Function of the nucleotide exchange activity of vav1 in T cell development and activation.

PubMed

Saveliev, Alexander; Vanes, Lesley; Ksionda, Olga; Rapley, Jonathan; Smerdon, Stephen J; Rittinger, Katrin; Tybulewicz, Victor L J

2009-12-15

The guanine nucleotide exchange factor (GEF) Vav1 is essential for transducing T cell antigen receptor (TCR) signals and therefore plays a critical role in the development and activation of T cells. It has been presumed that the GEF activity of Vav1 is important for its function; however, there has been no direct demonstration of this. Here, we generated mice expressing enzymatically inactive, but normally folded, Vav1 protein. Analysis of these mice showed that the GEF activity of Vav1 was necessary for the selection of thymocytes and for the optimal activation of T cells, including signal transduction to Rac1, Akt, and integrins. In contrast, the GEF activity of Vav1 was not required for TCR-induced calcium flux, activation of extracellular signal-regulated kinase and protein kinase D1, and cell polarization. Thus, in T cells, the GEF activity of Vav1 is essential for some, but not all, of its functions.

Function of the Nucleotide Exchange Activity of Vav1 in T cell Development and Activation*

PubMed Central

Saveliev, Alexander; Vanes, Lesley; Ksionda, Olga; Rapley, Jonathan; Smerdon, Stephen J.; Rittinger, Katrin; Tybulewicz, Victor L. J.

2012-01-01

The guanine nucleotide exchange factor (GEF) Vav1 is essential for transducing T cell antigen receptor (TCR) signals and therefore plays a critical role in the development and activation of T cells. It has been presumed that the GEF activity of Vav1 is important for its function; however, there has been no direct demonstration of this. Here, we generated mice expressing enzymatically inactive, but normally folded, Vav1 protein. Analysis of these mice showed that the GEF activity of Vav1 was necessary for the selection of thymocytes and for the optimal activation of T cells, including signal transduction to Rac1, Akt, and integrins. In contrast, the GEF activity of Vav1 was not required for TCR-induced calcium flux, activation of extracellular signal–regulated kinase (ERK) and protein kinase D1 (PKD1), and cell polarization. Thus, in T cells, the GEF activity of Vav1 is essential for some, but not all, of its functions. PMID:20009105

An Epistatic Interaction between Themis1 and Vav1 Modulates Regulatory T Cell Function and Inflammatory Bowel Disease Development.

PubMed

Pedros, Christophe; Gaud, Guillaume; Bernard, Isabelle; Kassem, Sahar; Chabod, Marianne; Lagrange, Dominique; Andréoletti, Olivier; Dejean, Anne S; Lesourne, Renaud; Fournié, Gilbert J; Saoudi, Abdelhadi

2015-08-15

The development of inflammatory diseases depends on complex interactions between several genes and various environmental factors. Discovering new genetic risk factors and understanding the mechanisms whereby they influence disease development is of paramount importance. We previously reported that deficiency in Themis1, a new actor of TCR signaling, impairs regulatory T cell (Treg) function and predisposes Brown-Norway (BN) rats to spontaneous inflammatory bowel disease (IBD). In this study, we reveal that the epistasis between Themis1 and Vav1 controls the occurrence of these phenotypes. Indeed, by contrast with BN rats, Themis1 deficiency in Lewis rats neither impairs Treg suppressive functions nor induces pathological manifestations. By using congenic lines on the BN genomic background, we show that the impact of Themis1 deficiency on Treg suppressive functions depends on a 117-kb interval coding for a R63W polymorphism that impacts Vav1 expression and functions. Indeed, the introduction of a 117-kb interval containing the Lewis Vav1-R63 variant restores Treg function and protects Themis1-deficient BN rats from spontaneous IBD development. We further show that Themis1 binds more efficiently to the BN Vav1-W63 variant and is required to stabilize its recruitment to the transmembrane adaptor LAT and to fully promote the activation of Erk kinases. Together, these results highlight the importance of the signaling pathway involving epistasis between Themis1 and Vav1 in the control of Treg suppressive function and susceptibility to IBD development. Copyright © 2015 by The American Association of Immunologists, Inc.

A Natural Variant of the T Cell Receptor-Signaling Molecule Vav1 Reduces Both Effector T Cell Functions and Susceptibility to Neuroinflammation.

PubMed

Kassem, Sahar; Gaud, Guillaume; Bernard, Isabelle; Benamar, Mehdi; Dejean, Anne S; Liblau, Roland; Fournié, Gilbert J; Colacios, Céline; Malissen, Bernard; Saoudi, Abdelhadi

2016-07-01

The guanine nucleotide exchange factor Vav1 is essential for transducing T cell antigen receptor signals and therefore plays an important role in T cell development and activation. Our previous genetic studies identified a locus on rat chromosome 9 that controls the susceptibility to neuroinflammation and contains a non-synonymous polymorphism in the major candidate gene Vav1. To formally demonstrate the causal implication of this polymorphism, we generated a knock-in mouse bearing this polymorphism (Vav1R63W). Using this model, we show that Vav1R63W mice display reduced susceptibility to experimental autoimmune encephalomyelitis (EAE) induced by MOG35-55 peptide immunization. This is associated with a lower production of effector cytokines (IFN-γ, IL-17 and GM-CSF) by autoreactive CD4 T cells. Despite increased proportion of Foxp3+ regulatory T cells in Vav1R63W mice, we show that this lowered cytokine production is intrinsic to effector CD4 T cells and that Treg depletion has no impact on EAE development. Finally, we provide a mechanism for the above phenotype by showing that the Vav1R63W variant has normal enzymatic activity but reduced adaptor functions. Together, these data highlight the importance of Vav1 adaptor functions in the production of inflammatory cytokines by effector T cells and in the susceptibility to neuroinflammation.

A Natural Variant of the T Cell Receptor-Signaling Molecule Vav1 Reduces Both Effector T Cell Functions and Susceptibility to Neuroinflammation

PubMed Central

Kassem, Sahar; Bernard, Isabelle; Dejean, Anne S.; Liblau, Roland; Fournié, Gilbert J.; Colacios, Céline

2016-01-01

The guanine nucleotide exchange factor Vav1 is essential for transducing T cell antigen receptor signals and therefore plays an important role in T cell development and activation. Our previous genetic studies identified a locus on rat chromosome 9 that controls the susceptibility to neuroinflammation and contains a non-synonymous polymorphism in the major candidate gene Vav1. To formally demonstrate the causal implication of this polymorphism, we generated a knock-in mouse bearing this polymorphism (Vav1R63W). Using this model, we show that Vav1R63W mice display reduced susceptibility to experimental autoimmune encephalomyelitis (EAE) induced by MOG35-55 peptide immunization. This is associated with a lower production of effector cytokines (IFN-γ, IL-17 and GM-CSF) by autoreactive CD4 T cells. Despite increased proportion of Foxp3+ regulatory T cells in Vav1R63W mice, we show that this lowered cytokine production is intrinsic to effector CD4 T cells and that Treg depletion has no impact on EAE development. Finally, we provide a mechanism for the above phenotype by showing that the Vav1R63W variant has normal enzymatic activity but reduced adaptor functions. Together, these data highlight the importance of Vav1 adaptor functions in the production of inflammatory cytokines by effector T cells and in the susceptibility to neuroinflammation. PMID:27438086

Studying the dynamics of SLP-76, Nck, and Vav1 multimolecular complex formation in live human cells with triple-color FRET.

PubMed

Pauker, Maor H; Hassan, Nirit; Noy, Elad; Reicher, Barak; Barda-Saad, Mira

2012-04-24

Protein-protein interactions regulate and control many cellular functions. A multimolecular complex consisting of the adaptor proteins SLP-76 (Src homology 2 domain-containing leukocyte protein of 76 kD), Nck, and the guanine nucleotide exchange factor Vav1 is recruited to the T cell side of the interface with an antigen-presenting cell during initial T cell activation. This complex is crucial for regulation of the actin machinery, antigen recognition, and signaling in T cells. We studied the interactions between these proteins as well as the dynamics of their recruitment into a complex that governs cytoskeletal reorganization. We developed a triple-color Förster resonance energy transfer (3FRET) system to observe the dynamics of the formation of this trimolecular signaling complex in live human T cells and to follow the three molecular interactions in parallel. Using the 3FRET system, we demonstrated that dimers of Nck and Vav1 were constitutively formed independently of both T cell activation and the association between SLP-76 and Nck. After T cell receptor stimulation, SLP-76 was phosphorylated, which enabled the binding of Nck. A point mutation in the proline-rich site of Vav1, which abolishes its binding to Nck, impaired actin rearrangement, suggesting that Nck-Vav1 dimers play a critical role in regulation of the actin machinery. We suggest that these findings revise the accepted model of the formation of a complex of SLP-76, Nck, and Vav1 and demonstrate the use of 3FRET as a tool to study signal transduction in live cells.

Molecular Basis for Failure of “Atypical” C1 Domain of Vav1 to Bind Diacylglycerol/Phorbol Ester*

PubMed Central

Geczy, Tamas; Peach, Megan L.; El Kazzouli, Saïd; Sigano, Dina M.; Kang, Ji-Hye; Valle, Christopher J.; Selezneva, Julia; Woo, Wonhee; Kedei, Noemi; Lewin, Nancy E.; Garfield, Susan H.; Lim, Langston; Mannan, Poonam; Marquez, Victor E.; Blumberg, Peter M.

2012-01-01

C1 domains, the recognition motif of the second messenger diacylglycerol and of the phorbol esters, are classified as typical (ligand-responsive) or atypical (not ligand-responsive). The C1 domain of Vav1, a guanine nucleotide exchange factor, plays a critical role in regulation of Vav activity through stabilization of the Dbl homology domain, which is responsible for exchange activity of Vav. Although the C1 domain of Vav1 is classified as atypical, it retains a binding pocket geometry homologous to that of the typical C1 domains of PKCs. This study clarifies the basis for its failure to bind ligands. Substituting Vav1-specific residues into the C1b domain of PKCδ, we identified five crucial residues (Glu9, Glu10, Thr11, Thr24, and Tyr26) along the rim of the binding cleft that weaken binding potency in a cumulative fashion. Reciprocally, replacing these incompatible residues in the Vav1 C1 domain with the corresponding residues from PKCδ C1b (δC1b) conferred high potency for phorbol ester binding. Computer modeling predicts that these unique residues in Vav1 increase the hydrophilicity of the rim of the binding pocket, impairing membrane association and thereby preventing formation of the ternary C1-ligand-membrane binding complex. The initial design of diacylglycerol-lactones to exploit these Vav1 unique residues showed enhanced selectivity for C1 domains incorporating these residues, suggesting a strategy for the development of ligands targeting Vav1. PMID:22351766

Tyrosine phosphorylation of 3BP2 is indispensable for the interaction with VAV3 in chicken DT40 cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chihara, Kazuyasu; Organization for Life Science Advancement Programs, University of Fukui, Fukui 910-1193; Kimura, Yukihiro

Adaptor protein c-Abl SH3 domain-binding protein-2 (3BP2) is known to play regulatory roles in immunoreceptor-mediated signal transduction. We have previously demonstrated that Tyr{sup 174}, Tyr{sup 183} and Tyr{sup 446} in mouse 3BP2 are predominantly phosphorylated by Syk, and the phosphorylation of Tyr{sup 183} and the Src homology 2 (SH2) domain of mouse 3BP2 are critical for B cell receptor (BCR)-induced activation of nuclear factor of activated T cells (NFAT) in human B cells. In this report, we have shown that Syk, but not Abl family protein-tyrosine kinases, is critical for BCR-mediated tyrosine phosphorylation of 3BP2 in chicken DT40 cells. Mutationalmore » analysis showed that Tyr{sup 174}, Tyr{sup 183} and Tyr{sup 426} of chicken 3BP2 are the major phosphorylation sites by Syk and the SH2 domain of 3BP2 is critical for tyrosine phosphorylation. In addition, phosphorylation of Tyr{sup 426} is required for the inducible interaction with the SH2 domain of Vav3. Moreover, the expression of the mutant form of 3BP2 in which Tyr{sup 426} was substituted to Phe resulted in the reduction in BCR-mediated Rac1 activation, when compared with the case of wild-type. Altogether, these data suggest that 3BP2 is involved in the activation of Rac1 through the regulation of Vav3 by Syk-dependent phosphorylation of Tyr{sup 426} following BCR stimulation. - Highlights: • 3BP2 is phosphorylated by Syk, but not Abl family kinases in BCR signaling. • Tyr183 and Tyr426 in chicken 3BP2 are the major phosphorylation sites by Syk. • The SH2 domain of 3BP2 is critical for tyrosine phosphorylation of 3BP2. • Phosphorylation of Tyr426 in 3BP2 is required for the inducible binding with Vav3. • 3BP2 is involved in the regulation of BCR-mediated Rac1 activation.« less

Tyrosine phosphorylation of 3BP2 is indispensable for the interaction with VAV3 in chicken DT40 cells.

PubMed

Chihara, Kazuyasu; Kimura, Yukihiro; Honjoh, Chisato; Yamauchi, Shota; Takeuchi, Kenji; Sada, Kiyonao

2014-03-10

Adaptor protein c-Abl SH3 domain-binding protein-2 (3BP2) is known to play regulatory roles in immunoreceptor-mediated signal transduction. We have previously demonstrated that Tyr(174), Tyr(183) and Tyr(446) in mouse 3BP2 are predominantly phosphorylated by Syk, and the phosphorylation of Tyr(183) and the Src homology 2 (SH2) domain of mouse 3BP2 are critical for B cell receptor (BCR)-induced activation of nuclear factor of activated T cells (NFAT) in human B cells. In this report, we have shown that Syk, but not Abl family protein-tyrosine kinases, is critical for BCR-mediated tyrosine phosphorylation of 3BP2 in chicken DT40 cells. Mutational analysis showed that Tyr(174), Tyr(183) and Tyr(426) of chicken 3BP2 are the major phosphorylation sites by Syk and the SH2 domain of 3BP2 is critical for tyrosine phosphorylation. In addition, phosphorylation of Tyr(426) is required for the inducible interaction with the SH2 domain of Vav3. Moreover, the expression of the mutant form of 3BP2 in which Tyr(426) was substituted to Phe resulted in the reduction in BCR-mediated Rac1 activation, when compared with the case of wild-type. Altogether, these data suggest that 3BP2 is involved in the activation of Rac1 through the regulation of Vav3 by Syk-dependent phosphorylation of Tyr(426) following BCR stimulation. Copyright © 2014 Elsevier Inc. All rights reserved.

Minimum airflow reset of single-duct VAV terminal boxes

NASA Astrophysics Data System (ADS)

Cho, Young-Hum

Single duct Variable Air Volume (VAV) systems are currently the most widely used type of HVAC system in the United States. When installing such a system, it is critical to determine the minimum airflow set point of the terminal box, as an optimally selected set point will improve the level of thermal comfort and indoor air quality (IAQ) while at the same time lower overall energy costs. In principle, this minimum rate should be calculated according to the minimum ventilation requirement based on ASHRAE standard 62.1 and maximum heating load of the zone. Several factors must be carefully considered when calculating this minimum rate. Terminal boxes with conventional control sequences may result in occupant discomfort and energy waste. If the minimum rate of airflow is set too high, the AHUs will consume excess fan power, and the terminal boxes may cause significant simultaneous room heating and cooling. At the same time, a rate that is too low will result in poor air circulation and indoor air quality in the air-conditioned space. Currently, many scholars are investigating how to change the algorithm of the advanced VAV terminal box controller without retrofitting. Some of these controllers have been found to effectively improve thermal comfort, indoor air quality, and energy efficiency. However, minimum airflow set points have not yet been identified, nor has controller performance been verified in confirmed studies. In this study, control algorithms were developed that automatically identify and reset terminal box minimum airflow set points, thereby improving indoor air quality and thermal comfort levels, and reducing the overall rate of energy consumption. A theoretical analysis of the optimal minimum airflow and discharge air temperature was performed to identify the potential energy benefits of resetting the terminal box minimum airflow set points. Applicable control algorithms for calculating the ideal values for the minimum airflow reset were developed and

T-Cell Receptor- and CD28-induced Vav1 activity is required for the accumulation of primed T cells into antigenic tissue

PubMed Central

David, Rachel; Ma, Liang; Ivetic, Aleksandar; Takesono, Aya; Ridley, Anne J.; Chai, Jian-Guo; Tybulewicz, Victor; Marelli-Berg, Federica M.

2016-01-01

Localization of primed T cells to antigenic tissue is essential for the development of effective immunity. Together with tissue-selective homing molecules, T-cell receptor (TCR)- and CD28-mediated signals have been shown to promote transendothelial migration of specific T cells into non-lymphoid antigen-rich tissue tissue. However, the cellular and molecular requirements for T-cell accumulation to target tissue following their recruitment are largely undefined. The guanine nucleotide exchange factor (GEF) Vav1 has an integral role in coupling TCR and CD28 to signalling pathways that regulate T cell activation and migration. Here, we have investigated the contribution of TCR- and CD28-induced Vav1 activity to the trafficking and localization of primed HY-specific CD4+ T cells to antigenic sites. Severe migratory defects displayed by Vav1-/- T cells in vitro were fully compensated by a combination of shear flow and chemokines, leading to normal recruitment of Vav1-/- T cells in vivo. In contrast, Vav1-/- T-cell retention into antigen-rich tissue was severely impaired, reflecting their inability to engage in sustained TCR- and CD28-mediated interactions with tissue-resident antigen-presenting cells (APCs). This novel function of APC-induced, TCR- and CD28-mediated Vav1 activity in the regulation of effector T-cell immunity highlights its potential as a therapeutic target in T-cell-mediated tissue damage. PMID:19060239

Bruton's Tyrosine Kinase (BTK) and Vav1 Contribute to Dectin1-Dependent Phagocytosis of Candida albicans in Macrophages

PubMed Central

Strijbis, Karin; Tafesse, Fikadu G.; Fairn, Gregory D.; Witte, Martin D.; Dougan, Stephanie K.; Watson, Nicki; Spooner, Eric; Esteban, Alexandre; Vyas, Valmik K.; Fink, Gerald R.; Grinstein, Sergio; Ploegh, Hidde L.

2013-01-01

Phagocytosis of the opportunistic fungal pathogen Candida albicans by cells of the innate immune system is vital to prevent infection. Dectin-1 is the major phagocytic receptor involved in anti-fungal immunity. We identify two new interacting proteins of Dectin-1 in macrophages, Bruton's Tyrosine Kinase (BTK) and Vav1. BTK and Vav1 are recruited to phagocytic cups containing C. albicans yeasts or hyphae but are absent from mature phagosomes. BTK and Vav1 localize to cuff regions surrounding the hyphae, while Dectin-1 lines the full length of the phagosome. BTK and Vav1 colocalize with the lipid PI(3,4,5)P3 and F-actin at the phagocytic cup, but not with diacylglycerol (DAG) which marks more mature phagosomal membranes. Using a selective BTK inhibitor, we show that BTK contributes to DAG synthesis at the phagocytic cup and the subsequent recruitment of PKCε. BTK- or Vav1-deficient peritoneal macrophages display a defect in both zymosan and C. albicans phagocytosis. Bone marrow-derived macrophages that lack BTK or Vav1 show reduced uptake of C. albicans, comparable to Dectin1-deficient cells. BTK- or Vav1-deficient mice are more susceptible to systemic C. albicans infection than wild type mice. This work identifies an important role for BTK and Vav1 in immune responses against C. albicans. PMID:23825946

Bruton's Tyrosine Kinase (BTK) and Vav1 contribute to Dectin1-dependent phagocytosis of Candida albicans in macrophages.

PubMed

Strijbis, Karin; Tafesse, Fikadu G; Fairn, Gregory D; Witte, Martin D; Dougan, Stephanie K; Watson, Nicki; Spooner, Eric; Esteban, Alexandre; Vyas, Valmik K; Fink, Gerald R; Grinstein, Sergio; Ploegh, Hidde L

2013-01-01

Phagocytosis of the opportunistic fungal pathogen Candida albicans by cells of the innate immune system is vital to prevent infection. Dectin-1 is the major phagocytic receptor involved in anti-fungal immunity. We identify two new interacting proteins of Dectin-1 in macrophages, Bruton's Tyrosine Kinase (BTK) and Vav1. BTK and Vav1 are recruited to phagocytic cups containing C. albicans yeasts or hyphae but are absent from mature phagosomes. BTK and Vav1 localize to cuff regions surrounding the hyphae, while Dectin-1 lines the full length of the phagosome. BTK and Vav1 colocalize with the lipid PI(3,4,5)P3 and F-actin at the phagocytic cup, but not with diacylglycerol (DAG) which marks more mature phagosomal membranes. Using a selective BTK inhibitor, we show that BTK contributes to DAG synthesis at the phagocytic cup and the subsequent recruitment of PKCε. BTK- or Vav1-deficient peritoneal macrophages display a defect in both zymosan and C. albicans phagocytosis. Bone marrow-derived macrophages that lack BTK or Vav1 show reduced uptake of C. albicans, comparable to Dectin1-deficient cells. BTK- or Vav1-deficient mice are more susceptible to systemic C. albicans infection than wild type mice. This work identifies an important role for BTK and Vav1 in immune responses against C. albicans.

Vav1-phospholipase C-γ1 (Vav1-PLC-γ1) pathway initiated by T cell antigen receptor (TCRγδ) activation is required to overcome inhibition by ubiquitin ligase Cbl-b during γδT cell cytotoxicity.

PubMed

Yin, Shanshan; Zhang, Jianmin; Mao, Yujia; Hu, Yu; Cui, Lianxian; Kang, Ning; He, Wei

2013-09-13

T cell antigen receptor γδ (TCRγδ) and natural killer group 2, member D (NKG2D) are two crucial receptors for γδT cell cytotoxicity. Compelling evidences suggest that γδT cell cytotoxicity is TCRγδ-dependent and can be co-stimulated by NKG2D. However, the molecular mechanism of underlying TCRγδ-dependent activation of γδT cells remains unclear. In this study we demonstrated that TCRγδ but not NKG2D engagement induced lytic granule polarization and promoted γδT cell cytotoxicity. TCRγδ activation alone was sufficient to trigger Vav1-dependent phospholipase C-γ1 signaling, resulting in lytic granule polarization and effective killing, whereas NKG2D engagement alone failed to trigger cytotoxicity-related signaling to overcome the inhibitory effect of Cbl-b; therefore, NKG2D engagement alone could not induce effective killing. However, NKG2D ligation augmented the activation of γδT cell cytotoxicity through the Vav1-phospholipase C-γ1 pathway. Vav1 overexpression or Cbl-b knockdown not only enhanced TCRγδ activation-initiated killing but also enabled NKG2D activation alone to induce γδT cell cytotoxicity. Taken together, our results suggest that the activation of γδT cell cytotoxicity requires a strong activation signal to overcome the inhibitory effect of Cbl-b. Our finding provides new insights into the molecular mechanisms underlying the initiation of γδT cell cytotoxicity and likely implications for optimizing γδT cell-based cancer immunotherapy.

PTP-PEST targets a novel tyrosine site in p120 catenin to control epithelial cell motility and Rho GTPase activity.

PubMed

Espejo, Rosario; Jeng, Yowjiun; Paulucci-Holthauzen, Adriana; Rengifo-Cam, William; Honkus, Krysta; Anastasiadis, Panos Z; Sastry, Sarita K

2014-02-01

Tyrosine phosphorylation is implicated in regulating the adherens junction protein, p120 catenin (p120), however, the mechanisms are not well defined. Here, we show, using substrate trapping, that p120 is a direct target of the protein tyrosine phosphatase, PTP-PEST, in epithelial cells. Stable shRNA knockdown of PTP-PEST in colon carcinoma cells results in an increased cytosolic pool of p120 concomitant with its enhanced tyrosine phosphorylation and decreased association with E-cadherin. Consistent with this, PTP-PEST knockdown cells exhibit increased motility, enhanced Rac1 and decreased RhoA activity on a collagen substrate. Furthermore, p120 localization is enhanced at actin-rich protrusions and lamellipodia and has an increased association with the guanine nucleotide exchange factor, VAV2, and cortactin. Exchange factor activity of VAV2 is enhanced by PTP-PEST knockdown whereas overexpression of a VAV2 C-terminal domain or DH domain mutant blocks cell motility. Analysis of point mutations identified tyrosine 335 in the N-terminal domain of p120 as the site of PTP-PEST dephosphorylation. A Y335F mutant of p120 failed to induce the 'p120 phenotype', interact with VAV2, stimulate cell motility or activate Rac1. Together, these data suggest that PTP-PEST affects epithelial cell motility by controlling the distribution and phosphorylation of p120 and its availability to control Rho GTPase activity.

Efficacy and Immunogenicity of Single-Dose AdVAV Intranasal Anthrax Vaccine Compared to Anthrax Vaccine Absorbed in an Aerosolized Spore Rabbit Challenge Model

PubMed Central

Krishnan, Vyjayanthi; Andersen, Bo H.; Shoemaker, Christine; Sivko, Gloria S.; Tordoff, Kevin P.; Stark, Gregory V.; Zhang, Jianfeng; Feng, Tsungwei; Duchars, Matthew

2015-01-01

AdVAV is a replication-deficient adenovirus type 5-vectored vaccine expressing the 83-kDa protective antigen (PA83) from Bacillus anthracis that is being developed for the prevention of disease caused by inhalation of aerosolized B. anthracis spores. A noninferiority study comparing the efficacy of AdVAV to the currently licensed Anthrax Vaccine Absorbed (AVA; BioThrax) was performed in New Zealand White rabbits using postchallenge survival as the study endpoint (20% noninferiority margin for survival). Three groups of 32 rabbits were vaccinated with a single intranasal dose of AdVAV (7.5 × 107, 1.5 × 109, or 3.5 × 1010 viral particles). Three additional groups of 32 animals received two doses of either intranasal AdVAV (3.5 × 1010 viral particles) or intramuscular AVA (diluted 1:16 or 1:64) 28 days apart. The placebo group of 16 rabbits received a single intranasal dose of AdVAV formulation buffer. All animals were challenged via the inhalation route with a targeted dose of 200 times the 50% lethal dose (LD50) of aerosolized B. anthracis Ames spores 70 days after the initial vaccination and were followed for 3 weeks. PA83 immunogenicity was evaluated by validated toxin neutralizing antibody and serum anti-PA83 IgG enzyme-linked immunosorbent assays (ELISAs). All animals in the placebo cohort died from the challenge. Three of the four AdVAV dose cohorts tested, including two single-dose cohorts, achieved statistical noninferiority relative to the AVA comparator group, with survival rates between 97% and 100%. Vaccination with AdVAV also produced antibody titers with earlier onset and greater persistence than vaccination with AVA. PMID:25673303

PTP-PEST targets a novel tyrosine site in p120 catenin to control epithelial cell motility and Rho GTPase activity

PubMed Central

Espejo, Rosario; Jeng, Yowjiun; Paulucci-Holthauzen, Adriana; Rengifo-Cam, William; Honkus, Krysta; Anastasiadis, Panos Z.; Sastry, Sarita K.

2014-01-01

ABSTRACT Tyrosine phosphorylation is implicated in regulating the adherens junction protein, p120 catenin (p120), however, the mechanisms are not well defined. Here, we show, using substrate trapping, that p120 is a direct target of the protein tyrosine phosphatase, PTP-PEST, in epithelial cells. Stable shRNA knockdown of PTP-PEST in colon carcinoma cells results in an increased cytosolic pool of p120 concomitant with its enhanced tyrosine phosphorylation and decreased association with E-cadherin. Consistent with this, PTP-PEST knockdown cells exhibit increased motility, enhanced Rac1 and decreased RhoA activity on a collagen substrate. Furthermore, p120 localization is enhanced at actin-rich protrusions and lamellipodia and has an increased association with the guanine nucleotide exchange factor, VAV2, and cortactin. Exchange factor activity of VAV2 is enhanced by PTP-PEST knockdown whereas overexpression of a VAV2 C-terminal domain or DH domain mutant blocks cell motility. Analysis of point mutations identified tyrosine 335 in the N-terminal domain of p120 as the site of PTP-PEST dephosphorylation. A Y335F mutant of p120 failed to induce the ‘p120 phenotype’, interact with VAV2, stimulate cell motility or activate Rac1. Together, these data suggest that PTP-PEST affects epithelial cell motility by controlling the distribution and phosphorylation of p120 and its availability to control Rho GTPase activity. PMID:24284071

Efficacy and immunogenicity of single-dose AdVAV intranasal anthrax vaccine compared to anthrax vaccine absorbed in an aerosolized spore rabbit challenge model.

PubMed

Krishnan, Vyjayanthi; Andersen, Bo H; Shoemaker, Christine; Sivko, Gloria S; Tordoff, Kevin P; Stark, Gregory V; Zhang, Jianfeng; Feng, Tsungwei; Duchars, Matthew; Roberts, M Scot

2015-04-01

AdVAV is a replication-deficient adenovirus type 5-vectored vaccine expressing the 83-kDa protective antigen (PA83) from Bacillus anthracis that is being developed for the prevention of disease caused by inhalation of aerosolized B. anthracis spores. A noninferiority study comparing the efficacy of AdVAV to the currently licensed Anthrax Vaccine Absorbed (AVA; BioThrax) was performed in New Zealand White rabbits using postchallenge survival as the study endpoint (20% noninferiority margin for survival). Three groups of 32 rabbits were vaccinated with a single intranasal dose of AdVAV (7.5 × 10(7), 1.5 × 10(9), or 3.5 × 10(10) viral particles). Three additional groups of 32 animals received two doses of either intranasal AdVAV (3.5 × 10(10) viral particles) or intramuscular AVA (diluted 1:16 or 1:64) 28 days apart. The placebo group of 16 rabbits received a single intranasal dose of AdVAV formulation buffer. All animals were challenged via the inhalation route with a targeted dose of 200 times the 50% lethal dose (LD50) of aerosolized B. anthracis Ames spores 70 days after the initial vaccination and were followed for 3 weeks. PA83 immunogenicity was evaluated by validated toxin neutralizing antibody and serum anti-PA83 IgG enzyme-linked immunosorbent assays (ELISAs). All animals in the placebo cohort died from the challenge. Three of the four AdVAV dose cohorts tested, including two single-dose cohorts, achieved statistical noninferiority relative to the AVA comparator group, with survival rates between 97% and 100%. Vaccination with AdVAV also produced antibody titers with earlier onset and greater persistence than vaccination with AVA. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Characteristics of lentiviral vectors harboring the proximal promoter of the vav proto-oncogene: a weak and efficient promoter for gene therapy.

PubMed

Almarza, Elena; Río, Paula; Meza, Nestor W; Aldea, Montserrat; Agirre, Xabier; Guenechea, Guillermo; Segovia, José C; Bueren, Juan A

2007-08-01

Recent published data have shown the efficacy of gene therapy treatments of certain monogenic diseases. Risks of insertional oncogenesis, however, indicate the necessity of developing new vectors with weaker or cell-restricted promoters to minimize the trans-activation activity of integrated proviruses. We have inserted the proximal promoter of the vav proto-oncogene into self-inactivating lentiviral vectors (vav-LVs) and investigated the expression pattern and therapeutic efficacy of these vectors. Compared with other LVs frequently used in gene therapy, vav-LVs mediated a weak, though homogeneous and stable, expression in in vitro-cultured cells. Transplantation experiments using transduced mouse bone marrow and human CD34(+) cells confirmed the stable activity of the promoter in vivo. To investigate whether the weak activity of this promoter was compatible with a therapeutic effect, a LV expressing the Fanconi anemia A (FANCA) gene was constructed (vav-FANCA LV). Although this vector induced a low expression of FANCA, compared to the expression induced by a LV harboring the spleen focus-forming virus (SFFV) promoter, the two vectors corrected the phenotype of cells from a patient with FA-A with the same efficacy. We propose that self-inactivating vectors harboring weak promoters, such as the vav promoter, will improve the safety of gene therapy and will be of particular interest for the treatment of diseases where a high expression of the transgene is not required.

Evaluation of energy savings potential of variable refrigerant flow (VRF) from variable air volume (VAV) in the U.S. climate locations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Dongsu; Cox, Sam J.; Cho, Heejin

Variable refrigerant flow (VRF) systems are known for their high energy performance and thus can improve energy efficiency both in residential and commercial buildings. The energy savings potential of this system has been demonstrated in several studies by comparing the system performance with conventional HVAC systems such as rooftop variable air volume systems (RTU-VAV) and central chiller and boiler systems. This paper evaluates the performance of VRF and RTU-VAV systems in a simulation environment using widely-accepted whole building energy modeling software, EnergyPlus. A medium office prototype building model, developed by the U.S. Department of Energy (DOE), is used to assessmore » the performance of VRF and RTU-VAV systems. Each system is placed in 16 different locations, representing all U.S. climate zones, to evaluate the performance variations. Both models are compliant with the minimum energy code requirements prescribed in ASHRAE standard 90.1-2010 — energy standard for buildings except low-rise residential buildings. Finally, a comparison study between the simulation results of VRF and RTU-VAV models is made to demonstrate energy savings potential of VRF systems. The simulation results show that the VRF systems would save around 15–42% and 18–33% for HVAC site and source energy uses compared to the RTU-VAV systems. In addition, calculated results for annual HVAC cost savings point out that hot and mild climates show higher percentage cost savings for the VRF systems than cold climates mainly due to the differences in electricity and gas use for heating sources.« less

Evaluation of energy savings potential of variable refrigerant flow (VRF) from variable air volume (VAV) in the U.S. climate locations

DOE PAGES

Kim, Dongsu; Cox, Sam J.; Cho, Heejin; ...

2017-05-22

Variable refrigerant flow (VRF) systems are known for their high energy performance and thus can improve energy efficiency both in residential and commercial buildings. The energy savings potential of this system has been demonstrated in several studies by comparing the system performance with conventional HVAC systems such as rooftop variable air volume systems (RTU-VAV) and central chiller and boiler systems. This paper evaluates the performance of VRF and RTU-VAV systems in a simulation environment using widely-accepted whole building energy modeling software, EnergyPlus. A medium office prototype building model, developed by the U.S. Department of Energy (DOE), is used to assessmore » the performance of VRF and RTU-VAV systems. Each system is placed in 16 different locations, representing all U.S. climate zones, to evaluate the performance variations. Both models are compliant with the minimum energy code requirements prescribed in ASHRAE standard 90.1-2010 — energy standard for buildings except low-rise residential buildings. Finally, a comparison study between the simulation results of VRF and RTU-VAV models is made to demonstrate energy savings potential of VRF systems. The simulation results show that the VRF systems would save around 15–42% and 18–33% for HVAC site and source energy uses compared to the RTU-VAV systems. In addition, calculated results for annual HVAC cost savings point out that hot and mild climates show higher percentage cost savings for the VRF systems than cold climates mainly due to the differences in electricity and gas use for heating sources.« less

T cell receptor-driven transendothelial migration of human effector memory CD4 T cells involves Vav, Rac and Myosin IIA

PubMed Central

Manes, Thomas D.; Pober, Jordan S.

2013-01-01

Human effector memory (EM) CD4 T cells may be recruited from the blood into a site of inflammation in response either to inflammatory chemokines displayed on or specific antigen presented by venular endothelial cells (ECs), designated as chemokine-driven or TCR-driven transendothelial migration (TEM), respectively. We have previously described differences in the morphological appearance of transmigrating T cells as well as in the molecules that mediate T cell-EC interactions distinguishing these two pathways. Here we report that TCR-driven TEM requires ZAP-70-dependent activation of a pathway involving Vav, Rac and myosin IIA. Chemokine-driven TEM also utilizes ZAP-70, albeit in a quantitatively and spatially different manner of activation, and is independent of Vav, Rac and mysosin IIA, depending instead on an as yet unidentified GTP exchange factor that activates Cdc42. The differential use of small Rho family GTPases to activate the cytoskeleton is consistent with the morphological differences observed in T cells that undergo TEM in response to these distinct recruitment signals. PMID:23420881

Probing the Tyrosine Phosphorylation State in Breast Cancer by Src Homology 2 Domain Binding

DTIC Science & Technology

2006-08-01

pervanadate, a potent tyrosine phosphatase inhibitor . In the absence of pervanadate, endogenous phosphatases very rapidly dephosphorylate tyrosine...Shd Loc90525 Crk CrkL Plcg1NCPlcg2NC P85aNC p55gNC Vav1 Vav2 Vav3 Tec Btk Emt Txk Bmx Slp76 Mist MistRK GapNC Chimerin Chimerin 2 Tensin Tem6 Tenc1...Plcg1NCPlcg2NC P85aNC Vav1 Vav2 Vav3 Tec Btk Emt Txk Bmx Slp76 Mist MistRK GapNC Chimerin Chimerin 2 Tensin Tem6 Tenc1 Cis1 Cten Nap4 Rin1 RIn2 Rin3

The Analysis for Energy Consumption of Marine Air Conditioning System Based on VAV and VWV

NASA Astrophysics Data System (ADS)

Xu, Sai Feng; Yang, Xing Lin; Le, Zou Ying

2018-06-01

For ocean-going vessels sailing in different areas on the sea, the change of external environment factors will cause frequent changes in load, traditional ship air-conditioning system is usually designed with a fixed cooling capacity, this design method causes serious waste of resources. A new type of sea-based air conditioning system is proposed in this paper, which uses the sea-based source heat pump system, combined with variable air volume, variable water technology. The multifunctional cabins' dynamic loads for a ship navigating in a typical Eurasian route were calculated based on Simulink. The model can predict changes in full voyage load. Based on the simulation model, the effects of variable air volume and variable water volume on the energy consumption of the air-conditioning system are analyzed. The results show that: When the VAV is coupled with the VWV, the energy saving rate is 23.2%. Therefore, the application of variable air volume and variable water technology to marine air conditioning systems can achieve economical and energy saving advantages.

Demonstration of Energy Savings in Commercial Buildings for Tiered Trim and Respond Method in Resetting Static Pressure for VAV Systems

DTIC Science & Technology

2017-03-01

FINAL REPORT Demonstration of Energy Savings in Commercial Buildings for Tiered Trim and Respond Method in Resetting Static Pressure for VAV...release Page Intentionally Left Blank This report was prepared under contract to the Department of Defense Environmental Security Technology...Certification Program (ESTCP). The publication of this report does not indicate endorsement by the Department of Defense, nor should the contents be

A chemokine-binding domain in the tumor necrosis factor receptor from variola (smallpox) virus

PubMed Central

Alejo, Alí; Ruiz-Argüello, M. Begoña; Ho, Yin; Smith, Vincent P.; Saraiva, Margarida; Alcami, Antonio

2006-01-01

Variola virus (VaV) is the causative agent of smallpox, one of the most devastating diseases encountered by man, that was eradicated in 1980. The deliberate release of VaV would have catastrophic consequences on global public health. However, the mechanisms that contribute to smallpox pathogenesis are poorly understood at the molecular level. The ability of viruses to evade the host defense mechanisms is an important determinant of viral pathogenesis. Here we show that the tumor necrosis factor receptor (TNFR) homologue CrmB encoded by VaV functions not only as a soluble decoy TNFR but also as a highly specific binding protein for several chemokines that mediate recruitment of immune cells to mucosal surfaces and the skin, sites of virus entry and viral replication at late stages of smallpox. CrmB binds chemokines through its C-terminal domain, which is unrelated to TNFRs, was named smallpox virus-encoded chemokine receptor (SECRET) domain and uncovers a family of poxvirus chemokine inhibitors. An active SECRET domain was found in another viral TNFR (CrmD) and three secreted proteins encoded by orthopoxviruses. These findings identify a previously undescribed chemokine-binding and inhibitory domain unrelated to host chemokine receptors and a mechanism of immune modulation in VaV that may influence smallpox pathogenesis. PMID:16581912

A chemokine-binding domain in the tumor necrosis factor receptor from variola (smallpox) virus.

PubMed

Alejo, Alí; Ruiz-Argüello, M Begoña; Ho, Yin; Smith, Vincent P; Saraiva, Margarida; Alcami, Antonio

2006-04-11

Variola virus (VaV) is the causative agent of smallpox, one of the most devastating diseases encountered by man, that was eradicated in 1980. The deliberate release of VaV would have catastrophic consequences on global public health. However, the mechanisms that contribute to smallpox pathogenesis are poorly understood at the molecular level. The ability of viruses to evade the host defense mechanisms is an important determinant of viral pathogenesis. Here we show that the tumor necrosis factor receptor (TNFR) homologue CrmB encoded by VaV functions not only as a soluble decoy TNFR but also as a highly specific binding protein for several chemokines that mediate recruitment of immune cells to mucosal surfaces and the skin, sites of virus entry and viral replication at late stages of smallpox. CrmB binds chemokines through its C-terminal domain, which is unrelated to TNFRs, was named smallpox virus-encoded chemokine receptor (SECRET) domain and uncovers a family of poxvirus chemokine inhibitors. An active SECRET domain was found in another viral TNFR (CrmD) and three secreted proteins encoded by orthopoxviruses. These findings identify a previously undescribed chemokine-binding and inhibitory domain unrelated to host chemokine receptors and a mechanism of immune modulation in VaV that may influence smallpox pathogenesis.

2-(trimethylammonium) ethyl (R)-3-methoxy-3-oxo-2-stearamidopropyl phosphate suppresses osteoclast maturation and bone resorption by targeting macrophage-colony stimulating factor signaling.

PubMed

Park, So Jeong; Park, Doo Ri; Bhattarai, Deepak; Lee, Kyeong; Kim, Jaesang; Bae, Yun Soo; Lee, Soo Young

2014-08-01

2-(Trimethylammonium) ethyl (R)-3-methoxy-3-oxo-2-stearamidopropyl phosphate [(R)-TEMOSPho], a derivative of an organic chemical identified from a natural product library, promotes highly efficient megakaryopoiesis. Here, we show that (R)-TEMOSPho blocks osteoclast maturation from progenitor cells of hematopoietic origin, as well as blocking the resorptive function of mature osteoclasts. The inhibitory effect of (R)-TEMOSPho on osteoclasts was due to a disruption of the actin cytoskeleton, resulting from impaired downstream signaling of c-Fms, a receptor for macrophage-colony stimulating factor linked to c-Cbl, phosphoinositol-3-kinase (PI3K), Vav3, and Rac1. In addition, (R)-TEMOSPho blocked inflammation-induced bone destruction by reducing the numbers of osteoclasts produced in mice. Thus, (R)-TEMOSPho may represent a promising new class of antiresorptive drugs for the treatment of bone loss associated with increased osteoclast maturation and activity.

Distinct mechanisms of a phosphotyrosyl peptide binding to two SH2 domains.

PubMed

Pang, Xiaodong; Zhou, Huan-Xiang

2014-05-01

Protein phosphorylation is very common post-translational modification, catalyzed by kinases, for signaling and regulation. Phosphotyrosines frequently target SH2 domains. The spleen tyrosine kinase (Syk) is critical for tyrosine phosphorylation of multiple proteins and for regulation of important pathways. Phosphorylation of both Y342 and Y346 in Syk linker B is required for optimal signaling. The SH2 domains of Vav1 and PLC-γ both bind this doubly phosphorylated motif. Here we used a recently developed method to calculate the effects of Y342 and Y346 phosphorylation on the rate constants of a peptide from Syk linker B binding to the SH2 domains of Vav1 and PLC-γ. The predicted effects agree well with experimental observations. Moreover, we found that the same doubly phosphorylated peptide binds the two SH2 domains via distinct mechanisms, with apparent rigid docking for Vav1 SH2 and dock-and-coalesce for PLC-γ SH2.

VAV1-Cre mediated hematopoietic deletion of CBL and CBL-B leads to JMML-like aggressive early-neonatal myeloproliferative disease

PubMed Central

An, Wei; Mohapatra, Bhopal C.; Zutshi, Neha; Bielecki, Timothy A.; Goez, Benjamin T.; Luan, Haitao; Iseka, Fany; Mushtaq, Insha; Storck, Matthew D.; Band, Vimla; Band, Hamid

2016-01-01

CBL and CBL-B ubiquitin ligases play key roles in hematopoietic stem cell homeostasis and their aberrations are linked to leukemogenesis. Mutations of CBL, often genetically-inherited, are particularly common in Juvenile Myelomonocytic Leukemia (JMML), a disease that manifests early in children. JMML is fatal unless corrected by bone marrow transplant, which is effective in only half of the recipients, stressing the need for animal models that recapitulate the key clinical features of this disease. However, mouse models established so far only develop hematological malignancy in adult animals. Here, using VAV1-Cre-induced conditional CBL/CBL-B double knockout (DKO) in mice, we established an animal model that exhibits a neonatal myeloproliferative disease (MPD). VAV1-Cre induced DKO mice developed a strong hematological phenotype at postnatal day 10, including severe leukocytosis and hepatomegaly, bone marrow cell hypersensitivity to cytokines including GM-CSF, and rapidly-progressive disease and invariable lethality. Interestingly, leukemic stem cells were most highly enriched in neonatal liver rather than bone marrow, which, along with the spleen and thymus, were hypo-cellular. Nonetheless, transplantation assays showed that both DKO bone marrow and liver cells can initiate leukemic disease in the recipient mice with seeding of both spleen and bone marrow. Together, our results support the usefulness of the new hematopoietic-specific CBL/CBL-B double KO animal model to study JMML-related pathogenesis and to further understand the function of CBL family proteins in regulating fetal and neonatal hematopoiesis. To our knowledge, this is the first mouse model that exhibits neonatal MPD in infancy, by day 10 of postnatal life. PMID:27449297

Intestinal Master Transcription Factor CDX2 Controls Chromatin Access for Partner Transcription Factor Binding

PubMed Central

Verzi, Michael P.; Shin, Hyunjin; San Roman, Adrianna K.

2013-01-01

Tissue-specific gene expression requires modulation of nucleosomes, allowing transcription factors to occupy cis elements that are accessible only in selected tissues. Master transcription factors control cell-specific genes and define cellular identities, but it is unclear if they possess special abilities to regulate cell-specific chromatin and if such abilities might underlie lineage determination and maintenance. One prevailing view is that several transcription factors enable chromatin access in combination. The homeodomain protein CDX2 specifies the embryonic intestinal epithelium, through unknown mechanisms, and partners with transcription factors such as HNF4A in the adult intestine. We examined enhancer chromatin and gene expression following Cdx2 or Hnf4a excision in mouse intestines. HNF4A loss did not affect CDX2 binding or chromatin, whereas CDX2 depletion modified chromatin significantly at CDX2-bound enhancers, disrupted HNF4A occupancy, and abrogated expression of neighboring genes. Thus, CDX2 maintains transcription-permissive chromatin, illustrating a powerful and dominant effect on enhancer configuration in an adult tissue. Similar, hierarchical control of cell-specific chromatin states is probably a general property of master transcription factors. PMID:23129810

Factors Associated with Long-Term Control of Type 2 Diabetes Mellitus.

PubMed

Badedi, Mohammed; Solan, Yahiya; Darraj, Hussain; Sabai, Abdullah; Mahfouz, Mohamed; Alamodi, Saleh; Alsabaani, Abdullah

2016-01-01

Aims. This study assessed factors associated with glycemic control among Saudi patients with Type 2 diabetes mellitus (T2DM). Methods. We conducted an analytical cross-sectional study, which included a random sample of 288 patients with T2DM proportional to the diabetes population of each primary health care center in Jazan city, Kingdom of Saudi Arabia. Results. More than two-thirds (74%) of patients had poor glycemic control. Lack of education, polypharmacy, and duration of diabetes ≥ 7 years were significantly associated with higher glycated hemoglobin (HbA1c). Moreover, patients who were smoker or divorced were significantly more likely to have higher HbA1c. The patients who did not comply with diet or take their medications as prescribed had poor glycemic control. The study found lower HbA1c levels among patients who received family support or had close relationship with their physicians. Similarly, knowledgeable patients towards diabetes or those with greater confidence in ability to manage self-care behaviors had a lower HbA1c. In contrast, risk factors such as depression or stress were significantly correlated with poorer glycemic control. Conclusion. The majority of T2DM patients had poor glycemic control. The study identified several factors associated with glycemic control. Effective and tailored interventions are needed to mitigate exposure to these risk factors. This would improve glycemic control and reduce the risks inherent to diabetes complications.

Direct Digital Control of HVAC (Heating, Ventilating, and Air Conditioning).

DTIC Science & Technology

1985-01-01

controller func- tions such as time-of-day, economizer cycles, reset, load shedding, chiller optimization , VAV fan synchronization, and optimum start/stop...control system such as that illustrated in Fig- urc 4. Data on setpoints , reset schedules, and event timing, such as that presented in Figure 6, are...program code (Figure 7). In addition to the control logic, setpoint and other data are readily available. Program logi:, setpoint and schedule data, and

Positive and negative regulation by SLP-76/ADAP and Pyk2 of chemokine-stimulated T-lymphocyte adhesion mediated by integrin α4β1

PubMed Central

Dios-Esponera, Ana; Isern de Val, Soledad; Sevilla-Movilla, Silvia; García-Verdugo, Rosa; García-Bernal, David; Arellano-Sánchez, Nohemí; Cabañas, Carlos; Teixidó, Joaquin

2015-01-01

Stimulation by chemokines of integrin α4β1–dependent T-lymphocyte adhesion is a crucial step for lymphocyte trafficking. The adaptor Vav1 is required for chemokine-activated T-cell adhesion mediated by α4β1. Conceivably, proteins associating with Vav1 could potentially modulate this adhesion. Correlating with activation by the chemokine CXCL12 of T-lymphocyte attachment to α4β1 ligands, a transient stimulation in the association of Vav1 with SLP-76, Pyk2, and ADAP was observed. Using T-cells depleted for SLP-76, ADAP, or Pyk2, or expressing Pyk2 kinase–inactive forms, we show that SLP-76 and ADAP stimulate chemokine-activated, α4β1-mediated adhesion, whereas Pyk2 opposes T-cell attachment. While CXCL12-promoted generation of high-affinity α4β1 is independent of SLP-76, ADAP, and Pyk2, the strength of α4β1-VCAM-1 interaction and cell spreading on VCAM-1 are targets of regulation by these three proteins. GTPase assays, expression of activated or dominant-negative Rac1, or combined ADAP and Pyk2 silencing indicated that Rac1 activation by CXCL12 is a common mediator response in SLP-76–, ADAP-, and Pyk2-regulated cell adhesion involving α4β1. Our data strongly suggest that chemokine-stimulated associations between Vav1, SLP-76, and ADAP facilitate Rac1 activation and α4β1-mediated adhesion, whereas Pyk2 opposes this adhesion by limiting Rac1 activation. PMID:26202465

GrpL, a Grb2-related Adaptor Protein, Interacts with SLP-76 to Regulate Nuclear Factor of Activated T Cell Activation

PubMed Central

Law, Che-Leung; Ewings, Maria K.; Chaudhary, Preet M.; Solow, Sasha A.; Yun, Theodore J.; Marshall, Aaron J.; Hood, Leroy; Clark, Edward A.

1999-01-01

Propagation of signals from the T cell antigen receptor (TCR) involves a number of adaptor molecules. SH2 domain–containing protein 76 (SLP-76) interacts with the guanine nucleotide exchange factor Vav to activate the nuclear factor of activated cells (NF-AT), and its expression is required for normal T cell development. We report the cloning and characterization of a novel Grb2-like adaptor molecule designated as Grb2-related protein of the lymphoid system (GrpL). Expression of GrpL is restricted to hematopoietic tissues, and it is distinguished from Grb2 by having a proline-rich region. GrpL can be coimmunoprecipitated with SLP-76 but not with Sos1 or Sos2 from Jurkat cell lysates. In contrast, Grb2 can be coimmunoprecipitated with Sos1 and Sos2 but not with SLP-76. Moreover, tyrosine-phosphorylated LAT/pp36/38 in detergent lysates prepared from anti-CD3 stimulated T cells associated with Grb2 but not GrpL. These data reveal the presence of distinct complexes involving GrpL and Grb2 in T cells. A functional role of the GrpL–SLP-76 complex is suggested by the ability of GrpL to act alone or in concert with SLP-76 to augment NF-AT activation in Jurkat T cells. PMID:10209041

Ofloxacin induces apoptosis via β1 integrin-EGFR-Rac1-Nox2 pathway in microencapsulated chondrocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sheng, Zhi-Guo; Huang, Wei; Liu, Yu-Xiang

2013-02-15

Quinolones (QNs)-induced arthropathy is an important toxic side-effect in immature animals leading to the restriction of their therapeutic use in pediatrics. Ofloxacin, a typical QN, was found to induce the chondrocytes apoptosis in the early phase (12–48 h) of arthropathy in our previous study. However, the exact mechanism(s) is unclear. Microencapsulated juvenile rabbit joint chondrocytes, a three-dimensional culture system, is utilized to perform the present study. Ofloxacin, at a therapeutically relevant concentration (10 μg/ml), disturbs the interaction between β1 integrin and activated intracellular signaling proteins at 12 h, which is inhibited when supplementing Mg{sup 2+}. Intracellular reactive oxygen species (ROS)more » significantly increases in a time-dependent manner after exposure to ofloxacin for 12–48 h. Furthermore, ofloxacin markedly enhances the level of activated Rac1 and epidermal growth factor receptor (EGFR) phosphorylation, and its inhibition in turn reduces the ROS production, apoptosis and Rac1 activation. Silencing Nox2, Rac1 or supplementing Mg{sup 2+} inhibits ROS accumulation, apoptosis occurrence and EGFR phosphorylation induced by ofloxacin. However, depletion of Nox2, Rac1 and inhibition of EGFR do not affect ofloxacin-mediated loss of interaction between β1 integrin and activated intracellular signaling proteins. In addition, ofloxacin also induces Vav2 phosphorylation, which is markedly suppressed after inactivating EGFR or supplementing Mg{sup 2+}. These results suggest that ofloxacin causes Nox2-mediated intracellular ROS production by disrupting the β1 integrin function and then activating the EGFR-Vav2-Rac1 pathway, finally resulting in apoptosis within 12–48 h exposure. The present study provides a novel insight regarding the potential role of Nox-driven ROS in QNs-induced arthropathy. - Highlights: ► Ofloxacin induces Nox2-driven ROS in encapsulated chondrocyte at 12–48 h. ► Ofloxacin stimulates ROS

Dissecting GRB7-mediated signals for proliferation and migration in HER2 overexpressing breast tumor cells: GTP-ase rules.

PubMed

Pradip, De; Bouzyk, Mark; Dey, Nandini; Leyland-Jones, Brian

2013-01-01

Amplification of human Her2 and its aberrant signaling in 20-30% of early breast cancer patients is responsible for highly aggressive tumors with poor outcome. Grb7 is reported to be co-amplified with Her2. We report a concurrent high expression of mRNA (from FFPE tumor samples; mRNA correlation, Pearson r(2)= 0.806), and high levels of GRB7 protein (immunoblot) in HER2+ breast cancer cell lines. We demonstrated the signaling mechanism of HER2 and downstream effectors that contributes to proliferation and migration. Using HER2+ and trastuzumab-resistant breast cancer cell lines, we identified the interaction between GRB7 and HER2 in the control of HER2+ cell proliferation. Our co-IP data show that GRB7 recruits SHC into the HER2-GRB7 signaling complex. This complex formation leads to activation of RAS-GTP. We also observed that following integrin engagement, GRB7 is phosphorylated at tyrosine in a p-FAK (Y397) dependent manner. This FAK-GRB7 complex leads to downstream activation of RAC1-GTP (responsible for migration) probably through the recruitment of VAV2. Our CO-IP data demonstrate that GRB7 directly binds with VAV2 following fibronectin engagement in HER2+ cells. To address whether GRB7 could serve as a pathway specific therapeutic target, we used siRNA to suppress GRB7 expression. Knockdown of GRB7 expression in the HER2+ breast cancer cell lines decreases RAS activation, cell proliferation, 2D and 3D colony formation and also blocked integrin-mediated RAC1 activation along with integrin-directed cell migration. These findings dissected the HER2-mediated signaling cascade into (1) HER2+ cell proliferation (HER2-GRB7-SHC-RAS) and (2) HER2+ cell migration (alpha5 beta1/alpha4 beta1-FAK-GRB7-VAV2-RAC1). Our data clearly demonstrate that a coupling of GRB7 with HER2 is required for the proliferative and migratory signals in HER2+ breast tumor cells.

Pak and Rac GTPases promote oncogenic KIT–induced neoplasms

PubMed Central

Martin, Holly; Mali, Raghuveer Singh; Ma, Peilin; Chatterjee, Anindya; Ramdas, Baskar; Sims, Emily; Munugalavadla, Veerendra; Ghosh, Joydeep; Mattingly, Ray R.; Visconte, Valeria; Tiu, Ramon V.; Vlaar, Cornelis P.; Dharmawardhane, Suranganie; Kapur, Reuben

2013-01-01

An acquired somatic mutation at codon 816 in the KIT receptor tyrosine kinase is associated with poor prognosis in patients with systemic mastocytosis and acute myeloid leukemia (AML). Treatment of leukemic cells bearing this mutation with an allosteric inhibitor of p21–activated kinase (Pak) or its genetic inactivation results in growth repression due to enhanced apoptosis. Inhibition of the upstream effector Rac abrogates the oncogene-induced growth and activity of Pak. Although both Rac1 and Rac2 are constitutively activated via the guanine nucleotide exchange factor (GEF) Vav1, loss of Rac1 or Rac2 alone moderately corrected the growth of KIT-bearing leukemic cells, whereas the combined loss resulted in 75% growth repression. In vivo, the inhibition of Vav or Rac or Pak delayed the onset of myeloproliferative neoplasms (MPNs) and corrected the associated pathology in mice. To assess the role of Rac GEFs in oncogene-induced transformation, we used an inhibitor of Rac, EHop-016, which specifically targets Vav1 and found that EHop-016 was a potent inhibitor of human and murine leukemic cell growth. These studies identify Pak and Rac GTPases, including Vav1, as potential therapeutic targets in MPN and AML involving an oncogenic form of KIT. PMID:24091327

Direct Digital Control of HVAC (Heating, Ventilating, and Air Conditioning Equipment (User’s Guide)

DTIC Science & Technology

1985-01-01

reset, load shedding, chiller optimization , VAV fan synchronization, and optimum start/stop. The prospective buyer of a DDC system should investigate...current and accurate drawings for a conventional, built-up control system such as that illustrated in Fig- ure 4. Data on setpoints , reset schedules, and...are always available in the form of the computer program code (Figure 7). In addition to the control logic, setpoint and other data are readily

Positive and negative regulation by SLP-76/ADAP and Pyk2 of chemokine-stimulated T-lymphocyte adhesion mediated by integrin α4β1.

PubMed

Dios-Esponera, Ana; Isern de Val, Soledad; Sevilla-Movilla, Silvia; García-Verdugo, Rosa; García-Bernal, David; Arellano-Sánchez, Nohemí; Cabañas, Carlos; Teixidó, Joaquin

2015-09-15

Stimulation by chemokines of integrin α4β1-dependent T-lymphocyte adhesion is a crucial step for lymphocyte trafficking. The adaptor Vav1 is required for chemokine-activated T-cell adhesion mediated by α4β1. Conceivably, proteins associating with Vav1 could potentially modulate this adhesion. Correlating with activation by the chemokine CXCL12 of T-lymphocyte attachment to α4β1 ligands, a transient stimulation in the association of Vav1 with SLP-76, Pyk2, and ADAP was observed. Using T-cells depleted for SLP-76, ADAP, or Pyk2, or expressing Pyk2 kinase-inactive forms, we show that SLP-76 and ADAP stimulate chemokine-activated, α4β1-mediated adhesion, whereas Pyk2 opposes T-cell attachment. While CXCL12-promoted generation of high-affinity α4β1 is independent of SLP-76, ADAP, and Pyk2, the strength of α4β1-VCAM-1 interaction and cell spreading on VCAM-1 are targets of regulation by these three proteins. GTPase assays, expression of activated or dominant-negative Rac1, or combined ADAP and Pyk2 silencing indicated that Rac1 activation by CXCL12 is a common mediator response in SLP-76-, ADAP-, and Pyk2-regulated cell adhesion involving α4β1. Our data strongly suggest that chemokine-stimulated associations between Vav1, SLP-76, and ADAP facilitate Rac1 activation and α4β1-mediated adhesion, whereas Pyk2 opposes this adhesion by limiting Rac1 activation. © 2015 Dios-Esponera, Isern de Val, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Type 2 Diabetes: Model of Factors Associated with Glycemic Control.

PubMed

Aghili, Rokhsareh; Polonsky, William H; Valojerdi, Ameneh Ebrahim; Malek, Mojtaba; Keshtkar, Abbas Ali; Esteghamati, Alireza; Heyman, Mark; Khamseh, Mohammad Ebrahim

2016-10-01

The purpose of this study was to evaluate the related factors and their intercorrelated impacts on glycemic control in people with type 2 diabetes mellitus. Patients with type 2 diabetes were recruited for this study during their regular clinic visits at a major medical centre in Iran. Glycated hemoglobin (A1C) levels were used as the indicator of glycemic control. Regression analysis was used to determine the relationships between glycemic control and demographics, self-care behaviours, resources and affective variables. Moreover, the associations between diabetes-related distress and measured variables were tested. Three hundred eighty people with type 2 diabetes completed the study. The mean duration of diabetes was 8.94±6.57 years, and the mean A1C levels were 7.78%±1.7%. Diabetes-related distress was significantly associated with A1C levels, controlling for all other variables (p=0.01). On the other hand, depression (p<0.001), self-management (p<0.001), anxiety (p<0.001) and patient-physician relationship (p=0.023) were significantly associated with diabetes-related distress. Diabetes-related distress was found to be associated with glycemic control in people with type 2 diabetes, whereas age, depression, anxiety, self-management and family and social support may affect glycemic control indirectly through diabetes-related distress. Thus, it is important to assess and, if appropriate, treat people with diabetes for diabetes-related distress in order to identify and help them overcome barriers to optimal glycemic control. Copyright © 2016 Canadian Diabetes Association. All rights reserved.

[Elucidating the molecular mechanism of prostate cancer progression under chronic hypoxia and development of the novel therapeutic approach].

PubMed

Nomura, Takeo; Yamasaki, Mutsushi; Mimata, Hiromitsu

2014-12-01

Cancer cells encounter a hypoxic microenvironment during tumor growth and progression. In addition, androgen-deprivation therapy against prostate cancer can develop secondary to a hypoxic condition caused by drastic blood supply reduction because androgen drives angiogenic inducers including vascular endothelial growth factor (VEGF) and inhibits angiogenesis inhibitor prostatic pigment epithelium-derived factor (PEDF). Extreme hypoxic conditions are not suitable for cancer survival, however, cancer cells soon adapt to a hypoxic environment and survive. We established a prostate cancer cell line cultured under chronic hypoxia and analyzed a castration-resistant phenotype. Here, the Vav3 was identified as a key oncogenic molecule associated with castration-resistance under chronic hypoxia. We analyzed the functions of Vav3 and Vav3-mediated signaling to establish a novel therapeutic target for castration-resistant prostate cancer.

DNMT3B modulates the expression of cancer-related genes and downregulates the expression of the gene VAV3 via methylation

PubMed Central

Peralta-Arrieta, Irlanda; Hernández-Sotelo, Daniel; Castro-Coronel, Yaneth; Leyva-Vázquez, Marco Antonio; Illades-Aguiar, Berenice

2017-01-01

Altered promoter DNA methylation is one of the most important epigenetic abnormalities in human cancer. DNMT3B, de novo methyltransferase, is clearly related to abnormal methylation of tumour suppressor genes, DNA repair genes and its overexpression contributes to oncogenic processes and tumorigenesis in vivo. The purpose of this study was to assess the effect of the overexpression of DNMT3B in HaCaT cells on global gene expression and on the methylation of selected genes to the identification of genes that can be target of DNMT3B. We found that the overexpression of DNMT3B in HaCaT cells, modulate the expression of genes related to cancer, downregulated the expression of 151 genes with CpG islands and downregulated the expression of the VAV3 gene via methylation of its promoter. These results highlight the importance of DNMT3B in gene expression and human cancer. PMID:28123849

DNMT3B modulates the expression of cancer-related genes and downregulates the expression of the gene VAV3 via methylation.

PubMed

Peralta-Arrieta, Irlanda; Hernández-Sotelo, Daniel; Castro-Coronel, Yaneth; Leyva-Vázquez, Marco Antonio; Illades-Aguiar, Berenice

2017-01-01

Altered promoter DNA methylation is one of the most important epigenetic abnormalities in human cancer. DNMT3B, de novo methyltransferase, is clearly related to abnormal methylation of tumour suppressor genes, DNA repair genes and its overexpression contributes to oncogenic processes and tumorigenesis in vivo . The purpose of this study was to assess the effect of the overexpression of DNMT3B in HaCaT cells on global gene expression and on the methylation of selected genes to the identification of genes that can be target of DNMT3B. We found that the overexpression of DNMT3B in HaCaT cells, modulate the expression of genes related to cancer, downregulated the expression of 151 genes with CpG islands and downregulated the expression of the VAV3 gene via methylation of its promoter. These results highlight the importance of DNMT3B in gene expression and human cancer.

Phage display discovery of novel molecular targets in glioblastoma-initiating cells.

PubMed

Liu, J K; Lubelski, D; Schonberg, D L; Wu, Q; Hale, J S; Flavahan, W A; Mulkearns-Hubert, E E; Man, J; Hjelmeland, A B; Yu, J; Lathia, J D; Rich, J N

2014-08-01

Glioblastoma is the most common primary intrinsic brain tumor and remains incurable despite maximal therapy. Glioblastomas display cellular hierarchies with self-renewing glioma-initiating cells (GICs) at the apex. To discover new GIC targets, we used in vivo delivery of phage display technology to screen for molecules selectively binding GICs that may be amenable for targeting. Phage display leverages large, diverse peptide libraries to identify interactions with molecules in their native conformation. We delivered a bacteriophage peptide library intravenously to a glioblastoma xenograft in vivo then derived GICs. Phage peptides bound to GICs were analyzed for their corresponding proteins and ranked based on prognostic value, identifying VAV3, a Rho guanine exchange factor involved tumor invasion, and CD97 (cluster of differentiation marker 97), an adhesion G-protein-coupled-receptor upstream of Rho, as potentially enriched in GICs. We confirmed that both VAV3 and CD97 were preferentially expressed by tumor cells expressing GIC markers. VAV3 expression correlated with increased activity of its downstream mediator, Rac1 (ras-related C3 botulinum toxin substrate 1), in GICs. Furthermore, targeting VAV3 by ribonucleic acid interference decreased GIC growth, migration, invasion and in vivo tumorigenesis. As CD97 is a cell surface protein, CD97 selection enriched for sphere formation, a surrogate of self-renewal. In silico analysis demonstrated VAV3 and CD97 are highly expressed in tumors and inform poor survival and tumor grade, and more common with epidermal growth factor receptor mutations. Finally, a VAV3 peptide sequence identified on phage display specifically internalized into GICs. These results show a novel screening method for identifying oncogenic pathways preferentially activated within the tumor hierarchy, offering a new strategy for developing glioblastoma therapies.

Phage display discovery of novel molecular targets in glioblastoma-initiating cells

PubMed Central

Liu, J K; Lubelski, D; Schonberg, D L; Wu, Q; Hale, J S; Flavahan, W A; Mulkearns-Hubert, E E; Man, J; Hjelmeland, A B; Yu, J; Lathia, J D; Rich, J N

2014-01-01

Glioblastoma is the most common primary intrinsic brain tumor and remains incurable despite maximal therapy. Glioblastomas display cellular hierarchies with self-renewing glioma-initiating cells (GICs) at the apex. To discover new GIC targets, we used in vivo delivery of phage display technology to screen for molecules selectively binding GICs that may be amenable for targeting. Phage display leverages large, diverse peptide libraries to identify interactions with molecules in their native conformation. We delivered a bacteriophage peptide library intravenously to a glioblastoma xenograft in vivo then derived GICs. Phage peptides bound to GICs were analyzed for their corresponding proteins and ranked based on prognostic value, identifying VAV3, a Rho guanine exchange factor involved tumor invasion, and CD97 (cluster of differentiation marker 97), an adhesion G-protein-coupled-receptor upstream of Rho, as potentially enriched in GICs. We confirmed that both VAV3 and CD97 were preferentially expressed by tumor cells expressing GIC markers. VAV3 expression correlated with increased activity of its downstream mediator, Rac1 (ras-related C3 botulinum toxin substrate 1), in GICs. Furthermore, targeting VAV3 by ribonucleic acid interference decreased GIC growth, migration, invasion and in vivo tumorigenesis. As CD97 is a cell surface protein, CD97 selection enriched for sphere formation, a surrogate of self-renewal. In silico analysis demonstrated VAV3 and CD97 are highly expressed in tumors and inform poor survival and tumor grade, and more common with epidermal growth factor receptor mutations. Finally, a VAV3 peptide sequence identified on phage display specifically internalized into GICs. These results show a novel screening method for identifying oncogenic pathways preferentially activated within the tumor hierarchy, offering a new strategy for developing glioblastoma therapies. PMID:24832468

Nuclear factor erythroid 2-related factor-2 activity controls 4-hydroxynonenal metabolism and activity in prostate cancer cells.

PubMed

Pettazzoni, Piergiorgio; Ciamporcero, Eric; Medana, Claudio; Pizzimenti, Stefania; Dal Bello, Federica; Minero, Valerio Giacomo; Toaldo, Cristina; Minelli, Rosalba; Uchida, Koji; Dianzani, Mario Umberto; Pili, Roberto; Barrera, Giuseppina

2011-10-15

4-Hydroxynonenal (HNE) is an end product of lipoperoxidation with antiproliferative and proapoptotic properties in various tumors. Here we report a greater sensitivity to HNE in PC3 and LNCaP cells compared to DU145 cells. In contrast to PC3 and LNCaP cells, HNE-treated DU145 cells showed a smaller reduction in growth and did not undergo apoptosis. In DU145 cells, HNE did not induce ROS production and DNA damage and generated a lower amount of HNE-protein adducts. DU145 cells had a greater GSH and GST A4 content and GSH/GST-mediated HNE detoxification. Nuclear factor erythroid 2-related factor-2 (Nrf2) is a regulator of the antioxidant response. Nrf2 protein content and nuclear accumulation were higher in DU145 cells compared to PC3 and LNCaP cells, whereas the expression of KEAP1, the main negative regulator of Nrf2 activity, was lower. Inhibition of Nrf2 expression with specific siRNA resulted in a reduction in GST A4 expression and GS-HNE formation, indicating that Nrf2 controls HNE metabolism. In addition, Nrf2 knockdown sensitized DU145 cells to HNE-mediated antiproliferative and proapoptotic activity. In conclusion, we demonstrated that increased Nrf2 activity resulted in a reduction in HNE sensitivity in prostate cancer cells, suggesting a potential mechanism of resistance to pro-oxidant therapy. Copyright © 2011 Elsevier Inc. All rights reserved.

Users Guide to Direct Digital Control of Heating, Ventilating, and Air Conditioning Equipment,

DTIC Science & Technology

1985-01-01

cycles, reset, load shedding, chiller optimization , VAV fan synchronization, and optimum start/stop. The prospective buyer of a DDC system should...in Fig- ure 4. Data on setpoints , reset schedules, and event timing, such as that presented in Figure 6, are often even more difficult to find. In con...control logic, setpoint and other data are readily available. Program logic, setpoint and schedule data, and other information stored in a DDC unit

Age-related obesity and type 2 diabetes dysregulate neuronal associated genes and proteins in humans

PubMed Central

Daghighi, Mojtaba; Özcan, Behiye; Akbarkhanzadeh, Vishtaseb; Sheedfar, Fareeba; Amini, Marzyeh; Mazza, Tommaso; Pazienza, Valerio; Motazacker, Mahdi M.; Mahmoudi, Morteza; De Rooij, Felix W. M.; Sijbrands, Eric; Peppelenbosch, Maikel P.; Rezaee, Farhad

2015-01-01

Despite numerous developed drugs based on glucose metabolism interventions for treatment of age-related diseases such as diabetes neuropathies (DNs), DNs are still increasing in patients with type 1 or type 2 diabetes (T1D, T2D). We aimed to identify novel candidates in adipose tissue (AT) and pancreas with T2D for targeting to develop new drugs for DNs therapy. AT-T2D displayed 15 (e.g. SYT4 up-regulated and VGF down-regulated) and pancreas-T2D showed 10 (e.g. BAG3 up-regulated, VAV3 and APOA1 down-regulated) highly differentially expressed genes with neuronal functions as compared to control tissues. ELISA was blindly performed to measure proteins of 5 most differentially expressed genes in 41 human subjects. SYT4 protein was upregulated, VAV3 and APOA1 were down-regulated, and BAG3 remained unchanged in 1- Obese and 2- Obese-T2D without insulin, VGF protein was higher in these two groups as well as in group 3- Obese-T2D receiving insulin than 4-lean subjects. Interaction networks analysis of these 5 genes showed several metabolic pathways (e.g. lipid metabolism and insulin signaling). Pancreas is a novel site for APOA1 synthesis. VGF is synthesized in AT and could be considered as good diagnostic, and even prognostic, marker for age-induced diseases obesity and T2D. This study provides new targets for rational drugs development for the therapy of age-related DNs. PMID:26337083

A Protein Scaffold Coordinates SRC-Mediated JNK Activation in Response to Metabolic Stress.

PubMed

Kant, Shashi; Standen, Claire L; Morel, Caroline; Jung, Dae Young; Kim, Jason K; Swat, Wojciech; Flavell, Richard A; Davis, Roger J

2017-09-19

Obesity is a major risk factor for the development of metabolic syndrome and type 2 diabetes. How obesity contributes to metabolic syndrome is unclear. Free fatty acid (FFA) activation of a non-receptor tyrosine kinase (SRC)-dependent cJun NH 2 -terminal kinase (JNK) signaling pathway is implicated in this process. However, the mechanism that mediates SRC-dependent JNK activation is unclear. Here, we identify a role for the scaffold protein JIP1 in SRC-dependent JNK activation. SRC phosphorylation of JIP1 creates phosphotyrosine interaction motifs that bind the SH2 domains of SRC and the guanine nucleotide exchange factor VAV. These interactions are required for SRC-induced activation of VAV and the subsequent engagement of a JIP1-tethered JNK signaling module. The JIP1 scaffold protein, therefore, plays a dual role in FFA signaling by coordinating upstream SRC functions together with downstream effector signaling by the JNK pathway. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Heating, ventilation and air conditioning system optimization: a study of the effect of climate, building design, system selection and control strategy on the energy consumption of a typical office building in London and Athens

NASA Astrophysics Data System (ADS)

Spasis, Georgios

The increasing demand for air conditioning in commercial buildings imposes a serious threat to Europe's CO2 reduction targets. Architects and engineers are therefore in a key position to help reduce the impact of buildings on the environment by taking appropriate decisions concerning the design of the building and the associated heating, ventilation and air conditioning (HVAC) system. The thesis studies the effect of a number of building and HVAC system related design factors on the energy performance of a notional air-conditioned office building employing either a variable air volume (VAV) system with terminal re-heaters, or a four-pipe fan coil unit (FCU) system with fresh air supply from a central plant, using mainly a dynamic simulation tool and the response surface methodology. The evaluation of the energy performance of the HVAC systems is for two types of climate, using typical weather data for London (UK) and Athens (Greece). It has been found that the design variables associated with the solar radiation through the transparent building elements and the internal heat gains should be the main concern of the building designer. On the other hand, the HVAC system engineer should give emphasis to the parameters associated with the plant performance and operation, as well as the temperature control set-points. It has been shown that it is possible to reduce the carbon emissions of the base case scenario by up to 88% depending on the HVAC system and the climate for which it is simulated. The carbon savings, however, are reduced by up to 22% where humidification is provided. This reduction differs depending on the HVAC system and the climatic conditions. The VAV system is more energy efficient than the FCU system, mainly due to the exploitation of the free cooling capacity of the outdoor air. The difference in carbon emissions between the two systems drops when both of them are simulated for the Athens as opposed to the London typical weather conditions. It has

Are elements of the chronic care model associated with cardiovascular risk factor control in type 2 diabetes?

PubMed

Parchman, Michael; Kaissi, Amer A

2009-03-01

Control of modifiable risk factors for cardiovascular (CV) disease, the most common cause of morbidity and mortality among people with Type 2 diabetes is dependent on both patient self-care behaviors and the characteristics of the clinic in which care is delivered. The relationship between control of CV risk factors, patient self-care behaviors, and the presence of CCM (Chronic Care Model) components across multiple primary care clinic settings was examined. Thirty consecutive patients presenting with Type 2 diabetes were enrolled from each of 20 primary care clinics from across South Texas. Patients were asked about their stage of change for four self-care behaviors: diet, exercise, glucose monitoring, and medication adherence. CV risk factors included the most recent values of glycosolated hemoglobin (A1C), blood pressure, and (low-density lipoprotein) cholesterol. Clinicians in each clinic completed the Assessment of Chronic Illness Care (ACIC) survey, a validated measure of the CCM components. Hierarchical logistic regression models were used. Only 25 (13%) of the 618 patients had good control of all three CV risk factors. Good control of these risk factors was positively associated with community linkages and delivery system design but was inversely associated with clinical information systems. Patients who were in the maintenance stage of change for all four self-care behaviors were more likely to have all three risk factors well controlled. Risk factors for CV disease among patients with diabetes are associated with the structure and design of the clinical microsystem where care is delivered. In addition to focusing on clinician knowledge, future interventions should address the clinical microsystem's structure and design to reduce the burden of CV disease among patients with Type 2 diabetes.

Assessment of the Activation of Rho Family GTP-Binding Proteins in Breast Cancer Cells and Specimens

DTIC Science & Technology

2001-08-01

lymphopenia Vav2 GEF for Rho, Rac, and Cdc42 proto-oncogene product; NM009500 Vav3 GEF for Rho and Rac proto-oncogene product; NM020505 hPEM -2 GEF for...junctions, and desmosomes play a fundamental role in maintaining the polarized phenotype and vectorial transport functions of epithelial cells. The tight

Tokamak Operation with Safety Factor q 95 < 2 via Control of MHD Stability

DOE PAGES

Piovesan, Paolo; Hanson, Jeremy M.; Martin, Piero; ...

2014-07-24

Magnetic feedback control of the resistive-wall mode has enabled DIII-D to access stable operation at safety factor q95 = 1:9 in divertor plasmas for 150 instability growth times. Magnetohydrodynamic stability sets a hard, disruptive limit on the minimum edge safety factor achievable in a tokamak, or on the maximum plasma current at given toroidal magnetic eld. In tokamaks with a divertor, the limit occurs at q95 = 2, as con rmed in DIII-D. Since the energy con cement time scales linearly with current, this also bounds the performance of a fusion reactor. DIII-D has overcome this limit, opening a wholemore » new high-current regime not accessible before. This result brings signi cant possible bene ts in terms of fusion performance, but it also extends resistive wall mode physics and its control to conditions never explored before. In present experiments, q95 < 2 operation is eventually halted by voltage limits reached in the feedback power supplies, not by intrinsic physics issues. Improvements to power supplies and to control algorithms have the potential to further extend this regime.« less

Commercialization of the power factor controller

NASA Technical Reports Server (NTRS)

1981-01-01

The purpose of the Motor Power Controller, also known as the Power Factor Controller, is to improve power factor and reduce power dissipation in induction motors operating below full load. These purposes were studied and tested in detail. The Motor Power Controller is capable of raising power factors from 0.2 to 0.8 and results in energy savings. It was found that many motors, in their present operating applications, are classified as unstable. The electronic nature of the controller vs. the electrical nature of the motor, compound this problem due to the differences in response time of the two devices. Many tests were successfully completed, the most indicating greater savings than anticipated. Also, there was an effect on efficiency which was not included in the calculations.

Cooperative interactions at the SLP-76 complex are critical for actin polymerization.

PubMed

Barda-Saad, Mira; Shirasu, Naoto; Pauker, Maor H; Hassan, Nirit; Perl, Orly; Balbo, Andrea; Yamaguchi, Hiroshi; Houtman, Jon C D; Appella, Ettore; Schuck, Peter; Samelson, Lawrence E

2010-07-21

T-cell antigen receptor (TCR) engagement induces formation of multi-protein signalling complexes essential for regulating T-cell functions. Generation of a complex of SLP-76, Nck and VAV1 is crucial for regulation of the actin machinery. We define the composition, stoichiometry and specificity of interactions in the SLP-76, Nck and VAV1 complex. Our data reveal that this complex can contain one SLP-76 molecule, two Nck and two VAV1 molecules. A direct interaction between Nck and VAV1 is mediated by binding between the C-terminal SH3 domain of Nck and the VAV1 N-terminal SH3 domain. Disruption of the VAV1:Nck interaction deleteriously affected actin polymerization. These novel findings shed new light on the mechanism of actin polymerization after T-cell activation.

Factors associated with poor Hemoglobin A1c control in Patients with Type 2 Diabetes.

PubMed

Alqudah, Salam; Jarab, Anan S; Alefishat, Eman A; Mayyas, Fadia; Khdour, Maher; Pinto, Sharrel

2018-05-10

Background The limited implementation of clinical pharmacy service programs and the lack of studies identifying barriers to achieve blood glucose control have all attributed to the increased proportion of type 2 diabetes patients who have poor glycemic control in Jordan. Objective To explore factors associated with higher HbA1c in patients with type 2 diabetes in Jordan. Method Variables including socio-demographics, disease and treatment factors were collected from171 patients with type2 diabetes at an outpatient diabetes clinic in Amman. Validated questionnaires were used to assess medication adherence, self-care activities, diabetes knowledge and health-related quality of life in addition to data collected from medical records. After the single-predictor analysis, stepwise linear regression was performed to develop a model with variables that best predicted hemoglobin A1c. Results Medication adherence was inversely associated with HbA1c values (β = -0.275; t = 2.666; P < 0.01), indicating better glycemic control. Receiving insulin therapy was also associated with less HbA1c values and better glycemic control (β = - 0.184; t = 2.080; P < 0.05). Patients who had one or more comorbid conditions (β = 0.215; t = 2.264; P < 0.05) and those with longer diabetes duration (β = 0.092; t = 1.339; P < 0.05) were found to have significantly higher HbA1c values. Conclusions Emphasizing medication adherence, particularly for patients with longer duration of diabetes and those with multiple comorbid diseases should be strongly considered in future diabetes management programs implemented to improve glycemic control in patients with type 2 diabetes. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

CD94/NKG2A inhibits NK cell activation by disrupting the actin network at the immunological synapse.

PubMed

Masilamani, Madhan; Nguyen, Connie; Kabat, Juraj; Borrego, Francisco; Coligan, John E

2006-09-15

An adequate immune response is the result of the fine balance between activation and inhibitory signals. The exact means by which inhibitory signals obviate activation signals in immune cells are not totally elucidated. Human CD94/NKG2A is an ITIM-containing inhibitory receptor expressed by NK cells and some CD8+ T cells that recognize HLA-E. We show that the engagement of this receptor prevents NK cell activation by disruption of the actin network and exclusion of lipid rafts at the point of contact with its ligand (inhibitory NK cell immunological synapse, iNKIS). CD94/NKG2A engagement leads to recruitment and activation of src homology 2 domain-bearing tyrosine phosphatase 1. This likely explains the observed dephosphorylation of guanine nucleotide exchange factor and regulator of actin, Vav1, as well as ezrin-radixin-moesin proteins that connect actin filaments to membrane structures. In contrast, NK cell activation by NKG2D induced Vav1 and ezrin-radixin-moesin phosphorylation. Thus, CD94/NKG2A prevents actin-dependent recruitment of raft-associated activation receptors complexes to the activating synapse. This was further substantiated by showing that inhibition of actin polymerization abolished lipid rafts exclusion at the iNKIS, whereas cholesterol depletion had no effect on actin disruption at the iNKIS. These data indicate that the lipid rafts exclusion at the iNKIS is an active process which requires an intact cytoskeleton to maintain lipid rafts outside the inhibitory synapse. The net effect is to maintain an inhibitory state in the proximity of the iNKIS, while allowing the formation of activation synapse at distal points within the same NK cell.

Risk factors for gallbladder cancer: a case-control study.

PubMed

Jain, Kajal; Sreenivas, V; Velpandian, T; Kapil, Umesh; Garg, Pramod Kumar

2013-04-01

Risk factors for gallbladder cancer (GBC) except gallstones are not well known. The objective was to study the risk factors for GBC. In a case-control study, 200 patients with GBC, 200 healthy controls and 200 gallstones patients as diseased controls were included prospectively. The risk factors studied were related to socioeconomic profile, life style, reproduction, diet and bile acids. On comparing GBC patients (mean age 51.7 years; 130 females) with healthy controls, risk factors were chemical exposure [odd ratios (OR): 7.0 (2.7-18.2); p < 0.001)], family history of gallstones [OR: 5.3 (1.5-18.9); p < 0.01)], tobacco [OR: 4.1 (1.8-9.7); p < 0.001)], fried foods [OR: 3.1 (1.7-5.6); p < 0.001], joint family [OR: 3.2 (1.7-6.2); p < 0.001], long interval between meals [OR: 1.4 (1.2-1.6); p < 0.001] and residence in Gangetic belt [OR: 3.3 (1.8-6.2); p < 0.001]. On comparing GBC cases with gallstone controls, risk factors were female gender [OR: 2.4 (1.3-4.3); p = 0.004], residence in Gangetic belt [OR: 2.3 (1.2-4.4); p = 0.012], fried foods [OR: 2.5 (1.4-4.4); p < 0.001], diabetes [OR: 2.7 (1.2-6.4); p = 0.02)], tobacco [OR 3.8 (1.7-8.1); p < 0.001)] and joint family [OR: 2.1 (1.2-3.4); p = 0.004]. The ratio of secondary to primary bile acids was significantly higher in GBC cases than gallstone controls (20.8 vs. 0.44). Fried foods, tobacco, chemical exposure, family history of gallstones, residence in Gangetic belt and secondary bile acids were significant risk factors for GBC. Copyright © 2012 UICC.

Neuropsychological functioning in older people with type 2 diabetes: the effect of controlling for confounding factors.

PubMed

Asimakopoulou, K G; Hampson, S E; Morrish, N J

2002-04-01

Neuropsychological functioning was examined in a group of 33 older (mean age 62.40 +/- 9.62 years) people with Type 2 diabetes (Group 1) and 33 non-diabetic participants matched with Group 1 on age, sex, premorbid intelligence and presence of hypertension and cardio/cerebrovascular conditions (Group 2). Data statistically corrected for confounding factors obtained from the diabetic group were compared with the matched control group. The results suggested small cognitive deficits in diabetic people's verbal memory and mental flexibility (Logical Memory A and SS7). No differences were seen between the two samples in simple and complex visuomotor attention, sustained complex visual attention, attention efficiency, mental double tracking, implicit memory, and self-reported memory problems. These findings indicate minimal cognitive impairment in relatively uncomplicated Type 2 diabetes and demonstrate the importance of control and matching for confounding factors.

Targeting AR Variant-Coactivator Interactions to Exploit Prostate Cancer Vulnerabilities.

PubMed

Magani, Fiorella; Peacock, Stephanie O; Rice, Meghan A; Martinez, Maria J; Greene, Ann M; Magani, Pablo S; Lyles, Rolando; Weitz, Jonathan R; Burnstein, Kerry L

2017-11-01

Castration-resistant prostate cancer (CRPC) progresses rapidly and is incurable. Constitutively active androgen receptor splice variants (AR-Vs) represent a well-established mechanism of therapeutic resistance and disease progression. These variants lack the AR ligand-binding domain and, as such, are not inhibited by androgen deprivation therapy (ADT), which is the standard systemic approach for advanced prostate cancer. Signaling by AR-Vs, including the clinically relevant AR-V7, is augmented by Vav3, an established AR coactivator in CRPC. Using mutational and biochemical studies, we demonstrated that the Vav3 Diffuse B-cell lymphoma homology (DH) domain interacted with the N-terminal region of AR-V7 (and full length AR). Expression of the Vav3 DH domain disrupted Vav3 interaction with and enhancement of AR-V7 activity. The Vav3 DH domain also disrupted AR-V7 interaction with other AR coactivators: Src1 and Vav2, which are overexpressed in PC. This Vav3 domain was used in proof-of-concept studies to evaluate the effects of disrupting the interaction between AR-V7 and its coactivators on CRPC cells. This disruption decreased CRPC cell proliferation and anchorage-independent growth, caused increased apoptosis, decreased migration, and resulted in the acquisition of morphological changes associated with a less aggressive phenotype. While disrupting the interaction between FL-AR and its coactivators decreased N-C terminal interaction, disrupting the interaction of AR-V7 with its coactivators decreased AR-V7 nuclear levels. Implications: This study demonstrates the potential therapeutic utility of inhibiting constitutively active AR-V signaling by disrupting coactivator binding. Such an approach is significant, as AR-Vs are emerging as important drivers of CRPC that are particularly recalcitrant to current therapies. Mol Cancer Res; 15(11); 1469-80. ©2017 AACR . ©2017 American Association for Cancer Research.

Factors influencing warfarin control in Australia and Singapore.

PubMed

Bernaitis, Nijole; Ching, Chi Keong; Teo, Siew Chong; Chen, Liping; Badrick, Tony; Davey, Andrew K; Crilly, Julia; Anoopkumar-Dukie, Shailendra

2017-09-01

Warfarin is widely used for patients with non-valvular atrial fibrillation (NVAF). Variations in warfarin control, as measured by time in therapeutic range (TTR), have been reported across different regions and ethnicities, particularly between Western and Asian countries. However, there is limited data on comparative factors influencing warfarin control in Caucasian and Asian patients. Therefore, the aim of this study was to determine warfarin control and potential factors influencing this in patients with NVAF in Australia and Singapore. Retrospective data was collected for patients receiving warfarin for January to June 2014 in Australia and Singapore. TTR was calculated for individuals with mean patient TTR used for analysis. Possible influential factors on TTR were analysed including age, gender, concurrent co-morbidities, and concurrent medication. The mean TTR was significantly higher in Australia (82%) than Singapore (58%). At both sites, chronic kidney disease significantly lowered this TTR. Further factors influencing control were anaemia and age<60years in Australia, and vascular disease, CHA 2 DS 2 -VASc score of 6, and concurrent platelet inhibitor therapy in Singapore. Warfarin control was significantly higher in Australia compared to Singapore, however chronic kidney disease reduced control at both sites. The different levels of control in these two countries, together with patient factors further reducing control may impact on anticoagulant choice in these countries with better outcomes from warfarin in Australia compared to Singapore. Copyright © 2017 Elsevier Ltd. All rights reserved.

Racial/ethnic differences in control of cardiovascular risk factors among type 2 diabetes patients in an insured, ambulatory care population.

PubMed

Holland, Ariel T; Zhao, Beinan; Wong, Eric C; Choi, Sarah E; Wong, Nathan D; Palaniappan, Latha P

2013-01-01

This paper examines differences in cardiovascular disease risk factor control among racial/ethnic minorities (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese, Hispanic/Latino, Black/African Americans) with type 2 diabetes compared to Non-Hispanic Whites with type 2 diabetes in an insured, outpatient setting. A three-year, cross-sectional sample of 15,826 patients with type 2 diabetes was studied between 2008 and 2010. Goal attainment rates for three cardiovascular disease risk factors (HbA1c, BP, LDL) were estimated. Logistic regression was used to determine the association between patient characteristics and control of risk factors. Only one fifth (21.1%) of patients achieved simultaneous goal attainment (HbA1c, BP, LDL). After adjustment for patient characteristics and treatment, Black/African American women and men, and Filipino and Hispanic/Latino men were significantly less likely to simultaneously achieve all three goals, compared to Non-Hispanic Whites. Of the three goals, patients were more likely to achieve HbA1c goals (68.7%) than BP (45.7%) or LDL (58.5%) goals. Racial/ethnic differences were more apparent in risk factors that were under better control (i.e. HbA1c). Cardiovascular risk factor control in type 2 diabetes is suboptimal, even in an insured population. Special attention may be required for specific racial/ethnic/gender groups. Copyright © 2013 Elsevier Inc. All rights reserved.

Health insurance status and control of diabetes and coronary artery disease risk factors on enrollment into the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial.

PubMed

Grogan, Mary; Jenkins, Margaret; Sansing, Veronica V; MacGregor, Joan; Brooks, Maria Mori; Julien-Williams, Patricia; Amendola, Angela; Abbott, J Dawn

2010-01-01

The purpose of this study was to examine measures of chronic disease severity and treatment according to insurance status in a clinical trial setting. Baseline insurance status of 776 patients with type 2 diabetes and stable coronary artery disease (CAD) enrolled in the United States in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial was analyzed with regard to measures of metabolic and cardiovascular risk factor control. Compared with patients with private or public insurance, the uninsured were younger, more often female, and less often white non-Hispanic. Uninsured patients had the greatest burden of CAD. Patients with public insurance were treated with the greatest number of medications, had the greatest self-reported functional status, and the lowest mean glycosylated hemoglobin and low-density lipoprotein (LDL) cholesterol values. Overall, for 5 measured risk factor targets, the mean number above goal was 2.49 ± 1.18. After adjustment for demographic and clinical variables, insurance status was not associated with a difference in risk factor control. In the BARI 2D trial, we did not observe a difference in baseline cardiovascular risk factor control according to insurance status. An important observation, however, was that risk factor control overall was suboptimal, which highlights the difficulty in treating type 2 diabetes and CAD irrespective of insurance status.

Control of glycemia and other cardiovascular disease risk factors in older adults with type 2 diabetes mellitus: data from the Adult Diabetes Control and Management.

PubMed

Sazlina, Shariff-Ghazali; Mastura, Ismail; Ahmad, Zaiton; Cheong, Ai-Theng; Adam, Bujang-Mohamad; Jamaiyah, Haniff; Lee, Ping-Yein; Syed-Alwi, Syed-Abdul-Rahman; Chew, Boon-How; Sriwahyu, Taher

2014-01-01

The aims of the present study were to assess the control of glycemia and other cardiovascular disease risk factors, and the association between age and these controls among older adults with type 2 diabetes in Malaysia. A cross-sectional study was carried out using cases notified to the Adult Diabetes Control and Management database between 1 January and 31 December 2009. A total of 10 363 people aged over 60 years with type 2 diabetes mellitus were included in the analyses. A standard online case report form was used to record demographic data, clinical factors (diabetes duration, comorbid condition and treatment modalities), cardiovascular disease risk factors, diabetes complications and laboratory assessments. The cardiovascular disease risk factors controls assessed included glycosylated hemoglobin (HbA(1c)) <7.0%, blood pressure, body mass index, waist circumference and lipid profiles. The proportion of older adults who achieved target HbA(1c) (<7.0%) was 41.7%. A greater proportion of older adults aged ≥80 years significantly achieved the targets of HbA(1c) <7% (P < 0.001), waist circumference (P < 0.001), low-density lipoprotein cholesterol <2.6 mmol/L (P = 0.007) and triglycerides <1.7 mmol/L (P = 0.001) when compared with the younger elderly groups. They were also associated with achieving target HbA(1c) <7.0% (OR = 1.90, 95% CI 1.68-2.26) and triglycerides <1.7 mmol/L (OR = 1.20, 95%CI 1.04-1.46) than those aged 60-69 years. The control of cardiovascular disease risk factors was suboptimal in older adults with type 2 diabetes. The oldest elderly were more likely to achieve target HbA(1c) (<7.0%) and triglycerides (<1.7 mmol/L) than older adults aged 60-69 years. © 2013 Japan Geriatrics Society.

Adding Salt to Meals as a Risk Factor of Type 2 Diabetes Mellitus: A Case-Control Study.

PubMed

Radzeviciene, Lina; Ostrauskas, Rytas

2017-01-13

Type 2 diabetes mellitus (T2DM) is thought to arise from the complex interplay between genetic and environmental factors. It is important to identify modifiable risk factors that may help to reduce the risk of diabetes. Data on salt intake and the risk of type 2 diabetes are limited. The aim of this study was to assess the relationship between adding salt to prepared meals and the risk of type 2 diabetes. In a case-control study, we included 234 cases, all of whom were patients aged 35-86 years with a newly confirmed diagnosis of T2DM, and 468 controls that were free of the disease. Cases and controls (ratio 1:2) were matched by gender and age (±5 years). A questionnaire was used to collect information on possible risk factors for diabetes. Adding salt to prepared meals was assessed according to: Never, when there was not enough, or almost every time without tasting. The odds ratios (OR), and 95% confidence intervals (CI) for type 2 diabetes was calculated using a conditional logistic regression. The cases had a higher body mass index and a significantly lower education level compared to the controls. Variables such as waist circumference, body mass index, eating speed, smoking, family history of diabetes, arterial hypertension, plasma triglycerides, educational level, occupational status, morning exercise, marital status, daily urine sodium excretion, and daily energy intake were retained in the models as confounders. After adjusting for possible confounders, an approximately two-fold increased risk of type 2 diabetes was determined in subjects who add salt to prepared meals when "it is not enough" or "almost every time without tasting" (1.82; 95% CI 1.19-2.78; p = 0.006) compared with never adding salt. Presented data suggest the possible relationship between additional adding of salt to prepared meals and an increased risk of type 2 diabetes.

A Knock-in Mouse Model of Human PHD2 Gene-associated Erythrocytosis Establishes a Haploinsufficiency Mechanism*

PubMed Central

Arsenault, Patrick R.; Pei, Fei; Lee, Rebecca; Kerestes, Heddy; Percy, Melanie J.; Keith, Brian; Simon, M. Celeste; Lappin, Terence R. J.; Khurana, Tejvir S.; Lee, Frank S.

2013-01-01

The central pathway for controlling red cell mass is the PHD (prolyl hydroxylase domain protein):hypoxia-inducible factor (HIF) pathway. HIF, which is negatively regulated by PHD, activates numerous genes, including ones involved in erythropoiesis, such as the ERYTHROPOIETIN (EPO) gene. Recent studies have implicated PHD2 as the key PHD isoform regulating red cell mass. Studies of humans have identified erythrocytosis-associated, heterozygous point mutations in the PHD2 gene. A key question concerns the mechanism by which human mutations lead to phenotypes. In the present report, we generated and characterized a mouse line in which a P294R knock-in mutation has been introduced into the mouse Phd2 locus to model the first reported human PHD2 mutation (P317R). Phd2P294R/+ mice display a degree of erythrocytosis equivalent to that seen in Phd2+/− mice. The Phd2P294R/+-associated erythrocytosis is reversed in a Hif2a+/−, but not a Hif1a+/− background. Additional studies using various conditional knock-outs of Phd2 reveal that erythrocytosis can be induced by homozygous and heterozygous knock-out of Phd2 in renal cortical interstitial cells using a Pax3-Cre transgene or by homozygous knock-out of Phd2 in hematopoietic progenitors driven by a Vav1-Cre transgene. These studies formally prove that a missense mutation in PHD2 is the cause of the erythrocytosis, show that this occurs through haploinsufficiency, and point to multifactorial control of red cell mass by PHD2. PMID:24121508

Oxidative stress-induced miR-27a targets the redox gene nuclear factor erythroid 2-related factor 2 in diabetic embryopathy.

PubMed

Zhao, Yang; Dong, Daoyin; Reece, E Albert; Wang, Ashley R; Yang, Peixin

2018-01-01

Maternal diabetes induces neural tube defects, and oxidative stress is a causal factor for maternal diabetes-induced neural tube defects. The redox gene nuclear factor erythroid 2-related factor 2 is the master regulator of the cellular antioxidant system. In this study, we aimed to determine whether maternal diabetes inhibits nuclear factor erythroid 2-related factor 2 expression and nuclear factor erythroid 2-related factor 2-controlled antioxidant genes through the redox-sensitive miR-27a. We used a well-established type 1 diabetic embryopathy mouse model induced by streptozotocin for our in vivo studies. Embryos at embryonic day 8.5 were harvested for analysis of nuclear factor erythroid 2-related factor 2, nuclear factor erythroid 2-related factor 2-controlled antioxidant genes, and miR-27a expression. To determine if mitigating oxidative stress inhibits the increase of miR-27a and the decrease of nuclear factor erythroid 2-related factor 2 expression, we induced diabetic embryopathy in superoxide dismutase 2 (mitochondrial-associated antioxidant gene)-overexpressing mice. This model exhibits reduced mitochondria reactive oxygen species even in the presence of hyperglycemia. To investigate the causal relationship between miR-27a and nuclear factor erythroid 2-related factor 2 in vitro, we examined C17.2 neural stem cells under normal and high-glucose conditions. We observed that the messenger RNA and protein levels of nuclear factor erythroid 2-related factor 2 were significantly decreased in embryos on embryonic day 8.5 from diabetic dams compared to those from nondiabetic dams. High-glucose also significantly decreased nuclear factor erythroid 2-related factor 2 expression in a dose- and time-dependent manner in cultured neural stem cells. Our data revealed that miR-27a was up-regulated in embryos on embryonic day 8.5 exposed to diabetes, and that high glucose increased miR-27a levels in a dose- and time-dependent manner in cultured neural stem cells. In

Cooperative Adaptive Cruise Control Human Factors Study : Experiment 2 : Merging Behavior

DOT National Transportation Integrated Search

2016-12-01

This study is the second in a series of four experiments exploring human factors issues associated with the introduction of cooperative adaptive cruise control (CACC). Specifically, this study explored drivers abilities to merge into a stream of c...

Factors controlling volume errors through 2D gully erosion assessment: guidelines for optimal survey design

NASA Astrophysics Data System (ADS)

Castillo, Carlos; Pérez, Rafael

2017-04-01

The assessment of gully erosion volumes is essential for the quantification of soil losses derived from this relevant degradation process. Traditionally, 2D and 3D approaches has been applied for this purpose (Casalí et al., 2006). Although innovative 3D approaches have recently been proposed for gully volume quantification, a renewed interest can be found in literature regarding the useful information that cross-section analysis still provides in gully erosion research. Moreover, the application of methods based on 2D approaches can be the most cost-effective approach in many situations such as preliminary studies with low accuracy requirements or surveys under time or budget constraints. The main aim of this work is to examine the key factors controlling volume error variability in 2D gully assessment by means of a stochastic experiment involving a Monte Carlo analysis over synthetic gully profiles in order to 1) contribute to a better understanding of the drivers and magnitude of gully erosion 2D-surveys uncertainty and 2) provide guidelines for optimal survey designs. Owing to the stochastic properties of error generation in 2D volume assessment, a statistical approach was followed to generate a large and significant set of gully reach configurations to evaluate quantitatively the influence of the main factors controlling the uncertainty of the volume assessment. For this purpose, a simulation algorithm in Matlab® code was written, involving the following stages: - Generation of synthetic gully area profiles with different degrees of complexity (characterized by the cross-section variability) - Simulation of field measurements characterised by a survey intensity and the precision of the measurement method - Quantification of the volume error uncertainty as a function of the key factors In this communication we will present the relationships between volume error and the studied factors and propose guidelines for 2D field surveys based on the minimal survey

Association Between Visceral Adiposity and Colorectal Polyps on CT Colonography

PubMed Central

Summers, Ronald M.; Liu, Jiamin; Sussman, Daniel L.; Dwyer, Andrew J.; Rehani, Bhavya; Pickhardt, Perry J.; Choi, J. Richard; Yao, Jianhua

2012-01-01

OBJECTIVE To determine if there is an association between visceral adiposity measured on CT colonography (CTC) and colorectal polyps. MATERIALS AND METHODS The study was HIPAA-compliant and approved by our Institutional Review Board and Office of Human Subjects Research. 1186 patients who underwent CTC and same day optical colonoscopy were analyzed. Visceral adipose tissue volumes (VAV) and volume percents relative to total internal body volume (VAV%) were measured on slices in the L2–L3 regions on supine CTC scan with validated fully-automated software. Student t-test, odds ratio (OR), logistic regression and receiver operating characteristic analyses were performed. RESULTS For subjects with and without adenomatous polyps, means and s. d. of VAV% were 31.2 ± 10.8% (n=345) and 28.2% ± 11.3% (n=841) (p<0.0001), respectively. For subjects with and without hyperplastic polyps they were 31.8% ± 10.7% (n=244) and 28.3% ± 11.2% (n=942) (p<0.0001), respectively. Comparing the lowest and highest quintiles of VAV%, the ORs for having at least one adenomatous polyp or hyperplastic polyp versus no polyp were 2.06 (95% CI: 1.36–3.13) and 1.71 [1.08, 2.71] and the prevalence of having adenomatous polyps or hyperplastic polyps increased 14% and 8%, respectively. CONCLUSION Subjects with higher visceral adiposity measurements on CTC have a greater risk for the presence of colonic polyps. PMID:22733893

Characterisation of Triticum vavilovii-derived stripe rust resistance using genetic, cytogenetic and molecular analyses and its marker-assisted selection.

PubMed

Bariana, H. S.; Brown, G. N.; Ahmed, N. U.; Khatkar, S.; Conner, R. L.; Wellings, C. R.; Haley, S.; Sharp, P. J.; Laroche, A.

2002-02-01

Stripe rust resistance was identified in Triticum vavilovii( T. vaviloviiAus22498)-derived Russian wheat aphid (RWA)-resistant germplasm. Inheritance studies indicated monogenic control of resistance. The resistance gene was tentatively designated as Yrvav and was located on chromosome 1B by monosomic analysis. A close association (1.5+/-0.9% recombination) of Yrvav with a T. vavilovii-derived gliadin allele ( Gli-B1vav) placed it in chromosome arm 1BS. Yrvavwas allelic with Yr10. Tests with Yr10 avirulent and virulent pathotypes showed that Yrvav and Yr10 possess identical pathogenic specificity. Yrvav and Yr10 showed close genetic associations with alternate alleles at the Xpsp3000(microsatellite marker), Gli-B1 and Rg1 loci. Based on these observations Yrvav was named as Yr10vav. The close association between Xpsp3000 and Gli-B1 was also confirmed. The Yr10vav-linked Xpsp3000 allele (285 bp) was not present in 65 Australian cultivars, whereas seven Australian wheats lacking Yr10 carried the same Xpsp3000 allele (260 bp) as Yr10carrying wheat cultivar Moro. Xpsp3000 and/or Gli-B1 could be used in marker-assisted selection for pyramiding Yr10vavor Yr10 with other stripe rust resistance genes. Yr10vav was inherited independently of the T. vavilovii-derived RWA resistance.

Eukaryotic elongation factor 2 controls TNF-α translation in LPS-induced hepatitis

PubMed Central

González-Terán, Bárbara; Cortés, José R.; Manieri, Elisa; Matesanz, Nuria; Verdugo, ρngeles; Rodríguez, María E.; González-Rodríguez, ρgueda; Valverde, ρngela; Martín, Pilar; Davis, Roger J.; Sabio, Guadalupe

2012-01-01

Bacterial LPS (endotoxin) has been implicated in the pathogenesis of acute liver disease through its induction of the proinflammatory cytokine TNF-α. TNF-α is a key determinant of the outcome in a well-established mouse model of acute liver failure during septic shock. One possible mechanism for regulating TNF-α expression is through the control of protein elongation during translation, which would allow rapid cell adaptation to physiological changes. However, the regulation of translational elongation is poorly understood. We found that expression of p38γ/δ MAPK proteins is required for the elongation of nascent TNF-α protein in macrophages. The MKK3/6-p38γ/δ pathway mediated an inhibitory phosphorylation of eukaryotic elongation factor 2 (eEF2) kinase, which in turn promoted eEF2 activation (dephosphorylation) and subsequent TNF-α elongation. These results identify a new signaling pathway that regulates TNF-α production in LPS-induced liver damage and suggest potential cell-specific therapeutic targets for liver diseases in which TNF-α production is involved. PMID:23202732

RpoH2 sigma factor controls the photooxidative stress response in a non-photosynthetic rhizobacterium, Azospirillum brasilense Sp7.

PubMed

Kumar, Santosh; Rai, Ashutosh Kumar; Mishra, Mukti Nath; Shukla, Mansi; Singh, Pradhyumna Kumar; Tripathi, Anil Kumar

2012-12-01

Bacteria belonging to the Alphaproteobacteria normally harbour multiple copies of the heat shock sigma factor (known as σ(32), σ(H) or RpoH). Azospirillum brasilense, a non-photosynthetic rhizobacterium, harbours five copies of rpoH genes, one of which is an rpoH2 homologue. The genes around the rpoH2 locus in A. brasilense show synteny with that found in rhizobia. The rpoH2 of A. brasilense was able to complement the temperature-sensitive phenotype of the Escherichia coli rpoH mutant. Inactivation of rpoH2 in A. brasilense results in increased sensitivity to methylene blue and to triphenyl tetrazolium chloride (TTC). Exposure of A. brasilense to TTC and the singlet oxygen-generating agent methylene blue induced several-fold higher expression of rpoH2. Comparison of the proteome of A. brasilense with its rpoH2 deletion mutant and with an A. brasilense strain overexpressing rpoH2 revealed chaperone GroEL, elongation factors (Ef-Tu and EF-G), peptidyl prolyl isomerase, and peptide methionine sulfoxide reductase as the major proteins whose expression was controlled by RpoH2. Here, we show that the RpoH2 sigma factor-controlled photooxidative stress response in A. brasilense is similar to that in the photosynthetic bacterium Rhodobacter sphaeroides, but that RpoH2 is not involved in the detoxification of methylglyoxal in A. brasilense.

Controls of Evapotranspiration and CO2 Fluxes from Scots Pine by Surface Conductance and Abiotic Factors

PubMed Central

Zha, Tianshan; Li, Chunyi; Kellomäki, Seppo; Peltola, Heli; Wang, Kai-Yun; Zhang, Yuqing

2013-01-01

Evapotranspiration (E) and CO2 flux (Fc) in the growing season of an unusual dry year were measured continuously over a Scots pine forest in eastern Finland, by eddy covariance techniques. The aims were to gain an understanding of their biological and environmental control processes. As a result, there were obvious diurnal and seasonal changes in E, Fc, surface conductance (gc), and decoupling coefficient (Ω), showing similar trends to those in radiation (PAR) and vapour pressure deficit (δ). The maximum mean daily values (24-h average) for E, Fc, gc, and Ω were 1.78 mmol m−2 s−1, −11.18 µmol m−2 s−1, 6.27 mm s−1, and 0.31, respectively, with seasonal averages of 0.71 mmol m−2 s−1, −4.61 µmol m−2 s−1, 3.3 mm s−1, and 0.16. E and Fc were controlled by combined biological and environmental variables. There was curvilinear dependence of E on gc and Fc on gc. Among the environmental variables, PAR was the most important factor having a positive linear relationship to E and curvilinear relationship to Fc, while vapour pressure deficit was the most important environmental factor affecting gc. Water use efficiency was slightly higher in the dry season, with mean monthly values ranging from 6.67 to 7.48 μmol CO2 (mmol H2O)−1 and a seasonal average of 7.06 μmol CO2 (μmol H2O)−1. Low Ω and its close positive relationship with gc indicate that evapotranspiration was sensitive to surface conductance. Mid summer drought reduced surface conductance and decoupling coefficient, suggesting a more biotic control of evapotranspiration and a physiological acclimation to dry air. Surface conductance remained low and constant under dry condition, supporting that a constant value of surface constant can be used for modelling transpiration under drought condition. PMID:23894401

Controls of evapotranspiration and CO2 fluxes from scots pine by surface conductance and abiotic factors.

PubMed

Zha, Tianshan; Li, Chunyi; Kellomäki, Seppo; Peltola, Heli; Wang, Kai-Yun; Zhang, Yuqing

2013-01-01

Evapotranspiration (E) and CO2 flux (Fc ) in the growing season of an unusual dry year were measured continuously over a Scots pine forest in eastern Finland, by eddy covariance techniques. The aims were to gain an understanding of their biological and environmental control processes. As a result, there were obvious diurnal and seasonal changes in E, Fc , surface conductance (gc ), and decoupling coefficient (Ω), showing similar trends to those in radiation (PAR) and vapour pressure deficit (δ). The maximum mean daily values (24-h average) for E, Fc , gc , and Ω were 1.78 mmol m(-2) s(-1), -11.18 µmol m(-2) s(-1), 6.27 mm s(-1), and 0.31, respectively, with seasonal averages of 0.71 mmol m(-2) s(-1), -4.61 µmol m(-2) s(-1), 3.3 mm s(-1), and 0.16. E and Fc were controlled by combined biological and environmental variables. There was curvilinear dependence of E on gc and Fc on gc . Among the environmental variables, PAR was the most important factor having a positive linear relationship to E and curvilinear relationship to Fc , while vapour pressure deficit was the most important environmental factor affecting gc . Water use efficiency was slightly higher in the dry season, with mean monthly values ranging from 6.67 to 7.48 μmol CO2 (mmol H2O)(-1) and a seasonal average of 7.06 μmol CO2 (μmol H2O)(-1). Low Ω and its close positive relationship with gc indicate that evapotranspiration was sensitive to surface conductance. Mid summer drought reduced surface conductance and decoupling coefficient, suggesting a more biotic control of evapotranspiration and a physiological acclimation to dry air. Surface conductance remained low and constant under dry condition, supporting that a constant value of surface constant can be used for modelling transpiration under drought condition.

PEST Motif Serine and Tyrosine Phosphorylation Controls Vascular Endothelial Growth Factor Receptor 2 Stability and Downregulation ▿

PubMed Central

Meyer, Rosana D.; Srinivasan, Srimathi; Singh, Amrik J.; Mahoney, John E.; Gharahassanlou, Kobra Rezazadeh; Rahimi, Nader

2011-01-01

The internalization and degradation of vascular endothelial growth factor receptor 2 (VEGFR-2), a potent angiogenic receptor tyrosine kinase, is a central mechanism for the regulation of the coordinated action of VEGF in angiogenesis. Here, we show that VEGFR-2 is ubiquitinated in response to VEGF, and Lys 48-linked polyubiquitination controls its degradation via the 26S proteosome. The degradation and ubiquitination of VEGFR-2 is controlled by its PEST domain, and the phosphorylation of Ser1188/Ser1191 is required for the ubiquitination of VEGFR-2. F-box-containing β-Trcp1 ubiquitin E3 ligase is recruited to S1188/S1191 VEGFR-2 and mediates the ubiquitination and degradation of VEGFR-2. The PEST domain also controls the activation of p38 mitogen-activated protein kinase (MAPK) through phospho-Y1173. The activation of p38 stabilizes VEGFR-2, and its inactivation accelerates VEGFR-2 downregulation. The VEGFR-2-mediated activation of p38 is established through the protein kinase A (PKA)/MKK6 pathway. PKA is recruited to VEGFR-2 through AKAP1/AKAP149, and its phosphorylation requires Y1173 of VEGFR-2. The study has identified a unique mechanism in which VEGFR-2 stability and degradation is modulated. The PEST domain acts as a dual modulator of VEGFR-2; the phosphorylation of S1188/S1191 controls ubiquitination and degradation via β-Trcp1, where the phosphorylation of Y1173 through PKA/p38 MAPK controls the stability of VEGFR-2. PMID:21402774

Risk Factor Knowledge, Perceived Threat, and Protective Health Behaviors: Implications for Type 2 Diabetes Control in Rural Communities.

PubMed

Paige, Samantha R; Bonnar, Kelly K; Black, David R; Coster, Daniel C

2018-02-01

Purpose The purpose of this study was to explore how perceived threat of type 2 diabetes (T2D) is shaped by risk factor knowledge and promotes the engagement of protective health behaviors among rural adults. Methods Participants (N = 252) completed a cross-sectional mixed-mode survey. Chi-squared analyses were computed to examine differences in perceived threat by demographic factors and knowledge of T2D risk factors. Logistic regressions were conducted to examine the relationship between T2D perceived threat and engagement in physical activity and health screenings. Results Perceived threat and knowledge of T2D risk factors were high. Perceived susceptibility was significantly higher among women, whites, and respondents with high body mass index (BMI). Respondents reporting physical activity most/almost every day had low perceived susceptibility to T2D. Perceived severity was significantly higher among respondents with high BMI. Blood cholesterol and glucose screenings were associated with greater T2D perceived susceptibility and severity. Higher BMI was associated with receiving a blood glucose screening. Conclusion Health education specialists and researchers should further explore the implications of using audience segmented fear appeal messages to promote T2D control through protective health behaviors.

Stage-specific control of connective tissue growth factor (CTGF/CCN2) expression in chondrocytes by Sox9 and beta-catenin.

PubMed

Huang, Bau-Lin; Brugger, Sean M; Lyons, Karen M

2010-09-03

CCN2/connective tissue growth factor is highly expressed in hypertrophic chondrocytes and is required for chondrogenesis. However, the transcriptional mechanisms controlling its expression in cartilage are largely unknown. The activity of the Ccn2 promoter was, therefore, investigated in osteochondro-progenitor cells and hypertrophic chondrocytes to ascertain these mechanisms. Sox9 and T-cell factor (TCF) x lymphoid enhancer factor (LEF) factors contain HMG domains and bind to related consensus sites. TCF x LEF factors are normally repressive but when bound to DNA in a complex with beta-catenin become activators of gene expression. In silico analysis of the Ccn2 proximal promoter identified multiple consensus TCF x LEF elements, one of which was also a consensus binding site for Sox9. Using luciferase reporter constructs, the TCF x LEF x Sox9 site was found to be involved in stage-specific expression of Ccn2. Luciferase, electrophoretic mobility shift assay (EMSA), and ChIP analysis revealed that Sox9 represses Ccn2 expression by binding to the consensus TCF x LEF x Sox9 site. On the other hand, the same assays showed that in hypertrophic chondrocytes, TCF x LEF x beta-catenin complexes occupy the consensus TCF x LEF x Sox9 site and activate Ccn2 expression. Furthermore, transgenic mice in which lacZ expression is driven under the control of the proximal Ccn2 promoter revealed that the proximal Ccn2 promoter responded to Wnt signaling in cartilage. Hence, we propose that differential occupancy of the TCF x LEF x Sox9 site by Sox9 versus beta-catenin restricts high levels of Ccn2 expression to hypertrophic chondrocytes.

Morris Water Maze Training in Mice Elevates Hippocampal Levels of Transcription Factors Nuclear Factor (Erythroid-derived 2)-like 2 and Nuclear Factor Kappa B p65

PubMed Central

Snow, Wanda M.; Pahlavan, Payam S.; Djordjevic, Jelena; McAllister, Danielle; Platt, Eric E.; Alashmali, Shoug; Bernstein, Michael J.; Suh, Miyoung; Albensi, Benedict C.

2015-01-01

Research has identified several transcription factors that regulate activity-dependent plasticity and memory, with cAMP-response element binding protein (CREB) being the most well-studied. In neurons, CREB activation is influenced by the transcription factor nuclear factor kappa B (NF-κB), considered central to immunity but more recently implicated in memory. The transcription factor early growth response-2 (Egr-2), an NF-κB gene target, is also associated with learning and memory. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), an antioxidant transcription factor linked to NF-κB in pathological conditions, has not been studied in normal memory. Given that numerous transcription factors implicated in activity-dependent plasticity demonstrate connections to NF-κB, this study simultaneously evaluated protein levels of NF-κB, CREB, Egr-2, Nrf2, and actin in hippocampi from young (1 month-old) weanling CD1 mice after training in the Morris water maze, a hippocampal-dependent spatial memory task. After a 6-day acquisition period, time to locate the hidden platform decreased in the Morris water maze. Mice spent more time in the target vs. non-target quadrants of the maze, suggestive of recall of the platform location. Western blot data revealed a decrease in NF-κB p50 protein after training relative to controls, whereas NF-κB p65, Nrf2 and actin increased. Nrf2 levels were correlated with platform crosses in nearly all tested animals. These data demonstrate that training in a spatial memory task results in alterations in and associations with particular transcription factors in the hippocampus, including upregulation of NF-κB p65 and Nrf2. Training-induced increases in actin protein levels caution against its use as a loading control in immunoblot studies examining activity-dependent plasticity, learning, and memory. PMID:26635523

Risk factors for syphilis in women: case-control study

PubMed Central

de Macêdo, Vilma Costa; de Lira, Pedro Israel Cabral; de Frias, Paulo Germano; Romaguera, Luciana Maria Delgado; Caires, Silvana de Fátima Ferreira; Ximenes, Ricardo Arraes de Alencar

2017-01-01

ABSTRACT OBJECTIVE To determine the sociodemographic, behavioral, and health care factors related to the occurrence of syphilis in women treated at public maternity hospitals. METHODS This is a case-control study (239 cases and 322 controls) with women admitted to seven maternity hospitals in the municipality of Recife, Brazil, from July 2013 to July 2014. Eligible women were recruited after the result of the VDRL (Venereal Disease Research Laboratory) under any titration. The selection of cases and controls was based on the result of the serology for syphilis using ELISA (enzyme-linked immunosorbent assay). The independent variables were grouped into: sociodemographic, behavioral, clinical and obstetric history, and health care in prenatal care and maternity hospital. Information was obtained by interview, during hospitalization, with the application of a questionnaire. Odds ratios and 95% confidence intervals were estimated using logistic regression to identify the predicting factors of the variable to be explained. RESULTS The logistic regression analysis identified as determinant factors for gestational syphilis: education level of incomplete basic education or illiterate (OR = 2.02), lack of access to telephone (OR = 2.4), catholic religion (OR = 1.70 ), four or more pregnancies (OR = 2.2), three or more sexual partners in the last year (OR = 3.1), use of illicit drugs before the age of 18 (OR = 3.0), and use of illicit drugs by the current partner (OR = 1.7). Only one to three prenatal appointments (OR = 3.5) and a previous history of sexually transmitted infection (OR = 9.7) were also identified as determinant factors. CONCLUSIONS Sociodemographic, behavioral, and health care factors are associated with the occurrence of syphilis in women and should be taken into account in the elaboration of universal strategies aimed at the prevention and control of syphilis, but with a focus on situations of greater vulnerability. PMID:28832758

Aircraft Loss of Control Causal Factors and Mitigation Challenges

NASA Technical Reports Server (NTRS)

Jacobson, Steven R.

2010-01-01

Loss of control is the leading cause of jet fatalities worldwide. Aside from their frequency of occurrence, accidents resulting from loss of aircraft control seize the public s attention by yielding a large number of fatalities in a single event. In response to the rising threat to aviation safety, the NASA Aviation Safety Program has conducted a study of the loss of control problem. This study gathered four types of information pertaining to loss of control accidents: (1) statistical data; (2) individual accident reports that cite loss of control as a contributing factor; (3) previous meta-analyses of loss of control accidents; and (4) inputs solicited from aircraft manufacturers, air carriers, researchers, and other industry stakeholders. Using these information resources, the study team identified the causal factors that were cited in the greatest number of loss of control accidents, and which were emphasized most by industry stakeholders. This report describes the study approach, the key causal factors for aircraft loss of control, and recommended mitigation strategies to make near-term impacts, mid-term impacts, and Next Generation Air Transportation System impacts on the loss of control accident statistics

Risk factors associated with sporadic salmonellosis in adults: a case-control study.

PubMed

Ziehm, D; Dreesman, J; Campe, A; Kreienbrock, L; Pulz, M

2013-02-01

In order to identify and assess recent risk factors for sporadic human infections with Salmonella enterica, we conducted a case-control study in Lower Saxony, Germany. The data collection was based on standardized telephone interviews with 1017 cases and 346 controls aged >14 years. Odds ratios were calculated in single-factor and multi-factor analyses for Salmonella cases and two different control groups, i.e. population controls and controls with rotavirus infection. Multi-factor analysis revealed associations between sporadic Salmonella infections for two exposures by both sets of controls: consumption of raw ground pork [adjusted odds ratio (aOR) 2·38, 95% confidence interval (CI) 1·27-4·44] and foreign travel (aOR 2·12, 95% CI 1·00-4·52). Other exposures included consumption of food items containing eggs (aOR 1·43, 95% CI 0·80-2·54), consumption of chicken meat (aOR 1·77, 95% CI 1·26-2·50), outdoor meals/barbecues (aOR 3·96, 95% CI 1·41-11·12) and taking gastric acidity inhibitors (aOR 2·42, 95% CI 1·19-4·92), all were significantly associated with respect to one of the two control groups. The impact of consuming food items containing eggs or chicken meat was lower than expected from the literature. This might be a consequence of Salmonella control programmes as well as increased public awareness of eggs and chicken products being a risk factor for salmonellosis. Efforts to reduce Salmonella infections due to raw pork products should be intensified.

Three phase power factor controller

NASA Technical Reports Server (NTRS)

Nola, F. J. (Inventor)

1984-01-01

A power control circuit for a three phase induction motor is described. Power factors for the three phases are summed to provide a control signal, and this control signal is particularly filtered and then employed to control the duty cycle of each phase of input power to the motor.

Dentine sensitivity risk factors: A case-control study.

PubMed

Mafla, Ana Cristina; Lopez-Moncayo, Luis Fernando

2016-01-01

To identify the clinical and psychological risk factors associated with dentine hypersensitivity (DH) in order to provide an early diagnosis and preventive therapy. A nested case-control study was design between 2011 and 2012. A total of 61 DH cases and 122 controls participated in this investigation. Cases and controls were matched for sex, group of age and socioeconomic status in a ratio of 1:2. DH to different stimuli such as cold, heat, acid, and sweet was asked in patient interviews, and dental examinations were used to detect DH. Clinical and psychological risk factors such as dental hygiene, periodontal disease, acid diet, alcohol consumption, psychological stress, and psychopathological symptoms were inquired. Psychological stress was measured through the PSS-10 and psychopathological symptoms were evaluated by SCL-90-R in Spanish. Descriptive and univariate binary logistic regression analysis were performed to estimate the association between clinical and psychological risk factors and the presence of DH. Toothpaste abrasivity (odds ratio [OR] 1.881, 95% confidence interval [CI] 1.010-3.502, P = 0.045), gingival recession (OR 2.196, 95% CI 1.020-4.728, P = 0.041), and periodontal therapy (OR 5.357, 95% CI 2.051-13.993, P < 0.001) were associated with DH. Subjects with perceived stress (OR 1.211, 95%, CI 0.518-2.833, P = 0.658), obsessive-compulsive (OR 1.266, 95%, CI 0.494-3.240, P = 0.623) and hostility (OR 1.235, 95%, CI 0.507-3.007, P = 0.642) symptoms had a clinical greater odd of DH. Oral hygiene products and periodontal conditions are important risk factors for DH. Individuals with perceived stress, obsessive-compulsive, and hostility symptoms may increase a clinical risk for this entity. Targeting to dental counseling focused on oral hygiene products, periodontal therapy and a psychological evaluation may be promising in DH prevention.

Controlling factors of evaporation and CO2 flux over an open water lake in southeastern margin of Tibetan Plateau

NASA Astrophysics Data System (ADS)

Du, Q.; Liu, H.; Liu, Y.; Wang, L.; Xu, L.

2017-12-01

Erhai lake is located in the southeastern margin of Tibetan Plateau. Based on the 4 years measurement over Erhai lake with eddy covariance technique (EC) from 2012 to 2015, the diurnal and seasonal variations of latent and sensible heat and CO2 fluxes, and their controlling factors over different time scales were analyzed. The diurnal average LE ranged from 31 to 171 Wm-2, while Hs ranged from -31 to 21 Wm-2. Bowen ratio was larger during January and May and smaller during June and October. The lake continued storing heat during January and June, and releasing heat since July. The diurnal average CO2 fluxes during nighttime were higher than the daytime, and carbon uptake was almost observed during the midday time of the day for the whole study period. The annual carbon budget fluctuated from 117.5 to 161.7 g C m-2 a-1, while annual total evaporation (ET) from 1120.8 to 1228.5 mm for the four-years period. The Erhai Lake behaved as a net carbon source over the whole period but carbon uptake was observed during the middle time of each year. The difference between water surface and air temperature (DeltaT) and the product of DeltaT and wind speed were the main controlling factors for Hs from halfhourly to monthly scale. There was significant relationship between wind speed, the product of wind speed and vapor pressure deficit (VPD) and LE on halfhourly and daily scales. The total cloud amount and net radiation (Rn) had a large effect on monthly variation of LE. Photosynthetic active radiation (PAR) and wind speed was mainly responsible for the variation of halfhourly and daily CO2 fluxes, respectively. The total cloud amount was the most important factors controlling for annual total ET. The annual rainfall, water surface temperature was observed to be negatively related with annual CO2 fluxes.

Impact of conditional deletion of the pro-apoptotic BCL-2 family member BIM in mice.

PubMed

Herold, M J; Stuchbery, R; Mérino, D; Willson, T; Strasser, A; Hildeman, D; Bouillet, P

2014-10-09

The pro-apoptotic BH3-only BCL-2 family member BIM is a critical determinant of hematopoietic cell development and homeostasis. It has been argued that the striking hematopoietic abnormalities of BIM-deficient mice (accumulation of lymphocytes and granulocytes) may be the result of the loss of the protein throughout the whole animal rather than a consequence intrinsic to the loss of BIM in hematopoietic cells. To address this issue and allow the deletion of BIM in specific cell types in future studies, we have developed a mouse strain with a conditional Bim allele as well as a new Cre transgenic strain, Vav-CreER, in which the tamoxifen-inducible CreER recombinase (fusion protein) is predominantly expressed in the hematopoietic system. We show that acute loss of BIM in the adult mouse rapidly results in the hematopoietic phenotypes previously observed in mice lacking BIM in all tissues. This includes changes in thymocyte subpopulations, increased white blood cell counts and resistance of lymphocytes to BIM-dependent apoptotic stimuli, such as cytokine deprivation. We have validated this novel conditional Bim knockout mouse model using established and newly developed CreER strains (Rosa26-CreER and Vav-CreER) and will make these exciting new tools for studies on cell death and cancer available.

Sprouty2 controls proliferation of palate mesenchymal cells via fibroblast growth factor signaling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Matsumura, Kaori; Taketomi, Takaharu, E-mail: taketomi@dent.kyushu-u.ac.jp; Yoshizaki, Keigo

2011-01-28

Research highlights: {yields} Sprouty2-deficient mice exhibit cleft palate as a result of failure of palatal shelf elevation. {yields} We examined palate cell proliferation in Sprouty2-deficient mice. {yields} Palate mesenchymal cell proliferation was increased in Sprouty2 KO mice. {yields} Sprouty2 plays roles in murine palatogenesis by regulating cell proliferation. -- Abstract: Cleft palate is one of the most common craniofacial deformities. The fibroblast growth factor (FGF) plays a central role in reciprocal interactions between adjacent tissues during palatal development, and the FGF signaling pathway has been shown to be inhibited by members of the Sprouty protein family. In this study, wemore » report the incidence of cleft palate, possibly caused by failure of palatal shelf elevation, in Sprouty2-deficient (KO) mice. Sprouty2-deficient palates fused completely in palatal organ culture. However, palate mesenchymal cell proliferation estimated by Ki-67 staining was increased in Sprouty2 KO mice compared with WT mice. Sprouty2-null palates expressed higher levels of FGF target genes, such as Msx1, Etv5, and Ptx1 than WT controls. Furthermore, proliferation and the extracellular signal-regulated kinase (Erk) activation in response to FGF was enhanced in palate mesenchymal cells transfected with Sprouty2 small interfering RNA. These results suggest that Sprouty2 regulates palate mesenchymal cell proliferation via FGF signaling and is involved in palatal shelf elevation.« less

Risk Factors of Rheumatic Heart Disease in Bangladesh: A Case-Control Study

PubMed Central

Riaz, Baizid Khoorshid; Karim, Md. Nazmul; Chowdhury, Kamrun Nahar; Chowdhury, Shahabul Huda; Rahman, Md. Ridwanur

2013-01-01

Not all cases of rheumatic fever (RF) end up as rheumatic heart disease (RHD). The fact raises the possibility of existence of a subgroup with characteristics that prevent RF patients from developing the RHD. The present study aimed at exploring the risk factors among patients with RHD. The study assessed the risk of RHD among people both with and without RF. In total, 103 consecutive RHD patients were recruited as cases who reported to the National Centre for Control of Rheumatic Fever and Heart Disease, Dhaka, Bangladesh. Of 309 controls, 103 were RF patients selected from the same centre, and the remaining 206 controls were selected from Shaheed Suhrawardy Medical College Hospital, who got admitted for other non-cardiac ailments. RHD was confirmed by auscultation and colour Doppler echocardiography. RF was diagnosed based on the modified Jones criteria. An unadjusted odds ratio was generated for each variable, with 95% confidence interval (CI), and only significant factors were considered candidate for multivariate analysis. Three separate binary logistic regression models were generated to assess the risk factors of RF, risk factors of RHD compared to non-rheumatic control patients, and risk factors of RHD compared to control with RF. RF and RHD shared almost a similar set of risk factors in the population. In general, age over 19 years was found to be protective of RF; however, age of the majority (62.1%) of the RHD cases was over 19 years. Women [odds ratio (OR)=2.2, 95% CI 1.1-4.3], urban resident (OR=3.1, 95% CI 1.2–8.4), dwellers in brick-built house (OR=3.6, 95% CI 1.6-8.1), having >2 siblings (OR=3.1, 95% CI 1.5- 6.3), offspring of working mothers (OR=7.6, 95% CI 2.0-24.2), illiterate mother (OR=2.6, 95% CI 1.2-5.8), and those who did not brush after taking meals (OR=2.5, 95% CI 1.0-6.3) were more likely to develop RF. However, more than 5 members in a family showed a reduced risk of RF. RHD shared almost a similar set of factors in general. More than

Reliable and Affordable Control Systems Active Combustor Pattern Factor Control

NASA Technical Reports Server (NTRS)

McCarty, Bob; Tomondi, Chris; McGinley, Ray

2004-01-01

Active, closed-loop control of combustor pattern factor is a cooperative effort between Honeywell (formerly AlliedSignal) Engines and Systems and the NASA Glenn Research Center to reduce emissions and turbine-stator vane temperature variations, thereby enhancing engine performance and life, and reducing direct operating costs. Total fuel flow supplied to the engine is established by the speed/power control, but the distribution to individual atomizers will be controlled by the Active Combustor Pattern Factor Control (ACPFC). This system consist of three major components: multiple, thin-film sensors located on the turbine-stator vanes; fuel-flow modulators for individual atomizers; and control logic and algorithms within the electronic control.

Heart Disease Risk Factors You Can't Control

MedlinePlus

... Submit Heart disease risk factors you can't control Some factors you can't control, like pregnancy ... 2018. Heart disease risk factors you can't control Age and menopause As you get older, your ...

[Case-control study on influence factors of birth defects].

PubMed

Xiu, Xin-hong; Yuan, Li; Wang, Xiao-ming; Chen, Yu-hua; Wan, Ai-hua; Fu, Ping

2011-07-01

To investigate the influence factors of birth defects. The congenital malformational fetuses born from 13 week of gestation to 7 days after birth were selected as the study group between April 1st, 2009 and March 31st, 2010. The health born fetuses were set as control in the same period. Case-control and the three-level of monitor network of birth defects were used in the study in the participating 75 hospitals (Qingdao Women and Children's Medical Center, Affiliated Hospital of Medical College Qingdao University, Qingdao Municipal Hospital, etc.). The study and control group's parents were interviewed by an uniformed questionnaire which was designed specially with influence factors of birth defects. (1) There are 466 congenital malformational fetuses in the total of 77 231 fetuses collected in 75 hospitals. The congenital malformational rate accounts for about 6.034‰. The top six defect diseases were congenital heart disease (112 cases), total harelip (cleft lip; cleft lip with palate: 85 cases), polydactyly (53 cases), neural tube defects (38 cases), congenital hydrocephalus (37 cases) and limb reduction defect (27 cases) in turn, which amounts to 353 cases (54.48%, 353/648). (2) Their mother education level in the birth-defect group (25.6%) were significantly lower than that in control group (30.0%, P<0.05). (3) The rate of passive smoking, drinking, raising pets of the parents in birth-defect group were significantly higher than that in control group (P<0.05). (4) The rate of exposure to harmful chemical and physical factors of mothers in birth defects group (13.9% and 20.5%, respectively) was higher than that in control group (1.1% and 11.7%, respectively), the difference between which were significant (P<0.01). The rate of disease (34.3%), fever (13.1%), taking drugs (33.8%) in pregnancy period in birth defect group were higher than that in control group (13.5%, 1.5% and 9.9%, respectively), the difference between which were significant (P<0.01). The rate

Dietary Adherence, Glycemic Control, and Psychological Factors Associated with Binge Eating Among Indigenous and Non-Indigenous Chileans with Type 2 Diabetes.

PubMed

Herbozo, Sylvia; Flynn, Patricia M; Stevens, Serena D; Betancourt, Hector

2015-12-01

Despite the strong association between obesity and binge eating, limited research has examined the implications of binge eating on dietary adherence and psychological factors in ethnically diverse type 2 diabetes patients. This study investigated the prevalence of binge eating and its association with dietary adherence, glycemic control, and psychological factors among indigenous and non-indigenous type 2 diabetes patients in Chile. Participants were 387 indigenous (Mapuche) and non-indigenous (non-Mapuche) adults with type 2 diabetes. Self-report measures of binge eating, dietary adherence, diet self-efficacy, body image dissatisfaction, and psychological well-being were administered. Participants' weight, height, and glycemic control (HbA(1c)) were also obtained. Approximately 8 % of the type 2 diabetes patients reported binge eating. The prevalence among Mapuche patients was 4.9 %, and among non-Mapuche patients, it was 9.9 %. Compared to non-binge eaters, binge eating diabetes patients had greater body mass index values, consumed more high-fat foods, were less likely to adhere to their eating plan, and reported poorer body image and emotional well-being. Results of this study extend previous research by examining the co-occurrence of binge eating and type 2 diabetes as well as the associated dietary behaviors, glycemic control, and psychological factors among indigenous and non-indigenous patients in Chile. These findings may increase our understanding of the health challenges faced by indigenous populations from other countries and highlight the need for additional research that may inform interventions addressing binge eating in diverse patients with type 2 diabetes.

Factor structure and validation of the Attentional Control Scale.

PubMed

Judah, Matt R; Grant, DeMond M; Mills, Adam C; Lechner, William V

2014-04-01

The Attentional Control Scale (ACS; Derryberry & Reed, 2002) has been used to assess executive control over attention in numerous studies, but no published data have examined the factor structure of the English version. The current studies addressed this need and tested the predictive and convergent validity of the ACS subscales. In Study 1, exploratory factor analysis yielded a two-factor model with Focusing and Shifting subscales. In Study 2, confirmatory factor analysis supported this model and suggested superior fit compared to the factor structure of the Icelandic version (Ólafsson et al., 2011). Study 3 examined correlations between the ACS subscales and measures of working memory, anxiety, and cognitive control. Study 4 examined correlations between the subscales and reaction times on a mixed-antisaccade task, revealing positive correlations for antisaccade performance and prosaccade latency with Focusing scores and between switch trial performance and Shifting scores. Additionally, the findings partially supported unique relationships between Focusing and trait anxiety and between Shifting and depression that have been noted in recent research. Although the results generally support the validity of the ACS, additional research using performance-based tasks is needed.

Risk factors for measles among adults in Tianjin, China: Who should be controls in a case-control study?

PubMed

Wagner, Abram L; Boulton, Matthew L; Gillespie, Brenda W; Zhang, Ying; Ding, Yaxing; Carlson, Bradley F; Luo, Xiaoyan; Montgomery, JoLynn P; Wang, Xiexiu

2017-01-01

Control groups in previous case-control studies of vaccine-preventable diseases have included people immune to disease. This study examines risk factors for measles acquisition among adults 20 to 49 years of age in Tianjin, China, and compares findings using measles IgG antibody-negative controls to all controls, both IgG-negative and IgG-positive. Measles cases were sampled from a disease registry, and controls were enrolled from community registries in Tianjin, China, 2011-2015. Through a best subsets selection procedure, we compared which variables were selected at different model sizes when using IgG-negative controls or all controls. We entered risk factors for measles in two separate logistic regression models: one with measles IgG-negative controls and the other with all controls. The study included 384 measles cases and 1,596 community controls (194 IgG-negative). Visiting a hospital was an important risk factor. For specialty hospitals, the odds ratio (OR) was 4.53 (95% confidence interval (CI): 1.28, 16.03) using IgG-negative controls, and OR = 5.27 (95% CI: 2.73, 10.18) using all controls. Variables, such as age or length of time in Tianjin, were differentially selected depending on the control group. Individuals living in Tianjin ≤3 years had 2.87 (95% CI: 1.46, 5.66) times greater odds of measles case status compared to all controls, but this relationship was not apparent for IgG-negative controls. We recommend that case-control studies examining risk factors for infectious diseases, particularly in the context of transmission dynamics, consider antibody-negative controls as the gold standard.

Nuclear factor-E2-related factor 2 is a major determinant of bile acid homeostasis in the liver and intestine

PubMed Central

Weerachayaphorn, Jittima; Mennone, Albert; Soroka, Carol J.; Harry, Kathy; Hagey, Lee R.; Kensler, Thomas W.

2012-01-01

The transcription factor nuclear factor-E2-related factor 2 (Nrf2) is a key regulator for induction of hepatic detoxification and antioxidant mechanisms, as well as for certain hepatobiliary transporters. To examine the role of Nrf2 in bile acid homeostasis and cholestasis, we assessed the determinants of bile secretion and bile acid synthesis and transport before and after bile duct ligation (BDL) in Nrf2−/− mice. Our findings indicate reduced rates of biliary bile acid and GSH excretion, higher levels of intrahepatic bile acids, and decreased expression of regulators of bile acid synthesis, Cyp7a1 and Cyp8b1, in Nrf2−/− compared with wild-type control mice. The mRNA expression of the bile acid transporters bile salt export pump (Bsep) and organic solute transporter (Ostα) were increased in the face of impaired expression of the multidrug resistance-associated proteins Mrp3 and Mrp4. Deletion of Nrf2 also decreased ileal apical sodium-dependent bile acid transporter (Asbt) expression, leading to reduced bile acid reabsorption and increased loss of bile acid in feces. Finally, when cholestasis is induced by BDL, liver injury was not different from that in wild-type BDL mice. These Nrf2−/− mice also had increased pregnane X receptor (Pxr) and Cyp3a11 mRNA expression in association with enhanced hepatic bile acid hydroxylation. In conclusion, this study finds that Nrf2 plays a major role in the regulation of bile acid homeostasis in the liver and intestine. Deletion of Nrf2 results in a cholestatic phenotype but does not augment liver injury following BDL. PMID:22345550

SLP-76 couples Syk to the osteoclast cytoskeleton.

PubMed

Reeve, Jennifer L; Zou, Wei; Liu, Yuli; Maltzman, Jonathan S; Ross, F Patrick; Teitelbaum, Steven L

2009-08-01

The capacity of the osteoclast (OC) to resorb bone is dictated by cytoskeletal organization, which in turn emanates from signals derived from the alpha(v)beta(3) integrin and c-Fms. Syk is key to these signals and, in other cells, this tyrosine kinase exerts its effects via intermediaries including the SLP adaptors, SLP-76 and BLNK (B cell linker). Thus, we asked whether these two SLP proteins regulate OC function. We find BLNK-deficient OCs are normal, whereas cytoskeletal organization of those lacking SLP-76 is delayed, thus modestly reducing bone resorption in vitro. Cytoskeletal organization and bone resorption are more profoundly arrested in cultured OCs deficient in BLNK and SLP-76 double knockout (DKO) phenotypes. In contrast, stimulated bone resorption in vivo is inhibited approximately 40% in either SLP-76(-/-) or DKO mice. This observation, taken with the fact that DKO OCs are rescued by retroviral transduction of only SLP-76, indicates that SLP-76 is the dominant SLP family member in the resorptive process. We also find SLP-76 is phosphorylated in a Syk-dependent manner. Furthermore, in the absence of the adaptor protein, integrin-mediated phosphorylation of Vav3, the OC cytoskeleton-organizing guanine nucleotide exchange factor, is abrogated. In keeping with a central role of SLP-76/Vav3 association in osteoclastic resorption, retroviral transduction of SLP-76, in which the Vav binding site is disrupted (3YF), fails to normalize the cytoskeleton of DKO OCs and the resorptive capacity of the cells. Finally, c-Fms-activated Syk also exerts its OC cytoskeleton-organizing effect in a SLP-76/Vav3-dependent manner.

Dentine sensitivity risk factors: A case–control study

PubMed Central

Mafla, Ana Cristina; Lopez-Moncayo, Luis Fernando

2016-01-01

Objective: To identify the clinical and psychological risk factors associated with dentine hypersensitivity (DH) in order to provide an early diagnosis and preventive therapy. Materials and Methods: A nested case–control study was design between 2011 and 2012. A total of 61 DH cases and 122 controls participated in this investigation. Cases and controls were matched for sex, group of age and socioeconomic status in a ratio of 1:2. DH to different stimuli such as cold, heat, acid, and sweet was asked in patient interviews, and dental examinations were used to detect DH. Clinical and psychological risk factors such as dental hygiene, periodontal disease, acid diet, alcohol consumption, psychological stress, and psychopathological symptoms were inquired. Psychological stress was measured through the PSS-10 and psychopathological symptoms were evaluated by SCL-90-R in Spanish. Descriptive and univariate binary logistic regression analysis were performed to estimate the association between clinical and psychological risk factors and the presence of DH. Results: Toothpaste abrasivity (odds ratio [OR] 1.881, 95% confidence interval [CI] 1.010–3.502, P = 0.045), gingival recession (OR 2.196, 95% CI 1.020–4.728, P = 0.041), and periodontal therapy (OR 5.357, 95% CI 2.051–13.993, P < 0.001) were associated with DH. Subjects with perceived stress (OR 1.211, 95%, CI 0.518–2.833, P = 0.658), obsessive-compulsive (OR 1.266, 95%, CI 0.494–3.240, P = 0.623) and hostility (OR 1.235, 95%, CI 0.507–3.007, P = 0.642) symptoms had a clinical greater odd of DH. Conclusion: Oral hygiene products and periodontal conditions are important risk factors for DH. Individuals with perceived stress, obsessive-compulsive, and hostility symptoms may increase a clinical risk for this entity. Targeting to dental counseling focused on oral hygiene products, periodontal therapy and a psychological evaluation may be promising in DH prevention. PMID:27011732

Electronic messaging intervention for management of cardiovascular risk factors in type 2 diabetes mellitus: A randomised controlled trial.

PubMed

Fang, Ronghua; Deng, Xuexue

2018-02-01

To determine the effectiveness of an electronic messaging support service for management of cardiovascular risk factors in patients with diabetes. Microletter and short message service are widely used, but their health education benefit for people with type 2 diabetes mellitus has not been investigated. Convenience sample study with randomised group assignment. Participants completed survey questionnaires, physical and laboratory evaluations between May 2015 and May 2016 and were then randomly assigned to two groups for receipt of a microletter + short message or a phone call (control). Appointment reminders and health information were sent to the intervention patients by microletter + short message. Every three months, intervention patients and control patients were followed up by telephone. After 12 months, changes in cardiovascular risk factors in each group were evaluated and compared. There were no statistically significant changes or between-group differences in daily smoking and drinking. There were statistically significant between-group differences in glycated haemoglobin (p = .034), postprandial plasma glucose (p = .001), postprandial insulin (p = .005), total cholesterol (p = .038) and low-density lipoprotein (p < .001). Levels of glycated haemoglobin (p = .011), fasting plasma glucose (p = .007), postprandial plasma glucose (p < .001), fasting insulin (p = 0.004), postprandial insulin (p < .001), total cholesterol (p < .001) and low-density lipoprotein (p < .001) were found to be decreased significantly in intervention patients. Systolic blood pressure decreased significantly in patients only followed by telephone (p = .014). The microletter + short message intervention was an effective means of reducing cardiovascular risk in patients with type 2 diabetes mellitus. Regular smartphone communication had a favourable impact on cardiovascular risk factors in patients with type 2 diabetes mellitus. Regular smartphone

Nuclear factor erythroid 2-related factor 2 antioxidant response element pathways protect bovine mammary epithelial cells against H2O2-induced oxidative damage in vitro.

PubMed

Ma, Y F; Wu, Z H; Gao, M; Loor, J J

2018-06-01

The experiment was conducted to determine the role of nuclear factor (erythroid-derived 2)-like factor 2 (NFE2L2, formerly Nrf2) antioxidant response element (ARE) pathway in protecting bovine mammary epithelial cells (BMEC) against H 2 O 2 -induced oxidative stress injury. An NFE2L2 small interfering RNA (siRNA) interference or a pCMV6-XL5-NFE2L2 plasmid fragment was transfected to independently downregulate or upregulate expression of NFE2L2. Isolated BMEC in triplicate were exposed to H 2 O 2 (600 μM) for 6 h to induce oxidative stress before transient transfection with scrambled siRNA, NFE2L2-siRNA, pCMV6-XL5, and pCMV6-XL5-NFE2L2. Cell proliferation, apoptosis and necrosis rates, antioxidant enzyme activities, reactive oxygen species (ROS) and malondialdehyde (MDA) production, protein and mRNA expression of NFE2L2 and downstream target genes, and fluorescence activity of ARE were measured. The results revealed that compared with the control, BMEC transfected with NFE2L2-siRNA3 had proliferation rates that were 9 or 65% lower without or with H 2 O 2 , respectively. These cells also had apoptosis and necrosis rates that were 27 and 3.5 times greater with H 2 O 2 compared with the control group, respectively. In contrast, transfected pCMV6-XL5-NFE2L2 had proliferation rates that were 64.3% greater or 17% lower without or with H 2 O 2 compared with the control group, respectively. Apoptosis rates were 1.8 times lower with H 2 O 2 compared with the control. In addition, compared with the control, production of ROS and MDA and activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and glutathione-S-transferase (GST) increased markedly in cells transfected with pCMV6-XL5-NFE2L2 and without H 2 O 2 . However, compared with the control, production of ROS and MDA and activity of CAT and GSH-Px increased markedly, whereas activities of SOD and GST decreased in cells transfected with pCMV6-XL5-NFE2L2 and incubated with H 2 O 2

Cardiovascular Risk Factors in Patients with Poorly Controlled Diabetes Mellitus.

PubMed

Dizdarevic-Bostandzic, Amela; Begovic, Ermin; Burekovic, Azra; Velija-Asimi, Zelija; Godinjak, Amina; Karlovic, Vanja

2018-02-01

Diabetes mellitus(DM) is considered an independent cardiovascular risk factor. Having in mind concomitant occurence of diabetes and other cardiovascular risk factors, it is expected that patients with poor glucoregulation will have more cardiovascular risk factors and higher cardiovascular risk than patients with good glucoregulation. To compare cardiovascular risk and cardiovascular risk factors between patients with poorly controlled and patients with well-controlled Diabetes mellitus. Hundered ten patients aged 40-70 years suffering from Diabetes mellitus type 2 were included. Research is designed as a retrospective, descriptive study. Patients with glycosylated hemoglobin (HbA1c) > 7% were considered to have poorly controlled diabetes. The following data and parameters were monitored: age,sex, family history, data on smoking and alcohol consumption, BMI (body mass index), blood pressure, blood glucose, total cholesterol, triglycerides, LDL, HDL, fibrinogen, uric acid. For the assessment of cardiovascular risk, the WHO / ISH (World Health Organization/International Society of hypertension) tables of the 10-year risk were used, and due to the assessment of the risk factors prevalence, the optimal values of individual numerical variables were defined. Differences in the mean values of systolic, diastolic blood pressure, fasting glucose, total cholesterol, LDL cholesterol are statistically significant higher in patients with poorly controlled diabetes. Hypertension more frequently occurre in patients with poorly controlled DM. The majority of patients with well-controlled DM belong to the group of low and medium cardiovascular risk, while the majority of patients with poorly controlled DM belong to the group of high and very high cardiovascular risk. In our research, there was a significant difference in cardiovascular risk in relation to the degree of DM regulation, and HbA1c proved to be an important indicator for the emergence of the CVD. There are significant

A Case-Control Study to Identify Risk Factors Associated with Avian Influenza Subtype H9N2 on Commercial Poultry Farms in Pakistan

PubMed Central

Chaudhry, Mamoona; Rashid, Hamad B.; Thrusfield, Michael; Welburn, Sue; Bronsvoort, Barend MdeC.

2015-01-01

A 1:1 matched case-control study was conducted to identify risk factors for avian influenza subtype H9N2 infection on commercial poultry farms in 16 districts of Punjab, and 1 administrative unit of Pakistan. One hundred and thirty-three laboratory confirmed positive case farms were matched on the date of sample submission with 133 negative control farms. The association between a series of farm-level characteristics and the presence or absence of H9N2 was assessed by univariable analysis. Characteristics associated with H9N2 risk that passed the initial screening were included in a multivariable conditional logistic regression model. Manual and automated approaches were used, which produced similar models. Key risk factors from all approaches included selling of eggs/birds directly to live bird retail stalls, being near case/infected farms, a previous history of infectious bursal disease (IBD) on the farm and having cover on the water storage tanks. The findings of current study are in line with results of many other studies conducted in various countries to identify similar risk factors for AI subtype H9N2 infection. Enhancing protective measures and controlling risks identified in this study could reduce spread of AI subtype H9N2 and other AI viruses between poultry farms in Pakistan. PMID:25774768

Analysis of DNA Methylation at Specific Loci in Stool Samples Detects Colorectal Cancer and High-grade Dysplasia in Patients with Inflammatory Bowel Disease.

PubMed

Kisiel, John B; Klepp, Pasquale; Allawi, Hatim T; Taylor, William R; Giakoumopoulos, Maria; Sander, Tamara; Yab, Tracy C; Moum, Bjorn A; Lidgard, Graham P; Brackmann, Stephan; Mahoney, Douglas W; Roseth, Arne; Ahlquist, David A

2018-05-15

Patients with inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), are at increased risk for colorectal cancer (CRC). Analyses of DNA methylation patterns in stool samples have been reported to detect CRC in patients with IBD. We sought to validate these findings in larger cohorts and assess the accuracy of analysis of DNA methylation patterns in stool for detection of CRC and high-grade dysplasia (HGD) normalized to methylation level at ZDHHC1. We obtained buffered, frozen stool samples from a United States case-control study and from 2 European surveillance cohorts (referral or population based) of patients with chronic UC (n=248), CD (n=82), indeterminate colitis (n=2), or IBD with primary sclerosing cholangitis (n=38). Stool samples were collected before bowel preparation for colonoscopy or at least 1 week after colonoscopy. Among the study samples, stools from individuals with IBD but without neoplasia were used as controls (n=291). DNA was isolated from stool, exposed to bisulfite, and then assayed by multiplex quantitative allele-specific real-time target and signal amplification. We analyzed methylation levels of BMP3, NDRG4, VAV3, and SFMBT2 relative to the methylation level of ZDHHC1, and compared these between patients with CRC or HGD and controls. Levels of methylation at BMP3 and VAV3, relative to ZDHHC1 methylation, identified patients with CRC and HGD with an area under curve value of 0.91 (95% CI, 0.77-1.00). Methylation levels at specific promotor regions of these genes identified 11 of the 12 patients with CRC and HGD, with 92% sensitivity (95% CI, 60%-100%) and 90% specificity (95% CI, 86%-93%). The proportion of false-positive results did not differ significantly among the case-control, referral cohort, and population cohort studies (P=.60) when the 90% specificity cut-off from the whole sample set was applied. In an analysis of stool samples from 3 independent studies, of 332 patients with IBD, we

Evaluation of Variable Refrigerant Flow Systems Performance on Oak Ridge National Laboratory s Flexible Research Platform: Part 2 Heating Season Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Im, Piljae; Malhotra, Mini; Munk, Jeffrey D.

The performance of two HVAC systems was evaluated using ORNL’s FRP, which is a two-story, 3,200 ft2 (297.3 m2) multi-zone unoccupied building that represents a typical low-rise, small office building common in the US existing building stock. The FRP is equipped with a conventional 12.5 ton (44 kW) RTU-VAV reheat system as the baseline system. For this study, a 12 ton (42 kW) VRF with a dedicated outdoor air system (DOAS) was installed to be compared with the baseline RTU system.

Influence of psychosocial factors on self-care behaviors and glycemic control in Turkish patients with type 2 diabetes mellitus.

PubMed

Cosansu, Gulhan; Erdogan, Semra

2014-01-01

The main purpose of this study was to investigate the direct and indirect effects of psychosocial factors on self-care behavior and glycemic control in Turkish patients with type 2 diabetes mellitus. The study used a cross-sectional questionnaire survey design (N = 350). Data were collected using the Summary of Diabetes Self-Care Activities Scale and the Multidimensional Diabetes Questionnaire. The relationship between the study variables was analyzed using Pearson's correlation coefficient and structural equation modeling. Self-efficacy was associated with social support, outcome expectancies, perceived interference, educational level, and self-care and A1C. According to the structural equation model, self-efficacy was the predictor variable that influenced both self-care and glycemic control. Self-efficacy in achieving desired health outcomes was found to play a central role in Turkish patients. Although interventions are planned and implemented to achieve and maintain self-management in individuals with diabetes, strengthening psychosocial factors, particularly self-efficacy, may contribute to adjustment to disease and good glycemic control in the long term.

Candidate Socioemotional Remediation Program for Individuals with Intellectual Disability

ERIC Educational Resources Information Center

Glaser, Bronwyn; Lothe, Amelie; Chabloz, Melanie; Dukes, Daniel; Pasca, Catherine; Redoute, Jerome; Eliez, Stephan

2012-01-01

The authors developed a computerized program, Vis-a-Vis (VAV), to improve socioemotional functioning and working memory in children with developmental disabilities. The authors subsequently tested whether participants showed signs of improving the targeted skills. VAV is composed of three modules: Focus on the Eyes, Emotion Recognition and…

Expression and activity of Rac1 is negatively affected in the dehydroepiandrosterone induced polycystic ovary of mouse

PubMed Central

2014-01-01

Background Polycystic ovarian syndrome (PCOS) is characterized by the presence of multiple follicular cysts, giving rise to infertility due to anovulation. This syndrome affects about 10% of women, worldwide. The exact molecular mechanism leading to PCOS remains obscure. RhoGTPase has been associated with oogenesis, but its role in PCOS remains unexplored. Therefore, we attempted to elucidate the Vav-Rac1 signaling in PCOS mice model. Methods We generated a PCOS mice model by injecting dehydroepiandrosterone (DHEA) for a period of 20 days. The expression levels of Rac1, pRac1, Vav, pVav and Caveolin1 were analyzed by employing immuno-blotting and densitometry. The association between Vav and Rac1 proteins were studied by immuno-precipitation. Furthermore, we analyzed the activity of Rac1 and levels of inhibin B and 17β-estradiol in ovary using biochemical assays. Results The presence of multiple follicular cysts in ovary were confirmed by histology. The activity of Rac1 (GTP bound state) was significantly reduced in the PCOS ovary. Similarly, the expression levels of Rac1 and its phosphorylated form (pRac1) were decreased in PCOS in comparison to the sham ovary. The expression level and activity (phosphorylated form) of guanine nucleotide exchanger of Rac1, Vav, was moderately down-regulated. We observed comparatively increased expressions of Caveolin1, 17β-estradiol, and inhibin B in the polycystic ovary. Conclusion We conclude that hyperandrogenization (PCOS) by DHEA diminishes ovarian Rac1 and Vav expression and activity along with an increase in expression of Caveolin1. This is accompanied by an increase in the intra-ovarian level of '17 β-estradiol and inhibin B. PMID:24628852

PTP1B inhibitor promotes endothelial cell motility by activating the DOCK180/Rac1 pathway.

PubMed

Wang, Yuan; Yan, Feng; Ye, Qing; Wu, Xiao; Jiang, Fan

2016-04-07

Promoting endothelial cell (EC) migration is important not only for therapeutic angiogenesis, but also for accelerating re-endothelialization after vessel injury. Several recent studies have shown that inhibition of protein tyrosine phosphatase 1B (PTP1B) may promote EC migration and angiogenesis by enhancing the vascular endothelial growth factor receptor-2 (VEGFR2) signalling. In the present study, we demonstrated that PTP1B inhibitor could promote EC adhesion, spreading and migration, which were abolished by the inhibitor of Rac1 but not RhoA GTPase. PTP1B inhibitor significantly increased phosphorylation of p130Cas, and the interactions among p130Cas, Crk and DOCK180; whereas the phosphorylation levels of focal adhesion kinase, Src, paxillin, or Vav2 were unchanged. Gene silencing of DOCK180, but not Vav2, abrogated the effects of PTP1B inhibitor on EC motility. The effects of PTP1B inhibitor on EC motility and p130Cas/DOCK180 activation persisted in the presence of the VEGFR2 antagonist. In conclusion, we suggest that stimulation of the DOCK180 pathway represents an alternative mechanism of PTP1B inhibitor-stimulated EC motility, which does not require concomitant VEGFR2 activation as a prerequisite. Therefore, PTP1B inhibitor may be a useful therapeutic strategy for promoting EC migration in cardiovascular patients in which the VEGF/VEGFR functions are compromised.

Leucine-Rich Repeat Kinase 2 Controls the Ca2+/Nuclear Factor of Activated T Cells/IL-2 Pathway during Aspergillus Non-Canonical Autophagy in Dendritic Cells.

PubMed

Wong, Alicia Yoke Wei; Oikonomou, Vasilis; Paolicelli, Giuseppe; De Luca, Antonella; Pariano, Marilena; Fric, Jan; Tay, Hock Soon; Ricciardi-Castagnoli, Paola; Zelante, Teresa

2018-01-01

The Parkinson's disease-associated protein, Leucine-rich repeat kinase 2 (LRRK2), a known negative regulator of nuclear factor of activated T cells (NFAT), is expressed in myeloid cells such as macrophages and dendritic cells (DCs) and is involved in the host immune response against pathogens. Since, the Ca 2+ /NFAT/IL-2 axis has been previously found to regulate DC response to the fungus Aspergillus , we have investigated the role played by the kinase LRRK2 during fungal infection. Mechanistically, we found that in the early stages of the non-canonical autophagic response of DCs to the germinated spores of Aspergillus , LRRK2 undergoes progressive degradation and regulates NFAT translocation from the cytoplasm to the nucleus. Our results shed new light on the complexity of the Ca 2+ /NFAT/IL-2 pathway, where LRRK2 plays a role in controlling the immune response of DCs to Aspergillus .

GABP transcription factor is required for development of chronic myelogenous leukemia via its control of PRKD2.

PubMed

Yang, Zhong-Fa; Zhang, Haojian; Ma, Leyuan; Peng, Cong; Chen, Yaoyu; Wang, Junling; Green, Michael R; Li, Shaoguang; Rosmarin, Alan G

2013-02-05

Hematopoietic stem cells (HSCs) are the source of all blood lineages, and HSCs must balance quiescence, self-renewal, and differentiation to meet lifelong needs for blood cell development. Transformation of HSCs by the breakpoint cluster region-ABL tyrosine kinase (BCR-ABL) oncogene causes chronic myelogenous leukemia (CML). The E-twenty six (ets) transcription factor GA binding protein (GABP) is a tetrameric transcription factor complex that contains GABPα and GABPβ proteins. Deletion in bone marrow of Gabpa, the gene that encodes the DNA-binding component, caused cell cycle arrest in HSCs and profound loss of hematopoietic progenitor cells. Loss of Gabpα prevented development of CML, although mice continued to generate BCR-ABL-expressing Gabpα-null cells for months that were serially transplantable and contributed to all lineages in secondary recipients. A bioinformatic screen identified the serine-threonine kinase protein kinase D2 (PRKD2) as a potential effector of GABP in HSCs. Prkd2 expression was markedly reduced in Gabpα-null HSCs and progenitor cells. Reduced expression of PRKD2 or pharmacologic inhibition decreased cell cycling, and PRKD2 rescued growth of Gabpα-null BCR-ABL-expressing cells. Thus, GABP is required for HSC cell cycle entry and CML development through its control of PRKD2. This offers a potential therapeutic target in leukemia.

Soft-Starting Power-Factor Motor Controller

NASA Technical Reports Server (NTRS)

Nola, F. J.

1983-01-01

Three-phase power-factor controller with soft start is based on earlier version that does not control starting transients. Additional components serve to turn off "run" command signal and substitute gradual startup command signal during preset startup interval. Improved controller reduces large current surge that usually accompanies starting. Controller applies power smoothly, without causing motor vibrations.

Power Factor Controller

NASA Technical Reports Server (NTRS)

1997-01-01

Frank Nola invented the Power Factor Controller (PFC) at Marshall Space Flight Center more than a decade ago. Nola came up with a way to curb power wastage in AC induction motors. The PFC matches voltage with the motor's actual need by continuously sensing shifts between voltage and current. When it senses a light load it cuts the voltage to the minimum needed. Potential energy savings range from 8 to 65 percent.

Primacy of the 3B approach to control risk factors for cardiovascular disease in type 2 diabetes patients.

PubMed

Ji, Linong; Hu, Dayi; Pan, Changyu; Weng, Jianping; Huo, Yong; Ma, Changsheng; Mu, Yiming; Hao, Chuanming; Ji, Qiuhe; Ran, Xingwu; Su, Benli; Zhuo, Hanjing; Fox, Keith A A; Weber, Michael; Zhang, Danyi

2013-10-01

. Achieving adequate control of risk factors for cardiovascular disease in patients with type 2 diabetes remains a clinical challenge. Interventions to achieve control of 3Bs coupled with modification of additional cardiovascular disease predictors are crucial for optimization of clinical outcomes in patients with type 2 diabetes. Copyright © 2013 Elsevier Inc. All rights reserved.

Laryngopharyngeal reflux and herpes simplex virus type 2 are possible risk factors for adult-onset recurrent respiratory papillomatosis (prospective case-control study).

PubMed

Formánek, M; Jančatová, D; Komínek, P; Matoušek, P; Zeleník, K

2017-06-01

The human papillomavirus (HPV) causes recurrent respiratory papillomatosis (RRP). Although HPV prevalence is high, the incidence of papillomatosis is low. Thus, factors other than HPV infection probably contribute to RRP. This study investigated whether patients with papillomatosis are more often infected with herpes simplex virus type 2 and chlamydia trachomatis (ChT) and whether laryngopharyngeal reflux (LPR) occurs in this group of patients more often. Prospective case-control study. Department of Otorhinolaryngology of University Hospital. The study included 20 patients with adult-onset RRP and 20 adult patients with vocal cord cyst and no pathology of laryngeal mucosa (control group). Immunohistochemical analysis of pepsin, HPV, herpes simplex virus type 2 and ChT was performed in biopsy specimens of laryngeal papillomas and of healthy laryngeal mucosa (control group) obtained from medial part of removed vocal cord cyst during microlaryngoscopy procedures. Pathologic LPR (pepsin in tissue) was diagnosed in 8/20 (40.0%) patients with papillomatosis and in 0/20 control patients (P = .003). Herpes simplex virus type 2 was present in 9/20 (45.0%) patients with papillomatosis and in 0/20 control patients (P = .001). Five specimens were positive for both pepsin and herpes simplex virus type 2. No samples were positive for ChT. There were no significant differences between groups for age, body mass index, diabetes mellitus and gastrooesophageal reflux disease. Tobacco exposure was not more frequent in RRP group either (P = .01). Results show that LPR and herpes simplex virus type 2 are significantly more often present in patients with RRP. LPR and herpes simplex virus type 2 might activate latent HPV infection and thereby be possible risk factors for RRP. © 2016 John Wiley & Sons Ltd.

Factor information retrieval system version 2. 0 (fire) (for microcomputers). Software

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

FIRE Version 2.0 contains EPA's unique recommended criteria and toxic air emission estimation factors. FIRE consists of: (1) an EPA internal repository system that contains emission factor data identified and collected, and (2) an external distribution system that contains only EPA's recommended factors. The emission factors, compiled from a review of the literature, are identified by pollutant name, CAS number, process and emission source descriptions, SIC code, SCC, and control status. The factors are rated for quality using AP-42 rating criteria.

SFA 2.0- Watershed Structure and Controls

DOE Office of Scientific and Technical Information (OSTI.GOV)

Williams, Ken

2015-01-23

Berkeley Lab Earth Scientist Ken Williams explains the watershed research within the Sustainable Systems SFA 2.0 project—including identification and monitoring of primary factors that control watershed biogeochemical functioning.

E3 ubiquitin ligase RFWD2 controls lung branching through protein-level regulation of ETV transcription factors.

PubMed

Zhang, Yan; Yokoyama, Shigetoshi; Herriges, John C; Zhang, Zhen; Young, Randee E; Verheyden, Jamie M; Sun, Xin

2016-07-05

The mammalian lung is an elaborate branching organ, and it forms following a highly stereotypical morphogenesis program. It is well established that precise control at the transcript level is a key genetic underpinning of lung branching. In comparison, little is known about how regulation at the protein level may play a role. Ring finger and WD domain 2 (RFWD2, also termed COP1) is an E3 ubiquitin ligase that modifies specific target proteins, priming their degradation via the ubiquitin proteasome system. RFWD2 is known to function in the adult in pathogenic processes such as tumorigenesis. Here, we show that prenatal inactivation of Rfwd2 gene in the lung epithelium led to a striking halt in branching morphogenesis shortly after secondary branch formation. This defect is accompanied by distalization of the lung epithelium while growth and cellular differentiation still occurred. In the mutant lung, two E26 transformation-specific (ETS) transcription factors essential for normal lung branching, ETS translocation variant 4 (ETV4) and ETV5, were up-regulated at the protein level, but not at the transcript level. Introduction of Etv loss-of-function alleles into the Rfwd2 mutant background attenuated the branching phenotype, suggesting that RFWD2 functions, at least in part, through degrading ETV proteins. Because a number of E3 ligases are known to target factors important for lung development, our findings provide a preview of protein-level regulatory network essential for lung branching morphogenesis.

Risk factors for type 2 diabetes mellitus among out-patients in Ho, the Volta regional capital of Ghana: a case-control study.

PubMed

Gudjinu, Horlali Yao; Sarfo, Bismark

2017-07-26

The prevalence of type 2 diabetes mellitus in developing countries like Ghana continues to rise. This study seeks to assess the risk factors of type 2 diabetes mellitus in a Ghanaian setting. An unmatched case-control study among patients receiving care at the out-patient departments of the two major hospitals in the Ho Municipality. Patients diagnosed with type 2 diabetes mellitus were recruited. Appropriate controls with similar ages who were also patients receiving care at the out-patient department of these hospitals were recruited. Both cases and controls were administered a questionnaire that comprises of standardized and validated tools. These tools include WHO STEPs instrument, general practice physical activity questionnaire and rapid eating and activity assessment for patients. Additionally, the research participants were made to undergo physical examinations for weight, height, waist circumference and laboratory testing of fasting venous blood to assess the biochemical factors of interest namely fasting blood glucose and fasting lipids. Analysis of data was done using STATA version 11. A total of 136 (48 cases and 88 controls) participants of which 95 [39 (81.25%) cases and 56 (63.64%) controls] respondents underwent laboratory testing for fasting blood glucose and fasting blood lipid (total cholesterol, HDL cholesterol and triglycerides). Participants were aged between 35 and 62 years. This study reveals a number of risk factors for type 2 diabetes mellitus. Individuals in the middle socio-economic class have a greater risk of developing type 2 diabetes mellitus with an OR of 5.03 (p < 0.003; 95% CI 1.71-14.74). Eating large quantities/servings of fruits per seating provides protection against development of type 2 diabetes mellitus. A low physical activity level is a valid determinant of type 2 diabetes mellitus irrespective of body mass index, socio-economic level or place of residence. Individuals within the middle socio-economic level, who are

ENGINEERING AND ECONOMIC FACTORS AFFECTING THE INSTALLATION OF CONTROL TECHNOLOGIES FOR MULTIPOLLUTANT STRATEGIES

EPA Science Inventory

The report evaluates the engineering and economic factors associated with installing air pollution control technologies to meet the requirements of strategies to control sulfur dioxide (SO2), oxides of nitrogen (NOX), and mercury under the Clear Skies Act multipollutant control s...

Environmental risk factors for oesophageal cancer in Malawi: A case-control study.

PubMed

Mlombe, Y B; Rosenberg, N E; Wolf, L L; Dzamalala, C P; Chalulu, K; Chisi, J; Shaheen, N J; Hosseinipour, M C; Shores, C G

2015-09-01

There is a high burden of oesophageal cancer in Malawi with dismal outcomes. It is not known whether environmental factors are associated with oesophageal cancer. Without knowing this critical information, prevention interventions are not possible. The purpose of this analysis was to explore environmental factors associated with oesophageal cancer in the Malawian context. A hospital-based case-control study of the association between environmental risk factors and oesophageal cancer was conducted at Kamuzu Central Hospital in Lilongwe, Malawi and Queen Elizabeth Central Hospital in Blantyre, Malawi. Ninety-six persons with squamous cell carcinoma and 180 controls were enrolled and analyzed. These two groups were compared for a range of environmental risk factors, using logistic regression models. Unadjusted and adjusted odds ratios and 95% confidence intervals (CI) were calculated. Firewood cooking, cigarette smoking, and use of white maize flour all had strong associations with squamous cell carcinoma of the oesophagus, with adjusted odds ratios of 12.6 (95% CI: 4.2-37.7), 5.4 (95% CI: 2.0-15.2) and 6.6 (95% CI: 2.3-19.3), respectively. Several modifiable risk factors were found to be strongly associated with squamous cell carcinoma. Research is needed to confirm these associations and then determine how to intervene on these modifiable risk factors in the Malawian context.

Risk factors for syphilis in women: case-control study.

PubMed

Macêdo, Vilma Costa de; Lira, Pedro Israel Cabral de; Frias, Paulo Germano de; Romaguera, Luciana Maria Delgado; Caires, Silvana de Fátima Ferreira; Ximenes, Ricardo Arraes de Alencar

2017-08-17

To determine the sociodemographic, behavioral, and health care factors related to the occurrence of syphilis in women treated at public maternity hospitals. This is a case-control study (239 cases and 322 controls) with women admitted to seven maternity hospitals in the municipality of Recife, Brazil, from July 2013 to July 2014. Eligible women were recruited after the result of the VDRL (Venereal Disease Research Laboratory) under any titration. The selection of cases and controls was based on the result of the serology for syphilis using ELISA (enzyme-linked immunosorbent assay). The independent variables were grouped into: sociodemographic, behavioral, clinical and obstetric history, and health care in prenatal care and maternity hospital. Information was obtained by interview, during hospitalization, with the application of a questionnaire. Odds ratios and 95% confidence intervals were estimated using logistic regression to identify the predicting factors of the variable to be explained. The logistic regression analysis identified as determinant factors for gestational syphilis: education level of incomplete basic education or illiterate (OR = 2.02), lack of access to telephone (OR = 2.4), catholic religion (OR = 1.70 ), four or more pregnancies (OR = 2.2), three or more sexual partners in the last year (OR = 3.1), use of illicit drugs before the age of 18 (OR = 3.0), and use of illicit drugs by the current partner (OR = 1.7). Only one to three prenatal appointments (OR = 3.5) and a previous history of sexually transmitted infection (OR = 9.7) were also identified as determinant factors. Sociodemographic, behavioral, and health care factors are associated with the occurrence of syphilis in women and should be taken into account in the elaboration of universal strategies aimed at the prevention and control of syphilis, but with a focus on situations of greater vulnerability. Determinar os fatores sociodemográficos, comportamentais e de assistência à sa

SFA 2.0- Watershed Structure and Controls

ScienceCinema

Williams, Ken

2018-05-23

Berkeley Lab Earth Scientist Ken Williams explains the watershed research within the Sustainable Systems SFA 2.0 project—including identification and monitoring of primary factors that control watershed biogeochemical functioning.

Motor power factor controller with a reduced voltage starter

NASA Technical Reports Server (NTRS)

Nola, F. J. (Inventor)

1981-01-01

A power factor type motor controller is disclosed in which the conventional power factor constant voltage command signal is replaced during a starting interval with a graduated control voltage. This continuation-impart of a pending patent application (Serial No. 199, 765: Three Phase Factor Controller) provides a means for modifying the operation of the system for a motor start-up interval of 5 to 30 second. Using a ramp generators, an initial ramp-like signal replaces a constant power factor signal supplied by a potentiometer. The ramp-like signal is applied to a 15 terminal where it is summed with an operating power factor signal from phase detectors in order to obtain a control signal for ultimately controlling SCR devices. The SCR devices are turned on at an advancing rate with time responsive to the combination signal described rather than simply a function of a ramp-like signal alone.

Nutritional status, glycemic control and its associated risk factors among a sample of type 2 diabetic individuals, a pilot study.

PubMed

Firouzi, Somayyeh; Barakatun-Nisak, Mohd Yusof; Azmi, Kamaruddin Nor

2015-01-01

The prevalence of type 2 diabetes is increasing in Malaysia, with most patients poorly controlled. Hence, this study aimed to determine nutritional and metabolic status as well as blood pressure of Malaysian patients with type 2 diabetes mellitus and identify associated risk factors for poor glycemic control. A total of 104 type 2 diabetic patients were recruited and completed a questionnaire covering socio-demographic status, 3-day diet records, and physical activity. Anthropometry and glycemic control parameters, lipid profile and blood pressure were also measured. Subjects were on average 56.7±9.9 years old with a mean duration of diabetes of 6.5 ± 5.0 years. The mean hemoglobin A1c of the subjects was 7.6% ± 1.4%, with only 20.2% achieving the target goal of <6.5% with no significant differences between genders. The mean body mass index was 26.9 ± 4.7 kg/m(2), with 86.5% either were overweight or obese. Only 10.6% of the subjects exercised daily. The proportions of macronutrients relative to total energy intake were consistent with the recommendations of most diabetes associations. The adjusted odds of having poor glycemic control were 3.235 (1.043-10.397) (P < 0.05) higher among those who had high density lipoprotein cholesterol levels below the normal range. Those taking one or two types of oral anti-diabetic drugs had 19.9 (2.959-87.391) (P < 0.01) and 14.3 (2.647-77.500) (P < 0.01) higher odds of poor glycemic control respectively compared to those who were being treated by diet alone. Poor glycemic control was prevalent among Malaysian diabetic patients, and this could be associated with low levels of HDL and being treated with oral anti-diabetes agents.

Nutritional status, glycemic control and its associated risk factors among a sample of type 2 diabetic individuals, a pilot study

PubMed Central

Firouzi, Somayyeh; Barakatun-Nisak, Mohd Yusof; Azmi, Kamaruddin Nor

2015-01-01

Background: The prevalence of type 2 diabetes is increasing in Malaysia, with most patients poorly controlled. Hence, this study aimed to determine nutritional and metabolic status as well as blood pressure of Malaysian patients with type 2 diabetes mellitus and identify associated risk factors for poor glycemic control. Materials and Methods: A total of 104 type 2 diabetic patients were recruited and completed a questionnaire covering socio-demographic status, 3-day diet records, and physical activity. Anthropometry and glycemic control parameters, lipid profile and blood pressure were also measured. Results: Subjects were on average 56.7±9.9 years old with a mean duration of diabetes of 6.5 ± 5.0 years. The mean hemoglobin A1c of the subjects was 7.6% ± 1.4%, with only 20.2% achieving the target goal of <6.5% with no significant differences between genders. The mean body mass index was 26.9 ± 4.7 kg/m2, with 86.5% either were overweight or obese. Only 10.6% of the subjects exercised daily. The proportions of macronutrients relative to total energy intake were consistent with the recommendations of most diabetes associations. The adjusted odds of having poor glycemic control were 3.235 (1.043-10.397) (P < 0.05) higher among those who had high density lipoprotein cholesterol levels below the normal range. Those taking one or two types of oral anti-diabetic drugs had 19.9 (2.959-87.391) (P < 0.01) and 14.3 (2.647-77.500) (P < 0.01) higher odds of poor glycemic control respectively compared to those who were being treated by diet alone. Conclusion: Poor glycemic control was prevalent among Malaysian diabetic patients, and this could be associated with low levels of HDL and being treated with oral anti-diabetes agents. PMID:25767521

[Type 2 diabetes mellitus and cardiovascular risk factors: is comprehensive treatment required?].

PubMed

Nadal, Josep Franch; Gutiérrez, Pedro Conthe

2013-09-01

Diabetes mellitus, especially type 2, is a metabolic disease involving the coexistence of several cardiovascular risk factors. Affected patients are therefore at high cardiovascular risk (2-3 times higher than that of men in the general population and 2-6 times higher than that of women). Cardiovascular disease is the main cause of death in the diabetic population, followed by cancer. Cardiovascular risk cannot be compared between diabetic patients and persons who have already shown one or more manifestations of cardiovascular disease (such as myocardial infarction). Single risk factors should be evaluated in combination with other risk factors and a person's cardiovascular risk should be individually assessed. Cardiovascular risk assessment in patients with diabetes through current calculations methods is complex because their ability to predict risk in individuals is very low. Studies such as that by Steno have demonstrated the validity of a comprehensive strategy to control all the risk factors present in persons with type 2 diabetes mellitus, which can reduce the development of micro- and macrovascular complications and mortality by almost 50%. The present article reviews each of the classical cardiovascular risk factors (hypertension, dyslipidemia, smoking, obesity, sedentariness) in relation to diabetes, as well as their recommended targets and the benefits of their control. In view of the above, a comprehensive approach is recommended to control the multiple risk factors that can coexist in persons with type 2 diabetes mellitus. Copyright © 2013 Elsevier España, S.L. All rights reserved.

[Cardiovascular risk factor control in a population with longstanding diabetes attending endocrinology departments].

PubMed

Comi-Diaz, Cristina; Miralles-García, José M; Cabrerizo, Lucio; Pérez, María; Masramon, Xavier; De Pablos-Velasco, Pedro

2010-12-01

To determine the degree of control of cardiovascular risk factors (CVRF) in a sample of patients with diabetes mellitus (DM) attending Endocrinology and Nutrition Departments in Spain. An epidemiological, cross-sectional, multicenter and observational study involving 41 Departments of Endocrinology and Nutrition in Spain. Each department selected patients with DM with over 10 years of evolution, which were treated in outpatient settings. Demographic, anthropometric, clinical and biochemical data, including medication, were collected for each participant. 1159 patients who met the inclusion criteria were recruited. 52% of the participants were patients with type 2 DM. The mean duration of DM was 19.6 years. A proportion of 37%, 44%, 27.6% and 25.5% had good control of their blood pressure (BP), low density cholesterol (LDLc), lipids and glucose, respectively, and only 4.3% did well in all factors evaluated. The percentage of poorly controlled BP was four times higher in type 2 than in type 1 DM. Obesity, low cultural level and aggregation of cardiovascular risk factors were associated with poorer control. The degree of control of CVRF in diabetic patients with long disease duration is insufficient. Copyright © 2010 SEEN. Published by Elsevier Espana. All rights reserved.

Bicycling to school improves the cardiometabolic risk factor profile: a randomised controlled trial

PubMed Central

Østergaard, Lars; Børrestad, Line A B; Tarp, Jakob; Andersen, Lars Bo

2012-01-01

Objectives To investigate whether bicycling to school improves cardiometabolic risk factor profile and cardiorespiratory fitness among children. Design Prospective, blinded, randomised controlled trial. Setting Single centre study in Odense, Denmark Participants 43 children previously not bicycling to school were randomly allocated to control group (n=20) (ie, no change in lifestyle) or intervention group (ie, bicycling to school) (n=23). Primary and secondary outcome measures Change in cardiometabolic risk factor score and change in cardiorespiratory fitness. Results All participants measured at baseline returned at follow-up. Based upon intention-to-treat (ITT) analyses, clustering of cardiometabolic risk factors was lowered by 0.58 SD (95% CI −1.03 to −0.14, p=0.012) in the bicycling group compared to the control group. Cardiorespiratory fitness (l O2/min) per se did not increase significantly more in the intervention than in the control group (β=0.0337, 95% CI −0.06 to 0.12, p=0.458). Conclusions Bicycling to school counteracted a clustering of cardiometabolic risk factors and should thus be recognised as potential prevention of type 2 diabetes mellitus and cardiovascular disease (CVD). The intervention did, however, not elicit a larger increase in cardiorespiratory fitness in the intervention group as compared with the control group. Trial registration Registered at http://www.clinicaltrials.gov (NCT01236222). PMID:23117560

FOG-2, a Heart- and Brain-Enriched Cofactor for GATA Transcription Factors

PubMed Central

Lu, Jian-rong; McKinsey, Timothy A.; Xu, Hongtao; Wang, Da-zhi; Richardson, James A.; Olson, Eric N.

1999-01-01

Members of the GATA family of zinc finger transcription factors have been shown to play important roles in the control of gene expression in a variety of cell types. GATA-1, -2, and -3 are expressed primarily in hematopoietic cell lineages and are required for proliferation and differentiation of multiple hematopoietic cell types, whereas GATA-4, -5, and -6 are expressed in the heart, where they activate cardiac muscle structural genes. Friend of GATA-1 (FOG) is a multitype zinc finger protein that interacts with GATA-1 and serves as a cofactor for GATA-1-mediated transcription. FOG is coexpressed with GATA-1 in developing erythroid and megakaryocyte cell lineages and cooperates with GATA-1 to control erythropoiesis. We describe a novel FOG-related factor, FOG-2, that is expressed predominantly in the developing and adult heart, brain, and testis. FOG-2 interacts with GATA factors, and interaction of GATA-4 and FOG-2 results in either synergistic activation or repression of GATA-dependent cardiac promoters, depending on the specific promoter and the cell type in which they are tested. The properties of FOG-2 suggest its involvement in the control of cardiac and neural gene expression by GATA transcription factors. PMID:10330188

Factors associated with glycemic control among diabetic adult out-patients in Northeast Ethiopia.

PubMed

Fiseha, Temesgen; Alemayehu, Ermiyas; Kassahun, Wongelawit; Adamu, Aderaw; Gebreweld, Angesom

2018-05-18

The aim of this study was to determine the status of glycemic control and identify factors associated with poor glycemic control among diabetic out-patients. A hospital based cross-sectional study was conducted among randomly selected 384 (126 type 1 and 258 type 2) diabetic adults attending a hospital in Northeast Ethiopia from January 1 to April 30, 2017. Of the total participants, 70.8% had poor status of glycemic control (defined as mean fasting blood glucose level above 130 mg/dl). In the multivariate analysis, rural residence (AOR = 2.61, 95% CI 1.37-4.96), low educational level (AOR = 7.10, 95% CI 2.94-17.17) and longer duration of diabetes (AOR = 2.20, 95% CI 1.18-4.08) were significantly associated with increased odds of poor glycemic control. Moreover, merchants (AOR = 3.39, 95% CI 1.16-9.96) were significantly more likely to have poor glycemic control compared to government employee. Diabetic patients receiving oral anti-diabetics (AOR = 5.12, 95% CI 2.10-12.52) or insulin (AOR = 3.26, 95% CI 1.26-8.48) were more likely to be poorly controlled. These results highlight the needed for appropriate management of patients focusing on associated factors identified for poor glycemic control to maintain good glycemic control and improve adverse outcomes of the disease in this study setting.

Detection of protein-protein interactions by ribosome display and protein in situ immobilisation.

PubMed

He, Mingyue; Liu, Hong; Turner, Martin; Taussig, Michael J

2009-12-31

We describe a method for identification of protein-protein interactions by combining two cell-free protein technologies, namely ribosome display and protein in situ immobilisation. The method requires only PCR fragments as the starting material, the target proteins being made through cell-free protein synthesis, either associated with their encoding mRNA as ribosome complexes or immobilised on a solid surface. The use of ribosome complexes allows identification of interacting protein partners from their attached coding mRNA. To demonstrate the procedures, we have employed the lymphocyte signalling proteins Vav1 and Grb2 and confirmed the interaction between Grb2 and the N-terminal SH3 domain of Vav1. The method has promise for library screening of pairwise protein interactions, down to the analytical level of individual domain or motif mapping.

Complementary Phosphorylation Sites in the Adaptor Protein SLP-76 Promote Synergistic Activation of Natural Killer Cells

PubMed Central

Kim, Hun Sik; Long, Eric O.

2013-01-01

The cytotoxic effects of natural killer (NK) cells and their ability to secrete cytokines require the induction of synergistic signals from co-activation receptors, such as CD314 (NKG2D) and CD244 (2B4), which bind to ligands expressed on target cells. Synergy is required to overcome inhibition of the guanine nucleotide exchange factor (GEF) Vav1, a central regulator of NK cell activation, by the E3 ubiquitin ligase c-Cbl. However, the molecular basis for this synergy is unknown. Here, we showed that the adaptor protein Src homology 2 (SH2) domain–containing leukocyte phosphoprotein of 76 kD (SLP-76) was required for this synergy, and that distinct tyrosine residues in SLP-76 were phosphorylated by each receptor of a synergistic pair. Selective phosphorylation of tyrosine 113 or tyrosine 128 in SLP-76, each of which enables binding of SLP-76 to Vav1, was unique to receptors that stimulate ligand-dependent target cell killing, because antibody-dependent stimulation by Fc receptor CD16 promoted phosphorylation at both sites. Knockdown and reconstitution experiments with SLP-76 showed the distinct role of each tyrosine in the synergistic mobilization of Ca2+, revealing an unexpected degree of selectivity in the phosphorylation of SLP-76 by NK cell co-activation receptors. Together, these data suggest that complementation of separate phospho-tyrosine targets in SLP-76 forms the basis of synergistic NK cell activation. PMID:22786724

Factors controlling sulfur concentrations in volcanic apatite

USGS Publications Warehouse

Peng, G.; Luhr, J.F.; McGee, J.J.

1997-01-01

Apatite crystals from two types of samples were analyzed by electron microprobe for 15 major and trace elements: (1) apatite in H2O- and S-saturated experimental charges of the 1982 El Chicho??n trachyandesite and (2) apatite in volcanic rocks erupted from 20 volcanoes. The SO3 contents of the experimental apatite increase with increasing oxygen fugacity (fo2), from ???0.04 wt% in reduced charges buffered by fayalite-magnetite-quartz (FMQ), to 1.0-2.6 wt% in oxidized charges buffered by manganosite-hausmanite (MNH) or magnetite-hematite (MTH). The SO3 contents of MNH- and MTH-buffered apatite also generally increase with increasing pressure from 2 to 4 kbar and decreasing temperature from 950 to 800??C. The partition coefficient for SO3 between apatite and oxidized melt increases with decreasing temperature but appears to be independent of pressure. Apatites in volcanic rocks show a wide range of SO3 contents (<0.04 to 0.63 wt%). Our sample set includes one group known to contain primary anhydrite and a second group inferred to have been free of primary anhydrite. No systematic differences in apatite S contents are observed between these two groups. Our study was initiated to define the factors controlling S contents in apatite and to evaluate the hypothesis that high S contents in apatite could be characteristic of S-rich anhydrite-bearing magmas such as those erupted from El Chicho??n in 1982 and Pinatubo in 1991. This hypothesis is shown to be invalid, probably chiefly a consequence of the slow intra-crystaline diffusion that limits re-equilibration between early formed apatite and the evolving silicate melt. Contributing factors include early crystallization of most apatite over a relatively small temperature interval, common late-stage magmatic enrichment of S, progressive oxidation during magmatic evolution, and strong controls on S contents in apatite exerted fo2, temperature, and pressure.

Therapeutic interventions and success in risk factor control for secondary prevention of stroke.

PubMed

Alvarez-Sabin, Jose; Quintana, Manuel; Hernandez-Presa, Miguel Angel; Alvarez, Carlos; Chaves, Jose; Ribo, Marc

2009-01-01

We sought to evaluate the success rates in achieving preventive therapeutic goals in patients who experienced an ischemic stroke (IS) and compare them with those achieved in patients with coronary artery disease (CAD). This was an observational multicenter case-control study (3 patients with IS and one control subject with CAD) performed in 1444 primary health centers in Spain. Preventive therapeutic objectives according to American Heart Association guidelines were predefined. Demographic data, vascular risk factors, and success/failure in achievement of objectives were recorded and compared between patients with IS and CAD. A total of 5458 patients were included, 4098 (75.1%) had IS and 1360 (24.9%) had CAD. Although more than 90% of patients with hypertension, diabetes, or dyslipidemia were under specific drug regimens, only about 25% achieved the recommended therapeutic objective for each risk factor. Success rate was especially low among patients with IS compared with CAD: hypertension (23.8% v 27.2%; P = .028); dyslipidemia (13.6% v 20.3%; P < .001); and abdominal obesity (49.1% v 54.6%; P = .002). The only objective widely achieved in both groups was the use of antithrombotic drugs in atrial fibrillation (97.2% v 94.7%; P = .125). Only 3.3% of patients with IS had all risk factors under control, compared with 5.6% of those with CAD (P = .006). For all patients, multivariate logistic regression model showed that independent predictors of full risk factor control were: presence of CAD as compared with IS (odds ratio [OR] 2.11; 95% confidence interval [CI] 1.35-3.29; P = .001), older age (OR 1.02; 95% CI 1.00-1.04; P = .028), and having less than 3 risk factors (OR 16.98; 95% CI 9.02-31.97; P < .001). Success in achieving preventive therapeutic objectives for secondary prevention of vascular events is low, especially among patients with IS. There is an urgent need to devise strategies to improve risk factor control.

Educational status-related disparities in awareness, treatment and control of cardiovascular risk factors in India

PubMed Central

Gupta, Rajeev; Sharma, Krishna Kumar; Gupta, Bal Kishan; Gupta, Arvind; Gupta, Revant R; Deedwania, Prakash C

2015-01-01

Objective To determine association of socioeconomic status, defined by educational status (ES), with awareness, treatment and control of cardiovascular risk factors. Methods We performed an epidemiological study at 11 cities in India using cluster sampling. 6198 subjects (3426 men, 2772 women, response 62%, age 48±10 years) were evaluated for sociodemographic, lifestyle, anthropometric and biochemical factors. ES was categorised according to years of schooling into low (≤10 years), medium (11–15 years) and high (>15 years). Risk factors were diagnosed according to current guidelines. Awareness, treatment and control status were determined for hypertension, diabetes and hypercholesterolaemia. For smoking/tobacco use, quit rate was determined. Descriptive statistics are reported. Results Age-adjusted and sex-adjusted prevalence (%) of various risk factors in low, medium and high ES subjects was hypertension 31.8, 29.5 and 34.1, diabetes 14.5, 15.3 and 14.3, hypercholesterolaemia 24.0, 23.9 and 27.3, and smoking/tobacco use 24.3, 14.4 and 19.0. Significantly increasing trends with low, medium and high ES were observed for hypertension awareness (30.7, 37.8, 47.0), treatment (24.3, 29.2, 35.5) and control (7.8, 11.6, 15.5); diabetes awareness (47.2, 51.5, 56.4), treatment (38.3, 41.3, 46.0) and control (18.3, 15.3, 22.8); hypercholesterolaemia awareness (8.9, 22.4, 18.4), treatment (4.1, 6.2, 7.9) and control (2.8, 3.2, 6.9), as well as for smoking/tobacco quit rates (1.6, 2.8, 5.5) (χ2 for trend, p<0.05). Conclusions Low ES subjects in India have lower awareness, treatment and control of hypertension, diabetes and hypercholesterolaemia and smoking quit rates. PMID:27326202

Growth factors FGF8 and FGF2 and their receptor FGFR1, transcriptional factors Msx-1 and MSX-2, and apoptotic factors p19 and RIP5 participate in the early human limb development.

PubMed

Becic, Tina; Kero, Darko; Vukojevic, Katarina; Mardesic, Snjezana; Saraga-Babic, Mirna

2018-04-01

The expression pattern of fibroblast growth factors FGF8 and FGF2 and their receptor FGFR1, transcription factors MSX-1 and MSX-2, as well as cell proliferation (Ki-67) and cell death associated caspase-3, p19 and RIP5 factors were analyzed in histological sections of eight 4th-9th-weeks developing human limbs by immunohistochemistry and semi-thin sectioning. Increasing expression of all analyzed factors (except FGF8) characterized both the multilayered human apical ectodermal ridge (AER), sub-ridge mesenchyme (progress zone) and chondrocytes in developing human limbs. While cytoplasmic co-expression of MSX-1 and MSX-2 was observed in both limb epithelium and mesenchyme, p19 displayed strong cytoplasmic expression in non-proliferating cells. Nuclear expression of Ki-67 proliferating cells, and partly of MSX-1 and MSX-2 was detected in the whole limb primordium. Strong expression of factors p19 and RIP5, both in the AER and mesenchyme of human developing limbs indicates their possible involvement in control of cell senescence and cell death. In contrast to animal studies, expression of FGFR1 in the surface ectoderm and p19 in the whole limb primordium might reflect interspecies differences in limb morphology. Expression of FGF2 and downstream RIP5 gene, and transcription factors Msx-1 and MSX-2 did not show human-specific changes in expression pattern. Based on their spatio-temporal expression during human limb development, our study indicates role of FGFs and Msx genes in stimulation of cell proliferation, limb outgrowth, digit elongation and separation, and additionally MSX-2 in control of vasculogenesis. The cascade of orchestrated gene expressions, including the analyzed developmental factors, jointly contribute to the complex human limb development. Copyright © 2018 Elsevier GmbH. All rights reserved.

FADD and the NF-κB family member Bcl-3 regulate complementary pathways to control T-cell survival and proliferation

PubMed Central

Rangelova, Svetla; Kirschnek, Susanne; Strasser, Andreas; Häcker, Georg

2008-01-01

Fas-associated protein with death domain/mediator of receptor induced toxicity (FADD/MORT1) was first described as a transducer of death receptor signalling but was later recognized also to be important for proliferation of T cells. B-cell lymphoma 3 (Bcl-3) is a relatively little understood member of the nuclear factor (NF)-κB family of transcription factors. We recently found that Bcl-3 is up-regulated in T cells from mice where FADD function is blocked by a dominant negative transgene (FADD-DN). To understand the importance of this, we generated FADD-DN/bcl-3−/− mice. Here, we report that T cells from these mice show massive cell death and severely reduced proliferation in response to T-cell receptor (TCR) stimulation in vitro. Transgenic co-expression of Bcl-2 (FADD-DN/bcl-3−/−/vav-bcl-2 mice) rescued the survival but not the proliferation of T cells. FADD-DN/bcl-3−/− mice had normal thymocyte numbers but reduced numbers of peripheral T cells despite an increase in cycling T cells in vivo. However, activation of the classical NF-κB and extracellular regulated kinase (ERK) pathways and expression of interleukin (IL)-2 mRNA upon stimulation were normal in T cells from FADD-DN/bcl-3−/− mice. These data suggest that FADD and Bcl-3 regulate separate pathways that both contribute to survival and proliferation in mouse T cells. PMID:18557791

Fuzzy comprehensive evaluation of multiple environmental factors for swine building assessment and control.

PubMed

Xie, Qiuju; Ni, Ji-Qin; Su, Zhongbin

2017-10-15

In confined swine buildings, temperature, humidity, and air quality are all important for animal health and productivity. However, the current swine building environmental control is only based on temperature; and evaluation and control methods based on multiple environmental factors are needed. In this paper, fuzzy comprehensive evaluation (FCE) theory was adopted for multi-factor assessment of environmental quality in two commercial swine buildings using real measurement data. An assessment index system and membership functions were established; and predetermined weights were given using analytic hierarchy process (AHP) combined with knowledge of experts. The results show that multi-factors such as temperature, humidity, and concentrations of ammonia (NH 3 ), carbon dioxide (CO 2 ), and hydrogen sulfide (H 2 S) can be successfully integrated in FCE for swine building environment assessment. The FCE method has a high correlation coefficient of 0.737 compared with the method of single-factor evaluation (SFE). The FCE method can significantly increase the sensitivity and perform an effective and integrative assessment. It can be used as part of environmental controlling and warning systems for swine building environment management to improve swine production and welfare. Copyright © 2017 Elsevier B.V. All rights reserved.

Environmental risk factors contributing to traffic accidents in children: a case-control study.

PubMed

Jamshidi, Ensiyeh; Moradi, Ali; Majdzadeh, Reza

2017-09-01

The aim of this study is to identify environmental risk factors related to road accidents in children of Tehran. This case-control study was performed in 2013. The cases were injured pedestrians aged 5-15 who were admitted to major hospitals supervised by Tehran University of Medical Sciences. The sample size for the cases was 273 and for the control group was 546. For the completeness of the clusters, 7 extra persons in case (total = 280) and 14 persons (total = 560) in control group were included. The interference of confounding variables assessed through forward conditional logistic regression. Result shows occurrence of traffic accidents was significantly associate with the width of the alleys or (<5 m: OR = 8.4, 95% CI: 3.3-21.5; 5-8 m: OR = 4.7, 95% CI: 1.8-12.2), distance from home to school((<100 m: OR = 1.7, 95% CI: 1.0-2.8), existence of parking lot (OR = 1.5, 95% CI: 1.0-2.3), traffic congestion (OR = 4.1, 95% CI: 2.6-6.4), traffic speed (OR = 2.1, 95% CI: 1.3-3.2) and existence of pedestrian bridges(OR = 4.2, 95% CI: 2.6-6.8). In the light of the important role of environmental factors in the occurrence of child traffic accidents, alleviating structural risk factors in addition to education and enforcement need more systematic efforts and planning by policymakers and urban planners to attain pedestrian safety goals.

Light meson form factors at high Q2 from lattice QCD

NASA Astrophysics Data System (ADS)

Koponen, Jonna; Zimermmane-Santos, André; Davies, Christine; Lepage, G. Peter; Lytle, Andrew

2018-03-01

Measurements and theoretical calculations of meson form factors are essential for our understanding of internal hadron structure and QCD, the dynamics that bind the quarks in hadrons. The pion electromagnetic form factor has been measured at small space-like momentum transfer |q2| < 0.3 GeV2 by pion scattering from atomic electrons and at values up to 2.5 GeV2 by scattering electrons from the pion cloud around a proton. On the other hand, in the limit of very large (or infinite) Q2 = -q2, perturbation theory is applicable. This leaves a gap in the intermediate Q2 where the form factors are not known. As a part of their 12 GeV upgrade Jefferson Lab will measure pion and kaon form factors in this intermediate region, up to Q2 of 6 GeV2. This is then an ideal opportunity for lattice QCD to make an accurate prediction ahead of the experimental results. Lattice QCD provides a from-first-principles approach to calculate form factors, and the challenge here is to control the statistical and systematic uncertainties as errors grow when going to higher Q2 values. Here we report on a calculation that tests the method using an ηs meson, a 'heavy pion' made of strange quarks, and also present preliminary results for kaon and pion form factors. We use the nf = 2 + 1 + 1 ensembles made by the MILC collaboration and Highly Improved Staggered Quarks, which allows us to obtain high statistics. The HISQ action is also designed to have small dicretisation errors. Using several light quark masses and lattice spacings allows us to control the chiral and continuum extrapolation and keep systematic errors in check. Warning, no authors found for 2018EPJWC.17506016.

Physiological Srsf2 P95H expression causes impaired hematopoietic stem cell functions and aberrant RNA splicing in mice.

PubMed

Kon, Ayana; Yamazaki, Satoshi; Nannya, Yasuhito; Kataoka, Keisuke; Ota, Yasunori; Nakagawa, Masahiro Marshall; Yoshida, Kenichi; Shiozawa, Yusuke; Morita, Maiko; Yoshizato, Tetsuichi; Sanada, Masashi; Nakayama, Manabu; Koseki, Haruhiko; Nakauchi, Hiromitsu; Ogawa, Seishi

2018-02-08

Splicing factor mutations are characteristic of myelodysplastic syndromes (MDS) and related myeloid neoplasms and implicated in their pathogenesis, but their roles in the development of MDS have not been fully elucidated. In the present study, we investigated the consequence of mutant Srsf2 expression using newly generated Vav1-Cre -mediated conditional knockin mice. Mice carrying a heterozygous Srsf2 P95H mutation showed significantly reduced numbers of hematopoietic stem and progenitor cells (HSPCs) and differentiation defects both in the steady-state condition and transplantation settings. Srsf2 -mutated hematopoietic stem cells (HSCs) showed impaired long-term reconstitution compared with control mice in competitive repopulation assays. Although the Srsf2 mutant mice did not develop MDS under the steady-state condition, when their stem cells were transplanted into lethally irradiated mice, the recipients developed anemia, leukopenia, and erythroid dysplasia, which suggests the role of replicative stress in the development of an MDS-like phenotype in Srsf2 -mutated mice. RNA sequencing of the Srsf2 -mutated HSPCs revealed a number of abnormal splicing events and differentially expressed genes, including several potential targets implicated in the pathogenesis of hematopoietic malignancies, such as Csf3r , Fyn , Gnas , Nsd1 , Hnrnpa2b1 , and Trp53bp1 Among the mutant Srsf2 -associated splicing events, most commonly observed were the enhanced inclusion and/or exclusion of cassette exons, which were caused by the altered consensus motifs for the recognition of exonic splicing enhancers. Our findings suggest that the mutant Srsf2 leads to a compromised HSC function by causing abnormal RNA splicing and expression, contributing to the deregulated hematopoiesis that recapitulates the MDS phenotypes, possibly as a result of additional genetic and/or environmental insults. © 2018 by The American Society of Hematology.

A global study of the unmet need for glycemic control and predictor factors among patients with type 2 diabetes mellitus who have achieved optimal fasting plasma glucose control on basal insulin.

PubMed

Raccah, Denis; Chou, Engels; Colagiuri, Stephen; Gaàl, Zsolt; Lavalle, Fernando; Mkrtumyan, Ashot; Nikonova, Elena; Tentolouris, Nikolaos; Vidal, Josep; Davies, Melanie

2017-03-01

This study used data from different sources to identify the extent of the unmet need for postprandial glycemic control in patients with type 2 diabetes mellitus (T2DM) after the initiation of basal insulin therapy in Europe, Asia Pacific, the United States, and Latin America. Different levels of evidence were used as available for each country/region, with data extracted from seven randomized controlled trials (RCTs), three clinical trial registries (CTRs), and three electronic medical record (EMR) databases. Glycemic status was categorized as "well controlled" (glycated hemoglobin [HbA 1c ] at target [<7%]), "residual hyperglycemia" (fasting plasma glucose [FPG] but not HbA 1c at target [FPG <7.2/7.8 mmol/L, <130/140 mg/dL, depending on country-specific recommendations]), or "uncontrolled" (both FPG and HbA 1c above target). Predictor factors were identified from the RCT data set using logistic regression analysis. RCT data showed that 16.9% to 28.0%, 42.7% to 54.4%, and 16.9% to 38.1% of patients with T2DM had well-controlled glycemia, residual hyperglycemia, and uncontrolled hyperglycemia, respectively. In CTRs, respective ranges were 21.8% to 33.6%, 31.5% to 35.6%, and 30.7% to 46.8%, and in EMR databases were 4.4% to 21.0%, 23.9% to 31.8%, and 53.6% to 63.8%. Significant predictor factors of residual hyperglycemia identified from RCT data included high baseline HbA 1c (all countries/regions except Brazil), high baseline FPG (United Kingdom/Japan), longer duration of diabetes (Brazil), and female sex (Europe/Latin America). Irrespective of intrinsic differences between data sources, 24% to 54% of patients with T2DM globally had residual hyperglycemia with HbA 1c not at target, despite achieving FPG control, indicating a significant unmet need for postprandial glycemic control. © 2016 The Authors. Diabetes/Metabolism Research and Reviews published by John Wiley & Sons Ltd.

Kelch-like ECH-associated Protein 1-dependent Nuclear Factor-E2-related Factor 2 Activation in Relation to Antioxidation Induced by Sevoflurane Preconditioning.

PubMed

Cai, Min; Tong, Li; Dong, Beibei; Hou, Wugang; Shi, Likai; Dong, Hailong

2017-03-01

The authors have reported that antioxidative effects play a crucial role in the volatile anesthetic-induced neuroprotection. Accumulated evidence shows that endogenous antioxidation could be up-regulated by nuclear factor-E2-related factor 2 through multiple pathways. However, whether nuclear factor-E2-related factor 2 activation is modulated by sevoflurane preconditioning and, if so, what is the signaling cascade underlying upstream of this activation are still unknown. Sevoflurane preconditioning in mice was performed with sevoflurane (2.5%) 1 h per day for five consecutive days. Focal cerebral ischemia/reperfusion injury was induced by middle cerebral artery occlusion. Expression of nuclear factor-E2-related factor 2, kelch-like ECH-associated protein 1, manganese superoxide dismutase, thioredoxin-1, and nicotinamide adenine dinucleotide phosphate quinolone oxidoreductase-1 was detected (n = 6). The antioxidant activities and oxidative product expression were also examined. To determine the role of kelch-like ECH-associated protein 1 inhibition-dependent nuclear factor-E2-related factor 2 activation in sevoflurane preconditioning-induced neuroprotection, the kelch-like ECH-associated protein 1-nuclear factor-E2-related factor 2 signal was modulated by nuclear factor-E2-related factor 2 knockout, kelch-like ECH-associated protein 1 overexpression lentivirus, and kelch-like ECH-associated protein 1 deficiency small interfering RNA (n = 8). The infarct volume, neurologic scores, and cellular apoptosis were assessed. Sevoflurane preconditioning elicited neuroprotection and increased nuclear factor-E2-related factor 2 nuclear translocation, which in turn up-regulated endogenous antioxidation and reduced oxidative injury. Sevoflurane preconditioning reduced kelch-like ECH-associated protein 1 expression. Nuclear factor-E2-related factor 2 ablation abolished neuroprotection and reversed sevoflurane preconditioning by mediating the up-regulation of antioxidants. Kelch

Complementary phosphorylation sites in the adaptor protein SLP-76 promote synergistic activation of natural killer cells.

PubMed

Kim, Hun Sik; Long, Eric O

2012-07-10

The cytotoxic effects of natural killer (NK) cells and their ability to secrete cytokines require synergistic signals from specific pairs of co-activation receptors, such as CD314 (also known as NKG2D) and CD244 (2B4), which bind to distinct ligands present on target cells. These signals are required to overcome inhibition mediated by the E3 ubiquitin ligase c-Cbl of the guanine nucleotide exchange factor Vav1, which promotes activation of NK cells. Here, we showed that the adaptor protein SLP-76 (Src homology 2 domain-containing leukocyte phosphoprotein of 76 kilodaltons) was required for this synergy and that distinct tyrosine residues in SLP-76 were phosphorylated by each member of a pair of synergistic receptors. Selective phosphorylation of tyrosine 113 or tyrosine 128 in SLP-76 enabled binding of SLP-76 to Vav1. Selective phosphorylation of SLP-76 at these residues was restricted to receptors that stimulated ligand-dependent target cell killing; antibody-dependent stimulation of the Fc receptor CD16 promoted phosphorylation at both sites. Knockdown and reconstitution experiments with SLP-76 mutant proteins showed the distinct role of each tyrosine in the synergistic mobilization of Ca2+, revealing an unexpected degree of selectivity in the phosphorylation of SLP-76 by NK cell co-activation receptors. Together, these data suggest that combined phosphorylation of separate tyrosine residues in SLP-76 forms the basis of synergistic NK cell activation.

[Risk factors of stillbirths in Fortaleza-Brazil: a case-control study].

PubMed

Rouquayrol, M Z; Correia, L L; Barbosa, L M; Xavier, L G; Oliveira, J W; Fonseca, W

1996-01-01

Stillbirths are a common event in areas where reproductive health care is poorly delivered, such as the Northeast region of Brazil. This case-control study aimed to identify risk factors associated to foetal deaths occurred in a major obstetric facility of Fortaleza, 1.7 million inhabitants, Northeastern Brazil. 125 stillborn foetus over 20 weeks of gestation (cases) were compared to 250 healthy newborns (controls), in relation to socioeconomic, reproductive, behavioral and morbidity characteristics of their mothers. Crude and adjusted Odds Ratios were then calculated. After adjustment for confounders, the following characteristics of the mother remained as risk factors for stillbirths, with OR statistically significant at the 95% level: attending <5 antenatal consultations during pregnancy (OR=3.30; CI=1.92 - 5.07 ), illiterate mother (OR=3.30; CI=1.84 - 5.92 ), mother's age above 19 (OR=2.73; CI=1.42 - 5.24 ), monthly family income of 1 minimum wage or less (OR=2.12; CI=1.03 - 4.35 ) and severe illnesses or complication during pregnancy (OR=1.75; CI=1.01 - 3.03 ). Inadequate attendance to antenatal care consultations was the risk factor most strongly associated to stillbirths. Similarly, it was the condition most amenable to change in a short term, among those identified as risk factors.

The Transcription Factors TBX2 and TBX3 Interact with Human Papillomavirus 16 (HPV16) L2 and Repress the Long Control Region of HPVs

PubMed Central

Schneider, Marc A.; Scheffer, Konstanze D.; Bund, Timo; Boukhallouk, Fatima; Lambert, Carsten; Cotarelo, Cristina; Pflugfelder, Gert O.

2013-01-01

The minor capsid protein L2 of human papillomaviruses (HPVs) has multiple functions during the viral life cycle. Although L2 is required for effective invasion and morphogenesis, only a few cellular interaction partners are known so far. Using yeast two-hybrid screening, we identified the transcription factor TBX2 as a novel interaction partner of HPV type 16 (HPV16) L2. Coimmunoprecipitations and immunofluorescence analyses confirmed the L2-TBX2 interaction and revealed that L2 also interacts with TBX3, another member of the T-box family. Transcription of the early genes during HPV infection is under the control of an upstream enhancer and early promoter region, the long control region (LCR). In promoter-reporter gene assays, we observed that TBX2 and TBX3 repress transcription from the LCR and that this effect is enhanced by L2. Repression of the HPV LCR by TBX2/3 seems to be a conserved mechanism, as it was also observed with the LCRs of different HPV types. Finally, interaction of TBX2 with the LCR was detected by chromatin immunoprecipitation, and we found a strong colocalization of L2 and TBX2 in HPV16-positive cervical intraepithelial neoplasia (CIN) I-II tissue sections. These results suggest that TBX2/3 might play a role in the regulation of HPV gene expression during the viral life cycle. PMID:23388722

A case-control study of factors associated with HIV infection among black women.

PubMed

Forna, Fatu M; Fitzpatrick, Lisa; Adimora, Adaora A; McLellan-Lemal, Eleanor; Leone, Peter; Brooks, John T; Marks, Gary; Greenberg, Alan

2006-11-01

To identify social, behavioral and epidemiologic factors associated with HIV infection among HIV-infected and HIV-uninfected black women residing in North Carolina. A case-control study conducted in August 2004 in North Carolina. Cases were 18-40-year-old women with HIV infections diagnosed from 2003-2004. Controls were 18-40-yearold, HIV-negative heterosexually active women recruited from HIV testing sites. Five focus group discussions were also conducted with women not participating in the case-control study. Multivariate analyses of 31 cases and 101 controls showed that HIV-positive women were more likely to receive public assistance [adjusted odds ratio (aOR) 7.3; 95% confidence interval (CI) 2.1, 26.0], to report a history of genital herpes infection (aOR 10.6; 95% CI 2.4, 47.2), and were less likely to have discussed a variety of sexual and behavioral issues relevant to risk of HIV infection with their male partners (aOR 0.6; 95% CI 0.4, 0.8). Focus group participants indicated that financial and social demands created competing challenges for making HIV prevention a priority. Inadequate communication between black women and their sexual partners may create barriers to sexual and behavioral risk reduction. A multidimensional approach that addresses both biological factors such as herpes infection and socioeconomic factors may be needed to reduce HIV transmission in this population.

Fast controller for a unity-power-factor PWM rectifier

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eissa, M.O.; Leeb, S.B.; Verghese, G.C.

1996-01-01

This paper presents an analog implementation of a fast controller for a unity-power-factor (UPF) PWM rectifier. The best settling times of many popular controllers for this type of converter are on the order of a few line cycles, corresponding to bandwidths under 20 Hz. The fast controller demonstrated in this paper can exercise control action at a rate comparable to the switching frequency rather than the line frequency. In order to accomplish this while maintaining unity power factor during steady-state operation, the fast controller employs a ripple-feedback cancellation scheme.

Targeted σ factor turnover inserts negative control into a positive feedback loop

PubMed Central

Donohue, Timothy J.

2009-01-01

Summary Since their classification as members of the σ70 super-family, Group IV alternative σ factors have been found to control gene expression in response to diverse environmental or stress signals. Activity of the Streptomyces coelicolor Group IV family member, σR (SigR), is increased by changes in the oxidation-reduction state of cytoplasmic disulphide bonds. Once released by its cognate anti-σ factor RsrA, σR activates expression of gene products that help cells reduce cytoplasmic disulphide bonds. In this issue of Molecular Microbiology, Kim and co-workers provide new insights into positive and negative control of σR activity. The authors show that a transcript derived from the inducible σR-dependent sigRrsrA p2 promoter operon encodes a σR protein of a higher molecular weight (termed σR′) than is found in uninduced cells. One major difference between σR′ and the smaller σR protein found in uninduced cells is the rapid proteolysis of σR′ by the ClpP1/P2 protease system. The genes for the ClpP1/ClpP2 protease subunits are themselves members of the σR regulon. The newly identified positive (σR′ synthesis) and negative control (selective σR′ turnover) aspects of this circuit are either found or predicted to exist in other related Group IV σ factor family members. PMID:19682265

Neonatal risk factors for cerebral palsy in very preterm babies: case-control study.

PubMed Central

Murphy, D. J.; Hope, P. L.; Johnson, A.

1997-01-01

OBJECTIVE: To identify neonatal risk factors for cerebral palsy among very preterm babies and in particular the associations independent of the coexistence of antenatal and intrapartum factors. DESIGN: Case-control study. SETTING: Oxford health region. SUBJECTS: Singleton babies born between 1984 and 1990 at less than 32 weeks' gestation who survived to discharge from hospital: 59 with cerebral palsy and 234 randomly selected controls without cerebral palsy. MAIN OUTCOME MEASURES: Adverse neonatal factors expressed as odds ratios and 95% confidence intervals. RESULTS: Factors associated with an increased risk of cerebral palsy after adjustment for gestational age and the presence of previously identified antenatal and intrapartum risk factors were patent ductus arteriosus (odds ratio 2.3; 95% confidence interval 1.2 to 4.5), hypotension (2.3; 1.3 to 4.7), blood transfusion (4.8; 2.5 to 9.3), prolonged ventilation (4.8; 2.5 to 9.0), pneumothorax (3.5; 1.6 to 7.6), sepsis (3.6; 1.8 to 7.4), hyponatraemia (7.9; 2.1 to 29.6) and total parenteral nutrition (5.5; 2.8 to 10.5). Seizures were associated with an increased risk of cerebral palsy (10.0; 4.1 to 24.7), as were parenchymal damage (32; 12.4 to 84.4) and appreciable ventricular dilatation (5.4; 3.0 to 9.8) detected by cerebral ultrasound. CONCLUSION: A reduction in the rate of cerebral palsy in very preterm babies requires an integrated approach to management throughout the antenatal, intrapartum, and neonatal periods. PMID:9040385

Risk factors for childhood burns: a case-control study of Ghanaian children.

PubMed Central

Forjuoh, S N; Guyer, B; Strobino, D M; Keyl, P M; Diener-West, M; Smith, G S

1995-01-01

STUDY OBJECTIVE--To study risk factors for childhood burns in order to identify possible preventive strategies. DESIGN--Case-control design with pair matching of controls to cases in relation to age, sex, and area of residence. The cases and controls were identified by a community based, multisite survey. The effects of host and socioenvironmental variables reported by mothers were investigated in a multivariate analysis using conditional logistic regression. SETTING--A developing country setting the Ashanti Region in Ghana. PARTICIPANTS--These comprised 610 cases aged 0-5 years who had been burned (as evidenced by a visible scar) and 610 controls with no burn history. MAIN RESULTS--The presence of a pre-existing impairment in a child was the strongest risk factor in this population (OR = 6.71; 95% CI 2.78, 16.16). Other significant risk factor included: sibling death from a burn (OR = 4.41; 95% CI 1.16, 16.68); history of burn in a sibling (OR = 1.79; 95% CI 1.24, 2.58); and storage of a flammable substance in the home (OR = 1.51; 95% CI 1.03; 2.21). Maternal education had a protective effect against childhood burns, although this effect was not strong (OR = 0.76; 95% CI 0.55, 1.05). CONCLUSIONS--Community programmes to ensure adequate child supervision and general child wellbeing, particularly for those with impairments, as well as parental education about burns are recommended, to reduce childhood burns in this region of Ghana. The public should bed advised against storing flammable substances in the home. PMID:7798049

Risk factors for childhood burns: a case-control study of Ghanaian children.

PubMed

Forjuoh, S N; Guyer, B; Strobino, D M; Keyl, P M; Diener-West, M; Smith, G S

1995-04-01

To study risk factors for childhood burns in order to identify possible preventive strategies. Case-control design with pair matching of controls to cases in relation to age, sex, and area of residence. The cases and controls were identified by a community based, multisite survey. The effects of host and socioenvironmental variables reported by mothers were investigated in a multivariate analysis using conditional logistic regression. A developing country setting the Ashanti Region in Ghana. These comprised 610 cases aged 0-5 years who had been burned (as evidenced by a visible scar) and 610 controls with no burn history. The presence of a pre-existing impairment in a child was the strongest risk factor in this population (OR = 6.71; 95% CI 2.78, 16.16). Other significant risk factor included: sibling death from a burn (OR = 4.41; 95% CI 1.16, 16.68); history of burn in a sibling (OR = 1.79; 95% CI 1.24, 2.58); and storage of a flammable substance in the home (OR = 1.51; 95% CI 1.03; 2.21). Maternal education had a protective effect against childhood burns, although this effect was not strong (OR = 0.76; 95% CI 0.55, 1.05). Community programmes to ensure adequate child supervision and general child wellbeing, particularly for those with impairments, as well as parental education about burns are recommended, to reduce childhood burns in this region of Ghana. The public should bed advised against storing flammable substances in the home.

[Risk factors associated with trigger finger. Case-control study].

PubMed

De la Parra-Márquez, Miguel Leonardo; Tamez-Cavazos, Roberto; Zertuche-Cedillo, Luis; Martínez-Pérez, Juan José; Velasco-Rodríguez, Víctor; Cisneros-Pérez, Vicente

2008-01-01

We undertook this study to identify risk factors in our population associated with trigger finger. The study was conducted at the Instituto Mexicano del Seguro Social, UMAE 21, Monterrey, Nuevo Leon, Mexico. This was a case-control, retrospective, and observational study. There were 250 patients in each group. For cases, patients who were operated on for trigger finger from March 2006 to August 2006 were included. Controls included patients admitted to the Emergency Department with hand injuries that fulfilled the selection criteria. Risk factors analyzed were diabetes, hypertension, smoking, sex, age, weight, and 19 different occupations. Mean age of the cases was 52 years (SE +/- 14.19 years) with a median and mode of 53 years. The right hand was the most common with the middle, thumb, ring, index and little fingers, respectively. A significant statistical relationship was found: females (OR 7.57, 95% CI 5.07-11.31); diabetes (OR 3.72, 95% CI 2.43-5.70); obesity (OR 1.49, 95% CI 1.02-2.19). With regard to occupation, a statistical relationship was found: homemaker (OR 2.44, 95% CI 1.62-3.69); seamstress (OR 4.8, 95% CI 1.3-21.6); and secretary (OR 2.74, 95% CI 1.38-5.52). Trigger finger is a common pathology in our population and is more frequent in women >53 years old. It may be related to diabetes, body mass index (obesity) and certain occupations such as secretary, seamstress and homemaker.

Risk factors for diabetic retinopathy in people with Type 2 diabetes: A case-control study in a UK primary care setting.

PubMed

Martín-Merino, Elisa; Fortuny, Joan; Rivero-Ferrer, Elena; Lind, Marcus; Garcia-Rodriguez, Luis Alberto

2016-08-01

To identify risk factors of diabetic retinopathy (DR) among people with Type 2 diabetes mellitus in UK primary care. A case-control study nested in a cohort of incident Type 2 diabetes identified in The Health Improvement Network database from 2000 to 2007. Cases were people with DR (N=7735) and controls were a DR-free sample (N=9395). No age restrictions were applied. Adjusted odds ratios and 95% CIs were estimated. 21% of DR cases were identified during the first semester after Type 2 diabetes diagnosis. After controlling for delay on the Type 2 diabetes diagnosis, the DR risk increased with the duration of diabetes. DR increased with a mean systolic BP ≥150mmHg (1.18; 1.10-1.27), high alcohol consumption (1.34; 1.11-1.61), glycated haemoglobin (≥75 to <86: 1.14; 1.00-1.31; ≥86 to <97mmol/mol: 1.25; 1.07-1.45; ≥97mmol/mol: 1.21; 1.07-1.37), microalbuminuria (1.16; 1.06-1.27), and retinal vein occlusion (2.47; 1.67-3.66). Glaucoma and retinal arterial occlusion showed an OR of 0.71 (0.60-0.84) and 0.63 (0.40-1.01), respectively. HDL ≥1.55mmol/l (0.88; 0.80-0.98), high triglycerides (2.3-5.6mmol/l: 0.90; 0.82-0.99; >5.6mmol/l: 0.85; 0.64-1.13) or smoking (0.89; 0.81-0.97) had a slightly reduced DR risk. Users of hypoglycaemic agents had an increased DR risk. Some DR cases were identified near the diabetes diagnosis date suggesting that a delayed diabetes diagnosis is still common. Glaucoma, retinal arterial occlusion and high HDL levels were inversely associated with DR, while retinal vein occlusion, alcohol and other well-known risk factors were positively associated. Copyright © 2016. Published by Elsevier Ltd.

Control of Huntington's Disease-Associated Phenotypes by the Striatum-Enriched Transcription Factor Foxp2.

PubMed

Hachigian, Lea J; Carmona, Vitor; Fenster, Robert J; Kulicke, Ruth; Heilbut, Adrian; Sittler, Annie; Pereira de Almeida, Luís; Mesirov, Jill P; Gao, Fan; Kolaczyk, Eric D; Heiman, Myriam

2017-12-05

Alteration of corticostriatal glutamatergic function is an early pathophysiological change associated with Huntington's disease (HD). The factors that regulate the maintenance of corticostriatal glutamatergic synapses post-developmentally are not well understood. Recently, the striatum-enriched transcription factor Foxp2 was implicated in the development of these synapses. Here, we show that, in mice, overexpression of Foxp2 in the adult striatum of two models of HD leads to rescue of HD-associated behaviors, while knockdown of Foxp2 in wild-type mice leads to development of HD-associated behaviors. We note that Foxp2 encodes the longest polyglutamine repeat protein in the human reference genome, and we show that it can be sequestered into aggregates with polyglutamine-expanded mutant Huntingtin protein (mHTT). Foxp2 overexpression in HD model mice leads to altered expression of several genes associated with synaptic function, genes that present additional targets for normalization of corticostriatal dysfunction in HD. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

A Systematic Review and Meta-Analysis on Self-Management for Improving Risk Factor Control in Stroke Patients.

PubMed

Sakakibara, Brodie M; Kim, Amy J; Eng, Janice J

2017-02-01

The aims of this review were to describe the self-management interventions used to improve risk factor control in stroke patients and quantitatively assess their effects on the following: 1) overall risk factor control from lifestyle behaviour (i.e. physical activity, diet and nutrition, stress management, smoking, alcohol, and medication adherence), and medical risk factors (i.e. blood pressure, cholesterol, blood glucose) and (2) individual risk factors. We systematically searched the PubMed, PsycINFO, CINAHL and Cochrane Database of Systematic Reviews databases to September 2015 to identify relevant randomized controlled trials investigating self-management to improve stroke risk factors. The self-management interventions were qualitatively described, and the data included in meta-analyses. Fourteen studies were included for review. The model estimating an effect averaged across all stroke risk factors was not significant, but became significant when four low-quality studies were removed (SMD = 0.10 [95 % CI = 0.02 to 0.17], I 2  = 0 %, p = 0.01). Subgroup analyses revealed a significant effect of self-management interventions on lifestyle behaviour risk factors (SMD = 0.15 [95 % CI = 0.04 to 0.25], I 2  = 0 %, p = 0.007) but not medical risk factors. Medication adherence was the only individual risk factor that self-management interventions significantly improved (SMD = 0.31 [95 % CI = 0.07 to 0.56], I 2  = 0 %, p = 0.01). Self-management interventions appear to be effective at improving overall risk factor control; however, more high-quality research is needed to corroborate this observation. Self-management has a greater effect on lifestyle behaviour risk factors than medical risk factors, with the largest effect at improving medication adherence.

Job strain (demands and control model) as a predictor of cardiovascular risk factors among petrochemical personnel

PubMed Central

Habibi, Ehsanollah; Poorabdian, Siamak; Shakerian, Mahnaz

2015-01-01

Background: One of the practical models for the assessment of stressful working conditions due to job strain is job demand and control model, which explains how physical and psychological adverse consequences, including cardiovascular risk factors can be established due to high work demands (the amount of workload, in addition to time limitations to complete that work) and low control of the worker on his/her work (lack of decision making) in the workplace. The aim of this study was to investigate how certain cardiovascular risk factors (including body mass index [BMI], heart rate, blood pressure, cholesterol and smoking) and the job demand and job control are related to each other. Materials and Methods: This prospective cohort study was conducted on 500 workers of the petrochemical industry in south of Iran, 2009. The study population was selected using simple random statistical method. They completed job demand and control questionnaire. The cardiovascular risk factors data was extracted from the workers hygiene profiles. Chi-square (χ2) test and hypothesis test (η) were used to assess the possible relationship between different quantified variables, individual demographic and cardiovascular risk factors. Results: The results of this study revealed that a significant relationship can be found between job demand control model and cardiovascular risk factors. Chi-square test result for the heart rate showed the highest (χ2 = 145.078) relationship, the corresponding results for smoking and BMI were χ2 = 85.652 and χ2 = 30.941, respectively. Subsequently, hypothesis testing results for cholesterol and hypertension was 0.469 and 0.684, respectively. Discussion: Job strain is likely to be associated with an increased risk of cardiovascular risk factors among male staff in a petrochemical company in Iran. The parameters illustrated in the Job demands and control model can act as acceptable predictors for the probability of job stress occurrence followed by showing

Risk factors in lateral epicondylitis (tennis elbow): a case-control study.

PubMed

Titchener, A G; Fakis, A; Tambe, A A; Smith, C; Hubbard, R B; Clark, D I

2013-02-01

Lateral epicondylitis is a common condition, but relatively little is known about its aetiology and associated risk factors. We have undertaken a large case-control study using The Health Improvement Network database to assess and quantify the relative contributions of some constitutional and environmental risk factors for lateral epicondylitis in the community. Our dataset included 4998 patients with lateral epicondylitis who were individually matched with a single control by age, sex, and general practice. The median age at diagnosis was 49 (interquartile range 42-56) years . Multivariate analysis showed that the risk factors associated with lateral epicondylitis were rotator cuff pathology (OR 4.95), De Quervain's disease (OR 2.48), carpal tunnel syndrome (OR 1.50), oral corticosteroid therapy (OR 1.68), and previous smoking history (OR 1.20). Diabetes mellitus, current smoking, trigger finger, rheumatoid arthritis, alcohol intake, and obesity were not found to be associated with lateral epicondylitis.

Effect of a group-based rehabilitation programme on glycaemic control and cardiovascular risk factors in type 2 diabetes patients: the Copenhagen Type 2 Diabetes Rehabilitation Project.

PubMed

Vadstrup, Eva Soelberg; Frølich, Anne; Perrild, Hans; Borg, Eva; Røder, Michael

2011-08-01

To compare the effectiveness of a group-based rehabilitation programme with an individual counselling programme at improving glycaemic control and cardiovascular risk factors among patients with type 2 diabetes. We randomised 143 adult type 2 diabetes patients to either a 6-month multidisciplinary group-based rehabilitation programme or a 6-month individual counselling programme. Outcome measures included glycated haemoglobin (HbA(1c)), blood pressure, lipid profile, weight, and waist circumference. Mean HbA(1c) decreased 0.3%-point (95% confidence interval [CI] = -0.5, -0.1) in the rehabilitation group and 0.6%-point (95% CI = -0.8, -0.4) among individual counselling participants (p<0.05). Within both groups, equal reductions occurred in body weight, waist circumference, systolic blood pressure and diastolic blood pressure, but no significant between-group differences between occurred for any of the cardiovascular outcomes. The group-based rehabilitation programme consumed twice as many personnel resources. The group-based rehabilitation programme resulted in changes in glycaemic control and cardiovascular risk factor reduction that were equivalent or inferior to those of an individual counselling programme. The group-based rehabilitation programme, tested in the current design, did not offer additionally improved outcomes and consumed more personnel resources than the individual counselling programme; its broad implementation is not supported by this study. Trial registration Clinicaltrials.gov NCT00284609. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Risk of venous thromboembolism in association with factor V leiden in cancer patients - The EDITH case-control study.

PubMed

Heraudeau, Adeline; Delluc, Aurélien; Le Henaff, Mickaël; Lacut, Karine; Leroyer, Christophe; Desrues, Benoit; Couturaud, Francis; Tromeur, Cécile

2018-01-01

Cancer and factor V Leiden mutation are both risk factors for venous thromboembolism (VTE). Cancer critically increases the thrombotic risk whereas Factor V Leiden is the most common pro-thrombotic mutation. The impact of the factor V Leiden on the risk of VTE in cancer patients remains uncertain. To assess the impact of factor V Leiden mutation in cancer-associated thrombosis. The EDITH hospital-based case-control study enrolled 182 patients with cancer and VTE as well as 182 control patients with cancer, matched for gender, age and cancer location, between 2000 and 2012, in the University Hospital of Brest. All cases and controls were genotyped for the factor V Leiden mutation and interviewed with a standardized questionnaire. Twenty one of 182 (11.5%) patients with cancer-associated thrombosis carried the factor V Leiden mutation and 4 of 182 (2.2%) controls with cancer but no venous thrombosis. In multivariate analysis including cancer stage and family history of VTE, cancer patients with factor V Leiden mutation had a seven-fold increased risk of venous thromboembolism (adjusted odds ratio [OR], 7.04; 95% CI, 2.01-24.63). The pro-thrombotic Factor V Leiden mutation was found to be an independent additional risk factor for venous thromboembolism in cancer patients and might therefore be considered in the individual thrombotic risk assessment.

Evaluation of Variable Refrigerant Flow Systems Performance and the Enhanced Control Algorithm on Oak Ridge National Laboratory s Flexible Research Platform

DOE Office of Scientific and Technical Information (OSTI.GOV)

Im, Piljae; Munk, Jeffrey D; Gehl, Anthony C

2015-06-01

A research project “Evaluation of Variable Refrigerant Flow (VRF) Systems Performance and the Enhanced Control Algorithm on Oak Ridge National Laboratory’s (ORNL’s) Flexible Research Platform” was performed to (1) install and validate the performance of Samsung VRF systems compared with the baseline rooftop unit (RTU) variable-air-volume (VAV) system and (2) evaluate the enhanced control algorithm for the VRF system on the two-story flexible research platform (FRP) in Oak Ridge, Tennessee. Based on the VRF system designed by Samsung and ORNL, the system was installed from February 18 through April 15, 2014. The final commissioning and system optimization were completed onmore » June 2, 2014, and the initial test for system operation was started the following day, June 3, 2014. In addition, the enhanced control algorithm was implemented and updated on June 18. After a series of additional commissioning actions, the energy performance data from the RTU and the VRF system were monitored from July 7, 2014, through February 28, 2015. Data monitoring and analysis were performed for the cooling season and heating season separately, and the calibrated simulation model was developed and used to estimate the energy performance of the RTU and VRF systems. This final report includes discussion of the design and installation of the VRF system, the data monitoring and analysis plan, the cooling season and heating season data analysis, and the building energy modeling study« less

Power-Factor Controllers: How Safe?

NASA Technical Reports Server (NTRS)

Long, K.; Christian, W.; Kovacik, J.; Grazyk, T.

1985-01-01

Potential safety problems with power-factor controllers (PFC's) evaluated. Based on study of PFCs in use with appliances, report recommends measures to prevent consumers from misapplying these energy saving devices. Device used on such appliances as refrigerators, sewing machines, pumps, hair dryers, and food processors. When misused, they fail to save energy and may cause damage.

Risk factors for pulmonary tuberculosis in Croatia: a matched case-control study.

PubMed

Jurcev-Savicevic, Anamarija; Mulic, Rosanda; Ban, Bozica; Kozul, Karlo; Bacun-Ivcek, Ljiljana; Valic, Jasna; Popijac-Cesar, Gordana; Marinovic-Dunatov, Snjezana; Gotovac, Majda; Simunovic, Aleksandar

2013-10-21

Mycobacterium tuberculosis is a necessary, but not sufficient, cause of tuberculosis. A number of studies have addressed the issue of risk factors for tuberculosis development. Croatia is a European country with an incidence rate of 14/100 000 which is slowly decreasing. The aim of this study is to evaluate the potential demographic, socioeconomic, behavioural and biological risk factors for tuberculosis in Croatia in comparison to other high-income, low-incidence European countries. A total of 300 tuberculosis patients were matched for age, sex and county of residence to 300 controls randomly selected from general practitioners' registers. They were interviewed and their medical records were evaluated for variables broadly described as potential risk factors. In multiple logistic regression, the following factors were significant: parents born in a particular neighbouring county (Bosnia and Herzegovina) (OR = 3.90, 95% CI 2.01-7.58), the lowest level of education (OR = 3.44, 95% CI 1.39-8.50), poor household equipment (OR = 4.72, 95% CI 1.51-14.76), unemployment (OR = 2.69, 95% CI 1.18-6.16), contact with tuberculosis (OR = 2.19, 95% CI 1.27-3.77), former (OR = 2.27, 95% CI 1.19-4.33) and current smoking habits (OR = 2.35, 95% CI 1.27-4.36), diabetes (OR = 2.38, 95% CI 1.05-5.38), a malignant disease (OR = 5.79, 95% CI 1.49-22.42), being underweight in the previous year (OR = 13.57, 95% CI 1.21-152.38). In our study, the identified risk groups for tuberculosis reflect a complex interaction between socioeconomic conditions, lifestyle and non-communicable diseases. Interventions focused on poverty will undoubtedly be useful, but not sufficient. Tuberculosis control would benefit from a combination of broad public health activities aimed at the prevention and control of risky lifestyles and non-communicable diseases, interventions outside the health sector, and efforts to constantly improve the Croatian national tuberculosis programme.

Risk factors for pulmonary tuberculosis in Croatia: a matched case–control study

PubMed Central

2013-01-01

Background Mycobacterium tuberculosis is a necessary, but not sufficient, cause of tuberculosis. A number of studies have addressed the issue of risk factors for tuberculosis development. Croatia is a European country with an incidence rate of 14/100 000 which is slowly decreasing. The aim of this study is to evaluate the potential demographic, socioeconomic, behavioural and biological risk factors for tuberculosis in Croatia in comparison to other high-income, low-incidence European countries. Methods A total of 300 tuberculosis patients were matched for age, sex and county of residence to 300 controls randomly selected from general practitioners’ registers. They were interviewed and their medical records were evaluated for variables broadly described as potential risk factors. Results In multiple logistic regression, the following factors were significant: parents born in a particular neighbouring county (Bosnia and Herzegovina) (OR = 3.90, 95% CI 2.01-7.58), the lowest level of education (OR = 3.44, 95% CI 1.39-8.50), poor household equipment (OR = 4.72, 95% CI 1.51-14.76), unemployment (OR = 2.69, 95% CI 1.18-6.16), contact with tuberculosis (OR = 2.19, 95% CI 1.27-3.77), former (OR = 2.27, 95% CI 1.19-4.33) and current smoking habits (OR = 2.35, 95% CI 1.27-4.36), diabetes (OR = 2.38, 95% CI 1.05-5.38), a malignant disease (OR = 5.79, 95% CI 1.49-22.42), being underweight in the previous year (OR = 13.57, 95% CI 1.21-152.38). Conclusion In our study, the identified risk groups for tuberculosis reflect a complex interaction between socioeconomic conditions, lifestyle and non-communicable diseases. Interventions focused on poverty will undoubtedly be useful, but not sufficient. Tuberculosis control would benefit from a combination of broad public health activities aimed at the prevention and control of risky lifestyles and non-communicable diseases, interventions outside the health sector, and efforts to constantly

Epidemiological risk factors in microscopic colitis: a prospective case-control study.

PubMed

Fernández-Bañares, Fernando; de Sousa, Monia R; Salas, Antonio; Beltrán, Belén; Piqueras, Marta; Iglesias, Eva; Gisbert, Javier P; Lobo, Beatriz; Puig-Diví, Valentí; García-Planella, Esther; Ordás, Ingrid; Andreu, Montserrat; Calvo, Marta; Montoro, Miguel; Esteve, Maria; Viver, Josep M

2013-02-01

The cause of collagenous colitis (CC) and lymphocytic colitis (LC) is unknown and epidemiological risk factors for CC and LC are not well studied. The aim was to evaluate in a case-control study epidemiological risk factors for CC and LC. In all, 120 patients with CC, 70 with CL, and 128 controls were included. For all cases and controls information was prospectively recorded. A binary logistic regression analysis was performed separately for CC and LC. Independent associations observed with the diagnosis of CC were: current smoking (odds ratio [OR], 2.4), history of polyarthritis (OR, 20.8), and consumption of lansoprazole (OR, 6.4), low-dose aspirin (OR, 3.8), beta-blockers (OR, 3.6), and angiotensin II receptor antagonists (OR 0.20). In the case of LC they were: current smoking (OR, 3.8), associated autoimmune diseases (OR, 8), and consumption of sertraline (OR, 17.5), omeprazole (OR 2.7), low-dose aspirin (OR, 4.7), and oral antidiabetic drugs (OR, 0.14). The consumption of drugs, current smoking, and associated autoimmune diseases were independently associated with the risk of microscopic colitis.

Differential growth factor control of bone formation through osteoprogenitor differentiation.

PubMed

Chaudhary, L R; Hofmeister, A M; Hruska, K A

2004-03-01

The osteogenic factors bone morphogenetic protein (BMP-7), platelet-derived growth factor (PDGF)-BB, and fibroblast growth factor (FGF-2) regulate the recruitment of osteoprogenitor cells and their proliferation and differentiation into mature osteoblasts. However, their mechanisms of action on osteoprogenitor cell growth, differentiation, and bone mineralization remain unclear. Here, we tested the hypothesis that these osteogenic agents were capable of regulating osteoblast differentiation and bone formation in vitro. Normal human bone marrow stromal (HBMS) cells were treated with BMP-7 (40 ng ml(-1)), PDGF-BB (20 ng ml(-1)), FGF-2 (20 ng ml(-1)), or FGF-2 plus BMP-7 for 28 days in a serum-containing medium with 10 mM beta-glycerophosphate and 50 microg ml(-1) ascorbic acid. BMP-7 stimulated a morphological change to cuboidal-shaped cells, increased alkaline phosphatase (ALKP) activity, bone sialoprotein (BSP) gene expression, and alizarin red S positive nodule formation. Hydroxyapatite (HA) crystal deposition in the nodules was demonstrated by Fourier transform infrared (FTIR) spectroscopy only in BMP-7- and dexamethasone (DEX)-treated cells. DEX-treated cells appeared elongated and fibroblast-like compared to BMP-7-treated cells. FGF-2 did not stimulate ALKP, and cell morphology was dystrophic. PDGF-BB had little or no effect on ALKP activity and biomineralization. Alizarin Red S staining of cells and calcium assay indicated that BMP-7, DEX, and FGF-2 enhanced calcium mineral deposition, but FTIR spectroscopic analysis demonstrated no formation of HA similar to human bone in control, PDGF-BB-, and FGF-2-treated samples. Thus, FGF-2 stimulated amorphous octacalcium phosphate mineral deposition that failed to mature into HA. Interestingly, FGF-2 abrogated BMP-7-induced ALKP activity and HA formation. Results demonstrate that BMP-7 was competent as a sole factor in the differentiation of human bone marrow stromal cells to bone-forming osteoblasts confirmed by FTIR

A study on the relationship between genetic and environmental factors of type 2 diabetes mellitus in humans.

PubMed

Chen, Yu; Zhou, Ling; Xu, Yaochu; Shen, Hongbing; Niu, Juying

2002-05-01

To study the relationship between the inheritable factor and environmental factors of type 2 diabetes mellitus in humans. A case-control study based on 154 type 2 diabetes mellitus and 130 healthy controls was carried out in Jiangsu Province in 1997. The age, family history of diabetes mellitus, hypertension history, high waist/hip ratio (WHR), high systolic blood pressure, huge fetus history, and the genotype of beta(3)-adrenergic receptor (beta(3)-AR) were the risk factors of type 2 diabetes mellitus; while occupational physical activity was protective factor of type 2 diabetes mellitus. The risk for diabetes mellitus distinctly increased while genetic factor and obesity, beta(3)-AR mutation were coexisting. Type 2 diabetes mellitus is caused by the effect of both genetic and environmental factors.

Soil moisture surpasses elevated CO2 and temperature as a control on soil carbon dynamics in a multi-factor climate change experiment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Garten Jr, Charles T; Classen, Aimee T; Norby, Richard J

2009-01-01

Some single-factor experiments suggest that elevated CO2 concentrations can increase soil carbon, but few experiments have examined the effects of interacting environmental factors on soil carbon dynamics. We undertook studies of soil carbon and nitrogen in a multi-factor (CO2 x temperature x soil moisture) climate change experiment on a constructed old-field ecosystem. After four growing seasons, elevated CO2 had no measurable effect on carbon and nitrogen concentrations in whole soil, particulate organic matter (POM), and mineral-associated organic matter (MOM). Analysis of stable carbon isotopes, under elevated CO2, indicated between 14 and 19% new soil carbon under two different watering treatmentsmore » with as much as 48% new carbon in POM. Despite significant belowground inputs of new organic matter, soil carbon concentrations and stocks in POM declined over four years under soil moisture conditions that corresponded to prevailing precipitation inputs (1,300 mm yr-1). Changes over time in soil carbon and nitrogen under a drought treatment (approximately 20% lower soil water content) were not statistically significant. Reduced soil moisture lowered soil CO2 efflux and slowed soil carbon cycling in the POM pool. In this experiment, soil moisture (produced by different watering treatments) was more important than elevated CO2 and temperature as a control on soil carbon dynamics.« less

Risk factors for achilles tendon rupture: A matched case control study.

PubMed

Noback, Peter C; Jang, Eugene S; Cuellar, Derly O; Seetharaman, Mani; Malagoli, Emiliano; Greisberg, Justin K; Vosseller, J Turner

2017-10-01

The purpose of this study was to elucidate whether body mass index (BMI), activity level, and other risk factors predispose patients to Achilles tendon ruptures. A retrospective review of 279 subjects was performed (93 with Achilles tendon rupture, matched 1:2 with 186 age/sex matched controls with ankle sprains). Demographic variables and risk factors for rupture were tabulated and compared. The rupture group mean BMI was 27.77 (95% CI, 26.94-28.49), and the control group mean BMI was 26.66 (95% CI, 26.06-27.27). These populations were found to be statistically equivalent (p=0.047 and p<0.001 by two one-sided t-test). A significantly higher proportion of those suffering ruptures reported regular athletic activity at baseline (74%) versus controls (59%, p=0.013). There was no clinically significant difference found in BMI between patients with ruptures and controls. Furthermore, it was found that patients who sustained ruptures were also more likely to be active at baseline than their ankle sprain counterparts. Copyright © 2017 Elsevier Ltd. All rights reserved.

Human factors considerations in the design and evaluation of flight deck displays and controls : version 2.0

DOT National Transportation Integrated Search

2016-12-01

The objective of this effort is to have a single source reference document for human factors regulatory and guidance material for flight deck displays and controls, in the interest of improving aviation safety. This document identifies guidance on hu...

Stress-controlled thermoelectric module for energy harvesting and its application for the significant enhancement of the power factor of Bi2Te3-based thermoelectrics

NASA Astrophysics Data System (ADS)

Korobeinikov, Igor V.; Morozova, Natalia V.; Lukyanova, Lidia N.; Usov, Oleg A.; Kulbachinskii, Vladimir A.; Shchennikov, Vladimir V.; Ovsyannikov, Sergey V.

2018-01-01

We propose a model of a thermoelectric module in which the performance parameters can be controlled by applied tuneable stress. This model includes a miniature high-pressure anvil-type cell and a specially designed thermoelectric module that is compressed between two opposite anvils. High thermally conductive high-pressure anvils that can be made, for instance, of sintered technical diamonds with enhanced thermal conductivity, would enable efficient heat absorption or rejection from a thermoelectric module. Using a high-pressure cell as a prototype of a stress-controlled thermoelectric converter, we investigated the effect of applied high pressure on the power factors of several single-crystalline thermoelectrics, including binary p-type Bi2Te3, and multi-component (Bi,Sb)2Te3 and Bi2(Te,Se,S)3 solid solutions. We found that a moderate applied pressure of a few GPa significantly enhances the power factors of some of these thermoelectrics. Thus, they might be more efficiently utilized in stress-controlled thermoelectric modules. In the example of one of these thermoelectrics crystallizing in the same rhombohedral structure, we examined the crystal lattice stability under moderate high pressures. We uncovered an abnormal compression of the rhombohedral lattice of (Bi0.25,Sb0.75)2Te3 along the c-axis in a hexagonal unit cell, and detected two phase transitions to the C2/m and C2/c monoclinic structures above 9.5 and 18 GPa, respectively.

Multiple risk factor control, mortality and cardiovascular events in type 2 diabetes and chronic kidney disease: a population-based cohort study

PubMed Central

Gulliford, Martin C

2018-01-01

Objectives This study aimed to evaluate the effectiveness of multiple risk factor control (MRFC) at reducing mortality and cardiovascular events in diabetes and chronic kidney disease (CKD) in clinical practice. Design Population-based cohort study. Setting Primary care database in the UK, linked with inpatient and mortality data. Participants Participants aged 40–79 years with type 2 diabetes and valid serum creatinine measurements, including 11 431 participants with CKD (estimated glomerular filtration rate: eGFR 15–59 mL/min/1.73 m2) and 36 429 participants with non-CKD (eGFR ≥60 mL/min/1.73 m2). Exposures MRFC consisted of four components: Haemoglobin A1c (HbA1c) <53 mmol/mol (<7.0%), blood pressure <140/90 mm Hg, total cholesterol <5 mmol/L and no smoking. The main exposure variable was the number of risk factors controlled at baseline. Outcome measures All-cause and cardiovascular mortality in the overall participants. Cardiovascular events, including coronary heart disease and stroke, in participants limited to those without a history of cardiovascular diseases at baseline. Results In participants with CKD, 37% or 13% met three or four MRFC criteria, respectively. Increasing numbers of risk factors controlled were associated with lower relative hazards for all outcomes studied compared with those meeting no or one criterion. For participants with CKD meeting four criteria, the adjusted HR for all-cause mortality was 0.60 (95% CI 0.53 to 0.69) and the adjusted subdistribution HR for cardiovascular mortality was 0.60 (95% CI 0.50 to 0.70), considering a competing risk of non-cardiovascular death. Participants meeting four criteria also had lower relative hazards for coronary heart disease (adjusted subdistribution HR 0.73, 95% CI 0.59 to 0.91) and stroke (0.63, 95% CI 0.45 to 0.89), considering death as a competing risk. Conclusions MRFC may lower the increased risks for mortality and cardiovascular events in people with diabetes and

Low-Cloud Feedbacks from Cloud-Controlling Factors: A Review

DOE PAGES

Klein, Stephen A.; Hall, Alex; Norris, Joel R.; ...

2017-10-24

Here, the response to warming of tropical low-level clouds including both marine stratocumulus and trade cumulus is a major source of uncertainty in projections of future climate. Climate model simulations of the response vary widely, reflecting the difficulty the models have in simulating these clouds. These inadequacies have led to alternative approaches to predict low-cloud feedbacks. Here, we review an observational approach that relies on the assumption that observed relationships between low clouds and the “cloud-controlling factors” of the large-scale environment are invariant across time-scales. With this assumption, and given predictions of how the cloud-controlling factors change with climate warming,more » one can predict low-cloud feedbacks without using any model simulation of low clouds. We discuss both fundamental and implementation issues with this approach and suggest steps that could reduce uncertainty in the predicted low-cloud feedback. Recent studies using this approach predict that the tropical low-cloud feedback is positive mainly due to the observation that reflection of solar radiation by low clouds decreases as temperature increases, holding all other cloud-controlling factors fixed. The positive feedback from temperature is partially offset by a negative feedback from the tendency for the inversion strength to increase in a warming world, with other cloud-controlling factors playing a smaller role. A consensus estimate from these studies for the contribution of tropical low clouds to the global mean cloud feedback is 0.25 ± 0.18 W m –2 K –1 (90% confidence interval), suggesting it is very unlikely that tropical low clouds reduce total global cloud feedback. Because the prediction of positive tropical low-cloud feedback with this approach is consistent with independent evidence from low-cloud feedback studies using high-resolution cloud models, progress is being made in reducing this key climate uncertainty.« less

Low-Cloud Feedbacks from Cloud-Controlling Factors: A Review

DOE Office of Scientific and Technical Information (OSTI.GOV)

Klein, Stephen A.; Hall, Alex; Norris, Joel R.

Here, the response to warming of tropical low-level clouds including both marine stratocumulus and trade cumulus is a major source of uncertainty in projections of future climate. Climate model simulations of the response vary widely, reflecting the difficulty the models have in simulating these clouds. These inadequacies have led to alternative approaches to predict low-cloud feedbacks. Here, we review an observational approach that relies on the assumption that observed relationships between low clouds and the “cloud-controlling factors” of the large-scale environment are invariant across time-scales. With this assumption, and given predictions of how the cloud-controlling factors change with climate warming,more » one can predict low-cloud feedbacks without using any model simulation of low clouds. We discuss both fundamental and implementation issues with this approach and suggest steps that could reduce uncertainty in the predicted low-cloud feedback. Recent studies using this approach predict that the tropical low-cloud feedback is positive mainly due to the observation that reflection of solar radiation by low clouds decreases as temperature increases, holding all other cloud-controlling factors fixed. The positive feedback from temperature is partially offset by a negative feedback from the tendency for the inversion strength to increase in a warming world, with other cloud-controlling factors playing a smaller role. A consensus estimate from these studies for the contribution of tropical low clouds to the global mean cloud feedback is 0.25 ± 0.18 W m –2 K –1 (90% confidence interval), suggesting it is very unlikely that tropical low clouds reduce total global cloud feedback. Because the prediction of positive tropical low-cloud feedback with this approach is consistent with independent evidence from low-cloud feedback studies using high-resolution cloud models, progress is being made in reducing this key climate uncertainty.« less

Potential drugs which activate nuclear factor E2-related factor 2 signaling to prevent diabetic cardiovascular complications: A focus on fumaric acid esters.

PubMed

Zhou, Shanshan; Jin, Jingpeng; Bai, Tao; Sachleben, Leroy R; Cai, Lu; Zheng, Yang

2015-08-01

Diabetes and its cardiovascular complications have been a major public health issue. These complications are mainly attributable to a severe imbalance between free radical and reactive oxygen species production and the antioxidant defense systems. Nuclear factor E2-related factor 2 (Nrf2) is a transcription factor that controls the basal and inducible expression of a battery of antioxidant enzyme genes and other cyto-protective phase II detoxifying enzymes. As a result, Nrf2 has gained great attention as a promising drug target for preventing diabetic cardiovascular complications. And while animal studies have shown that several Nrf2 activators manifest a potential to efficiently prevent the diabetic complications, their use in humans has not been approved due to the lack of substantial evidence regarding safety and efficacy of the Nrf2 activation. We provide here a brief review of a few clinically-used drugs that can up-regulate Nrf2 with the potential of extending their usage to diabetic patients for the prevention of cardiovascular complications and conclude with a closer inspection of dimethyl fumarate and its mimic members. Copyright © 2015 Elsevier Inc. All rights reserved.

Risk factors for choledocholithiasis in a south Indian population: a case-control study.

PubMed

Chandran, Alexander Palapatti; Sivarajan, Ramya Ramakrishnan; Srinivas, Melpakkam; Srinivasan, Vijaya; Venkataraman, Jayanthi

2013-11-01

To identify risk factors for common bile duct (CBD) stones in a south Indian population. Demographic characteristics and diet details were obtained from patients with isolated CBD stones (Gp I) and those with combined CBD and gallstones (Gp II) and age- and sex-matched controls. The risk factors were compared between the two groups. The demographic characteristics were similar between the two groups and matched controls. The significant risk factors for Gp I were infrequent consumption of green vegetable (odds ratio (OR), 2.3; p < 0.05), intake of tea/coffee (OR 3.3; p < 0.01) and less consumption of sugar (p < 0.01). For Gp II, the risk factors were frequent intake (>3 times per week) of spices (OR, 2.8; p < 0.05), fried foods (OR, 2.7; p < 0.05), tamarind (OR, 2.8; p < 0.01), and quantum of oil (p < 0.01) per month. Green vegetables (OR, 8.5; p < 0.00001) and sugar (9.5 + 4.2 vs. 13.8 + 11.2 g; p < 0.00001) were protective. Between the two groups, the risk factors for Gp II were less frequent green vegetable intake (OR: 6.4; p < 0.00001), more frequent spicy food (0-3 times per week) (OR, 7.0; p < 0.05), and higher monthly oil intake (251 + 105 vs. 292 + 89 mL; p < 0.05). CBD stones in both groups were associated with reduced intake of sugar and green vegetables. Our findings need to be validated in larger studies.

Weight Loss, Glycemic Control, and Cardiovascular Disease Risk Factors in Response to Differential Diet Composition in a Weight Loss Program in Type 2 Diabetes: A Randomized Controlled Trial

PubMed Central

Rock, Cheryl L.; Flatt, Shirley W.; Pakiz, Bilge; Taylor, Kenneth S.; Leone, Angela F.; Brelje, Kerrin; Heath, Dennis D.; Quintana, Elizabeth L.; Sherwood, Nancy E.

2014-01-01

OBJECTIVE To test whether a weight loss program promotes greater weight loss, glycemic control, and improved cardiovascular disease risk factors compared with control conditions and whether there is a differential response to higher versus lower carbohydrate intake. RESEARCH DESIGN AND METHODS This randomized controlled trial at two university medical centers enrolled 227 overweight or obese adults with type 2 diabetes and assigned them to parallel in-person diet and exercise counseling, with prepackaged foods in a planned menu during the initial phase, or to usual care (UC; two weight loss counseling sessions and monthly contacts). RESULTS Relative weight loss was 7.4% (95% CI 5.7–9.2%), 9.0% (7.1–10.9%), and 2.5% (1.3–3.8%) for the lower fat, lower carbohydrate, and UC groups (P < 0.001 intervention effect). Glycemic control markers and triglyceride levels were lower in the intervention groups compared with UC group at 1 year (fasting glucose 141 [95% CI 133–149] vs. 159 [144–174] mg/dL, P = 0.023; hemoglobin A1c 6.9% [6.6–7.1%] vs. 7.5% [7.1–7.9%] or 52 [49–54] vs. 58 [54–63] mmol/mol, P = 0.001; triglycerides 148 [134–163] vs. 204 [173–234] mg/dL, P < 0.001). The lower versus higher carbohydrate groups maintained lower hemoglobin A1c (6.6% [95% CI 6.3–6.8%] vs. 7.2% [6.8–7.5%] or 49 [45–51] vs. 55 [51–58] mmol/mol) at 1 year (P = 0.008). CONCLUSIONS The weight loss program resulted in greater weight loss and improved glycemic control in type 2 diabetes. PMID:24760261

Pain in adolescents and its risk factors: A case-control study.

PubMed

Agüero, Gonzalo; Salmain, Soledad; Manzur, Belén; Berner, Enrique

2018-04-01

The most common painful syndromes (headache, abdominal pain and musculoskeletal pain) develop or worsen during adolescence and are a common reason for consultation. Evaluate the association of age, sex, obesity, pubertal development, schooling level, employment and family structure with consultation for pain in adolescents. Case-control study conducted between February 1st, 2014 and June 30th, 2015. ages 10 to 20 years, both sexes, consultation for pain (cases), or a checkup and/or school physical (controls). χ 2 test and Student" s tests were used. Odds ratios (OR) were calculated. A binary logistic regression model was constructed to independently assess each pain-related variable. A total of 4224 medical records were evaluated; 237 cases and 468 controls were included. Adolescents with pain exhibited: greater age (p < 0.0001; OR 2.3; 95% CI: 1.63.2); greater number of females (p < 0.0001; OR 2.24; 95% CI: 1.61-3.12); greater pubertal development (p < 0.0035; OR 2.16; 95% CI: 1.33.6); greater school dropout level (p < 0.0001; OR 13.4; 95% CI: 3.9-42.9); greater employment levels (p < 0.0001; OR 3.04; 95% CI: 1.7-5.3). Only age, female sex and school dropout were independently associated with consultation for pain. There were no significant differences with obesity and family structure. Older age, female sex and school dropout were independent risk factors in consultation for pain in adolescents. Puberty and employment were associated, but were not found to be independent risk factors. Sociedad Argentina de Pediatría.

[Diabetic Foot Neuropathy and Related Factors in Patients With Type 2 Diabetes Mellitus].

PubMed

Chen, Tzu-Yu; Lin, Chia-Huei; Chang, Yue-Cune; Wang, Chih-Hsin; Hung, Yi-Jen; Tzeng, Wen-Chii

2018-06-01

Patients with type 2 diabetes mellitus (T2DM) face a higher risk of diabetic foot neuropathy, which increases the risk of death. The early detection of factors that influence diabetic neuropathy reduces the risk of foot lesions, including foot ulcerations, lower extremity amputation, and mortality. To explore the demographic, disease-characteristic, health-literacy, and foot-self-care-behavior factors that affect diabetic foot neuropathy in patients with T2DM. A case-control study design was employed in which cases (Michigan Neuropathy Screening Instrument, MNSI) ≥ 2 were matched to controls based on age and gender in a medical center. A total of 114 patients diagnosed with T2DM in a medical center were recruited as participants. Data were collected using a structured questionnaire. The collected data were analyzed using Fisher's exact test, Mann-Whitney U test, and logistic regression. The results of multiple logistic regression showed that glycated hemoglobin (B = 1.696, p = .041) and communication and critical health literacy (B = -0.082, p = .034) were significant factors of diabetic foot neuropathy. The findings of this study suggest that nurses should assess the health literacy of patients with T2DM before providing health education and should develop a specific foot-care intervention for individuals with poor glycemic control.

Controlled release of basic fibroblast growth factor for angiogenesis using acoustically-responsive scaffolds.

PubMed

Moncion, Alexander; Lin, Melissa; O'Neill, Eric G; Franceschi, Renny T; Kripfgans, Oliver D; Putnam, Andrew J; Fabiilli, Mario L

2017-09-01

The clinical translation of pro-angiogenic growth factors for treatment of vascular disease has remained a challenge due to safety and efficacy concerns. Various approaches have been used to design spatiotemporally-controlled delivery systems for growth factors in order to recapitulate aspects of endogenous signaling and thus assist in translation. We have developed acoustically-responsive scaffolds (ARSs), which are fibrin scaffolds doped with a payload-containing, sonosensitive emulsion. Payload release can be controlled non-invasively and in an on-demand manner using focused, megahertz-range ultrasound (US). In this study, we investigate the in vitro and in vivo release from ARSs containing basic fibroblast growth factor (bFGF) encapsulated in monodispersed emulsions. Emulsions were generated in a two-step process utilizing a microfluidic device with a flow focusing geometry. At 2.5 MHz, controlled release of bFGF was observed for US pressures above 2.2 ± 0.2 MPa peak rarefactional pressure. Superthreshold US yielded a 12.6-fold increase in bFGF release in vitro. The bioactivity of the released bFGF was also characterized. When implanted subcutaneously in mice, ARSs exposed to superthreshold US displayed up to 3.3-fold and 1.7-fold greater perfusion and blood vessel density, respectively, than ARSs without US exposure. Scaffold degradation was not impacted by US. These results highlight the utility of ARSs in both basic and applied studies of therapeutic angiogenesis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Control and the Aged: Environmental or Personality Factors.

ERIC Educational Resources Information Center

Tiffany, Phyllis G.; Dey, Kay

Control over self, lifestyle, and environment is a major factor in how one ages. To investigate how age acts as an environmental force in affecting perceptions of control, 45 adults, aged 60-80, from western Kansas were administered the Wechsler Adult Intelligence Scale (WAIS), the Tiffany Experienced Control Scales (ECS), the Minnesota…

The effects of internal and external control factors on college students' marijuana use and cessation of use.

PubMed

Lo, C C; Globetti, G

1995-01-01

The purpose of this study was to examine how selected internal and external control variables influence lifetime use, frequency of use, and cessation of use of marijuana. The internal control factor, comprising the variables 1) perceived risk of marijuana use and 2) attitudes toward prohibition of marijuana use, refers to a built-in personal tendency toward conventionality. The external control factor refers to social-environmental forces which discourage marijuana use. External control is indicated by factors including the number of extra-curricular activities in which an individual is involved; place of residence; the availability of marijuana; peer attitudes toward marijuana use; the number of an individual's friends who use marijuana; and the number of occasions on which an individual has observed others using marijuana. The study's results show that both internal and external control factors are significant predictors of the frequency of marijuana use. The external control factor, however, plays a more important role in explaining lifetime marijuana use and cessation of marijuana use.

Under Pressure: Controlling Factors Faced by Classroom Literacy Teachers as They Work through a Professional Development Program

ERIC Educational Resources Information Center

Wallace, Faith H.

2006-01-01

This critical constructivist inquiry was designed to understand controlling factors faced by classroom literacy teachers involved in a professional development program. Two guiding questions framed this critical inquiry: (1) how can I describe controlling factors faced by teachers in their respective school cultures; and (2) what is the resultant…

Risk factors control for primary prevention of cardiovascular disease in men: Evidence from the Aragon Workers Health Study (AWHS).

PubMed

Aguilar-Palacio, Isabel; Malo, Sara; Feja, Cristina; Lallana, MªJesús; León-Latre, Montserrat; Casasnovas, José Antonio; Rabanaque, MªJosé; Guallar, Eliseo

2018-01-01

Benefits of cardiovascular disease (CVD) risk factors control are well known, but goals achievement remains low. The objective of this study is to evaluate the prevalence of CVD risk factors among men ina worker's cohort with no previous CVD, to study control variations across time and the factors associated with poor control. To this end, we conducted a cohort reexamination (2010-2014) within the context of the Aragon Workers Health Study (AWHS). Data from working characteristics, analytical values and pharmacological prescription were included in the analysis. Prevalences of risk factor diagnosis and control were calculated, as well as factors associated with poor control. The prevalence of CVD risk factors was high. In 2014dyslipidaemia was the most prevalent (85.2%) followed by Hypertension (HT) (42.0%). People under treatment increased for the period analysed (p<0.001). The proportion of people treated varied from 72.2% in Diabetes Mellitus to 31.1% in dyslipidaemia in 2014. 46.2% of the workers with HT were controlled, decreasing to 21.9% in Diabetes and 11.0% in dyslipidaemia (2014). Working in a turn different to central shift was associated with poor control, especially for those working at night with HT (Odds Ratio in 2010: 3.6; Confidence Interval 95% 1.8-7.4) and dyslipidaemia (Odds Ratio 2010: 4.7; Confidence Interval 95% 1.3-16.4). We conclude that, although CVD control has increased significantly for the period studied, there are still many people that do not receive any treatment, and control goals are normally not achieved.

Risk and protective factors for spasmodic dysphonia: a case-control investigation.

PubMed

Tanner, Kristine; Roy, Nelson; Merrill, Ray M; Kimber, Kamille; Sauder, Cara; Houtz, Daniel R; Doman, Darrin; Smith, Marshall E

2011-01-01

Spasmodic dysphonia (SD) is a chronic, incurable, and often disabling voice disorder of unknown pathogenesis. The purpose of this study was to identify possible endogenous and exogenous risk and protective factors uniquely associated with SD. Prospective, exploratory, case-control investigation. One hundred fifty patients with SD and 150 medical controls (MCs) were interviewed regarding their personal and family histories, environmental exposures, illnesses, injuries, voice use patterns, and general health using a previously vetted and validated epidemiologic questionnaire. Odds ratios and multiple logistic regression analyses (α<0.15) identified several factors that significantly increased the likelihood of having SD. These factors included (1) a personal history of mumps, blepharospasm, tremor, intense occupational and avocational voice use, and a family history of voice disorders; (2) an immediate family history of meningitis, tremor, tics, cancer, and compulsive behaviors; and (3) an extended family history of tremor and cancer. SD is likely multifactorial in etiology, involving both genetic and environmental factors. Viral infections/exposures, along with intense voice use, may trigger the onset of SD in genetically predisposed individuals. Future studies should examine the interaction among genetic and environmental factors to determine the pathogenesis of SD. Copyright © 2011 The Voice Foundation. Published by Mosby, Inc. All rights reserved.

Preferential association of interferon regulatory factor 5 gene variants with seronegative rheumatoid arthritis in 2 Swedish case-control studies.

PubMed

Wang, Chuan; Kokkonen, Heidi; Sandling, Johanna K; Johansson, Martin; Seddighzadeh, Maria; Padyukov, Leonid; Rantapää-Dahlqvist, Solbritt; Syvänen, Ann-Christine

2011-10-01

Two interferon regulatory factor 5 (IRF5) gene variants were examined for association with rheumatoid arthritis (RA). A total of 2300 patients with RA and 1836 controls were recruited from 2 independent RA studies in Sweden. One insertion-deletion polymorphism (CGGGG indel) and one single-nucleotide polymorphism (rs10488631) in the IRF5 gene were genotyped and analyzed within RA subgroups stratified by rheumatoid factor (RF) and anticitrullinated peptide antibodies (ACPA). The CGGGG indel was preferentially associated with the RF-negative (OR 1.29, p = 7.9 × 10(-5)) and ACPA-negative (OR 1.27, p = 7.3 × 10(-5)) RA subgroups compared to the seropositive counterparts. rs10488631 was exclusively associated within the seronegative RA subgroups (RF-negative: OR 1.24, p = 0.016; ACPA-negative: OR 1.27, p = 4.1 × 10(-3)). Both the CGGGG indel and rs10488631 are relevant for RA susceptibility, especially for seronegative RA.

A multi-factor designation method for mapping particulate-pollution control zones in China.

PubMed

Qin, Y; Xie, S D

2011-09-01

A multi-factor designation method for mapping particulate-pollution control zones was brought out through synthetically considering PM(10) pollution status, PM(10) anthropogenic emissions, fine particle pollution, long-range transport and economic situation. According to this method, China was divided into four different particulate-pollution control regions: PM Suspended Control Region, PM(10) Pollution Control Region, PM(2.5) Pollution Control Region and PM(10) and PM(2.5) Common Control Region, which accounted for 69.55%, 9.66%, 4.67% and 16.13% of China's territory, respectively. The PM(10) and PM(2.5) Common Control Region was mainly distributed in Bohai Region, Yangtze River Delta, Pearl River Delta, eastern of Sichuan province and Chongqing municipality, calling for immediate control of both PM(10) and PM(2.5). Cost-effective control effects can be achieved through concentrating efforts on PM(10) and PM(2.5) Common Control Region to address 60.32% of national PM(10) anthropogenic emissions. Air quality in districts belonging to PM(2.5) Pollution Control Region suggested that Chinese national ambient air quality standard for PM(10) was not strict enough. The result derived from application to China proved that this approach was feasible for mapping pollution control regions for a country with vast territory, complicated pollution characteristics and limited available monitoring data. Copyright © 2011 Elsevier B.V. All rights reserved.

Quality of Vitamin K Antagonist Anticoagulation in Spain: Prevalence of Poor Control and Associated Factors.

PubMed

Anguita Sánchez, Manuel; Bertomeu Martínez, Vicente; Cequier Fillat, Ángel

2015-09-01

To study the prevalence of poorly controlled vitamin K antagonist anticoagulation in Spain in patients with nonvalvular atrial fibrillation, and to identify associated factors. We studied 1056 consecutive patients seen at 120 cardiology clinics in Spain between November 2013 and March 2014. We analyzed the international normalized ratio from the 6 months prior to the patient's visit, calculating the prevalence of poorly controlled anticoagulation, defined as < 65% time in therapeutic range using the Rosendaal method. Mean age was 73.6 years (standard deviation, 9.8 years); women accounted for 42% of patients. The prevalence of poorly controlled anticoagulation was 47.3%. Mean time in therapeutic range was 63.8% (25.9%). The following factors were independently associated with poorly controlled anticoagulation: kidney disease (odds ratio = 1.53; 95% confidence interval, 1.08-2.18; P = .018), routine nonsteroidal anti-inflammatory drugs (odds ratio = 1.79; 95% confidence interval, 1.20-2.79; P = .004), antiplatelet therapy (odds ratio = 2.16; 95% confidence interval, 1.49-3.12; P < .0001) and absence of angiotensin receptor blockers (odds ratio = 1.39; 95% confidence interval, 1.08-1.79; P = .011). There is a high prevalence of poorly controlled vitamin K antagonist anticoagulation in Spain. Factors associated with poor control are kidney disease, routine nonsteroidal anti-inflammatory drugs, antiplatelet use, and absence of angiotensin receptor blockers. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Perinatal risk factors for neonatal encephalopathy: an unmatched case-control study.

PubMed

Tann, Cally J; Nakakeeto, Margaret; Willey, Barbara A; Sewegaba, Margaret; Webb, Emily L; Oke, Ibby; Mutuuza, Emmanuel Derek; Peebles, Donald; Musoke, Margaret; Harris, Kathryn A; Sebire, Neil J; Klein, Nigel; Kurinczuk, Jennifer J; Elliott, Alison M; Robertson, Nicola J

2018-05-01

Neonatal encephalopathy (NE) is the third leading cause of child mortality. Preclinical studies suggest infection and inflammation can sensitise or precondition the newborn brain to injury. This study examined perinatal risks factor for NE in Uganda. Unmatched case-control study. Mulago National Referral Hospital, Kampala, Uganda. 210 term infants with NE and 409 unaffected term infants as controls were recruited over 13 months. Data were collected on preconception, antepartum and intrapartum exposures. Blood culture, species-specific bacterial real-time PCR, C reactive protein and placental histology for chorioamnionitis and funisitis identified maternal and early newborn infection and inflammation. Multivariable logistic regression examined associations with NE. Neonatal bacteraemia (adjusted OR (aOR) 8.67 (95% CI 1.51 to 49.74), n=315) and histological funisitis (aOR 11.80 (95% CI 2.19 to 63.45), n=162) but not chorioamnionitis (aOR 3.20 (95% CI 0.66 to 15.52), n=162) were independent risk factors for NE. Among encephalopathic infants, neonatal case fatality was not significantly higher when exposed to early neonatal bacteraemia (OR 1.65 (95% CI 0.62 to 4.39), n=208). Intrapartum antibiotic use did not improve neonatal survival (p=0.826). After regression analysis, other identified perinatal risk factors (n=619) included hypertension in pregnancy (aOR 3.77), male infant (aOR 2.51), non-cephalic presentation (aOR 5.74), lack of fetal monitoring (aOR 2.75), augmentation (aOR 2.23), obstructed labour (aOR 3.8) and an acute intrapartum event (aOR 8.74). Perinatal infection and inflammation are independent risk factors for NE in this low-resource setting, supporting a role in the aetiological pathway of term brain injury. Intrapartum antibiotic administration did not mitigate against adverse outcomes. The importance of intrapartum risk factors in this sub-Saharan African setting is highlighted. © Article author(s) (or their employer(s) unless otherwise stated in the

Perinatal risk factors for neonatal encephalopathy: an unmatched case-control study

PubMed Central

Nakakeeto, Margaret; Willey, Barbara A; Sewegaba, Margaret; Webb, Emily L; Oke, Ibby; Mutuuza, Emmanuel Derek; Peebles, Donald; Musoke, Margaret; Harris, Kathryn A; Sebire, Neil J; Kurinczuk, Jennifer J; Elliott, Alison M

2018-01-01

Objective Neonatal encephalopathy (NE) is the third leading cause of child mortality. Preclinical studies suggest infection and inflammation can sensitise or precondition the newborn brain to injury. This study examined perinatal risks factor for NE in Uganda. Design Unmatched case–control study. Setting Mulago National Referral Hospital, Kampala, Uganda. Methods 210 term infants with NE and 409 unaffected term infants as controls were recruited over 13 months. Data were collected on preconception, antepartum and intrapartum exposures. Blood culture, species-specific bacterial real-time PCR, C reactive protein and placental histology for chorioamnionitis and funisitis identified maternal and early newborn infection and inflammation. Multivariable logistic regression examined associations with NE. Results Neonatal bacteraemia (adjusted OR (aOR) 8.67 (95% CI 1.51 to 49.74), n=315) and histological funisitis (aOR 11.80 (95% CI 2.19 to 63.45), n=162) but not chorioamnionitis (aOR 3.20 (95% CI 0.66 to 15.52), n=162) were independent risk factors for NE. Among encephalopathic infants, neonatal case fatality was not significantly higher when exposed to early neonatal bacteraemia (OR 1.65 (95% CI 0.62 to 4.39), n=208). Intrapartum antibiotic use did not improve neonatal survival (p=0.826). After regression analysis, other identified perinatal risk factors (n=619) included hypertension in pregnancy (aOR 3.77), male infant (aOR 2.51), non-cephalic presentation (aOR 5.74), lack of fetal monitoring (aOR 2.75), augmentation (aOR 2.23), obstructed labour (aOR 3.8) and an acute intrapartum event (aOR 8.74). Conclusions Perinatal infection and inflammation are independent risk factors for NE in this low-resource setting, supporting a role in the aetiological pathway of term brain injury. Intrapartum antibiotic administration did not mitigate against adverse outcomes. The importance of intrapartum risk factors in this sub-Saharan African setting is highlighted. PMID:28780500

Medical and drug risk factors associated with neuroblastoma: a case-control study.

PubMed

Kramer, S; Ward, E; Meadows, A T; Malone, K E

1987-05-01

A matched case-control study of prenatal risk factors for neuroblastoma was conducted, including 104 cases diagnosed over the period 1970-79 in the Greater Delaware Valley. Significantly elevated odds ratios (ORs) were associated with maternal use of a neurally active drug during pregnancy (OR = 2.83), sex hormone exposure 3 months prior to or during pregnancy (OR = 2.25), frequent alcohol consumption during pregnancy (OR = 9.0), and maternal use of diuretic drugs during pregnancy (OR = 5.75). Significantly more case mothers than control mothers reported use of hair coloring products during pregnancy (OR = 3.0). No association was found between cigarette smoking, coffee consumption, or medical irradiation and case-control status.

Population prevalence and control of cardiovascular risk factors: what electronic medical records tell us.

PubMed

Catalán-Ramos, Arantxa; Verdú, Jose M; Grau, María; Iglesias-Rodal, Manuel; del Val García, José L; Consola, Alicia; Comin, Eva

2014-01-01

To analyze the prevalence, control, and management of hypertension, hypercholesterolemia, and diabetes mellitus type 2 (DM2). Cross-sectional analysis of all individuals attended in the Catalan primary care centers between 2006 and 2009. History of cardiovascular diseases, diagnosis and treatment of hypertension, hypercholesterolemia, DM2, lipid profile, glycemia and blood pressure data were extracted from electronic medical records. Age-standardized prevalence and levels of management and control were estimated. Individuals aged 35-74 years using primary care databases. A total of 2,174,515 individuals were included (mean age 52 years [SD 11], 47% men). Hypertension was the most prevalent cardiovascular risk factor (39% in women, 41% in men) followed by hypercholesterolemia (38% and 40%) and DM2 (12% and 16%), respectively. Diuretics and angiotensin-converting enzyme inhibitors were most often prescribed for hypertension control (<140/90mmHg, achieved in 68% of men and 60% of women treated). Hypercholesterolemia was controlled (low-density lipoprotein cholesterol <130mg/dl) in just 31% of men and 26% of women with no history of cardiovascular disease, despite lipid-lowering treatment, primarily (90%) with statins. The percentage of women and men with DM2 and with glycated hemoglobin <7% was 64.7% and 59.2%, respectively; treatment was predominantly with oral hypoglycemic agents alone (70%), or combined with insulin (15%). Hypertension was the most prevalent cardiovascular risk factor in the Catalan population attended at primary care centers. About two thirds of individuals with hypertension or DM2 were adequately controlled; hypercholesterolemia control was particularly low. Copyright © 2013 Elsevier España, S.L. All rights reserved.

A case control study of nutritional factors and cervical dysplasia.

PubMed

Liu, T; Soong, S J; Wilson, N P; Craig, C B; Cole, P; Macaluso, M; Butterworth, C E

1993-01-01

The association of nutritional factors with cervical dysplasia was examined through a case-control study. Analysis was conducted in 257 cases and 133 controls confirmed both by cytological examination and colposcopic findings. A 24-h dietary recall questionnaire was used to assess nutritional intake. Various risk factors (including age at first intercourse, number of sexual partners, parity, cigarette smoking, oral contraceptive use, human papillomavirus type 16 infection, and age and race) were adjusted for their potential confounding effects. While analyses were also performed to adjust for total calories, results were not changed significantly. Among the nutrients examined, vitamin A intake showed a significantly increased risk at the lowest quartile compared to the highest quartile, with an odds ratio of 2.2 (95% confidence interval, 1.2-4.2). A significant trend of increasing risk was also observed with lower intake of vitamin A (P = 0.05). Riboflavin showed increased risk at the two lower quartiles of intake with a trend test P value of 0.04. Increased risk was also found for lower intakes of vitamin C compared to the highest intake level. For folate, increased risk was found in the second highest quartile compared with the highest quartile with an odds ratio of 2.0 (95% confidence interval, 1.0-3.8). The calcium:phosphorus ratio showed an increased risk at the lowest level (odds ratio, 2.0; 95% confidence interval, 1.0-4.3). Insufficient intake of vitamin A, riboflavin, ascorbate, and folate is associated with an increased risk of cervical dysplasia.

Risk Factors for Stillbirth: Findings from a Population-Based Case-Control Study, Haryana, India.

PubMed

Neogi, Sutapa Bandyopadhyay; Negandhi, Preeti; Chopra, Sapna; Das, Ankan Mukherjee; Zodpey, Sanjay; Gupta, Ravi Kant; Gupta, Rakesh

2016-01-01

Stillbirth is a prevalent adverse outcome of pregnancy in India despite efforts to improve care of women during pregnancy. Risk factors for stillbirths include sociodemographic factors, medical complications during pregnancy, intake of harmful drugs, and complications during delivery. The objective of the study was to examine the risk factors for stillbirth with a focus on sex selection drugs (SSDs). A population-based case-control study was undertaken in Haryana. Cases of stillbirths were identified from the Maternal Infant Death Review System portal of Haryana state for the months of August-September 2014. A consecutive birth from the same geographical area as the case was selected as the control. The sample size was 325 per group. Mothers were interviewed using a validated tool. Bivariate analyses and logistic regression were conducted to examine the association between risk factors and stillbirth. Attributable risk proportions (ARP) and population attributable risk proportions (PARP) were estimated. The sociodemographic profiles of the cases and controls were similar. History of intake of SSDs [adjusted odds ratio (OR) 2.6, 95% confidence interval (CI) 1.5, 4.5] emerged as a risk factor. Other significant factors were preterm <37 weeks (OR 3.5, 95% CI 2.1, 6.0), history of previous stillbirths (OR 4.0, 95% CI 2.1, 7.8), and complications during labour (OR 3.3, 95% CI 2.1, 5.3). Estimates of the ARP and PARP for intake of SSDs were 0.60 (95% CI 0.32, 0.77) and 0.1 (95% CI -0.13, 0.28), respectively. SSDs could be attributed as a risk factor in a fifth of the cases of stillbirths. The number needed to harm for the use of SSDs in causing adverse effect of stillbirths was 5, suggesting thereby that for every five mothers exposed to SSDs, one would have stillbirth. Greater efforts are required to inform people about the harmful effects of SSD consumption during pregnancy. © 2015 John Wiley & Sons Ltd.

Awareness, treatment, control of diabetes mellitus and the risk factors: survey results from northeast China.

PubMed

Wang, Chang; Yu, Yaqin; Zhang, Xiangyang; Li, Yong; Kou, Changgui; Li, Bo; Tao, Yuchun; Zhen, Qing; He, Huan; Kanu, Joseph Sam; Huang, Xufeng; Han, Mei; Liu, Yawen

2014-01-01

The awareness, treatment and control of diabetes mellitus (DM) can effectively reflect on the social status of diabetes conditions. Although several researchers have investigated the awareness, treatment and control rates of diabetes mellitus in China, little is known about their association with risk factors. This study aims to examine the relationship between risk factors and awareness, treatment and control of diabetes mellitus in northeast China. A cross-sectional survey was conducted in 2012. Multistage stratified random cluster sampling design was used to select participants aged 18 to 79 years old. The analysis was based on a representative sample of 1,854 adult subjects. Multivariable logistic regression analysis was used to examine socio-demographic factors associated with the levels of awareness, treatment and control of diabetes mellitus. The awareness, treatment, and control rates of diabetes mellitus were 64.1%, 52.9% and 44.2%, respectively. In the multivariable logistic regression analysis, family history of diabetes was significantly positively associated with awareness (OR, 2.145; 95% CI, 1.600-2.875) and treatment (OR, 2.021; 95% CI, 1.559-2.619) of diabetes mellitus, while negatively associated with control (OR, 0.671; 95% CI, 0.529-0.951). Cigarette smokers and alcohol drinkers were less likely than non-smokers and non-drinkers to be aware of their blood glucose levels (OR, 0.895, 0.614; 95% CI, 0.659-1.216, 0.446-0.844, respectively). Participants who frequently exercise were more likely to be aware of their diabetic conditions than people who never or rarely exercise (OR, 2.003; 95% CI, 1.513-2.651). We found that the awareness and treatment of diabetes mellitus were positively associated with age and were high in participants with a family history of diabetes and those who exercise frequently, but low for cigarette smokers and alcohol drinkers. Participants with a family history of diabetes had their diabetic condition poorly controlled.

Modifiable risk factors for chronic back pain: insights using the co-twin control design.

PubMed

Suri, Pradeep; Boyko, Edward J; Smith, Nicholas L; Jarvik, Jeffrey G; Williams, Frances M K; Jarvik, Gail P; Goldberg, Jack

2017-01-01

Inconsistent associations between modifiable risk factors and chronic back pain (CBP) may be due to the inability of traditional epidemiologic study designs to properly account for an array of potential genetic and environmental confounding factors. The co-twin control research design, comparing modifiable risk factors in twins discordant for CBP, offers a unique way to remove numerous confounding factors. The study aimed to examine the association of modifiable lifestyle and psychological factors with lifetime CBP. This is a cross-sectional co-twin control study in a nationwide sample of male twin members of the Vietnam Era Twin Registry. The sample is composed of 7,108 participants, including 1,308 monozygotic (MZ) pairs and 793 dizygotic pairs. The outcome measure is the self-reported lifetime history of CBP. Lifestyle factors included body mass index (BMI), smoking history, alcohol consumption, habitual physical activity, and typical sleep duration. Psychological factors included depression (Patient Health Questionnaire-9) and posttraumatic stress disorder (PTSD) symptoms (PTSD Checklist). Covariates included age, race, education, and income. Odds ratios (ORs) and 95% confidence intervals (CI) were estimated for the association of risk factors with lifetime CBP when considering twins as individuals, and a within-pair co-twin control analysis that accounted for familial and genetic factors. Funding was through VA Grant 5IK2RX001515; there were no study-specific conflicts of interest. The mean age of respondents was 62 years and the prevalence of lifetime CBP was 28%. All lifestyle factors were associated with CBP in the individual level analysis. However, none of these persisted in the within-pair analyses, except for severe obesity (BMI ≥35.0), which was associated with lifetime CBP in both individual-level (OR=1.6, 95% CI: 1.3-1.9) and within-pair analyses (MZ analysis: OR=3.7, 95% CI: 1.2-11.4). Symptoms of PTSD and depression were strongly associated with

Incidence of and risk factors for severe hypoglycaemia in treated type 2 diabetes mellitus patients in the UK--a nested case-control analysis.

PubMed

Bruderer, S G; Bodmer, M; Jick, S S; Bader, G; Schlienger, R G; Meier, C R

2014-09-01

To assess incidence rates (IRs) of and identify risk factors for incident severe hypoglycaemia in patients with type 2 diabetes newly treated with antidiabetic drugs. Using the UK-based General Practice Research Database, we performed a retrospective cohort study between 1994 and 2011 and a nested case-control analysis. Ten controls from the population at risk were matched to each case with a recorded severe hypoglycaemia during follow-up on general practice, years of history in the database and calendar time. Using multivariate conditional logistic regression analyses, we adjusted for potential confounders. Of 130,761 patients with newly treated type 2 diabetes (mean age 61.7 ± 13.0 years), 690 (0.5%) had an incident episode of severe hypoglycaemia recorded [estimated IR 11.97 (95% confidence interval, CI, 11.11-12.90) per 10,000 person-years (PYs)]. The IR was markedly higher in insulin users [49.64 (95% CI, 44.08-55.89) per 10,000 PYs] than in patients not using insulin [8.03 (95% CI, 7.30-8.84) per 10,000 PYs]. Based on results of the nested case-control analysis increasing age [≥ 75 vs. 20-59 years; adjusted odds ratio (OR), 2.27; 95% CI, 1.65-3.12], cognitive impairment/dementia (adjusted OR, 2.00; 95% CI, 1.37-2.91), renal failure (adjusted OR, 1.34; 95% CI, 1.04-1.71), current use of sulphonylureas (adjusted OR, 4.45; 95% CI, 3.53-5.60) and current insulin use (adjusted OR, 11.83; 95% CI, 9.00-15.54) were all associated with an increased risk of severe hypoglycaemia. Severe hypoglycaemia was recorded in 12 cases per 10,000 PYs. Risk factors for severe hypoglycaemia included increasing age, renal failure, cognitive impairment/dementia, and current use of insulin or sulphonylureas. © 2014 John Wiley & Sons Ltd.

Roughness of Ti Substrates for Control of the Preferred Orientation of TiO 2 Nanotube Arrays as a New Orientation Factor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Seong, Won Mo; Kim, Dong Hoe; Park, Ik Jae

2015-06-11

We report the surface roughness of a Ti substrate as a critical factor for controlling the degree of the preferred orientation of anatase TiO2 nanotube arrays (NTAs) which are synthesized by anodization and a subsequent annealing process. The degree of the preferred orientation to the (004) plane of the anatase crystal structure has a strong dependency on the root-mean-square roughness (Sq) of the initial Ti substrate when the roughness-controlled substrates are anodized in an ethylene glycol-based electrolyte containing ~2 wt % of water. Highly preferred oriented NTAs were obtained from low-Sq (<10 nm) substrates, which were accompanied by uniform poremore » distribution and low concentration of hydroxyl ions in as-anodized amorphous NTAs. The mechanism of the preferred oriented crystallization of nanometer-scaled tube walls is explained considering the microscopic geometrical uniformity of the oxide barrier and nanopores at the early stage of anodization, which affected the local electric field and thus the insertion of the hydroxyl group into the amorphous TiO2 tube walls.« less

Controlling factors of nitrous oxide (N2O) emissions at the field-scale in an agricultural slope

NASA Astrophysics Data System (ADS)

Vilain, Guillaume; Garnier, Josette; Tallec, Gaëlle; Tournebize, Julien; Cellier, Pierre; Flipo, Nicolas

2010-05-01

Agricultural practices widely contribute to the atmospheric nitrous oxide (N2O) concentration increase and are the major source of N2O which account for 24% of the global annual emission (IPCC, 2007). Soil nitrification and denitrification are the microbial processes responsible for the production of N2O, which also depends on soil characteristics and management. Besides their control by various factors, such as climate, soil conditions and management (content of NO3- and NH4+, soil water content, presence of degradable organic material…), the role of topography is less known although it can play an important role on N2O emissions (Izaurralde et al., 2004). Due to the scarcity of data on N2O direct vs. indirect emission rate from agriculture in the Seine Basin (Garnier et al., 2009), one of the objectives of the study conducted here was to determine the N2O emission rates of the various land use representative for the Seine Basin, in order to better assess the direct N2O emissions, and to explore controlling factor such as meteorology, topography, soil properties and crop successions. The main objective of this study was at the same time to characterize N2O fluxes variability along a transect from an agricultural plateau to a river and to analyze the influence of landscape position on these emissions. We conducted this study in the Orgeval catchment (Seine basin, France; between 48°47' and 48°55' N, and 03°00' and 03°55' E) from May 2008 to August 2009 on two agricultural fields cropped with wheat, barley, oats, corn. N2O fluxes were monitored from weekly to bimonthly using static manual chambers placed along the chosen transect in five different landscape positions from the plateau to the River. This study has shown that soil moisture (expressed as Water Filled Pore Space) and NO3- soil concentrations explained most of the N2O flux variability during the sampling period. Most of N2O was emitted directly after N fertilization application during a relatively

16 CFR 1105.2 - Factors.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Factors. 1105.2 Section 1105.2 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS CONTRIBUTIONS TO COSTS OF PARTICIPANTS IN DEVELOPMENT OF CONSUMER PRODUCT SAFETY STANDARDS § 1105.2 Factors. The Commission...

Internet-based control recruitment for a case-control study of major risk factors for stroke in Korea: lessons from the experience.

PubMed

Park, Jong-Moo; Cho, Yong-Jin; Lee, Kyung Bok; Park, Tai Hwan; Lee, Soo Joo; Han, Moon-Ku; Ko, Youngchai; Lee, Jun; Cha, Jae-Kwan; Lee, Byung-Chul; Yu, Kyung-Ho; Oh, Mi-Sun; Lee, Ji Sung; Lee, Juneyoung; Bae, Hee-Joon

2014-01-01

This study aimed to estimate the population-attributable risks (PARs) of 9 major risk factors for stroke in Korea through a case-control study and to test the feasibility and validity of internet-based control recruitment. From April 2008 to September 2009, controls were enrolled via internet after providing consent for participation through a web-based survey. The cases included patients who were admitted to the participating centers due to acute stroke or transient ischemic attack within 7 days of onset during the study period. Each control was age- and sex-matched with 2 cases. Adjusted odd ratios, age-standardized prevalence, and PARs were estimated for the 9 major risk factors using the prevalence of risk factors in the control group and the age and sex characteristics from Korea's national census data. In total, 1041 controls were matched to 2082 stroke cases. Because of a shortage of elderly controls in the internet-based recruitment, 248 controls were recruited off-line. The PARs were 23.44%, 10.95%, 51.32%, and 6.35% for hypertension, diabetes, smoking, and stroke history, respectively. Hypercholesterolemia, atrial fibrillation, obesity, coronary heart disease, and a family history of stroke were not associated with stroke. Comparison with education and religion of the control group with that mentioned in the national census data showed a notable difference. The study results imply that internet-based control recruitment for a case-control study requires careful selection of risk factors with high self-awareness and effective strategies to facilitate the recruitment of elderly participants. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Risk factors for burns at home in Kurdish preschool children: a case-control study.

PubMed

Othman, Nasih; Kendrick, Denise

2013-06-01

It is globally reported that young children are at a higher risk of burns but little is known about the individual risk factors. This study was undertaken in 2008 to investigate factors associated with burn injuries in children aged 0-5 years. This was a case-control study with cases recruited prospectively from children attending hospital for a new burn injury and controls recruited from children admitted for other conditions. A total of 248 cases and 248 controls were recruited. Cases included scalds (79%), contact burns (17%) and flame injuries (4%). Burns were most commonly caused by tea utensils (42%) and kerosene stoves (36%). Multivariable analyses found that a poor living standard (OR 5.4, 95% CI 2.6 to 11.7), having a child with a higher activity score (OR 5.3, 95% CI 3.4 to 8.5), having a history of burns in other family members (OR 2.8, 95% CI 1.5 to 5.2) and a higher number of home hazards (OR for a one unit increase in hazards score 1.32, 95% CI 1.02 to 1.70) were all associated with a significant increase in the odds of a burn injury. The presence of a second carer (OR 0.42, 95% CI 0.2 to 0.7) and having disability (OR 0.14, 95% CI 0.03 to 0.6) were protective factors. This information about risk factors for burn injuries can be used to target preventive interventions towards families at the greatest risk of injury.

Anti-Sigma Factors in E. coli: Common Regulatory Mechanisms Controlling Sigma Factors Availability

PubMed Central

Treviño-Quintanilla, Luis Gerardo; Freyre-González, Julio Augusto; Martínez-Flores, Irma

2013-01-01

In bacteria, transcriptional regulation is a key step in cellular gene expression. All bacteria contain a core RNA polymerase that is catalytically competent but requires an additional σ factor for specific promoter recognition and correct transcriptional initiation. The RNAP core is not able to selectively bind to a given σ factor. In contrast, different σ factors have different affinities for the RNAP core. As a consequence, the concentration of alternate σ factors requires strict regulation in order to properly control the delicate interplay among them, which favors the competence for the RNAP core. This control is archived by different σ/anti-σ controlling mechanisms that shape complex regulatory networks and cascades, and enable the response to sudden environmental cues, whose global understanding is a current challenge for systems biology. Although there have been a number of excellent studies on each of these σ/anti-σ post-transcriptional regulatory systems, no comprehensive comparison of these mechanisms in a single model organism has been conducted. Here, we survey all these systems in E. coli dissecting and analyzing their inner workings and highlightin their differences. Then, following an integral approach, we identify their commonalities and outline some of the principles exploited by the cell to effectively and globally reprogram the transcriptional machinery. These principles provide guidelines for developing biological synthetic circuits enabling an efficient and robust response to sudden stimuli. PMID:24396271

Natural Killer Cells Control Tumor Growth by Sensing a Growth Factor.

PubMed

Barrow, Alexander D; Edeling, Melissa A; Trifonov, Vladimir; Luo, Jingqin; Goyal, Piyush; Bohl, Benjamin; Bando, Jennifer K; Kim, Albert H; Walker, John; Andahazy, Mary; Bugatti, Mattia; Melocchi, Laura; Vermi, William; Fremont, Daved H; Cox, Sarah; Cella, Marina; Schmedt, Christian; Colonna, Marco

2018-01-25

Many tumors produce platelet-derived growth factor (PDGF)-DD, which promotes cellular proliferation, epithelial-mesenchymal transition, stromal reaction, and angiogenesis through autocrine and paracrine PDGFRβ signaling. By screening a secretome library, we found that the human immunoreceptor NKp44, encoded by NCR2 and expressed on natural killer (NK) cells and innate lymphoid cells, recognizes PDGF-DD. PDGF-DD engagement of NKp44 triggered NK cell secretion of interferon gamma (IFN)-γ and tumor necrosis factor alpha (TNF-α) that induced tumor cell growth arrest. A distinctive transcriptional signature of PDGF-DD-induced cytokines and the downregulation of tumor cell-cycle genes correlated with NCR2 expression and greater survival in glioblastoma. NKp44 expression in mouse NK cells controlled the dissemination of tumors expressing PDGF-DD more effectively than control mice, an effect enhanced by blockade of the inhibitory receptor CD96 or CpG-oligonucleotide treatment. Thus, while cancer cell production of PDGF-DD supports tumor growth and stromal reaction, it concomitantly activates innate immune responses to tumor expansion. Copyright © 2017 Elsevier Inc. All rights reserved.

Preventable coronary heart disease events from control of cardiovascular risk factors in US adults with diabetes (projections from utilizing the UKPDS risk engine).

PubMed

Wong, Nathan D; Patao, Christopher; Malik, Shaista; Iloeje, Uchenna

2014-04-15

Type 2 diabetes mellitus (T2DM) carries significant risks for coronary heart disease (CHD). We examined the potential US population impact of single and composite risk factor control. Among US adults with diagnosed T2DM aged≥30 years in the National Health and Nutrition Examination Survey 2007 to 2012, we assessed CHD events preventable using the United Kingdom Prospective Diabetes Study CHD risk engine. We examined in all those not at goal the impact of statistical control of smoking, glycated hemoglobin, systolic blood pressure, and total and high-density lipoprotein cholesterol, according to the predefined criteria setting risk factors at different levels of control representing (1) "All to Goal," (2) at "Nominal Control," or (3) at "Aggressive Control." Preventable CHD events represented the difference between the number of events estimated from the control of these risk factors versus current levels of the risk factors. Of 606 men (representing 6.2 million) and 603 women (6.3 million) with DM and no previous CHD, 1.3 million men and 0.7 million women would develop a CHD event within 10 years if left uncontrolled. Controlling all risk factors to goal was projected to prevent 35% and 45% of CHD events in men and women, respectively. Nominal risk factor control was projected to prevent 36% and 38% and aggressive control 51% and 61% of CHD events, respectively. In conclusion, a significant proportion of CHD events in adults with T2DM could be prevented from composite control of risk factors often not at goal. Copyright © 2014 Elsevier Inc. All rights reserved.

Role of Nuclear Factor Erythroid 2-Related Factor 2 in Diabetic Nephropathy

PubMed Central

Min, Xu; Xu, Xiaohong

2017-01-01

Diabetic nephropathy (DN) is manifested as increased urinary protein level, decreased glomerular filtration rate, and final renal dysfunction. DN is the leading cause of end-stage renal disease worldwide and causes a huge societal healthcare burden. Since satisfied treatments are still limited, exploring new strategies for the treatment of this disease is urgently needed. Oxidative stress takes part in the initiation and development of DN. In addition, nuclear factor erythroid 2-related factor 2 (Nrf2) plays a key role in the cellular response to oxidative stress. Thus, activation of Nrf2 seems to be a new choice for the treatment of DN. In current review, we discussed and summarized the therapeutic effects of Nrf2 activation on DN from both basic and clinical studies. PMID:28512642

Risk Factors for Incident Peripheral Arterial Disease in Type 2 Diabetes: Results From the Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes (BARI 2D) Trial

PubMed Central

Althouse, Andrew D.; Abbott, J. Dawn; Forker, Alan D.; Bertolet, Marnie; Barinas-Mitchell, Emma; Thurston, Rebecca C.; Mulukutla, Suresh; Aboyans, Victor; Brooks, Maria Mori

2014-01-01

OBJECTIVE The aim of this article was to define risk factors for incidence of peripheral arterial disease (PAD) in a large cohort of patients with type 2 diabetes mellitus (T2DM), overall and within the context of differing glycemic control strategies. RESEARCH DESIGN AND METHODS The Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes (BARI 2D) randomized controlled trial assigned participants to insulin-sensitizing (IS) therapy versus insulin-providing (IP) therapy. A total of 1,479 participants with normal ankle-brachial index (ABI) at study entry were eligible for analysis. PAD outcomes included new ABI ≤0.9 with decrease at least 0.1 from baseline, lower extremity revascularization, or lower extremity amputation. Baseline risk factors within the overall cohort and time-varying risk factors within each assigned glycemic control arm were assessed using Cox proportional hazards models. RESULTS During an average 4.6 years of follow-up, 303 participants (20.5%) experienced an incident case of PAD. Age, sex, race, and baseline smoking status were all significantly associated with incident PAD in the BARI 2D cohort. Additional baseline risk factors included pulse pressure, HbA1c, and albumin-to-creatinine ratio (P < 0.05 for each). In stratified analyses of time-varying covariates, changes in BMI, LDL, HDL, systolic blood pressure, and pulse pressure were most predictive among IS patients, while change in HbA1c was most predictive among IP patients. CONCLUSIONS Among patients with T2DM, traditional cardiovascular risk factors were the main predictors of incident PAD cases. Stratified analyses showed different risk factors were predictive for patients treated with IS medications versus those treated with IP medications. PMID:24595631

Risk factors for incident peripheral arterial disease in type 2 diabetes: results from the Bypass Angioplasty Revascularization Investigation in type 2 Diabetes (BARI 2D) Trial.

PubMed

Althouse, Andrew D; Abbott, J Dawn; Forker, Alan D; Bertolet, Marnie; Barinas-Mitchell, Emma; Thurston, Rebecca C; Mulukutla, Suresh; Aboyans, Victor; Brooks, Maria Mori

2014-01-01

The aim of this article was to define risk factors for incidence of peripheral arterial disease (PAD) in a large cohort of patients with type 2 diabetes mellitus (T2DM), overall and within the context of differing glycemic control strategies. The Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes (BARI 2D) randomized controlled trial assigned participants to insulin-sensitizing (IS) therapy versus insulin-providing (IP) therapy. A total of 1,479 participants with normal ankle-brachial index (ABI) at study entry were eligible for analysis. PAD outcomes included new ABI ≤0.9 with decrease at least 0.1 from baseline, lower extremity revascularization, or lower extremity amputation. Baseline risk factors within the overall cohort and time-varying risk factors within each assigned glycemic control arm were assessed using Cox proportional hazards models. During an average 4.6 years of follow-up, 303 participants (20.5%) experienced an incident case of PAD. Age, sex, race, and baseline smoking status were all significantly associated with incident PAD in the BARI 2D cohort. Additional baseline risk factors included pulse pressure, HbA1c, and albumin-to-creatinine ratio (P < 0.05 for each). In stratified analyses of time-varying covariates, changes in BMI, LDL, HDL, systolic blood pressure, and pulse pressure were most predictive among IS patients, while change in HbA1c was most predictive among IP patients. Among patients with T2DM, traditional cardiovascular risk factors were the main predictors of incident PAD cases. Stratified analyses showed different risk factors were predictive for patients treated with IS medications versus those treated with IP medications.

Translational control of Nrf2 within the open reading frame

DOE Office of Scientific and Technical Information (OSTI.GOV)

Perez-Leal, Oscar, E-mail: operez@temple.edu; Barrero, Carlos A.; Merali, Salim, E-mail: smerali@temple.edu

2013-07-19

Highlights: •Identification of a novel Nrf2 translational repression mechanism. •The repressor is within the 3′ portion of the Nrf2 ORF. •The translation of Nrf2 or eGFP is reduced by the regulatory element. •The translational repression can be reversed with synonymous codon substitutions. •The molecular mechanism requires the mRNA sequence, but not the encoded amino acids. -- Abstract: Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) is a transcription factor that is essential for the regulation of an effective antioxidant and detoxifying response. The regulation of its activity can occur at transcription, translation and post-translational levels. Evidence suggests that under environmental stressmore » conditions, new synthesis of Nrf2 is required – a process that is regulated by translational control and is not fully understood. Here we described the identification of a novel molecular process that under basal conditions strongly represses the translation of Nrf2 within the open reading frame (ORF). This mechanism is dependent on the mRNA sequence within the 3′ portion of the ORF of Nrf2 but not in the encoded amino acid sequence. The Nrf2 translational repression can be reversed with the use of synonymous codon substitutions. This discovery suggests an additional layer of control to explain the reason for the low Nrf2 concentration under quiescent state.« less

Risk factors for tuberculosis in Greenland: case-control study.

PubMed

Ladefoged, K; Rendal, T; Skifte, T; Andersson, M; Søborg, B; Koch, A

2011-01-01

Despite several efforts aiming at disease control, the incidence of tuberculosis (TB) remains high in Greenland, averaging 131 per 100,000 population during the period 1998-2007. The purpose of the present study was to disclose risk factors for TB. A case-control study was performed among 146 patients diagnosed with TB in the period 2004-2006. For each patient, four healthy age- and sex-matched control persons living in the same district were included. All participants completed a questionnaire regarding socio-demographic and lifestyle factors. Risk factor analyses were carried out using logistic regression models. Factors associated with TB were Inuit ethnicity, living in a small settlement, unemployment, no access to tap water, no bathroom or flushing toilet, underweight, smoking, frequent intake of alcohol and immunosuppressive treatment. The multivariate model showed that Inuit ethnicity (OR 15.3), living in a settlement (OR 5.1), being unemployed (OR 4.1) and frequent alcohol use (OR 3.1) were independent determinants of risk. Unemployment was associated with the highest population-attributable risk (29%). Risk factors associated with living in a settlement should be further explored and an investigation of genetic susceptibility is warranted.

Risk factors for nonspecific low-back pain in Chinese adolescents: a case-control study.

PubMed

Yao, WeiGuang; Luo, ChenLing; Ai, FuZhi; Chen, Qing

2012-05-01

The objective of this study was to gain a basic understanding of the influential factors for nonspecific low-back pain (LBP) among adolescents of southern China. The study was designed as a school-based case control study. Nonspecific LBP is a common health problem in adolescence. Although some behaviors and socio-demographic factors are believed to contribute to the disorder, influential factors of LBP remain undefined. Moreover, until now there is no available information of influential factors for LBP in Chinese adolescents. A total of 1,214 adolescents were involved in the study, including 607 cases with nonspecific LBP and 607 controls without history of nonspecific LBP. A self-administered questionnaire was designed for epidemiological survey to investigate the risk factors for nonspecific LBP. All cases and controls were investigated for their family histories of nonspecific LBP, physical activities, sedentary activities, schoolbag weights, school performances, living conditions, and etc. A 1:1 matched case-control study was conducted on 1,214 adolescents from an elementary school and a secondary school in Guangzhou City, southern China. Family history (odds ratio [OR] 2.57, 95% confidence interval [CI] 1.85-3.58), long duration of carrying schoolbag (OR 1.38, 95% CI 1.11-1.72) and rest position between classes (OR 1.18, 95% CI 1.01-1.39) were positively correlated with self-reported nonspecific LBP. Students regularly playing basketball (OR 1.58, 95% CI 1.09-2.30) was found to be significantly more likely to have LBP. Also, students who feel schoolbag uncomfortable (OR 1.38, 95% CI 1.11-1.72) was found to experience more LBP. Family history, feeling schoolbag uncomfortable, duration of schoolbag carrying, basketball playing and rest position between classes are the major risk factors for nonspecific LBP in adolescents. Wiley Periodicals, Inc.

Confirmatory Factor Analysis of the Cancer Locus of Control Scale.

ERIC Educational Resources Information Center

Henderson, Jessica W.; Donatelle, Rebecca J.; Acock, Alan C.

2002-01-01

Conducted a confirmatory factor analysis of the Cancer Locus of Control scale (M. Watson and others, 1990), administered to 543 women with a history of breast cancer. Results support a three-factor model of the scale and support use of the scale to assess control dimensions. (SLD)

Occupational risk factors for mycosis fungoides: a European multicenter case-control study.

PubMed

Morales-Suárez-Varela, Maria M; Olsen, Jorn; Johansen, Preben; Kaerlev, Linda; Guénel, Pascal; Arveux, Patrick; Wingren, Gun; Hardell, Lennart; Ahrens, Wolfgang; Stang, Andreas; Llopis, Agustin; Merletti, Franco; Aurrekoetxea, Juan Jose; Masala, Giovanna

2004-03-01

Mycosis fungoides (MF) is a rare disease with an unknown etiology. Its distribution suggests that occupational exposures may play a role. In the present study, we searched for occupational factors associated with MF. A European multicenter case-control study on seven rare cancers, including MF, was conducted from 1995 to 1997. Patients between 35 and 69 years of age diagnosed with MF (n = 134) were identified and their diagnoses were checked by a reference pathologist who classified 83 cases as definitive, 35 cases as possible, and 16 cases as not histologically verified. Of the 118 histologically verified cases, 104 were interviewed, of which 76 were definitive cases. As controls, we selected population controls and colon cancer controls to serve all seven case groups. Altogether, 833 colon cancer controls and 2071 population controls were interviewed. The response rate was 91.5% for cases (76 of the 83 definitive cases), and 66.6% for controls. A high risk of MF for men was observed in the industries of other non-metallic mineral products (Odds Ratio [OR] 5.3, 95% confidence interval [CI] = 1.7-16.2) and of wholesale trade (OR 3.6, 95% CI = 1.3-10.5). A high risk was found for female employees in the sector of pulp paper manufacture (OR 14.4, 95% CI = 2.2-95.1). The male occupations with the highest risks were glass formers, potters, and ceramics workers (OR 17.9, 95% CI = 5.4-59.4) and technical salesmen (OR 8.6, 95% CI = 2.4-30.8). For women, the occupations associated with the highest risks were government executives (OR 4.8, 95% CI = 1.0-22.6) and railway and road vehicles loaders (OR 3.9, 95% CI = 1.0-14.0). The results suggest that some occupational factors are associated with MF. Working as glass formers, pottery, and ceramics workers carried the highest risk, and these findings deserve further attention and replication. Females working in the paper and pulp industries may also be exposed to carcinogens of relevance to MF.

Prevalence and factors associated with use of placebo control groups in randomized controlled trials in psoriasis: a cross-sectional study.

PubMed

Katz, Kenneth A; Karlawish, Jason H; Chiang, David S; Bognet, Rachel A; Propert, Katherine J; Margolis, David J

2006-11-01

The ethics and science of using placebo control groups in clinical trials have been widely debated. Few studies, however, have examined factors associated with choice of control group. Our aim was to assess the prevalence of use of placebo controls in randomized controlled trials in psoriasis and to identify factors associated with use of placebo controls in these trials. This is a cross-sectional study of randomized controlled trials in psoriasis published from January 1, 2001 to December 20, 2005 and indexed in the Cochrane Central Register of Controlled Trials. We extracted data on types of control groups used, design issues (number of patients enrolled, primary end point), disease characteristics (psoriasis type and severity), and extrascientific issues (trial location, funding source, and year of publication). We used bivariable and multivariable logistic regression to determine factors associated with use of a placebo control group. Of 194 citations, 187 were available for review. One hundred thirty-five trials from 134 articles in 38 journals met inclusion criteria. Eighty-three trials (61.5%) enrolling 8171 subjects (41.7%) used active controls only, and 52 trials (38.5%) enrolling 11,406 subjects (58.3%) used placebo controls. Adjusted for trial location and funding source, trials significantly more likely to have used placebo controls included those conducted in the United States (odds ratio [OR], 5.79; 95% confidence interval [CI], 2.45-13.68; P < .001) and those funded by pharmaceutical companies (OR, 2.61; 95% CI, 1.19-5.73; P = .02). Predicted frequencies of placebo use ranged from 77.6% (industry-funded, conducted trials in the United States) to 18.6% (non-industry-funded trials not conducted in the United States). Our searches may not have identified all published trials, and we did not have access to data from unpublished trials. Use of placebo controls has been more common in psoriasis trials conducted in the United States and funded by

Family intervention to control type 2 diabetes: a controlled clinical trial.

PubMed

García-Huidobro, Diego; Bittner, Marcela; Brahm, Paulina; Puschel, Klaus

2011-02-01

Chilean patients with type 2 diabetes mellitus (T2DM) have a low rate of blood sugar control. We studied the effectiveness of a culturally sensitive family oriented intervention designed to improve metabolic control in primary care patients with uncontrolled T2DM. Patients with T2DM from three primary care clinics in Santiago, Chile were randomly selected for inclusion if they had a recent HbA1c ≥7%, were between 18 and 70 years old and lived with a family member. Patients from one clinic received the family oriented intervention; patients from the other two (control) clinics received standard care. The intervention involved family members in care and included family counselling during clinic visits, family meetings and home visits. The primary outcome was HbA1c, measured at 6 and 12 months. A total of 243 patients were enrolled and 209 (86%) completed the study. The intervention was fully administered to only 34% of patients in the intervention clinic. The reduction in the HbA1c from baseline to 12 months was not significantly different between clinics. During the second 6-month period, when the intervention was more intensive, the patients in the intervention clinic significantly improved their HbA1c (P < 0.001) compared to the control patients. A family intervention for the control of T2DM was associated with a significant reduction in HbA1c when the intervention was provided. Incomplete implementation, low statistical power and potential confounding variables between groups could be some of the main factors that explain the lack of difference between clinics in the 12-month period.

Alcohol and type 2 diabetes: The role of socioeconomic, lifestyle and psychosocial factors.

PubMed

Agardh, Emilie E; Lundin, Andreas; Lager, Anton; Allebeck, Peter; Koupil, Ilona; Andreasson, Sven; Östenson, Claes-Göran; Danielsson, Anna-Karin

2018-05-01

We investigate (a) alcohol consumption in association with type 2 diabetes, taking heavy episodic drinking (HED), socioeconomic, health and lifestyle, and psychosocial factors into account, and (b) whether a seemingly protective effect of moderate alcohol consumption on type 2 diabetes persists when stratified by occupational position. This population-based longitudinal cohort study comprises 16,223 Swedes aged 18-84 years who answered questionnaires about lifestyle, including alcohol consumption in 2002, and who were followed-up for self-reported or register-based diabetes in 2003-2011. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated in a multivariable-adjusted logistic regression model for all participants and stratified by high and low occupational position. We adjusted for HED, socioeconomic (occupational position, cohabiting status and unemployment), health and lifestyle (body mass index (BMI), blood pressure, smoking, physical inactivity, poor general health, anxiety/depression and psychosocial (low job control and poor social support) characteristics one by one, and the sets of these factors. Moderate consumption was inversely associated with type 2 diabetes after controlling for health and lifestyle (OR=0.47; 95% CI: 0.29-0.79) and psychosocial factors (OR=0.40; 95% CI: 0.22-0.79) when compared to non-drinkers. When adjusting for socioeconomic factors, there was still an inverse but non-significant association (OR=0.59; 95% CI: 0.35-1.00). In those with high occupational position, there was no significant association between moderate consumption and type 2 diabetes after adjusting for socioeconomic (OR=0.67; 95% CI: 0.3-1.52), health and lifestyle (OR=0.70; 95% CI: 0.32-1.5), and psychosocial factors (OR=0.75; 95% CI: 0.23-2.46). On the contrary, in those with low occupational position, ORs decreased from 0.55 (95% CI: 0.28-1.1) to 0.35 (95% CI: 0.15-0.82) when adjusting for psychosocial factors, a decrease that was solely due to low

Environmental factors in the development of narcolepsy with cataplexy. A case-control study.

PubMed

Peraita-Adrados, R; del Rio-Villegas, R; Vela-Bueno, A

2015-06-16

Epidemiological studies suggest the importance of environmental factors in the etiology of narcolepsy-cataplexy in genetically predisposed subjects. To assess the role of environmental factors in the development of narcolepsy-cataplexy, using a case-control design with control subjects being matched for ethnicity and age. All patients were recruited through two outpatient clinics at the community of Madrid, ant the diagnosis of narcolepsy fulfilled the criteria of the International Classification on Sleep Disorders-2005. A questionnaire, including 54 environmental psychological stressor life events and 42 infectious diseases items, was administered to 54 patients. We specifically assessed the stressful factors and infectious diseases that occurred in the year preceding the onset of the first symptom of narcolepsy (excessive daytime sleepiness and/or cataplexy). The same questionnaire was administered to 84 control subjects recruited from non-related family members of the same community. Fifty four patients (55.6% males) answered the questionnaire, The mean age at onset of the first symptom was 21.6 ± 9.3 years, and the mean age at diagnosis was 36.5 ± 12.4 years. The main finding in narcoleptic patients as compared to control subjects was major changes in the 'number of arguments with partner, family, or friends' (odds ratio: 5.2; 95% confidence interval: 1.8-14.5). This can be interpreted as having a protective function and it suggests that psychological mechanisms are present since the beginning of the disease. As for the infectious factors, chickenpox was the most frequently reported. No significant differences were found in terms of total numbers of stress-related and infectious factors between cases and controls. Prospective studies regarding the interaction between environmental and genetic factors are warranted.

Association of Autism with Maternal Infections, Perinatal and Other Risk Factors: A Case-Control Study.

PubMed

Guisso, Dikran Richard; Saadeh, Fadi S; Saab, Dahlia; El Deek, Joud; Chamseddine, Sarah; El Hassan, Hadi Abou; Majari, Ghidaa; Boustany, Rose-Mary

2018-06-01

This case-control study explores the association between pregnancy/birth complications and other factors with Autism Spectrum Disorder (ASD) in Lebanese subjects aged 2-18 years. Researchers interviewed 136 ASD cases from the American University of Beirut Medical Center Special Kids Clinic, and 178 controls selected by systematic digit dialing in the Greater-Beirut area. Male gender (Adjusted Odds Ratio [95% CI]: 3.9 [2.2-7.0]); postpartum feeding difficulties (2.5 [1.2-5.4]); maternal infections/complications during pregnancy (2.9 [1.5-5.5], 2.1 [1.1-3.9]); consanguinity (2.5 [1.0-6.0]); family history of psychiatric disorders (2.2 [1.1-4.4]) were risk factors for ASD. Being born first/second (0.52 [0.28-0.95]) and maternal psychological support during pregnancy (0.49 [0.27-0.89]) were negatively associated with ASD. Identifying ASD correlates is crucial for instigating timely screening and subsequent early intervention.

Tissue Factor-Factor VIIa Complex Triggers Protease Activated Receptor 2-Dependent Growth Factor Release and Migration in Ovarian Cancer

PubMed Central

Chanakira, Alice; Westmark, Pamela R.; Ong, Irene M.; Sheehan, John P.

2017-01-01

Objective Enhanced tissue factor (TF) expression in epithelial ovarian cancer (EOC) is associated with aggressive disease. Our objective was to evaluate the role of the TF-factor VIIa-protease-activated receptor-2 (PAR-2) pathway in human EOC. Methods TCGA RNAseq data from EOC databases were analyzed for PAR expression. Cell and microparticle (MP) associated TF protein expression (Western blot) and MP-associated coagulant activity were determined in human EOC (SKOV-3, OVCAR-3 and CaOV-3) and control cell lines. PAR-1 and PAR-2 protein expression were similarly examined. The PAR dependence of VEGF-A release (ELISA) and chemotactic migration in response to FVIIa and cellular proliferation in response to thrombin was evaluated with small molecule antagonists. Results Relative mRNA expression consistently demonstrated PAR-2>PAR-1≫PAR-3/4 in multiple EOC datasets. Human EOC cell line lysates confirmed expression of TF, PAR-1 and PAR-2 proteins. MPs isolated from EOC cell lines demonstrated markedly enhanced (4–10 fold) TF coagulant activity relative to control cell lines. FVIIa induced a dose-dependent increase in VEGF-A release (2.5-3 fold) from EOC cell lines that was abrogated by the PAR-2 antagonist ENMD-1068. FVIIa treatment of CaOV-3 and OVCAR-3 cells resulted in increased chemotactic migration that was abolished by ENMD-1068. Thrombin induced dose-dependent EOC cell line proliferation was completely reversed by the PAR-1 antagonist vorapaxar. Small molecule antagonists had no effect on these phenotypes without protease present. Conclusions Enhanced activity of the TF-FVIIa-PAR-2 axis may contribute to the EOC progression via PAR-2 dependent signaling that supports an angiogenic and invasive phenotype and local thrombin generation supporting PAR-1 dependent proliferation. PMID:28148395

Controlling Factors of Soil CO2 Efflux in Pinus yunnanensis across Different Stand Ages

PubMed Central

Wang, Shaojun; Zhao, Jixia; Chen, Qibo

2015-01-01

The characteristics of soil respiration (Rs) across different stand ages have not been well investigated. In this study, we identified temporal variation of Rs and its driving factors under three nature forest stands (e.g. 15-yr-old, 30-yr-old, and 45-yr-old) of Pinus yunnanensis in the Plateau of Mid-Yunnan, China. No consistent tendency was found on the change of Rs with the stand ages. Rs was ranked in the order of 30-yr-old > 45-yr-old >15-yr-old. Rs in 15-yr-old stand was the most sensitive to soil temperature (Ts) among the three sites. However, Ts only explained 30-40% of the seasonal dynamics of Rs at the site. Soil water content (Sw) was the major controlling factor of temporal variation at the three sites. Sw explained 88-93% of seasonal variations of Rs in the 30-yr-old stand, and 63.7-72.7% in the 15-yr-old and 79.1-79.6% in the 45-yr-old stands. In addition, we found that pH, available nitrogen (AN), C/N and total phosphorus (TP) contributed significantly to the seasonal variation of Rs. Sw was significantly related with pH, total nitrogen (TN), AN and TP, suggesting that Sw can affect Rs through improving soil acid-base property and soil texture, and increasing availability of soil nutrient. The results indicated that besides soil water, soil properties (e. g. pH, AN, C/N and TP) were also the important in controlling the temporal variations of Rs across different stand ages in the nature forestry. PMID:25996943

Krüppel-Like Factor 1 (KLF1), KLF2, and Myc Control a Regulatory Network Essential for Embryonic Erythropoiesis

PubMed Central

Pang, Christopher J.; Lemsaddek, Wafaa; Alhashem, Yousef N.; Bondzi, Cornelius; Redmond, Latasha C.; Ah-Son, Nicolas; Dumur, Catherine I.; Archer, Kellie J.; Haar, Jack L.

2012-01-01

The Krüppel-like factor 1 (KLF1) and KLF2 positively regulate embryonic β-globin expression and have additional overlapping roles in embryonic (primitive) erythropoiesis. KLF1−/− KLF2−/− double knockout mice are anemic at embryonic day 10.5 (E10.5) and die by E11.5, in contrast to single knockouts. To investigate the combined roles of KLF1 and KLF2 in primitive erythropoiesis, expression profiling of E9.5 erythroid cells was performed. A limited number of genes had a significantly decreasing trend of expression in wild-type, KLF1−/−, and KLF1−/− KLF2−/− mice. Among these, the gene for Myc (c-Myc) emerged as a central node in the most significant gene network. The expression of the Myc gene is synergistically regulated by KLF1 and KLF2, and both factors bind the Myc promoters. To characterize the role of Myc in primitive erythropoiesis, ablation was performed specifically in mouse embryonic proerythroblast cells. After E9.5, these embryos exhibit an arrest in the normal expansion of circulating red cells and develop anemia, analogous to KLF1−/− KLF2−/− embryos. In the absence of Myc, circulating erythroid cells do not show the normal increase in α- and β-like globin gene expression but, interestingly, have accelerated erythroid cell maturation between E9.5 and E11.5. This study reveals a novel regulatory network by which KLF1 and KLF2 regulate Myc to control the primitive erythropoietic program. PMID:22566683

Control of Glycemia and Cardiovascular Risk Factors in Patients With Type 2 Diabetes in Primary Care in Catalonia (Spain)

PubMed Central

Vinagre, Irene; Mata-Cases, Manel; Hermosilla, Eduard; Morros, Rosa; Fina, Francesc; Rosell, Magdalena; Castell, Conxa; Franch-Nadal, Josep; Bolíbar, Bonaventura; Mauricio, Didac

2012-01-01

OBJECTIVE The objective of this study was to analyze the clinical characteristics and levels of glycemic and cardiovascular risk factor control in patients with type 2 diabetes that are in primary health care centers in Catalonia (Spain). RESEARCH DESIGN AND METHODS This was a cross-sectional study of a total population of 3,755,038 individuals aged 31–90 years at the end of 2009. Clinical data were obtained retrospectively from electronic clinical records. RESULTS A total of 286,791 patients with type 2 diabetes were identified (7.6%). Fifty-four percent were men, mean (SD) age was 68.2 (11.4) years, and mean duration of disease was 6.5 (5.1) years. The mean (SD) A1C value was 7.15 (1.5)%, and 56% of the patients had A1C values ≤7%. The mean (SD) blood pressure (BP) values were 137.2 (13.8)/76.4 (8.3) mmHg, mean total cholesterol concentration was 192 (38.6) mg/dL, mean HDL cholesterol concentration was 49.3 (13.2) mg/dL, mean LDL cholesterol (LDL-C) concentration was 112.5 (32.4) mg/dL, and mean BMI was 29.6 (5) kg/m2. Thirty-one percent of the patients had BP values ≤130/80 mmHg, 37.9% had LDL-C values ≤100 mg/dL, and 45.4% had BMI values ≤30 kg/m2. Twenty-two percent were managed exclusively with lifestyle changes. Regarding medicated diabetic patients, 46.9, 22.9, and 2.8% were prescribed one, two, or three antidiabetic drugs, respectively, and 23.4% received insulin therapy. CONCLUSIONS The results from this study indicate a similar or improved control of glycemia, lipids, and BP in patients with type 2 diabetes when compared with previous studies performed in Spain and elsewhere. PMID:22344609

Pore structure characterization of Chang-7 tight sandstone using MICP combined with N2GA techniques and its geological control factors

NASA Astrophysics Data System (ADS)

Cao, Zhe; Liu, Guangdi; Zhan, Hongbin; Li, Chaozheng; You, Yuan; Yang, Chengyu; Jiang, Hang

2016-11-01

Understanding the pore networks of unconventional tight reservoirs such as tight sandstones and shales is crucial for extracting oil/gas from such reservoirs. Mercury injection capillary pressure (MICP) and N2 gas adsorption (N2GA) are performed to evaluate pore structure of Chang-7 tight sandstone. Thin section observation, scanning electron microscope, grain size analysis, mineral composition analysis, and porosity measurement are applied to investigate geological control factors of pore structure. Grain size is positively correlated with detrital mineral content and grain size standard deviation while negatively related to clay content. Detrital mineral content and grain size are positively correlated with porosity, pore throat radius and withdrawal efficiency and negatively related to capillary pressure and pore-to-throat size ratio; while interstitial material is negatively correlated with above mentioned factors. Well sorted sediments with high debris usually possess strong compaction resistance to preserve original pores. Although many inter-crystalline pores are produced in clay minerals, this type of pores is not the most important contributor to porosity. Besides this, pore shape determined by N2GA hysteresis loop is consistent with SEM observation on clay inter-crystalline pores while BJH pore volume is positively related with clay content, suggesting N2GA is suitable for describing clay inter-crystalline pores in tight sandstones.

Factors associated with obesity: a case-control study of young adult Singaporean males.

PubMed

Shi, Haiyuan; Jiang, Bo; Wei Sim, Joshua Dao; Chum, Zhi Zhen; Ali, Noreffendy Bin; Toh, Mun Heng

2014-10-01

A case-control study among Singapore Armed Forces' newly enlisted Servicemen was conducted to examine factors associated with male obesity. Four hundred and fifty-nine individuals from the Obese Basic Military Training program were selected as "cases" (average age: 19.5, body mass index: 30.4) and another 340 individuals were selected from the Normal Basic Military Training program as "controls" (average age: 19.3, body mass index: 21.4). Information such as family background, socioeconomic factors, and lifestyle practices were captured using facilitator-led questionnaires. Several variables were significantly associated with obesity after adjustments for possible confounders. These include childhood obesity (odds ratio [OR] = 2.06), less than an hour of exercise per day (OR = 2.97), Indian ethnicity (OR = 2.22), specific education backgrounds (especially that of Institute of Technical Education-OR = 2.75), father's employment at nonmanagerial/professional jobs (OR = 1.52), mother's employment at managerial/professional jobs (OR = 2.02), regular smoking (OR = 1.73) and alcohol consumption (OR = 2.26), 6 hours or less of sleep (OR = 3.73), obesity among family members (OR = 1.86 for mother; OR = 2.98 for siblings), parental history of diabetes mellitus (OR = 2.22 for father; OR = 2.70 for mother), and eating at inexpensive local food stalls (OR = 1.82). Our study found that a number of factors, ranging from personal and family backgrounds to lifestyle choices, were significantly associated with obesity among male youths. Reprint & Copyright © 2014 Association of Military Surgeons of the U.S.

Power factor improvement in three-phase networks with unbalanced inductive loads using the Roederstein ESTAmat RPR power factor controller

NASA Astrophysics Data System (ADS)

Diniş, C. M.; Cunţan, C. D.; Rob, R. O. S.; Popa, G. N.

2018-01-01

The paper presents the analysis of a power factor with capacitors banks, without series coils, used for improving power factor for a three-phase and single-phase inductive loads. In the experimental measurements, to improve the power factor, the Roederstein ESTAmat RPR power factor controller can command up to twelve capacitors banks, while experimenting using only six capacitors banks. Six delta capacitors banks with approximately equal reactive powers were used for experimentation. The experimental measurements were carried out with a three-phase power quality analyser which worked in three cases: a case without a controller with all capacitors banks permanently parallel connected with network, and two other cases with power factor controller (one with setting power factor at 0.92 and the other one at 1). When performing experiments with the power factor controller, a current transformer was used to measure the current on one phase (at a more charged or less loaded phase).

Factors associated with home delivery in Bahirdar, Ethiopia: a case control study.

PubMed

Abebe, Fantu; Berhane, Yemane; Girma, Belaineh

2012-11-24

In Ethiopia although pregnant mothers increasingly attend antenatal clinics, utilization of skilled delivery service remains very low. The individual or health system factors that affect women's preferences for delivery places are not well known. A case control study was conducted in July 2010 to assess factors associated with utilization of institutional delivery service. A total of 324 mothers who recently delivered and visited either postnatal care or sought immunization services were included. Cases (n = 108) were mothers who gave birth at home and controls (n = 216) were those who delivered at health facility. Pre-tested and standardized questionnaires were used to collect relevant data by trained data collectors. Logistic regression model was used to control for confounding. The likelihood of delivering at home was greater among mothers with inadequate knowledge of pregnancy related services (AOR = 62, 95% CI: 3, 128.4), those who started attending ANC after 24 weeks of gestation (AOR 8.7, 95% CI: 2.2, 33.3), mothers having no formal education (Adjusted OR 4.2, 95% CI 1.63, 11.27) and rural residents (AOR = 3.6, 95%CI: 1.4, 9.0). The predominant factors associated with home delivery services were lack of knowledge about obstetrics care, delay in starting Antenatal Care (ANC) follow up, having, Illiteracy and rural residence. Audience specific behavioral change communication should be designed to improve the demand for delivery services. Health professionals should take the opportunity to encourage mothers attend delivery services during ANC follow up. Improvements should be made in social conditions including literacy and major social mobilization endeavors.

Three-phase power factor controller with induced EMF sensing

NASA Technical Reports Server (NTRS)

Nola, F. J. (Inventor)

1984-01-01

A power factor controller for an ac induction motor is provided which is of the type comprising thyristor switches connected in series with the motor, phase detectors for sensing the motor current and voltage and providing an output proportional to the phase difference between the motor voltage and current, and a control circuit, responsive to the output of the phase detector and to a power factor command signal, for controlling switching of the thyristor. The invention involves sensing the induced emf produced by the motor during the time interval when the thyristor is off and for producing a corresponding feedback signal for controlling switching of the thyristor. The sensed emf is also used to enhance soft starting of the motor.

Experience with multiple control groups in a large population-based case-control study on genetic and environmental risk factors.

PubMed

Pomp, E R; Van Stralen, K J; Le Cessie, S; Vandenbroucke, J P; Rosendaal, F R; Doggen, C J M

2010-07-01

We discuss the analytic and practical considerations in a large case-control study that had two control groups; the first control group consisting of partners of patients and the second obtained by random digit dialling (RDD). As an example of the evaluation of a general lifestyle factor, we present body mass index (BMI). Both control groups had lower BMIs than the patients. The distribution in the partner controls was closer to that of the patients, likely due to similar lifestyles. A statistical approach was used to pool the results of both analyses, wherein partners were analyzed with a matched analysis, while RDDs were analyzed without matching. Even with a matched analysis, the odds ratio with partner controls remained closer to unity than with RDD controls, which is probably due to unmeasured confounders in the comparison with the random controls as well as intermediary factors. However, when studying injuries as a risk factor, the odds ratio remained higher with partner control subjects than with RRD control subjects, even after taking the matching into account. Finally we used factor V Leiden as an example of a genetic risk factor. The frequencies of factor V Leiden were identical in both control groups, indicating that for the analyses of this genetic risk factor the two control groups could be combined in a single unmatched analysis. In conclusion, the effect measures with the two control groups were in the same direction, and of the same order of magnitude. Moreover, it was not always the same control group that produced the higher or lower estimates, and a matched analysis did not remedy the differences. Our experience with the intricacies of dealing with two control groups may be useful to others when thinking about an optimal research design or the best statistical approach.

CaAP2 transcription factor is a candidate gene for a flowering repressor and a candidate for controlling natural variation of flowering time in Capsicum annuum.

PubMed

Borovsky, Yelena; Sharma, Vinod K; Verbakel, Henk; Paran, Ilan

2015-06-01

The APETALA2 transcription factor homolog CaAP2 is a candidate gene for a flowering repressor in pepper, as revealed by induced-mutation phenotype, and a candidate underlying a major QTL controlling natural variation in flowering time. To decipher the genetic control of transition to flowering in pepper (Capsicum spp.) and determine the extent of gene function conservation compared to model species, we isolated and characterized several ethyl methanesulfonate (EMS)-induced mutants that vary in their flowering time compared to the wild type. In the present study, we report on the isolation of an early-flowering mutant that flowers after four leaves on the primary stem compared to nine leaves in the wild-type 'Maor'. By genetic mapping and sequencing of putative candidate genes linked to the mutant phenotype, we identified a member of the APETALA2 (AP2) transcription factor family, CaAP2, which was disrupted in the early-flowering mutant. CaAP2 is a likely ortholog of AP2 that functions as a repressor of flowering in Arabidopsis. To test whether CaAP2 has an effect on controlling natural variation in the transition to flowering in pepper, we performed QTL mapping for flowering time in a cross between early and late-flowering C. annuum accessions. We identified a major QTL in a region of chromosome 2 in which CaAP2 was the most significant marker, explaining 52 % of the phenotypic variation of the trait. Sequence comparison of the CaAP2 open reading frames in the two parents used for QTL mapping did not reveal significant variation. In contrast, significant differences in expression level of CaAP2 were detected between near-isogenic lines that differ for the flowering time QTL, supporting the putative function of CaAP2 as a major repressor of flowering in pepper.

Transcriptional repression by ApiAP2 factors is central to chronic toxoplasmosis

PubMed Central

Worth, Danielle; Huang, Sherri

2018-01-01

Tachyzoite to bradyzoite development in Toxoplasma is marked by major changes in gene expression resulting in a parasite that expresses a new repertoire of surface antigens hidden inside a modified parasitophorous vacuole called the tissue cyst. The factors that control this important life cycle transition are not well understood. Here we describe an important transcriptional repressor mechanism controlling bradyzoite differentiation that operates in the tachyzoite stage. The ApiAP2 factor, AP2IV-4, is a nuclear factor dynamically expressed in late S phase through mitosis/cytokinesis of the tachyzoite cell cycle. Remarkably, deletion of the AP2IV-4 locus resulted in the expression of a subset of bradyzoite-specific proteins in replicating tachyzoites that included tissue cyst wall components BPK1, MCP4, CST1 and the surface antigen SRS9. In the murine animal model, the mis-timing of bradyzoite antigens in tachyzoites lacking AP2IV-4 caused a potent inflammatory monocyte immune response that effectively eliminated this parasite and prevented tissue cyst formation in mouse brain tissue. Altogether, these results indicate that suppression of bradyzoite antigens by AP2IV-4 during acute infection is required for Toxoplasma to successfully establish a chronic infection in the immune-competent host. PMID:29718996

Transcriptional repression by ApiAP2 factors is central to chronic toxoplasmosis.

PubMed

Radke, Joshua B; Worth, Danielle; Hong, David; Huang, Sherri; Sullivan, William J; Wilson, Emma H; White, Michael W

2018-05-01

Tachyzoite to bradyzoite development in Toxoplasma is marked by major changes in gene expression resulting in a parasite that expresses a new repertoire of surface antigens hidden inside a modified parasitophorous vacuole called the tissue cyst. The factors that control this important life cycle transition are not well understood. Here we describe an important transcriptional repressor mechanism controlling bradyzoite differentiation that operates in the tachyzoite stage. The ApiAP2 factor, AP2IV-4, is a nuclear factor dynamically expressed in late S phase through mitosis/cytokinesis of the tachyzoite cell cycle. Remarkably, deletion of the AP2IV-4 locus resulted in the expression of a subset of bradyzoite-specific proteins in replicating tachyzoites that included tissue cyst wall components BPK1, MCP4, CST1 and the surface antigen SRS9. In the murine animal model, the mis-timing of bradyzoite antigens in tachyzoites lacking AP2IV-4 caused a potent inflammatory monocyte immune response that effectively eliminated this parasite and prevented tissue cyst formation in mouse brain tissue. Altogether, these results indicate that suppression of bradyzoite antigens by AP2IV-4 during acute infection is required for Toxoplasma to successfully establish a chronic infection in the immune-competent host.

The relationship between microalbuminuria, cardiovascular risk factors and disease management in type 2 diabetes.

PubMed

Udenze, I C; Azinge, E C; Ebuehi, O A T; Awolola, N A; Adekola, O O; Menkiti, I; Irurhe, N K

2012-01-01

In patients with type 2 diabetes, microalbuminuria is an early clinical sign suggestive of vascular damage to the glomerulus. Microalbuminuria has also been currently reported as an important risk factor for cardiovascular disease and becomes relevant in the management of type 2 diabetes. This study is to determine the prevalence of microalbuminuria, identify the risk factors associated with microalbuminuria in type 2 diabetes, and to asses the achievement of treatment goals for cardiovascular risk reduction in type 2 diabetics. Seventy- two subjects with microalbuminuria were recruited from three hundred consecutively screened type 2 diabetics attending the Diabetic Clinic at the Lagos University Teaching Hospital. Clinical data were obtained by interviewing the participants. Anthropometric measurements were made and blood specimens were collected for analysis. The prevalence of microalbuminuria was twenty-four percent (24%) in type 2 diabetes. Multiple logistic regression identified duration of diabetes (odds ratio 1.3 (95% CI; 0.03-1.58), hypertension(odds ratio 5.2 (95% Cl; 1.24-18.62), Body mass index (BMI) (odds ratio 1.27 (95% CI; 1.0-1.6), waist/hip ratio (WHR) (odds ratio 1.9 (95% Cl; 1.3-3.5), andHbA,c (odds ratio 6.6 (95% Cl; 1.02-27) as independent risk factors associated with microalbuminuria in type 2 diabetics. Optimum blood pressure, glycemic and weight control were achieved in eighty five percent (85%), fifty eight percent (58%) and nineteen percent (19%) of the type 2 diabetes respectively. This study showed that microalbuminuria is common among patients with type 2 diabetes. It also showed improvement in glycemic control and modifiable cardiovascular risk factor control when compared with previous studies.

Prenatal and perinatal risk factors and testicular cancer: a hospital-based case-control study.

PubMed

Sonke, Gabe S; Chang, Shine; Strom, Sara S; Sweeney, Anne M; Annegers, J Fred; Sigurdson, Alice J

2007-01-01

Some evidence exists to support the hypothesis that elevated levels of circulating maternal estrogens during early pregnancy may increase risk of testicular germ cell cancer. However, the results from studies evaluating maternal factors have been mixed. We evaluated maternal factors, particularly those associated with excess estrogen levels, as risk factors for testicular cancer. We conducted a hospital-based case-control study at The University of Texas M. D. Anderson Cancer Center in Houston, Texas of 144 testicular cancer patients diagnosed between 1990 and 1996 and 86 friend controls matched to cases on age, race, and state of residence. Risk factor data about the mother, the son, and the pregnancy were obtained from the mothers by telephone interviews and from the sons by self-administered questionnaires. Extreme nausea during the first trimester of pregnancy was associated with an elevated risk of testicular cancer [odds ratio (OR) = 2.0; 95% confidence interval (CI) = 1.0-3.9]. Adjustment for potential confounders slightly lowered this risk (OR = 1.8; 95% CI = 0.9-3.8). Risks were modestly increased for other factors that are proxy measures for maternal estrogens, including preterm delivery (OR = 2.2; 95% CI = 0.4-12.9), birth weight <3000 g (OR = 2.4: 95% CI = 0.7-8.1), and birth weight >4000 g (OR = 1.7; 95% CI = 0.9-3.2), albeit nonsignificantly so. Our finding that severe nausea was associated with increased testicular cancer risk adds evidence to support the in utero estrogen exposure hypothesis because nausea early in pregnancy is related to rising levels of circulating estrogens. For other factors, which are less direct measures of maternal estrogens, the modest associations found indicate a suggestive pattern in support of the excess estrogen hypothesis.

Krüppel-like factors: three fingers in control.

PubMed

Swamynathan, Shivalingappa K

2010-04-01

Krüppel-like factors (KLFs), members of the zinc-finger family of transcription factors capable of binding GC-rich sequences, have emerged as critical regulators of important functions all over the body. They are characterised by a highly conserved C-terminal DNA-binding motif containing three C2H2 zinc-finger domains, with variable N-terminal regulatory domains. Currently, there are 17 KLFs annotated in the human genome. In spite of their structural similarity to one another, the genes encoding different KLFs are scattered all over the genome. By virtue of their ability to activate and/or repress the expression of a large number of genes, KLFs regulate a diverse array of developmental events and cellular processes, such as erythropoiesis, cardiac remodelling, adipogenesis, maintenance of stem cells, epithelial barrier formation, control of cell proliferation and neoplasia, flow-mediated endothelial gene expression, skeletal and smooth muscle development, gluconeogenesis, monocyte activation, intestinal and conjunctival goblet cell development, retinal neuronal regeneration and neonatal lung development. Characteristic features, nomenclature, evolution and functional diversities of the human KLFs are reviewed here.

Maternal sleep deprivation, sedentary lifestyle and cooking smoke: Risk factors for miscarriage: A case control study.

PubMed

Samaraweera, Yasindu; Abeysena, Chrishantha

2010-08-01

To determine risk factors for miscarriage. A case control study was carried out at the gynaecological wards and antenatal clinics of the De Soysa Maternity Hospital in Sri Lanka. A case was defined as that of mothers with a confirmed diagnosis of partial or full expulsion of the fetus during the first 28 weeks of gestation. Controls comprised ante-natal clinic attendees whose period of gestation was <28 weeks and carrying a viable fetus. Two hundred and thirty cases and 504 controls were selected. A pre-tested interviewer-administered questionnaire and modified life events inventory were used to gather data. Multivariate logistic regression was applied separately for first and second trimester miscarriages and the results were expressed as odds ratios (OR) and as 95% confidence intervals (95% CI). Sleeping < or =8 h/day (OR:3.80, 95% CI:1.01-14.3) was found to be a risk factor for first trimester miscarriage controlling for the effect of period of gestation. Sleeping < or =8 h/day (OR:2.04, 95% CI:1.24-3.37), standing < or =3 h/day (OR:1.83, 95% CI:1.08-3.10), exposure to cooking smoke (OR:3.83, 95% CI:1.50-9.90) and physical trauma during the pregnancy (OR:43.2, 95% CI:4.55-411.4) were found to be risk factors for second trimester miscarriage controlling for the effect of period of gestation. Sleep deprivation, a sedentary lifestyle, exposure to cooking smoke and physical trauma during pregnancy were risk factors for miscarriage. Most of the risk factors are therefore modifiable.

[Risk factors associated with non-alcoholic fatty liver disease: a case-control study].

PubMed

Caballería, Llorenç; Arteaga, Ingrid; Pera, Guillem; Rodríguez, Lluís; Alumà, Alba; Auladell, Maria Antònia; Torán, Pere

2013-09-21

To establish the factors associated with the presence of non-alcoholic fatty liver disease (NAFLD) and evaluate the influence of each component constituting the metabolic syndrome (MS) and the risk of developing NAFLD. We performed a multicenter, population-based, observational, analytical study of cases and controls. A case was defined as any patient fulfilling the inclusion criteria and presenting NAFLD by abdominal echography for any reason. A control was randomly selected for each case, from the same health center and of the same age and sex. All the cases underwent anamnesis, physical examination, complete biochemical analyses and determination of MS according to the National Cholesterol Education Program-Adult Treatment Panel III criteria. All the controls also underwent an abdominal echography. We included 327 cases and 377 controls with a mean age of 56 ± 12 years for the cases and of 55 ± 13 years for the controls (range: 17 and 80 years); 52.0% of the cases were males and 49.1% of males were controls. The risk factors associated with NAFLD were obesity (odds ratio [OR] 3.82, 95% confidence interval [95% CI] 2.19-6.66), MS (OR 1.73, 95% CI 1.09-2.75), insulin resistance (OR 3.65, 95% CI 2.18-6.12), and an increase in alanine aminotransferase (ALT) (OR 4.72, 95% CI 2.58-8.61) and gamma glutamyl transferase values (GGT) (OR 1.95, 95% CI 1.14-3.34). The components of the MS best predicting NAFLD were hyperglycemia (OR 1.65, 95% CI1.06-2.56) and triglyceride values (OR 1.75, 95% CI1.13-2.72). The independent variables associated with NAFLD were obesity, insulin resistance and elevated ALT and GGT. The components of MS best predicting NAFLD were hyperglycemia and an increase in triglyceride values. Copyright © 2012 Elsevier España, S.L. All rights reserved.

Syk Mediates BCR- and CD40-Signaling Intergration during B Cell Activation

PubMed Central

Ying, Haiyan; Li, Zhenping; Yang, Lifen; Zhang, Jian

2010-01-01

CD40 is essential for optimal B cell activation. It has been shown that CD40 stimulation can augment BCR-induced B cell responses, but the molecular mechanism(s) by which CD40 regulates BCR signaling is poorly understood. In this report, we attempted to characterize the signaling synergy between BCR- and CD40-mediated pathways during B cell activation. We found that spleen tyrosine kinase (Syk) is involved in CD40 signaling, and is synergistically activated in B cells in response to BCR/CD40 costimulation. CD40 stimulation alone also activates B cell linker (BLNK), Bruton tyrosine kinase (Btk), and Vav-2 downstream of Syk, and significantly enhances BCR-induced formation of complex consisting of, Vav-2, Btk, BLNK, and phospholipase C-gamma2 (PLC-γ2) leading to activation of extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase, Akt, and NF-κB required for optimal B cell activation. Therefore, our data suggest that CD40 can strengthen BCR-signaling pathway and quantitatively modify BCR signaling during B cell activation. PMID:21074890

Priming Dental Pulp Stem Cells With Fibroblast Growth Factor-2 Increases Angiogenesis of Implanted Tissue-Engineered Constructs Through Hepatocyte Growth Factor and Vascular Endothelial Growth Factor Secretion

PubMed Central

Gorin, Caroline; Rochefort, Gael Y.; Bascetin, Rumeyza; Ying, Hanru; Lesieur, Julie; Sadoine, Jérémy; Beckouche, Nathan; Berndt, Sarah; Novais, Anita; Lesage, Matthieu; Hosten, Benoit; Vercellino, Laetitia; Merlet, Pascal; Le-Denmat, Dominique; Marchiol, Carmen; Letourneur, Didier; Nicoletti, Antonino; Vital, Sibylle Opsahl; Poliard, Anne; Salmon, Benjamin; Germain, Stéphane

2016-01-01

Tissue engineering strategies based on implanting cellularized biomaterials are promising therapeutic approaches for the reconstruction of large tissue defects. A major hurdle for the reliable establishment of such therapeutic approaches is the lack of rapid blood perfusion of the tissue construct to provide oxygen and nutrients. Numerous sources of mesenchymal stem cells (MSCs) displaying angiogenic potential have been characterized in the past years, including the adult dental pulp. Establishment of efficient strategies for improving angiogenesis in tissue constructs is nevertheless still an important challenge. Hypoxia was proposed as a priming treatment owing to its capacity to enhance the angiogenic potential of stem cells through vascular endothelial growth factor (VEGF) release. The present study aimed to characterize additional key factors regulating the angiogenic capacity of such MSCs, namely, dental pulp stem cells derived from deciduous teeth (SHED). We identified fibroblast growth factor-2 (FGF-2) as a potent inducer of the release of VEGF and hepatocyte growth factor (HGF) by SHED. We found that FGF-2 limited hypoxia-induced downregulation of HGF release. Using three-dimensional culture models of angiogenesis, we demonstrated that VEGF and HGF were both responsible for the high angiogenic potential of SHED through direct targeting of endothelial cells. In addition, FGF-2 treatment increased the fraction of Stro-1+/CD146+ progenitor cells. We then applied in vitro FGF-2 priming to SHED before encapsulation in hydrogels and in vivo subcutaneous implantation. Our results showed that FGF-2 priming is more efficient than hypoxia at increasing SHED-induced vascularization compared with nonprimed controls. Altogether, these data demonstrate that FGF-2 priming enhances the angiogenic potential of SHED through the secretion of both HGF and VEGF. Significance The results from the present study show that fibroblast growth factor-2 (FGF-2) priming is more

Risk factors for the development of colorectal carcinoma: A case control study from South India

PubMed Central

Iswarya, Santhana Krishnan; Premarajan, Kariyarath Cheriyath; Kar, Sitanshu Sekhar; Kumar, Sathasivam Suresh; Kate, Vikram

2016-01-01

AIM: To study the association of colorectal carcinoma (CRC) with diet, smoking, alcohol, physical activity, body mass index, family history and diabetes. METHODS: All consecutive patients with CRC confirmed by histopathology diagnosis were included. Age (± 5 years) and gender matched controls were selected among the patients admitted in surgery ward for various conditions without any co-existing malignancy. Food frequency questionnaire (FFQ) was developed and validated after pretesting by investigator trained in data collection techniques. Cases and controls were interviewed ensuring privacy, in similar interview setting, with same duration of time for both cases and controls without any leading question. Biological variables like family history of CRC in first degree relatives, history of diabetes mellitus; behavioral factors like tobacco use both smoking and smokeless form, alcohol consumption and physical activity were recorded. Dietary details were recorded using a FFQ consisting 29 food items with seven categories. Analysis was done using appropriate statistical methods. RESULTS: Ninety-four histopathologically confirmed cases of CRC and equal number of age and gender matched controls treated over a period of two years were studied. Age distribution, mean age, male to female ratio, education level and socioeconomic status were similar in cases and controls. Intake of food items was categorized into tertile due to skewed distribution of subjects as per recommended cut off for consumption of food item. On univariate analysis red meat [OR = 7.4 (2.935-18.732)], egg [OR = 5.1 (2.26-11.36)], fish, fried food and oil consumption were found to be risk factors for CRC. On multivariate analysis red meat consumption of more than 2-3 times a month (OR = 5.4; 95%CI: 1.55-19.05) and egg consumption of more than 2-3 times a week (OR = 3.67; 95%CI: 1.23-9.35) were found to be independent risk factors for the development of CRC. CONCLUSION: Egg and red meat consumption found

Control of trichome formation in Arabidopsis by poplar single-repeat R3 MYB transcription factors

PubMed Central

Zhou, Limei; Zheng, Kaijie; Wang, Xiaoyu; Tian, Hainan; Wang, Xianling; Wang, Shucai

2014-01-01

In Arabidopsis, trichome formation is regulated by the interplay of R3 MYBs and several others transcription factors including the WD40-repeat protein TRANSPARENT TESTA GLABRA1 (TTG1), the R2R3 MYB transcription factor GLABRA1 (GL1), the bHLH transcription factor GLABRA3 (GL3) or ENHANCER OF GLABRA3 (EGL3), and the homeodomain protein GLABRA2 (GL2). R3 MYBs including TRICHOMELESS1 (TCL1), TCL2, TRYPTICHON (TRY), CAPRICE (CPC), ENHANCER OF TRY AND CPC1 (ETC1), ETC2 and ETC3 negatively regulate trichome formation by competing with GL1 for binding GL3 or EGL3, thus blocking the formation of TTG1–GL3/EGL3–GL1, an activator complex required for the activation of the trichome positive regulator gene GL2. However, it is largely unknown if R3 MYBs in other plant species especially woody plants have similar functions. By BLASTing the Populus trichocarpa protein database using the entire amino acid sequence of TCL1, an Arabidopsis R3 MYB transcription factor, we identified a total of eight R3 MYB transcription factor genes in poplar, namely P. trichocarpa TRICHOMELESS1 through 8 (PtrTCL1–PtrTCL8). The amino acid signature required for interacting with bHLH transcription factors and the amino acids required for cell-to-cell movement of R3 MYBs are not fully conserved in all PtrTCLs. When tested in Arabidopsis protoplasts, however, all PtrTCLs interacted with GL3. Expressing each of the eight PtrTCL genes in Arabidopsis resulted in either glabrous phenotypes or plants with reduced trichome numbers, and expression levels of GL2 in all transgenic plants tested were greatly reduced. Expression of PtrTCL1 under the control of TCL1 native promoter almost completely complemented the mutant phenotype of tcl. In contrast, expression of PtrTCL1 under the control of TRY native promoter in the try mutant, or under the control of CPC native promoter in the cpc mutant resulted in glabrous phenotypes, suggesting that PtrTCL1 functions similarly to TCL1, but not TRY and CPC. PMID

The Acetylase/Deacetylase Couple CREB-binding Protein/Sirtuin 1 Controls Hypoxia-inducible Factor 2 Signaling*

PubMed Central

Chen, Rui; Xu, Min; Hogg, Richard T.; Li, Jiwen; Little, Bertis; Gerard, Robert D.; Garcia, Joseph A.

2012-01-01

Hypoxia-inducible factors (HIFs) are oxygen-sensitive transcription factors. HIF-1α plays a prominent role in hypoxic gene induction. HIF-2α target genes are more restricted but include erythropoietin (Epo), one of the most highly hypoxia-inducible genes in mammals. We previously reported that HIF-2α is acetylated during hypoxia but is rapidly deacetylated by the stress-responsive deacetylase Sirtuin 1. We now demonstrate that the lysine acetyltransferases cAMP-response element-binding protein-binding protein (CBP) and p300 are required for efficient Epo induction during hypoxia. However, despite close structural similarity, the roles of CBP and p300 differ in HIF signaling. CBP acetylates HIF-2α, is a major coactivator for HIF-2-mediated Epo induction, and is required for Sirt1 augmentation of HIF-2 signaling during hypoxia in Hep3B cells. In comparison, p300 is a major contributor for HIF-1 signaling as indicated by induction of Pgk1. Whereas CBP can bind with HIF-2α independent of the HIF-2α C-terminal activation domain via enzyme/substrate interactions, p300 only complexes with HIF-2α through the C-terminal activation domain. Maximal CBP/HIF-2 signaling requires intact CBP acetyltransferase activity in both Hep3B cells as well as in mice. PMID:22807441

Risk factors of post-traumatic stress disorder (PTSD) after Wenchuan earthquake: a case control study.

PubMed

Cheng, Yongzhong; Wang, Fang; Wen, Jin; Shi, Yingkang

2014-01-01

Few clues were found in the literature about the independent risk factors for PTSD among earthquake survivors in Sichuan province three years after the 2008 earthquake. Ours was the first case-control study with matching factors of age and distance from the epicenter among survivors age 16 years or older, three years after the catastrophe. To identify independent risk factors for PTSD among earthquake survivors. We performed a population-based matched case-control study. The cases were drawn from earthquake areas three years after the Wenchuan earthquake, including 113 cases who met positive criteria for PTSD symptoms according to the PCL-C (PTSD Checklist-Civilian Version) score and 452 controls who did not meet the criteria. Cases and controls were matched individually by birth year (+ three years) and the town they lived in when the earthquake occurred. Independent risk factors for PTSD symptoms included two-week disease prevalence (odds ratio [OR],1.92; 95% confidence interval [CI],1.18-3.13), witnessing someone being killed in the earthquake (OR, 2.04;95%CI, 1.17-3.58), having no regular income after the earthquake (OR, 0.52; 95%CI, 0.28-0.98), receiving mental health support only one time after the earthquake (OR, 2.43; 95%CI, 1.09-5.42) and lower social support (lower PSSS score) (OR, 0.95; 95%CI, 0.93-0.97). Earthquake experience, suffering from physical illnesses, lack of stable income, and lower social support were associated with PTSD symptoms.

Elevated-CO2 Response of Stomata and Its Dependence on Environmental Factors

PubMed Central

Xu, Zhenzhu; Jiang, Yanling; Jia, Bingrui; Zhou, Guangsheng

2016-01-01

Stomata control the flow of gases between plants and the atmosphere. This review is centered on stomatal responses to elevated CO2 concentration and considers other key environmental factors and underlying mechanisms at multiple levels. First, an outline of general responses in stomatal conductance under elevated CO2 is presented. Second, stomatal density response, its development, and the trade-off with leaf growth under elevated CO2 conditions are depicted. Third, the molecular mechanism regulating guard cell movement at elevated CO2 is suggested. Finally, the interactive effects of elevated CO2 with other factors critical to stomatal behavior are reviewed. It may be useful to better understand how stomata respond to elevated CO2 levels while considering other key environmental factors and mechanisms, including molecular mechanism, biochemical processes, and ecophysiological regulation. This understanding may provide profound new insights into how plants cope with climate change. PMID:27242858

Control of risk factors for cardiovascular disease among adults with previously diagnosed type 2 diabetes mellitus: a descriptive study from a middle eastern arab population.

PubMed

Al-Lawati, Jawad A; N Barakat, Mohammed; Al-Zakwani, Ibrahim; Elsayed, Medhat K; Al-Maskari, Masoud; M Al-Lawati, Nawar; Mohammed, Ali Jaffer

2012-01-01

Despite the high burden of type 2 diabetes mellitus (T2DM) in Oman, there are scarce data from a nationally representative sample on the level of glycaemia and other cardiovascular (CVD) risk factor control. To estimate the proportion of patients with T2DM at goal for glycaemia and CVD risk factors using the National Diabetes Guidelines (NDG) and the American Diabetes Association (ADA) clinical care guidelines; and to assess the quality of selected services provided to patients with T2DM. A sample of 2,551 patients (47% men) aged ≥20 years with T2DM treated at primary health care centers was selected. Patient characteristics, medical history and treatment were collected from case notes, Diabetes Registers and computer frameworks including the use of the last 3 laboratory investigations results and blood pressure (BP) readings recorded in 2007. The overall mean age of the cohort was 54±13 years with an average median duration of diabetes of 4 (range 2 to 6) years. Over 80% of patients were overweight or obese (body mass index (BMI) of ≥25 Kg/m(2)). Sixty-nine percent were on oral anti-diabetic medication, 52% on anti-hypertensives and 40% on lipid lowering drugs. Thirty percent of patients were at goal for glycosylated haemoglobin level (<7%), 26% for BP (systolic/diastolic <130/80 mmHg), 55% for total cholesterol (<5.2 mmol/l), 4.5% for low-density lipoprotein cholesterol (<1.8 mmol/l), 52% for high-density lipoprotein cholesterol (>1 mmol/l for men, >1.3 mmol/l for women), and 61% for triglycerides (<1.7 mmol/l). Over 37% had micro-albuminuria and 5% had diabetic nephropathy. Control of hyperglycaemia and other CVD risk factor appears to be suboptimal in Omani patients with T2DM and need to be addressed in the triad of patient, physician and health system.

Fibromyalgia: epidemiology and risk factors, a population-based case-control study in Lebanon.

PubMed

Moukaddem, Afaf; Chaaya, Monique; Slim, Zeinab F N; Jaffa, Miran; Sibai, Abla Mehio; Uthman, Imad

2017-02-01

To investigate the epidemiology of fibromyalgia (FM) and assess its risk factors. Using data from the 2009 Community Oriented Program for Control of Rheumatic Diseases (COPCORD) study conducted in Lebanon, a population-based case control study was performed. The sample included 34 FM patients, frequency matched with 136 controls free from any musculoskeletal complaints and randomly sampled from the population. The controls were frequency matched with cases by age and gender. The 34 female FM cases were prevalent cases which existed for a long period of time and all those who consulted a doctor were previously misdiagnosed. Family history of joint problems (OR = 4.93, 95% CI: 1.56-15.58) and working status (OR = 2.69, 95% CI: 1.04-6.93) were significant risk factors for FM, after adjusting for body mass index, distress level, smoking status and residence location. This was the first study to address the epidemiology of FM in Lebanon and the region. The chronic nature of FM that is characterized by frequent bouts of intense disabling pain and symptoms constitutes a significant health and economic burden. Clustering of cases in coastal areas was partially explained by other factors such as body mass index, distress level, smoking and work status. The high burden of FM found in our study calls for further investigation of potential risk factors of this condition. © 2015 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

The APETALA-2-like transcription factor OsAP2-39 controls key interactions between abscisic acid and gibberellin in rice.

PubMed

Yaish, Mahmoud W; El-Kereamy, Ashraf; Zhu, Tong; Beatty, Perrin H; Good, Allen G; Bi, Yong-Mei; Rothstein, Steven J

2010-09-09

The interaction between phytohormones is an important mechanism which controls growth and developmental processes in plants. Deciphering these interactions is a crucial step in helping to develop crops with enhanced yield and resistance to environmental stresses. Controlling the expression level of OsAP2-39 which includes an APETALA 2 (AP2) domain leads to phenotypic changes in rice. Overexpression of OsAP2-39 leads to a reduction in yield by decreasing the biomass and the number of seeds in the transgenic rice lines. Global transcriptome analysis of the OsAP2-39 overexpression transgenic rice revealed the upregulation of a key abscisic acid (ABA) biosynthetic gene OsNCED-I which codes for 9-cis-epoxycarotenoid dioxygenase and leads to an increase in the endogenous ABA level. In addition to OsNCED-1, the gene expression analysis revealed the upregulation of a gene that codes for the Elongation of Upper most Internode (EUI) protein, an enzyme that catalyzes 16α, 17-epoxidation of non-13-hydroxylated GAs, which has been shown to deactivate gibberellins (GAs) in rice. The exogenous application of GA restores the wild-type phenotype in the transgenic line and ABA application induces the expression of EUI and suppresses the expression of OsAP2-39 in the wild-type line. These observations clarify the antagonistic relationship between ABA and GA and illustrate a mechanism that leads to homeostasis of these hormones. In vivo and in vitro analysis showed that the expression of both OsNCED-1 and EUI are directly controlled by OsAP2-39. Together, these results reveal a novel mechanism for the control of the ABA/GA balance in rice which is regulated by OsAP2-39 that in turn regulates plant growth and seed production.

The APETALA-2-Like Transcription Factor OsAP2-39 Controls Key Interactions between Abscisic Acid and Gibberellin in Rice

PubMed Central

Yaish, Mahmoud W.; El-kereamy, Ashraf; Zhu, Tong; Beatty, Perrin H.; Good, Allen G.; Bi, Yong-Mei; Rothstein, Steven J.

2010-01-01

The interaction between phytohormones is an important mechanism which controls growth and developmental processes in plants. Deciphering these interactions is a crucial step in helping to develop crops with enhanced yield and resistance to environmental stresses. Controlling the expression level of OsAP2-39 which includes an APETALA 2 (AP2) domain leads to phenotypic changes in rice. Overexpression of OsAP2-39 leads to a reduction in yield by decreasing the biomass and the number of seeds in the transgenic rice lines. Global transcriptome analysis of the OsAP2-39 overexpression transgenic rice revealed the upregulation of a key Abscisic Acid (ABA) biosynthetic gene OsNCED-I which codes for 9-cis-epoxycarotenoid dioxygenase and leads to an increase in the endogenous ABA level. In addition to OsNCED-1, the gene expression analysis revealed the upregulation of a gene that codes for the Elongation of Upper most Internode (EUI) protein, an enzyme that catalyzes 16α, 17-epoxidation of non-13-hydroxylated GAs, which has been shown to deactivate gibberellins (GAs) in rice. The exogenous application of GA restores the wild-type phenotype in the transgenic line and ABA application induces the expression of EUI and suppresses the expression of OsAP2-39 in the wild-type line. These observations clarify the antagonistic relationship between ABA and GA and illustrate a mechanism that leads to homeostasis of these hormones. In vivo and in vitro analysis showed that the expression of both OsNCED-1 and EUI are directly controlled by OsAP2-39. Together, these results reveal a novel mechanism for the control of the ABA/GA balance in rice which is regulated by OsAP2-39 that in turn regulates plant growth and seed production. PMID:20838584

PGE2 is a UVR-inducible autocrine factor for human melanocytes that stimulates tyrosinase activation

PubMed Central

Starner, Renny J.; McClelland, Lindy; Abdel-Malek, Zalfa; Fricke, Alex; Scott, Glynis

2013-01-01

Melanocyte proliferation, dendrite formation, and pigmentation are controlled by paracrine factors, particularly following exposure to ultraviolet radiation (UVR). Little is known about autocrine factors for melanocytes. Prostaglandins activate signaling pathways involved in growth, differentiation and apoptosis. Prostaglandin E2 (PGE2) is the most abundant prostaglandin released by keratinocytes following UVR, and stimulates the formation of dendrites in melanocytes. Synthesis of PGE2 is controlled by cPLA2, which releases arachidonic acid from membranes, and COX-2 and prostaglandin E2 synthases (PGES), which convert arachidonic acid to PGH2 and PGH2 to PGE2, respectively. In this report we show that multiple irradiations of human melanocytes with UVR stimulates tyrosinase activity, independent of expression of a functional melanocortin 1 receptor, suggesting the presence of a non-melanocortin autocrine factor. Irradiation of melanocytes activated cPLA2, the rate-limiting step in eicosanoid synthesis, and stimulated PGE2 secretion. PGE2 increased cAMP production, tyrosinase activity and proliferation in melanocytes. PGE2 binds to four distinct G-protein coupled receptors (EP1–4). We show that EP4 receptor signaling stimulates cAMP production in melanocytes. Conversely, stimulation of the EP3 receptor lowered basal cAMP levels. These data suggest that relative levels or activity of these receptors controls effects of PGE2 on cAMP in melanocytes. The data are the first to identify PGE2 as an UVR-inducible autocrine factor for melanocytes that stimulates tyrosinase activity and proliferation, and to show that EP3 and EP4 receptor signaling have opposing effects on cAMP production, a critical signaling pathway that regulates proliferation and melanogenesis in melanocytes. PMID:20500768

Using coordinate-based meta-analyses to explore structural imaging genetics.

PubMed

Janouschek, Hildegard; Eickhoff, Claudia R; Mühleisen, Thomas W; Eickhoff, Simon B; Nickl-Jockschat, Thomas

2018-05-05

Imaging genetics has become a highly popular approach in the field of schizophrenia research. A frequently reported finding is that effects from common genetic variation are associated with a schizophrenia-related structural endophenotype. Genetic contributions to a structural endophenotype may be easier to delineate, when referring to biological rather than diagnostic criteria. We used coordinate-based meta-analyses, namely the anatomical likelihood estimation (ALE) algorithm on 30 schizophrenia-related imaging genetics studies, representing 44 single-nucleotide polymorphisms at 26 gene loci investigated in 4682 subjects. To test whether analyses based on biological information would improve the convergence of results, gene ontology (GO) terms were used to group the findings from the published studies. We did not find any significant results for the main contrast. However, our analysis enrolling studies on genotype × diagnosis interaction yielded two clusters in the left temporal lobe and the medial orbitofrontal cortex. All other subanalyses did not yield any significant results. To gain insight into possible biological relationships between the genes implicated by these clusters, we mapped five of them to GO terms of the category "biological process" (AKT1, CNNM2, DISC1, DTNBP1, VAV3), then five to "cellular component" terms (AKT1, CNNM2, DISC1, DTNBP1, VAV3), and three to "molecular function" terms (AKT1, VAV3, ZNF804A). A subsequent cluster analysis identified representative, non-redundant subsets of semantically similar terms that aided a further interpretation. We regard this approach as a new option to systematically explore the richness of the literature in imaging genetics.

Tuberculosis risk factors among tuberculosis patients in Kampala, Uganda: implications for tuberculosis control.

PubMed

Kirenga, Bruce J; Ssengooba, Willy; Muwonge, Catherine; Nakiyingi, Lydia; Kyaligonza, Stephen; Kasozi, Samuel; Mugabe, Frank; Boeree, Martin; Joloba, Moses; Okwera, Alphonse

2015-01-21

Slow decline in the incidence of tuberculosis (TB) has been observed in most high TB burden countries. Knowledge of the prevalence of different TB risk factors can help expand TB control strategies. However with the exception of Human Immunodeficiency Virus (HIV) the prevalence of the other TB risk factors are poorly studied in Uganda. We aimed to determine the prevalence of different TB risk factors and TB disease presentation among TB patients in Kampala Uganda. We assessed 365 adult TB patients and used descriptive statistics to summarize their socio-demographic, clinical, radiological, sputum mycobacteriology and TB risk factors (HIV, diabetes, TB contact, alcohol use, tobacco smoking, poverty and overcrowding) data. A total of 158 (43.3%) patients were male and the median age was 29 (IQR 28-30). Majority of the patients (89.2%) had pulmonary TB, 86.9% were new and 13.2% were retreatment. Wasting (i.e. body mass index of <18.5 kg/m(2)) was found in 38.5% of the patients and 63% presented with cough. Constitutional symptoms (fever, anorexia, night sweats and weight loss) were reported by 32.1%. Most patients (78.6%) presented with non-cavity lung parenchyma disease (infiltrates, nodules, masses) but 35.2% had cavity disease. Pleural disease was detected in 19.3% of patients. Positive smear microscopy and culture (irrespective of month of treatment) was found in 52.7% and 36.5% of patients respectively. Any drug resistance was detected in 21.1% of patients while multidrug resistance (MDR) TB defined as resistance to rifampicin and isoniazid was detected in 6.3% of patients. All MDR patients were new patients. The prevalence of TB risk factors were as follows: HIV 41.4%, diabetes 5.4%, close contact 11.5%, family history 17.5%, smoking 26.37%, poverty 39.5%, overcrowding 57.3% and alcohol use 50.7%. Overcrowding increased smear positive rate, prevalence ratio 1.22, p = 0.09 but all the other studied risk factors did not affect clinical, radiological and

Interferon beta 2/B-cell stimulatory factor type 2 shares identity with monocyte-derived hepatocyte-stimulating factor and regulates the major acute phase protein response in liver cells.

PubMed Central

Gauldie, J; Richards, C; Harnish, D; Lansdorp, P; Baumann, H

1987-01-01

One of the oldest and most preserved of the homeostatic responses of the body to injury is the acute phase protein response associated with inflammation. The liver responds to hormone-like mediators by the increased synthesis of a series of plasma proteins called acute phase reactants. In these studies, we examined the relationship of hepatocyte-stimulating factor derived from peripheral blood monocytes to interferon beta 2 (IFN-beta 2), which has been cloned. Antibodies raised against fibroblast-derived IFN-beta having neutralizing activity against both IFN-beta 1 and -beta 2 inhibited the major hepatocyte-stimulating activity derived from monocytes. Fibroblast-derived mediator elicited the identical stimulated response in human HepG2 cells and primary rat hepatocytes as the monocyte cytokine. Finally, recombinant-derived human B-cell stimulatory factor type 2 (IFN-beta 2) from Escherichia coli induced the synthesis of all major acute phase proteins studied in human hepatoma HepG2 and primary rat hepatocyte cultures. These data demonstrate that monocyte-derived hepatocyte-stimulating factor and IFN-beta 2 share immunological and functional identity and that IFN-beta 2, also known as B-cell stimulatory factor and hybridoma plasmacytoma growth factor, has the hepatocyte as a major physiologic target and thereby is essential in controlling the hepatic acute phase response. Images PMID:2444978

Pore structure characterization of Chang-7 tight sandstone using MICP combined with N2GA techniques and its geological control factors

PubMed Central

Cao, Zhe; Liu, Guangdi; Zhan, Hongbin; Li, Chaozheng; You, Yuan; Yang, Chengyu; Jiang, Hang

2016-01-01

Understanding the pore networks of unconventional tight reservoirs such as tight sandstones and shales is crucial for extracting oil/gas from such reservoirs. Mercury injection capillary pressure (MICP) and N2 gas adsorption (N2GA) are performed to evaluate pore structure of Chang-7 tight sandstone. Thin section observation, scanning electron microscope, grain size analysis, mineral composition analysis, and porosity measurement are applied to investigate geological control factors of pore structure. Grain size is positively correlated with detrital mineral content and grain size standard deviation while negatively related to clay content. Detrital mineral content and grain size are positively correlated with porosity, pore throat radius and withdrawal efficiency and negatively related to capillary pressure and pore-to-throat size ratio; while interstitial material is negatively correlated with above mentioned factors. Well sorted sediments with high debris usually possess strong compaction resistance to preserve original pores. Although many inter-crystalline pores are produced in clay minerals, this type of pores is not the most important contributor to porosity. Besides this, pore shape determined by N2GA hysteresis loop is consistent with SEM observation on clay inter-crystalline pores while BJH pore volume is positively related with clay content, suggesting N2GA is suitable for describing clay inter-crystalline pores in tight sandstones. PMID:27830731

Human factors aspects of air traffic control

NASA Technical Reports Server (NTRS)

Older, H. J.; Cameron, B. J.

1972-01-01

An overview of human factors problems associated with the operation of present and future air traffic control systems is presented. A description is included of those activities and tasks performed by air traffic controllers at each operational position within the present system. Judgemental data obtained from controllers concerning psychological dimensions related to these tasks and activities are also presented. The analysis includes consideration of psychophysiological dimensions of human performance. The role of the human controller in present air traffic control systems and his predicted role in future systems is described, particularly as that role changes as the result of the system's evolution towards a more automated configuration. Special attention is directed towards problems of staffing, training, and system operation. A series of ten specific research and development projects are recommended and suggested work plans for their implementation are included.

Risk factors for sporadic Giardia infection in the USA: a case-control study in Colorado and Minnesota.

PubMed

Reses, H E; Gargano, J W; Liang, J L; Cronquist, A; Smith, K; Collier, S A; Roy, S L; Vanden Eng, J; Bogard, A; Lee, B; Hlavsa, M C; Rosenberg, E S; Fullerton, K E; Beach, M J; Yoder, J S

2018-05-09

Giardia duodenalis is the most common intestinal parasite of humans in the USA, but the risk factors for sporadic (non-outbreak) giardiasis are not well described. The Centers for Disease Control and Prevention and the Colorado and Minnesota public health departments conducted a case-control study to assess risk factors for sporadic giardiasis in the USA. Cases (N = 199) were patients with non-outbreak-associated laboratory-confirmed Giardia infection in Colorado and Minnesota, and controls (N = 381) were matched by age and site. Identified risk factors included international travel (aOR = 13.9; 95% CI 4.9-39.8), drinking water from a river, lake, stream, or spring (aOR = 6.5; 95% CI 2.0-20.6), swimming in a natural body of water (aOR = 3.3; 95% CI 1.5-7.0), male-male sexual behaviour (aOR = 45.7; 95% CI 5.8-362.0), having contact with children in diapers (aOR = 1.6; 95% CI 1.01-2.6), taking antibiotics (aOR = 2.5; 95% CI 1.2-5.0) and having a chronic gastrointestinal condition (aOR = 1.8; 95% CI 1.1-3.0). Eating raw produce was inversely associated with infection (aOR = 0.2; 95% CI 0.1-0.7). Our results highlight the diversity of risk factors for sporadic giardiasis and the importance of non-international-travel-associated risk factors, particularly those involving person-to-person transmission. Prevention measures should focus on reducing risks associated with diaper handling, sexual contact, swimming in untreated water, and drinking untreated water.

Control circuit maintains unity power factor of reactive load

NASA Technical Reports Server (NTRS)

Kramer, M.; Martinage, L. H.

1966-01-01

Circuit including feedback control elements automatically corrects the power factor of a reactive load. It maintains power supply efficiency where negative load reactance changes and varies by providing corrective error signals to the control windings of a power supply transformer.

Zebrafish bcl2l is a survival factor in thyroid development.

PubMed

Porreca, Immacolata; De Felice, Elena; Fagman, Henrik; Di Lauro, Roberto; Sordino, Paolo

2012-06-15

Regulated cell death, defined in morphological terms as apoptosis, is crucial for organ morphogenesis. While differentiation of the thyroid gland has been extensively studied, nothing is yet known about the survival mechanisms involved in the development of this endocrine gland. Using the zebrafish model system, we aim to understand whether genes belonging to the Bcl-2 family that control apoptosis are implicated in regulation of cell survival during thyroid development. Evidence of strong Bcl-2 gene expression in mouse thyroid precursors prompted us to investigate the functions played by its zebrafish homologs during thyroid development. We show that the bcl2-like (bcl2l) gene is expressed in the zebrafish thyroid primordium. Morpholino-mediated knockdown and mutant analyses revealed that bcl2l is crucial for thyroid cell survival and that this function is tightly modulated by the transcription factors pax2a, nk2.1a and hhex. Also, the bcl2l gene appears to control a caspase-3-dependent apoptotic mechanism during thyroid development. Thyroid precursor cells require an actively maintained survival mechanism to properly proceed through development. The bcl2l gene operates in the inhibition of cell death under direct regulation of a thyroid specific set of transcription factors. This is the first demonstration of an active mechanism to ensure survival of the thyroid primordium during morphogenesis. Copyright © 2012 Elsevier Inc. All rights reserved.

Canine diabetes mellitus risk factors: A matched case-control study.

PubMed

Pöppl, Alan Gomes; de Carvalho, Guilherme Luiz Carvalho; Vivian, Itatiele Farias; Corbellini, Luis Gustavo; González, Félix Hilário Díaz

2017-10-01

Different subtypes of canine diabetes mellitus (CDM) have been described based on their aetiopathogenesis. Therefore, manifold risk factors may be involved in CDM development. This study aims to investigate canine diabetes mellitus risk factors. Owners of 110 diabetic dogs and 136 healthy controls matched by breed, sex, and age were interviewed concerning aspects related to diet, weight, physical activity, oral health, reproductive history, pancreatitis, and exposure to exogenous glucocorticoids. Two multivariate multivariable statistical models were created: The UMod included males and females without variables related to oestrous cycle, while the FMod included only females with all analysed variables. In the UMod, "Not exclusively commercial diet" (OR 4.86, 95%CI 2.2-10.7, P<0.001) and "Overweight" (OR 3.51, 95%CI 1.6-7.5, P=0.001) were statistically significant, while in the FMod, "Not exclusively commercial diet" (OR 4.14, 95%CI 1.3-12.7, P=0.01), "Table scraps abuse" (OR 3.62, 95%CI 1.1-12.2, P=0.03), "Overweight" (OR 3.91, 95%CI 1.2-12.6, P=0.02), and "Dioestrus" (OR 5.53, 95%CI 1.9-16.3, P=0.002) were statistically significant. The findings in this study support feeding not exclusively balanced commercial dog food, overweight, treats abuse, and diestrus, as main CDM risk factors. Moreover, those results give subside for preventive care studies against CDM development. Copyright © 2017 Elsevier Ltd. All rights reserved.

Colorectal cancer risk factors: a case-control study in Bangkok.

PubMed

Lohsoonthorn, P; Danvivat, D

1995-01-01

A case-control study for colorectal cancer risk factors was conducted in Bangkok, Thailand. A total of 279 incident cases of colorectal cancer were individually matched by sex, age and same hospital to 279 hospital controls with other cancers except gastrointestinal cancer. Each subject was interviewed with regard to bowel pattern information, family history, past history of illness and dietary information. The major findings were elevated risk for those with a history of bowel polyps (OR = 14.69, 95%CI = 2.01-301.46), parent's history of colon cancer (OR = 4.00, 95%CI = 1.39-12.43), anal abscess (OR = 3.78, 95%CI = 0.97-17.24), chronic colitis (OR = 3.61, 95%CI = 1.67-8.00), chronic hemorrhoid (OR = 3.13, 95%CI = 2.03-4.86) and the frequency of stools every three days or more (OR = 2.16, 95%CI = 1.17-4.01). The results also indicated an increased risk for dietary factors; bacon (OR = 12.49, 95%CI = 1.68-269.1) and butter (OR = 2.68, 95%CI = 1.29-5.68). There was a protective effect provided by banana (OR = 0.54, 95%CI = 0.37-0.79) and papaya (OR = 0.58, 95%CI = 0.40-0.84) for colorectal cancer. In unconditional logistic regression analysis, bacon showed the highest risk for colorectal cancer (OR = 8.82, 95%CI = 1.03-75.57), instead of bowel polyps (OR = 4.50, 95%CI = 0.48-42.59). The data suggest that nitrite-treated meat increases colorectal cancer risk while dietary fiber decreases colorectal cancer risk.

Factors affecting health care workers' adoption of a website with infection control guidelines.

PubMed

Verhoeven, Fenne; Steehouder, Michaël F; Hendrix, Ron M G; van Gemert-Pijnen, Julia E W C

2009-10-01

To identify factors that could affect health care workers' (HCWs) adoption of a website for communicating infection control guidelines. In total, 20 semi-structured interviews were conducted with HCWs in 5 different occupational groups and 4 different hospitals in the Netherlands and Germany. A website communicating guidelines for the prevention and control of Methicillin Resistant Staphylococcus aureus served as a casus. The HCWs, the majority of whom had prior experience with the website, were asked to give their opinions about factors that hinder or facilitate adoption of the website in practice. The interviews were based on the PRECEDE (Predisposing, Reinforcing, and Enabling Causes in Educational Diagnosis and Evaluation) model complemented by quality criteria for health-related websites. This model encompasses different categories of factors relevant to technology adoption in health care. A total of 361 interview statements were relevant to the four main categories of the PRECEDE model, yielding the following observations: (1) Technological factors (72 statements): The usability, design, and relevance of the website were positively valued. The website enabled HCWs to access contextually relevant information quickly. The website's credibility was evaluated rather negatively, as respondents perceived that the website's guidelines were not in concurrence with the best available evidence and it was not clear to HCWs who created the website. (2) Individual factors (85 statements): Respondents, particular infection control professionals, showed individual resistance to the website because they preferred to use their personal knowledge and experience (and communication with colleagues) over online sources. (3) Work-related factors (53 statements): Respondents perceived high work pressure during working hours as an impediment to consulting the website. In contrast, respondents thought the website might lower work pressure for infection control professionals, as they

Pleiotropic effects of type 2 diabetes management strategies on renal risk factors.

PubMed

Muskiet, Marcel H A; Tonneijck, Lennart; Smits, Mark M; Kramer, Mark H H; Heerspink, Hiddo J Lambers; van Raalte, Daniël H

2015-05-01

In parallel with the type 2 diabetes pandemic, diabetic kidney disease has become the leading cause of end-stage renal disease worldwide, and is associated with high cardiovascular morbidity and mortality. As established in landmark randomised trials and recommended in clinical guidelines, prevention and treatment of diabetic kidney disease focuses on control of the two main renal risk factors, hyperglycaemia and systemic hypertension. Treatment of systemic hypertension with angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers is advocated because these drugs seem to exert specific renoprotective effects beyond blood pressure lowering. Emerging evidence shows that obesity, glomerular hyperfiltration, albuminuria, and dyslipidaemia might also adversely affect the kidney in diabetes. Control of these risk factors could have additional benefits on renal outcome in patients with type 2 diabetes. However, despite multifactorial treatment approaches, residual risk for the development and progression of diabetic kidney disease in patients with type 2 diabetes remains, and novel strategies or therapies to treat the disease are urgently needed. Several drugs used in the treatment of type 2 diabetes are associated with pleiotropic effects that could favourably or unfavourably change patients' renal risk profile. We review the risk factors and treatment of diabetic kidney disease, and describe the pleiotropic effects of widely used drugs in type 2 diabetes management on renal outcomes, with special emphasis on antihyperglycaemic drugs. Copyright © 2015 Elsevier Ltd. All rights reserved.

The contribution of socioeconomic factors to PM2.5 pollution in urban China.

PubMed

Jiang, Peng; Yang, Jun; Huang, Conghong; Liu, Huakui

2018-02-01

PM 2.5 pollution poses severe health risks to urban residents in low and middle-income countries. Existing studies have shown that the problem is affected by multiple socioeconomic factors. However, the relative contribution of these factors is not well understood, which sometimes leads to controversial controlling measures. In this study, we quantified the relative contribution of different socioeconomic factors, including the city size, industrial activities, and residents' activities, to PM 2.5 pollution in urban China between 2014 and 2015 by using structural equation model (SEM). Our results showed that industrial activities contributed more to PM 2.5 pollution than other factors. The city size and residents' activities also had significant impacts on PM 2.5 pollution. The combined influence of all socioeconomic factors could explain between 44% and 48% of variation in PM 2.5 pollution, which indicated the existence of influences from other factors such as weather conditions and outside sources of pollutants. Findings from our study can contribute to a more comprehensive understanding of the socioeconomic causes of PM 2.5 pollution. Copyright © 2017 Elsevier Ltd. All rights reserved.

Factors associated with suicide: Case-control study in South Tyrol.

PubMed

Giupponi, Giancarlo; Innamorati, Marco; Baldessarini, Ross J; De Leo, Diego; de Giovannelli, Francesca; Pycha, Roger; Conca, Andreas; Girardi, Paolo; Pompili, Maurizio

2018-01-01

As suicide is related to many factors in addition to psychiatric illness, broad and comprehensive risk-assessment for risk of suicide is required. This study aimed to differentiate nondiagnostic risk factors among suicides versus comparable psychiatric patients without suicidal behavior. We carried out a pilot, case-control comparison of 131 cases of suicide in South Tyrol matched for age and sex with 131 psychiatric controls, using psychological autopsy methods to evaluate differences in clinically assessed demographic, social, and clinical factors, using bivariate conditional Odds Risk comparisons followed by conditional regression modeling controlled for ethnicity. Based on multivariable conditional regression modeling, suicides were significantly more likely to have experienced risk factors, ranking as: [a] family history of suicide or attempt≥[b] recent interpersonal stressors≥[c] childhood traumatic events≥[d] lack of recent clinician contacts≥[e] previous suicide attempt≥[f] non-Italian ethnicity, but did not differ in education, marital status, living situation, or employment, nor by psychiatric or substance-abuse diagnoses. Both recent and early factors were associated with suicide, including lack of recent clinical care, non-Italian cultural subgroup-membership, familial suicidal behavior, and recent interpersonal distress. Copyright © 2017 Elsevier Inc. All rights reserved.

A role for multiple chimeric antigen receptor-expressing leukocytes in antigen-specific responses to cancer

PubMed Central

Yong, Carmen S.M.; John, Liza B.; Devaud, Christel; Prince, Miles H.; Johnstone, Ricky W.; Trapani, Joseph A.

2016-01-01

While adoptive immunotherapy using chimeric antigen receptor (CAR)-modified T cells can induce remission of some tumors, the role of other CAR-modified leukocytes is not well characterized. In this study, we characterize the function of leukocytes including natural killer (NK) cells, macrophages and CAR T cells from transgenic mice expressing a CAR under the control of the pan-hematopoietic promoter, vav, and determine the ability of these mice to respond to ERB expressing tumors. We demonstrate the anti-tumor functions of leukocytes, including antigen specific cytotoxicity and cytokine secretion. The adoptive transfer of CAR T cells provided a greater survival advantage in the E0771ERB tumor model than their wildtype (WT) counterparts. In addition, CAR NK cells and CAR T cells also mediated increased survival in the RMAERB tumor model. When challenged with Her2 expressing tumors, F38 mice were shown to mount an effective immune response, resulting in tumor rejection and long-term survival. This was shown to be predominantly dependent on both CD8+ T cells and NK cells. However, macrophages and CD4+ T cells were also shown to contribute to this response. Overall, this study highlights the use of the vav-CAR mouse model as a unique tool to determine the anti-tumor function of various immune subsets, either alone or when acting alongside CAR T cells in adoptive immunotherapy. PMID:27153556

The Small Molecule Inhibitor G6 Significantly Reduces Bone Marrow Fibrosis and the Mutant Burden in a Mouse Model of Jak2-Mediated Myelofibrosis

PubMed Central

Kirabo, Annet; Park, Sung O.; Wamsley, Heather L.; Gali, Meghanath; Baskin, Rebekah; Reinhard, Mary K.; Zhao, Zhizhuang J.; Bisht, Kirpal S.; Keserű, György M.; Cogle, Christopher R.; Sayeski, Peter P.

2013-01-01

Philadelphia chromosome–negative myeloproliferative neoplasms, including polycythemia vera, essential thrombocytosis, and myelofibrosis, are disorders characterized by abnormal hematopoiesis. Among these myeloproliferative neoplasms, myelofibrosis has the most unfavorable prognosis. Furthermore, currently available therapies for myelofibrosis have little to no efficacy in the bone marrow and hence, are palliative. We recently developed a Janus kinase 2 (Jak2) small molecule inhibitor called G6 and found that it exhibits marked efficacy in a xenograft model of Jak2-V617F–mediated hyperplasia and a transgenic mouse model of Jak2-V617F–mediated polycythemia vera/essential thrombocytosis. However, its efficacy in Jak2-mediated myelofibrosis has not previously been examined. Here, we hypothesized that G6 would be efficacious in Jak2-V617F–mediated myelofibrosis. To test this, mice expressing the human Jak2-V617F cDNA under the control of the vav promoter were administered G6 or vehicle control solution, and efficacy was determined by measuring parameters within the peripheral blood, liver, spleen, and bone marrow. We found that G6 significantly reduced extramedullary hematopoiesis in the liver and splenomegaly. In the bone marrow, G6 significantly reduced pathogenic Jak/STAT signaling by 53%, megakaryocytic hyperplasia by 70%, and the Jak2 mutant burden by 68%. Furthermore, G6 significantly improved the myeloid to erythroid ratio and significantly reversed the myelofibrosis. Collectively, these results indicate that G6 is efficacious in Jak2-V617F–mediated myelofibrosis, and given its bone marrow efficacy, it may alter the natural history of this disease. PMID:22796437

Dominant factors in controlling marine gas pools in South China

USGS Publications Warehouse

Xu, S.; Watney, W.L.

2007-01-01

In marine strata from Sinian to Middle Triassic in South China, there develop four sets of regional and six sets of local source rocks, and ten sets of reservoir rocks. The occurrence of four main formation periods in association with five main reconstruction periods, results in a secondary origin for the most marine gas pools in South China. To improve the understanding of marine gas pools in South China with severely deformed geological background, the dominant control factors are discussed in this paper. The fluid sources, including the gas cracked from crude oil, the gas dissolved in water, the gas of inorganic origin, hydrocarbons generated during the second phase, and the mixed pool fluid source, were the most significant control factors of the types and the development stage of pools. The period of the pool formation and the reconstruction controlled the pool evolution and the distribution on a regional scale. Owing to the multiple periods of the pool formation and the reconstruction, the distribution of marine gas pools was complex both in space and in time, and the gas in the pools is heterogeneous. Pool elements, such as preservation conditions, traps and migration paths, and reservoir rocks and facies, also served as important control factors to marine gas pools in South China. Especially, the preservation conditions played a key role in maintaining marine oil and gas accumulations on a regional or local scale. According to several dominant control factors of a pool, the pool-controlling model can be constructed. As an example, the pool-controlling model of Sinian gas pool in Weiyuan gas field in Sichuan basin was summed up. ?? Higher Education Press and Springer-Verlag 2007.

Methylation of eukaryotic elongation factor 2 induced by basic fibroblast growth factor via mitogen-activated protein kinase.

PubMed

Jung, Gyung Ah; Shin, Bong Shik; Jang, Yeon Sue; Sohn, Jae Bum; Woo, Seon Rang; Kim, Jung Eun; Choi, Go; Lee, Kyung Mi; Min, Bon Hong; Lee, Kee Ho; Park, Gil Hong

2011-10-31

Protein arginine methylation is important for a variety of cellular processes including transcriptional regulation, mRNA splicing, DNA repair, nuclear/cytoplasmic shuttling and various signal transduction pathways. However, the role of arginine methylation in protein biosynthesis and the extracellular signals that control arginine methylation are not fully understood. Basic fibroblast growth factor (bFGF) has been identified as a potent stimulator of myofibroblast dedifferentiation into fibroblasts. We demonstrated that symmetric arginine dimethylation of eukaryotic elongation factor 2 (eEF2) is induced by bFGF without the change in the expression level of eEF2 in mouse embryo fibroblast NIH3T3 cells. The eEF2 methylation is preceded by ras-raf-mitogen-activated protein kinase kinase (MEK)-extracellular signal-regulated kinase (ERK1/2)- p21Cip/WAF1 activation, and suppressed by the mitogenactivated protein kinase (MAPK) inhibitor PD98059 and p21Cip/WAF1 short interfering RNA (siRNA). We determined that protein arginine methyltransferase 7 (PRMT7) is responsible for the methylation, and that PRMT5 acts as a coordinator. Collectively, we demonstrated that eEF2, a key factor involved in protein translational elongation is symmetrically arginine-methylated in a reversible manner, being regulated by bFGF through MAPK signaling pathway.

Methylation of eukaryotic elongation factor 2 induced by basic fibroblast growth factor via mitogen-activated protein kinase

PubMed Central

Jung, Gyung Ah; Shin, Bong Shik; Jang, Yeon Sue; Sohn, Jae Bum; Woo, Seon Rang; Kim, Jung Eun; Choi, Go; Lee, Kyung-Mi; Min, Bon Hong

2011-01-01

Protein arginine methylation is important for a variety of cellular processes including transcriptional regulation, mRNA splicing, DNA repair, nuclear/cytoplasmic shuttling and various signal transduction pathways. However, the role of arginine methylation in protein biosynthesis and the extracellular signals that control arginine methylation are not fully understood. Basic fibroblast growth factor (bFGF) has been identified as a potent stimulator of myofibroblast dedifferentiation into fibroblasts. We demonstrated that symmetric arginine dimethylation of eukaryotic elongation factor 2 (eEF2) is induced by bFGF without the change in the expression level of eEF2 in mouse embryo fibroblast NIH3T3 cells. The eEF2 methylation is preceded by ras-raf-mitogen-activated protein kinase kinase (MEK)-extracellular signal-regulated kinase (ERK1/2)-p21Cip/WAF1 activation, and suppressed by the mitogen-activated protein kinase (MAPK) inhibitor PD98059 and p21Cip/WAF1 short interfering RNA (siRNA). We determined that protein arginine methyltransferase 7 (PRMT7) is responsible for the methylation, and that PRMT5 acts as a coordinator. Collectively, we demonstrated that eEF2, a key factor involved in protein translational elongation is symmetrically arginine-methylated in a reversible manner, being regulated by bFGF through MAPK signaling pathway. PMID:21778808

Risk factors for pneumonic and ulceroglandular tularaemia in Finland: a population-based case-control study.

PubMed

Rossow, H; Ollgren, J; Klemets, P; Pietarinen, I; Saikku, J; Pekkanen, E; Nikkari, S; Syrjälä, H; Kuusi, M; Nuorti, J P

2014-10-01

Few population-based data are available on factors associated with pneumonic and ulceroglandular type B tularaemia. We conducted a case-control study during a large epidemic in 2000. Laboratory-confirmed case patients were identified through active surveillance and matched control subjects (age, sex, residency) from the national population information system. Data were collected using a self-administered questionnaire. A conditional logistic regression model addressing missing data with Bayesian full-likelihood modelling included 227 case patients and 415 control subjects; reported mosquito bites [adjusted odds ratio (aOR) 9·2, 95% confidence interval (CI) 4·4-22, population-attributable risk (PAR) 82%] and farming activities (aOR 4·3, 95% CI 2·5-7·2, PAR 32%) were independently associated with ulceroglandular tularaemia, whereas exposure to hay dust (aOR 6·6, 95% CI 1·9-25·4, PAR 48%) was associated with pneumonic tularaemia. Although the bulk of tularaemia type B disease burden is attributable to mosquito bites, risk factors for ulceroglandular and pneumonic forms of tularaemia are different, enabling targeting of prevention efforts accordingly.

Risk factors of visceral leishmaniasis: a case control study in north-western Ethiopia.

PubMed

Yared, Solomon; Deribe, Kebede; Gebreselassie, Araya; Lemma, Wessenseged; Akililu, Essayas; Kirstein, Oscar D; Balkew, Meshesha; Warburg, Alon; Gebre-Michael, Teshome; Hailu, Asrat

2014-10-14

Visceral leishmaniasis (VL, also called ''kala-azar"), is a life threatening neglected tropical infectious disease which mainly affects the poorest of the poor. VL is prevalent in Ethiopia particularly in the northwest of the country. Understanding the risk factors of VL infection helps in its prevention and control. The aim of the present study was to identify the factors associated with VL. A case-control study was carried out during the period of January-July 2013 in northwest Ethiopia. Cases and controls were diagnosed using clinical presentation, the rk39 rapid diagnostic test and Direct Agglutination Test (DAT). A total of 283 (84.8% males versus 15.2% females) participants were interviewed. 90 cases and 193 controls were involved, matched by age, sex and geographical location with a ratio of 1:2 (case: controls). Univariate and backward multivariate conditional logistic regression were used to identify risk factors of VL. Elevated odds of VL was associated with goat ownership (OR = 6.4; 95%: confidence interval [Cl]: 1.5-28.4), living in houses with cracked wall (OR = 6.4; 95% Cl: 1.6-25.6), increased family size (OR = 1.3; 95% Cl: 1.0-1.8) and the number of days spent in the farm field (OR = 1.1; 95% Cl: 1.0-1.2). However, daily individual activities around the home and farm fields, mainly sleeping on a bed (OR = 0.2; 95%: Cl 0.03-0.9), sleeping outside the house under a bed net (OR = 0.1; 95% Cl: 0.02-0.36)] and smoking plant parts in the house during the night time (OR = 0.1; 95% Cl: 0.01-0.6) were associated with decreased odds of being VL case. Our findings showed that use of bed net and smoke could be helpful for the prevention of VL in the area particularly among individuals who spend most of their time in the farm. VL control effort could be focused on improving housing conditions, such as sealing cracks and crevices inside and outside houses. Further research is warranted to elucidate the role of goats in the transmission

The factors controlling species density in herbaceous plant communities: An assessment

USGS Publications Warehouse

Grace, J.B.

1999-01-01

This paper evaluates both the ideas and empirical evidence pertaining to the control of species density in herbaceous plant communities. While most theoretical discussions of species density have emphasized the importance of habitat productivity and disturbance regimes, many other factors (e.g. species pools, plant litter accumulation, plant morphology) have been proposed to be important. A review of literature presenting observations on the density of species in small plots (in the vicinity of a few square meters or less), as well as experimental studies, suggests several generalizations: (1) Available data are consistent with an underlying unimodal relationship between species density and total community biomass. While variance in species density is often poorly explained by predictor variables, there is strong evidence that high levels of community biomass are antagonistic to high species density. (2) Community biomass is just one of several factors affecting variations in species density. Multivariate analyses typically explain more than twice as much variance in species density as can be explained by community biomass alone. (3) Disturbance has important and sometimes complex effects on species density. In general, the evidence is consistent with the intermediate disturbance hypothesis but exceptions exist and effects can be complex. (4) Gradients in the species pool can have important influences on patterns of species density. Evidence is mounting that a considerable amount of the observed variability in species density within a landscape or region may result from environmental effects on the species pool. (5) Several additional factors deserve greater consideration, including time lags, species composition, plant morphology, plant density and soil microbial effects. Based on the available evidence, a conceptual model of the primary factors controlling species density is presented here. This model suggests that species density is controlled by the effects of

Eczema in early childhood, sociodemographic factors and lifestyle habits are associated with food allergy: a nested case-control study.

PubMed

Ben-Shoshan, Moshe; Soller, Lianne; Harrington, Daniel W; Knoll, Megan; La Vieille, Sebastian; Fragapane, Joseph; Joseph, Lawrence; St Pierre, Yvan; Wilson, Kathie; Elliott, Susan J; Clarke, Ann E

2015-01-01

Studies suggest an increase in food allergy prevalence over the last decade, but the contributing factors remain unknown. The aim of this study was to evaluate the association between the most common food allergies and atopic history, sociodemographic characteristics and lifestyle habits. We conducted a case-control study nested within the SPAACE study (Surveying Prevalence of Food Allergy in All Canadian Environments) – a cross-Canada, random telephone survey. Cases consisted of individuals with probable food allergy (self-report of convincing symptoms and/or physician diagnosis) to milk, egg, peanut, tree nut, shellfish, fish, wheat, soy, or sesame. Controls consisted of nonallergic individuals, matched for age. Cases and controls were queried on personal and family history of atopy, sociodemographic characteristics and lifestyle habits. Multivariate logistic regression was used to evaluate the association between atopy, sociodemographic characteristics and lifestyle habits with probable food allergy. Between September 2010 and September 2011, 480 cases and 4,950 controls completed the questionnaire. For all 9 allergens, factors associated with a higher risk of probable allergy were as follows: (1) personal history of eczema (in the first 2 years of life), asthma or hay fever (odds ratio, OR 2.3, 95% CI 1.6-3.5; OR 2.8, 95% CI 2.2-3.6, and OR 2.3, 95% CI 1.8-3.0, respectively), (2) maternal, paternal or sibling's food allergy (OR 3.7, 95% CI 2.5-5.6; OR 3.0, 95% CI 1.8-5.1, and OR 3.1, 95% CI 2.2-4.2), (3) high household income (top 20%; OR 1.5, 95% CI 1.2-2.0). Males and older individuals were less likely to have food allergy (OR 0.7, 95% CI 0.6-0.9, and OR 0.99, 95% CI 0.99-1.00). Eczema in the first 2 years of life was the strongest risk factor for egg, peanut, tree nut and fish allergy. This is the largest population-based nested case-control study exploring factors associated with food allergies. Our results reveal that, in addition to previously reported

Physiological levels of blood coagulation factors IX and X control coagulation kinetics in an in vitro model of circulating tissue factor

NASA Astrophysics Data System (ADS)

Tormoen, Garth W.; Khader, Ayesha; Gruber, András; McCarty, Owen J. T.

2013-06-01

Thrombosis significantly contributes to cancer morbidity and mortality. The mechanism behind thrombosis in cancer may be circulating tissue factor (TF), as levels of circulating TF are associated with thrombosis. However, circulating TF antigen level alone has failed to predict thrombosis in patients with cancer. We hypothesize that coagulation factor levels regulate the kinetics of circulating TF-induced thrombosis. Coagulation kinetics were measured as a function of individual coagulation factor levels and TF particle concentration. Clotting times increased when pooled plasma was mixed at or above a ratio of 4:6 with PBS. Clotting times increased when pooled plasma was mixed at or above a ratio of 8:2 with factor VII-depleted plasma, 7:3 with factor IX- or factor X-depleted plasmas, or 2:8 with factor II-, V- or VIII-depleted plasmas. Addition of coagulation factors VII, X, IX, V and II to depleted plasmas shortened clotting and enzyme initiation times, and increased enzyme generation rates in a concentration-dependent manner. Only additions of factors IX and X from low-normal to high-normal levels shortened clotting times and increased enzyme generation rates. Our results demonstrate that coagulation kinetics for TF particles are controlled by factor IX and X levels within the normal physiological range. We hypothesize that individual patient factor IX and X levels may be prognostic for susceptibility to circulating TF-induced thrombosis.

Risk factors for developing tuberculosis in remand prisons in St. Petersburg, Russia - a case-control study.

PubMed

Lobacheva, Tatiana; Asikainen, Tommi; Giesecke, Johan

2007-01-01

Detainees have a substantial risk to develop tuberculosis (TB) due to a higher incidence of TB in remand prison compared to the civil community. They develop TB during incarceration not only due to poor living conditions in remand prison, but also due to some factors affecting their life before imprisonment. Prevention measures against TB spread from penitentiary institutions to society include study of factors, which contribute to TB development. Current study aims at identification of important risk factors of TB development in remand prison in St. Petersburg, Russia. A retrospective matched case-control study was performed from May 2002 to May 2003 in two remand prisons in St. Petersburg. One hundred and fourteen prisoners (57 cases, 57 controls) were interviewed by using standardised questionnaire. Logistic regression analysis was performed to identify risk factors. Six factors were significantly linked to the risk of developing TB: narcotic drug use (odds ratio (OR): 2.6, 95% confidence interval (CI): 1.0-6.9), low income (OR: 3.2, CI: 1.2-8.6), high ratio of prisoners per available bed (OR: 4.0, CI: 1.1-15.0), not having own bed clothes (OR: 13.0, CI: 2.7-61.6), and little time outdoors (OR: 3.3, CI: 1.3-8.5). However, good housing before imprisonment (OR: 4.2, CI: 1.1-15.7) was a separate risk factor for TB. Three of the risk factors (high number of prisoners per bed, not having own bed clothes, and little time outdoors) are certainly possible to approach by improvement of conditions in remand prisons. The remaining three factors (narcotic drug use, good housing before imprisonment, and low income) provide knowledge about study population, but cannot be intervened by prison's medical staff.

[Risk factors for schizophrenia patients with type 2 diabetes: a metaanalysis].

PubMed

Zhou, Min; Xiao, Chuan; Yang, Min; Yuan, Ping; Liu, Yuanyuan

2015-03-01

To investigate risk factors for schizophrenia patients with complication of type 2 diabetes mellitus and to provide scientific evidence for prevention and management of this disease. Relevant studies on schizophrenia with type 2 diabetes mellitus in China were searched through PubMed, Medline, CBM, CNKI and VIP from 1997 to 2014. Meta-analysis was performed using RevMan 5.2 soft ware. A total of 26 studies involving 6 373 participants (including 957 cases and 5 416 controls) were included. The results of Meta-analysis showed that the risk factors for schizophrenic patients with complication of type 2 diabetes mellitus were: gender (female) (OR=1.28, 95%CI: 1.09-1.50), age (≥ 40 year) (OR=6.02, 95%CI: 4.48-8.09), overweight (OR=2.32, 95%CI: 1.52-2.88), family history of diabetes (OR=6.12, 95%CI: 3.16-11.86), duration of schizophrenia (>10 years) (OR=3.60, 95%CI: 2.39-5.41), triglycerides (MD=0.38, 95%CI: 0.05-0.71). Male, old age, overweight, family history of diabetes, longer duration and high level of triglycerides are risk factors for schizophrenic patients with complication of diabetes mellitus.

The trypanocidal benznidazole promotes adaptive response to oxidative injury: Involvement of the nuclear factor-erythroid 2-related factor-2 (Nrf2) and multidrug resistance associated protein 2 (MRP2)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rigalli, Juan Pablo

Oxidative stress is a frequent cause underlying drug-induced hepatotoxicity. Benznidazole (BZL) is the only trypanocidal agent available for treatment of Chagas disease in endemic areas. Its use is associated with side effects, including increases in biomarkers of hepatotoxicity. However, BZL potential to cause oxidative stress has been poorly investigated. Here, we evaluated the effect of a pharmacologically relevant BZL concentration (200 μM) at different time points on redox status and the counteracting mechanisms in the human hepatic cell line HepG2. BZL increased reactive oxygen species (ROS) after 1 and 3 h of exposure, returning to normality at 24 h. Additionally,more » BZL increased glutathione peroxidase activity at 12 h and the oxidized glutathione/total glutathione (GSSG/GSSG + GSH) ratio that reached a peak at 24 h. Thus, an enhanced detoxification of peroxide and GSSG formation could account for ROS normalization. GSSG/GSSG + GSH returned to control values at 48 h. Expression of the multidrug resistance-associated protein 2 (MRP2) and GSSG efflux via MRP2 were induced by BZL at 24 and 48 h, explaining normalization of GSSG/GSSG + GSH. BZL activated the nuclear erythroid 2-related factor 2 (Nrf2), already shown to modulate MRP2 expression in response to oxidative stress. Nrf2 participation was confirmed using Nrf2-knockout mice in which MRP2 mRNA expression was not affected by BZL. In summary, we demonstrated a ROS increase by BZL in HepG2 cells and a glutathione peroxidase- and MRP2 driven counteracting mechanism, being Nrf2 a key modulator of this response. Our results could explain hepatic alterations associated with BZL therapy. - Highlights: • BZL triggers a redox imbalance in the human hepatic cell line HepG2. • Concomitantly BZL triggers compensatory mechanisms to alleviate the redox injury. • Response mechanisms comprise an enhanced glutathione peroxidase and MRP2 activity. • Transcription factor Nrf2 plays a key role orchestrating

PH motifs in PAR1&2 endow breast cancer growth.

PubMed

Kancharla, A; Maoz, M; Jaber, M; Agranovich, D; Peretz, T; Grisaru-Granovsky, S; Uziely, B; Bar-Shavit, R

2015-11-24

Although emerging roles of protease-activated receptor1&2 (PAR1&2) in cancer are recognized, their underlying signalling events are poorly understood. Here we show signal-binding motifs in PAR1&2 that are critical for breast cancer growth. This occurs via the association of the pleckstrin homology (PH) domain with Akt/PKB as a key signalling event of PARs. Other PH-domain signal-proteins such as Etk/Bmx and Vav3 also associate with PAR1 and PAR2 through their PH domains. PAR1 and PAR2 bind with priority to Etk/Bmx. A point mutation in PAR2, H349A, but not in R352A, abrogates PH-protein association and is sufficient to markedly reduce PAR2-instigated breast tumour growth in vivo and placental extravillous trophoblast (EVT) invasion in vitro. Similarly, the PAR1 mutant hPar1-7A, which is unable to bind the PH domain, reduces mammary tumours and EVT invasion, endowing these motifs with physiological significance and underscoring the importance of these previously unknown PAR1 and PAR2 PH-domain-binding motifs in both pathological and physiological invasion processes.

Four Genes of Medicago truncatula Controlling Components of a Nod Factor Transduction Pathway

PubMed Central

Catoira, Romy; Galera, Christine; de Billy, Francoise; Penmetsa, R. Varma; Journet, Etienne-Pascal; Maillet, Fabienne; Rosenberg, Charles; Cook, Douglas; Gough, Clare; Dénarié, Jean

2000-01-01

Rhizobium nodulation (Nod) factors are lipo-chitooligosaccharides that act as symbiotic signals, eliciting several key developmental responses in the roots of legume hosts. Using nodulation-defective mutants of Medicago truncatula, we have started to dissect the genetic control of Nod factor transduction. Mutants in four genes (DMI1, DMI2, DMI3, and NSP) were pleiotropically affected in Nod factor responses, indicating that these genes are required for a Nod factor–activated signal transduction pathway that leads to symbiotic responses such as root hair deformations, expressions of nodulin genes, and cortical cell divisions. Mutant analysis also provides evidence that Nod factors have a dual effect on the growth of root hair: inhibition of endogenous (plant) tip growth, and elicitation of a novel tip growth dependent on (bacterial) Nod factors. dmi1, dmi2, and dmi3 mutants are also unable to establish a symbiotic association with endomycorrhizal fungi, indicating that there are at least three common steps to nodulation and endomycorrhization in M. truncatula and providing further evidence for a common signaling pathway between nodulation and mycorrhization. PMID:11006338

Human Factors in Automated and Robotic Space Systems: Proceedings of a symposium. Part 2

NASA Technical Reports Server (NTRS)

1987-01-01

Human factors research likely to produce results applicable to the development of a NASA space station is discussed. The particular sessions covered in Part 2 include: (1) computer aided monitoring and decision making; (2) telepresence and supervisory control; (3) social factors in productivity and performance; and (4) the human role in space systems. Papers from each subject area are reproduced and the discussions from each area are summarized.

Risk factors in facial hyperpigmentation in Maghrebian population - a case-control study.

PubMed

Benchikhi, H; Atide, N; Jroundi, I; Humbert, P; Lakhdar, H

2012-10-01

Triggering factors seem to be multiple in the pathogenesis of facial hyperpigmentation (FH), as dark skin types, pregnancy, sun exposure… The aim of this study was to investigate the risk factors for FH in Maghrebian population. Patients with FH were included in a case-controlled study. Following data were recorded: age, sex, parity, phototype, FH and hormonal-related history, endocrinological features, sunlight exposure, specific cultural behaviours, use of topic corticosteroids and sunscreens. One hundred women (mean age 29.5 ± 13.7 years) were included with 200 age-matched controls. Duration of FH was 32.9 ± 42.2 months. There was a statistically significant relation between FH and hirsutism (P = 0.009), troubles of menstruations (P = 0.008), but not with acne (P = 0.23) and contraceptive oral (P = 0.06) drugs or with history of thyroid disorders (P = 0.13). For cultural factors, there were a statistical significant relation with rubbing by flannel glove (P < 0.05), use of dark soap (P = 0.009) and traditional masks (P < 0.05) but both groups were used to go to hammam. A strong relation was observed between FH and use of topical corticosteroids: 40% in the FH group vs. 5% in the control group (P < 0.05). Both groups used to apply sunscreens: 70% in the FH group and 67% in the control group where as there were no differences in the two groups for sun exposure. No statistical differences were observed regarding to age, phototypes and grade of parity. Our study demonstrated a relation between FH and hyperestrogenemia, rubbing with a friction glove, use of moroccan traditional masks and application of topical steroids. The eviction of all these triggering factors could be an adjuvant recommendation in the assessment of FH. © 2012 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

N2O and NO2 Emissions from Heavy-Duty Diesel Trucks with Advanced Emission Controls

NASA Astrophysics Data System (ADS)

Preble, C.; Harley, R.; Kirchstetter, T.

2014-12-01

Diesel engines are the largest source of nitrogen oxides (NOx) emissions nationally, and also a major contributor to the black carbon (BC) fraction of fine particulate matter (PM). Recently, diesel particle filter (DPF) and selective catalytic reduction (SCR) emission control systems that target exhaust PM and NOx have become standard equipment on new heavy-duty diesel trucks. However, the deliberate catalytic oxidation of engine-out nitric oxide (NO) to nitrogen dioxide (NO2) in continuously regenerating DPFs leads to increased tailpipe emission of NO2. This is of potential concern due to the toxicity of NO2 and the resulting increases in atmospheric formation of other air pollutants such as ozone, nitric acid, and fine PM. While use of SCR reduces emissions of both NO and NO2, it may lead to increased emissions of nitrous oxide (N2O), a potent greenhouse gas. Here we report results from on-road measurements of heavy-duty diesel truck emissions conducted at the Port of Oakland and the Caldecott Tunnel in the San Francisco Bay Area. Emission factors (g pollutant per kg of diesel) were linked via recorded license plates to individual truck attributes, including engine model year and installed emission control equipment. Between 2009 and 2013, the fraction of DPF-equipped trucks at the Port of Oakland increased from 2 to 99%, and median engine age decreased from 11 to 6 years. Over the same period, fleet-average emission factors for black carbon and NOx decreased by 76 ± 22% and 53 ± 8%, respectively. However, direct emissions of NO2 increased, and consequently the NO2/NOx emission ratio increased from 0.03 ± 0.02 to 0.18 ± 0.03. Older trucks retrofitted with DPFs emitted approximately 3.5 times more NO2 than newer trucks equipped with both DPF and SCR. Preliminary data from summer 2014 measurements at the Caldecott Tunnel suggest that some older trucks have negative emission factors for N2O, and that for newer trucks, N2O emission factors have changed sign and

Potential risk factors for dental caries in Type 2 diabetic patients.

PubMed

Almusawi, M A; Gosadi, I; Abidia, R; Almasawi, M; Khan, H A

2018-05-11

Diabetic patients are known to be at higher risk for dental caries. However, the role of potential risk factors such as blood glucose, salivary glucose and glycaemic control in the occurrence of dental caries in type 2 diabetes (T2D) is not clearly understood so far, and therefore, it was evaluated in this study. This cross-sectional study was conducted on 100 T2D patients from Saudi Arabia. The caries risk assessment was evaluated using the guidelines of Caries Management by Risk Assessment (CAMBRA). Cariogenic bacteria load in saliva was determined by a chair-side test kit. The levels of fasting blood glucose (FBG), salivary glucose and HbA1c were analysed. Majority of the patients had dental caries (84%), exposed root surfaces (92%) and heavy plaque (73%), whereas 66% of patients suffered from xerostomia. The frequency of patients with high counts of Streptococcus mutans and Lactobacilli (LB) were 78% and 42%, respectively. There were significant associations between dental caries risk and FBG, HbA1c and salivary glucose. After categorizing the patients into 3 categories of glycaemic control, we observed a significant association between glycaemic control and dental caries risk. Type 2 diabetes patients are at high risk for dental caries, which is directly associated with FBG, HbA1c and salivary glucose. This is the first study measuring dental caries and its risk factors in T2D patients from Saudi Arabia. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Modifiable lifestyle factors associated with osteoporosis in Korean men: a case-control study.

PubMed

Park, Kye-Yeung; Hwang, Hwan-Sik; Park, Hoon-Ki

2017-12-01

The prevention, education, and treatment of osteoporosis are all recognized as important components in men as well as women. This study revealed that the lifestyle factors associated with male osteoporosis included being underweight and being a current smoker. Being overweight or obese and having a regular exercise habit were negatively associated with male osteoporosis. Osteoporosis is a significant health problem in Korea and worldwide. Although osteoporosis is less prevalent in males than in females, the fracture-related mortality rate is higher in males than in females. The aim of this study was to investigate the relationship of modifiable lifestyle factors in males with osteoporosis. A case-control study was performed in men who visited a single university hospital for a medical check-up between August 2003 and July 2016. Patients were classified in the case group according to the World Health Organization (WHO) Osteoporosis Criteria. The control group was created by matching patients according to age and check-up date. Lifestyle factors were evaluated by a self-assessment questionnaire. Multivariate conditional logistic regression was used to examine the association between lifestyle factors and male osteoporosis with age stratification at 50 years. A total of 1304 subjects were included in this analysis, 326 of whom were in the case group and 978 of whom were in the control group. Within their age group, subjects with osteoporosis were more often underweight (odds ratio [OR] = 2.35, 95% confidence interval [CI], 1.11-4.98) or more often current smokers (2.22, 1.50-3.28) than control subjects. The subjects who were overweight (0.45, 0.32-0.64), obese (0.19, 0.13-0.27), had an irregular exercise habit (0.64, 0.43-0.94), or had a regular exercise habit (0.40, 0.28-0.57) were more likely to have normal bone status. Alcohol drinking habit had no significant association with male osteoporosis. Several modifiable lifestyle factors were associated with male

A unique stylopod patterning mechanism by Shox2-controlled osteogenesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ye, Wenduo; Song, Yingnan; Huang, Zhen

Here, vertebrate appendage patterning is programmed by Hox-TALE factorbound regulatory elements. However, it remains unclear which cell lineages are commissioned by Hox-TALE factors to generate regional specific patterns and whether other Hox-TALE co-factors exist. In this study, we investigated the transcriptional mechanisms controlled by the Shox2 transcriptional regulator in limb patterning. Harnessing an osteogenic lineage-specific Shox2 inactivation approach we show that despite widespread Shox2 expression in multiple cell lineages, lack of the stylopod observed upon Shox2 deficiency is a specific result of Shox2 loss of function in the osteogenic lineage. ChIP-Seq revealed robust interaction of Shox2 with cis-regulatory enhancers clusteringmore » around skeletogenic genes that are also bound by Hox-TALE factors, supporting a lineage autonomous function of Shox2 in osteogenic lineage fate determination and skeleton patterning. Pbx ChIP-Seq further allowed the genome-wide identification of cis-regulatory modules exhibiting co-occupancy of Pbx, Meis and Shox2 transcriptional regulators. Integrative analysis of ChIP-Seq and RNA-Seq data and transgenic enhancer assays indicate that Shox2 patterns the stylopod as a repressor via interaction with enhancers active in the proximal limb mesenchyme and antagonizes the repressive function of TALE factors in osteogenesis.« less

A unique stylopod patterning mechanism by Shox2-controlled osteogenesis

DOE PAGES

Ye, Wenduo; Song, Yingnan; Huang, Zhen; ...

2016-06-10

Here, vertebrate appendage patterning is programmed by Hox-TALE factorbound regulatory elements. However, it remains unclear which cell lineages are commissioned by Hox-TALE factors to generate regional specific patterns and whether other Hox-TALE co-factors exist. In this study, we investigated the transcriptional mechanisms controlled by the Shox2 transcriptional regulator in limb patterning. Harnessing an osteogenic lineage-specific Shox2 inactivation approach we show that despite widespread Shox2 expression in multiple cell lineages, lack of the stylopod observed upon Shox2 deficiency is a specific result of Shox2 loss of function in the osteogenic lineage. ChIP-Seq revealed robust interaction of Shox2 with cis-regulatory enhancers clusteringmore » around skeletogenic genes that are also bound by Hox-TALE factors, supporting a lineage autonomous function of Shox2 in osteogenic lineage fate determination and skeleton patterning. Pbx ChIP-Seq further allowed the genome-wide identification of cis-regulatory modules exhibiting co-occupancy of Pbx, Meis and Shox2 transcriptional regulators. Integrative analysis of ChIP-Seq and RNA-Seq data and transgenic enhancer assays indicate that Shox2 patterns the stylopod as a repressor via interaction with enhancers active in the proximal limb mesenchyme and antagonizes the repressive function of TALE factors in osteogenesis.« less

Risk factors for pediatric arachnoid cyst rupture/hemorrhage: a case-control study.

PubMed

Cress, Marshall; Kestle, John R W; Holubkov, Richard; Riva-Cambrin, Jay

2013-05-01

As the availability of imaging modalities has increased, the finding of arachnoid cysts has become common. Accurate patient counseling regarding physical activity or risk factors for cyst rupture or hemorrhage has been hampered by the lack of definitive association studies. This case-control study evaluated factors that are associated with arachnoid cyst rupture (intracystic hemorrhage, adjacent subdural hematoma, or adjacent subdural hygroma) in pediatric patients with previously asymptomatic arachnoid cysts. Patients with arachnoid cysts and intracystic hemorrhage, adjacent subdural hygroma, or adjacent subdural hematoma treated at a single institution from 2005 to 2010 were retrospectively identified. Two unruptured/nonhemorrhagic controls were matched to each case based on patient age, sex, anatomical cyst location, and side. Risk factors evaluated included arachnoid cyst size, recent history of head trauma, and altitude at residence. The proportion of imaged arachnoid cysts that presented either originally or subsequently with a rupture or hemorrhage was 6.0%. Larger cyst size, as defined by maximal cyst diameter, was significantly associated with cyst rupture/hemorrhage (P < .001). When dichotomized with a 5-cm cutoff, 9/13 larger cysts ruptured and/or hemorrhaged, whereas only 5/29 smaller cysts ruptured/hemorrhaged (odds ratio = 16.5 (confidence interval [2.5, ∞]). A recent history of head trauma was also significantly associated with the outcome (P < .001; odds ratio = 25.1 (confidence interval [4.0, ∞]). Altitude was not associated with arachnoid cyst rupture or hemorrhage. This case-control study suggests that larger arachnoid cyst size and recent head trauma are risk factors for symptomatic arachnoid cyst rupture/hemorrhage.

Factors Controlling Fluxes of Nitrous Oxide (N-N2O) in AN Upland Tropical Forest (atlantic Forest) - Brazil, Rio de Janeiro

NASA Astrophysics Data System (ADS)

Perry, I.; de Mello, W. Z.; McDowell, W. H.

2010-12-01

Atlantic Forest is located along the Brazilian coast and inland to Paraguay and Argentina. It has been largely devastated years ago by anthropogenic activities, such as agriculture and urbanization. Only ten percent of its original area remains (100.000 km2), which is concentrated on high lands. Atlantic Forest is a biodiversity hotspot that receives high nitrogen (N) input through atmospheric deposition in forests of Rio de Janeiro; however, not much is known about the consequences of this N addition. This study has been conducted in the Serra dos Orgaos National Park (SONP - 22.782 km2) located a few kilometers Northeast of Rio de Janeiro Metropolitan Region, Sea Mountain. The forest, characterized as Tropical Moist Forest, is rigorously protected. Vegetation varies along the altitudinal gradient, where the highest peak is at 2,200m asl. Previous studies reported that N atmospheric deposition in SONP varies from 14 to 24 kg ha-1 year-1. The high N deposition on tropical forests increases emission to the atmosphere of N-N2O, a greenhouse gas. There is a lack of N-N2O measurements in tropical forests, mainly in upland tropical forests. We present fluxes of N-N2O from a Brazilian upland tropical forest, and assess the factors controlling N-N2O fluxes. Samples were collected from eight grids (48m2), between 330-451m asl (Subtropical vegetation) and eight grids between 1137-1251m (Montane vegetation), during the dry (July 2008) and wet (Jan-Feb 2009) seasons. Daily, N-N2O (N=372) and soil (N=185) were collected. Nitrous oxide emission was 0,7 (lower altitude) and 0,3 kgN ha-1 year-1 (higher altitude), which is lower than in other upland tropical forests, such as Luquillo Experimental Forest, Puerto Rico, where atmospheric N input (4 kg ha-1 year-1) is not as high as in SONP. Water filled pore space, soil temperature, phosphorus and C:N are the main factors controlling N-N2O fluxes. Manganese was not a good indicator for presence or absence of N-N2O. Higher N-N2O

Daughter-Specific Transcription Factors Regulate Cell Size Control in Budding Yeast

PubMed Central

Di Talia, Stefano; Wang, Hongyin; Skotheim, Jan M.; Rosebrock, Adam P.; Futcher, Bruce; Cross, Frederick R.

2009-01-01

In budding yeast, asymmetric cell division yields a larger mother and a smaller daughter cell, which transcribe different genes due to the daughter-specific transcription factors Ace2 and Ash1. Cell size control at the Start checkpoint has long been considered to be a main regulator of the length of the G1 phase of the cell cycle, resulting in longer G1 in the smaller daughter cells. Our recent data confirmed this concept using quantitative time-lapse microscopy. However, it has been proposed that daughter-specific, Ace2-dependent repression of expression of the G1 cyclin CLN3 had a dominant role in delaying daughters in G1. We wanted to reconcile these two divergent perspectives on the origin of long daughter G1 times. We quantified size control using single-cell time-lapse imaging of fluorescently labeled budding yeast, in the presence or absence of the daughter-specific transcriptional regulators Ace2 and Ash1. Ace2 and Ash1 are not required for efficient size control, but they shift the domain of efficient size control to larger cell size, thus increasing cell size requirement for Start in daughters. Microarray and chromatin immunoprecipitation experiments show that Ace2 and Ash1 are direct transcriptional regulators of the G1 cyclin gene CLN3. Quantification of cell size control in cells expressing titrated levels of Cln3 from ectopic promoters, and from cells with mutated Ace2 and Ash1 sites in the CLN3 promoter, showed that regulation of CLN3 expression by Ace2 and Ash1 can account for the differential regulation of Start in response to cell size in mothers and daughters. We show how daughter-specific transcriptional programs can interact with intrinsic cell size control to differentially regulate Start in mother and daughter cells. This work demonstrates mechanistically how asymmetric localization of cell fate determinants results in cell-type-specific regulation of the cell cycle. PMID:19841732

Glycemic control and antidiabetic drugs in type 2 diabetes mellitus patients with renal complications

PubMed Central

Huri, Hasniza Zaman; Lim, Lay Peng; Lim, Soo Kun

2015-01-01

Background Good glycemic control can delay the progression of kidney diseases in type 2 diabetes mellitus (T2DM) patients with renal complications. To date, the association between antidiabetic agents and glycemic control in this specific patient population is not well established. Purpose This study aimed to identify antidiabetic regimens as well as other factors that associated with glycemic control in T2DM patients with different stages of chronic kidney disease (CKD). Patients and methods This retrospective, cross-sectional study involved 242 T2DM inpatients and outpatients with renal complications from January 2009 to March 2014 and was conducted in a tertiary teaching hospital in Malaysia. Glycated hemoglobin (A1C) was used as main parameter to assess patients’ glycemic status. Patients were classified to have good (A1C <7%) or poor glycemic control (A1C ≥7%) based on the recommendations of the American Diabetes Association. Results Majority of the patients presented with CKD stage 4 (43.4%). Approximately 55.4% of patients were categorized to have poor glycemic control. Insulin (57.9%) was the most commonly prescribed antidiabetic medication, followed by sulfonylureas (43%). Of all antidiabetic regimens, sulfonylureas monotherapy (P<0.001), insulin therapy (P=0.005), and combination of biguanides with insulin (P=0.038) were found to be significantly associated with glycemic control. Other factors including duration of T2DM (P=0.004), comorbidities such as anemia (P=0.024) and retinopathy (P=0.033), concurrent medications such as erythropoietin therapy (P=0.047), α-blockers (P=0.033), and antigouts (P=0.003) were also correlated with A1C. Conclusion Identification of factors that are associated with glycemic control is important to help in optimization of glucose control in T2DM patients with renal complication. PMID:26300627

Indoor environmental risk factors in young asthmatics: a case-control study.

PubMed

Lindfors, A; Wickman, M; Hedlin, G; Pershagen, G; Rietz, H; Nordvall, S L

1995-11-01

One hundred and ninety three children with asthma and 318 controls aged 1-4 years were evaluated for atopic heredity and exposure to possible indoor risk factors for asthma-for example exposure to furred pets, tobacco smoke, and home dampness. A subgroup of cases were classified as cat and/or dog allergic on the basis of skin prick tests. Heredity for asthma was a significant risk factor (odds ratio (OR) 3.0, confidence interval (CI) 2.1 to 4.6). Environmental tobacco smoke was associated with an excess risk for asthma (OR 1.7, CI 1.1 to 2.3) and signs of home dampness tended to increase this risk (OR 1.3, CI 0.9 to 2.0). High dose exposure to cat and/or dog resulted in an increased risk only in asthma cases sensitised to cat and/or dog (OR 2.7, CI 1.0 to 7.3). A combination of high dose exposure to cat and/or dog, environmental tobacco smoke and damp housing was associated with an OR of 8.0 (CI 1.9 to 34.1). Raised indoor humidity has been shown to reflect low air exchange, which may also lead to increased doses of inhaled aeroallergens and tobacco smoke, and contribute to the interaction between the three risk factors.

Indoor environmental risk factors in young asthmatics: a case-control study.

PubMed Central

Lindfors, A; Wickman, M; Hedlin, G; Pershagen, G; Rietz, H; Nordvall, S L

1995-01-01

One hundred and ninety three children with asthma and 318 controls aged 1-4 years were evaluated for atopic heredity and exposure to possible indoor risk factors for asthma-for example exposure to furred pets, tobacco smoke, and home dampness. A subgroup of cases were classified as cat and/or dog allergic on the basis of skin prick tests. Heredity for asthma was a significant risk factor (odds ratio (OR) 3.0, confidence interval (CI) 2.1 to 4.6). Environmental tobacco smoke was associated with an excess risk for asthma (OR 1.7, CI 1.1 to 2.3) and signs of home dampness tended to increase this risk (OR 1.3, CI 0.9 to 2.0). High dose exposure to cat and/or dog resulted in an increased risk only in asthma cases sensitised to cat and/or dog (OR 2.7, CI 1.0 to 7.3). A combination of high dose exposure to cat and/or dog, environmental tobacco smoke and damp housing was associated with an OR of 8.0 (CI 1.9 to 34.1). Raised indoor humidity has been shown to reflect low air exchange, which may also lead to increased doses of inhaled aeroallergens and tobacco smoke, and contribute to the interaction between the three risk factors. PMID:8554356

Environmental factors in infancy and ulcerative colitis in the Central South of Chile: a case-control study.

PubMed

Boneberger, Anja; Weiss, Eduardo Hebel; Calvo, Mario; Torres, Lilibeth; Wagner, Johanna; Kabesch, Michael; Radon, Katja

2011-10-01

Evidence for the role of the hygiene hypothesis and the development of Ulcerative Colitis (UC) is unclear. We aimed to explore the association between environmental factors in infancy and UC. A hospital-based case-control study (52 UC cases, response: 77%, 174 age- , sex and place of living matched controls, response: 62%) was carried out in the Central South of Chile in 2009/2010. Patients or parents underwent a personal interview about early life experiences. High paternal education (adjusted Odds Ratio (aOR): 2.1; 95% CI: 1.0-4.5) as proxy for socioeconomic status was positively associated with case status in the final multivariate logistic regression model. Likewise, having older siblings was a risk factor for UC (aOR: 2.2; 95%CI: 1.1.-4.4). The importance for some early life environmental factors in the development of UC was established. However, the role of the hygiene hypothesis could not be confirmed for all environmental factors. Copyright © 2011 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Therapeutic potential of fibroblast growth factor-2 for hypertrophic scars: upregulation of MMP-1 and HGF expression.

PubMed

Eto, Hitomi; Suga, Hirotaka; Aoi, Noriyuki; Kato, Harunosuke; Doi, Kentaro; Kuno, Shinichiro; Tabata, Yasuhiko; Yoshimura, Kotaro

2012-02-01

Although hypertrophic scars (HTSs) and keloids are challenging problems, their pathogenesis is not well understood, making therapy difficult. We showed that matrix metalloproteinase (MMP)-1 expression was downregulated in HTS compared with normal skin from the same patients, whereas type 1 and 3 collagen and transforming growth factor-β (TGF-β) were upregulated. These differences, however, were not seen in cultured fibroblasts, suggesting the involvement of microenvironmental factors in the pathogenesis of HTS. Fibroblast growth factor-2 (FGF-2) highly upregulated the expression of MMP-1 and hepatocyte growth factor (HGF) in both HTS-derived and control fibroblasts; the upregulation was reversed by extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) inhibitors. An animal study using human HTS tissue implanted into nude mice indicated that controlled-release FGF-2 resulted in significantly less weight and decreased hydroxyproline content in HTS. Degradation of collagen fibers in FGF-2-treated HTS was also confirmed histologically. Western blotting showed that FGF-2-treated HTS expressed significantly higher MMP-1 protein than control. Decreased MMP-1 expression may be an important transcriptional change in HTS, and its reversal as well as upregulation of HGF by FGF-2 could be a new therapeutic approach for HTS.

Antepartum risk factors for newborn encephalopathy: the Western Australian case-control study

PubMed Central

Badawi, Nadia; Kurinczuk, Jennifer J; Keogh, John M; Alessandri, Louisa M; O’Sullivan, Fiona; Burton, Paul R; Pemberton, Patrick J; Stanley, Fiona J

1998-01-01

Objective To ascertain antepartum predictors of newborn encephalopathy in term infants. Design Population based, unmatched case-control study. Setting Metropolitan area of Western Australia, June 1993 to September 1995. Subjects All 164 term infants with moderate or severe newborn encephalopathy; 400 randomly selected controls. Main outcome measures Adjusted odds ratio estimates. Results The birth prevalence of moderate or severe newborn encephalopathy was 3.8/1000 term live births. The neonatal fatality was 9.1%. The risk of newborn encephalopathy increased with increasing maternal age and decreased with increasing parity. There was an increased risk associated with having a mother who was unemployed (odds ratio 3.60), an unskilled manual worker (3.84), or a housewife (2.48). Other risk factors from before conception were not having private health insurance (3.46), a family history of seizures (2.55), a family history of neurological disease (2.73), and infertility treatment (4.43). Risk factors during pregnancy were maternal thyroid disease (9.7), severe pre-eclampsia (6.30), moderate or severe bleeding (3.57), a clinically diagnosed viral illness (2.97), not having drunk alcohol (2.91); and placenta described at delivery as abnormal (2.07). Factors related to the baby were birth weight adjusted for gestational age between the third and ninth centile (4.37) or below the third centile (38.23). The risk relation with gestational age was J shaped with 38 and 39 weeks having the lowest risk. Conclusions The causes of newborn encephalopathy are heterogeneous and many of the causal pathways start before birth. Key messagesThe birth prevalence of moderate or severe newborn encephalopathy was 3.8 per 1000 term live births and the neonatal case fatality was 9.1%Independent risk factors before conception and in the antepartum period for newborn encephalopathy include socioeconomic status, family history of seizures or other neurological disease, conception after

Intermittent Vagal Nerve Block for Improvements in Obesity, Cardiovascular Risk Factors, and Glycemic Control in Patients with Type 2 Diabetes Mellitus: 2-Year Results of the VBLOC DM2 Study.

PubMed

Shikora, Scott A; Toouli, James; Herrera, Miguel F; Kulseng, Bård; Brancatisano, Roy; Kow, Lilian; Pantoja, Juan P; Johnsen, Gjermund; Brancatisano, Anthony; Tweden, Katherine S; Knudson, Mark B; Billington, Charles J; Billingto, Charles J

2016-05-01

One-year results of the VBLOC DM2 study found that intermittent vagal blocking (VBLOC therapy) was safe among subjects with obesity and type 2 diabetes mellitus (T2DM) and led to significant weight loss and improvements in glycemic parameters and cardiovascular risk factors. Longer-term data are needed to determine whether the results are sustained. VBLOC DM2 is a prospective, observational study of 28 subjects with T2DM and body mass index (BMI) between 30 and 40 kg/m(2) to assess mid-term safety and weight loss and improvements in glycemic parameters, and other cardiovascular risk factors with VBLOC therapy. Continuous outcome variables are reported using mixed models. At 24 months, the mean percentage of excess weight loss was 22% (95% CI, 15 to 28, p < 0.0001) or 7.0% total body weight loss (95% CI, 5.0 to 9.0, p < 0.0001). Hemoglobin A1c decreased by 0.6 percentage points (95% CI, 0.2 to 1.0, p = 0.0026) on average from 7.8% at baseline. Fasting plasma glucose declined by 15 mg/dL (95% CI, 0 to 29, p = 0.0564) on average from 151 mg/dL at baseline. Among subjects who were hypertensive at baseline, systolic blood pressure declined 10 mmHg (95% CI, 2 to 19, p = 0.02), diastolic blood pressure declined by 6 mmHg (95% CI, 0 to 12, p = 0.0423), and mean arterial pressure declined 7 mmHg (95% CI, 2 to 13, p = 0.014). Waist circumference was significantly reduced by 7 cm (95% CI, 4 to 10, p < 0.0001) from a baseline of 120 cm. The most common adverse events were mild or moderate heartburn, implant site pain, and constipation. Improvements in obesity and glycemic control were largely sustained after 2 years of treatment with VBLOC therapy with a well-tolerated risk profile.

Gender, diabetes education, and psychosocial factors are associated with persistent poor glycemic control in patients with type 2 diabetes in the Joint Asia Diabetes Evaluation (JADE) program.

PubMed

Yin, Junmei; Yeung, Roseanne; Luk, Andrea; Tutino, Greg; Zhang, Yuying; Kong, Alice; Chung, Harriet; Wong, Rebecca; Ozaki, Risa; Ma, Ronald; Tsang, Chiu-Chi; Tong, Peter; So, Wingyee; Chan, Juliana

2016-01-01

Factors associated with persistent poor glycemic control were explored in patients with type 2 diabetes under the Joint Asia Diabetes Evaluation (JADE) program. Chinese adults enrolled in JADE with HbA1c ≥8% at initial comprehensive assessment (CA1) and repeat assessment were analyzed. The improved group was defined as those with a ≥1% absolute reduction in HbA1c, and the unimproved group was those with <1% reduction at the repeat CA (CA2). Of 4458 enrolled patients with HbA1c ≥8% at baseline, 1450 underwent repeat CA. After a median interval of 1.7 years (interquartile range[IQR] 1.1-2.2) between CA1 and CA2, the unimproved group (n = 677) had a mean 0.4% (95% confidence interval [CI] 0.3%, 0.5%) increase in HbA1c compared with a mean 2.8% reduction (95% CI -2.9, -2.6%) in the improved group (n = 773). The unimproved group had a female preponderance with lower education level, and was more likely to be insulin treated. Patients in the improved group received more diabetes education between CAs with improved self-care behaviors, whereas the unimproved group had worsening of health-related quality of life at CA2. Apart from female gender, long disease duration, low educational level, obesity, retinopathy, history of hypoglycemia, and insulin use, lack of education from diabetes nurses between CAs had the strongest association for persistent poor glycemic control. These results highlight the multidimensional nature of glycemic control, and the importance of diabetes education and optimizing diabetes care by considering psychosocial factors. © 2015 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

Factors Influencing Prevention and Control of Malaria among Pregnant Women Resident in Urban Slums, Southern Ghana.

PubMed

Dako-Gyeke, Mavis; Kofie, Humphrey M

2015-03-01

Throughout Africa and particularly in Ghana, there are concerns about malaria infection during pregnancy. This study aimed to investigate factors that influence malaria prevention and control practices among pregnant women residing in Chorkor and Korle-Gonno in Accra, Ghana. One hundred and twenty pregnant women between ages 18-49 were randomly recruited during antenatal sessions at a maternity facility in Accra, as participants for the study. An interviewer-administered questionnaire was used to collect data, which were analysed using SPSS version16.0. It was found that in Chorkor and Korle-Gonno, 57.4% and 42.6% participants respectively reported having been infected with malaria during their current pregnancy. There was no significant relationship between religious beliefs of participants and their malaria prevention and control practices (X2 = 0.28, P = .53). However, there was a significant relationship between malaria prevention and control practices of participants and their income earning (X2 = 53.94, P = .00) and employment (X2 = 61.76, P = .00) statuses. With the exception of ethnicity (X2 = 35.62, P =.22), other socio-cultural conditions had a significant relationship with malaria prevention and control practices of the participants. The findings suggest the need to consider and integrate factors, such as poverty and poor living conditions in malaria prevention and control strategies.

Human Factors Considerations for Safe Recovery from Faults In Flight Control Systems

NASA Technical Reports Server (NTRS)

Pritchett, Amy; Belcastro, C. M. (Technical Monitor)

2003-01-01

It is now possible - and important - to develop systems to help resolve Flight Control System (FCS) faults. From a human factors viewpoint, it is imperative that these systems take on roles, and provide functions, that are the most supportive to the pilot, given the stress, time pressure and workload they may experience following a FCS fault. FCS fault recovery systems may provide several different functions, including alerting, control assistance, and decision aiding. The biggest human factors questions are in the role suitable for the technology, and its specific functioning to achieve that role. Specifically, for these systems to be effective, they must meet the fundamental requirements that (1) they alert pilots to problems early enough that the pilot can reasonably resolve the fault and regain control of the aircraft and that (2) if the aircraft s handling qualities are severely degraded the HMS provide the appropriate stability augmentation to help the pilot stabilize and control the aircraft. This project undertook several research steps to develop such systems, focusing on the capabilities of pilots and on realistically attainable technologies. The ability to estimate which functions are the most valuable will help steer system development in the directions that can establish the highest safety levels.

A gene regulatory network controlled by the NAC transcription factor ANAC092/AtNAC2/ORE1 during salt-promoted senescence.

PubMed

Balazadeh, Salma; Siddiqui, Hamad; Allu, Annapurna D; Matallana-Ramirez, Lilian P; Caldana, Camila; Mehrnia, Mohammad; Zanor, Maria-Inés; Köhler, Barbara; Mueller-Roeber, Bernd

2010-04-01

The onset and progression of senescence are under genetic and environmental control. The Arabidopsis thaliana NAC transcription factor ANAC092 (also called AtNAC2 and ORE1) has recently been shown to control age-dependent senescence, but its mode of action has not been analysed yet. To explore the regulatory network administered by ANAC092 we performed microarray-based expression profiling using estradiol-inducible ANAC092 overexpression lines. Approximately 46% of the 170 genes up-regulated upon ANAC092 induction are known senescence-associated genes, suggesting that the NAC factor exerts its role in senescence through a regulatory network that includes many of the genes previously reported to be senescence regulated. We selected 39 candidate genes and confirmed their time-dependent response to enhanced ANAC092 expression by quantitative RT-PCR. We also found that the majority of them (24 genes) are up-regulated by salt stress, a major promoter of plant senescence, in a manner similar to that of ANAC092, which itself is salt responsive. Furthermore, 24 genes like ANAC092 turned out to be stage-dependently expressed during seed growth with low expression at early and elevated expression at late stages of seed development. Disruption of ANAC092 increased the rate of seed germination under saline conditions, whereas the opposite occurred in respective overexpression plants. We also detected a delay of salinity-induced chlorophyll loss in detached anac092-1 mutant leaves. Promoter-reporter (GUS) studies revealed transcriptional control of ANAC092 expression during leaf and flower ageing and in response to salt stress. We conclude that ANAC092 exerts its functions during senescence and seed germination through partly overlapping target gene sets.

Function and regulation of heat shock factor 2 during mouse embryogenesis

PubMed Central

Rallu, M.; Loones, Mt.; Lallemand, Y.; Morimoto, R.; Morange, M.; Mezger, V.

1997-01-01

The spontaneous expression of heat shock genes during development is well documented in many animal species, but the mechanisms responsible for this developmental regulation are only poorly understood. In vertebrates, additional heat shock transcription factors, distinct from the heat shock factor 1 (HSF1) involved in the stress response, were suggested to be involved in this developmental control. In particular, the mouse HSF2 has been found to be active in testis and during preimplantation development. However, the role of HSF2 and its mechanism of activation have remained elusive due to the paucity of data on its expression during development. In this study, we have examined HSF2 expression during the postimplantation phase of mouse development. Our data show a developmental regulation of HSF2, which is expressed at least until 15.5 days of embryogenesis. It becomes restricted to the central nervous system during the second half of gestation. It is expressed in the ventricular layer of the neural tube which contains mitotically active cells but not in postmitotic neurons. Parallel results were obtained for mRNA, protein, and activity levels, demonstrating that the main level of control was transcriptional. The detailed analysis of the activity of a luciferase reporter gene under the control of the hsp70.1 promoter, as well as the description of the protein expression patterns of the major heat shock proteins in the central nervous system, show that HSF2 and heat shock protein expression domains do not coincide. This result suggests that HFS2 might be involved in other regulatory developmental pathways and paves the way to new functional approaches. PMID:9122205

Risk and protective factors for falls on stairs in young children: multicentre case–control study

PubMed Central

Kendrick, D; Zou, K; Ablewhite, J; Watson, M; Coupland, C; Kay, B; Hawkins, A; Reading, R

2016-01-01

Aim To investigate risk and protective factors for stair falls in children aged <5 years. Methods Multicentre case–control study at hospitals, minor injury units and general practices in and around four UK study centres. Cases were children with medically attended stair fall injuries. Controls were matched on age, sex, calendar time and study centre. A total of 610 cases and 2658 controls participated. Results Cases’ most common injuries were bangs on the head (66%), cuts/grazes not requiring stitches (14%) and fractures (12%). Parents of cases were significantly more likely not to have stair gates (adjusted OR (AOR) 2.50, 95% CI 1.90 to 3.29; population attributable fraction (PAF) 21%) or to leave stair gates open (AOR 3.09, 95% CI 2.39 to 4.00; PAF 24%) both compared with having closed stair gates. They were more likely not to have carpeted stairs (AOR 1.52, 95% CI 1.09 to 2.10; PAF 5%) and not to have a landing part-way up their stairs (AOR 1.34, 95% CI 1.08 to 1.65; PAF 18%). They were more likely to consider their stairs unsafe to use (AOR 1.46, 95% CI 1.07 to 1.99; PAF 5%) or to be in need of repair (AOR 1.71, 95% CI 1.16 to 2.50; PAF 5%). Conclusion Structural factors including having landings part-way up the stairs and keeping stairs in good repair were associated with reduced stair fall injury risk. Family factors including having stair gates, not leaving gates open and having stair carpets were associated with reduced injury risk. If these associations are causal, addressing these factors in housing policy and routine child health promotion could reduce stair fall injuries. PMID:26662926

Modulation of quorum sensing-controlled virulence factors by Nymphaea tetragona (water lily) extract.

PubMed

Hossain, Md Akil; Lee, Seung-Jin; Park, Ji-Yong; Reza, Md Ahsanur; Kim, Tae-Hwan; Lee, Ki-Ja; Suh, Joo-Won; Park, Seung-Chun

2015-11-04

Nymphaea tetragona is a widely distributed ornamental species with ethnomedicinal uses in the treatment of diarrhea, dysentery, eruptive fevers, and infections. The anti-infectious activities of this herb have already been assessed to clarify its traditional use as a medicine. In this study, we aimed to verify the inhibitory effects of N. tetragona 50% methanol extract (NTME) on quorum sensing (QS)-controlled virulence factors of bacteria since QS and its virulence factors are novel targets for antimicrobial therapy. The antibacterial activity of this extract was evaluated against Chromobacterium violaceum and Pseudomonas aeruginosa. The inhibition of the violacein pigment of C. violaceum by NTME was determined qualitative and quantitative using standard methods. The effects of NTME on swarming motility, biofilm viability, pyocyanin production, and LasA protease activity were evaluated using P. aeruginosa. Finally, the in vitro and in vivo cytotoxicity of NTME were verified by MTT assay and oral administration to rats, respectively. The extract had concentration-dependent antibacterial activity against gram-negative bacteria. NTME at 1/2× minimum inhibitory concentration (MIC), 1× MIC and 2× MIC significantly lowered the levels of violacein of C. violaceum compared to that of the control. The swarming motility of P. aeruginosa was inhibited by ≥70% by treatment with 1/2× MIC of NTME. There were remarkable reductions in pyocyanin production and LasA protease activity in the overnight culture supernatant of P. aeruginosa supplemented with NTME when compared with that of the untreated control. The confocal micrographs of 24h biofilms of P. aeruginosa exposed to NTME exhibited a lower number of live cells than the control. No toxic effect was observed in in vitro and in vivo cytotoxicity assays of NTME. NTME was demonstrated to have significant concentration-dependent inhibitory effects on quorum sensing-mediated virulence factors of bacteria with non

Molecular mechanisms of OLIG2 transcription factor in brain cancer

PubMed Central

Lian, Nathan; Kesari, Santosh

2016-01-01

Oligodendrocyte lineage transcription factor 2 (OLIG2) plays a pivotal role in glioma development. Here we conducted a comprehensive study of the critical gene regulatory networks involving OLIG2. These include the networks responsible for OLIG2 expression, its translocation to nucleus, cell cycle, epigenetic regulation, and Rho-pathway interactions. We described positive feedback loops including OLIG2: loops of epigenetic regulation and loops involving receptor tyrosine kinases. These loops may be responsible for the prolonged oncogenic activity of OLIG2. The proposed schemes for epigenetic regulation of the gene networks involving OLIG2 are confirmed by patient survival (Kaplan–Meier) curves based on the cancer genome atlas (TCGA) datasets. Finally, we elucidate the Coherent-Gene Modules (CGMs) networks—framework of OLIG2 involvement in cancer. We showed that genes interacting with OLIG2 formed eight CGMs having a set of intermodular connections. We showed also that among the genes involved in these modules the most connected hub is EGFR, then, on lower level, HSP90 and CALM1, followed by three lower levels including epigenetic genes KDM1A and NCOR1. The genes on the six upper levels of the hierarchy are involved in interconnections of all eight CGMs and organize functionally defined gene-signaling subnetworks having specific functions. For example, CGM1 is involved in epigenetic control. CGM2 is significantly related to cell proliferation and differentiation. CGM3 includes a number of interconnected helix–loop–helix transcription factors (bHLH) including OLIG2. Many of these TFs are partially controlled by OLIG2. The CGM4 is involved in PDGF-related: angiogenesis, tumor cell proliferation and differentiation. These analyses provide testable hypotheses and approaches to inhibit OLIG2 pathway and relevant feed-forward and feedback loops to be interrogated. This broad approach can be applied to other TFs. PMID:27447975

Mitochondrial respiratory control is lost during growth factor deprivation.

PubMed

Gottlieb, Eyal; Armour, Sean M; Thompson, Craig B

2002-10-01

The ability of cells to maintain a bioenergetically favorable ATP/ADP ratio confers a tight balance between cellular events that consume ATP and the rate of ATP production. However, after growth factor withdrawal, the cellular ATP/ADP ratio declines. To investigate these changes, mitochondria from growth factor-deprived cells isolated before the onset of apoptosis were characterized in vitro. Mitochondria from growth factor-deprived cells have lost their ability to undergo matrix condensation in response to ADP, which is accompanied by a failure to perform ADP-coupled respiration. At the time of analysis, mitochondria from growth factor-deprived cells were not depleted of cytochrome c and cytochrome c-dependent respiration was unaffected, demonstrating that the inhibition of the respiratory rate is not due to loss of cytochrome c. Agents that disrupt the mitochondrial outer membrane, such as digitonin, or maintain outer membrane exchange of adenine nucleotide, such as Bcl-x(L), restored ADP-dependent control of mitochondrial respiration. Together, these data suggest that the regulation of mitochondrial outer membrane permeability contributes to respiratory control.

Mitochondrial respiratory control is lost during growth factor deprivation

PubMed Central

Gottlieb, Eyal; Armour, Sean M.; Thompson, Craig B.

2002-01-01

The ability of cells to maintain a bioenergetically favorable ATP/ADP ratio confers a tight balance between cellular events that consume ATP and the rate of ATP production. However, after growth factor withdrawal, the cellular ATP/ADP ratio declines. To investigate these changes, mitochondria from growth factor-deprived cells isolated before the onset of apoptosis were characterized in vitro. Mitochondria from growth factor-deprived cells have lost their ability to undergo matrix condensation in response to ADP, which is accompanied by a failure to perform ADP-coupled respiration. At the time of analysis, mitochondria from growth factor-deprived cells were not depleted of cytochrome c and cytochrome c-dependent respiration was unaffected, demonstrating that the inhibition of the respiratory rate is not due to loss of cytochrome c. Agents that disrupt the mitochondrial outer membrane, such as digitonin, or maintain outer membrane exchange of adenine nucleotide, such as Bcl-xL, restored ADP-dependent control of mitochondrial respiration. Together, these data suggest that the regulation of mitochondrial outer membrane permeability contributes to respiratory control. PMID:12228733

Human Factors Analysis of Pipeline Monitoring and Control Operations: Final Technical Report

DOT National Transportation Integrated Search

2008-11-26

The purpose of the Human Factors Analysis of Pipeline Monitoring and Control Operations project was to develop procedures that could be used by liquid pipeline operators to assess and manage the human factors risks in their control rooms that may adv...

Family-Environmental Factors Associated with Attention Deficit Hyperactivity Disorder in Chinese Children: A Case-Control Study

PubMed Central

du Prel Carroll, Xianming; Yi, Honggang; Liang, Yuezhu; Pang, Ke; Leeper-Woodford, Sandra; Riccardi, Patrizia; Liang, Xianhong

2012-01-01

Background Attention deficit hyperactivity disorder (ADHD) is one of the most common psychiatric disorders, affecting an estimated 5 to 12% of school-aged children worldwide. From 15 to 19 million Chinese children suffer from ADHD. The aim of this study was to investigate the association between family-environmental factors and ADHD in a sample of Chinese children. Methods A pair-matched, case-control study was conducted with 161 ADHD children and 161 non-ADHD children of matching age and sex, all from 5–18 years of age. The ADHD subjects and the normal controls were all evaluated via structured diagnostic interviews. We examined the association between family-environmental factors and ADHD using the conditional multiple logistic regression with backward stepwise selection to predict the associated factors of ADHD. Results Having experienced emotional abuse and being a single child were both significant factors associated with children diagnosed with ADHD. ADHD subjects were more likely to have suffered from emotional abuse (OR = 11.09, 95% CI = 2.15–57.29, P = 0.004) and have been a single child in the family (OR = 6.32, 95% CI = 2.09–19.14, P = 0.001) when compared to normal controls. The results were not modified by other confounding factors. Conclusion Our findings provide evidence that family-environmental factors are associated with ADHD among children in China. These findings, if confirmed by future research, may help to decrease ADHD by increasing the awareness of the effects of childhood emotional abuse. PMID:23209774

L-2-Oxothiazolidine-4-Carboxylic Acid or α-Lipoic Acid Attenuates Airway Remodeling: Involvement of Nuclear Factor-κB (NF-κB), Nuclear Factor Erythroid 2p45-Related Factor-2 (Nrf2), and Hypoxia-Inducible Factor (HIF)

PubMed Central

Park, Seoung Ju; Lee, Kyung Sun; Lee, Su Jeong; Kim, So Ri; Park, Seung Yong; Jeon, Myoung Shin; Lee, Heung Bum; Lee, Yong Chul

2012-01-01

Reactive oxygen species (ROS) play a crucial role in the pathogenesis of acute and chronic respiratory diseases. Antioxidants have been found to ameliorate airway inflammation and hyperresponsiveness in animal models employing short-term exposure to allergen. However, little data are available on the effect of antioxidants on airway remodeling and signaling pathways in chronic asthma. In the present study, we used a long-term exposure murine model of allergic airway disease to evaluate the effects of an antioxidant, L-2-oxothiazolidine-4-carboxylic acid (OTC) or α-lipoic acid (LA) on airway remodeling, focusing on the ROS-related hypoxia-inducible signaling. Long-term challenge of ovalbumin (OVA) increased ROS production, airway inflammation, and airway hyperresponsiveness, and developed features of airway remodeling such as excessive mucus secretion, subepithelial fibrosis, and thickening of the peribronchial smooth muscle layer. Administration of OTC or LA reduced these features of asthma, including airway remodeling, which was accompanied by suppression of transforming growth factor-β1, vascular endothelial growth factor, and T-helper 2 cytokines. In addition, OVA-induced activation of nuclear factor-κB (NF-κB), nuclear factor erythroid 2p45-related factor-2 (Nrf2), hypoxia-inducible factor (HIF)-1α, and HIF-2α was reduced by OTC or LA. Our results also showed that OTC or LA down-regulated phosphoinositide 3-kinase activity and decreased phosphorylation of p38 mitogen-activated protein kinase but not extracellular signal-regulated kinase 1/2 or c-Jun N-terminal kinase. These findings demonstrate that OTC and LA can inhibit activation of NF-κB, Nrf2, and HIF, leading to attenuate allergen-induced airway remodeling. PMID:22942681

Factor Specific Differences in Locus of Control for Emotionally Disturbed and Normal Children

ERIC Educational Resources Information Center

Kendall, Philip C.; And Others

1976-01-01

Institutionalized emotionally disturbed boys and noninstitutionalized normal boys were administered the Nowicki-Strickland Locus of Control Scale for Children. Locus of control and separate factor scores were calculated. Helplessness factor scores, but not overall locus of control scores, differentiated the two groups. (BJG)

Early life course risk factors for childhood obesity: the IDEFICS case-control study.

PubMed

Bammann, Karin; Peplies, Jenny; De Henauw, Stefaan; Hunsberger, Monica; Molnar, Denes; Moreno, Luis A; Tornaritis, Michael; Veidebaum, Toomas; Ahrens, Wolfgang; Siani, Alfonso

2014-01-01

The early life course is assumed to be a critical phase for childhood obesity; however the significance of single factors and their interplay is not well studied in childhood populations. The investigation of pre-, peri- and postpartum risk factors on the risk of obesity at age 2 to 9. A case-control study with 1,024 1:1-matched case-control pairs was nested in the baseline survey (09/2007-05/2008) of the IDEFICS study, a population-based intervention study on childhood obesity carried out in 8 European countries in pre- and primary school settings. Conditional logistic regression was used for identification of risk factors. For many of the investigated risk factors, we found a raw effect in our study. In multivariate models, we could establish an effect for gestational weight gain (adjusted OR = 1.02; 95%CI 1.00-1.04), smoking during pregnancy (adjusted OR = 1.48; 95%CI 1.08-2.01), Caesarian section (adjusted OR = 1.38; 95%CI 1.10-1.74), and breastfeeding 4 to 11 months (adjusted OR = 0.77; 95%CI 0.62-0.96). Birth weight was related to lean mass rather than to fat mass, the effect of smoking was found only in boys, but not in girls. After additional adjustment for parental BMI and parental educational status, only gestational weight gain remained statistically significant. Both, maternal as well as paternal BMI were the strongest risk factors in our study, and they confounded several of the investigated associations. Key risk factors of childhood obesity in our study are parental BMI and gestational weight gain; consequently prevention approaches should target not only children but also adults. The monitoring of gestational weight seems to be of particular importance for early prevention of childhood obesity.

Risk factors for operated carpal tunnel syndrome: a multicenter population-based case-control study

PubMed Central

Mattioli, Stefano; Baldasseroni, Alberto; Bovenzi, Massimo; Curti, Stefania; Cooke, Robin MT; Campo, Giuseppe; Barbieri, Pietro G; Ghersi, Rinaldo; Broccoli, Marco; Cancellieri, Maria Pia; Colao, Anna Maria; dell'Omo, Marco; Fateh-Moghadam, Pirous; Franceschini, Flavia; Fucksia, Serenella; Galli, Paolo; Gobba, Fabriziomaria; Lucchini, Roberto; Mandes, Anna; Marras, Teresa; Sgarrella, Carla; Borghesi, Stefano; Fierro, Mauro; Zanardi, Francesca; Mancini, Gianpiero; Violante, Francesco S

2009-01-01

Background Carpal tunnel syndrome (CTS) is a socially and economically relevant disease caused by compression or entrapment of the median nerve within the carpal tunnel. This population-based case-control study aims to investigate occupational/non-occupational risk factors for surgically treated CTS. Methods Cases (n = 220) aged 18-65 years were randomly drawn from 13 administrative databases of citizens who were surgically treated with carpal tunnel release during 2001. Controls (n = 356) were randomly sampled from National Health Service registry records and were frequency matched by age-gender-specific CTS hospitalization rates. Results At multivariate analysis, risk factors were blue-collar/housewife status, BMI ≥ 30 kg/m2, sibling history of CTS and coexistence of trigger finger. Being relatively tall (cut-offs based on tertiles: women ≥165 cm; men ≥175 cm) was associated with lower risk. Blue-collar work was a moderate/strong risk factor in both sexes. Raised risks were apparent for combinations of biomechanical risk factors that included frequent repetitivity and sustained force. Conclusion This study strongly underlines the relevance of biomechanical exposures in both non-industrial and industrial work as risk factors for surgically treated CTS. PMID:19758429

Renshaw cell interneuron specialization is controlled by a temporally restricted transcription factor program

PubMed Central

Stam, Floor J.; Hendricks, Timothy J.; Zhang, Jingming; Geiman, Eric J.; Francius, Cedric; Labosky, Patricia A.; Clotman, Frederic; Goulding, Martyn

2012-01-01

The spinal cord contains a diverse array of physiologically distinct interneuron cell types that subserve specialized roles in somatosensory perception and motor control. The mechanisms that generate these specialized interneuronal cell types from multipotential spinal progenitors are not known. In this study, we describe a temporally regulated transcriptional program that controls the differentiation of Renshaw cells (RCs), an anatomically and functionally discrete spinal interneuron subtype. We show that the selective activation of the Onecut transcription factors Oc1 and Oc2 during the first wave of V1 interneuron neurogenesis is a key step in the RC differentiation program. The development of RCs is additionally dependent on the forkhead transcription factor Foxd3, which is more broadly expressed in postmitotic V1 interneurons. Our demonstration that RCs are born, and activate Oc1 and Oc2 expression, in a narrow temporal window leads us to posit that neuronal diversity in the developing spinal cord is established by the composite actions of early spatial and temporal determinants. PMID:22115757

Modified model of VX2 tumor overexpressing vascular endothelial growth factor.

PubMed

Pascale, Florentina; Ghegediban, Saida-Homayra; Bonneau, Michel; Bedouet, Laurent; Namur, Julien; Verret, Valentin; Schwartz-Cornil, Isabelle; Wassef, Michel; Laurent, Alexandre

2012-06-01

To determine whether upregulated expression of vascular endothelial growth factor (VEGF) in VX2 cells can increase vessel density (VD) and reduce tumor necrosis. The VX2 cell line was transfected with expression vectors containing cDNA for rabbit VEGF. Stable clones producing rabbit VEGF (VEGF-VX2) were selected. VEGF-VX2 cells (n = 5 rabbits) or nontransfected VX2 cells (controls; n = 5 rabbits) were implanted into leg muscle of 10 rabbits. The animals were sacrificed at day 21. Tumor volume, percentage of necrosis, VD, and VEGF concentration in tumor protein extract were quantified. Overexpression of VEGF by VX2 cells augmented tumor implantation efficiency 100% and favored cyst formation. The tumor volume was significantly larger for VEGF-VX2 transfected tumors versus controls (P = .0143). Overexpression of VEGF in VX2 cells significantly increased the VD of the tumors (P = .0138). The percentage of necrosis was reduced in VEGF-VX2 tumors versus controls (19.5% vs 38.5 %; P = .002). VEGF concentration in VEGF-VX2 tumors was significantly higher than in control tumors (P = .041) and was correlated with tumor volume (ρ = .883, P = .012). The overexpression of VEGF increased tumor growth and vascularization, favored cyst formation, and reduced tumor necrosis. This new phenotype of the VX2 tumor may offer some advantages over classic models of VX2 tumor for evaluating anticancer therapies. Copyright © 2012 SIR. Published by Elsevier Inc. All rights reserved.

ASVCP quality assurance guidelines: control of general analytical factors in veterinary laboratories.

PubMed

Flatland, Bente; Freeman, Kathy P; Friedrichs, Kristen R; Vap, Linda M; Getzy, Karen M; Evans, Ellen W; Harr, Kendal E

2010-09-01

Owing to lack of governmental regulation of veterinary laboratory performance, veterinarians ideally should demonstrate a commitment to self-monitoring and regulation of laboratory performance from within the profession. In response to member concerns about quality management in veterinary laboratories, the American Society for Veterinary Clinical Pathology (ASVCP) formed a Quality Assurance and Laboratory Standards (QAS) committee in 1996. This committee recently published updated and peer-reviewed Quality Assurance Guidelines on the ASVCP website. The Quality Assurance Guidelines are intended for use by veterinary diagnostic laboratories and veterinary research laboratories that are not covered by the US Food and Drug Administration Good Laboratory Practice standards (Code of Federal Regulations Title 21, Chapter 58). The guidelines have been divided into 3 reports on 1) general analytic factors for veterinary laboratory performance and comparisons, 2) hematology and hemostasis, and 3) clinical chemistry, endocrine assessment, and urinalysis. This report documents recommendations for control of general analytical factors within veterinary clinical laboratories and is based on section 2.1 (Analytical Factors Important In Veterinary Clinical Pathology, General) of the newly revised ASVCP QAS Guidelines. These guidelines are not intended to be all-inclusive; rather, they provide minimum guidelines for quality assurance and quality control for veterinary laboratory testing. It is hoped that these guidelines will provide a basis for laboratories to assess their current practices, determine areas for improvement, and guide continuing professional development and education efforts. ©2010 American Society for Veterinary Clinical Pathology.

Neurocognitive and personality factors in homo- and heterosexual pedophiles and controls.

PubMed

Kruger, Tillmann H C; Schiffer, Boris

2011-06-01

Several neuropsychological studies have suggested an association between pedophilia, neurocognitive disturbances, and specific personality profiles. However, inconsistencies in the findings have not been explained sufficiently, because many studies did not control for possible confounding factors, such as age, education level, or gender orientation. Therefore, the present investigation examined neurocognitive performance and personality profiles in pedophiles in dependence of sexual gender preferences and sexual deviance, as well as with regard to age and education level. Scores on the different neurocognitive tests, personality questionnaires, and Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV (SCID) interviews. An extensive neurocognitive test battery (including a reduced version of the German Wechsler Adult Intelligence Scale, the Wisconsin card-sorting test, d2 Attention-Deficit Test, and the Corsi block-tapping test) as well as two personality questionnaires (Minnessota Multiphasic Personality Inventory [MMPI-2] and the Multiphasic Sex Inventory [MSI]) were used to examine a consecutive sample of 20 psychiatrically assessed (SCID I and II) pedophile inpatients (nine exclusively attracted to females and 11 to males) from two high security forensic hospitals and 28 healthy controls (14 heterosexual, 14 homosexual). Compared with controls, pedophiles showed neurocognitive impairments and personality specifics in the majority of tests and questionnaires, such as reduced values on the intelligence scale and weaker performances in information processing, together with high scores for psychopathy and paranoia, and signs of sexual obsessiveness and sexual dysfunction. In contrast to previous reports, some of these alterations were at least partly explained by factors other than pedophilia, such as education level or age. These alterations may be seen to be in line with the hypothesis of a perturbation of

Risk factors and clinical features of ovarian pregnancy: a case–control study

PubMed Central

Zhu, Qian; Li, Cheng; Zhao, Wei-Hong; Yuan, Jiang-Jing; Yan, Ming-Xing; Qin, Guo-Juan; Zhang, Jian

2014-01-01

Objective To identify risk factors for ovarian pregnancy (OP) and compare clinical features between OP and tubal pregnancy (TP) patients. Design Case–control study. Setting University hospital. Participants A case–control study was conducted from January 2005 to May 2014. Women diagnosed with OP were recruited as the case group (n=71), 145 women with TP and 146 with intrauterine pregnancy (IUP) were matched as controls at a ratio of 1:2:2. Women who refused interviews or provided incomplete information were excluded. Results OP risk was lower than TP risk in women with serological evidence of Chlamydia trachomatis infection (adjusted OR1 0.17, 95% CI 0.06 to 0.52), previous adnexal surgery (adjusted OR1 0.25, 95% CI 0.07 to 0.95), and current levonorgestrel emergency contraceptive use (adjusted OR1 0.24, 95% CI 0.07 to 0.78). In vitro fertilisation-embryo transfer (IVF-ET) carried a higher risk of OP (adjusted OR1 12.18, 95% CI 2.23 to 66.58) than natural conception. When Controlled by IUP women, current users of intrauterine devices (IUDs) carried a higher risk of OP than non-users of any contraceptives (adjusted OR2 9.60, 95% CI 1.76 to 42.20). β-Human chorionic gonadotropin (hCG) levels on the day of surgery were higher in OP patients than in TP patients (p<0.01). Women with OP were less likely to initially present with vaginal bleeding than those with TP (p=0.02). Moreover, shock (p=0.02), rupture (p<0.01), haemoperitoneum (p<0.01) and emergency laparotomy (p<0.01) were more common in the OP group than in the TP group. Conclusions IVF-ET and IUD use may be risk factors for OP, and OP patients tend to have high β-hCG levels and a poor clinical outcome (shock, rupture, haemoperitoneum and need for emergency laparotomy). Our findings may contribute to the prevention and early diagnosis of OP. PMID:25472658

Effects of royal jelly supplementation on glycemic control and oxidative stress factors in type 2 diabetic female: a randomized clinical trial.

PubMed

Pourmoradian, Samira; Mahdavi, Reza; Mobasseri, Majid; Faramarzi, Elnaz; Mobasseri, Mehrnoosh

2014-05-01

It has been proposed that royal jelly has antioxidant properties and may improve oxidative stress and glycemic control. Therefore, we investigated the effects of royal jelly supplementation in diabetic females. In this pilot, parallel design randomized clinical trial, 50 female volunteers with type 2 diabetes were randomly allocated to the supplemented (25, cases) and placebo (25, cases) groups, based on random block procedure produced by Random Allocation Software, given a daily dose of 1,000 mg royal jelly soft gel or placebo, respectively, for 8 weeks. Before and after intervention, glycemic control indices, antioxidant and oxidative stress factors were measured. After royal jelly supplementation, the mean fasting blood glucose decreased remarkably (163.05±42.51 mg/dL vs. 149.68±42.7 mg/dL). Royal jelly supplementation resulted in significant reduction in the mean serum glycosylated hemoglobin levels (8.67%±2.24% vs. 7.05%±1.45%, P=0.001) and significant elevation in the mean insulin concentration (70.28±29.16 pmol/L vs. 86.46±27.50 pmol/L, P=0.01). Supplementation significantly increased erythrocyte superoxidase dismutase and glutathione peroxidase activities and decreased malondialdehyde levels (P<0.05). At the end of study, the mean total antioxidant capacity elevated insignificantly in both groups. On the basis of our findings, it seems that royal jelly supplementation may be beneficial in controlling diabetes outcomes. Further studies with larger sample size are warranted.

Snail1 transcription factor controls telomere transcription and integrity

PubMed Central

Mazzolini, Rocco; Gonzàlez, Núria; Garcia-Garijo, Andrea; Millanes-Romero, Alba; Peiró, Sandra; Smith, Susan

2018-01-01

Abstract Besides controlling epithelial-to-mesenchymal transition (EMT) and cell invasion, the Snail1 transcriptional factor also provides cells with cancer stem cell features. Since telomere maintenance is essential for stemness, we have examined the control of telomere integrity by Snail1. Fluorescence in situ hybridization (FISH) analysis indicates that Snail1-depleted mouse mesenchymal stem cells (MSC) have both a dramatic increase of telomere alterations and shorter telomeres. Remarkably, Snail1-deficient MSC present higher levels of both telomerase activity and the long non-coding RNA called telomeric repeat-containing RNA (TERRA), an RNA that controls telomere integrity. Accordingly, Snail1 expression downregulates expression of the telomerase gene (TERT) as well as of TERRA 2q, 11q and 18q. TERRA and TERT are transiently downregulated during TGFβ-induced EMT in NMuMG cells, correlating with Snail1 expression. Global transcriptome analysis indicates that ectopic expression of TERRA affects the transcription of some genes induced during EMT, such as fibronectin, whereas that of TERT does not modify those genes. We propose that Snail1 repression of TERRA is required not only for telomere maintenance but also for the expression of a subset of mesenchymal genes. PMID:29059385

Range of Risk Factor Levels: Control, Mortality, and Cardiovascular Outcomes in Type 1 Diabetes Mellitus.

PubMed

Rawshani, Aidin; Rawshani, Araz; Franzén, Stefan; Eliasson, Björn; Svensson, Ann-Marie; Miftaraj, Mervete; McGuire, Darren K; Sattar, Naveed; Rosengren, Annika; Gudbjörnsdottir, Soffia

2017-04-18

Individuals with type 1 diabetes mellitus (T1DM) have a high risk of cardiovascular complications, but it is unknown to what extent fulfilling all cardiovascular treatment goals is associated with residual risk of mortality and cardiovascular outcomes in those with T1DM compared with the general population. We included all patients ≥18 years of age with T1DM who were registered in the Swedish National Diabetes Register from January 1, 1998, through December 31, 2014, a total of 33 333 patients, each matched for age and sex with 5 controls without diabetes mellitus randomly selected from the population. Patients with T1DM were categorized according to number of risk factors not at target: glycohemoglobin, blood pressure, albuminuria, smoking, and low-density lipoprotein cholesterol. Risk of all-cause mortality, acute myocardial infarction, heart failure hospitalization, and stroke was examined in relation to the number of risk factors at target. The mean follow-up was 10.4 years in the diabetes group. Overall, 2074 of 33 333 patients with diabetes mellitus and 4141 of 166 529 controls died. Risk for all outcomes increased stepwise for each additional risk factor not at target. Adjusted hazard ratios for patients achieving all risk factor targets compared with controls were 1.31 (95% confidence interval [CI], 0.93-1.85) for all-cause mortality, 1.82 (95% CI, 1.15-2.88) for acute myocardial infarction, 1.97 (95% CI, 1.04-3.73) for heart failure hospitalization, and 1.17 (95% CI, 0.51-2.68) for stroke. The hazard ratio for patients versus controls with none of the risk factors meeting target was 7.33 (95% CI, 5.08-10.57) for all-cause mortality, 12.34 (95% CI, 7.91-19.48) for acute myocardial infarction, 15.09 (95% CI, 9.87-23.09) for heart failure hospitalization, and 12.02 (95% CI, 7.66-18.85) for stroke. A steep-graded association exists between decreasing number of cardiovascular risk factors at target and major adverse cardiovascular outcomes among