 played important roles in the regulation of sulfate assimilation and translocation during SO 2 exposure. The content of glutathione (GSH), an important sulfur-containing antioxidant, was enhanced with the changes in sulfur metabolism in Arabidopsis shoots under SO 2 stress. These results showed that both miR398 and miR395 were involved in protecting plants from oxidative damage during SO 2 exposure. Many stress-responsive cis-elements were found in the promoter regions of MIR398 and MIR395, suggesting that these miRNAs might respond to various environmental conditions, including SO 2 stress. Overall, our study provides an insight into the regulatory roles of miRNAs in response to SO 2 stress in plants, and highlights the molecular mechanisms of plant adaptation to environmental stress.

  9. miRNA Expression Profile after Status Epilepticus and Hippocampal Neuroprotection by Targeting miR-132

    Jimenez-Mateos, Eva M.; Bray, Isabella; Sanz-Rodriguez, Amaya; Engel, Tobias; McKiernan, Ross C.; Mouri, Genshin; Tanaka, Katsuhiro; Sano, Takanori; Saugstad, Julie A.; Simon, Roger P.; Stallings, Raymond L.; Henshall, David C.

    2011-01-01

    When an otherwise harmful insult to the brain is preceded by a brief, noninjurious stimulus, the brain becomes tolerant, and the resulting damage is reduced. Epileptic tolerance develops when brief seizures precede an episode of prolonged seizures (status epilepticus). MicroRNAs (miRNAs) are small, noncoding RNAs that function as post-transcriptional regulators of gene expression. We investigated how prior seizure preconditioning affects the miRNA response to status epilepticus evoked by intra-amygdalar kainic acid in mice. The miRNA was extracted from the ipsilateral CA3 subfield 24 hours after focal-onset status epilepticus in animals that had previously received either seizure preconditioning (tolerance) or no preconditioning (injury), and mature miRNA levels were measured using TaqMan low-density arrays. Expression of 21 miRNAs was increased, relative to control, after status epilepticus alone, and expression of 12 miRNAs was decreased. Increased miR-132 levels were matched with increased binding to Argonaute-2, a constituent of the RNA-induced silencing complex. In tolerant animals, expression responses of >40% of the injury-group-detected miRNAs differed, being either unchanged relative to control or down-regulated, and this included miR-132. In vivo microinjection of locked nucleic acid-modified oligonucleotides (antagomirs) against miR-132 depleted hippocampal miR-132 levels and reduced seizure-induced neuronal death. Thus, our data strongly suggest that miRNAs are important regulators of seizure-induced neuronal death. PMID:21945804

  10. Does high sugar consumption exacerbate cardiometabolic risk factors and increase the risk of type 2 diabetes and cardiovascular disease?

    David E. Laaksonen

    2012-07-01

    Full Text Available Consumption of sugar has been relatively high in the Nordic countries; the impact of sugar intake on metabolic risk factors and related diseases has been debated. The objectives were to assess the effect of sugar intake (sugar-sweetened beverages, sucrose and fructose on association with type 2 diabetes, cardiovascular disease and related metabolic risk factors (impaired glucose tolerance, insulin sensitivity, dyslipidemia, blood pressure, uric acid, inflammation markers, and on all-cause mortality, through a systematic review of prospective cohort studies and randomised controlled intervention studies published between January 2000 and search dates. The methods adopted were as follows: the first search was run in PubMed in October 2010. A second search with uric acid as risk marker was run in April 2011. The total search strategy was rerun in April 2011 in SveMed+. An update was run in PubMed in January 2012. Two authors independently selected studies for inclusion from the 2,743 abstracts according to predefined eligibility criteria. The outcome was that out of the 17 studies extracted, 15 were prospective cohort studies and two were randomised controlled crossover trials. All of the studies included only adults. With respect to incident type 2 diabetes (nine studies, four of six prospective cohort studies found a significant positive association for sugar-sweetened beverage intake. In general, larger cohort studies with longer follow-up more often reported positive associations, and BMI seemed to mediate part of the increased risk. For other metabolic or cardiovascular risk factors or outcomes, too few studies have been published to draw conclusions. In conclusion, data from prospective cohort studies published in the years 2000–2011 suggest that sugar-sweetened beverages probably increase the risk of type 2 diabetes. For related metabolic risk factors, cardiovascular disease or all-cause mortality and other types of sugars, too few studies

  11. Impact of Type 2 Myocardial Infarction (MI) on Hospital-Level MI Outcomes: Implications for Quality and Public Reporting.

    Arora, Sameer; Strassle, Paula D; Qamar, Arman; Wheeler, Evan N; Levine, Alexandra L; Misenheimer, Jacob A; Cavender, Matthew A; Stouffer, George A; Kaul, Prashant

    2018-03-26

    The International Classification of Diseases (ICD) coding system does not recognize type 2 myocardial infarction (MI) as a separate entity; therefore, patients with type 2 MI continue to be categorized under the general umbrella of non-ST-segment-elevation myocardial infarction (NSTEMI). We aim to evaluate the impact of type 2 MI on hospital-level NSTEMI metrics and discuss the implications for quality and public reporting. We conducted a single-center retrospective analysis of 1318 patients discharged with a diagnosis of NSTEMI between July 2013 and October 2014. The Third Universal Definition was used to define type 1 and type 2 MI. Weighted Kaplan-Meier curves were used to analyze risk of mortality and readmission. Overall, 1039 patients met NSTEMI criteria per the Third Universal Definition; of those, 264 (25.4%) had type 2 MI. Patients with type 2 MI were older, were more likely to have chronic kidney disease, and had lower peak troponin levels. Compared with type 1 MI patients, those with type 2 MI had higher inpatient mortality (17.4% versus 4.7%, P <0.0001) and were more likely to die from noncardiovascular causes (71.7% versus 25.0%, P <0.0001). Despite weighting for patient characteristics and discharge medications, patients with type 2 MI had higher mortality at both 30 days (risk ratio: 3.63; 95% confidence interval, 1.67-7.88) and 1 year (risk ratio: 1.98; 95% confidence interval, 1.44-2.73) after discharge. Type 2 MI was also associated with a lower 30-day cardiovascular-related readmission (risk ratio: 0.49; 95% confidence interval, 0.12-2.06). NSTEMI metrics are significantly affected by type 2 MI patients. Type 2 MI patients have distinct etiologies, are managed differently, and have higher mortality compared with patients with type 1 MI. Moving forward, it may be appropriate to exclude type 2 MI data from NSTEMI quality metrics. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  12. E-cigarettes: Comparing the Possible Risks of Increasing Smoking Initiation with the Potential Benefits of Increasing Smoking Cessation.

    Warner, Kenneth E; Mendez, David

    2018-03-29

    The public health community is divided regarding electronic cigarettes. Skeptics emphasize potential vaping-induced increases in smoking among children and possible health hazards for adults. Enthusiasts consider e-cigarettes much less dangerous than smoking and believe they increase adult smoking cessation. We compare potential health benefits and costs to put these two perspectives in context. Using a dynamic model that tracks the US adult population's smoking status and smoking-related deaths over time, we simulate the effects of vaping-induced smoking initiation and cessation on life-years saved or lost to the year 2070. The base case assumes that vaping annually increases smoking initiation by 2% and smoking cessation by 10%. Sensitivity analyses raise the initiation rate increase to 6% while decreasing the cessation rate increase to 5%. Sensitivity analyses also test vaping's reducing the health benefits of quitting smoking by 10%. With base-case assumptions, the population gains almost 3.3 million life-years by 2070. If all people who quit smoking by vaping lose 10% of the benefit of quitting smoking, the net life-year gain falls to 2.4 million. Under worst-case assumptions, in which vaping increases smoking initiation by 6% and cessation by 5%, and vaping-induced quitters lose 10% of the health benefits, the population gains over 580,000 life-years. Potential life-years gained as a result of vaping-induced smoking cessation are projected to exceed potential life-years lost due to vaping-induced smoking initiation. These results hold over a wide range of plausible parameters. Our analysis strongly suggests that the upside health benefit associated with e-cigarettes, in terms of their potential to increase adult smoking cessation, exceeds their downside risk to health as a result of their possibly increasing the number of youthful smoking initiators. Public messaging and policy should continue to strive to reduce young people's exposure to all nicotine and

  13. Behavioural adjustment in response to increased predation risk: a study in three duck species.

    Cédric Zimmer

    Full Text Available Predation directly triggers behavioural decisions designed to increase immediate survival. However, these behavioural modifications can have long term costs. There is therefore a trade-off between antipredator behaviours and other activities. This trade-off is generally considered between vigilance and only one other behaviour, thus neglecting potential compensations. In this study, we considered the effect of an increase in predation risk on the diurnal time-budget of three captive duck species during the wintering period. We artificially increased predation risk by disturbing two groups of 14 mallard and teals at different frequencies, and one group of 14 tufted ducks with a radio-controlled stressor. We recorded foraging, vigilance, preening and sleeping durations the week before, during and after disturbance sessions. Disturbed groups were compared to an undisturbed control group. We showed that in all three species, the increase in predation risk resulted in a decrease in foraging and preening and led to an increase in sleeping. It is worth noting that contrary to common observations, vigilance did not increase. However, ducks are known to be vigilant while sleeping. This complex behavioural adjustment therefore seems to be optimal as it may allow ducks to reduce their predation risk. Our results highlight the fact that it is necessary to encompass the whole individual time-budget when studying behavioural modifications under predation risk. Finally, we propose that studies of behavioural time-budget changes under predation risk should be included in the more general framework of the starvation-predation risk trade-off.

  14. A computer code for Cohort Analysis of Increased Risks of Death (CAIRD). Technical report

    Cook, J.R.; Bunger, B.M.; Barrick, M.K.

    1978-06-01

    The most serious health risk confronting individuals exposed to radiation is death from an induced cancer. Since cancers usually do no develop until many years after exposure, other causes of death may intervene and take the lives of those destined to die from cancer. This computer code has been developed to aid risk analysis by calculating the number of premature deaths and loss of years of life produced by a hypothetical population after exposure to a given risk situation. The code generates modified life tables and estimates the impact of increased risk through several numerical comparisons with the appropriate reference life tables. One of the code's frequent applications is in estimating the number of radiation induced deaths that would result from exposing an initial population of 100,000 individuals to an annual radiation dose. For each risk situation analyzed, the computer code generates a summary table which documents the input, data and contains the results of the comparisons with reference life tables

  15. Increased sensitivity to positive social stimuli in monozygotic twins at risk of bipolar vs. unipolar disorder

    Kærsgaard, S; Meluken, I; Kessing, L V

    2018-01-01

    BACKGROUND: Abnormalities in affective cognition are putative endophenotypes for bipolar and unipolar disorders but it is unclear whether some abnormalities are disorder-specific. We therefore investigated affective cognition in monozygotic twins at familial risk of bipolar disorder relative...... to those at risk of unipolar disorder and to low-risk twins. METHODS: Seventy monozygotic twins with a co-twin history of bipolar disorder (n = 11), of unipolar disorder (n = 38) or without co-twin history of affective disorder (n = 21) were included. Variables of interest were recognition of and vigilance...... to emotional faces, emotional reactivity and -regulation in social scenarios and non-affective cognition. RESULTS: Twins at familial risk of bipolar disorder showed increased recognition of low to moderate intensity of happy facial expressions relative to both unipolar disorder high-risk twins and low...

  16. No increased risk of developing depression in diabetes compared to other chronic illness

    Kessing, Lars Vedel; Nilsson, Flemming Mørkeberg; Siersma, Volkert

    2003-01-01

    of patients. There was no difference in the risk for Type 1 and Type 2 diabetes. It is concluded that older patients with diabetes do not seem to have an increased risk of developing severe depression compared with patients with other chronic illness.......Several studies have found that the prevalence of depression in patients with diabetes is higher than in the general population but it is unclear whether patients with diabetes have an increased risk of developing depression compared with patients with other chronic illnesses. In a nationwide case...... register study, all patients who had a discharge diagnosis of diabetes or of osteoarthritis at first admission in a period from 1977 to 1997 were identified. The probability of being readmitted and discharged with a diagnosis of depression was estimated with competing risks models in survival analysis...

  17. Increased relative risk of subsequent affective disorders in patients with a hospital diagnosis of obesity

    Thomsen, A F; Kvist, T K; Andersen, P K

    2006-01-01

    OBJECTIVE: To investigate the risk of clinical affective disorders of patients who were hospitalized because of obesity in the study period 1 January 1977 to 31 December 1999. METHOD: Using data from Danish hospital registers, three study cohorts were identified by their diagnoses at discharge from...... discharged with an index diagnosis was identified. In total, 1081 events occurred in the observation period. An index diagnosis of obesity was associated with an increased risk of affective-disorders hospitalization when compared with patients with osteoarthritis (Rate ratio: 1.35 (95% CI: 1.......09-1.67)) and tended to be associated with an increased risk when compared to patients with non-toxic goiter (Rate ratio: 1.23 (95% CI: 0.99-1.53)). Patients with obesity diagnoses who did not have additional hospital diagnoses of substance- or alcohol abuse had a risk of affective disorders that was 1.55 (95% CI: 1...

  18. The racing-game effect: why do video racing games increase risk-taking inclinations?

    Fischer, Peter; Greitemeyer, Tobias; Morton, Thomas; Kastenmüller, Andreas; Postmes, Tom; Frey, Dieter; Kubitzki, Jörg; Odenwälder, Jörg

    2009-10-01

    The present studies investigated why video racing games increase players' risk-taking inclinations. Four studies reveal that playing video racing games increases risk taking in a subsequent simulated road traffic situation, as well as risk-promoting cognitions and emotions, blood pressure, sensation seeking, and attitudes toward reckless driving. Study 1 ruled out the role of experimental demand in creating such effects. Studies 2 and 3 showed that the effect of playing video racing games on risk taking was partially mediated by changes in self-perceptions as a reckless driver. These effects were evident only when the individual played racing games that reward traffic violations rather than racing games that do not reward traffic violations (Study 3) and when the individual was an active player of such games rather than a passive observer (Study 4). In sum, the results underline the potential negative impact of racing games on traffic safety.

  19. Identification of a DMBT1 polymorphism associated with increased breast cancer risk and decreased promoter activity

    Tchatchou, Sandrine; Riedel, Angela; Lyer, Stefan

    2010-01-01

    ,466 unrelated German controls. Promoter studies in breast cancer cells demonstrate that the risk-increasing DMBT1 -93T allele displays significantly decreased promoter activity compared to the DMBT1 -93C allele, resulting in a loss of promoter activity. The data suggest that DMBT1 polymorphisms in the 5'-region......According to present estimations, the unfavorable combination of alleles with low penetrance but high prevalence in the population might account for the major part of hereditary breast cancer risk. Deleted in Malignant Brain Tumors 1 (DMBT1) has been proposed as a tumor suppressor for breast cancer...... and other cancer types. Genomewide mapping in mice further identified Dmbt1 as a potential modulator of breast cancer risk. Here, we report the association of two frequent and linked single-nucleotide polymorphisms (SNPs) with increased breast cancer risk in women above the age of 60 years: DMBT1 c.-93C...

  20. Delay in blood sampling for routine newborn screening is associated with increased risk of schizophrenia

    Nordentoft, Merete; Tidselbak Larsen, Janne; Pedersen, Carsten Bøcker

    2015-01-01

    for this association. Therefore, we investigated whether the increased risk can be explained by other risk factors for schizophrenia. METHODS: A case-control design was applied. A total of 846 cases with schizophrenia were selected from the Danish Psychiatric Case Register. One control was selected for each case......BACKGROUND: The Danish Neonatal Screening Biobank, containing dried blood spot samples from all newborn in Denmark, is a unique source of data that can be utilized for analyses of genetic and environmental exposures related to schizophrenia and other mental disorders. In previous analyses, we have...... found that early and late blood sampling, compared to sampling at day 5, was associated with increased risk of schizophrenia. As delay in sampling of blood for neonatal screening cannot in itself influence the risk of schizophrenia, it must be seen as a proxy for unknown underlying causes responsible...

  1. Increased sensitivity to positive social stimuli in monozygotic twins at risk of bipolar vs. unipolar disorder.

    Kærsgaard, S; Meluken, I; Kessing, L V; Vinberg, M; Miskowiak, K W

    2018-05-01

    Abnormalities in affective cognition are putative endophenotypes for bipolar and unipolar disorders but it is unclear whether some abnormalities are disorder-specific. We therefore investigated affective cognition in monozygotic twins at familial risk of bipolar disorder relative to those at risk of unipolar disorder and to low-risk twins. Seventy monozygotic twins with a co-twin history of bipolar disorder (n = 11), of unipolar disorder (n = 38) or without co-twin history of affective disorder (n = 21) were included. Variables of interest were recognition of and vigilance to emotional faces, emotional reactivity and -regulation in social scenarios and non-affective cognition. Twins at familial risk of bipolar disorder showed increased recognition of low to moderate intensity of happy facial expressions relative to both unipolar disorder high-risk twins and low-risk twins. Bipolar disorder high-risk twins also displayed supraliminal attentional avoidance of happy faces compared with unipolar disorder high-risk twins and greater emotional reactivity in positive and neutral social scenarios and less reactivity in negative social scenarios than low-risk twins. In contrast with our hypothesis, there was no negative bias in unipolar disorder high-risk twins. There were no differences between the groups in demographic characteristics or non-affective cognition. The modest sample size limited the statistical power of the study. Increased sensitivity and reactivity to positive social stimuli may be a neurocognitive endophenotype that is specific for bipolar disorder. If replicated in larger samples, this 'positive endophenotype' could potentially aid future diagnostic differentiation between unipolar and bipolar disorder. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Does breast density measured through population-based screening independently increase breast cancer risk in Asian females?

    Park B

    2017-12-01

    Full Text Available Boyoung Park,1,2 Hye Mi Cho,2 Eun Hye Lee,3 Seunghoon Song,2 Mina Suh,2 Kui Son Choi,1,2 Bong Joo Kang,4 Kyungran Ko,5 Ann Yi,6 Hae Kyoung Jung,7 Joo Hee Cha,8 Jae Kwan Jun,1,2 1National Cancer Center Graduate School of Cancer Science and Policy, Goyang, Republic of Korea; 2National Cancer Control Institute, National Cancer Center, Goyang, Republic of Korea; 3Department of Radiology, Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, Republic of Korea; 4Department of Radiology, Seoul St Mary’s Hospital, Catholic University of Korea College of Medicine, Seoul, Republic of Korea; 5Center for Breast Cancer, National Cancer Center Hospital, National Cancer Center, Goyang, Republic of Korea; 6Department of Radiology, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Republic of Korea; 7Department of Radiology, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea; 8Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea Purpose: The purpose of this study was to investigate the effects of breast density on breast cancer risk among women screened via a nationwide mammographic screening program. Patients and methods: We conducted a nested case–control study for a randomly selected population of 1,561 breast cancer patients and 6,002 matched controls from the National Cancer Screening Program. Breast density was measured and recorded by two independent radiologists using the Breast Imaging Reporting and Data System (BI-RADS. Associations between BI-RADS density and breast cancer risk were evaluated according to screening results, time elapsed since receiving non-recall results, age, and menopausal status after adjusting for possible covariates. Results: Breast cancer risk for women with extremely dense breasts was five times higher (adjusted odds ratio [aOR] =5.0; 95% confidence interval [CI] =3

  3. Transcriptome association analysis identifies miR-375 as a major determinant of variable acetaminophen glucuronidation by human liver.

    Papageorgiou, Ioannis; Freytsis, Marina; Court, Michael H

    2016-10-01

    Acetaminophen is the leading cause of acute liver failure (ALF) in many countries including the United States. Hepatic glucuronidation by UDP-glucuronosyltransferase (UGT) 1A subfamily enzymes is the major route of acetaminophen elimination. Reduced glucuronidation may predispose some individuals to acetaminophen-induced ALF, but mechanisms underlying reduced glucuronidation are poorly understood. We hypothesized that specific microRNAs (miRNAs) may reduce UGT1A activity by direct effects on the UGT1A 3'-UTR shared by all UGT1A enzyme transcripts, or by indirect effects on transcription factors regulating UGT1A expression. We performed an unbiased miRNA whole transcriptome association analysis using a bank of human livers with known acetaminophen glucuronidation activities. Of 754 miRNAs evaluated, 9 miRNAs were identified that were significantly overexpressed (p2-fold) in livers with low acetaminophen glucuronidation activities compared with those with high activities. miR-375 showed the highest difference (>10-fold), and was chosen for further mechanistic validation. We demonstrated using in silico analysis and luciferase reporter assays that miR-375 has a unique functional binding site in the 3'-UTR of the aryl hydrocarbon receptor (AhR) gene. Furthermore overexpression of miR-375 in LS180 cells demonstrated significant repression of endogenous AhR protein (by 40%) and mRNA (by 10%), as well as enzyme activity and/or mRNA of AhR regulated enzymes including UGT1A1, UGT1A6, and CYP1A2, without affecting UGT2B7, which is not regulated by AhR. Thus miR-375 is identified as a novel repressor of UGT1A-mediated hepatic acetaminophen glucuronidation through reduced AhR expression, which could predispose some individuals to increased risk for acetaminophen-induced ALF. Published by Elsevier Inc.

  4. Elderly individuals with increased risk of falls show postural balance impairment

    Oliveira, Márcio Rogério de; Inokuti, Thiago Tadashi; Bispo, Nuno Noronha da Costa; Oliveira, Deise Aparecida de Almeida Pires; Oliveira, Rodrigo Franco de; Silva Jr., Rubens Alexandre da

    2015-01-01

    Introduction Falls are a serious public health problem. Objective The aim of this study was to evaluate whether elderly individuals with increased risk of falls have a postural balance deficit, evaluated using a force platform during a one-leg stance. Materials and methods The sample consisted of 94 physically independent elderly individuals from the EELO project. The instruments used were the Downton scale, in order to assess the risk as well as the history of falls, and the force platf...

  5. Cardiovascular risk factors are associated with increased lesion burden and brain atrophy in multiple sclerosis.

    Kappus, Natalie; Weinstock-Guttman, Bianca; Hagemeier, Jesper; Kennedy, Cheryl; Melia, Rebecca; Carl, Ellen; Ramasamy, Deepa P; Cherneva, Mariya; Durfee, Jacqueline; Bergsland, Niels; Dwyer, Michael G; Kolb, Channa; Hojnacki, David; Ramanathan, Murali; Zivadinov, Robert

    2016-02-01

    Cardiovascular (CV) risk factors have been associated with changes in clinical outcomes in patients with multiple sclerosis (MS). To investigate the frequency of CV risks in patients with MS and their association with MRI outcomes. In a prospective study, 326 patients with relapsing-remitting MS and 163 patients with progressive MS, 61 patients with clinically isolated syndrome (CIS) and 175 healthy controls (HCs) were screened for CV risks and scanned on a 3T MRI scanner. Examined CV risks included hypertension, heart disease, smoking, overweight/obesity and type 1 diabetes. MRI measures assessed lesion volumes (LVs) and brain atrophy. Association between individual or multiple CV risks and MRI outcomes was examined adjusting for age, sex, race, disease duration and treatment status. Patients with MS showed increased frequency of smoking (51.7% vs 36.5%, p = 0.001) and hypertension (33.9% vs 24.7%, p=0.035) compared with HCs. In total, 49.9% of patients with MS and 36% of HCs showed ≥ 2 CV risks (p = 0.003), while the frequency of ≥ 3 CV risks was 18.8% in the MS group and 8.6% in the HCs group (p = 0.002). In patients with MS, hypertension and heart disease were associated with decreased grey matter (GM) and cortical volumes (p < 0.05), while overweight/obesity was associated with increased T1-LV (p < 0.39) and smoking with decreased whole brain volume (p = 0.049). Increased lateral ventricle volume was associated with heart disease (p = 0.029) in CIS. Patients with MS with one or more CV risks showed increased lesion burden and more advanced brain atrophy. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  6. Tourette syndrome increases risk of bone fractures: a population-based cohort study.

    Lu, Yuan-Yuan; Wang, Ming-Yu; Wei, I-Hua; Lin, Che-Chen; Huang, Chih-Chia

    2017-05-01

    This study assesses the risk of fractures among children with Tourette syndrome (TS), and identifies the effects of comorbidities and antipsychotics. We randomly sampled the claims data of 1 million enrollees in the National Health Insurance program of Taiwan, and identified 1258 children with TS diagnosed between 2000 and 2010. Additionally, 12,580 children without TS who were frequency matched for sex, age, residential area, parental occupation, and index year were identified for comparison. The children's cases were followed until December 31, 2010, or censored to ascertain incident fractures cases and associations with comorbidities of attention-deficit/hyperactivity disorder (ADHD) or obsessive-compulsive disorder (OCD) and treatments with antipsychotics, antidepressants, or clonidine. The TS cohort had a 1.27-fold higher incidence of fractures than did the comparison cohort (190.37 vs. 149.94 per 10,000 person-years), with an adjusted hazard ratio (HR) of 1.28 [95% confidence interval (CI) 1.06-1.55] based on multivariable Cox regression analysis. This increased risk of fractures was apparent for fractures of the skull, neck, and spine. Comorbid ADHD and OCD did not result in an additional risk of fractures. The children without both ADHD and OCD were also at a higher risk of fractures, indicating that TS alone increases the risk of fractures. The children taking antipsychotics had a reduced risk of fractures, and the adjusted HR decreased to 1.17 (95% CI 0.90-1.52). Children with TS have an increased risk of fractures. ADHD and OCD do not increase the risk further.

  7. 86Rubidium uptake in mononuclear leucocytes from young subjects at increased risk of developing essential hypertension

    Nielsen, J R; Johansen, Torben; Pedersen, K E

    1988-01-01

    This study was designed to assess any changes in mononuclear leucocytes from young men at increased risk of developing essential hypertension and to determine whether any changes found were associated with borderline hypertension and/or heredity. To this end we used mononuclear leucocytes......, and especially in those borderline hypertensives with at least one hypertensive parent. The latter group was also the group at greatest risk of developing essential hypertension....

  8. Novel Triazole linked 2-phenyl benzoxazole derivatives induce apoptosis by inhibiting miR-2, miR-13 and miR-14 function in Drosophila melanogaster.

    Mondal, Tanmoy; Lavanya, A V S; Mallick, Akash; Dadmala, Tulshiram L; Kumbhare, Ravindra M; Bhadra, Utpal; Bhadra, Manika Pal

    2017-06-01

    Apoptosis is an important phenomenon in multi cellular organisms for maintaining tissue homeostasis and embryonic development. Defect in apoptosis leads to a number of disorders like- autoimmune disorder, immunodeficiency and cancer. 21-22 nucleotides containing micro RNAs (miRNAs/miRs) function as a crucial regulator of apoptosis alike other cellular pathways. Recently, small molecules have been identified as a potent inducer of apoptosis. In this study, we have identified novel Triazole linked 2-phenyl benzoxazole derivatives (13j and 13h) as a negative regulator of apoptosis inhibiting micro RNAs (miR-2, miR-13 and miR-14) in a well established in vivo model Drosophila melanogaster where the process of apoptosis is very similar to human apoptosis. These compounds inhibit miR-2, miR-13 and miR-14 activity at their target sites, which induce an increased caspase activity, and in turn influence the caspase dependent apoptotic pathway. These two compounds also increase the mitochondrial reactive oxygen species (ROS) level to trigger apoptotic cell death.

  9. The Adequate Corpus Luteum: miR-96 Promotes Luteal Cell Survival and Progesterone Production.

    Mohammed, Bushra T; Sontakke, Sadanand D; Ioannidis, Jason; Duncan, W Colin; Donadeu, F Xavier

    2017-07-01

    Inadequate progesterone production from the corpus luteum is associated with pregnancy loss. Data available in model species suggest important roles of microRNAs (miRNAs) in luteal development and maintenance. To comprehensively investigate the involvement of miRNAs during the ovarian follicle-luteal transition. The effects of specific miRNAs on survival and steroid production by human luteinized granulosa cells (hLGCs) were tested using specific miRNA inhibitors. Candidate miRNAs were identified through microarray analyses of follicular and luteal tissues in a bovine model. An academic institution in the United Kingdom associated with a teaching hospital. hLGCs were obtained by standard transvaginal follicular-fluid aspiration from 35 women undergoing assisted conception. Inhibition of candidate miRNAs in vitro. Levels of miRNAs, mRNAs, FOXO1 protein, apoptosis, and steroids were measured in tissues and/or cultured cells. Two specific miRNA clusters, miR-183-96-182 and miR-212-132, were dramatically increased in luteal relative to follicular tissues. miR-96 and miR-132 were the most upregulated miRNAs within each cluster. Database analyses identified FOXO1 as a putative target of both these miRNAs. In cultured hLGCs, inhibition of miR-96 increased apoptosis and FOXO1 protein levels, and decreased progesterone production. These effects were prevented by small interfering RNA-mediated downregulation of FOXO1. In bovine luteal cells, miR-96 inhibition also led to increases in apoptosis and FOXO1 protein levels. miR-96 targets FOXO1 to regulate luteal development through effects on cell survival and steroid production. The miR-183-96-182 cluster could provide a novel target for the manipulation of luteal function. Copyright © 2017 Endocrine Society

  10. A Western Dietary Pattern Increases Prostate Cancer Risk: A Systematic Review and Meta-Analysis.

    Fabiani, Roberto; Minelli, Liliana; Bertarelli, Gaia; Bacci, Silvia

    2016-10-12

    Dietary patterns were recently applied to examine the relationship between eating habits and prostate cancer (PC) risk. While the associations between PC risk with the glycemic index and Mediterranean score have been reviewed, no meta-analysis is currently available on dietary patterns defined by "a posteriori" methods. A literature search was carried out (PubMed, Web of Science) to identify studies reporting the relationship between dietary patterns and PC risk. Relevant dietary patterns were selected and the risks estimated were calculated by a random-effect model. Multivariable-adjusted odds ratios (ORs), for a first-percentile increase in dietary pattern score, were combined by a dose-response meta-analysis. Twelve observational studies were included in the meta-analysis which identified a "Healthy pattern" and a "Western pattern". The Healthy pattern was not related to PC risk (OR = 0.96; 95% confidence interval (CI): 0.88-1.04) while the Western pattern significantly increased it (OR = 1.34; 95% CI: 1.08-1.65). In addition, the "Carbohydrate pattern", which was analyzed in four articles, was positively associated with a higher PC risk (OR = 1.64; 95% CI: 1.35-2.00). A significant linear trend between the Western ( p = 0.011) pattern, the Carbohydrate ( p = 0.005) pattern, and the increment of PC risk was observed. The small number of studies included in the meta-analysis suggests that further investigation is necessary to support these findings.

  11. Acceptance and adherence to chemoprevention among women at increased risk of breast cancer.

    Roetzheim, Richard G; Lee, Ji-Hyun; Fulp, William; Matos Gomez, Elizabeth; Clayton, Elissa; Tollin, Sharon; Khakpour, Nazanin; Laronga, Christine; Lee, Marie Catherine; Kiluk, John V

    2015-02-01

    Chemoprevention is an option for women who are at increased risk of breast cancer (five year risk ≥1.7%). It is uncertain, however, how often women accept and complete five years of therapy and whether clinical or demographic factors predict completion. Medical records were abstracted for 219 women whose five year risk of breast cancer was ≥1.7% and who were offered chemoprevention while attending a high risk breast clinic at the Moffitt Cancer Center. We examined the likelihood of accepting chemoprevention and completing five years of therapy, and potential clinical and demographic predictors of these outcomes, using multivariable logistic regression and survival analysis models. There were 118/219 women (54.4%) who accepted a recommendation for chemoprevention and began therapy. The likelihood of accepting chemoprevention was associated with lifetime breast cancer risk and was higher for women with specific high risk conditions (lobular carcinoma in situ and atypical ductal hyperplasia). Women with osteoporosis and those that consumed alcohol were also more likely to accept medication. There were 58/118 (49.2%) women who stopped medication at least temporarily after starting therapy. Based on survival curves, an estimated 60% of women who begin chemoprevention will complete five years of therapy. A substantial percentage of women at increased risk of breast cancer will decline chemoprevention and among those that accept therapy, approximately 40% will not be able to complete five years of therapy because of side effects. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Threshold-dependent repression of SPL gene expression by miR156/miR157 controls vegetative phase change in Arabidopsis thaliana.

    Jia He

    2018-04-01

    Full Text Available Vegetative phase change is regulated by a decrease in the abundance of the miRNAs, miR156 and miR157, and the resulting increase in the expression of their targets, SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL transcription factors. To determine how miR156/miR157 specify the quantitative and qualitative changes in leaf morphology that occur during vegetative phase change, we measured their abundance in successive leaves and characterized the phenotype of mutations in different MIR156 and MIR157 genes. miR156/miR157 decline rapidly between leaf 1&2 and leaf 3 and decrease more slowly after this point. The amount of miR156/miR157 in leaves 1&2 greatly exceeds the threshold required to specify their identity. Subsequent leaves have relatively low levels of miR156/miR157 and are sensitive to small changes in their abundance. In these later-formed leaves, the amount of miR156/miR157 is close to the threshold required to specify juvenile vs. adult identity; a relatively small decrease in the abundance of miR156/157 in these leaves produces a disproportionately large increase in SPL proteins and a significant change in leaf morphology. miR157 is more abundant than miR156 but has a smaller effect on shoot morphology and SPL gene expression than miR156. This may be attributable to the inefficiency with which miR157 is loaded onto AGO1, as well as to the presence of an extra nucleotide at the 5' end of miR157 that is mis-paired in the miR157:SPL13 duplex. miR156 represses different targets by different mechanisms: it regulates SPL9 by a combination of transcript cleavage and translational repression and regulates SPL13 primarily by translational repression. Our results offer a molecular explanation for the changes in leaf morphology that occur during shoot development in Arabidopsis and provide new insights into the mechanism by which miR156 and miR157 regulate gene expression.

  13. Clinical and Surgical Factors Associated With Increased Epilepsy Risk in Children With Hydrocephalus.

    Tully, Hannah M; Kukull, Walter A; Mueller, Beth A

    2016-06-01

    Children with hydrocephalus are at risk for epilepsy both due to their underlying condition and as a consequence of surgical treatment; however, the relative contributions of these factors remain unknown. The authors sought to characterize epilepsy among children with infancy-onset hydrocephalus and to examine the risks of epilepsy associated with hydrocephalus subtype and with factors related to surgical treatment. We conducted a longitudinal cohort study of all children with infancy-onset hydrocephalus treated at a major regional children's hospital during 2002 to 2012, with follow-up to ascertain risk factors and epilepsy outcome through April 2015. Poisson regression was used to calculate adjusted risk ratios and 95% confidence intervals for associations. Among 379 children with hydrocephalus, 86 (23%) developed epilepsy (mean onset age = 2.7 years), almost one fifth of whom had a history of infantile spasms. Relative to spina bifida-associated hydrocephalus, children with other major hydrocephalus subtypes had fourfold higher risks of developing epilepsy. Among children who underwent surgery, surgical infection doubled the risk of epilepsy (risk ratio = 2.0, 95% confidence interval = 1.4 to 3.0). Epilepsy was associated with surgical failure for intracranial reasons but not extracranial reasons (risk ratio = 1.7, 95% confidence interval = 1.1 to 2.7; risk ratio = 1.1, 95% confidence interval = 0.7 to 1.9, respectively). Epilepsy is common among children with hydrocephalus. Compared with children with spina bifida-associated hydrocephalus, children with other major hydrocephalus subtypes have a markedly increased risk of epilepsy. Surgical infection doubles the risk of epilepsy. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Gene polymorphisms of micrornas in Helicobacter pylori-induced high risk atrophic gastritis and gastric cancer.

    Juozas Kupcinskas

    Full Text Available BACKGROUND AND AIMS: MicroRNAs (miRNAs are known for their function as translational regulators of tumor suppressor or oncogenes. Single nucleotide polymorphisms (SNPs in miRNAs related genes have been shown to affect the regulatory capacity of miRNAs and were linked with gastric cancer (GC and premalignant gastric conditions. The purpose of this study was to evaluate potential associations between miRNA-related gene polymorphisms (miR-27a, miR-146a, miR-196a-2, miR-492 and miR-608 and the presence of GC or high risk atrophic gastritis (HRAG in European population. METHODS: Gene polymorphisms were analyzed in 995 subjects (controls: n = 351; GC: n = 363; HRAG: n = 281 of European descent. MiR-27a T>C (rs895819, miR-146a G>C (rs2910164, miR-196a-2 C>T (rs11614913, miR-492 G>C (rs2289030 and miR-608 C>G (rs4919510 SNPs were genotyped by RT-PCR. RESULTS: Overall, SNPs of miRNAs were not associated with the presence of GC or HRAG. We observed a tendency for miR-196a-2 CT genotype to be associated with higher risk of GC when compared to CC genotype, however, the difference did not reach the adjusted P-value (odds ratio (OR - 1.46, 95% confidence interval (CI 1.03-2.07, P = 0.032. MiR-608 GG genotype was more frequent in GC when compared to controls (OR -2.34, 95% CI 1.08-5.04, but significance remained marginal (P = 0.029. A similar tendency was observed in a recessive model for miR-608, where CC + CG vs GG genotype comparison showed a tendency for increased risk of GC with OR of 2.44 (95% CI 1.14-5.22, P = 0.021. The genotypes and alleles of miR-27a, miR-146a, miR-196a-2, miR-492 and miR-608 SNPs had similar distribution between histological subtypes of GC and were not linked with the presence of diffuse or intestinal-type GC. CONCLUSIONS: Gene polymorphisms of miR-27a, miR-146a, miR-196a-2, miR-492, miR-492a and miR-608 were not associated with the presence of HRAG, GC or different histological subtypes of GC in European

  15. Mechanism and preclinical prevention of increased breast cancer risk caused by pregnancy.

    Haricharan, Svasti; Dong, Jie; Hein, Sarah; Reddy, Jay P; Du, Zhijun; Toneff, Michael; Holloway, Kimberly; Hilsenbeck, Susan G; Huang, Shixia; Atkinson, Rachel; Woodward, Wendy; Jindal, Sonali; Borges, Virginia F; Gutierrez, Carolina; Zhang, Hong; Schedin, Pepper J; Osborne, C Kent; Tweardy, David J; Li, Yi

    2013-12-31

    While a first pregnancy before age 22 lowers breast cancer risk, a pregnancy after age 35 significantly increases life-long breast cancer risk. Pregnancy causes several changes to the normal breast that raise barriers to transformation, but how pregnancy can also increase cancer risk remains unclear. We show in mice that pregnancy has different effects on the few early lesions that have already developed in the otherwise normal breast-it causes apoptosis evasion and accelerated progression to cancer. The apoptosis evasion is due to the normally tightly controlled STAT5 signaling going astray-these precancerous cells activate STAT5 in response to pregnancy/lactation hormones and maintain STAT5 activation even during involution, thus preventing the apoptosis normally initiated by oncoprotein and involution. Short-term anti-STAT5 treatment of lactation-completed mice bearing early lesions eliminates the increased risk after a pregnancy. This chemoprevention strategy has important implications for preventing increased human breast cancer risk caused by pregnancy. DOI: http://dx.doi.org/10.7554/eLife.00996.001.

  16. Setting the Threshold for Surgical Prevention in Women at Increased Risk of Ovarian Cancer.

    Manchanda, Ranjit; Menon, Usha

    2018-01-01

    considered at younger than 45. In other moderate-risk gene mutation carriers and those with polygenic risk, RRSO needs be considered at 50. There is need for establishment/expansion of well-defined pathways to increase clinical access to RRSO. It is time to lower the risk threshold for RRSO to enable introduction of a targeted primary prevention approach, which could significantly impact the future burden of ovarian cancer.

  17. Risk perception, risk management and safety assessment: what can governments do to increase public confidence in their vaccine system?

    MacDonald, Noni E; Smith, Jennifer; Appleton, Mary

    2012-09-01

    For decades vaccine program managers and governments have devoted many resources to addressing public vaccine concerns, vaccine risk perception, risk management and safety assessment. Despite ever growing evidence that vaccines are safe and effective, public concerns continue. Education and evidence based scientific messages have not ended concerns. How can governments and programs more effectively address the public's vaccine concerns and increase confidence in the vaccine safety system? Vaccination hesitation has been attributed to concerns about vaccine safety, perceptions of high vaccine risks and low disease risk and consequences. Even when the public believes vaccines are important for protection many still have concerns about vaccine safety. This overview explores how heuristics affect public perception of vaccines and vaccine safety, how the public finds and uses vaccine information, and then proposes strategies for changes in the approach to vaccine safety communications. Facts and evidence confirming the safety of vaccines are not enough. Vaccine beliefs and behaviours must be shaped. This will require a shift in the what, when, how and why of vaccine risk and benefit communication content and practice. A change to a behavioural change strategy such as the WHO COMBI program that has been applied to disease eradication efforts is suggested. Copyright © 2011. Published by Elsevier Ltd.. All rights reserved.

  18. Better consenting for thyroidectomy: who has an increased risk of postoperative hypocalcaemia?

    Harris, Andrew S; Prades, Eduardo; Tkachuk, Olena; Zeitoun, Hisham

    2016-12-01

    Hypocalcaemia is the most common complication following thyroidectomy. This study aimed to establish the factors associated with increased risk of hypocalcaemia on day 1 following thyroidectomy. All patients who underwent thyroidectomy under a single consultant during a 5-year period were included. A multivariate analysis was undertaken to ascertain which variables had the most effect on the risk of hypocalcaemia. A prognosis table was constructed to allow risk to be predicted for individual patients based on these factors. Included in the analysis were 210 procedures and 194 patients. Eighty-two percent of patients had no calcium derangement postoperatively. Fourteen point nine percent were categorised as early hypocalcaemia, 1 % had protracted hypocalcaemia and 2.1 % had permanent hypocalcaemia. For hemi-thyroidectomies 2.8 % had postoperative hypocalcaemia and 0.9 % had permanent hypocalcaemia. The multivariate analysis revealed total thyroidectomy (risk ratio 26.5, p < 0.0001), diabetes (risk ratio 4.8, p = 0.07) and thyrotoxicosis (risk ratio 3.1, p = 0.04) as statistically significant variables for early postoperative hypocalcaemia. Gender as an isolated factor did not reach significance but was included in the model. The p value for the model was p < 1 × 10 -12 . Total thyroidectomy increases risk of early hypocalcaemia when compared to hemithyroidectomy. Gender, diabetes and thyrotoxicosis were also been found to influence the risk. All of these factors are available pre-operatively and can therefore be used to predict a more specific risk for individual patients. It is hoped that this can lead to better informed consent, prevention and better resource allocation.

  19. Increased Wildfire Risk Driven by Climate and Development Interactions in the Bolivian Chiquitania, Southern Amazonia.

    Devisscher, Tahia; Anderson, Liana O; Aragão, Luiz E O C; Galván, Luis; Malhi, Yadvinder

    2016-01-01

    Wildfires are becoming increasingly dominant in tropical landscapes due to reinforcing feedbacks between land cover change and more severe dry conditions. This study focused on the Bolivian Chiquitania, a region located at the southern edge of Amazonia. The extensive, unique and well-conserved tropical dry forest in this region is susceptible to wildfires due to a marked seasonality. We used a novel approach to assess fire risk at the regional level driven by different development trajectories interacting with changing climatic conditions. Possible future risk scenarios were simulated using maximum entropy modelling with presence-only data, combining land cover, anthropogenic and climatic variables. We found that important determinants of fire risk in the region are distance to roads, recent deforestation and density of human settlements. Severely dry conditions alone increased the area of high fire risk by 69%, affecting all categories of land use and land cover. Interactions between extreme dry conditions and rapid frontier expansion further increased fire risk, resulting in potential biomass loss of 2.44±0.8 Tg in high risk area, about 1.8 times higher than the estimates for the 2010 drought. These interactions showed particularly high fire risk in land used for 'extensive cattle ranching', 'agro-silvopastoral use' and 'intensive cattle ranching and agriculture'. These findings have serious implications for subsistence activities and the economy in the Chiquitania, which greatly depend on the forestry, agriculture and livestock sectors. Results are particularly concerning if considering the current development policies promoting frontier expansion. Departmental protected areas inhibited wildfires when strategically established in areas of high risk, even under drought conditions. However, further research is needed to assess their effectiveness accounting for more specific contextual factors. This novel and simple modelling approach can inform fire and land

  20. Increased Wildfire Risk Driven by Climate and Development Interactions in the Bolivian Chiquitania, Southern Amazonia.

    Tahia Devisscher

    Full Text Available Wildfires are becoming increasingly dominant in tropical landscapes due to reinforcing feedbacks between land cover change and more severe dry conditions. This study focused on the Bolivian Chiquitania, a region located at the southern edge of Amazonia. The extensive, unique and well-conserved tropical dry forest in this region is susceptible to wildfires due to a marked seasonality. We used a novel approach to assess fire risk at the regional level driven by different development trajectories interacting with changing climatic conditions. Possible future risk scenarios were simulated using maximum entropy modelling with presence-only data, combining land cover, anthropogenic and climatic variables. We found that important determinants of fire risk in the region are distance to roads, recent deforestation and density of human settlements. Severely dry conditions alone increased the area of high fire risk by 69%, affecting all categories of land use and land cover. Interactions between extreme dry conditions and rapid frontier expansion further increased fire risk, resulting in potential biomass loss of 2.44±0.8 Tg in high risk area, about 1.8 times higher than the estimates for the 2010 drought. These interactions showed particularly high fire risk in land used for 'extensive cattle ranching', 'agro-silvopastoral use' and 'intensive cattle ranching and agriculture'. These findings have serious implications for subsistence activities and the economy in the Chiquitania, which greatly depend on the forestry, agriculture and livestock sectors. Results are particularly concerning if considering the current development policies promoting frontier expansion. Departmental protected areas inhibited wildfires when strategically established in areas of high risk, even under drought conditions. However, further research is needed to assess their effectiveness accounting for more specific contextual factors. This novel and simple modelling approach can

  1. Failure to Redose Antibiotic Prophylaxis in Long Surgery Increases Risk of Surgical Site Infection.

    Kasatpibal, Nongyao; Whitney, Joanne D; Dellinger, E Patchen; Nair, Bala G; Pike, Kenneth C

    Antibiotic prophylaxis is a key component of the prevention of surgical site infection (SSI). Failure to manage antibiotic prophylaxis effectively may increase the risk of SSI. This study aimed to examine the effects of antibiotic prophylaxis on SSI risk. A retrospective cohort study was conducted among patients having general surgery between May 2012 and June 2015 at the University of Washington Medical Center. Peri-operative data extracted from hospital databases included patient and operation characteristics, intra-operative medication and fluid administration, and survival outcome. The effects of antibiotic prophylaxis and potential factors on SSI risk were estimated using multiple logistic regression and were expressed as risk ratios (RRs). A total of 4,078 patients were eligible for analysis. Of these, 180 had an SSI. Mortality rates within and after 30 days were 0.8% and 0.3%, respectively. Improper antibiotic redosing increased the risk of SSI (RR 4.61; 95% confidence interval [CI] 1.33-15.91). Other risk factors were in-patient status (RR 4.05; 95% CI 1.69-9.66), smoking (RR 1.63; 95% CI 1.03-2.55), emergency surgery (RR 1.97; 95% CI 1.26-3.08), colectomy (RR 3.31; 95% CI 1.19-9.23), pancreatectomy (RR 4.52; 95% CI 1.53-13.39), proctectomy (RR 5.02; 95% CI 1.72-14.67), small bowel surgery (RR 6.16; 95% CI 2.13-17.79), intra-operative blood transfusion >500 mL (RR 2.76; 95% CI 1.45-5.26), and multiple procedures (RR 1.40; 95% CI 1.01-1.95). These data demonstrate that failure to redose prophylactic antibiotic during long operations increases the risk of SSI. Strengthening a collaborative surgical quality improvement program may help to eradicate this risk.

  2. Increased risk of stomach and esophageal malignancies in people with AIDS.

    Persson, E Christina; Shiels, Meredith S; Dawsey, Sanford M; Bhatia, Kishor; Anderson, Lesley A; Engels, Eric A

    2012-10-01

    People infected with human immunodeficiency virus (HIV) have an increased risk of some malignancies, but little is known about the effects of infection on risk of cancers of the upper gastrointestinal tract. We evaluated the risks of different histologic and anatomic subtypes of carcinomas and non-Hodgkin lymphomas (NHLs) of the stomach and esophagus in people with acquired immunodeficiency syndrome (AIDS). We analyzed data from the HIV/AIDS Cancer Match Study, which links data collected from 1980 to 2007 for 16 US population-based HIV and AIDS and cancer registries. We compared risks of stomach and esophageal malignancies in people with AIDS (N = 596,955) with those of the general population using standardized incidence ratios (SIRs). We assessed calendar trends using Poisson regression. People with AIDS had increased risks of carcinomas of the esophagus (SIR, 1.69; 95% confidence interval [CI], 1.37-2.07; n = 95) and stomach (SIR, 1.44; 95% CI, 1.17-1.76; n = 96). Risk was increased for esophageal adenocarcinoma (SIR, 1.91; 95% CI, 1.31-2.70) and squamous cell carcinoma (SIR, 1.47; 95% CI, 1.10-1.92). People with AIDS had greater risks of carcinomas of the gastric cardia (SIR, 1.36; 95% CI, 0.83-2.11) and noncardia (SIR, 1.53; 95% CI, 1.12-2.05) than the general population. Although most stomach and esophageal NHLs that developed in people with AIDS were diffuse large B-cell lymphomas, these individuals also had an increased risk of stomach mucosa-associated lymphoid tissue lymphoma (SIR, 5.99; 95% CI, 3.19-10.2; n = 13). The incidence of carcinomas remained fairly constant over time, but rates of NHL decreased from 1980 to 2007 (P(trend) AIDS are at increased risk for developing esophageal and stomach carcinomas and NHLs. Although the incidence of NHL decreased from 1980 to 2007 as treatments for HIV infection improved, HIV-infected individuals face continued risks of esophageal and stomach carcinomas. Copyright © 2012 AGA Institute. Published by Elsevier Inc

  3. Stormwater Volume Control to Prevent Increases in Lake Flooding and Dam Failure Risk

    Potter, K. W.

    2017-12-01

    Urban expansion is not often considered a major factor contributing to dam failure. But if urbanization occurs without mitigation of the hydrologic impacts, the risk of dam failure will increase. Of particular concern are increases in the volume of storm runoff resulting from increases in the extent of impervious surfaces. Storm runoff volumes are not regulated for much the U.S, and where they are, the required control is commonly less than 100%. Unmitigated increases in runoff volume due to urbanization can pose a risk to dams. A recent technical advisory committee of Dane County has recommended that the county require 100% control of stormwater volumes for new developments. The primary motivation was to prevent increases in the water levels in the Yahara Lakes, slowly draining lakes that are highly sensitive to runoff volume. The recommendations included the use of "volume trading" to achieve efficient compliance. Such recommendations should be considered for other slowly draining lakes, including those created by artificial structures.

  4. Effects of epilepsy and selected antiepileptic drugs on risk of myocardial infarction, stroke, and death in patients with or without previous stroke: a nationwide cohort study

    Olesen, Jonas Bjerring; Abildstrøm, Steen Zabell; Erdal, Jesper

    2011-01-01

    Patients with epilepsy have increased morbidity and mortality. We evaluated the risk of myocardial infarction (MI), stroke, and death associated with epilepsy and examined if this risk was modified by treatment with antiepileptic drugs (AEDs).......Patients with epilepsy have increased morbidity and mortality. We evaluated the risk of myocardial infarction (MI), stroke, and death associated with epilepsy and examined if this risk was modified by treatment with antiepileptic drugs (AEDs)....

  5. Increased fracture rate in women with breast cancer: a review of the hidden risk

    Body Jean-Jacques

    2011-08-01

    Full Text Available Abstract Background Women with breast cancer, particularly individuals diagnosed at a relatively early age, have an increased incidence of fractures. Fractures can have serious clinical consequences including the need for major surgery, increased morbidity and mortality, increased cost of disease management, and reduced quality of life for patients. The primary cause of the increased fracture risk appears to be an accelerated decrease in bone mineral density (BMD resulting from the loss of estrogenic signaling that occurs with most treatments for breast cancer, including aromatase inhibitors. However, factors other than BMD levels alone may influence treatment decisions to reduce fracture risk in this setting. Our purpose is to review current evidence for BMD loss and fracture risk during treatment for breast cancer and discuss pharmacologic means to reduce this risk. Results Fracture risk during treatment for breast cancer may be influenced by the rate of BMD loss and the consequent rapid alterations in bone microarchitecture, in addition to the established fracture risk factors in postmenopausal osteoporosis. The rapid decrease in BMD during adjuvant chemoendocrine therapy for breast cancer may necessitate more aggressive pharmacotherapy than is indicated for healthy postmenopausal women who develop osteoporosis. Over the last few years, clinical trials have established the effectiveness of bisphosphonates and other antiresorptive agents to preserve BMD during adjuvant therapy for early breast cancer. In addition, some bisphosphonates (eg, zoledronic acid may also delay disease recurrence in women with hormone-responsive tumors, thereby providing an adjuvant benefit in addition to preserving BMD and potentially preventing fractures. Conclusions It is likely that a combined fracture risk assessment (eg, as in the WHO FRAX algorithm will more accurately identify both women with postmenopausal osteoporosis and women with breast cancer who require

  6. Hypoglycemia is associated with increased risk for brain injury and adverse neurodevelopmental outcome in neonates at risk for encephalopathy.

    Tam, Emily W Y; Haeusslein, Laurel A; Bonifacio, Sonia L; Glass, Hannah C; Rogers, Elizabeth E; Jeremy, Rita J; Barkovich, A James; Ferriero, Donna M

    2012-07-01

    To investigate the contribution of hypoglycemia in the first 24 hours after birth to brain injury in term newborns at risk for neonatal encephalopathy. A prospective cohort of 94 term neonates born between 1994 and 2010 with early postnatal brain magnetic resonance imaging studies were analyzed for regions of brain injury. Neurodevelopmental outcome was assessed at 1 year of age. Hypoglycemia (glucose encephalopathy with increased corticospinal tract injury and adverse motor and cognitive outcomes. Copyright © 2012 Mosby, Inc. All rights reserved.

  7. Stress-activated miR-21/miR-21* in hepatocytes promotes lipid and glucose metabolic disorders associated with high-fat diet consumption.

    Calo, Nicolas; Ramadori, Pierluigi; Sobolewski, Cyril; Romero, Yannick; Maeder, Christine; Fournier, Margot; Rantakari, Pia; Zhang, Fu-Ping; Poutanen, Matti; Dufour, Jean-François; Humar, Bostjan; Nef, Serge; Foti, Michelangelo

    2016-11-01

    miR-21 is an oncomir highly upregulated in hepatocellular carcinoma and in early stages of liver diseases characterised by the presence of steatosis. Whether upregulation of miR-21 contributes to hepatic metabolic disorders and their progression towards cancer is unknown. This study aims at investigating the role of miR-21/miR-21* in early stages of metabolic liver disorders associated with diet-induced obesity (DIO). Constitutive miR-21/miR-21* knockout (miR21KO) and liver-specific miR-21/miR-21* knockout (LImiR21KO) mice were generated. Mice were then fed with high-fat diet (HFD) and alterations of the lipid and glucose metabolism were investigated. Serum and ex vivo explanted liver tissue were analysed. Under normal breeding conditions and standard diet, miR-21/miR-21* deletion in mice was not associated with any detectable phenotypic alterations. However, when mice were challenged with an obesogenic diet, glucose intolerance, steatosis and adiposity were improved in mice lacking miR-21/miR-21* . Deletion of miR-21/miR-21* specifically in hepatocytes led to similar improvements in mice fed an HFD, indicating a crucial role for hepatic miR-21/miR-21* in metabolic disorders associated with DIO. Further molecular analyses demonstrated that miR-21/miR-21* deletion in hepatocytes increases insulin sensitivity and modulates the expression of multiple key metabolic transcription factors involved in fatty acid uptake, de novo lipogenesis, gluconeogenesis and glucose output. Hepatic miR-21/miR-21* deficiency prevents glucose intolerance and steatosis in mice fed an obesogenic diet by altering the expression of several master metabolic regulators. This study points out miR-21/miR-21 * as a potential therapeutic target for non-alcoholic fatty liver disease and the metabolic syndrome. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  8. Estimation of transient increases in bleeding risk associated with physical activity in children with haemophilia

    Latimer Jane

    2008-06-01

    Full Text Available Abstract Background Although it is widely appreciated that vigorous physical activity can increase the risk of bleeding episodes in children with haemophilia, the magnitude of the increase in risk is not known. Accurate risk estimates could inform decisions made by children with haemophilia and their parents about participation in physical activity and aid the development of optimal prophylactic schedules. The aim of this study is to provide an accurate estimate of the risks of bleeding associated with vigorous physical activity in children with haemophilia. Methods/Design The study will be a case-crossover study nested within a prospective cohort study. Children with moderate or severe haemophilia A or B, recruited from two paediatric haematology departments in Australia, will participate in the study. The child, or the child's parent or guardian, will report bleeding episodes experienced over a 12-month period. Following a bleeding episode, the participant will be interviewed by telephone about exposures to physical activity in the case period (8 hours before the bleed and 2 control periods (an 8 hour period at the same time on the day preceding the bleed and an 8 hour period two days preceding the bleed. Conditional logistic regression will be used to estimate the risk of participating in vigorous physical activity from measures of exposure to physical activity in the case and control periods. Discussion This case-control study will provide estimates of the risk of participation in vigorous physical activity in children with haemophilia.

  9. Joint modeling of genetically correlated diseases and functional annotations increases accuracy of polygenic risk prediction.

    Yiming Hu

    2017-06-01

    Full Text Available Accurate prediction of disease risk based on genetic factors is an important goal in human genetics research and precision medicine. Advanced prediction models will lead to more effective disease prevention and treatment strategies. Despite the identification of thousands of disease-associated genetic variants through genome-wide association studies (GWAS in the past decade, accuracy of genetic risk prediction remains moderate for most diseases, which is largely due to the challenges in both identifying all the functionally relevant variants and accurately estimating their effect sizes. In this work, we introduce PleioPred, a principled framework that leverages pleiotropy and functional annotations in genetic risk prediction for complex diseases. PleioPred uses GWAS summary statistics as its input, and jointly models multiple genetically correlated diseases and a variety of external information including linkage disequilibrium and diverse functional annotations to increase the accuracy of risk prediction. Through comprehensive simulations and real data analyses on Crohn's disease, celiac disease and type-II diabetes, we demonstrate that our approach can substantially increase the accuracy of polygenic risk prediction and risk population stratification, i.e. PleioPred can significantly better separate type-II diabetes patients with early and late onset ages, illustrating its potential clinical application. Furthermore, we show that the increment in prediction accuracy is significantly correlated with the genetic correlation between the predicted and jointly modeled diseases.

  10. Social and economic factors of the natural risk increasing: estimation of the Russian regions

    E. Petrova

    2004-01-01

    Full Text Available This study is an attempt to assess quantitatively social and economic factors that determine vulnerability of Russian regions to natural risk, to trace the space differences of the considered factors, and to group the regions by their similarity. In order to indicate the regional differences in social and economic development, equipment condition, dangerous substances accumulation, and social trouble four the most suitable parameters were estimated, including the per capita production of Gross Regional Product (GRP, capital consumption, volume of total toxic waste, and crime rate. Increase of the first parameter causes vulnerability reducing, the increase of the last three causes its increasing. Using multidimensional cluster analysis five types of regions were found for Russia according to similarity of the considered parameters. These types are characterized with higher value of a single (rarely two chosen parameter, which seems to be sufficient enough to affect natural risks increasing in these regions in near future. Only few regions belonging to the fifth type proved to have rather high value of GRP and relatively low values of the other parameters. The negative correlation was found between a number of natural disasters (ND and the per capita GRP in case when some parameters reached anomalously high value. The distinctions between regions by prevailing different parameters, which result in natural risk increasing, help risk management to find directions where to focus on.

  11. Increased Default Mode Network Connectivity in Individuals at High Familial Risk for Depression.

    Posner, Jonathan; Cha, Jiook; Wang, Zhishun; Talati, Ardesheer; Warner, Virginia; Gerber, Andrew; Peterson, Bradley S; Weissman, Myrna

    2016-06-01

    Research into the pathophysiology of major depressive disorder (MDD) has focused largely on individuals already affected by MDD. Studies have thus been limited in their ability to disentangle effects that arise as a result of MDD from precursors of the disorder. By studying individuals at high familial risk for MDD, we aimed to identify potential biomarkers indexing risk for developing MDD, a critical step toward advancing prevention and early intervention. Using resting-state functional connectivity MRI (rs-fcMRI) and diffusion MRI (tractography), we examined connectivity within the default mode network (DMN) and between the DMN and the central executive network (CEN) in 111 individuals, aged 11-60 years, at high and low familial risk for depression. Study participants were part of a three-generation longitudinal, cohort study of familial depression. Based on rs-fcMRI, individuals at high vs low familial risk for depression showed increased DMN connectivity, as well as decreased DMN-CEN-negative connectivity. These findings remained significant after excluding individuals with a current or lifetime history of depression. Diffusion MRI measures based on tractography supported the findings of decreased DMN-CEN-negative connectivity. Path analyses indicated that decreased DMN-CEN-negative connectivity mediated a relationship between familial risk and a neuropsychological measure of impulsivity. Our findings suggest that DMN and DMN-CEN connectivity differ in those at high vs low risk for depression and thus suggest potential biomarkers for identifying individuals at risk for developing MDD.

  12. Does maternal psychopathology increase the risk of pre-schooler obesity? A systematic review.

    Benton, Pree M; Skouteris, Helen; Hayden, Melissa

    2015-04-01

    The preschool years may be a critical period for child obesity onset; however, literature examining obesity risk factors to date has largely focused on school-aged children. Several links have been made between maternal depression and childhood obesity risks; however, other types of maternal psychopathology have been widely neglected. The aim of the present review was to systematically identify articles that examined relationships between maternal psychopathology variables, including depressive and anxiety symptoms, self-esteem and body dissatisfaction, and risks for pre-schooler obesity, including weight outcomes, physical activity and sedentary behaviour levels, and nutrition/diet variables. Twenty articles meeting review criteria were identified. Results showed positive associations between maternal depressive symptoms and increased risks for pre-schooler obesity in the majority of studies. Results were inconsistent depending on the time at which depression was measured (i.e., antenatal, postnatal, in isolation or longitudinally). Anxiety and body dissatisfaction were only measured in single studies; however, both were linked to pre-schooler obesity risks; self-esteem was not measured by any studies. We concluded that maternal depressive symptoms are important to consider when assessing risks for obesity in preschool-aged children; however, more research is needed examining the impact of other facets of maternal psychopathology on obesity risk in pre-schoolers. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Increasing stress on disaster-risk finance due to large floods

    Jongman, Brenden; Hochrainer-Stigler, Stefan; Feyen, Luc; Aerts, Jeroen C. J. H.; Mechler, Reinhard; Botzen, W. J. Wouter; Bouwer, Laurens M.; Pflug, Georg; Rojas, Rodrigo; Ward, Philip J.

    2014-04-01

    Recent major flood disasters have shown that single extreme events can affect multiple countries simultaneously, which puts high pressure on trans-national risk reduction and risk transfer mechanisms. So far, little is known about such flood hazard interdependencies across regions and the corresponding joint risks at regional to continental scales. Reliable information on correlated loss probabilities is crucial for developing robust insurance schemes and public adaptation funds, and for enhancing our understanding of climate change impacts. Here we show that extreme discharges are strongly correlated across European river basins. We present probabilistic trends in continental flood risk, and demonstrate that observed extreme flood losses could more than double in frequency by 2050 under future climate change and socio-economic development. We suggest that risk management for these increasing losses is largely feasible, and we demonstrate that risk can be shared by expanding risk transfer financing, reduced by investing in flood protection, or absorbed by enhanced solidarity between countries. We conclude that these measures have vastly different efficiency, equity and acceptability implications, which need to be taken into account in broader consultation, for which our analysis provides a basis.

  14. Mi-spillet

    Larsen, Lea Lund; Hejlesen, Stine

    2003-01-01

    MI-spillet er et undervisningsspil til folkeskolens mellemtrin og udskolingen. Spillet omformer Howard Gardners teori om de mange intelligenser til et praktisk og håndgribeligt værktøj til brug i folkeskolen. Spillet indeholder et undervisningsmateriale bestående af lærervejledning og kopimappe...... emnebaseret eller tværfagligt arbejde. Alt materialet ligger samlet på en cd-rom, hvorfra materialet printes. Skolen kan derfor ved køb af én cd-rom printe og producere et ubegrænset antal spil. Cd-rommen indeholder: 1. Lærervejledning 2. MI-spillet * Gulvpladerne * Spørgsmål til spillet * Bilag til...

  15. Delay in blood sampling for routine newborn screening is associated with increased risk of schizophrenia.

    Nordentoft, Merete; Larsen, Janne Tidselbak; Pedersen, Carsten Bøcker; Sørensen, Holger Jelling; Hollegaard, Mads Villiam; Hougaard, David Michael; Mortensen, Preben Bo; Petersen, Liselotte

    2015-03-01

    The Danish Neonatal Screening Biobank, containing dried blood spot samples from all newborn in Denmark, is a unique source of data that can be utilized for analyses of genetic and environmental exposures related to schizophrenia and other mental disorders. In previous analyses, we have found that early and late blood sampling, compared to sampling at day 5, was associated with increased risk of schizophrenia. As delay in sampling of blood for neonatal screening cannot in itself influence the risk of schizophrenia, it must be seen as a proxy for unknown underlying causes responsible for this association. Therefore, we investigated whether the increased risk can be explained by other risk factors for schizophrenia. A case-control design was applied. A total of 846 cases with schizophrenia were selected from the Danish Psychiatric Case Register. One control was selected for each case, matched on sex and exact date of birth. Both early and late blood sampling was associated with increased risk for schizophrenia. Compared to blood sampling at day 5, sampling at days 0 to 4 after birth was associated with an incidence rate ratio (IRR) of 1.46 (95% CI 1.15-1.87) for development of schizophrenia, and sampling at days 6 to 9 and at days 10 to 53 was associated with an IRR of 1.5 (95% CI 1.13-1.98) and 3.00 (95% CI 1.59-5.67), respectively. After adjusting the estimates for place of birth, both parents' psychiatric illness, maternal and paternal age, parents' country of origin, child admission, and parental education and income, the estimates were slightly different. Thus, blood collection at 0-4days was associated with an IRR of 1.27 (95% CI 0.94-1.71), 6-9days 1.31 (95% CI 0.94-1.84) and 10+days 3.52 (95% CI 1.50 to 8.24). After adjusting risk estimates for well-known risk factors, delay in sampling of blood for neonatal screening was associated with unexplained increased risk of schizophrenia. Thus, a key finding is that age at test is a proxy for unobserved risk factors

  16. Do hypertension and diuretic treatment in pregnancy increase the risk of schizophrenia in offspring?

    Sørensen, Holger J; Mortensen, Erik L; Reinisch, June M

    2003-01-01

    OBJECTIVE: Diuretics prescribed after the first trimester for treatment of hypertension in pregnant women may interfere with normal plasma volume expansion and cause volume depletion. The authors hypothesized that prenatal exposure to diuretics and maternal hypertension might disrupt fetal...... neurodevelopment and increase the risk of schizophrenia in offspring. METHOD: Using data from the Copenhagen Perinatal Cohort of individuals born between 1959 and 1961, the authors studied the relationship of maternal hypertension and diuretic treatment during pregnancy with the risk of schizophrenia (ICD-8 code...... treatment during pregnancy. RESULTS: In a risk set of 7,866 individuals, 84 cases of schizophrenia were found (1.1% prevalence). Logistic multiple regression analysis identified the following independent risk factors: maternal hypertension (odds ratio=1.69 [95% CI=1.02-2.80]), diuretic treatment...

  17. Allergic asthma is associated with increased risk of infections requiring antibiotics

    Woehlk, Christian; von Bülow, Anna; Kriegbaum, Margit

    2018-01-01

    : To investigate allergy as a risk factor for respiratory infections requiring antibiotics based on register data from a nationwide population of patients with asthma. METHODS: A register-based prospective follow-up study was performed using the Danish prescription database. In the inclusion period from 2010......BACKGROUND: Viral infection and allergy have been identified as major risk factors for exacerbation in asthma, especially in the presence of both. However, whether patients with allergic asthma are more susceptible to respiratory infections requiring antibiotics remains unknown. OBJECTIVE...... asthma was associated with an increased risk of filling at least 2 antibiotic prescriptions per year compared with nonallergic asthma (odds ratio 1.28, 95% confidence interval 1.24-1.33, P effect of immunotherapy against the risk...

  18. Do hypertension and diuretic treatment in pregnancy increase the risk of schizophrenia in offspring?

    Sørensen, Holger J; Mortensen, Erik L; Reinisch, June M

    2003-01-01

    treatment during pregnancy. RESULTS: In a risk set of 7,866 individuals, 84 cases of schizophrenia were found (1.1% prevalence). Logistic multiple regression analysis identified the following independent risk factors: maternal hypertension (odds ratio=1.69 [95% CI=1.02-2.80]), diuretic treatment...... neurodevelopment and increase the risk of schizophrenia in offspring. METHOD: Using data from the Copenhagen Perinatal Cohort of individuals born between 1959 and 1961, the authors studied the relationship of maternal hypertension and diuretic treatment during pregnancy with the risk of schizophrenia (ICD-8 code...... 295) in the offspring. Prenatal medical information was linked to the Danish National Psychiatric Register. The effects of maternal hypertension and diuretic treatment were adjusted for the maternal history of schizophrenia, social status of the family breadwinner, mother's age, and concomitant drug...

  19. Cost effectiveness of withdrawal of fall-risk-increasing drugs in geriatric outpatients.

    van der Velde, Nathalie; Meerding, Willen Jan; Looman, Caspar W; Pols, Huibert A P; van der Cammen, Tischa J M

    2008-01-01

    Withdrawal of fall-risk-increasing drugs has been proven to be effective in older persons. However, given the enormous rise in healthcare costs in recent decades, the effect of such withdrawals on healthcare costs also needs to be considered. Within a common geriatric outpatient population, patients with a history of falls were assessed for falls risk (n = 139). Fall-risk-increasing drugs were withdrawn when appropriate (n = 75). All participants had a 2-month follow-up for fall incidents. The number of prevented falls was calculated using a loglinear regression model. The savings on health expenditures as a result of prevented injuries (estimated from a literature review) and reduced consumption of pharmaceuticals were compared with the intervention costs. After adjustment for confounders, drug withdrawal resulted in a falls risk reduction of 0.89 (95% CI 0.33, 0.98) per patient compared with the non-withdrawal group. Net cost savings were euro1691 (95% CI 662, 2181) per patient in the cohort. This resulted in a cost saving of euro491 (95% CI 465, 497) per prevented fall. Withdrawal of fall-risk-increasing drugs generates significant cost savings. Extrapolation of these findings to a national scale results in an estimated reduction of euro60 million in healthcare expenditures, that is, 15% of fall-related health costs.

  20. Increased Risk of Tics in Children Infected with Enterovirus: A Nationwide Population-Based Study.

    Lin, Jiun-Nong; Lin, Cheng-Li; Yen, Hung-Rong; Yang, Chi-Hui; Lai, Chung-Hsu; Lin, Hsi-Hsun; Kao, Chia-Hung

    2017-05-01

    Both tics and enterovirus (EV) infections are common in children. The association between EV infections and tics has been seldom evaluated. The aim of this study was to evaluate the risk of diagnosed tics after EV infections in children. A nationwide retrospective cohort study was conducted to determine the risk of tics after EV infections by analyzing data from the National Health Insurance Research Database in Taiwan. Children aged tics, death, loss to follow-up, withdrawal from the insurance system, or December 31, 2008. A total of 282,321 EV-infected and 282,317 non-EV-infected children were included in this study. The mean age was 2.39 years in both cohorts. The overall incidences of tics were 9.12 and 6.21 per 10,000 person-years in the EV-infected and non-EV-infected cohorts, respectively. Children with EV infection were significantly associated with an increased risk of tics compared with those without EV infection (adjusted hazard ratio, 1.38; 95% confidence interval, 1.27-1.5). Multivariable analyses showed that boys, children living in urbanized areas, children whose parents had white-collar jobs, and children with allergic rhinitis or bronchial asthma exhibited a significantly increased risk of tics. This study revealed an increased risk of tics after EV infection in children.

  1. Alcohol Abuse Increases Rebleeding Risk and Mortality in Patients with Non-variceal Upper Gastrointestinal Bleeding.

    Kärkkäinen, Jussi M; Miilunpohja, Sami; Rantanen, Tuomo; Koskela, Jenni M; Jyrkkä, Johanna; Hartikainen, Juha; Paajanen, Hannu

    2015-12-01

    No current data are available on rebleeding and mortality risk in patients who use alcohol excessively and are admitted for non-variceal upper gastrointestinal bleeding (NVUGIB). This information could help in planning interventions and follow-up protocols for these patients. This study provides contemporary data on the long-term outcome after first-time NVUGIB in alcohol abusers (AAs) compared to non-abusers (NAs). Consecutive patients hospitalized for their first acute gastrointestinal bleeding from 2009 through 2011 were retrospectively recorded and categorized as AA or NA. Risk factors for one-year mortality and rebleeding were identified, and patients were further monitored for long-term mortality until 2015. Alcohol abuse was identified in 19.7% of patients with NVUGIB (n = 518). The one-year rebleeding rate was 16.7% in AAs versus 9.1% in NAs (P = 0.027). Alcohol abuse was associated with a twofold increase in rebleeding risk (P = 0.025); the risk especially increased 6 months after the initial bleeding. The study groups did not differ significantly in 30-day (6.0%) or one-year mortality rates (20.5%). However, there was a tendency for higher overall mortality in AAs than NAs after adjustment of comorbidities. AAs with NVUGIB are at high risk of rebleeding, and mortality is increased in AA patients. A close follow-up strategy and long-term proton pump inhibitor therapy are recommended for AA patients with peptic ulcer or esophagitis.

  2. Assay reproducibility in clinical studies of plasma miRNA.

    Jonathan Rice

    Full Text Available There are increasing reports of plasma miRNAs as biomarkers of human disease but few standards in methodologic reporting, leading to inconsistent data. We systematically reviewed plasma miRNA studies published between July 2013-June 2014 to assess methodology. Six parameters were investigated: time to plasma extraction, methods of RNA extraction, type of miRNA, quantification, cycle threshold (Ct setting, and methods of statistical analysis. We compared these data with a proposed standard methodologic technique. Beginning with initial screening for 380 miRNAs using microfluidic array technology and validation in an additional cohort of patients, we compared 11 miRNAs that exhibited differential expression between 16 patients with benign colorectal neoplasms (advanced adenomas and 16 patients without any neoplasm (controls. Plasma was isolated immediately, 12, 24, 48, or 72 h following phlebotomy. miRNA was extracted using two different techniques (Trizol LS with pre-amplification or modified miRNeasy. We performed Taqman-based RT-PCR assays for the 11 miRNAs with subsequent analyses using a variable Ct setting or a fixed Ct set at 0.01, 0.03, 0.05, or 0.5. Assays were performed in duplicate by two different operators. RNU6 was the internal reference. Systematic review yielded 74 manuscripts meeting inclusion criteria. One manuscript (1.4% documented all 6 methodological parameters, while < 5% of studies listed Ct setting. In our proposed standard technique, plasma extraction ≤12 h provided consistent ΔCt. miRNeasy extraction yielded higher miRNA concentrations and fewer non-expressed miRNAs compared to Trizol LS (1/704 miRNAs [0.14%] vs 109/704 miRNAs [15%], not expressed, respectively. A fixed Ct bar setting of 0.03 yielded the most reproducible data, provided that <10% miRNA were non-expressed. There was no significant intra-operator variability. There was significant inter-operator variation using Trizol LS extraction, while this was

  3. Antiphospholipid antibody-induced miR-146a-3p drives trophoblast interleukin-8 secretion through activation of Toll-like receptor 8.

    Gysler, Stefan M; Mulla, Melissa J; Guerra, Marta; Brosens, Jan J; Salmon, Jane E; Chamley, Lawrence W; Abrahams, Vikki M

    2016-07-01

    What is the role of microRNAs (miRs) in antiphospholipid antibody (aPL)-induced trophoblast inflammation? aPL-induced up-regulation of trophoblast miR-146a-3p is mediated by Toll-like receptor 4 (TLR4), and miR-146a-3p in turn drives the cells to secrete interleukin (IL)-8 by activating the RNA sensor, TLR8. Obstetric antiphospholipid syndrome (APS) is an autoimmune disorder characterized by circulating aPL and an increased risk of pregnancy complications. We previously showed that aPL recognizing beta2 glycoprotein I (β2GPI) elicit human first trimester trophoblast secretion of IL-8 by activating TLR4. Since some miRs control TLR responses, their regulation in trophoblast cells by aPL and functional role in the aPL-mediated inflammatory response was investigated. miRs can be released from cells via exosomes, and therefore, miR exosome expression was also examined. A panel of miRs was selected based on their involvement with TLR signaling: miR-9; miR-146a-5p and its isomiR, miR-146a-3p; miR-155, miR-210; and Let-7c. Since certain miRs can activate the RNA sensor, TLR8, this was also investigated. For in vitro studies, the human first trimester extravillous trophoblast cell line, HTR8 was studied. HTR8 cells transfected to express a TLR8 dominant negative (DN) were also used. Plasma was evaluated from pregnant women who have aPL, either with or without systemic lupus erythematous (SLE) (n = 39); SLE patients without aPL (n = 30); and healthy pregnant controls (n = 20). Trophoblast HTR8 wildtype and TLR8-DN cells were incubated with or without aPL (mouse anti-human β2GPI mAb) for 48-72 h. HTR8 cells were also treated with or without aPL in the presence and the absence of a TLR4 antagonist (lipopolysaccharide from Rhodobacter sphaeroides; LPS-RS), specific miR inhibitors or specific miR mimics. miR expression levels in trophoblast cells, trophoblast-derived exosomes and exosomes isolated from patient plasma were measured by qPCR. Trophoblast IL-8 secretion was

  4. Downregulation of miR-99a/let-7c/miR-125b miRNA cluster predicts clinical outcome in patients with unresected malignant pleural mesothelioma.

    Truini, Anna; Coco, Simona; Nadal, Ernest; Genova, Carlo; Mora, Marco; Dal Bello, Maria Giovanna; Vanni, Irene; Alama, Angela; Rijavec, Erika; Biello, Federica; Barletta, Giulia; Merlo, Domenico Franco; Valentino, Alessandro; Ferro, Paola; Ravetti, Gian Luigi; Stigliani, Sara; Vigani, Antonella; Fedeli, Franco; Beer, David G; Roncella, Silvio; Grossi, Francesco

    2017-09-15

    Malignant pleural mesothelioma (MPM) is an aggressive tumor with a dismal overall survival (OS) and to date no molecular markers are available to guide patient management. This study aimed to identify a prognostic miRNA signature in MPM patients who did not undergo tumor resection. Whole miRNA profiling using a microarray platform was performed using biopsies on 27 unresected MPM patients with distinct clinical outcome: 15 patients had short survival (OS36 months). Three prognostic miRNAs (mir-99a, let-7c, and miR-125b) encoded at the same cluster (21q21) were selected for further validation and tested on publicly available miRNA sequencing data from 72 MPM patients with survival data. A risk model was built based on these 3 miRNAs that was validated by quantitative PCR in an independent set of 30 MPM patients. High-risk patients had shorter median OS (7.6 months) as compared with low-risk patients (median not reached). In the multivariate Cox model, a high-risk score was independently associated with shorter OS (HR=3.14; 95% CI, 1.18-8.34; P=0.022). Our study identified that the downregulation of the miR-99a/let-7/miR-125b miRNA cluster predicts poor outcome in unresected MPM.

  5. Does topical isotretinoin exposure during pregnancy increase the risk of congenital malformations?

    İsmail Yılmaz

    2015-06-01

    Full Text Available A 34-year-old patient learned that she was 7 weeks pregnant while she was using topical isotretinoin + erythromycin gel for acne treatment and referred to Izmir Katip Celebi University Teratology Information Service for information regarding the risk of teratogenicity. Systemic use of isotretinoin is well-known for its teratogenic effects and case reports suggesting possible teratogenic effects regarding topical exposure to retinoids in pregnancy exist in the literature. However, findings reported in four prospective controlled studies do not suggest an increased congenital malformation risk in case of inadvertent exposure during pregnancy. This manuscript aims to give a summary and evaluation of available data for counseling pregnant patients regarding the possible teratogenic risk of inadvertent topical isotretinoin exposure during pregnancy. It also aims to emphasize the importance of increasing communication between pregnant patients, clinicians and teratology information services for the benefit of mother and unborn.

  6. Facilitators and Challenges in Psychosocial Adaptation to Being at Increased Familial Risk of Breast Cancer.

    Heiniger, Louise; Price, Melanie A; Charles, Margaret; Butow, Phyllis N

    2015-12-01

    Little is known about the process of psychosocial adaptation to familial risk in tested and untested individuals at increased familial risk of cancer. This paper presents findings from a qualitative study of 36 women participating in the Kathleen Cuningham Consortium for Research into Familial Breast cancer (kConFab) Psychosocial study. Facilitators and challenges in psychosocial adaptation were identified through semi-structured interviews. The women, who were either tested (carriers or non-carriers of breast cancer susceptibility mutations) or untested (ineligible for testing or eligible but delayed or declined testing), described personal, support network and healthcare characteristics that impacted on the adaptation process. Challenges in one domain could be overcome by facilitators in other domains and key differences relating to whether women had undergone testing, or not, were identified. Tested and untested women with an increased familial risk of breast cancer may benefit from support tailored to their mutation testing status in order to enhance adaptation.

  7. Anticipating divine protection? Reminders of god can increase nonmoral risk taking.

    Kupor, Daniella M; Laurin, Kristin; Levav, Jonathan

    2015-04-01

    Religiosity and participation in religious activities have been linked with decreased risky behavior. In the current research, we hypothesized that exposure to the concept of God can actually increase people's willingness to engage in certain types of risks. Across seven studies, reminders of God increased risk taking in nonmoral domains. This effect was mediated by the perceived danger of a risky option and emerged more strongly among individuals who perceive God as a reliable source of safety and protection than among those who do not. Moreover, in an eighth study, when participants were first reminded of God and then took a risk that produced negative consequences (i.e., when divine protection failed to materialize), participants reported feeling more negatively toward God than did participants in the same situation who were not first reminded of God. This research contributes to an understanding of the divergent effects that distinct components of religion can exert on behavior. © The Author(s) 2015.

  8. Enduring increased risk of developing depression and mania in patients with dementia

    Nilsson, Flemming Mørkeberg; Kessing, Lars Vedel; Sørensen, Tine Møller

    2002-01-01

    OBJECTIVE: To investigate the time relation between dementia and major affective disorders (major depression and mania). METHODS: Register linkage study of the Danish Hospital Register and the Danish Psychiatric Central Research Register, to establish study cohorts of patients with dementia...... and control groups (osteoarthritis or diabetes) on first discharge from hospital. Follow up of cohorts was for up to 21 years. Hazard of death was allowed for by the use of competing risks models. RESULTS: Patients with dementia had an increased risk of being admitted to hospital for major depression or mania...... during the course of the illness. The incidence remained elevated throughout the rest of the patient's life. CONCLUSIONS: Patients with dementia have an increased risk of developing depression or mania. Proper treatment of affective disorders in patients with dementia is important in reducing suffering...

  9. Increasing awareness in African American BSN students of the health risks of obesity.

    Williamson, Wanda; Kautz, Donald D

    2013-01-01

    This paper reports on the perceived effectiveness of a program to increase awareness of the health risks of obesity among African-American students. Thirty (n = 30) senior level Bachelor of Science in Nursing students attending a Historically Black College and University (HBCU) took a knowledge test, then participated in an hour-long educational session on obesity. Following the session, the students completed a 10-item post-test to evaluate the effectiveness of the program in increasing awareness of obesity as a risk for heart disease and diabetes. The findings suggested a need to further educate African-American students on the consequences of obesity as well as recommendations to advance the science of personal and family risk awareness in nursing students.

  10. Prenatal Maternal Smoking and Increased Risk for Tourette Syndrome and Chronic Tic Disorders.

    Browne, Heidi A; Modabbernia, Amirhossein; Buxbaum, Joseph D; Hansen, Stefan N; Schendel, Diana E; Parner, Erik T; Reichenberg, Abraham; Grice, Dorothy E

    2016-09-01

    We assessed the role of prenatal maternal smoking in risk for Tourette syndrome and chronic tic disorder (TS/CT) and pediatric-onset obsessive-compulsive disorder (OCD). In an analysis of 73,073 singleton pregnancies from the Danish National Birth Cohort, we calculated incidence rates (IR) per 1,000 person-year for TS/CT and OCD. We then determined crude and adjusted hazard ratios and 95% CIs associated with prenatal maternal smoking, considering smoking as a dichotomous (yes/no) variable or a stratified variable (no smoking, light smoking, and heavy smoking [≥10 cigarettes/day]). Additional analyses examined the effect of maternal smoking on risk for TS/CT with other comorbid psychiatric conditions. In final adjusted analyses, heavy smoking was associated with a 66% increased risk for TS/CT (adjusted hazard ratio = 1.66, 95% CI = 1.17-2.35). In addition, heavy smoking was associated with a 2-fold increased risk for TS/CT with comorbid attention-deficit/hyperactivity disorder (ADHD), and both light and heavy smoking were associated with a more than 2-fold increased risk for TS/CT with any non-ADHD psychiatric comorbidity. Our parallel analyses of pediatric-onset OCD were likely underpowered but showed similar relationships. Prenatal maternal smoking was associated with increased risk for TS/CT as well as TS/CT with comorbid psychiatric conditions, even after adjustment for several important variables, including maternal psychiatric history, socioeconomic status, and partner smoking. Our findings point to a pathway linking prenatal tobacco exposure and altered brain development to TS/CT. Copyright © 2016 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

  11. Prediabetes Is Associated with an Increased Risk of Testosterone Deficiency, Independent of Obesity and Metabolic Syndrome

    Ho, Chen-Hsun; Yu, Hong-Jeng; Wang, Chih-Yuan; Jaw, Fu-Shan; Hsieh, Ju-Ton; Liao, Wan-Chung; Pu, Yeong-Shiau; Liu, Shih-Ping

    2013-01-01

    Objective The association between type 2 diabetes and low testosterone has been well recognized. However, testosterone levels in men with prediabetes have been rarely reported. We aimed to investigate whether prediabetes was associated with an increased risk of testosterone deficiency. Methods This study included 1,306 men whose sex hormones was measured during a medical examination. Serum total testosterone and sex hormone-binding globulin were measured; free and bioavailable testosterone concentrations were calculated by Vermeulen’s formula. Prediabetes was defined by impaired fasting glucose (IFG), impaired postprandial glucose (IPG), or glycated hemoglobin (HbA1c) 5.7%-6.4%. Logistic regression was performed to obtain the odds ratios (OR) for subnormal total testosterone (prediabetic and diabetic men compared with normoglycemic individuals, while adjusting for age, BMI, waist circumference, and metabolic syndrome (MetS). Results Normoglycemia, prediabetes, and diabetes were diagnosed in 577 (44.2%), 543 (41.6%), and 186 (14.2%) men, respectively. Prediabetes was associated with an increased risk of subnormal total testosterone compared to normoglycemic individuals (age-adjusted OR=1.87; 95%CI=1.38-2.54). The risk remained significant in all multivariate analyses. After adjusting for MetS, the OR in prediabetic men equals that of diabetic patients (1.49 versus 1.50). IFG, IPG, and HbA1c 5.7%-6.4% were all associated with an increased risk of testosterone deficiency, with different levels of significance in multivariate analyses. However, neither prediabetes nor diabetes was associated with subnormal free testosterone in multivariate analyses. Conclusions Prediabetes is associated with an increased risk of testosterone deficiency, independent of obesity and MetS. After adjusting for MetS, the risk equals that of diabetes. Our data suggest that testosterone should be measured routinely in men with prediabetes. PMID:24069277

  12. Increased risk of breast cancer in splenectomized patients undergoing radiation therapy for Hodgkin's disease

    Chung, Chung T.; Bogart, Jeffrey A.; Adams, James F.; Sagerman, Robert H.; Numann, Patricia J.; Tassiopoulos, Apostolos; Duggan, David B.

    1997-01-01

    Purpose: Second malignancies have been reported among patients who were treated by radiation therapy or chemotherapy alone or in combination. Studies have implied an increased risk of breast cancer in women who received radiotherapy as part of their treatment for Hodgkin's disease. This review was performed to determine if there is an association between splenectomy and subsequent breast cancer. Methods and Materials: One hundred and thirty-six female patients with histologically proven Hodgkin's disease were seen in the Division of Radiation Oncology between 1962 and 1985. All patients received mantle or mediastinal irradiation as part of their therapy. The risk of breast cancer was assessed and multiple linear regression analysis was performed on the following variables: patient age, stage, dose and extent of radiation field, time after completing radiation therapy, splenectomy, and chemotheraphy. Results: Breast cancer was observed in 11 of 74 splenectomized patients and in none of 62 patients not splenectomized. The mean follow-up was 13 years in splenectomized patients and 16 years, 7 months in nonsplenectomized patients. Nine patients developed invasive breast cancer and two developed ductal carcinoma in situ. Splenectomy was the only variable independently associated with an increased risk of breast cancer (p < 0.005) in multiple linear regression analysis; age, latency, and splenectomy considered together were also associated with an increased risk of breast cancer (p < 0.01). Conclusion: Our data show an increased risk of breast cancer in splenectomized patients who had treatment for Hodgkin's disease. A multiinstitutional survey may better define the influence of splenectomy relative to developing breast cancer in patients treated for Hodgkin's disease. The risk of breast cancer should be considered when recommending staging laparotomy, and we recommend close follow-up examination including routine mammograms for female patients successfully treated for

  13. Increased Risk of Hemorrhagic and Ischemic Strokes in Patients With Splenic Injury and Splenectomy

    Lin, Jiun-Nong; Lin, Cheng-Li; Lin, Ming-Chia; Lai, Chung-Hsu; Lin, Hsi-Hsun; Yang, Chih-Hui; Kao, Chia-Hung

    2015-01-01

    Abstract The spleen is a crucial organ in humans. Little is known about the association between stroke and splenic injury or splenectomy. The aim of this study was to determine the risk of stroke in patients with splenic injury and splenectomy. A nationwide cohort study was conducted by analyzing the National Health Insurance Research Database in Taiwan. For comparison, control patients were selected and matched with splenic injury patients in a ratio of 4:1 according to age, sex, and the year of hospitalization. We analyzed the risks of stroke using a Cox proportional-hazards regression analysis. A total of 11,273 splenic injury patients, including 5294 splenectomized and 5979 nonsplenectomized patients, and 45,092 control patients were included in this study. The incidence rates of stroke were 8.05, 6.53, and 4.25 per 1000 person-years in splenic injury patients with splenectomy, those without splenectomy, and the control cohort, respectively. Compared with the control cohort, splenic injury patients with splenectomy exhibited a 2.05-fold increased risk of stroke (95% confidence interval [CI] 1.8–2.34), whereas those without splenectomy exhibited a 1.74-fold increased risk (95% CI 1.51–2). Splenectomy entailed an additional 1.21-fold increased risk of stroke compared with nonsplenectomy in patients with splenic injury. This study revealed that splenic injury and splenectomy were significantly associated with an increased risk of hemorrhagic and ischemic strokes. The results of this study may alert physicians and patients to the complications of splenic injury and splenectomy. PMID:26334909

  14. Increased colorectal cancer risk in first-degree relatives of patients with hyperplastic polyposis syndrome

    Boparai, K. S.; Reitsma, J. B.; Lemmens, V.; van Os, T. A. M.; Mathus-Vliegen, E. M. H.; Koornstra, J. J.; Nagengast, F. M.; van Hest, L. P.; Keller, J. J.; Dekker, E.

    2010-01-01

    Introduction Hyperplastic polyposis syndrome (HPS) is characterised by the presence of multiple colorectal hyperplastic polyps and is associated with an increased colorectal cancer (CRC) risk. For first-degree relatives of HPS patients (FDRs) this has not been adequately quantified. Reliable

  15. No increased risk of perforation during colonoscopy in patients undergoing Nurse Administered Propofol Sedation

    Okholm, Cecilie; Hadikhadem, Talie; Andersen, Lærke Toftegård

    2013-01-01

    Abstract Objective. Nurse Administered Propofol Sedation (NAPS) contributes to a deeper sedation of the patients, making them unable to respond to pain and an increased incidence of perforations has been speculated. The objective of this study was to evaluate the risk of perforations during...

  16. Increased risk of asthma in overweight children born large for gestational age

    Pinto, L. A.; Guerra, S.; Anto, J. M.; Postma, D.; Koppelman, G. H.; de Jongste, J. C.; Gehring, U.; Smit, H. A.; Wijga, A. H.

    Background: Being born large for gestational age (LGA) is a marker of increased growth velocity in fetal life and a risk factor for childhood overweight. Both being born LGA and childhood overweight may influence the development of asthma, although the role of overweight in the association between

  17. Benign Thyroid Conditions Associated with Increased Risk of Thyroid Cancer Later in Life

    In a new study from the National Cancer Institute and Aarhus University Hospital in Denmark, researchers report an association between diagnosis of hyperthyroidism and thyroiditis (inflammation of the thyroid gland), two benign thyroid conditions, and increased risk of differentiated thyroid cancer.

  18. Inappropriate complementary feeding practice increases risk of stunting in children aged 12-24 months

    Hijra Hijra

    2016-12-01

    Inappropriate complementary feeding practice increased the risk of stunting in 12-24 months old children by 8.26. This study confirms the need to scale up interventions during the first 2 years of life, including appropriate infant feeding practices.

  19. Does Discretion in Lending Increase Bank Risk? Borrower Self-Selection and Loan Officer Capture Effects

    Gropp, R.; Grundl, C.; Guttler, A.

    2012-01-01

    Abstract: In this paper we analyze whether discretionary lending increases bank risk. We use a panel dataset of matched bank and borrower data. It offers the chief advantages that we can directly identify soft information in banks’ lending decisions and that we observe ex post defaults of borrowers.

  20. Does Discretion in Lending Increase Bank Risk? Borrower Self-Selection and Loan Officer Capture Effects

    Gropp, R.; Grundl, C.; Guttler, A.

    2012-01-01

    In this paper we analyze whether discretionary lending increases bank risk. We use a panel dataset of matched bank and borrower data. It offers the chief advantages that we can directly identify soft information in banks’ lending decisions and that we observe ex post defaults of borrowers.Consistent

  1. Cost effectiveness of withdrawal of fall-risk-increasing drugs in geriatric outpatients

    van der Velde, Nathalie; Meerding, Willen Jan; Looman, Caspar W.; Pols, Huibert A. P.; van der Cammen, Tischa J. M.

    2008-01-01

    BACKGROUND: Withdrawal of fall-risk-increasing drugs has been proven to be effective in older persons. However, given the enormous rise in healthcare costs in recent decades, the effect of such withdrawals on healthcare costs also needs to be considered. METHOD: Within a common geriatric outpatient

  2. Increased colorectal cancer risk in first-degree relatives of patients with hyperplastic polyposis syndrome.

    Boparai, K.S.; Reitsma, J.B.; Lemmens, V.; Os, T.A. van; Mathus-Vliegen, E.M.H.; Koornstra, J.J.; Nagengast, F.M.; Hest, L.P. van; Keller, J.J.; Dekker, E. den

    2010-01-01

    INTRODUCTION: Hyperplastic polyposis syndrome (HPS) is characterised by the presence of multiple colorectal hyperplastic polyps and is associated with an increased colorectal cancer (CRC) risk. For first-degree relatives of HPS patients (FDRs) this has not been adequately quantified. Reliable

  3. Increased colorectal cancer risk in first-degree relatives of patients with hyperplastic polyposis syndrome

    Boparai, K. S.; Lemmens, V.; van Os, T. A. M.; Mathus-Vliegen, E. M. H.; Koornstra, J. J.; Nagengast, F. M.; van Hest, L. P.; Keller, J. J.; Dekker, E.; Reitsma, J.

    Introduction Hyperplastic polyposis syndrome (HPS) is characterised by the presence of multiple colorectal hyperplastic polyps and is associated with an increased colorectal cancer (CRC) risk. For first-degree relatives of HPS patients (FDRs) this has not been adequately quantified. Reliable

  4. Increased risk of breast cancer development after diagnosis of salivary gland tumour

    In der Maur, Caroline D.; Klokman, Willem J.; van Leeuwen, Floor E.; Tan, I. Bing; Rutgers, Emiel J. Th; Balm, Alfons J. M.

    2005-01-01

    The aim of this study was to evaluate whether patients with salivary gland tumours are at increased risk of developing breast cancer. A retrospective cohort study was performed. Female patients (n = 439) with a salivary gland tumour (major and minor) were included. The diagnosis was confirmed

  5. Early Erythropoietin Administration does not Increase the Risk of Retinopathy in Preterm Infants

    Hsin-Hsu Chou

    2017-02-01

    Conclusion: EPO administration did not significantly increase the risk of ROP of any stage reported or Stage ≥3. Further clinical trials investigating the impact of EPO on ROP in premature infants should include all confounding factors to clarify this important issue.

  6. Infections Increase Risk of Arterial and Venous Thromboses in Danish Patients with Systemic Lupus Erythematosus

    Baronaite Hansen, Renata; Jacobsen, Søren

    2014-01-01

    OBJECTIVE: Infections and thromboses are known complications of systemic lupus erythematosus (SLE). We investigated if infectious episodes in patients with SLE were followed by an increased risk of thrombotic events. METHODS: A cohort of 571 patients with prevalent or incident SLE was followed...

  7. When Combined with Chemotherapy, Bevacizumab Is Associated with Increased Risk of Death

    Cancer patients who receive the targeted therapy bevacizumab (Avastin) in combination with chemotherapy are at increased risk of serious side effects that may lead to death, according to a meta-analysis of 16 clinical trials that was published February 2,

  8. Withdrawal of fall-risk-increasing drugs in older persons: Effect on mobility test outcomes

    N. van der Velde (Nathalie); B.H.Ch. Stricker (Bruno); H.A.P. Pols (Huib); T.J.M. van der Cammen (Tischa)

    2007-01-01

    textabstractBackground: Previously, we have shown that withdrawal of fall-risk-increasing drugs (FRIDs) as a single intervention reduces falls incidence. Improvement of mobility may be an important factor in this finding and we therefore tested whether mobility tests improved after FRID withdrawal.

  9. Withdrawal of fall-risk-increasing drugs in older persons: effect on mobility test outcomes

    van der Velde, Nathalie; Stricker, Bruno H. Ch; Pols, Huibert A. P.; van der Cammen, Tischa J. M.

    2007-01-01

    BACKGROUND: Previously, we have shown that withdrawal of fall-risk-increasing drugs (FRIDs) as a single intervention reduces falls incidence. Improvement of mobility may be an important factor in this finding and we therefore tested whether mobility tests improved after FRID withdrawal. METHODS: In

  10. Polycystic ovary syndrome and early-onset preeclampsia : reproductive manifestations of increased cardiovascular risk

    Veltman-Verhulst, Susanne M.; van Rijn, Bas B.; Westerveld, H. Egbertine; Franx, Arie; Bruinse, Hein W.; Fauser, Bart C. J. M.; Goverde, Angelique J.

    2010-01-01

    Objective: Primary prevention of cardiovascular disease (CVD) in women is a major healthcare issue. Detection of premenopausal women with increased risk of CVD could enhance prevention strategies and reduce first event-related morbidity and mortality. In this study, we argue that an unfavorable

  11. Genetically predicted longer telomere length is associated with increased risk of B-cell lymphoma subtypes

    Machiela, Mitchell J; Lan, Qing; Slager, Susan L; Vermeulen, Roel C H; Teras, Lauren R; Camp, Nicola J; Cerhan, James R; Spinelli, John J; Wang, Sophia S; Nieters, Alexandra; Vijai, Joseph; Yeager, Meredith; Wang, Zhaoming; Ghesquières, Hervé; McKay, James; Conde, Lucia; de Bakker, Paul I W; Cox, David G; Burdett, Laurie; Monnereau, Alain; Flowers, Christopher R; De Roos, Anneclaire J; Brooks-Wilson, Angela R; Giles, Graham G; Melbye, Mads; Gu, Jian; Jackson, Rebecca D; Kane, Eleanor; Purdue, Mark P; Vajdic, Claire M; Albanes, Demetrius; Kelly, Rachel S; Zucca, Mariagrazia; Bertrand, Kimberly A; Zeleniuch-Jacquotte, Anne; Lawrence, Charles; Hutchinson, Amy; Zhi, Degui; Habermann, Thomas M; Link, Brian K; Novak, Anne J; Dogan, Ahmet; Asmann, Yan W; Liebow, Mark; Thompson, Carrie A; Ansell, Stephen M; Witzig, Thomas E; Tilly, Hervé; Haioun, Corinne; Molina, Thierry J; Hjalgrim, Henrik; Glimelius, Bengt; Adami, Hans-Olov; Roos, Göran; Bracci, Paige M; Riby, Jacques; Smith, Martyn T; Holly, Elizabeth A; Cozen, Wendy; Hartge, Patricia; Morton, Lindsay M; Severson, Richard K; Tinker, Lesley F; North, Kari E; Becker, Nikolaus; Benavente, Yolanda; Boffetta, Paolo; Brennan, Paul; Foretova, Lenka; Maynadie, Marc; Staines, Anthony; Lightfoot, Tracy; Crouch, Simon; Smith, Alex; Roman, Eve; Diver, W Ryan; Offit, Kenneth; Zelenetz, Andrew; Klein, Robert J; Villano, Danylo J; Zheng, Tongzhang; Zhang, Yawei; Holford, Theodore R; Turner, Jenny; Southey, Melissa C; Clavel, Jacqueline; Virtamo, Jarmo; Weinstein, Stephanie; Riboli, Elio; Vineis, Paolo; Kaaks, Rudolph; Boeing, Heiner; Tjønneland, Anne; Angelucci, Emanuele; Di Lollo, Simonetta; Rais, Marco; De Vivo, Immaculata; Giovannucci, Edward; Kraft, Peter; Huang, Jinyan; Ma, Baoshan; Ye, Yuanqing; Chiu, Brian C H; Liang, Liming; Park, Ju-Hyun; Chung, Charles C; Weisenburger, Dennis D; Fraumeni, Joseph F; Salles, Gilles; Glenn, Martha; Cannon-Albright, Lisa; Curtin, Karen; Wu, Xifeng; Smedby, Karin E; de Sanjose, Silvia; Skibola, Christine F; Berndt, Sonja I; Birmann, Brenda M; Chanock, Stephen J; Rothman, Nathaniel

    2016-01-01

    Evidence from a small number of studies suggests that longer telomere length measured in peripheral leukocytes is associated with an increased risk of non-Hodgkin lymphoma (NHL). However, these studies may be biased by reverse causation, confounded by unmeasured environmental exposures and might

  12. Possible increased risk of rhabdomyolysis during concomitant use of simvastatin and gemfibrozil