Gemcitabine treatment induces endoplasmic reticular (ER) stress and subsequently upregulates urokinase plasminogen activator (uPA) to block mitochondrial-dependent apoptosis in Panc-1 cancer stem-like cells (CSCs)

PubMed Central

Wang, Weiguo; Zhu, Yunjie; Chen, Yang

2017-01-01

Background Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with poor survival rates. The presence of cancer stem-like cells (CSCs) is believed to be among the underlying reasons for the aggressiveness of PDAC, which contributes to chemoresistance and recurrence. However, the mechanisms that induce chemoresistance and inhibit apoptosis remain largely unknown. Methods We used serum-free medium to enrich CSCs from panc-1 human pancreatic cancer cells and performed sphere formation testing, flow cytometry, quantitative reverse transcription polymerase chain reaction (RT-qPCR) and semi-quantitative western blotting to confirm the stemness of panc-1 CSCs. Hallmarks of endoplasmic reticulum (ER) stress, including IRE1, PERK, ATF4, ATF6α, GRP78 and uPA expression, were detected after gemcitabine treatment. Effects of gemcitabine-induced uPA expression on cell invasion, sphere formation, colony formation and gemcitabine sensitivity were detected. Electrophoretic mobility shift assays (EMSAs) and RNA-immunoprecipitation (RIP) were performed to detect interaction between the uPA mRNA 3’-UTR and mutant p53-R273H expressed by panc-1 CSCs. The effects of upregulated uPA by gemcitabine on apoptosis were detected by Annexin V-FITC/PI staining, and the impact of uPA on small molecule CP-31398-restored mutant p53 transcriptional activity was measured by a luciferase reporter assay. Results Enriched panc-1 CSCs expressing high levels of CD44 and CD133 also produced significantly higher amounts of Oct4 and Nanog. Compared with panc-1 cells, panc-1 CSCs presented chemoresistance to gemcitabine. ER stress gene detections demonstrated effects of gemcitabine-induced ER stress on both the pro-apoptotic and pro-survival branches. ER stress-induced ATF6α upregulated level of uPA by transcriptionally activating GRP78. Gemcitabine-induced uPA promoted invasion, sphere formation and colony formation and attenuated apoptosis induced by gemcitabine in panc-1 CSCs, depending on

What is the value of conducting a trial of r-tPA for the treatment of mild stroke patients?

PubMed

Guzauskas, Gregory F; Chen, Er; Lalla, Deepa; Yu, Elaine; Tayama, Darren; Veenstra, David L

2017-02-01

Background The Phase IIIb, Double-Blind, Multicenter Study to Evaluate the Efficacy and Safety of Alteplase in Patients With Mild Stroke: Rapidly Improving Symptoms and Minor Neurologic Deficits (PRISMS) trial will assess r-tPA in ischemic stroke patients who present with mild deficits (i.e. mild stroke). Aims To assess PRISMS's societal value in clarifying the optimal care for patients with mild ischemic stroke. Methods A value of information (VOI) decision model was developed to compare the outcomes of mild stroke patients treated vs. not treated with r-tPA. Model inputs were derived from a subset of Third International Stroke Trial patients, a recent meta-analysis of r-tPA trials, expert opinion, and other published sources. VOI analyses were also used to assess the expected US societal value of the PRISMS trial and the expected value of reducing uncertainty in key trial estimates. Results The expected net societal value of the PRISMS trial was approximately $210 million ($160 m-$260 m), representing a six-fold return on investment. The value of reducing uncertainty in r-tPA efficacy was approximately $150 million ($100 m-$200 m), while reducing uncertainty in r-tPA safety (increased risk for symptomatic intracranial hemorrhage) did not add additional value in comparison. Conclusions Developing a better understanding of the outcomes of r-tPA treatment in patients with mild ischemic stroke will provide tremendous societal value by clarifying current uncertainty around treatment effectiveness. Enrollment in the PRISMS trial for patients presenting with mild ischemic stroke within 0-3 h of symptom onset should be highly encouraged.

Psychological Correlates of Self-Reported and Objectively Measured Physical Activity among Chinese Children—Psychological Correlates of PA

PubMed Central

Wang, Jing-Jing; Baranowski, Tom; Lau, Patrick W. C.; Chen, Tzu-An; Zhang, Shu-Ge

2016-01-01

This study aimed to explore the associations among psychological correlates and physical activity (PA) in Chinese children and to further examine whether these associations varied by different PA measures. PA self-efficacy, motivation, and preference were reported in 449 8–13-year-old Chinese children (252 males). Moderate- to vigorous- intensity PA (MVPA) was measured by the Physical Activity Questionnaire for Older Children (PAQ-C) and with an ActiGraph GT3X accelerometer. Correlations and hierarchical regressions were performed to explore their associations. The study psychological variables were all positively related to PAQ-C and objective MVPA (r: 0.22–0.63). The associations with PAQ-C were all substantially stronger than those with accelerometry. Beyond the explained variance accounted for by demographics and social desirability, the addition of the psychological correlates accounted for 45% of the variance of the PAQ-C score, while only 13% for accelerometry-based MVPA. The associations of specific variables with the PAQ-C score (age, PA self-efficacy, autonomous motivation and preference) were somewhat different from those associated with objective MVPA (PA self-efficacy, autonomous motivation, and negatively associated with female gender). This study demonstrated the importance of self-efficacy and autonomous motivation in association with PA and indicated the difference in level of their associations with different PA measures. PMID:27754396

Psychological Correlates of Self-Reported and Objectively Measured Physical Activity among Chinese Children-Psychological Correlates of PA.

PubMed

Wang, Jing-Jing; Baranowski, Tom; Lau, Patrick W C; Chen, Tzu-An; Zhang, Shu-Ge

2016-10-13

This study aimed to explore the associations among psychological correlates and physical activity (PA) in Chinese children and to further examine whether these associations varied by different PA measures. PA self-efficacy, motivation, and preference were reported in 449 8-13-year-old Chinese children (252 males). Moderate- to vigorous- intensity PA (MVPA) was measured by the Physical Activity Questionnaire for Older Children (PAQ-C) and with an ActiGraph GT3X accelerometer. Correlations and hierarchical regressions were performed to explore their associations. The study psychological variables were all positively related to PAQ-C and objective MVPA ( r : 0.22-0.63). The associations with PAQ-C were all substantially stronger than those with accelerometry. Beyond the explained variance accounted for by demographics and social desirability, the addition of the psychological correlates accounted for 45% of the variance of the PAQ-C score, while only 13% for accelerometry-based MVPA. The associations of specific variables with the PAQ-C score (age, PA self-efficacy, autonomous motivation and preference) were somewhat different from those associated with objective MVPA (PA self-efficacy, autonomous motivation, and negatively associated with female gender). This study demonstrated the importance of self-efficacy and autonomous motivation in association with PA and indicated the difference in level of their associations with different PA measures.

Discovery of novel urokinase plasminogen activator (uPA) inhibitors using ligand-based modeling and virtual screening followed by in vitro analysis.

PubMed

Al-Sha'er, Mahmoud A; Khanfar, Mohammad A; Taha, Mutasem O

2014-01-01

Urokinase plasminogen activator (uPA)-a serine protease-is thought to play a central role in tumor metastasis and angiogenesis and, therefore, inhibition of this enzyme could be beneficial in treating cancer. Toward this end, we explored the pharmacophoric space of 202 uPA inhibitors using seven diverse sets of inhibitors to identify high-quality pharmacophores. Subsequently, we employed genetic algorithm-based quantitative structure-activity relationship (QSAR) analysis as a competition arena to select the best possible combination of pharmacophoric models and physicochemical descriptors that can explain bioactivity variation within the training inhibitors (r (2) 162 = 0.74, F-statistic = 64.30, r (2) LOO = 0.71, r (2) PRESS against 40 test inhibitors = 0.79). Three orthogonal pharmacophores emerged in the QSAR equation suggesting the existence of at least three binding modes accessible to ligands within the uPA binding pocket. This conclusion was supported by receiver operating characteristic (ROC) curve analyses of the QSAR-selected pharmacophores. Moreover, the three pharmacophores were comparable with binding interactions seen in crystallographic structures of bound ligands within the uPA binding pocket. We employed the resulting pharmacophoric models and associated QSAR equation to screen the national cancer institute (NCI) list of compounds. The captured hits were tested in vitro. Overall, our modeling workflow identified new low micromolar anti-uPA hits.

Children and adolescent physical activity participation and enjoyment during active play.

PubMed

Moghaddaszadeh, Asal; Ahmadi, Yasamin; Belcastro, Angelo N

2017-10-01

Girls' (9-19 years) participation in physical activity (PA) is known to decrease at a faster rate than boys. A reduction in PA attractiveness (enjoyment) and lower psychosocial profile of girls approaching biological maturity may underlie the decreasing rate of PA participation. Since engaging children in active play programs improves health related quality of life indictors and enjoyment levels; the purposes of this study were to: 1) assess psychosocial status and PA attractiveness/enjoyment of boys and girls to an eight-week active play program; and 2) investigate the relationships among PA participation, psychosocial status and PA attractiveness with both age and maturity status for boys and girls following an active play PA program. Thirty-three children (age 9.8±1.3 years; weight 43.1±13.4 kg; BMI 20.8±3.2 kg/m2) were recruited to participate in an active play program for 8 weeks (4x/week; 1hr/d). M-S estimates ranged from -6.7 to -2.5 years away from biological maturity Daily program PA was assessed and compared to pre-post measures of psychosocial functioning and PA attractiveness. Statistical procedures were performed using ANOVA and/or Pearson's correlation r (SPSS v. 22.0) with P=0.05. PA participation in the active play program showed a group average of 39±11% time spent in moderate-vigorous PA (%MVPA) with boys averaging 45% MVPA and girls averaging 30% MVPA (P<0.05). PA attractiveness scores for boys did not change following the program; whereas girls improved from 67±13% to 76±9% (P<0.05). Minimal changes were noted for the health-related quality of life measures as a result of the PA program. Comparing PA attractiveness to %MVPA, 80% of girls reporting positive changes or no change; in contrast 56% of boys responded with negative/less PA attractiveness. PA attractiveness for all children was negatively associated with age (r=-0.19) and/or M-S (r=-0.29). The relationships, however, were gender specific with boys exhibiting a coefficient of -0

Recombinant protective antigen 102 (rPA102): profile of a second-generation anthrax vaccine.

PubMed

Keitel, Wendy A

2006-08-01

Recent terrorist attacks involving the use of Bacillus anthracis spores have stimulated interest in the development of new vaccines for anthrax prevention. Studies of the pathogenesis of anthrax and of the immune responses following infection and immunization underscore the pivotal role that antibodies to the protective antigen play in protection. The most promising vaccine candidates contain purified recombinant protective antigen. Clinical trials of one of these, recombinant protective antigen (rPA)102, are underway. Initial results suggest that rPA102 is well tolerated and immunogenic. Additional trials are necessary to identify optimal formulations and immunization regimens for pre- and postexposure prophylaxis. Future licensure of these and other candidate vaccines will depend on their safety and immunogenicity profiles in humans, and their ability to confer protection in animal models of inhalational anthrax.

Binding of anti-SSA antibodies to apoptotic fetal cardiocytes stimulates urokinase plasminogen activator (uPA)/uPA receptor-dependent activation of TGF-β and potentiates fibrosis.

PubMed

Briassouli, Paraskevi; Rifkin, Daniel; Clancy, Robert M; Buyon, Jill P

2011-11-15

In congenital heart block (CHB), binding of maternal anti-SSA/Ro Abs to fetal apoptotic cardiocytes impairs their removal by healthy cardiocytes and increases urokinase plasminogen activator (uPA)/uPA receptor (uPAR)-dependent plasmin activation. Because the uPA/uPAR system plays a role in TGF-β activation, we evaluated whether anti-Ro binding to apoptotic cardiocytes enhances plasmin-mediated activation of TGF-β, thereby promoting a profibrosing phenotype. Supernatants from cocultures of healthy cardiocytes and apoptotic cardiocytes bound by IgG from a mother whose child had CHB (apoptotic-CHB-IgG [apo-CHB-IgG]) exhibited significantly increased levels of active TGF-β compared with supernatants from cocultures of healthy cardiocytes and apoptotic cardiocytes preincubated with IgG from a healthy donor. Treatment of the culture medium with anti-TGF-β Ab or TGF-β inhibitor (SB431542) abrogated the luciferase response, thereby confirming TGF-β dependency. Increased uPA levels and activity were present in supernatants generated from cocultures of healthy cardiocytes and apo-CHB-IgG cardiocytes compared with healthy cardiocytes and apoptotic cardiocytes preincubated with IgG from a healthy donor, respectively. Treatment of apo-CHB-IgG cardiocytes with anti-uPAR or anti-uPA Abs or plasmin inhibitor aprotinin prior to coculturing with healthy cardiocytes attenuated TGF-β activation. Supernatants derived from cocultures of healthy cardiocytes and apo-CHB-IgG cardiocytes promoted Smad2 phosphorylation and fibroblast transdifferentiation, as evidenced by increased smooth muscle actin and collagen expression, which decreased when fibroblasts were treated with supernatants from cocultures pretreated with uPAR Abs. These data suggested that binding of anti-Ro Abs to apoptotic cardiocytes triggers TGF-β activation, by virtue of increasing uPAR-dependent uPA activity, thus initiating and amplifying a cascade of events that promotes myofibroblast transdifferentiation and

Determinants of activity of the HIV-1 maturation inhibitor PA-457.

PubMed

Li, Feng; Zoumplis, Dorian; Matallana, Claudia; Kilgore, Nicole R; Reddick, Mary; Yunus, Abdul S; Adamson, Catherine S; Salzwedel, Karl; Martin, David E; Allaway, Graham P; Freed, Eric O; Wild, Carl T

3-O-(3',3'-dimethylsuccinyl) betulinic acid, also termed PA-457 or DSB, is a novel HIV-1 inhibitor that blocks virus maturation by disrupting cleavage of the capsid precursor, CA-SP1. To better define the molecular target for PA-457, we prepared a panel of mutant viruses with point deletions spanning the CA-SP1 cleavage domain and characterized each of these viruses for PA-457 sensitivity. Our results indicate that amino acid residues in the N-terminal half of SP1 serve as determinants of PA-457 activity, while residues in the C-terminal half of SP1 were not involved in compound activity. These findings support and extend previous observations that PA-457 is a specific inhibitor of CA-SP1 cleavage and identify the CA-SP1 domain as the primary viral determinant for this novel inhibitor of HIV-1 replication.

Phase I study of safety and immunogenicity of an Escherichia coli-derived recombinant protective antigen (rPA) vaccine to prevent anthrax in adults.

PubMed

Brown, Bruce K; Cox, Josephine; Gillis, Anita; VanCott, Thomas C; Marovich, Mary; Milazzo, Mark; Antonille, Tanya Santelli; Wieczorek, Lindsay; McKee, Kelly T; Metcalfe, Karen; Mallory, Raburn M; Birx, Deborah; Polonis, Victoria R; Robb, Merlin L

2010-11-05

The fatal disease caused by Bacillus anthracis is preventable with a prophylactic vaccine. The currently available anthrax vaccine requires a lengthy immunization schedule, and simpler and more immunogenic options for protection against anthrax are a priority for development. In this report we describe a phase I clinical trial testing the safety and immunogenicity of an anthrax vaccine using recombinant Escherichia coli-derived, B. anthracis protective antigen (rPA). A total of 73 healthy adults ages 18-40 were enrolled and 67 received 2 injections separated by 4 weeks of either buffered saline placebo, or rPA formulated with or without 704 µg/ml Alhydrogel® adjuvant in increasing doses (5, 25, 50, 100 µg) of rPA. Participants were followed for one year and safety and immunologic data were assessed. Tenderness and warmth were the most common post-injection site reactions. No serious adverse events related to the vaccine were observed. The most robust humoral immune responses were observed in subjects receiving 50 µg of rPA formulated with Alhydrogel® with a geometric mean concentration of anti-rPA IgG antibodies of 283 µg/ml and a toxin neutralizing geometric 50% reciprocal geometric mean titer of 1061. The highest lymphoproliferative peak cellular response (median Lymphocyte Stimulation Index of 29) was observed in the group receiving 25 µg Alhydrogel®-formulated rPA. The vaccine was safe, well tolerated and stimulated a robust humoral and cellular response after two doses. ClinicalTrials.gov NCT00057525.

Celastrol reverses palmitic acid (PA)-caused TLR4-MD2 activation-dependent insulin resistance via disrupting MD2-related cellular binding to PA.

PubMed

Zhang, Xue; Wang, Ying; Ge, Hui-Ya; Gu, Yi-Jun; Cao, Fan-Fan; Yang, Chun-Xin; Uzan, Georges; Peng, Bin; Zhang, Deng-Hai

2018-04-18

Elevated plasma statured fatty acids (FFAs) cause TLR4/MD2 activation-dependent inflammation and insulin tolerance, which account for the occurrence and development of obesity. It has been confirmed that statured palmitic acid (PA) (the most abundant FFA) could bind MD2 to cause cellular inflammation. The natural compound celastrol could improve obesity, which is suggested via inhibiting inflammation, yet the detailed mechanism for celastrol is still unclear. As celastrol is reported to directly target MD2, we thought disrupting the binding between FFAs and MD2 might be one of the ways for celastrol to inhibit FFAs-caused inflammation and insulin resistance. In this study, we found evidence to support our hypothesis: celastrol could reverse PA-caused TLR4/MD2 activation-dependent insulin resistance, as determined by glucose-lowering ability, cellular glucose uptake, insulin action-related proteins and TLR4/MD2/NF-κB activation. Bioinformatics and cellular experiments showed that both celastrol and PA could bind MD2, and that celastrol could expel PA from cells. Finally, celastrol could reverse high fat diet caused hyperglycemia and obesity, and liver NF-kB activations. Taking together, we proved that celastrol could reverses PA-caused TLR4-MD2 activation-dependent insulin resistance via disrupting PA binding to MD2. © 2018 Wiley Periodicals, Inc.

Crystal structure of an avian influenza polymerase PA[subscript N] reveals an endonuclease active site

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

Yuan, Puwei; Bartlam, Mark; Lou, Zhiyong

2009-11-10

The heterotrimeric influenza virus polymerase, containing the PA, PB1 and PB2 proteins, catalyses viral RNA replication and transcription in the nucleus of infected cells. PB1 holds the polymerase active site and reportedly harbours endonuclease activity, whereas PB2 is responsible for cap binding. The PA amino terminus is understood to be the major functional part of the PA protein and has been implicated in several roles, including endonuclease and protease activities as well as viral RNA/complementary RNA promoter binding. Here we report the 2.2 angstrom (A) crystal structure of the N-terminal 197 residues of PA, termed PA(N), from an avian influenzamore » H5N1 virus. The PA(N) structure has an alpha/beta architecture and reveals a bound magnesium ion coordinated by a motif similar to the (P)DX(N)(D/E)XK motif characteristic of many endonucleases. Structural comparisons and mutagenesis analysis of the motif identified in PA(N) provide further evidence that PA(N) holds an endonuclease active site. Furthermore, functional analysis with in vivo ribonucleoprotein reconstitution and direct in vitro endonuclease assays strongly suggest that PA(N) holds the endonuclease active site and has critical roles in endonuclease activity of the influenza virus polymerase, rather than PB1. The high conservation of this endonuclease active site among influenza strains indicates that PA(N) is an important target for the design of new anti-influenza therapeutics.« less

A novel plasminogen activator from Agkistrodon blomhoffii Ussurensis venom (ABUSV-PA): Purification and characterization

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

Liu Shuqing; Sun Mingzhong; Greenaway, Frederick T.

2006-10-06

A plasminogen activator with arginine ester hydrolysis activity (ABUSV-PA) has been identified and purified to homogeneity from Chinese Agkistrodon blomhoffii Ussurensis snake venom. ABUSV-PA, a monomeric protein with molecular mass of 27815.2 Da, was purified 180-fold with 0.02% recovery for protein and 3.6% recovery for esterase activity. ABUSV-PA reacts optimally with its substrate N {sub {alpha}}-tosyl-L-arginine-methyl ester (TAME) at {approx}pH 7.5 and at 51 {sup o}C. Measurement from inductively coupled plasma-atomic emission spectroscopy (ICP-AES) reveals that ABUSV-PA is a Zn{sup 2+}-containing protein with a stoichiometry of 1:1 [Zn{sup 2+}]:[ABUSV-PA]. Analyses of esterase hydrolysis and UV absorption and CD spectra indicatemore » that Zn{sup 2+} plays an important role in maintaining the structural integrity rather than the esterase activity of ABUSV-PA. Divalent metal ions, including Ca{sup 2+}, Mg{sup 2+}, Cu{sup 2+}, Ni{sup 2+}, Mn{sup 2+}, and Co{sup 2+}, increase the TAME hydrolysis activity of ABUSV-PA. A red-shift of the emission wavelengths of the synchronous fluorescence of ABUSV-PA, compared to those of free Tyr and Trp, indicates a conformation where the Tyr and Trp residues are in exposed hydrophilic environments. The presence of zinc increases the hydrophobicity of the conformational environments surrounding the Trp residues of ABUSV-PA and affects the secondary structure of ABUSV-PA, as proved by UV absorption and CD spectroscopy.« less

Recruitment rates in workplace physical activity interventions: characteristics for success.

PubMed

Ryde, Gemma C; Gilson, Nicholas D; Burton, Nicola W; Brown, Wendy J

2013-01-01

To conduct a systematic review to assess recruitment rates in workplace physical activity (PA) intervention studies and describe characteristics of studies with high recruitment rates. Data Source. Electronic and manual searches were conducted. Workplace PA intervention studies that reported the number of employees invited to participate and the number who responded were included. Studies with recruitment rates of ≥70% were categorized as high with the remaining studies (<70%) used as comparison. Key study characteristics were assessed. An approach called positive deviance was used to identify the extent to which study characteristics were unique to high recruitment rate. Seventy-six percent of studies failed to report recruitment rates (n = 30 included for review). Studies with high recruitment rates (n = 8) tended to have longer study duration (mean 1.6 years) and target smaller cohorts of employees (mean n = 199) than comparison studies (3.9 months; n = 1241). For recruitment strategies and intervention components of high studies, involvement of employees was driven by the organization, with PA interventions provided as part of the working day in paid time. These findings suggest a potential to improve recruitment through targeting small cohorts of employees, incorporating PA as a long-term strategy, facilitating organizationally driven employee involvement, and providing PA interventions during paid time.

77 FR 46125 - Sunoco, Inc., R&M, Refining Division, Marcus Hook, PA; Sunoco, Inc., 10 Industrial Hwy., MS4...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-02

... DEPARTMENT OF LABOR Employment and Training Administration [TA-W-81,145; TA-W-81,145A] Sunoco, Inc., R&M, Refining Division, Marcus Hook, PA; Sunoco, Inc., 10 Industrial Hwy., MS4 Building G, Lester, PA; Notice of Negative Determination on Reconsideration On April 30, 2012, the Department of Labor issued an Affirmative Determination Regarding...

77 FR 29362 - Sunoco, Inc., R&M Refining Division, Marcus Hook, PA; Sunoco, Inc., 10 Industrial Hwy, MS4...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-17

... DEPARTMENT OF LABOR Employment and Training Administration [TA-W-81,145; TA-W-81,145A] Sunoco, Inc., R&M Refining Division, Marcus Hook, PA; Sunoco, Inc., 10 Industrial Hwy, MS4 Building G, Lester, PA; Notice of Affirmative Determination Regarding Application for Reconsideration By application dated March 26, 2012, the United Steel Workers Union...

[Tumor-associated prognostic factors of the plasminogen activator family: determination and clinical value of u-PA, t-PA, PAI-1, and PAI-2].

PubMed

Mengele, K; Harbeck, N; Reuning, U; Magdolen, V; Schmitt, M

2005-08-01

Proteolytic factors belonging t the plasminogen activator family (plasmin, u-PA, t-PA, u-PAR, PAI-1, and PAI-2), which usually are involved in blood clotting and degradation of blood clots, are also present in healthy and diseased tissue of the kidney, lung, liver, gastro-intestinal tract, breast, prostate, ovary, and brain. These factors are engaged in brain development, angiogenesis and vascular invasion, wound healing as well as in placenta development and embryogenesis. Plasminogen activators u-PA and t-PA, their inhibitors PAI-1 and PAI-2, and the u-PA-receptor (u-PAR, CD87) are often elevated in solid malignant tumour tissues compared to their normal counterparts. In breast cancer patients, an elevated tumour tissue extract antigen content of u-PA, PAI-1, and u-PAR is associated with increased tumour aggressiveness and poor prognosis; in contrary, an elevated content of t-PA and PAI-2 indicates a favourable prognosis. For clinical relevant determination of these proteolytic factors in tumour tissue extracts, only enzymo-immunometric tests (ELISA) are recommended. Enzymometric and enzymographic tests are actually conducted only in an experimental, preclinical context.

Good outcome rate of 35% in IV-tPA-treated patients with computed tomography angiography confirmed severe anterior circulation occlusive stroke.

PubMed

González, R Gilberto; Furie, Karen L; Goldmacher, Gregory V; Smith, Wade S; Kamalian, Shervin; Payabvash, Seyedmehdi; Harris, Gordon J; Halpern, Elkan F; Koroshetz, Walter J; Camargo, Erica C S; Dillon, William P; Lev, Michael H

2013-11-01

To determine the effect of intravenous tissue plasminogen activator (IV-tPA) on outcomes in patients with severe major anterior circulation ischemic stroke. Prospectively, 649 patients with acute stroke had admission National Institutes of Health stroke scale (NIHSS) scores, noncontrast computed tomography (CT), CT angiography (CTA), and 6-month outcome assessed using modified Rankin scale. IV-tPA treatment decisions were made before CTA, at the time of noncontrast CT scanning, as per routine clinical protocol. Severe symptoms were defined as NIHSS>10. Poor outcome was defined as modified Rankin scale >2. Major occlusions were identified on CTA. Univariate and multivariate stepwise-forward logistic regression analyses of the full cohort were performed. Of 649 patients, 188 (29%) patients presented with NIHSS>10, and 64 out of 188 (34%) patients received IV-tPA. Admission NIHSS, large artery occlusion, and IV-tPA all independently predicted good outcomes; however, a significant interaction existed between IV-tPA and occlusion (P<0.001). Of the patients who presented with NIHSS>10 with anterior circulation occlusion, twice the percentage had good outcomes if they received IV-tPA (17 out of 49 patients, 35%) than if they did not (13 out of 77 patients, 17%; P=0.031). The number needed to treat was 7 (95% confidence interval, 3-60). IV-tPA treatment resulted in significantly better outcomes in patients with severely symptomatic stroke with major anterior circulation occlusions. The 35% good outcome rate was similar to rates found in endovascular therapy trials. Vascular imaging may help in patient selection and stratification for trials of IV-thrombolytic and endovascular therapies.

Intraarterial Thrombolysis with r-tPA for Treatment of Anterior Circulation Acute Ischemic Stroke

PubMed Central

Baltacioğlu, F.; Afşar, N.; Ekinci, G.; Tuncer-Elmaci, N.; Çagatay Çimşit, N; Aktan, S.; Erzen, C.

2003-01-01

Summary To investigate factors effecting the safety and recanalization efficacy of local intraarterial (IA) recombinant tissue plasminogen activator (r-tPA) delivery in patients with acute ischemic stroke. Eleven patients with anterior circulation acute ischemic stroke were treated. The neurological status of the patients were graded with the Glasgow Coma Scale (GCS) and National Institute of Health Stroke Scale (NIHSS). All patients underwent a computed tomography (CT) examination at admission. In addition four patients had diffusion-weighted and one patient had a perfusion magnetic resonance (MR) examinations. Patients were treated within six hours from stroke onset. Immediate, six hours, and 24 hours follow-up CT examinations were performed in order to evaluate the haemorrhagic complications and the extent of the ischemic area. The Rankin Scale (RS) was used as an outcome measure. Two of the 11 patients had carotid “T” occlusion (CTO), nine had middle cerebral artery (MCA) main trunk occlusion. Four patients had symptomatic haemorrhage with a large haematoma rupturing into the ventricles and subarachnoid space. Of these, three patients died within 24 hours. The remaining seven patients had asymptomatic haematomas that were smaller compared to symptomatic ones, and showed regression in size and density on follow-up CTs. At third month five patients had a good outcome and three patients had a poor outcome. In acute ischemic stroke, local IA thrombolysis is a feasible treatment when you select the right patient. Haemorrhage rate does not seem to exceed that occuring in the natural history of the disease and in other treatment modalities. PMID:20591253

The story of an exceptional serine protease, tissue-type plasminogen activator (tPA).

PubMed

Hébert, M; Lesept, F; Vivien, D; Macrez, R

2016-03-01

The only acute treatment of ischemic stroke approved by the health authorities is tissue recombinant plasminogen activator (tPA)-induced thrombolysis. Under physiological conditions, tPA, belonging to the serine protease family, is secreted by endothelial and brain cells (neurons, astrocytes, microglia, oligodendrocytes). Although revascularisation induced by tPA is beneficial during a stroke, research over the past 20 years shows that tPA can also be deleterious for the brain parenchyma. Thus, in this review of the literature, after a brief history on the discovery of tPA, we reviewed current knowledge of mechanisms by which tPA can influence brain function in physiological and pathological conditions. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

The cognition-enhancing activity of E1R, a novel positive allosteric modulator of sigma-1 receptors.

PubMed

Zvejniece, L; Vavers, E; Svalbe, B; Vilskersts, R; Domracheva, I; Vorona, M; Veinberg, G; Misane, I; Stonans, I; Kalvinsh, I; Dambrova, M

2014-02-01

Here, we describe the in vitro and in vivo effects of (4R,5S)-2-(5-methyl-2-oxo-4-phenyl-pyrrolidin-1-yl)-acetamide (E1R), a novel positive allosteric modulator of sigma-1 receptors. E1R was tested for sigma receptor binding activity in a [³H](+)-pentazocine assay, in bradykinin (BK)-induced intracellular Ca²⁺ concentration ([Ca²⁺](i)) assays and in an electrically stimulated rat vas deferens model. E1R's effects on cognitive function were tested using passive avoidance (PA) and Y-maze tests in mice. A selective sigma-1 receptor antagonist (NE-100), was used to study the involvement of the sigma-1 receptor in the effects of E1R. The open-field test was used to detect the effects of E1R on locomotion. Pretreatment with E1R enhanced the selective sigma-1 receptor agonist PRE-084's stimulating effect during a model study employing electrically stimulated rat vasa deferentia and an assay measuring the BK-induced [Ca²⁺](i) increase. Pretreatment with E1R facilitated PA retention in a dose-related manner. Furthermore, E1R alleviated the scopolamine-induced cognitive impairment during the PA and Y-maze tests in mice. The in vivo and in vitro effects of E1R were blocked by treatment with the selective sigma-1 receptor antagonist NE-100. E1R did not affect locomotor activity. E1R is a novel 4,5-disubstituted derivative of piracetam that enhances cognition and demonstrates efficacy against scopolamine-induced cholinergic dysfunction in mice. These effects are attributed to its positive modulatory action on the sigma-1 receptor and this activity may be relevant when developing new drugs for treating cognitive symptoms related to neurodegenerative diseases. © 2013 The British Pharmacological Society.

The cognition-enhancing activity of E1R, a novel positive allosteric modulator of sigma-1 receptors

PubMed Central

Zvejniece, L; Vavers, E; Svalbe, B; Vilskersts, R; Domracheva, I; Vorona, M; Veinberg, G; Misane, I; Stonans, I; Kalvinsh, I; Dambrova, M

2014-01-01

Background and Purpose Here, we describe the in vitro and in vivo effects of (4R,5S)-2-(5-methyl-2-oxo-4-phenyl-pyrrolidin-1-yl)-acetamide (E1R), a novel positive allosteric modulator of sigma-1 receptors. Experimental Approach E1R was tested for sigma receptor binding activity in a [3H](+)-pentazocine assay, in bradykinin (BK)-induced intracellular Ca2+ concentration ([Ca2+]i) assays and in an electrically stimulated rat vas deferens model. E1R's effects on cognitive function were tested using passive avoidance (PA) and Y-maze tests in mice. A selective sigma-1 receptor antagonist (NE-100), was used to study the involvement of the sigma-1 receptor in the effects of E1R. The open-field test was used to detect the effects of E1R on locomotion. Key Results Pretreatment with E1R enhanced the selective sigma-1 receptor agonist PRE-084's stimulating effect during a model study employing electrically stimulated rat vasa deferentia and an assay measuring the BK-induced [Ca2+]i increase. Pretreatment with E1R facilitated PA retention in a dose-related manner. Furthermore, E1R alleviated the scopolamine-induced cognitive impairment during the PA and Y-maze tests in mice. The in vivo and in vitro effects of E1R were blocked by treatment with the selective sigma-1 receptor antagonist NE-100. E1R did not affect locomotor activity. Conclusion and Implications E1R is a novel 4,5-disubstituted derivative of piracetam that enhances cognition and demonstrates efficacy against scopolamine-induced cholinergic dysfunction in mice. These effects are attributed to its positive modulatory action on the sigma-1 receptor and this activity may be relevant when developing new drugs for treating cognitive symptoms related to neurodegenerative diseases. PMID:24490863

The Q223R polymorphism in the leptin receptor associates with objectively measured light physical activity in free-living Japanese.

PubMed

Murakami, Haruka; Iemitsu, Motoyuki; Fuku, Noriyuki; Sanada, Kiyoshi; Gando, Yuko; Kawakami, Ryoko; Miyachi, Motohiko

2014-04-22

Physical activity (PA) is associated with reductions in the risk of all-cause mortality and in the prevalence of cardiovascular disease and stroke. Nevertheless, a large proportion of the general population may not be sufficiently active. PA level has been reported to be influenced by genetic factors, and we investigated whether Q223R polymorphism in the leptin receptor (LEPR) gene was associated with PA level. A total of 556 Japanese adults aged 24-65years old participated in this cross-sectional study. The duration and intensity of PA were objectively evaluated by triaxial accelerometry. Q223R polymorphism was determined by the TaqMan method. The distribution of Q223R polymorphism was: QQ 0.7%, QR 22.6%, and RR 76.6%. The relation between the LEPR genotype and PA level was analyzed by ANCOVA with age and sex as covariates in the Q dominant genetic model. There were significant differences between LEPR genotypes and the time spent in light PA or inactive time. The subjects with RR genotype showed significantly shorter time spent in light PA (RR genotype: 559.4±102.9min/day, QQ/QR genotype: 579.9±103.1min/day) and longer inactive time (RR genotype: 815.5±107.5min/day, QQ/QR genotype: 792.3±107.7min/day) than the subjects with QQ/QR genotype (P<0.05). There were no such differences in the time spent in moderate or vigorous PA. These results suggest that the variety of PA level, especially spontaneous PA in humans, is partly caused by diversity in the LEPR gene. Copyright © 2014. Published by Elsevier Inc.

Differences in leisure-time activities according to level of physical activity in adolescents.

PubMed

Mota, Jorge; Santos, Maria Paula; Ribeiro, Jose Carlos

2008-03-01

The main goals of this study were: (1) to examine the relationship between physical activity (PA) involvement and other leisure activities in a sample of Portuguese youth and (2) to analyze gender differences in PA and leisure-time activity structure. The sample comprised 1123 adolescents that were classified according to PA levels as active (n = 589) and nonactive (n = 534). A questionnaire assessing leisure-time activities was used. Girls were significantly more engaged in social leisure, dutiful, and individual artistic activities during leisure time, whereas boys were more involved in sports and computer and TV viewing activities. Significant associations between PA and social leisure were found in girls (r = .18, P < or = .001) and boys (r = .13, P < or = .01) after adjustment for age. The same was found between level of PA and sports engagement during leisure (girls: r = .56, P < or = .001; boys: r = .51, P < or = .001). In girls (r = .10, P < or = .05), but not in boys, a statistically significant association was found between PA and individual artistic activities. This study has certain implications for health-related PA promotion efforts. Our data give additional reinforcement to the importance of organized and nonorganized sports/PA during leisure time for overall levels of PA in adolescents.

Tissue plasminogen activator (tPA) as a reporter gene in transient gene expression.

PubMed

Cheng, S M; Lee, S G; Kalyan, N K; McCloud, S; Levner, M; Hung, P P

1987-01-01

Using the gene coding for tissue plasminogen activator (tPA) as a reporter gene, a transient gene expression system has been established. Vectors containing the full-length cDNA of tPA with its signal sequences were introduced into mammalian recipient cells by a modified gene transfer procedure. Thirty hours after transfection, the secreted tPA was found in serum-free medium and measured by a fibrin-agarose plate assay (FAPA). In this assay, tPA converts plasminogen into plasmin which then degrades high-Mr fibrin to produce cleared zones. The sizes of these zones correspond to quantities of tPA. The combination of transient tPA expression system and the FAPA provides a quick, sensitive, quantitative and non-destructive method to examine the strength of eukaryotic regulatory elements in tissue-culture cells.

Physical activity level of postmenopausal women in Nigeria: Association with self-rated health status, overall obesity, and abdominal obesity.

PubMed

Ogwumike, Omoyemi O; Adeniyi, Ade F; Orogbemi, Oluwakemi O

2016-07-01

Regular physical activity (PA) has been shown to have many health benefits in various populations, including postmenopausal women (n = 310). Self-rated health has been positively associated with PA. This cross-sectional survey of postmenopausal women in Nigeria was conducted from April to September 2012 to investigate associations among PA level, self-rated health, overall obesity (body mass index [BMI]), and abdominal obesity (waist-height ratio, waist-hip ratio, and waist circumference). The International Physical Activity Questionnaire was used to classify PA. Chi-square and logistic regression were used for analyses with level of significance set at .05. Participants were aged 53.0 ± 4.2 years; moderate to vigorous PA was reported by 188 (60.0%), while 26 (8.4%) self-rated their health as poor/fair, and 242 (78.1%) were either predominantly overweight or obese when classified according to BMI. Participants with fair/poor self-rated health had less odds of involvement in moderate to vigorous PA. Obese postmenopausal women had greater odds of reporting lower PA. PA was positively related to self-rated health, which was negatively associated with overall obesity but not abdominal obesity. Measures to control obesity among postmenopausal women are essential in view of its direct association with poor self-rated health and low PA in this group of women.

Differences in resting metabolic rate and physical activity patterns in lean and overweight/obese pregnant women

USDA-ARS?s Scientific Manuscript database

Energy requirements vary during pregnancy due to changes in physical activity (PA) and maternal fat stores. This study measured resting metabolic rate (RMR) and PA patterns in healthy lean and overweight/obese (OW) pregnant women. RMR was measured using indirect calorimetry (MOXUS), activity pattern...

Prognostic value of tissue-type plasminogen activator (tPA) and its complex with the type-1 inhibitor (PAI-1) in breast cancer

PubMed Central

Witte, J H de; Sweep, C G J; Klijn, J G M; Grebenschikov, N; Peters, H A; Look, M P; Tienoven, ThH van; Heuvel, J J T M; Vries, J Bolt-De; Benraad, ThJ; Foekens, J A

1999-01-01

The prognostic value of tissue-type plasminogen activator (tPA) measured in samples derived from 865 patients with primary breast cancer using a recently developed enzyme-linked immunosorbent assay (ELISA) was evaluated. Since the assay could easily be adapted to the assessment of the complex of tPA with its type-1 inhibitor (PAI-1), it was investigated whether the tPA:PAI-1 complex also provides prognostic information. To this end, cytosolic extracts and corresponding detergent extracts of 100 000 g pellets obtained after ultracentrifugation when preparing the cytosolic fractions for routine steroid hormone receptor determination were assayed. Statistically significant correlations were found between the cytosolic levels and those determined in the pellet extracts (Spearman correlation coefficient rs = 0.75, P < 0.001 for tPA and r = 0.50, P < 0.001 for tPA:PAI-1 complex). In both Cox univariate and multivariate analysis elevated levels of (total) tPA determined in the pellet extracts, but not in cytosols, were associated with prolonged relapse-free (RFS) and overall survival (OS). In contrast, high levels of the tPA:PAI-1 complex measured in cytosols, but not in the pellet extracts, were associated with a poor RFS and OS. The prognostic information provided by the cytosolic tPA:PAI-1 complex was comparable to that provided by cytosolic (total) PAI-1. Furthermore, the estimated levels of free, uncomplexed tPA and PAI-1, in cytosols and in pellet extracts, were related to patient prognosis in a similar way as the (total) levels of tPA and PAI-1 respectively. Determination of specific forms of components of the plasminogen activation system, i.e. tPA:PAI-1 complex and free, uncomplexed tPA and/or PAI-1, may be considered a useful adjunct to the analyses of the separate components (tPA and/or PAI-1) and provide valuable additional prognostic information with respect to survival of breast cancer patients. © 1999 Cancer Research Campaign PMID:10390010

Using complexity metrics with R-R intervals and BPM heart rate measures.

PubMed

Wallot, Sebastian; Fusaroli, Riccardo; Tylén, Kristian; Jegindø, Else-Marie

2013-01-01

Lately, growing attention in the health sciences has been paid to the dynamics of heart rate as indicator of impending failures and for prognoses. Likewise, in social and cognitive sciences, heart rate is increasingly employed as a measure of arousal, emotional engagement and as a marker of interpersonal coordination. However, there is no consensus about which measurements and analytical tools are most appropriate in mapping the temporal dynamics of heart rate and quite different metrics are reported in the literature. As complexity metrics of heart rate variability depend critically on variability of the data, different choices regarding the kind of measures can have a substantial impact on the results. In this article we compare linear and non-linear statistics on two prominent types of heart beat data, beat-to-beat intervals (R-R interval) and beats-per-min (BPM). As a proof-of-concept, we employ a simple rest-exercise-rest task and show that non-linear statistics-fractal (DFA) and recurrence (RQA) analyses-reveal information about heart beat activity above and beyond the simple level of heart rate. Non-linear statistics unveil sustained post-exercise effects on heart rate dynamics, but their power to do so critically depends on the type data that is employed: While R-R intervals are very susceptible to non-linear analyses, the success of non-linear methods for BPM data critically depends on their construction. Generally, "oversampled" BPM time-series can be recommended as they retain most of the information about non-linear aspects of heart beat dynamics.

Using complexity metrics with R-R intervals and BPM heart rate measures

PubMed Central

Wallot, Sebastian; Fusaroli, Riccardo; Tylén, Kristian; Jegindø, Else-Marie

2013-01-01

Lately, growing attention in the health sciences has been paid to the dynamics of heart rate as indicator of impending failures and for prognoses. Likewise, in social and cognitive sciences, heart rate is increasingly employed as a measure of arousal, emotional engagement and as a marker of interpersonal coordination. However, there is no consensus about which measurements and analytical tools are most appropriate in mapping the temporal dynamics of heart rate and quite different metrics are reported in the literature. As complexity metrics of heart rate variability depend critically on variability of the data, different choices regarding the kind of measures can have a substantial impact on the results. In this article we compare linear and non-linear statistics on two prominent types of heart beat data, beat-to-beat intervals (R-R interval) and beats-per-min (BPM). As a proof-of-concept, we employ a simple rest-exercise-rest task and show that non-linear statistics—fractal (DFA) and recurrence (RQA) analyses—reveal information about heart beat activity above and beyond the simple level of heart rate. Non-linear statistics unveil sustained post-exercise effects on heart rate dynamics, but their power to do so critically depends on the type data that is employed: While R-R intervals are very susceptible to non-linear analyses, the success of non-linear methods for BPM data critically depends on their construction. Generally, “oversampled” BPM time-series can be recommended as they retain most of the information about non-linear aspects of heart beat dynamics. PMID:23964244

A compact ECG R-R interval, respiration and activity recording system.

PubMed

Yoshimura, Takahiro; Yonezawa, Yoshiharu; Maki, Hiromichi; Ogawa, Hidekuni; Hahn, Allen W; Thayer, Julian F; Caldwell, W Morton

2003-01-01

An ECG R-R interval, respiration and activity recording system has been developed for monitoring variability of heart rate and respiratory frequency during daily life. The recording system employs a variable gain instrumentation amplifier, an accelerometer, a low power 8-bit single-chip microcomputer and a 1024 KB EEPROM. It is constructed on three ECG chest electrodes. The R-R interval and respiration are detected from the ECG. Activity during walking and running is calculated from an accelerator. The detected data are stored in an EEPROM and after recording, are downloaded to a desktop computer for analysis.

Tissue plasminogen activator (tPA) and matrix metalloproteinases in the pathogenesis of stroke: therapeutic strategies.

PubMed

Adibhatla, Rao Muralikrishna; Hatcher, James F

2008-06-01

Today there exists only one FDA-approved treatment for ischemic stroke; i.e., the serine protease tissue-type plasminogen activator (tPA). In the aftermath of the failed stroke clinical trials with the nitrone spin trap/radical scavenger, NXY-059, a number of articles raised the question: are we doing the right thing? Is the animal research truly translational in identifying new agents for stroke treatment? This review summarizes the current state of affairs with plasminogen activators in thrombolytic therapy. In addition to therapeutic value, potential side effects of tPA also exist that aggravate stroke injury and offset the benefits provided by reperfusion of the occluded artery. Thus, combinational options (ultrasound alone or with microspheres/nanobubbles, mechanical dissociation of clot, activated protein C (APC), plasminogen activator inhibitor-1 (PAI-1), neuroserpin and CDP-choline) that could offset tPA toxic side effects and improve efficacy are also discussed here. Desmoteplase, a plasminogen activator derived from the saliva of Desmodus rotundus vampire bat, antagonizes vascular tPA-induced neurotoxicity by competitively binding to low-density lipoprotein related-receptors (LPR) at the blood-brain barrier (BBB) interface, minimizing the tPA uptake into brain parenchyma. tPA can also activate matrix metalloproteinases (MMPs), a family of endopeptidases comprised of 24 mammalian enzymes that primarily catalyze the turnover and degradation of the extracellular matrix (ECM). MMPs have been implicated in BBB breakdown and neuronal injury in the early times after stroke, but also contribute to vascular remodeling, angiogenesis, neurogenesis and axonal regeneration during the later repair phase after stroke. tPA, directly or by activation of MMP-9, could have beneficial effects on recovery after stroke by promoting neurovascular repair through vascular endothelial growth factor (VEGF). However, any treatment regimen directed at MMPs must consider their

Overexpression of PaFT gene in the wild orchid Phalaenopsis amabilis (L.) Blume

NASA Astrophysics Data System (ADS)

Semiarti, Endang; Mercuriani, Ixora S.; Rizal, Rinaldi; Slamet, Agus; Utami, Bekti S.; Bestari, Ida A.; Aziz-Purwantoro, Moeljopawiro, S.; Jang, Soenghoe; Machida, Y.; Machida, C.

2015-09-01

To shorten vegetative stage and induce transition from vegetative to reproductive stage in orchids, we overexpressed Phalaenopsis amabilis Flowering LocusT (PaFT) gene under the control of Ubiquitin promoter into protocorm of Indonesian Wild Orchid Phalaenopsis amabilis (L.) Blume. The dynamic expression of vegetative gene Phalaenopsis Homeobox1 (POH1) and flowering time gene PaFT has been analyzed. Accumulation of mRNA was detected in shoot and leaves of both transgenic and non transgenic plants by using Reverse transcriptase-PCR (RT-PCR) with specific gene primers for POH1 and PaFT in 24 months old plants. To analyze the POH1 and PaFT genes, three pairs of degenerate primers PaFT degF1R1, F2R2 and F3R3 that amplified 531 bp PaFT cDNA were used. We detected 700 bp PaFTcDNA from leaves and shoots of transgenic plants, but not in NT plants. POH1 mRNA was detected in plants. PaFT protein consists of Phospatidyl Ethanolamine-Binding Protein (PEBP) in interval base 73-483 and CETS family protein at base 7-519, which are important motif for transmembrane protein. We inserted Ubipro::PaFT/pGAS101 into P. amabilis protocorm using Agrobacterium. Analysis of transgenic plants showed that PaFTmRNA was accumulated in leaves of 12 months after sowing, although it is not detected in non transgeic plants. Compare to the wild type (NT plants), ectopic expression of PaFT shows alter phenotype as follows: 31% normal, 19% with short-wavy leaves, 5% form rosette leaves and 45% produced multishoots. Analysis of protein profiles of trasgenic plants showed that a putative PaFT protein (MW 19,7 kDa) was produced in 1eaves and shoots.This means that at 12 months, POH1 gene expression gradually decreased/negatively regulated, the expression of PaFT gene was activated, although there is no flower initiation yet. Some environmental factors might play a role to induce inflorescens. This experiment is in progress.

35% Good Outcome Rate in IV-tPA treated Patients with CTA Confirmed Severe Anterior Circulation Occlusive Stroke

PubMed Central

González, R. Gilberto; Furie, Karen L.; Goldmacher, Gregory V.; Smith, Wade S.; Kamalian, Shervin; Payabvash, Seyedmehdi; Harris, Gordon J.; Halpern, Elkan F.; Koroshetz, Walter J.; Camargo, Erica C. S.; Dillon, William P.; Lev, Michael H.

2015-01-01

BACKGROUND AND PURPOSE To determine the effect of IV-tPA on outcomes in patients with severe major anterior circulation ischemic stroke. METHODS Prospectively, 649 acute stroke patients had admission NIH stroke scale scores (NIHSS), non-contrast CT, CT angiography (CTA), and 6-month outcome assessed using modified Rankin scale (mRS). IV-tPA treatment decisions were made prior to CTA, at the time of non-contrast CT scanning, as per routine clinical protocol. Severe symptoms were defined as NIHSS>10. Poor outcome was defined as mRS>2. Major occlusions were identified on CTA. Univariate and multivariate stepwise-forward logistic regression analyses of the full cohort were performed. RESULTS Of 649 patients, 188 (29%) presented with NIHSS>10, and 64/188 (34%) of these received IV-tPA. Admission NIHSS, large artery occlusion, and IV-tPA all independently predicted good outcomes, however a significant interaction existed between IV-tPA and occlusion (p<0.001). Of NIHSS>10 patients with anterior circulation occlusion, twice the percentage had good outcomes if they received IV-tPA (17/49, 35%), than if they did not (13/77, 17%; p=0.031). The “number needed to treat” was 7 (95% CI = 3–60). CONCLUSIONS IV-tPA treatment resulted in significantly more good outcomes in severely symptomatic stroke patients with major anterior circulation occlusions. The 35% good outcome rate was similar to rates found in endovascular therapy trials. Vascular imaging may help in patient selection and stratification for trials of IV-thrombolytic and endovascular therapies. PMID:24003051

Post-exercise heart rate recovery in healthy, obeses, and COPD subjects: relationships with blood lactic acid and PaO2 levels.

PubMed

Ba, Abdoulaye; Delliaux, Stephane; Bregeon, Fabienne; Levy, Samuel; Jammes, Yves

2009-01-01

Because blood acidosis and arterial oxygenation (PaO(2)) play key roles in the chemoreflex control of cardiac activity, we hypothesized that heart rate (HR) decay rate after maximal exercise may be linked to post-exercise increase in blood lactate (LA) level and/or the resting PaO(2). Twenty healthy subjects and thirty five patients at risks of cardiovascular diseases (20 obeses; 15 patients with chronic obstructive pulmonary disease, COPD) performed a maximal cycling exercise. During the recovery period, HR was continuously measured for consecutive 10-s epochs allowing to compute linear or second order polynomial equations and to calculate every minute HR variations compared to peak HR value (DeltaHR). PaO(2) was measured at rest and post-exercise maximal LA level was determined. A second order polynomial equation (y = a(2) x (2) + b(2) x + c) best fitted the post-exercise HR decay rate. The a(2) and b(2) coefficients and DeltaHR did not depend on age, sex, and body mass index. Despite a large scattering of HR decay rate, even present in healthy subjects, a(2) and DeltaHR were significantly lower in obeses and COPDs. In the whole population, both a(2) coefficient and DeltaHR were negatively correlated with maximal post-exercise LA level. DeltaHR was lowered in hypoxemic patients. Thus, the slowest post-exercise HR decay rate was measured in subjects having the highest peak LA increase or hypoxemia. Thus, even in healthy subjects, the post-exercise HR decay rate is lowered in individuals having an accentuated exercise-induced LA increase and/or hypoxemia. The mechanisms of delayed post-exercise HR recovery are only suspected because significant correlations cannot assess cause-to-effect relationships.

Level of agreement between physical activity levels measured by ActiHeart and the International Physical Activity Questionnaire in persons with intellectual disability.

PubMed

Moss, Sarah J; Czyz, Stanislaw H

2018-02-01

The purpose of this study was to determine the level of agreement between objective physical activity (PA) (ActiHeart ® ) and subjective proxy-respondent International Physical Activity Questionnaire-short version (IPAQ-S) data in adults with intellectual disabilities (IDs). Fifty-eight participants wore ActiHeart ® monitors for seven consecutive days. Caregivers of each participant completed the IPAQ-S on behalf of the participant. Total PA, time spent in light, moderate, and vigorous activity as well as time spent being sedentary were assessed by the IPAQ-S and the ActiHeart ® . Results were compared by means of correlation analyses. The level of agreement was presented with Bland-Altman plots. Objective PA (ActiHeart ® ) was higher (225.57 ± 91.96 min/week) than IPAQ-S PA reported by care-givers (177.06 ± 309.17 min/week). Weak significant correlations were observed between the ActiHeart ® and IPAQ-S instruments for sedentary behavior (r = 0.31; p = 0.04); no significant correlations for light (r= -0.04; p = 0.8), moderate (r= -0.07; p = 0.63), or vigorous PA (r= -0.2; p = 0.18) were found. Limited agreement between objectively determine PA (ActiHeart ® ) and IPAQ-S was found. IPAQ-S is inaccurate when determining PA in persons with ID as it significantly underestimates the true levels of PA in this cohort. Implications for Rehabilitation Persons with intellectual disability (ID) report insufficient physical activity for health benefits. Physical activity is often determined by means of subjective proxy reporting. Objective physical activity measurements by means of combined heart rate and accelerometer are necessary to determine accurate levels of physical activity in persons with ID. Exercise interventions should be based on objective physical activity measurements.

Comparison of the college alumnus questionnaire physical activity index with objective monitoring.

PubMed

Strath, Scott J; Bassett, David R; Swartz, Ann M

2004-07-01

Two methods of measuring physical activity (PA) were compared over a consecutive 7-day period among 25 adults (12 men and 13 women). Each day estimates of energy expended in light, moderate, vigorous, and total PA were derived from the simultaneous heart-rate motion sensor (HR+M) technique. At the end of the 7-day period participants completed the College Alumnus Questionnaire Physical Activity Index (CAQ-PAI) and results were compared with HR+M technique estimates. Correlations between the two methods in the four activity categories ranged from r=0.20 to r=0.47, with vigorous and total PA showing higher associations than light and moderate PA. Mean levels of PA (MET-minxwk(-1)) obtained using the two methods were similar in the moderate and vigorous categories, but individual differences were large. Energy expended in light PA was significantly underestimated on the CAQ-PAI, resulting in lower total activity scores on this questionnaire as compared with the HR+M. The CAQ-PAI accurately reflected mean moderate and vigorous activity in comparison with the HR+M technique. The results are consistent with other studies which have shown that physical activity questionnaires are better at assessing vigorous PA than ubiquitous light-moderate activities.

Psychological correlates of self-reported and objectively measured physical activity among Chinese children—psychological correlates of PA

USDA-ARS?s Scientific Manuscript database

This study aimed to explore the associations among psychological correlates and physical activity (PA) in Chinese children and to further examine whether these associations varied by different PA measures. PA self-efficacy, motivation, and preference were reported in 449 8–13-year-old Chinese childr...

Protease-activated receptor 2 (PAR2) is upregulated by Acanthamoeba plasminogen activator (aPA) and induces proinflammatory cytokine in human corneal epithelial cells.

PubMed

Tripathi, Trivendra; Abdi, Mahshid; Alizadeh, Hassan

2014-05-29

Acanthamoeba plasminogen activator (aPA) is a serine protease elaborated by Acanthamoeba trophozoites that facilitates the invasion of trophozoites to the host and contributes to the pathogenesis of Acanthamoeba keratitis (AK). The aim of this study was to explore if aPA stimulates proinflammatory cytokine in human corneal epithelial (HCE) cells via the protease-activated receptors (PARs) pathway. Acanthamoeba castellanii trophozoites were grown in peptone-yeast extract glucose for 7 days, and the supernatants were collected and centrifuged. The aPA was purified using the fast protein liquid chromatography system, and aPA activity was determined by zymography assays. Human corneal epithelial cells were incubated with or without aPA (100 μg/mL), PAR1 agonists (thrombin, 10 μM; TRAP-6, 10 μM), and PAR2 agonists (SLIGRL-NH2, 100 μM; AC 55541, 10 μM) for 24 and 48 hours. Inhibition of PAR1 and PAR2 involved preincubating the HCE cells for 1 hour with the antagonist of PAR1 (SCH 79797, 60 μM) and PAR2 (FSLLRY-NH2, 100 μM) with or without aPA. Human corneal epithelial cells also were preincubated with PAR1 and PAR2 antagonists and then incubated with or without PAR1 agonists (thrombin and TRAP-6) and PAR2 agonists (SLIGRL-NH2 and AC 55541). Expression of PAR1 and PAR2 was examined by quantitative RT-PCR (qRT-PCR), flow cytometry, and immunocytochemistry. Interleukin-8 expression was quantified by qRT-PCR and ELISA. Human corneal epithelial cells constitutively expressed PAR1 and PAR2 mRNA. Acanthamoeba plasminogen activator and PAR2 agonists significantly upregulated PAR2 mRNA expression (1- and 2-fold, respectively) (P < 0.05). Protease-activated receptor 2 antagonist significantly inhibited aPA, and PAR2 agonists induced PAR2 mRNA expression in HCE cells (P < 0.05). Protease-activated receptor 1 agonists, but not aPA, significantly upregulated PAR1 mRNA expression, which was significantly inhibited by PAR1 antagonist in HCE cells. Acanthamoeba plasminogen

Epistatic Effects of Polymorphisms in Genes from the Renin-Angiotensin, Bradykinin, and Fibrinolytic Systems on Plasma t-PA and PAI-1 Levels

PubMed Central

Asselbergs, Folkert W.; Williams, Scott M.; Hebert, Patricia R.; Coffey, Christopher S.; Hillege, Hans L.; Navis, Gerjan; Vaughan, Douglas E.; van Gilst, Wiek H.; Moore, Jason H.

2007-01-01

Tissue plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1) directly influence thrombus formation and degradation and thereby risk for arterial thrombosis. Activation of the renin-angiotensin system has been linked to the production of PAI-1 expression via the angiotensin II type 1 receptor (AT1R). In addition, bradykinin can induce the release of t-PA through a B2 receptor mechanism. In the present study, we aimed to investigate the epistatic effects of polymorphisms in genes from the renin-angiotensin, bradykinin and fibrinolytic systems on plasma t-PA and PAI-1 levels in a large population-based sample (n=2,527). We demonstrated a strong significant interaction within genetic variations of the bradykinin B2 gene (p=0.002) and between ACE and bradykinin B2 (p=0.003) polymorphisms on t-PA levels in females. In males, polymorphisms in the bradykinin B2 and AT1R gene showed the most strong effect on t-PA levels (p=0.006). In both females as well as males, the bradykinin B2 gene interacted with AT1R gene on plasma PAI-1 levels (p=0.026 and p=0.039, respectively). In addition, the current study found a borderline significant interaction between PAI 4G5G and ACE I/D on plasma t-PA and PAI-1 levels. These results support the idea that the interplay between the renin-angiotensin, bradykinin, and fibrinolytic systems might play an important role in t-PA and PAI-1 biology. PMID:17207964

Curcumin suppresses colon cancer cell invasion via AMPK-induced inhibition of NF-κB, uPA activator and MMP9.

PubMed

Tong, Weihua; Wang, Quan; Sun, Donghui; Suo, Jian

2016-11-01

Curcumin, an active nontoxic ingredient of turmeric, possesses potent anti-inflammatory, antioxidant and anti-cancer properties; however, the molecular mechanisms of curcumin are not fully understood. The transcription factor nuclear factor-κB (NF-κB) is key in cellular processes, and the expression/activation of urokinase-type plasminogen activator (uPA) and matrix metalloproteinase-9 (MMP9) are crucial for cell invasion. The present study investigated the hypothesis that curcumin inhibits colon cancer cell invasion by modulating NF-κB-mediated expression and activation of uPA and MMP9. Human colon cancer SW480 and LoVo cells were treated with various concentrations of curcumin. Curcumin was demonstrated to dose-dependently inhibit the adhesion and proliferation ability of LoVo and SW480 cells using Transwell and MTT assays, respectively. In addition, curcumin activated 5' AMP-activated protein kinase (AMPK) and suppressed p65 NF-κB phosphorylation, as shown by western blot analysis. Compound C, a potent AMPK inhibitor, abolished curcumin-induced inhibition of NF-κB, uPA and MMP9, suggesting that AMPK activation is responsible for curcumin-mediated NF-κB, uPA and MMP9 inhibition. The binding activity of NF-κB to DNA was examined and western blotting and quantitative polymerase reaction was performed to detect the effect of curcumin on the expression of uPA and MMP9. The present results revealed that curcumin significantly decreased the expression of uPA and MMP9 and NF-κB DNA binding activity. Furthermore, curcumin decreased the level of the p65 subunit of NF-κB binding to the promoter of the gene encoding uPA and MMP9, which suppressed transcriptional activation of uPA and MMP9. Overall, the present data suggest that curcumin inhibits colon cancer cell invasion via AMPK activation and subsequent inhibition of p65 NF-κB, uPA and MMP9. The therapeutic potential of curcumin for colon cancer metastasis required additional study.

The influence of ethnicity and gender on the association between measured obesity and cardiorespiratory fitness with self-rated overweight, physical activity and health.

PubMed

Kuk, Jennifer L; Ardern, Chris I

2014-01-01

Little is known about how ethnicity may influence how self-rated physical activity (PA) and obesity relates to measured obesity, cardiorespiratory fitness and self-rated health. To examine the influence of ethnicity on the association between: (1) self-rated and measured obesity; (2) self-reported PA and cardiorespiratory fitness; and (3) obesity and PA with self-rated health. Data from NHANES 1999-2004 (2,981 adults) was used. Compared to white and overweight black men, Hispanic men were less likely to consider themselves overweight (OR = 0.36-0.56). Compared to white men, black active men were more likely to report being more active than their peers (OR = 1.44) but were less likely to be fit (OR = 0.74). Black active women and non-white overweight women were less likely to self-rate as having very good or excellent health as compared to white women with similar self-reported and measured health factors. Ethnicity and gender influence how self-rated and measured health factors interrelate.

Synergy of combined tPA-edaravone therapy in experimental thrombotic stroke.

PubMed

Sun, Yu-Yo; Morozov, Yury M; Yang, Dianer; Li, Yikun; Dunn, R Scott; Rakic, Pasko; Chan, Pak H; Abe, Koji; Lindquist, Diana M; Kuan, Chia-Yi

2014-01-01

Edaravone, a potent antioxidant, may improve thrombolytic therapy because it benefits ischemic stroke patients on its own and mitigates adverse effects of tissue plasminogen activator (tPA) in preclinical models. However, whether the combined tPA-edaravone therapy is more effective in reducing infarct size than singular treatment is uncertain. Here we investigated this issue using a transient hypoxia-ischemia (tHI)-induced thrombotic stroke model, in which adult C57BL/6 mice were subjected to reversible ligation of the unilateral common carotid artery plus inhalation of 7.5% oxygen for 30 min. While unilateral occlusion of the common carotid artery suppressed cerebral blood flow transiently, the addition of hypoxia triggered reperfusion deficits, endogenous thrombosis, and attenuated tPA activity, leading up to infarction. We compared the outcomes of vehicle-controls, edaravone treatment, tPA treatment at 0.5, 1, or 4 h post-tHI, and combined tPA-edaravone therapies with mortality rate and infarct size as the primary end-points. The best treatment was further compared with vehicle-controls in behavioral, biochemical, and diffusion tensor imaging (DTI) analyses. We found that application of tPA at 0.5 or 1 h--but not at 4 h post-tHI--significantly decreased infarct size and showed synergistic (p<0.05) or additive benefits with the adjuvant edaravone treatment, respectively. The acute tPA-edaravone treatment conferred >50% reduction of mortality, ∼ 80% decline in infarct size, and strong white-matter protection. It also improved vascular reperfusion and decreased oxidative stress, inflammatory cytokines, and matrix metalloproteinase activities. In conclusion, edaravone synergizes with acute tPA treatment in experimental thrombotic stroke, suggesting that clinical application of the combined tPA-edaravone therapy merits investigation.

Synergy of Combined tPA-Edaravone Therapy in Experimental Thrombotic Stroke

PubMed Central

Sun, Yu-Yo; Morozov, Yury M.; Yang, Dianer; Li, Yikun; Dunn, R. Scott; Rakic, Pasko; Chan, Pak H.; Abe, Koji; Lindquist, Diana M.; Kuan, Chia-Yi

2014-01-01

Edaravone, a potent antioxidant, may improve thrombolytic therapy because it benefits ischemic stroke patients on its own and mitigates adverse effects of tissue plasminogen activator (tPA) in preclinical models. However, whether the combined tPA-edaravone therapy is more effective in reducing infarct size than singular treatment is uncertain. Here we investigated this issue using a transient hypoxia-ischemia (tHI)-induced thrombotic stroke model, in which adult C57BL/6 mice were subjected to reversible ligation of the unilateral common carotid artery plus inhalation of 7.5% oxygen for 30 min. While unilateral occlusion of the common carotid artery suppressed cerebral blood flow transiently, the addition of hypoxia triggered reperfusion deficits, endogenous thrombosis, and attenuated tPA activity, leading up to infarction. We compared the outcomes of vehicle-controls, edaravone treatment, tPA treatment at 0.5, 1, or 4 h post-tHI, and combined tPA-edaravone therapies with mortality rate and infarct size as the primary end-points. The best treatment was further compared with vehicle-controls in behavioral, biochemical, and diffusion tensor imaging (DTI) analyses. We found that application of tPA at 0.5 or 1 h – but not at 4 h post-tHI – significantly decreased infarct size and showed synergistic (p<0.05) or additive benefits with the adjuvant edaravone treatment, respectively. The acute tPA-edaravone treatment conferred >50% reduction of mortality, ∼80% decline in infarct size, and strong white-matter protection. It also improved vascular reperfusion and decreased oxidative stress, inflammatory cytokines, and matrix metalloproteinase activities. In conclusion, edaravone synergizes with acute tPA treatment in experimental thrombotic stroke, suggesting that clinical application of the combined tPA-edaravone therapy merits investigation. PMID:24911517

Dual activities of ritanserin and R59022 as DGKα inhibitors and serotonin receptor antagonists.

PubMed

Boroda, Salome; Niccum, Maria; Raje, Vidisha; Purow, Benjamin W; Harris, Thurl E

2017-01-01

Diacylglycerol kinase alpha (DGKα) catalyzes the conversion of diacylglycerol (DAG) to phosphatidic acid (PA). Recently, DGKα was identified as a therapeutic target in various cancers, as well as in immunotherapy. Application of small-molecule DGK inhibitors, R59022 and R59949, induces cancer cell death in vitro and in vivo. The pharmacokinetics of these compounds in mice, however, are poor. Thus, there is a need to discover additional DGK inhibitors not only to validate these enzymes as targets in oncology, but also to achieve a better understanding of their biology. In the present study, we investigate the activity of ritanserin, a compound structurally similar to R59022, against DGKα. Ritanserin, originally characterized as a serotonin (5-HT) receptor (5-HTR) antagonist, underwent clinical trials as a potential medicine for the treatment of schizophrenia and substance dependence. We document herein that ritanserin attenuates DGKα kinase activity while increasing the enzyme's affinity for ATP in vitro. In addition, R59022 and ritanserin function as DGKα inhibitors in cultured cells and activate protein kinase C (PKC). While recognizing that ritanserin attenuates DGK activity, we also find that R59022 and R59949 are 5-HTR antagonists. In conclusion, ritanserin, R59022 and R59949 are combined pharmacological inhibitors of DGKα and 5-HTRs in vitro. Copyright © 2016 Elsevier Inc. All rights reserved.

TRUST-tPA trial: Telemedicine for remote collaboration with urgentists for stroke-tPA treatment.

PubMed

Mazighi, Mikael; Meseguer, Elena; Labreuche, Julien; Miroux, Patrick; Le Gall, Catherine; Roy, Patricia; Tubach, Florence; Amarenco, Pierre

2017-01-01

Background Previous observational studies have shown that telemedicine is feasible and safe to deliver intravenous (IV) recombinant tissue plasminogen activator (rt-PA). However, implementation of telemedicine may be challenging. To illustrate this fact, we report a study showing that telemedicine failed to improve clinical outcome and analyze the reasons for this shortcoming. Methods We established a tele-stroke network of 10 emergency rooms (ERs) of community hospitals connected to a stroke center to perform a randomized, open-label clinical trial with blinded outcome evaluation. Eligible patients were randomly assigned to either a usual care arm (i.e. immediate transfer to the stroke center and administration of IV rt-PA if indication was confirmed upon stroke arrival) or tele-thrombolysis arm (i.e. immediate administration of IV rt-PA in ER and transfer to the stroke center). The primary efficacy outcome was an excellent outcome (modified Rankin scale (mRS) 0-1 at 90 days). Secondary endpoints included favorable outcome (90-day mRS 0-2) and early neurological improvement (NIHSS score 0-1 at 24 hours or a decrease of ≥ 4 points within 24 hours). Safety outcomes included symptomatic intracerebral hemorrhage (ICH) per ECASS II definition, any ICH and all-cause mortality. Results During an accrual time of 48 months, because of a slow enrollment rate, only 49 of 270 patients initially planned for inclusion were randomized into usual care ( n = 23) and tele-thrombolysis ( n = 26). Despite random assignment, patients allocated to tele-thrombolysis were older and had more severe stroke than patients allocated to usual care. The median duration of video-conference was 23 minutes in the usual care arm and 73 minutes in the tele-thrombolysis arm. Eighty-four percent of patients in the tele-thrombolysis arm were treated by IV rt-PA in comparison to 18% in the usual care arm. In univariate analysis but not after adjustment for age and baseline NIHSS, patients

GROUND-BASED Paα NARROW-BAND IMAGING OF LOCAL LUMINOUS INFRARED GALAXIES. I. STAR FORMATION RATES AND SURFACE DENSITIES

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

Tateuchi, Ken; Konishi, Masahiro; Motohara, Kentaro

2015-03-15

Luminous infrared galaxies (LIRGs) are enshrouded by a large amount of dust produced by their active star formation, and it is difficult to measure their activity in optical wavelengths. We have carried out Paα narrow-band imaging observations of 38 nearby star forming galaxies including 33 LIRGs listed in the IRAS Revised Bright Galaxy Sample catalog with the Atacama Near InfraRed camera on the University of Tokyo Atacama Observatory (TAO) 1.0 m telescope (miniTAO). Star formation rates (SFRs) estimated from the Paα fluxes, corrected for dust extinction using the Balmer decrement method (typically A{sub V} ∼ 4.3 mag), show a good correlation with thosemore » from the bolometric infrared luminosity of the IRAS data within a scatter of 0.27 dex. This suggests that the correction of dust extinction for the Paα flux is sufficient in our sample. We measure the physical sizes and surface densities of infrared luminosities (Σ{sub L(IR)}) and the SFR (Σ{sub SFR}) of star forming regions for individual galaxies, and we find that most of the galaxies follow a sequence of local ultra-luminous or luminous infrared galaxies (U/LIRGs) on the L(IR)-Σ{sub L(IR)} and SFR-Σ{sub SFR} plane. We confirm that a transition of the sequence from normal galaxies to U/LIRGs is seen at L(IR) = 8 × 10{sup 10} L {sub ☉}. Also, we find that there is a large scatter in physical size, different from normal galaxies or ULIRGs. Considering the fact that most U/LIRGs are merging or interacting galaxies, this scatter may be caused by strong external factors or differences in their merging stages.« less

Functional Characterization of Phalaenopsis aphrodite Flowering Genes PaFT1 and PaFD

PubMed Central

Jang, Seonghoe; Choi, Sang-Chul; Li, Hsing-Yi; An, Gynheung; Schmelzer, Elmon

2015-01-01

We show that the key flowering regulators encoded by Phalaenopsis aphrodite FLOWERING LOCUS T1 (PaFT1) and PaFD share high sequence homologies to these from long-day flowering Arabidopsis and short-day flowering rice. Interestingly, PaFT1 is specifically up-regulated during flowering inductive cooling treatment but is not subjected to control by photoperiod in P. aphrodite. Phloem or shoot apex-specific expression of PaFT1 restores the late flowering of Arabidopsis ft mutants. Moreover, PaFT1 can suppress the delayed flowering caused by SHORT VEGATATIVE PHASE (SVP) overexpression as well as an active FRIGIDA (FRI) allele, indicating the functional conservation of flowering regulatory circuit in different plant species. PaFT1 promoter:GUS in Arabidopsis showed similar staining pattern to that of Arabidopsis FT in the leaves and guard cells but different in the shoot apex. A genomic clone or heat shock-inducible expression of PaFT1 is sufficient to the partial complementation of the ft mutants. Remarkably, ectopic PaFT1 expression also triggers precocious heading in rice. To further demonstrate the functional conservation of the flowering regulators, we show that PaFD, a bZIP transcription factor involved in flowering promotion, interacts with PaFT1, and PaFD partially complemented Arabidopsis fd mutants. Transgenic rice expressing PaFD also flowered early with increased expression of rice homologues of APETALA1 (AP1). Consistently, PaFT1 knock-down Phalaenopsis plants generated by virus-induced gene silencing exhibit delayed spiking. These studies suggest functional conservation of FT and FD genes, which may have evolved and integrated into distinct regulatory circuits in monopodial orchids, Arabidopsis and rice that promote flowering under their own inductive conditions. PMID:26317412

Daily Steps in Midlife and Older Adults: Relationship with Demographic, Self-Rated Health, and Self-Reported Physical Activity

ERIC Educational Resources Information Center

Payn, Tamara; Pfeiffer, Karin A.; Hutto, Brent; Vena, John E.; LaMonte, Michael J.; Blair, Steven N.; Hooker, Steven P.

2008-01-01

The relationship between average daily step counts and age, body mass index (BMI), self-reported physical activity (PA) level, and perceived health was determined in 85 middle-aged and older adults who wore a pedometer for 7 consecutive days. Average daily steps were significantly (p less than 0.05) correlated with BMI (r = -0.26), age (r = -0.44)…

Biological and Sociocultural Differences in Perceived Barriers to Physical Activity Among Fifth- to Seventh-Grade Urban Girls.

PubMed

Vermeesch, Amber L; Ling, Jiying; Voskuil, Vicki R; Bakhoya, Marion; Wesolek, Stacey M; Bourne, Kelly A; Pfeiffer, Karin A; Robbins, Lorraine B

2015-01-01

Inadequate physical activity (PA) contributes to the high prevalence of overweight and obesity among U.S. adolescent girls. Barriers preventing adolescent girls from meeting PA guidelines have not been thoroughly examined. The threefold purpose of this study was to (a) determine pubertal stage, racial/ethnic, and socioeconomic status (SES) differences in ratings of interference of barriers to PA; (b) examine relationships between perceived barriers and age, body mass index, recreational screen time, sedentary activity, and PA; and (c) identify girls' top-rated perceived barriers to PA. Girls (N = 509) from eight Midwestern U.S. schools participated. Demographic, pubertal stage, perceived barriers, and recreational screen time data were collected via surveys. Height and weight were measured. Accelerometers measured sedentary activity, moderate-to-vigorous PA (MVPA), and light plus MVPA. Girls of low SES reported greater interference of perceived barriers to PA than those who were not of low SES (1.16 vs. 0.97, p = .01). Girls in early/middle puberty had lower perceived barriers than those in late puberty (1.03 vs. 1.24, p < .001). Girls' perceived barriers were negatively related to MVPA (r = -.10, p = .03) and light plus MVPA (r = -.11, p = .02). Girls' top five perceived barriers included lack of skills, hating to sweat, difficulty finding programs, being tired, and having pain. Innovative interventions, particularly focusing on skill development, are needed to assist girls in overcoming their perceived barriers to PA.

Biological and Sociocultural Differences in Perceived Barriers to Physical Activity among 5th–7th Grade Urban Girls

PubMed Central

Vermeesch, Amber L.; Ling, Jiying; Voskuil, Vicki R.; Bakhoya, Marion; Wesolek, Stacey M.; Bourne, Kelly A.; Pfeiffer, Karin A.; Robbins, Lorraine B.

2015-01-01

Background Inadequate physical activity (PA) contributes to the high prevalence of overweight and obesity among U.S. adolescent girls. Barriers preventing adolescent girls from meeting PA guidelines have not been thoroughly examined. Objectives The threefold purpose of this study was to: (a) determine pubertal stage, racial/ethnic, and socioeconomic status (SES) differences in ratings of interference of barriers to PA; (b) examine relationships between perceived barriers and age, body mass index (BMI), recreational screen time, sedentary activity, and PA; and (c) identify girls’ top-rated perceived barriers to PA. Methods Girls (N = 509) from eight Midwestern U.S. schools participated. Demographic, pubertal stage, perceived barriers, and recreational screen time data were collected via surveys. Height and weight were measured. Accelerometers measured sedentary activity, moderate-to-vigorous physical activity (MVPA), and light plus MVPA. Results Girls of low SES reported greater interference of perceived barriers to PA than those who were not of low SES (1.16 vs. 0.97, p = .01). Girls in early/middle puberty had lower perceived barriers than those in late puberty (1.03 vs. 1.24, p < .001). Girls’ perceived barriers were negatively related to MVPA (r = −.10, p = .03) and light plus MVPA (r = −.11, p = .02). Girls’ top five perceived barriers included lack of skills, hating to sweat, difficulty finding programs, being tired, and having pain. Discussion Innovative interventions, particularly focusing on skill development, are needed to assist girls in overcoming their perceived barriers to PA. PMID:26325276

A cluster-randomised controlled trial to promote physical activity in adolescents: the Raising Awareness of Physical Activity (RAW-PA) Study.

PubMed

Ridgers, Nicola D; Timperio, Anna; Brown, Helen; Ball, Kylie; Macfarlane, Susie; Lai, Samuel K; Richards, Kara; Ngan, Winsfred; Salmon, Jo

2017-01-04

Recent technological advances provide an alternative yet underutilised opportunity for promoting physical activity in youth. The primary aim of the Raising Awareness of Physical Activity (RAW-PA) Study is to examine the short- and longer-term impact of a wearable activity monitor combined with digital behaviour change resources on adolescents' daily physical activity levels. RAW-PA is a 12 week, multicomponent physical activity intervention that utilises a popular activity tracker (Fitbit® Flex) and supporting digital materials that will be delivered online via social media. The resources target key behaviour change techniques. The intervention structure and components have been informed by participatory research principles. RAW-PA will be evaluated using a cluster randomised controlled trial design with schools as the unit of randomisation. Twelve schools located in Melbourne, Australia, will allocated to either the intervention or wait-list control group. The target sample size is 300 Year 8 adolescents (aged 13-14 years). Participants' moderate- to vigorous-intensity physical activity will be the primary outcome. Survey measures will be completed. Process factors (e.g. feasibility, acceptability/appeal, fidelity) will also be collected. To our knowledge, this study will provide some of the first evidence concerning the effect of wearable activity trackers and digital behaviour change resources on adolescents' physical activity levels. This study will provide insights into the use of such technologies for physical activity promotion, which may have a significant impact on health education, promotion, practice and policy. Australian and New Zealand Clinical Trials Registry No: ACTRN12616000899448 . Date of registration: July 7, 2016.

Genome-Wide Association Study for Circulating Tissue Plasminogen Activator (tPA) Levels and Functional Follow-up Implicates Endothelial STXBP5 and STX2

PubMed Central

Huang, Jie; Huffman, Jennifer E.; Yamkauchi, Munekazu; Trompet, Stella; Asselbergs, Folkert W.; Sabater-Lleal, Maria; Trégouët, David-Alexandre; Chen, Wei-Min; Smith, Nicholas L.; Kleber, Marcus E.; Shin, So-Youn; Becker, Diane M.; Tang, Weihong; Dehghan, Abbas; Johnson, Andrew D.; Truong, Vinh; Folkersen, Lasse; Yang, Qiong; Oudot-Mellakh, Tiphaine; Buckley, Brendan M.; Moore, Jason H.; Williams, Frances M.K.; Campbell, Harry; Silbernagel, Günther; Vitart, Veronique; Rudan, Igor; Tofler, Geoffrey H.; Navis, Gerjan J.; DeStefano, Anita; Wright, Alan F.; Chen, Ming-Huei; de Craen, Anton J.M.; Worrall, Bradford B.; Rudnicka, Alicja R.; Rumley, Ann; Bookman, Ebony B.; Psaty, Bruce M.; Chen, Fang; Keene, Keith L.; Franco, Oscar H.; Böhm, Bernhard O.; Uitterlinden, Andre G.; Carter, Angela M.; Jukema, J. Wouter; Sattar, Naveed; Bis, Joshua C.; Ikram, Mohammad A.; Sale, Michèle M.; McKnight, Barbara; Fornage, Myriam; Ford, Ian; Taylor, Kent; Slagboom, P. Eline; McArdle, Wendy L.; Hsu, Fang-Chi; Franco-Cereceda, Anders; Goodall, Alison H.; Yanek, Lisa R.; Furie, Karen L.; Cushman, Mary; Hofman, Albert; Witteman, Jacqueline CM.; Folsom, Aaron R.; Basu, Saonli; Matijevic, Nena; van Gilst, Wiek H.; Wilson, James F.; Westendorp, Rudi G.J.; Kathiresan, Sekar; Reilly, Muredach P.; Tracy, Russell P.; Polasek, Ozren; Winkelmann, Bernhard R.; Grant, Peter J.; Hillege, Hans L.; Cambien, Francois; Stott, David J.; Lowe, Gordon D.; Spector, Timothy D.; Meigs, James B.; Marz, Winfried; Eriksson, Per; Becker, Lewis C.; Morange, Pierre-Emmanuel; Soranzo, Nicole; Williams, Scott M.; Hayward, Caroline; van der Harst, Pim; Hamsten, Anders; Lowenstein, Charles J.; Strachan, David P.; O'Donnell, Christopher J.

2014-01-01

Objective Tissue plasminogen activator (tPA), a serine protease, catalyzes the conversion of plasminogen to plasmin, the major enzyme responsible for endogenous fibrinolysis. In some populations, elevated plasma levels of tPA have been associated with myocardial infarction and other cardiovascular diseases (CVD). We conducted a meta-analysis of genome-wide association studies (GWAS) to identify novel correlates of circulating levels of tPA. Approach and Results Fourteen cohort studies with tPA measures (N=26,929) contributed to the meta-analysis. Three loci were significantly associated with circulating tPA levels (P <5.0×10−8). The first locus is on 6q24.3, with the lead SNP (rs9399599, P=2.9×10−14) within STXBP5. The second locus is on 8p11.21. The lead SNP (rs3136739, P=1.3×10−9) is intronic to POLB and less than 200kb away from the tPA encoding gene PLAT. We identified a non-synonymous SNP (rs2020921) in modest LD with rs3136739 (r2 = 0.50) within exon 5 of PLAT (P=2.0×10−8). The third locus is on 12q24.33, with the lead SNP (rs7301826, P=1.0×10−9) within intron 7 of STX2. We further found evidence for association of lead SNPs in STXBP5 and STX2 with expression levels of the respective transcripts. In in vitro cell studies, silencing STXBP5 decreased release of tPA from vascular endothelial cells, while silencing of STX2 increased tPA release. Through an in-silico lookup, we found no associations of the three lead SNPs with coronary artery disease or stroke. Conclusions We identified three loci associated with circulating tPA levels, the PLAT region, STXBP5 and STX2. Our functional studies implicate a novel role for STXBP5 and STX2 in regulating tPA release. PMID:24578379

US geographic distribution of rt-PA utilization by hospital for acute ischemic stroke.

PubMed

Kleindorfer, Dawn; Xu, Yingying; Moomaw, Charles J; Khatri, Pooja; Adeoye, Opeolu; Hornung, Richard

2009-11-01

Previously, we have estimated US national rates of recombinant tissue plasminogen activator (rt-PA) use to be 1.8% to 3.0% of all ischemic stroke patients. However, we hypothesized that the rate of rt-PA use may vary widely depending on regional variation, and that a large percentage of the US population likely does not have access to hospitals using rt-PA regularly. We describe the US geographic distribution of hospitals using rt-PA for acute ischemic stroke. This analysis used the MEDPAR database, which is a claims-based dataset that contains every fee-for-service Medicare-eligible hospital discharge in the US. Cases potentially eligible for rt-PA treatment based on diagnosis were defined as those with a hospital DRG code of 14, 15, or 559, and that also had an ICD-9 code of 433, 434, or 436. Thrombolysis use was defined as an ICD-9 code of 99.1. Study interval was July 1, 2005 to June 30, 2007. Hospital locations were mapped using ArcView software; population densities and regions of the US are based on US Census 2000. There were 4750 hospitals in the MEDPAR database, which included 495 186 ischemic stroke admissions during the study period. Of these hospitals, 64% had no reported treatments with rt-PA for ischemic stroke, and 0.9% reported >10% treatment rates within the MEDPAR dataset. Bed size, rural or underserved designation, and population density were significantly associated with reported rt-PA treatment rates, and remained significant in the multivariable regression. Approximately 162 million US citizens reside in counties containing a hospital reporting a >or=2.4% treatment rate within the MEDPAR dataset. We report the first description of US hospital rt-PA treatment rates by hospital. Unfortunately, we found that 64% of US hospitals did not report giving rt-PA at all within the MEDPAR database within a 2-year period. These tended to be hospitals that were smaller (average bed size of 95), located in less densely populated areas, or located in the

Contribution of the Nitroimidazoles PA-824 and TBA-354 to the Activity of Novel Regimens in Murine Models of Tuberculosis

PubMed Central

Tasneen, Rokeya; Williams, Kathy; Amoabeng, Opokua; Minkowski, Austin; Mdluli, Khisimuzi E.; Upton, Anna M.

2014-01-01

New regimens based on two or more novel agents are sought in order to shorten or simplify the treatment of both drug-susceptible and drug-resistant forms of tuberculosis. PA-824 is a nitroimidazo-oxazine now in phase II trials and has shown significant early bactericidal activity alone and in combination with the newly approved agent bedaquiline or with pyrazinamide with or without moxifloxacin. While the development of PA-824 continues, a potential next-generation derivative, TBA-354, has been discovered to have in vitro potency superior to that of PA-824 and greater metabolic stability than that of the other nitroimidazole derivative in clinical development, delamanid. In the present study, we compared the activities of PA-824 and TBA-354 as monotherapies in murine models of the initial intensive and continuation phases of treatment, as well as in combination with bedaquiline plus pyrazinamide, sutezolid, and/or clofazimine. The monotherapy studies demonstrated that TBA-354 is 5 to 10 times more potent than PA-824, but selected mutants are cross-resistant to PA-824 and delamanid. The combination studies revealed that TBA-354 is 2 to 4 times more potent than PA-824 when combined with bedaquiline, and when administered at a dose equivalent to that of PA-824, TBA-354 demonstrated superior sterilizing efficacy. Perhaps most importantly, the addition of either nitroimidazole significantly improved the sterilizing activities of bedaquiline and sutezolid, with or without pyrazinamide, confirming the value of each agent in this potentially universally active short-course regimen. PMID:25331697

Contribution of the nitroimidazoles PA-824 and TBA-354 to the activity of novel regimens in murine models of tuberculosis.

PubMed

Tasneen, Rokeya; Williams, Kathy; Amoabeng, Opokua; Minkowski, Austin; Mdluli, Khisimuzi E; Upton, Anna M; Nuermberger, Eric L

2015-01-01

New regimens based on two or more novel agents are sought in order to shorten or simplify the treatment of both drug-susceptible and drug-resistant forms of tuberculosis. PA-824 is a nitroimidazo-oxazine now in phase II trials and has shown significant early bactericidal activity alone and in combination with the newly approved agent bedaquiline or with pyrazinamide with or without moxifloxacin. While the development of PA-824 continues, a potential next-generation derivative, TBA-354, has been discovered to have in vitro potency superior to that of PA-824 and greater metabolic stability than that of the other nitroimidazole derivative in clinical development, delamanid. In the present study, we compared the activities of PA-824 and TBA-354 as monotherapies in murine models of the initial intensive and continuation phases of treatment, as well as in combination with bedaquiline plus pyrazinamide, sutezolid, and/or clofazimine. The monotherapy studies demonstrated that TBA-354 is 5 to 10 times more potent than PA-824, but selected mutants are cross-resistant to PA-824 and delamanid. The combination studies revealed that TBA-354 is 2 to 4 times more potent than PA-824 when combined with bedaquiline, and when administered at a dose equivalent to that of PA-824, TBA-354 demonstrated superior sterilizing efficacy. Perhaps most importantly, the addition of either nitroimidazole significantly improved the sterilizing activities of bedaquiline and sutezolid, with or without pyrazinamide, confirming the value of each agent in this potentially universally active short-course regimen. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Schoolyard physical activity in 14-year-old adolescents assessed by mobile GPS and heart rate monitoring analysed by GIS.

PubMed

Fjørtoft, Ingunn; Löfman, Owe; Halvorsen Thorén, Kine

2010-11-01

Environmental settings seem to influence the activity patterns of children in neighbourhoods and schoolyards, the latter being an important arena to promote physical activity (PA) in school children. New technology has made it possible to describe free-living PA in interaction with the environment. This study focused on how schoolyard environments influenced the activity patterns and intensity levels in 14-year-old children and whether PA levels in adolescents complied with official recommendations. Another objective was to introduce methodology of using a mobile global positioning system (GPS) device with synchronous heart rate (HR) recordings as a proxy for PA level and a geographical information system (GIS) for spatial analyses. The sample constituted of 81 children (aged 14 years) from two schools. Movement patterns and activity levels were recorded during lunch break applying a GPS Garmin Forerunner 305 with combined HR monitoring and analysed in a GIS by an overlaid grid and kriging interpolation. Spatial data from GPS recordings showed particular movement patterns in the schoolyards. Low activity levels (mean HR < 120 bpm) dominated in both schools with no gender differences. Activities located to a handball goal area showed the highest monitored HR (>160 bpm) with higher intensity in girls than in boys. Movement patterns and PA generated in GIS for visualisation and analysis enabled direct and realistic description of utilising of schoolyard facilities and activity levels. Linking GPS data and PA levels to spatial structures made it possible to visualise the environmental interaction with PA and which environments promoted low or high PA.

Pilot surveillance for childhood encephalitis in Australia using the Paediatric Active Enhanced Disease Surveillance (PAEDS) network.

PubMed

Britton, P N; Dale, R C; Elliott, E; Festa, M; Macartney, K; Booy, R; Jones, C A

2016-07-01

We aimed to assess the performance of active surveillance for hospitalized childhood encephalitis in New South Wales (NSW) using the Paediatric Active Enhanced Disease Surveillance (PAEDS) network to inform methodology for the nationwide Australian childhood encephalitis (ACE) study. We piloted active surveillance for suspected encephalitis from May to December 2013 at the Children's Hospital at Westmead, Sydney, NSW. Cases were ascertained using four screening methods: weekday nurse screening of admission records (PAEDS), cerebrospinal fluid (CSF) microscopy records, magnetic resonance imaging (MRI) reports, and pharmacy dispensing records. Comprehensive clinical data were prospectively collected on consented participants and subsequently reviewed by an expert panel. Cases were categorized as confirmed encephalitis or 'not encephalitis'; encephalitis cases were sub-categorized as infectious, immune-mediated or unknown. We performed an ICD-10 diagnostic code audit of hospitalizations for the pilot period. We compared case ascertainment in the four screening methods and with the ICD code audit. Forty-eight cases of suspected encephalitis were identified by one or more methods. PAEDS was the most efficient mechanism (yield 34%), followed by MRI, CSF, and pharmacy audits (yield 14%, 12%, and 7% respectively). Twenty-five cases met the criteria for confirmed encephalitis. PAEDS was the most sensitive of the mechanisms for confirmed encephalitis (92%) with a positive predictive value (PPV) of 72%. The ICD audit was moderately sensitive (64%) but poorly specific (Sp 9%, PPV 14%). Of the 25 confirmed encephalitis cases, 19 (76%) were sub-categorized as infectious, three (12%) were immune-mediated, and three (12%) were 'unknown'. We identified encephalitis cases associated with two infectious disease outbreaks (enterovirus 71, parechovirus 3). PAEDS is an efficient, sensitive and accurate surveillance mechanism for detecting cases of childhood encephalitis including those

Measurement of absorption rates of HFC single and blended refrigerants in POE oils

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

Leung, M.; Jotshi, C.K.; Goswami, D.Y.

1999-07-01

Thermophysical properties of refrigerant/lubricant mixtures play an important role in refrigeration and air-conditioning system design. Therefore it is important to have a good understanding of the mixture composition in each system component such as the compressor or evaporator. Because the system operation is dynamic the rates of absorption and desorption become significant parameters. In this paper measured absorption rates of alternative refrigerants in polyolester (POE) oils are reported. An effective online mass gain method was designed and constructed to measure the absorption rates and solubility of refrigerants in lubricants. HFC single refrigerants (R-32, R-125, R-134a, and R-143a), and blended refrigerantsmore » (R-404A, R-407C, and R-410A) were tested with POE ISO 68 lubricant under various conditions. The experimental results showed that, at room temperature, R-134a is the most soluble in POE ISO 68 oil among all the refrigerants tested at pressures of 239 kPa (20 psig) to 446 kPa (70 psig). Among the blended refrigerants tested, R-407C was found to be the most soluble at room temperature and pressures of 239 kPa and 446 kPa. Experimental solubility data from this new measurement method were compared with data available in the literature. Good agreement between the two indicates the feasibility of the new method employed in this investigation.« less

Single Cell Analysis Linking Ribosomal (r)DNA and rRNA Copy Numbers to Cell Size and Growth Rate Provides Insights into Molecular Protistan Ecology.

PubMed

Fu, Rao; Gong, Jun

2017-11-01

Ribosomal (r)RNA and rDNA have been golden molecular markers in microbial ecology. However, it remains poorly understood how ribotype copy number (CN)-based characteristics are linked with diversity, abundance, and activity of protist populations and communities observed at organismal levels. Here, we applied a single-cell approach to quantify ribotype CNs in two ciliate species reared at different temperatures. We found that in actively growing cells, the per-cell rDNA and rRNA CNs scaled with cell volume (CV) to 0.44 and 0.58 powers, respectively. The modeled rDNA and rRNA concentrations thus appear to be much higher in smaller than in larger cells. The observed rRNA:rDNA ratio scaled with CV 0.14 . The maximum growth rate could be well predicted by a combination of per-cell ribotype CN and temperature. Our empirical data and modeling on single-cell ribotype scaling are in agreement with both the metabolic theory of ecology and the growth rate hypothesis, providing a quantitative framework for linking cellular rDNA and rRNA CNs with body size, growth (activity), and biomass stoichiometry. This study also demonstrates that the expression rate of rRNA genes is constrained by cell size, and favors biomass rather than abundance-based interpretation of quantitative ribotype data in population and community ecology of protists. © 2017 The Authors. Journal of Eukaryotic Microbiology published by Wiley Periodicals, Inc. on behalf of International Society of Protistologists.

An anthrax toxin variant with an improved activity in tumor targeting

PubMed Central

Wein, Alexander N.; Peters, Diane E.; Valivullah, Zaheer; Hoover, Benjamin J.; Tatineni, Aparna; Ma, Qian; Fattah, Rasem; Bugge, Thomas H.; Leppla, Stephen H.; Liu, Shihui

2015-01-01

Anthrax lethal toxin (LT) is an A-B type toxin secreted by Bacillus anthracis, consisting of the cellular binding moiety, protective antigen (PA), and the catalytic moiety, lethal factor (LF). To target cells, PA binds to cell-surface receptors and is then proteolytically processed forming a LF-binding competent PA oligomer where each LF binding site is comprised of three subsites on two adjacent PA monomers. We previously generated PA-U2-R200A, a urokinase-activated PA variant with LF-binding subsite II residue Arg200 mutated to Ala, and PA-L1-I210A, a matrix metalloproteinase-activated PA variant with subsite III residue Ile210 mutated to Ala. PA-U2-R200A and PA-L1-I210A displayed reduced cytotoxicity when used singly. However, when combined, they formed LF-binding competent heterogeneous oligomers by intermolecular complementation, and achieved high specificity in tumor targeting. Nevertheless, each of these proteins, in particular PA-L1-I210A, retained residual LF-binding ability. In this work, we screened a library containing all possible amino acid substitutions for LF-binding site to find variants with activity strictly dependent upon intermolecular complementation. PA-I207R was identified as an excellent replacement for the original clockwise-side variant, PA-I210A. Consequently, the new combination of PA-L1-I207R and PA-U2-R200A showed potent anti-tumor activity and low toxicity, exceeding the performance of the original combination, and warranting further investigation. PMID:26584669

32 CFR 701.120 - Processing requests that cite or imply PA, Freedom of Information (FOIA), or PA/FOIA.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Privacy Program § 701.120 Processing requests that cite or imply PA, Freedom of Information (FOIA), or PA... maximum release of information allowed under the Acts. (d) Processing time limits. DON activities shall... 32 National Defense 5 2010-07-01 2010-07-01 false Processing requests that cite or imply PA...

PaR Tensile Truss for Nuclear Decontamination and Decommissioning - 12467

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

Doebler, Gary R.

2012-07-01

Remote robotics and manipulators are commonly used in nuclear decontamination and decommissioning (D and D) processes. D and D robots are often deployed using rigid telescoping masts in order to apply and counteract side loads. However, for very long vertical reaches (15 meters or longer) and high lift capacities, a telescopic is usually not practical due to the large cross section and weight required to make the mast stiff and resist seismic forces. For those long vertical travel applications, PaR Systems has recently developed the Tensile Truss, a rigid, hoist-driven 'structure' that employs six independent wire rope hoists to achievemore » long vertical reaches. Like a mast, the Tensile Truss is typically attached to a bridge-mounted trolley and is used as a platform for robotic manipulators and other remotely operated tools. For suspended, rigid deployment of D and D tools with very long vertical reaches, the Tensile Truss can be a better alternative than a telescoping mast. Masts have length limitations that can make them impractical or unworkable as lengths increase. The Tensile Truss also has the added benefits of increased safety, ease of decontamination, superior stiffness and ability to withstand excessive side loading. A Tensile Truss system is currently being considered for D and D operations and spent fuel recovery at the Fukushima Daiichi Nuclear Power Plant in Japan. This system will deploy interchangeable tools such as underwater hydraulic manipulators, hydraulic shears and crushers, grippers and fuel grapples. (authors)« less

[Assessment of radiation exposure level for hydrobionts in some special industrial ponds at the "Mayak" PA].

PubMed

Triapitsyna, G A; Andreev, S S; Osipov, D I; Stukalov, P M; Ivanov, I A; Aleksandrova, O N; Kostiuchenko, A V; Priakhin, E A; Akleev, A V

2012-01-01

Evaluation of the radionuclide content in the ecosystem components (water, sediments, aquatic organisms) of industrial reservoirs-storages of liquid radioactive waste of the "Mayak" PA (reservoirs R-4, R-10, R-11, R-17, R-9) and the estimation of the absorbed dose rate in aquatic organisms of these reservoirs using the software package ERICA Assessment Tool 1.0 May 2009 have been performed. Gradient of the absorbed dose rate for the detected taxonomic groups of hydrobionts in the series of the studied reservoirs R-11 --> R-10 --> R-4 --> R-17 --> R-9 was almost equal to one order of magnitude. The estimated absorbed dose rate for phytoplankton ranged from 5.4 x 10(0) mGy/day (R-11) to 4.0 x 10(4) mGy/day (R-9), for zooplankton--from 6.4 x 10(-1) mGy/day (R-11) to 3.8 x 10(3) mGy/day (R-9), for zoobenthos (chironomids)--from 5.6 x 10(0) mGy/day (R-11) to 1.1 x 10(3) mGy/day (R-17), for fish (roach)--from 8.0 x 10(-1) mGy/day (R-11) to 1.9 x 10(1) mGy/day (R-4).

Physical activity, mindfulness meditation, or heart rate variability biofeedback for stress reduction: a randomized controlled trial.

PubMed

van der Zwan, Judith Esi; de Vente, Wieke; Huizink, Anja C; Bögels, Susan M; de Bruin, Esther I

2015-12-01

In contemporary western societies stress is highly prevalent, therefore the need for stress-reducing methods is great. This randomized controlled trial compared the efficacy of self-help physical activity (PA), mindfulness meditation (MM), and heart rate variability biofeedback (HRV-BF) in reducing stress and its related symptoms. We randomly allocated 126 participants to PA, MM, or HRV-BF upon enrollment, of whom 76 agreed to participate. The interventions consisted of psycho-education and an introduction to the specific intervention techniques and 5 weeks of daily exercises at home. The PA exercises consisted of a vigorous-intensity activity of free choice. The MM exercises consisted of guided mindfulness meditation. The HRV-BF exercises consisted of slow breathing with a heart rate variability biofeedback device. Participants received daily reminders for their exercises and were contacted weekly to monitor their progress. They completed questionnaires prior to, directly after, and 6 weeks after the intervention. Results indicated an overall beneficial effect consisting of reduced stress, anxiety and depressive symptoms, and improved psychological well-being and sleep quality. No significant between-intervention effect was found, suggesting that PA, MM, and HRV-BF are equally effective in reducing stress and its related symptoms. These self-help interventions provide easily accessible help for people with stress complaints.

Accumulation rates of Th-230, Pa-231, and some transition metals on the Bermuda Rise

USGS Publications Warehouse

Bacon, M.P.; Rosholt, J.N.

1982-01-01

Measurements of 238U, 234U, 230Th, 232Th, 231Pa, Mn, Fe, Co, Ni, Cu, and Zn were made on 23 samples from core GPC-5, a 29-m giant piston core from a water depth of 4583 m on the northeastern Bermuda Rise (33??41.2???N, 57??36.9???W). This area is characterized by rapid deposition of sediment transported by abyssal currents. Unsupported 230Th and 231Pa are present throughout the core but, because of large variations in the sedimentation rate, show marked departures from exponential decay with depth. The trend with depth of the 231Paex 230Thex ratio is consistent with the average accumulation rate of 36 cm/1000 y reported earlier on the basis of radiocarbon dating and CaCO3 stratigraphy. When expressed on a carbonate-free basis, concentrations of Mn, Co, Ni, Cu, Zn, 230Thex, and 231Paex all show cyclic variations positively correlated with those of CaCO3. The correlations can be explained by a model in which all of these constituents, including CaCO3, are supplied to the sediments from the water column at a constant rate. Concentration variations are controlled mainly by varying inputs of terrigenous detritus, with low inputs occurring during interglacials and high inputs during glacials. Relationships between the metal and 230Thex concentrations permit estimates of the rates at which the metals are removed to the sediment by scavenging from the water column. The results, in ??g/cm2-1000 y, are: 4300 ?? 1100 for Mn, 46 ?? 16 for Ni and 76 ?? 26 for Cu. These rates are somewhat larger than ocean-wide averages estimated by other methods, and the absolute rate of 230Th accumulation in GPC-5 averages about nine times higher than production in the overlying water column. This part of the Bermuda Rise and similar bottom-current deposits may act as important accumulators of elements scavenged from seawater. ?? 1982.

Serum creatinine may indicate risk of symptomatic intracranial hemorrhage after intravenous tissue plasminogen activator (IV tPA).

PubMed

Marsh, Elisabeth B; Gottesman, Rebecca F; Hillis, Argye E; Urrutia, Victor C; Llinas, Rafael H

2013-11-01

Symptomatic intracranial hemorrhage (sICH) is a known complication following administration of intravenous tissue plasminogen activator (IV tPA) for acute ischemic stroke. sICH results in high rates of death or long-term disability. Our ability to predict its occurrence is important in clinical decision making and when counseling families. The initial National Institute of Neurological Disorders and Stroke (NINDS) investigators developed a list of relative contraindications to IV tPA meant to decrease the risk of subsequent sICH. To date, the impact of renal impairment has not been well studied. In the current study we evaluate the potential association between renal impairment and post-tPA intracranial hemorrhage (ICH). Admission serum creatinine and estimated glomerular filtration rate (eGFR) were recorded in 224 patients presenting within 4.5 hours from symptom onset and treated with IV tPA based on NINDS criteria. Neuroimaging was obtained 1 day post-tPA and for any change in neurologic status to evaluate for ICH. Images were retrospectively evaluated for hemorrhage by a board-certified neuroradiologist and 2 reviewers blinded to the patient's neurologic status. Medical records were reviewed retrospectively for evidence of neurologic decline indicating a "symptomatic" hemorrhage. sICH was defined as subjective clinical deterioration (documented by the primary neurology team) and hemorrhage on neuroimaging that was felt to be the most likely cause. Renal impairment was evaluated using both serum creatinine and eGFR in a number of ways: 1) continuous creatinine; 2) any renal impairment by creatinine (serum creatinine >1.0 mg/dL); 3) continuous eGFR; and 4) any renal impairment by eGFR (eGFR <60 mL/min per 1.73 m²). Student paired t tests, Fisher exact tests, and multivariable logistic regression (adjusted for demographics and vascular risk factors) were used to evaluate the relationship between renal impairment and ICH. Fifty-seven (25%) of the 224 patients had

Serum Creatinine May Indicate Risk of Symptomatic Intracranial Hemorrhage After Intravenous Tissue Plasminogen Activator (IV tPA)

PubMed Central

Marsh, Elisabeth B.; Gottesman, Rebecca F.; Hillis, Argye E.; Urrutia, Victor C.

2013-01-01

Abstract Symptomatic intracranial hemorrhage (sICH) is a known complication following administration of intravenous tissue plasminogen activator (IV tPA) for acute ischemic stroke. sICH results in high rates of death or long-term disability. Our ability to predict its occurrence is important in clinical decision making and when counseling families. The initial National Institute of Neurological Disorders and Stroke (NINDS) investigators developed a list of relative contraindications to IV tPA meant to decrease the risk of subsequent sICH. To date, the impact of renal impairment has not been well studied. In the current study we evaluate the potential association between renal impairment and post-tPA intracranial hemorrhage (ICH). Admission serum creatinine and estimated glomerular filtration rate (eGFR) were recorded in 224 patients presenting within 4.5 hours from symptom onset and treated with IV tPA based on NINDS criteria. Neuroimaging was obtained 1 day post-tPA and for any change in neurologic status to evaluate for ICH. Images were retrospectively evaluated for hemorrhage by a board-certified neuroradiologist and 2 reviewers blinded to the patient’s neurologic status. Medical records were reviewed retrospectively for evidence of neurologic decline indicating a “symptomatic” hemorrhage. sICH was defined as subjective clinical deterioration (documented by the primary neurology team) and hemorrhage on neuroimaging that was felt to be the most likely cause. Renal impairment was evaluated using both serum creatinine and eGFR in a number of ways: 1) continuous creatinine; 2) any renal impairment by creatinine (serum creatinine >1.0 mg/dL); 3) continuous eGFR; and 4) any renal impairment by eGFR (eGFR <60 mL/min per 1.73 m2). Student paired t tests, Fisher exact tests, and multivariable logistic regression (adjusted for demographics and vascular risk factors) were used to evaluate the relationship between renal impairment and ICH. Fifty-seven (25%) of the 224

Phosphatidic acid (PA) binds PP2AA1 to regulate PP2A activity and PIN1 polar localization.

PubMed

Gao, Hong-Bo; Chu, Yu-Jia; Xue, Hong-Wei

2013-09-01

Phospholipase D (PLD) exerts broad biological functions in eukaryotes through regulating downstream effectors by its product, phosphatidic acid (PA). Protein kinases and phosphatases, such as mammalian target of rapamycin (mTOR), Protein Phosphatase 1 (PP1) and Protein Phosphatase 2C (PP2C), are PA-binding proteins that execute crucial regulatory functions in both animals and plants. PA participates in many signaling pathways by modulating the enzymatic activity and/or subcellular localization of bound proteins. In this study, we demonstrated that PLD-derived PA interacts with the scaffolding A1 subunit of Protein Phosphatase 2A (PP2A) and regulates PP2A-mediated PIN1 dephosphorylation in Arabidopsis. Genetic and pharmacological studies showed that both PA and PP2A participate in the regulation of auxin distribution. In addition, both the phosphorylation status and polar localization of PIN1 protein were affected by PLD inhibitors. Exogenous PA triggered the membrane accumulation of PP2AA1 and enhanced the PP2A activity at membrane, while PLD inhibition resulted in the reduced endosomal localization and perinuclear aggregation of PP2AA1. These results demonstrate the important role of PLD-derived PA in normal PP2A-mediated PIN dephosphorylation and reveal a novel mechanism, in which PA recruits PP2AA1 to the membrane system and regulates PP2A function on membrane-targeted proteins. As PA and PP2A are conserved among eukaryotes, other organisms might use similar mechanisms to mediate multiple biological processes.

Validity of a short questionnaire to assess physical activity in 10 European countries.

PubMed

Peters, Tricia; Brage, Soren; Westgate, Kate; Franks, Paul W; Gradmark, Anna; Tormo Diaz, Maria Jose; Huerta, Jose Maria; Bendinelli, Benedetta; Vigl, Mattheaus; Boeing, Heiner; Wendel-Vos, Wanda; Spijkerman, Annemieke; Benjaminsen-Borch, Kristin; Valanou, Elisavet; de Lauzon Guillain, Blandine; Clavel-Chapelon, Françoise; Sharp, Stephen; Kerrison, Nicola; Langenberg, Claudia; Arriola, Larraitz; Barricarte, Aurelio; Gonzales, Carlos; Grioni, Sara; Kaaks, Rudolf; Key, Timothy; Khaw, Kay Tee; May, Anne; Nilsson, Peter; Norat, Teresa; Overvad, Kim; Palli, Domenico; Panico, Salvatore; Ramón Quirós, Jose; Ricceri, Fulvio; Sanchez, Maria-Jose; Slimani, Nadia; Tjonneland, Anne; Tumino, Rosario; Feskins, Edith; Riboli, Elio; Ekelund, Ulf; Wareham, Nick

2012-01-01

To accurately examine associations of physical activity (PA) with disease outcomes, a valid method of assessing free-living activity is required. We examined the validity of a brief PA questionnaire (PAQ) used in the European Prospective Investigation into Cancer and Nutrition (EPIC). PA energy expenditure (PAEE) and time spent in moderate and vigorous physical activity (MVPA) was measured in 1,941 healthy individuals from 10 European countries using individually-calibrated combined heart-rate and movement sensing. Participants also completed the short EPIC-PAQ, which refers to past year's activity. Pearson (r) and Spearman (σ) correlation coefficients were calculated for each country, and random effects meta-analysis was used to calculate the combined correlation across countries to estimate the validity of two previously- and one newly-derived ordered, categorical PA indices ("Cambridge index", "total PA index", and "recreational index") that categorized individuals as inactive, moderately inactive, moderately active, or active. The strongest associations with PAEE and MVPA were observed for the Cambridge index (r = 0.33 and r = 0.25, respectively). No significant heterogeneity by country was observed for this index (I(2) = 36.3%, P = 0.12; I(2) = 0.0%, P = 0.85), whereas heterogeneity was suggested for other indices (I(2) > 48%, P < 0.05, I(2) > 47%, P < 0.05). PAEE increased linearly across self-reported PA categories (P for trend <0.001), with an average difference of approximately 460 kJ/d for men and 365 kJ/d for women, between categories of the Cambridge index. The EPIC-PAQ is suitable for categorizing European men and women into four distinct categories of overall physical activity. The difference in PAEE between categories may be useful when estimating effect sizes from observational research.

Endovascular Therapy after Intravenous t-PA versus t-PA Alone for Stroke

PubMed Central

Broderick, Joseph P.; Palesch, Yuko Y.; Demchuk, Andrew M.; Yeatts, Sharon D.; Khatri, Pooja; Hill, Michael D.; Jauch, Edward C.; Jovin, Tudor G.; Yan, Bernard; Silver, Frank L.; von Kummer, Rüdiger; Molina, Carlos A.; Demaerschalk, Bart M.; Budzik, Ronald; Clark, Wayne M.; Zaidat, Osama O.; Malisch, Tim W.; Goyal, Mayank; Schonewille, Wouter J.; Mazighi, Mikael; Engelter, Stefan T.; Anderson, Craig; Spilker, Judith; Carrozzella, Janice; Ryckborst, Karla J.; Janis, L. Scott; Martin, Renée H.; Foster, Lydia D.; Tomsick, Thomas A.

2013-01-01

BACKGROUND Endovascular therapy is increasingly used after the administration of intravenous tissue plasminogen activator (t-PA) for patients with moderate-to-severe acute ischemic stroke, but whether a combined approach is more effective than intravenous t-PA alone is uncertain. METHODS We randomly assigned eligible patients who had received intravenous t-PA within 3 hours after symptom onset to receive additional endovascular therapy or intravenous t-PA alone, in a 2:1 ratio. The primary outcome measure was a modified Rankin scale score of 2 or less (indicating functional independence) at 90 days (scores range from 0 to 6, with higher scores indicating greater disability). RESULTS The study was stopped early because of futility after 656 participants had undergone randomization (434 patients to endovascular therapy and 222 to intravenous t-PA alone). The proportion of participants with a modified Rankin score of 2 or less at 90 days did not differ significantly according to treatment (40.8% with endovascular therapy and 38.7% with intravenous t-PA; absolute adjusted difference, 1.5 percentage points; 95% confidence interval [CI], −6.1 to 9.1, with adjustment for the National Institutes of Health Stroke Scale [NIHSS] score [8–19, indicating moderately severe stroke, or ≥20, indicating severe stroke]), nor were there significant differences for the predefined subgroups of patients with an NIHSS score of 20 or higher (6.8 percentage points; 95% CI, −4.4 to 18.1) and those with a score of 19 or lower (−1.0 percentage point; 95% CI, −10.8 to 8.8). Findings in the endovascular-therapy and intravenous t-PA groups were similar for mortality at 90 days (19.1% and 21.6%, respectively; P = 0.52) and the proportion of patients with symptomatic intracerebral hemorrhage within 30 hours after initiation of t-PA (6.2% and 5.9%, respectively; P = 0.83). CONCLUSIONS The trial showed similar safety outcomes and no significant difference in functional independence with

Co-morbid conditions in use of recombinant tissue plasminogen activator (rt-PA) for the treatment of acute ischaemic stroke.

PubMed

Nathaniel, Thomas I; Cochran, Thomas; Chaves, Jose; Fulmer, Eric; Sosa, Crystal; Yi, Sara; Fredwall, Megan; Sternberg, Shannon; Blackhurst, Dawn; Nelson, Alfred; Leacock, Rodney

2016-01-01

The objective of this study was to characterize the comorbidities in a population of patients with an acute ischaemic stroke, comparing patients that received recombinant tissue plasminogen activator (rt-PA) to those that did not receive rt-PA. In a retrospective sample of 663 patients admitted for acute ischaemic stroke, this study analysed the effects of co-morbid conditions in the use of rt-PA. It determined non-cerebrovascular risk factors (comorbidities) that differentiate patients who received rt-PA from those who did not receive rt-PA. Patients with a history of carotid stenosis, CHF and previous strokes are significantly (p < 0.05) associated with high risk of not receiving rt-PA. A significant number of patients with a history of hypertension and smoking received rt-PA (p < 0.05). The findings indicate that certain risk factors including carotid stenosis, CHF and previous stroke history impact the treatment of patients with acute ischaemic stroke, specifically the decision to administer rt-PA. Treatment with rt-PA is dependent on stroke severity and onset to treatment time, but the findings suggest that rt-PA use may also depend on patient comorbidities.

Are Active Australia physical activity questions valid for older adults?

PubMed

Heesch, Kristiann C; Hill, Robert L; van Uffelen, Jannique G Z; Brown, Wendy J

2011-05-01

The Active Australia Survey (AAS) is used for physical activity (PA) surveillance in the general Australian adult population, but its validity in older adults has not been evaluated. Our aim was to examine the convergent validity of the AAS questions in older adults. The AAS was validated against pedometer step counts as an objective measure of PA, self-reported physical function, and a step-test to assess cardiorespiratory fitness. Participants were community-dwelling adults, aged 65-89 y, with the ability to walk 100 m. They completed a self-administered AAS and the step-test in one interview. One week earlier, they completed the Short Form-36 physical function subscale. Between these two interviews, they each wore a YAMAX Digiwalker SW200 pedometer and recorded daily steps. Using the AAS data, daily walking minutes and total PA minutes (walking, moderate-intensity PA and vigorous-intensity PA) were compared with the validity measures using Spearman rank-order correlations. Fifty-three adults completed the study. Median daily walking minutes were 34.2 (interquartile range [IQR] 17.1, 60.0), and median daily total PA minutes were 68.6 (IQR 31.4, 113.6). Walking and total PA minutes were both moderately correlated with pedometer steps (Spearman correlation r=0.42, p=0.003, for each) but not with step-test seconds to completion (r=-0.11, p=0.44; r=-0.25, p=0.08, respectively). Total PA minutes were significantly correlated with physical function scores (r=0.39, p=0.004), but walking minutes were not (r=0.15, p=0.29). This initial examination of the psychometric properties of the AAS for older adults suggests that this surveillance tool has acceptable convergent validity for ambulatory, community-dwelling older adults. Copyright © 2010 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

High-level expression of a novel recombinant human plasminogen activator (rhPA) in the milk of transgenic rabbits and its thrombolytic bioactivity in vitro.

PubMed

Song, Shaozheng; Ge, Xin; Cheng, Yaobin; Lu, Rui; Zhang, Ting; Yu, Baoli; Ji, Xueqiao; Qi, Zhengqiang; Rong, Yao; Yuan, Yuguo; Cheng, Yong

2016-08-01

The human tissue-type plasminogen activator (tPA) is a key kinase of fibrinolysis that plays an important role in dissolving fibrin clots to promote thrombolysis. The recombinant human plasminogen activator (rhPA) has more thrombolytic advantages than the wild type tPA. To increase the half-life and thrombolytic activity of tPA, a mutant containing only the essential K2 fibrin-binding and P activating plasminogen domains of the wild type tPA was cloned. This fragment was then inserted into goat β-casein regulatory sequences. Then, a mammary gland-specific expression vector, PCL25/rhPA, was constructed, and the transgenic rabbits were generated. In this study, 18 live transgenic founders (12♀, 6♂) were generated using pronuclear microinjection. Six transgenic rabbits were obtained, and the expression levels of rhPA in the milk had a range of 15.2-630 µg/ml. A fibrin agarose plate assay of rhPA showed that it had strong thrombolytic bioactivity in vitro, and the highest specific activity was >360 (360 times more than that of alteplase). The results indicated that the rhPA containing only the K2 and P domains is efficiently expressed with higher thrombolytic bioactivity in the milk of transgenic rabbits. Our study also demonstrated a new method for the large-scale production of clinically relevant recombinant pharmaceutical proteins in the mammary glands of transgenic rabbits.

Comparison of physical activity sensors and heart rate monitoring for real-time activity detection in type 1 diabetes and control subjects.

PubMed

Manohar, Chinmay; O'Keeffe, Derek T; Hinshaw, Ling; Lingineni, Ravi; McCrady-Spitzer, Shelly K; Levine, James A; Carter, Rickey E; Basu, Ananda; Kudva, Yogish C

2013-09-01

Currently, patients with type 1 diabetes decide on the amount of insulin to administer based on several factors, including current plasma glucose value, expected meal input, and physical activity (PA). One future therapeutic modality for patients with type 1 diabetes is the artificial endocrine pancreas (AEP). Incorporation of PA could enhance the efficacy of AEP significantly. We compared the main technologies used for PA quantitation. Data were collected during inpatient studies involving healthy control subjects and type 1 diabetes. We report PA quantified from accelerometers (acceleration units [AU]) and heart rate (HR) monitors during a standardized activity protocol performed after a dinner meal at 7 p.m. from nine control subjects (four were males, 37.4±12.7 years old, body mass index of 24.8±3.8 kg/m(2), and fasting plasma glucose of 4.71±0.63 mmol/L) and eight with type 1 diabetes (six were males, 45.2±13.4 years old, body mass index of 25.1±2.9 kg/m(2), and fasting plasma glucose of 8.44±2.31 mmol/L). The patient-to-patient variability was considerably less when examining AU compared with HR monitors. Furthermore, the exercise bouts and rest periods were more evident from the data streams when AUs were used to quantify activity. Unlike the AU, the HR measurements provided little insight for active and rest stages, and HR data required patient-specific standardizations to discern any meaningful pattern in the data. Our results indicated that AU provides a reliable signal in response to PA, including low-intensity activity. Correlation of this signal with continuous glucose monitoring data would be the next step before exploring inclusion as input for AEP control.

Serine Hydroxymethyltransferase ShrA (PA2444) Controls Rugose Small-Colony Variant Formation in Pseudomonas aeruginosa

PubMed Central

Pu, Mingming; Sheng, Lili; Song, Sooyeon; Gong, Ting; Wood, Thomas K.

2018-01-01

Pseudomonas aeruginosa causes many biofilm infections, and the rugose small-colony variants (RSCVs) of this bacterium are important for infection. We found here that inactivation of PA2444, which we determined to be a serine hydroxymethyltransferase (SHMT), leads to the RSCV phenotype of P. aeruginosa PA14. In addition, loss of PA2444 increases biofilm formation by two orders of magnitude, increases exopolysaccharide by 45-fold, and abolishes swarming. The RSCV phenotype is related to higher cyclic diguanylate concentrations due to increased activity of the Wsp chemosensory system, including diguanylate cyclase WspR. By characterizing the PA2444 enzyme in vitro, we determined the physiological function of PA2444 protein by relating it to S-adenosylmethionine (SAM) concentrations and methylation of a membrane bound methyl-accepting chemotaxis protein WspA. A whole transcriptome analysis also revealed PA2444 is related to the redox state of the cells, and the altered redox state was demonstrated by an increase in the intracellular NADH/NAD+ ratio. Hence, we provide a mechanism for how an enzyme of central metabolism controls the community behavior of the bacterium, and suggest the PA2444 protein should be named ShrA for serine hydroxymethyltransferase related to rugose colony formation. PMID:29535691

The role of physical activity and heart rate variability for the control of work related stress.

PubMed

Tonello, Laís; Rodrigues, Fábio B; Souza, Jeniffer W S; Campbell, Carmen S G; Leicht, Anthony S; Boullosa, Daniel A

2014-01-01

Physical activity (PA) and exercise are often used as tools to reduce stress and therefore the risk for developing cardiovascular diseases (CVD). Meanwhile, heart rate variability (HRV) has been utilized to assess both stress and PA or exercise influences. The objective of the present review was to examine the current literature in regards to workplace stress, PA/exercise and HRV to encourage further studies. We considered original articles from known databases (PubMed, ISI Web of Knowledge) over the last 10 years that examined these important factors. A total of seven studies were identified with workplace stress strongly associated with reduced HRV in workers. Longitudinal workplace PA interventions may provide a means to improve worker stress levels and potentially cardiovascular risk with mechanisms still to be clarified. Future studies are recommended to identify the impact of PA, exercise, and fitness on stress levels and HRV in workers and their subsequent influence on cardiovascular health.

Validity of physical activity and cardiorespiratory fitness in the Danish cohort "Diet, Cancer and Health-Next Generations".

PubMed

Lerche, L; Olsen, A; Petersen, K E N; Rostgaard-Hansen, A L; Dragsted, L O; Nordsborg, N B; Tjønneland, A; Halkjaer, J

2017-12-01

Valid assessments of physical activity (PA) and cardiorespiratory fitness (CRF) are essential in epidemiological studies to define dose-response relationship for formulating thorough recommendations of an appropriate pattern of PA to maintain good health. The aim of this study was to validate the Danish step test, the physical activity questionnaire Active-Q, and self-rated fitness against directly measured maximal oxygen uptake (VO 2 max). A population-based subsample (n=125) was included from the "Diet, Cancer and Health-Next Generations" (DCH-NG) cohort which is under establishment. Validity coefficients, which express the correlation between measured and "true" exposure, were calculated, and misclassification across categories was evaluated. The validity of the Danish step test was moderate (women: r=.66, and men: r=.56); however, men were systematically underestimated (43% misclassification). When validating the questionnaire-derived measures of PA, leisure-time physical activity was not correlated with VO 2 max. Positive correlations were found for sports overall, but these were only significant for men: total hours per week of sports (r=.26), MET-hours per week of sports (r=.28) and vigorous sports (0.28) alone were positively correlated with VO 2 max. Finally, the percentage of misclassification was low for self-rated fitness (women: 9% and men: 13%). Thus, self-rated fitness was found to be a superior method to the Danish step test, as well as being less cost prohibitive and more practical than the VO 2 max method. Finally, even if correlations were low, they support the potential for questionnaire outcomes, particularly sports, vigorous sports, and self-rated fitness to be used to estimate CRF. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The core structure of ginsenan PA, a phagocytosis-activating polysaccharide from the root of Panax ginseng.

PubMed

Tomoda, M; Hirabayashi, K; Shimizu, N; Gonda, R; Ohara, N

1994-09-01

Controlled Smith degradation and limited hydrolysis of ginsenan PA, the main phagocytosis-activating polysaccharide isolated from the root of Panax ginseng C. A. Meyer, were performed. The reticuloendothelial system-potentiating and anti-complementary activities of the degradation products were investigated. Methylation analysis of the primary and secondary Smith degradation products indicated that the core structural features of ginsenan PA include a backbone chain mainly composed of beta-1,3-linked D-galactose. Almost half of the galactose units in the backbone carry side-chains composed of beta-1,6-linked D-galactosyl residues at position 6. Further 3,6-branching of D-galactose units was observed in a part of the side-chains. alpha-L-Arabinose units are connected mainly to the core galactose moieties via position 6. Removal of most of the arabinose units had a considerable effect on immunological activity.

Pseudomonas aeruginosa phage PaP1 DNA polymerase is an A-family DNA polymerase demonstrating ssDNA and dsDNA 3'-5' exonuclease activity.

PubMed

Liu, Binyan; Gu, Shiling; Liang, Nengsong; Xiong, Mei; Xue, Qizhen; Lu, Shuguang; Hu, Fuquan; Zhang, Huidong

2016-08-01

Most phages contain DNA polymerases, which are essential for DNA replication and propagation in infected host bacteria. However, our knowledge on phage-encoded DNA polymerases remains limited. This study investigated the function of a novel DNA polymerase of PaP1, which is the lytic phage of Pseudomonas aeruginosa. PaP1 encodes its sole DNA polymerase called Gp90 that was predicted as an A-family DNA polymerase with polymerase and 3'-5' exonuclease activities. The sequence of Gp90 is homologous but not identical to that of other A-family DNA polymerases, such as T7 DNA polymerases (Pol) and DNA Pol I. The purified Gp90 demonstrated a polymerase activity. The processivity of Gp90 in DNA replication and its efficiency in single-dNTP incorporation are similar to those of T7 Pol with processive thioredoxin (T7 Pol/trx). Gp90 can degrade ssDNA and dsDNA in 3'-5' direction at a similar rate, which is considerably lower than that of T7 Pol/trx. The optimized conditions for polymerization were a temperature of 37 °C and a buffer consisting of 40 mM Tris-HCl (pH 8.0), 30 mM MgCl2, and 200 mM NaCl. These studies on DNA polymerase encoded by PaP1 help advance our knowledge on phage-encoded DNA polymerases and elucidate PaP1 propagation in infected P. aeruginosa.

The relationship between body temperature, heart rate, breathing rate, and rate of oxygen consumption, in the tegu lizard (Tupinambis merianae) at various levels of activity.

PubMed

Piercy, Joanna; Rogers, Kip; Reichert, Michelle; Andrade, Denis V; Abe, Augusto S; Tattersall, Glenn J; Milsom, William K

2015-12-01

The present study determined whether EEG and/or EMG recordings could be used to reliably define activity states in the Brazilian black and white tegu lizard (Tupinambis merianae) and then examined the interactive effects of temperature and activity states on strategies for matching O2 supply and demand. In a first series of experiments, the rate of oxygen consumption (VO2), breathing frequency (fR), heart rate (fH), and EEG and EMG (neck muscle) activity were measured in different sleep/wake states (sleeping, awake but quiet, alert, or moving). In general, metabolic and cardio-respiratory changes were better indictors of the transition from sleep to wake than were changes in the EEG and EMG. In a second series of experiments, the interactive effects of temperature (17, 27 and 37 °C) and activity states on fR, tidal volume (VT), the fraction of oxygen extracted from the lung per breath (FIO2-FEO2), fH, and the cardiac O2 pulse were quantified to determine the relative roles of each of these variables in accommodating changes in VO2. The increases in oxygen supply to meet temperature- and activity-induced increases in oxygen demand were produced almost exclusively by increases in fH and fR. Regression analysis showed that the effects of temperature and activity state on the relationships between fH, fR and VO2 was to extend a common relationship along a single curve, rather than separate relationships for each metabolic state. For these lizards, the predictive powers of fR and fH were maximized when the effects of changes in temperature, digestive state and activity were pooled. However, the best r(2) values obtained were 0.63 and 0.74 using fR and fH as predictors of metabolic rate, respectively.

Biological Activity and Binding Site Characteristics of the PA1b Entomotoxin on Insects from Different Orders

PubMed Central

Gressent, Frédéric; Duport, Gabrielle; Rahioui, Isabelle; Pauchet, Yannick; Bolland, Patrice; Specty, Olivier; Rahbe, Yvan

2007-01-01

The aim of this work was to investigate both the biological activity of an entomotoxin, the pea albumin 1b (PA1b), and the presence or absence of its binding site within an array of insect species. The data obtained showed that insect sensitivity was not related to its taxonomic position. Moreover, PA1b was not toxic to several tested microorganisms. However, the binding site was found to be conserved among very different insects, displaying similar thermodynamic constants regardless of the in vivo species sensitivity. The binding site alone was, therefore, not sufficient for toxicity. One exception was the pea weevil, Bruchus pisorum, which was the only tested species without any detectable binding activity. These findings indicate that the binding site probably has an important endogenous function in insects and that adaptation to pea seeds resulted in the elimination of the toxin binding activity in two independent insect lineages. Other mechanisms are likely to interact with the toxin effects, although they are still largely unknown, but there is no evidence of any specific degradation of PA1b in the midgut of insects insensitive to the toxin, such as Drosophila melanogaster or Mamestra brassicae. PMID:20331395

The association between exercise enjoyment and physical activity in women with fibromyalgia.

PubMed

Umeda, M; Marino, C A; Lee, W; Hilliard, S C

2014-11-01

Evidence suggests the role of physical activity (PA) in management of clinical symptoms of fibromyalgia. However, very little is known regarding the psychological correlates of PA in patients with fibromyalgia. Therefore, this study examined the association between exercise enjoyment (EE) and PA in women with fibromyalgia. 19 women with fibromyalgia completed a laboratory session, where EE was assessed using a self-report questionnaire immediately after 20 min of light-intensity biking. Muscle pain ratings (MPR) in the legs were assessed during exercise, and changes in clinical pain intensity after exercise were computed. PA was assessed subjectively using a self-report questionnaire and objectively using an accelerometer for one week. Results from correlation analyses indicated that EE was associated with the self-reported amount of PA (rs=0.61, R(2)=0.37, p<0.01) and the minutes spent for moderate intensity PA (rs=0.48, R(2)=0.23, p<0.05). However, neither MPR nor changes in clinical pain intensity were associated with PA. These results suggest that EE may serve as a determinant of PA in women with fibromyalgia. Future research is needed to develop interventions to maximize EE to promote PA in this clinical population. © Georg Thieme Verlag KG Stuttgart · New York.

Physical activity in persons with late effects of polio: a descriptive study.

PubMed

Winberg, Cecilia; Flansbjer, Ulla-Britt; Carlsson, Gunilla; Rimmer, James; Lexell, Jan

2014-07-01

To promote a healthy and active lifestyle there is a need to increase our knowledge of the level of physical activity (PA) among people with late effects of polio. To examine PA in people with late effects of polio and to assess the relationship between PA, life satisfaction and various sociodemographic factors. PA was assessed in 81 persons with late effects of polio using the Physical Activity and Disability Survey (PADS) and by a pedometer. Life satisfaction was assessed with the Life Satisfaction Questionnaire (LiSat-11). The amount of PA varied considerably but on average the participants were physically active almost 3 h per day, mostly in household activities. The mean value of the pedometer counts was 6212 steps per day (SD = 3208). Sixty-nine percent of the participants rated themselves as satisfied with life as a whole. The sum of PADS was positively and significantly related to the number of steps (r = 0.39, p < 0.001), increasing age (r = 0.26, p < 0.05) and to the level of global satisfaction with life (rho = 0.23, p < 0.05). The number of steps was also positively and significantly associated with level of global satisfaction with life (rho = 0.37, p < 0.001). Despite a progressive physical disability, people with late effects of polio are physically active, but much of the activities are performed as part of their household activities and not as traditional exercise. The relationship between PA, life satisfaction and age further supports the general contention that an active lifestyle is an important factor for perceived well-being among older people. Copyright © 2014 Elsevier Inc. All rights reserved.

Characterization of biocenoses in the storage reservoirs of liquid radioactive wastes of Mayak PA. Initial descriptive report.

PubMed

Pryakhin, E A; Mokrov, Yu G; Tryapitsina, G A; Ivanov, I A; Osipov, D I; Atamanyuk, N I; Deryabina, L V; Shaposhnikova, I A; Shishkina, E A; Obvintseva, N A; Egoreichenkov, E A; Styazhkina, E V; Osipova, O F; Mogilnikova, N I; Andreev, S S; Tarasov, O V; Geras'kin, S A; Trapeznikov, A V; Akleyev, A V

2016-01-01

As a result of operation of the Mayak Production Association (Mayak PA), Chelyabinsk Oblast, Russia, an enterprise for production and separation of weapon-grade plutonium in the Soviet Union, ecosystems of a number of water bodies have been radioactively contaminated. The article presents information about the current state of ecosystems of 6 special industrial storage reservoirs of liquid radioactive waste from Mayak PA: reservoirs R-3, R-4, R-9, R-10, R-11 and R-17. At present the excess of the radionuclide content in the water of the studied reservoirs and comparison reservoirs (Shershnyovskoye and Beloyarskoye reservoirs) is 9 orders of magnitude for (90)Sr and (137)Cs, and 6 orders of magnitude for alpha-emitting radionuclides. According to the level of radioactive contamination, the reservoirs of the Mayak PA could be arranged in the ascending order as follows: R-11, R-10, R-4, R-3, R-17 and R-9. In 2007-2012 research of the status of the biocenoses of these reservoirs in terms of phytoplankton, zooplankton, bacterioplankton, zoobenthos, aquatic plants, ichthyofauna, avifauna parameters was performed. The conducted studies revealed decrease in species diversity in reservoirs with the highest levels of radioactive and chemical contamination. This article is an initial descriptive report on the status of the biocenoses of radioactively contaminated reservoirs of the Mayak PA, and is the first article in a series of publications devoted to the studies of the reaction of biocenoses of the fresh-water reservoirs of the Mayak PA to a combination of natural and man-made factors, including chronic radiation exposure. Copyright © 2015 Elsevier Ltd. All rights reserved.

Self-administered physical activity questionnaires for the elderly: a systematic review of measurement properties.

PubMed

Forsén, Lisa; Loland, Nina Waaler; Vuillemin, Anne; Chinapaw, Mai J M; van Poppel, Mireille N M; Mokkink, Lidwine B; van Mechelen, Willem; Terwee, Caroline B

2010-07-01

To systematically review and appraise studies examining self-administered physical activity questionnaires (PAQ) for the elderly. This article is one of a group of four articles in Sports Medicine on the content and measurement properties of PAQs. LITERATURE SEARCH METHODOLOGY: Searches in PubMed, EMBASE and SportDiscu (until May 2009) on self-administered PAQ. Inclusion criteria were as follows: (i) the study examined (at least one of) the measurement properties of a self-administered PAQ; (ii) the questionnaire aimed to measure physical activity (PA) in older people; (iii) the average age of the study population was >55 years; (iv) the article was written in English. We excluded PA interviews, diaries and studies that evaluated the measurement properties of a self-administered PAQ in a specific population, such as patients. We used a standard checklist (qualitative attributes and measurement properties of PA questionnaires [QAPAQ]) for appraising the measurement properties of PAQs. Eighteen articles on 13 PAQs were reviewed, including 16 reliability analyses and 25 validity analyses (of which 15 were on construct validity, seven on health/functioning associations, two on known-groups validity and one on responsiveness). Many studies suffered from methodological flaws, e.g. too small sample size or inadequate time interval between test and retest. Three PAQs received a positive rating on reliability: IPAQ-C (International Physical Activity Questionnaire-Chinese), intraclass correlation coefficient (ICC) > or = 0.81; WHI-PAQ (Women's Health Initiative-PAQ), ICC = 0.76; and PASE (Physical Activity Scale for the Elderly), Pearson correlation coefficient (r) = 0.84. However, PASE was negatively rated on reliability in another study (ICC = 0.65). One PAQ received a positive rating on construct validity: PASE against Mini-Logger (r > 0.52), but PASE was negatively rated in another study against accelerometer and another PAQ, Spearman correlation coefficient = 0.17 and 0

Molecular requirements for the insecticidal activity of the plant peptide pea albumin 1 subunit b (PA1b).

PubMed

Da Silva, Pedro; Rahioui, Isabelle; Laugier, Christian; Jouvensal, Laurence; Meudal, Hervé; Chouabe, Christophe; Delmas, Agnès F; Gressent, Frédéric

2010-10-22

PA1b (pea albumin 1, subunit b) is a small and compact 37-amino acid protein, isolated from pea seeds (Pisum sativum), that adopts a cystine knot fold. It acts as a potent insecticidal agent against major pests in stored crops and vegetables, making it a promising bioinsecticide. Here, we investigate the influence of individual residues on the structure and bioactivity of PA1b. A collection of 13 PA1b mutants was successfully chemically synthesized in which the residues involved in the definition of PA1b amphiphilic and electrostatic characteristics were individually replaced with an alanine. The three-dimensional structure of PA1b was outstandingly tolerant of modifications. Remarkably, receptor binding and insecticidal activities were both dependent on common well defined clusters of residues located on one single face of the toxin, with Phe-10, Arg-21, Ile-23, and Leu-27 being key residues of the binding interaction. The inactivity of the mutants is clearly due to a change in the nature of the side chain rather than to a side effect, such as misfolding or degradation of the peptide, in the insect digestive tract. We have shown that a hydrophobic patch is the putative site of the interaction of PA1b with its binding site. Overall, the mutagenesis data provide major insights into the functional elements responsible for PA1b entomotoxic properties and give some clues toward a better understanding of the PA1b mode of action.

Racial disparities in tissue plasminogen activator treatment rate for stroke: a population-based study.

PubMed

Hsia, Amie W; Edwards, Dorothy F; Morgenstern, Lewis B; Wing, Jeffrey J; Brown, Nina C; Coles, Regina; Loftin, Sarah; Wein, Andrea; Koslosky, Sara S; Fatima, Sabiha; Sánchez, Brisa N; Fokar, Ali; Gibbons, M Chris; Shara, Nawar; Jayam-Trouth, Annapurni; Kidwell, Chelsea S

2011-08-01

Some prior studies have shown that racial disparities exist in intravenous tissue plasminogen activator (tPA) use for acute ischemic stroke. We sought to determine whether race was associated with tPA treatment for stroke in a predominantly black urban population. Systematic chart abstraction was performed on consecutive hospitalized patients with ischemic stroke from all 7 acute care hospitals in the District of Columbia from February 1, 2008, to January 31, 2009. Of 1044 patients with ischemic stroke, 74% were black, 19% non-Hispanic white, and 5% received intravenous tPA. Blacks were one third less likely than whites to receive intravenous tPA (3% versus 10%, P<0.001). However, blacks were also less likely than whites to present within 3 hours of symptom onset (13% versus 21%, P=0.004) and also less likely to be tPA-eligible (5% versus 13%, P<0.001). Of those who presented within 3 hours, blacks were almost half as likely to be treated with intravenous tPA than whites (27% versus 46%, P=0.023). The treatment rate for tPA-eligible patients was similar for blacks and whites (70% versus 76%, P=0.62). In this predominantly black urban population hospitalized for acute ischemic stroke, blacks were significantly less likely to be treated with intravenous tPA due to contraindications to treatment, delayed presentation, and stroke severity. Effective interventions designed to increase treatment in this population need to focus on culturally relevant education programs designed to address barriers specific to this population.

PaASK1, a mitogen-activated protein kinase kinase kinase that controls cell degeneration and cell differentiation in Podospora anserina.

PubMed Central

Kicka, Sébastien; Silar, Philippe

2004-01-01

MAPKKK are kinases involved in cell signaling. In fungi, these kinases are known to regulate development, pathogenicity, and the sensing of external conditions. We show here that Podospora anserina strains mutated in PaASK1, a MAPKKK of the MEK family, are impaired in the development of crippled growth, a cell degeneration process caused by C, a nonconventional infectious element. They also display defects in mycelium pigmentation, differentiation of aerial hyphae, and making of fruiting bodies, three hallmarks of cell differentiation during stationary phase in P. anserina. Overexpression of PaASK1 results in exacerbation of crippled growth. PaASK1 is a large protein of 1832 amino acids with several domains, including a region rich in proline and a 60-amino-acid-long polyglutamine stretch. Deletion analysis reveals that the polyglutamine stretch is dispensable for PaASK1 activity, whereas the region that contains the prolines is essential but insufficient to promote full activity. We discuss a model based on the hysteresis of a signal transduction cascade to account for the role of PaASK1 in both cell degeneration and stationary-phase cell differentiation. PMID:15082544

PaASK1, a mitogen-activated protein kinase kinase kinase that controls cell degeneration and cell differentiation in Podospora anserina.

PubMed

Kicka, Sébastien; Silar, Philippe

2004-03-01

MAPKKK are kinases involved in cell signaling. In fungi, these kinases are known to regulate development, pathogenicity, and the sensing of external conditions. We show here that Podospora anserina strains mutated in PaASK1, a MAPKKK of the MEK family, are impaired in the development of crippled growth, a cell degeneration process caused by C, a nonconventional infectious element. They also display defects in mycelium pigmentation, differentiation of aerial hyphae, and making of fruiting bodies, three hallmarks of cell differentiation during stationary phase in P. anserina. Overexpression of PaASK1 results in exacerbation of crippled growth. PaASK1 is a large protein of 1832 amino acids with several domains, including a region rich in proline and a 60-amino-acid-long polyglutamine stretch. Deletion analysis reveals that the polyglutamine stretch is dispensable for PaASK1 activity, whereas the region that contains the prolines is essential but insufficient to promote full activity. We discuss a model based on the hysteresis of a signal transduction cascade to account for the role of PaASK1 in both cell degeneration and stationary-phase cell differentiation.

Relationships of self-reported physical activity domains with accelerometry recordings in French adults.

PubMed

Jacobi, David; Charles, Marie-Aline; Tafflet, Muriel; Lommez, Agnès; Borys, Jean-Michel; Oppert, Jean-Michel

2009-01-01

The objective was to examine the relationships of self-reported physical activity (PA) by domain (leisure, occupational, other) with PA and sedentary time as measured objectively by accelerometry. Subjects were adults with low habitual PA levels from a community in northern France. Among subjects in the lowest tertile of a PA score from a screening questionnaire, 160 (37% males, age: 41.0 +/- 10.8 years, BMI: 25.1 +/- 4.1 kg/m(2), mean +/- SD) completed a detailed instrument (Modifiable Activity Questionnaire), and wore an accelerometer (Actigraph) for seven consecutive days. Relationships between questionnaire domains (occupational, leisure, and "non-occupational non-leisure") and accelerometry measures (total activity and sedentary time) were assessed using Spearman correlation coefficients. In this population, the highest contributor to total reported PA (h/week) was occupational PA. Time spent in non-occupational non-leisure PA ranked second in women and third in men. The most frequent non-occupational non-leisure PA were shopping and household chores. In women, non-occupational non-leisure PA contributed more than occupational or leisure-time PA to total PA energy expenditure (median: 18.0, 9.1, and 4.9 MET-h/week, respectively). Total PA by accelerometry (count/day) was correlated to leisure-time PA in women (r = 0.22, P < 0.05) and to occupational (r = 0.43, P < 0.01) and total reported PA (r = 0.39, P < 0.01) in men (all in MET-h/week). There was an inverse relationship between accelerometry sedentary time (h/day) and non-occupational non-leisure PA (MET-h/week, r = -0.30, P < 0.001). These findings indicate the importance of assessing non-occupational non-leisure PA for a better understanding of how individuals partition their time between active or sedentary occupations.

76 FR 29176 - Airworthiness Directives; Piper Aircraft, Inc. PA-23, PA-31, and PA-42 Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-20

...-0218; Directorate Identifier 2009-CE-006-AD] RIN 2120-AA64 Airworthiness Directives; Piper Aircraft... (AD) that applies to Piper Aircraft, Inc. PA-23, PA-31, and PA-42 airplanes. The existing AD currently... Federal holidays. For service information identified in this AD, contact Piper Aircraft, Inc., 2926 Piper...

Simulated rRNA/DNA Ratios Show Potential To Misclassify Active Populations as Dormant

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

Steven, Blaire; Hesse, Cedar; Soghigian, John

The use of rRNA/DNA ratios derived from surveys of rRNA sequences in RNA and DNA extracts is an appealing but poorly validated approach to infer the activity status of environmental microbes. To improve the interpretation of rRNA/DNA ratios, we performed simulations to investigate the effects of community structure, rRNA amplification, and sampling depth on the accuracy of rRNA/DNA ratios in classifying bacterial populations as “active” or “dormant.” Community structure was an insignificant factor. In contrast, the extent of rRNA amplification that occurs as cells transition from dormant to growing had a significant effect (P < 0.0001) on classification accuracy, withmore » misclassification errors ranging from 16 to 28%, depending on the rRNA amplification model. The error rate increased to 47% when communities included a mixture of rRNA amplification models, but most of the inflated error was false negatives (i.e., active populations misclassified as dormant). Sampling depth also affected error rates (P < 0.001). Inadequate sampling depth produced various artifacts that are characteristic of rRNA/DNA ratios generated from real communities. These data show important constraints on the use of rRNA/DNA ratios to infer activity status. Whereas classification of populations as active based on rRNA/DNA ratios appears generally valid, classification of populations as dormant is potentially far less accurate.« less

Simulated rRNA/DNA Ratios Show Potential To Misclassify Active Populations as Dormant

DOE PAGES

Steven, Blaire; Hesse, Cedar; Soghigian, John; ...

2017-03-31

The use of rRNA/DNA ratios derived from surveys of rRNA sequences in RNA and DNA extracts is an appealing but poorly validated approach to infer the activity status of environmental microbes. To improve the interpretation of rRNA/DNA ratios, we performed simulations to investigate the effects of community structure, rRNA amplification, and sampling depth on the accuracy of rRNA/DNA ratios in classifying bacterial populations as “active” or “dormant.” Community structure was an insignificant factor. In contrast, the extent of rRNA amplification that occurs as cells transition from dormant to growing had a significant effect (P < 0.0001) on classification accuracy, withmore » misclassification errors ranging from 16 to 28%, depending on the rRNA amplification model. The error rate increased to 47% when communities included a mixture of rRNA amplification models, but most of the inflated error was false negatives (i.e., active populations misclassified as dormant). Sampling depth also affected error rates (P < 0.001). Inadequate sampling depth produced various artifacts that are characteristic of rRNA/DNA ratios generated from real communities. These data show important constraints on the use of rRNA/DNA ratios to infer activity status. Whereas classification of populations as active based on rRNA/DNA ratios appears generally valid, classification of populations as dormant is potentially far less accurate.« less

Suppressive effects of RXR agonist PA024 on adrenal CYP11B2 expression, aldosterone secretion and blood pressure.

PubMed

Suzuki, Dai; Saito-Hakoda, Akiko; Ito, Ryo; Shimizu, Kyoko; Parvin, Rehana; Shimada, Hiroki; Noro, Erika; Suzuki, Susumu; Fujiwara, Ikuma; Kagechika, Hiroyuki; Rainey, William E; Kure, Shigeo; Ito, Sadayoshi; Yokoyama, Atsushi; Sugawara, Akira

2017-01-01

The effects of retinoids on adrenal aldosterone synthase gene (CYP11B2) expression and aldosterone secretion are still unknown. We therefore examined the effects of nuclear retinoid X receptor (RXR) pan-agonist PA024 on CYP11B2 expression, aldosterone secretion and blood pressure, to elucidate its potential as a novel anti-hypertensive drug. We demonstrated that PA024 significantly suppressed angiotensin II (Ang II)-induced CYP11B2 mRNA expression, promoter activity and aldosterone secretion in human adrenocortical H295R cells. Human CYP11B2 promoter functional analyses using its deletion and point mutants indicated that the suppression of CYP11B2 promoter activity by PA024 was in the region from -1521 (full length) to -106 including the NBRE-1 and the Ad5 elements, and the Ad5 element may be mainly involved in the PA024-mediated suppression. PA024 also significantly suppressed the Ang II-induced mRNA expression of transcription factors NURR1 and NGFIB that bind to and activate the Ad5 element. NURR1 overexpression demonstrated that the decrease of NURR1 expression may contribute to the PA024-mediated suppression of CYP11B2 transcription. PA024 also suppressed the Ang II-induced mRNA expression of StAR, HSD3β2 and CYP21A2, a steroidogenic enzyme group involved in aldosterone biosynthesis. Additionally, the PA024-mediated CYP11B2 transcription suppression was shown to be exerted via RXRα. Moreover, the combination of PPARγ agonist pioglitazone and PA024 caused synergistic suppressive effects on CYP11B2 mRNA expression. Finally, PA024 treatment significantly lowered both the systolic and diastolic blood pressure in Tsukuba hypertensive mice (hRN8-12 x hAG2-5). Thus, RXR pan-agonist PA024 may be a candidate anti-hypertensive drugs that acts via the suppression of aldosterone synthesis and secretion.

Nutrients removal and substrate enzyme activities in vertical subsurface flow constructed wetlands for mariculture wastewater treatment: Effects of ammonia nitrogen loading rates and salinity levels.

PubMed

Li, Meng; Liang, Zhenlin; Callier, Myriam D; Roque d'orbcastel, Emmanuelle; Sun, Guoxiang; Ma, Xiaona; Li, Xian; Wang, Shunkui; Liu, Ying; Song, Xiefa

2018-06-01

This study aims to investigate the effects of ammonia nitrogen loading rates and salinity levels on nutrients removal rates and substrate enzyme activities of constructed wetland (CW) microcosms planted with Salicornia bigelovii treating mariculture wastewater. Activities of urease (UA), dehydrogenase (DA), protease (PrA) and phosphatase (PA) were considered. Using principal component analysis (PCA), nutrient removal index (NRI) and enzyme activity index (EAI) were developed to evaluate the effects. The results revealed that increasing ammonia nitrogen loading rates had positive effects on nitrogen removal rates (i.e. NH 4 -N and DIN) and enhanced substrate enzyme activities. Compared with low salinity (i.e. 15 and 22), high salinity levels (i.e. 29 and 36) enhanced nutrients removal rates, DA and UA, but weaken PA and PrA. In conclusion, CW microcosms with Salicornia bigelovii can be used for the removal of nutrients under a range of ammonia nitrogen loadings and high salinity levels. Copyright © 2018 Elsevier Ltd. All rights reserved.

PaTrx1 and PaTrx3, two cytosolic thioredoxins of the filamentous ascomycete Podospora anserina involved in sexual development and cell degeneration.

PubMed

Malagnac, Fabienne; Klapholz, Benjamin; Silar, Philippe

2007-12-01

In various organisms, thioredoxins are known to be involved in the reduction of protein disulfide bonds and in protecting the cell from oxidative stress. Genes encoding thioredoxins were found by searching the complete genome sequence of the filamentous ascomycete Podospora anserina. Among them, PaTrx1, PaTrx2, and PaTrx3 are predicted to be canonical cytosolic proteins without additional domains. Targeted disruption of PaTrx1, PaTrx2, and PaTrx3 shows that PaTrx1 is the major thioredoxin involved in sulfur metabolism. Deletions have no effect on peroxide resistance; however, data show that either PaTrx1 or PaTrx3 is necessary for sexual reproduction and for the development of the crippled growth cell degeneration (CG), processes that also required the PaMpk1 mitogen-activated protein kinase (MAPK) pathway. Since PaTrx1 PaTrx3 mutants show not an enhancement but rather an impairment in CG, it seems unlikely that PaTrx1 and PaTrx3 thioredoxins participate in the inhibition of this MAPK pathway. Altogether, these results underscore a role for thioredoxins in fungal development.

Reliability and validity of a school recess physical activity recall in Spanish youth.

PubMed

Martínez-Gómez, David; Calabro, M Andres; Welk, Gregory J; Marcos, Ascension; Veiga, Oscar L

2010-05-01

Recess is a frequent target in school-based physical activity (PA) promotion research but there are challenges in assessing PA during this time period. The purpose of this study was to evaluate the reliability and validity of a recess PA recall (RPAR) instrument designed to assess total PA and time spent in moderate to vigorous PA (MVPA) during recess. One hundred twenty-five 7th and 8th-grade students (59 females), age 12-14 years, participated in the study. Activity levels were objectively monitored on Mondays using different activity monitors (Yamax Digiwalker, Biotrainer and ActiGraph). On Tuesdays, 2 RPAR self-reports were administered within 1-hr. Test-retest reliability showed ICC = 0.87 and 0.88 for total PA and time spent in MVPA, respectively. The RPAR was correlated against Yamax (r = .35), Biotrainer (r = .40 and 0.54) and ActiGraph (r = .42) to assess total PA during recess. The RPAR was also correlated against ActiGraph (r = .54) to assess time spent in MVPA during recess. Mean difference between the RPAR and ActiGraph to assess time spent in MVPA during recess was no significant (2.15 +/- 3.67 min, p = .313). The RPAR showed an adequate reliability and a reasonable validity for assessing PA during the school recess in youth.

Parental R-rated movie restriction and early-onset alcohol use.

PubMed

Tanski, Susanne E; Dal Cin, Sonya; Stoolmiller, Mike; Sargent, James D

2010-05-01

The aim of this study was to determine if parental restriction regarding Restricted-rated movies (R movies) predicts lower rates of early-onset alcohol use. Students from 15 northern New England middle schools were surveyed in 1999, and never-drinkers were resurveyed 13-26 months later to determine alcohol use. Drinking was determined by the question, "Have you ever had beer, wine, or other drink with alcohol that your parents didn't know about?" R-movie restriction was assessed by the question, "How often do your parents allow you to watch movies that are rated R?" The sample included 2,406 baseline never-drinkers who were surveyed at follow-up, of whom 14.8% had initiated alcohol use. At baseline, 20% reported never being allowed to watch R movies, and 21% reported being allowed all the time. Adolescents allowed to watch R-rated movies had higher rates of alcohol initiation (2.9% initiation among never allowed, 12.5% once in a while, 18.8% sometimes, and 24.4% all the time). Controlling for sociodemographics, personality characteristics, and authoritative parenting style, the adjusted odds ratios for initiating alcohol use were 3.0 (95% CI [1.7, 5.1]) for those once in a while allowed, 3.3 [1.9, 5.6] for those sometimes allowed, and 3.5 [2.0, 6.0] for those always allowed to watch R-rated movies. Alcohol initiation was more likely if R-rated movie restriction relaxed over time; tightening of restriction had a protective effect (p < .001). A structural model was developed that modeled two latent parenting constructs: (a) authoritative parenting and (b) media parenting. Both constructs had direct inverse paths to trying alcohol and indirect paths through lower exposure to R-rated movies. After accounting for differences in authoritative parenting style, adolescents reporting lesser restrictions for R movies have higher odds of future alcohol use. The structural model suggests that media parenting operates independently from authoritative parenting and should be

Parental R-Rated Movie Restriction and Early-Onset Alcohol Use*

PubMed Central

Tanski, Susanne E.; Dal Cin, Sonya; Stoolmiller, Mike; Sargent, James D.

2010-01-01

Objective: The aim of this study was to determine if parental restriction regarding Restricted-rated movies (R movies) predicts lower rates of early-onset alcohol use. Method: Students from 15 northern New England middle schools were surveyed in 1999, and never-drinkers were resurveyed 13–26 months later to determine alcohol use. Drinking was determined by the question, “Have you ever had beer, wine, or other drink with alcohol that your parents didn't know about?” R-movie restriction was assessed by the question, “How often do your parents allow you to watch movies that are rated R?” Results: The sample included 2,406 baseline never-drinkers who were surveyed at follow-up, of whom 14.8% had initiated alcohol use. At baseline, 20% reported never being allowed to watch R movies, and 21% reported being allowed all the time. Adolescents allowed to watch R-rated movies had higher rates of alcohol initiation (2.9% initiation among never allowed, 12.5% once in a while, 18.8% sometimes, and 24.4% all the time). Controlling for sociodemographics, personality characteristics, and authoritative parenting style, the adjusted odds ratios for initiating alcohol use were 3.0 (95% CI [1.7, 5.1]) for those once in a while allowed, 3.3 [1.9, 5.6] for those sometimes allowed, and 3.5 [2.0, 6.0] for those always allowed to watch R-rated movies. Alcohol initiation was more likely if R-rated movie restriction relaxed over time; tightening of restriction had a protective effect (p < .001). A structural model was developed that modeled two latent parenting constructs: (a) authoritative parenting and (b) media parenting. Both constructs had direct inverse paths to trying alcohol and indirect paths through lower exposure to R-rated movies. Conclusions: After accounting for differences in authoritative parenting style, adolescents reporting lesser restrictions for R movies have higher odds of future alcohol use. The structural model suggests that media parenting operates

Adenosine A3 receptors regulate heart rate, motor activity and body temperature

PubMed Central

Yang, Jiangning; Wang, Yingqing; Garcia-Roves, Pablo; Björnholm, Marie; Fredholm, Bertil B.

2010-01-01

Aim We wanted to examine the phenotype of mice that lack the adenosine A3 receptor (A3R). Methods We examined the heart rate, body temperature and locomotion continuously by telemetry over several days. In addition the effect of the adenosine analogue R - N6- phenylisopropyl-adenosine (R-PIA) was examined. In addition, we examined heat production and food intake. Results We found that the marked diurnal variation in activity, heart rate and body temperature, with markedly higher values at night than during day time, was reduced in the A3R knockout mice. Surprisingly, the reduction in heart rate, activity and body temperature seen after injection of R-PIA in wild type mice was virtually eliminated in the A3R knock-out mice. The marked reduction in activity was associated with a decreased heat production, as expected. However, the A3R knock-out mice, surprisingly, had a higher food intake but no difference in body weight compared to wild type mice. Conclusions The mice lacking adenosine A3 receptors exhibit a surprisingly clear phenotype with changes in e.g. diurnal rhythm and temperature regulation. Whether these effects are due to a physiological role of A3 receptors in these processes or if they represent a role in development remains to be elucidated. PMID:20121716

Time-extended local rtPA infiltration for acutely thrombosed hemodialysis fistulas.

PubMed

Regus, Susanne; Lang, Werner; Heinz, Marco; Rother, Ulrich; Meyer, Alexander; Almási-Sperling, Veronika; Uder, Michael; Schmid, Axel

2018-01-01

This study describes results of a modified local thrombolysis technique for acutely thrombosed hemodialysis (HD) arteriovenous fistulas (AVF), which is characterized by prolonged recombinant tissue plasminogen activator (rtPA) local exposure times. Contrary to the standard lyse- and- wait (L&W) technique with local reaction times of 20-40 minutes, the modified protocol allows timing of challenging angioplasty maneuvers to the next regular working day. From February 2009 to April 2014, 84 patients on HD presented with 152 acutely thrombosed AVF. They proceeded to local thrombolysis including a single shot infiltration of rtPA, local reaction time up to 40 hours and finally percutaneous stenosis angioplasty. Success rates, major adverse events and need for temporary catheter placements (TCP) were retrospectively analyzed. The local thrombolysis time after single shot infiltration was 18.6 ± 6.2 (range 2-40) hours. Mean rtPA- dosage was 2.7 mg ± 1.2. The overall success rate was 89.5% and the major complication rate was 3.3%, whereas TCP was necessary in 12.5%. The PP/SP at 1, 3, 6, 12, 18, and 24 month were 86% ± 3%/95% ± 2%, 68% ± 4%/92% ± 2%, 43% ± 4%/90% ± 2%, 28% ± 4%/82% ± 3%, 12% ± 3%/82% ± 3%, 7% ± 2%/63% ± 4%, respectively. The modified L&W technique with prolonged local rtPA reaction times is a safe and effective declotting procedure. The need for TCP was not increased and therefore comparable to the standard technique. © 2017 International Society for Hemodialysis.

The PA influenza virus polymerase subunit is a phosphorylated protein.

PubMed

Sanz-Ezquerro, J J; Fernández Santarén, J; Sierra, T; Aragón, T; Ortega, J; Ortín, J; Smith, G L; Nieto, A

1998-03-01

The induction of proteolysis by expression of the influenza virus PA polymerase subunit is the only biochemical activity ascribed to this protein. In the course of studying viral protein synthesis by two-dimensional gel electrophoresis, we observed the existence of several PA isoforms with different isoelectric points. These isoforms were also present when the PA gene was singly expressed in three different expression systems, indicating that a cellular activity is responsible for its post-translational modification. In vivo labelling with [32P]orthophosphate, followed by two-dimensional gel electrophoresis, clearly demonstrated the incorporation of phosphate into the PA molecule. Phosphoserine and phosphothreonine epitopes were present in PA, while phosphotyrosine residues were absent, as tested by immunoblotting with specific antibodies. These facts, as well as the presence of multiple consensus sites for casein kinase II (CKII) phosphorylation, prompted us to test the involvement of this kinase in PA covalent modification. PA protein purified by immunoprecipitation could be specifically labelled by the catalytic alpha subunit of human CKII, which was expressed and purified from bacteria. Collectively, these data demonstrate that the PA subunit of the influenza virus RNA polymerase is a phosphoprotein.

Physical Activity and Heart Rate Variability in Older Adults: The Cardiovascular Health Study

PubMed Central

Soares-Miranda, Luisa; Sattelmair, Jacob; Chaves, Paulo; Duncan, Glen; Siscovick, David S; Stein, Phyllis K; Mozaffarian, Dariush

2014-01-01

Background Cardiac mortality and electrophysiologic dysfunction both increase with age. Heart rate variability (HRV) provides indices of autonomic function and electrophysiology that are associated with cardiac risk. How habitual physical activity (PA) among older adults prospectively relates to HRV, including nonlinear indices of erratic sinus patterns, is not established. We hypothesized that increasing levels of both total leisure-time activity and walking would be prospectively associated with more favorable time-domain, frequency-domain, and nonlinear HRV measures in older adults. Methods and Results We evaluated serial longitudinal measures of both PA and 24-hour Holter HRV over 5 years among 985 older US adults in the community-based Cardiovascular Health Study. After multivariable adjustment, greater total leisure-time activity, walking distance, and walking pace were each prospectively associated with specific, more favorable HRV indices, including higher 24-hour standard-deviation-of-all-normal-to-normal-intervals (SDNN, p-trend=0.009, 0.02, 0.06, respectively) and ultra-low-frequency-power (p-trend=0.02, 0.008, 0.16, respectively). Greater walking pace was also associated with higher short-term-fractal-scaling-exponent (p-trend=0.003) and lower Poincare ratio (p-trend=0.02), markers of less erratic sinus patterns. Conclusions Greater total leisure-time activity, as well as walking alone, were prospectively associated with more favorable and specific indices of autonomic function in older adults, including several suggestive of more normal circadian fluctuations and less erratic sinoatrial firing. Our results suggest potential mechanisms that might contribute to lower cardiovascular mortality with habitual PA later in life. PMID:24799513

Detection of anthrax protective antigen (PA) using europium labeled anti-PA monoclonal antibody and time-resolved fluorescence ◊

PubMed Central

Stoddard, Robyn A.; Quinn, Conrad P.; Schiffer, Jarad M.; Boyer, Anne E.; Goldstein, Jason; Bagarozzi, Dennis A.; Soroka, Stephen D.; Dauphin, Leslie A.; Hoffmaster, Alex R.

2015-01-01

Inhalation anthrax is a rare but acute infectious disease following adsorption of Bacillus anthracis spores through the lungs. The disease has a high fatality rate if untreated, but early and correct diagnosis has a significant impact on case patient recovery. The early symptoms of inhalation anthrax are, however, non-specific and current anthrax diagnostics are primarily dependent upon culture and confirmatory real-time PCR. Consequently, there may be a significant delay in diagnosis and targeted treatment. Rapid, culture-independent diagnostic tests are therefore needed, particularly in the context of a large scale emergency response. The aim of this study was to evaluate the ability of monoclonal antibodies to detect anthrax toxin proteins that are secreted early in the course of B. anthracis infection using a time-resolved fluorescence (TRF) immunoassay. We selected monoclonal antibodies that could detect protective antigen (PA), as PA83 and also PA63 and LF in the lethal toxin complex. The assay reliable detection limit (RDL) was 6.63 × 10−6 μM (0.551 ng/ml) for PA83 and 2.51 × 10−5 μM (1.58 ng/ml) for PA63. Despite variable precision and accuracy of the assay, PA was detected in 9 out of 10 sera samples from anthrax confirmed case patients with cutaneous (n=7), inhalation (n=2), and gastrointestinal (n=1) disease. Anthrax Immune Globulin (AIG), which has been used in treatment of clinical anthrax, interfered with detection of PA. This study demonstrates a culture-independent method of diagnosing anthrax through use of monoclonal antibodies to detect PA and LF in the lethal toxin complex. PMID:24857756

High Physical Activity is Associated with an Improved Lipid Profile and Resting Heart Rate among Healthy Middle-aged Chinese People.

PubMed

Hu, Bo; Liu, Xiao Yu; Zheng, Yao; Fan, Hong Min; Yin, Su Feng; Guo, Chun Yue; Li, Yun; Wu, Shou Ling; Feng, Fu Min; Yuan, Ju Xiang

2015-04-01

To investigate the effects of physical activity (PA) on dyslipidemia and elevated resting heart rate (RHR) in a large-scale cross-sectional study in China. We recruited community-based individuals who were 40-60 years old using a cluster sampling method. The PA levels of the participants were classified as low, moderate, or high, using the International Physical Activity Questionnaire. Dyslipidemia was defined as the detection of abnormalities in lipid indicators, and 4 lipid parameters were evaluated using fasting blood samples. Multivariate logistic regression analyses were used to evaluate the associations of PA with dyslipidemia and RHR. A total of 10,321 participants (38.88% men) were included in this study. The percentages of individuals with high, moderate, and low PA levels were 46.5%, 43.9%, and 9.6%, respectively. In both men and women, high PA provided odds ratios of 0.88 [95% confidence interval (CI): 0.83, 0.94] for dyslipidemia and 0.82 (95% CI: 0.73, 0.92) for elevated RHR, compared to participants with low PA. Our data suggested that substantial health benefits (related to dyslipidemia and elevated RHR) occurred at higher intensity PA, with greater energy consumption, in middle-aged Chinese people, and particularly in men. Copyright © 2015 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

PaTrx1 and PaTrx3, Two Cytosolic Thioredoxins of the Filamentous Ascomycete Podospora anserina Involved in Sexual Development and Cell Degeneration▿ †

PubMed Central

Malagnac, Fabienne; Klapholz, Benjamin; Silar, Philippe

2007-01-01

In various organisms, thioredoxins are known to be involved in the reduction of protein disulfide bonds and in protecting the cell from oxidative stress. Genes encoding thioredoxins were found by searching the complete genome sequence of the filamentous ascomycete Podospora anserina. Among them, PaTrx1, PaTrx2, and PaTrx3 are predicted to be canonical cytosolic proteins without additional domains. Targeted disruption of PaTrx1, PaTrx2, and PaTrx3 shows that PaTrx1 is the major thioredoxin involved in sulfur metabolism. Deletions have no effect on peroxide resistance; however, data show that either PaTrx1 or PaTrx3 is necessary for sexual reproduction and for the development of the crippled growth cell degeneration (CG), processes that also required the PaMpk1 mitogen-activated protein kinase (MAPK) pathway. Since PaTrx1 PaTrx3 mutants show not an enhancement but rather an impairment in CG, it seems unlikely that PaTrx1 and PaTrx3 thioredoxins participate in the inhibition of this MAPK pathway. Altogether, these results underscore a role for thioredoxins in fungal development. PMID:17933907

77 FR 27085 - R.R. Donnelley, Inc., Bloomsburg, PA; Notice of Negative Determination on Reconsideration

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-08

... DEPARTMENT OF LABOR Employment and Training Administration [TA-W-80,485] R.R. Donnelley, Inc... workers of R.R. Donnelley, Inc., Bloomsburg, Pennsylvania (subject firm). The Department's Notice of... eligibility to apply for worker adjustment assistance for workers and former workers of R.R. Donnelley, Inc...

Apparatus to measure the vapor pressure of slowly decomposing compounds from 1 Pa to 105 Pa

PubMed Central

Berg, Robert F.

2016-01-01

This article describes an apparatus and method for measuring vapor pressures in the range from 1 Pa to 105 Pa. Its three distinctive elements are : (1) the static pressure measurements were made with only a small temperature difference between the vapor and the condensed phase, (2) the sample was degassed in situ, and (3) the temperature range extended up to 200 °C. The apparatus was designed to measure metal-organic precursors, which often are toxic, pyrophoric, or unstable. Vapor pressures are presented for naphthalene, ferrocene, diethyl phthalate, and TEMAH (tetrakisethylmethylaminohafnium). Also presented are data for the temperature-dependent decomposition rate of TEMAH. PMID:27274567

Proteomic profiling of Pseudomonas aeruginosa AES-1R, PAO1 and PA14 reveals potential virulence determinants associated with a transmissible cystic fibrosis-associated strain.

PubMed

Hare, Nathan J; Solis, Nestor; Harmer, Christopher; Marzook, N Bishara; Rose, Barbara; Harbour, Colin; Crossett, Ben; Manos, Jim; Cordwell, Stuart J

2012-01-22

Pseudomonas aeruginosa is an opportunistic pathogen that is the major cause of morbidity and mortality in patients with cystic fibrosis (CF). While most CF patients are thought to acquire P. aeruginosa from the environment, person-person transmissible strains have been identified in CF clinics worldwide. The molecular basis for transmissibility and colonization of the CF lung remains poorly understood. A dual proteomics approach consisting of gel-based and gel-free comparisons were undertaken to analyse protein profiles in a transmissible, early (acute) isolate of the Australian epidemic strain 1 (AES-1R), the virulent burns/wound isolate PA14, and the poorly virulent, laboratory-associated strain PAO1. Over 1700 P. aeruginosa proteins were confidently identified. AES-1R protein profiles revealed elevated abundance of proteins associated with virulence and siderophore biosynthesis and acquisition, antibiotic resistance and lipopolysaccharide and fatty acid biosynthesis. The most abundant protein in AES-1R was confirmed as a previously hypothetical protein with sequence similarity to carbohydrate-binding proteins and database search revealed this gene is only found in the CF-associated strain PA2192. The link with CF infection may suggest that transmissible strains have acquired an ability to rapidly interact with host mucosal glycoproteins. Our data suggest that AES-1R expresses higher levels of proteins, such as those involved in antibiotic resistance, iron acquisition and virulence that may provide a competitive advantage during early infection in the CF lung. Identification of novel proteins associated with transmissibility and acute infection may aid in deciphering new strategies for intervention to limit P. aeruginosa infections in CF patients.

The influence of physical activity during pregnancy on maternal, fetal or infant heart rate variability: a systematic review.

PubMed

Dietz, Pavel; Watson, Estelle D; Sattler, Matteo C; Ruf, Wolfgang; Titze, Sylvia; van Poppel, Mireille

2016-10-26

Physical activity (PA) during pregnancy has been shown to be associated with several positive effects for mother, fetus, and offspring. Heart rate variability (HRV) is a noninvasive and surrogate marker to determine fetal overall health and the development of fetal autonomic nervous system. In addition, it has been shown to be significantly influenced by maternal behavior. However, the influence of maternal PA on HRV has not yet been systematically reviewed. Therefore, the aim of this systematic review was to assess the influence of regular maternal PA on maternal, fetal or infant HRV. A systematic literature search following a priori formulated criteria of studies that examined the influence of regular maternal PA (assessed for a minimum period of 6 weeks) on maternal, fetal or infant HRV was performed in the databases Pubmed and SPORTDiscus. Quality of each study was assessed using the standardized Quality Assessment Tool for Quantitative Studies (QATQS). Nine articles were included into the present systematic review: two intervention studies, one prospective longitudinal study, and six post-hoc analysis of subsets of the longitudinal study. Of these articles four referred to maternal HRV, five to fetal HRV, and one to infant HRV. The overall global rating for the standardized quality assessment of the articles was moderate to weak. The articles regarding the influence of maternal PA on maternal HRV indicated contrary results. Five of five articles regarding the influence of maternal PA on fetal HRV showed increases of fetal HRV on most parameters depending on maternal PA. The article referring to infant HRV (measured one month postnatal) showed an increased HRV. Based on the current evidence available, our overall conclusion is that the hypothesis that maternal PA influences maternal HRV cannot be supported, but there is a trend that maternal PA might increase fetal and infant HRV (clinical conclusion). Therefore, we recommend that further, high quality studies

miR-143 decreases COX-2 mRNA stability and expression in pancreatic cancer cells

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

Pham, Hung; Department of Medicine, Veterans Affair Greater Los Angeles Healthcare System, Los Angeles, CA 90073; Ekaterina Rodriguez, C.

2013-09-13

Highlights: •Pancreatic cancer cells express low miR-143 levels and elevated p-MEK, p-MAPK and RREB1. •MEK inhibitors U0126 and PD98059 increase miR-143 expression. •miR-143 decreases COX-2 mRNA stability and expression and PGE{sub 2}. •miR-143 decreases p-p38MAPK, p-MEK, p-MAPK and RREB1 expression. -- Abstract: Small non-coding RNAs, microRNAs (miRNA), inhibit the translation or accelerate the degradation of message RNA (mRNA) by targeting the 3′-untranslated region (3′-UTR) in regulating growth and survival through gene suppression. Deregulated miRNA expression contributes to disease progression in several cancers types, including pancreatic cancers (PaCa). PaCa tissues and cells exhibit decreased miRNA, elevated cyclooxygenase (COX)-2 and increased prostaglandinmore » E{sub 2} (PGE{sub 2}) resulting in increased cancer growth and metastases. Human PaCa cell lines were used to demonstrate that restoration of miRNA-143 (miR-143) regulates COX-2 and inhibits cell proliferation. miR-143 were detected at fold levels of 0.41 ± 0.06 in AsPC-1, 0.20 ± 0.05 in Capan-2 and 0.10 ± 0.02 in MIA PaCa-2. miR-143 was not detected in BxPC-3, HPAF-II and Panc-1 which correlated with elevated mitogen-activated kinase (MAPK) and MAPK kinase (MEK) activation. Treatment with 10 μM of MEK inhibitor U0126 or PD98059 increased miR-143, respectively, by 187 ± 18 and 152 ± 26-fold in BxPC-3 and 182 ± 7 and 136 ± 9-fold in HPAF-II. miR-143 transfection diminished COX-2 mRNA stability at 60 min by 2.6 ± 0.3-fold in BxPC-3 and 2.5 ± 0.2-fold in HPAF-II. COX-2 expression and cellular proliferation in BxPC-3 and HPAF-II inversely correlated with increasing miR-143. PGE{sub 2} levels decreased by 39.3 ± 5.0% in BxPC-3 and 48.0 ± 3.0% in HPAF-II transfected with miR-143. Restoration of miR-143 in PaCa cells suppressed of COX-2, PGE{sub 2}, cellular proliferation and MEK/MAPK activation, implicating this pathway in regulating miR-143 expression.« less

Cardiothoracic and Vascular Surgeons Achieve High Rates of K-Award Conversion Into R01 Funding.

PubMed

Narahari, Adishesh K; Mehaffey, J Hunter; Hawkins, Robert B; Baderdinni, Pranav K; Chandrabhatla, Anirudha S; Tribble, Curtis G; Kron, Irving L; Roeser, Mark E; Walters, Dustin M; Ailawadi, Gorav

2018-03-14

Obtaining National Institutes of Health (NIH) R01 funding remains extremely difficult. The utility of career development grants (K awards) for achieving the goal of R01 funding remains debated, particularly for surgeon-scientists. We examined the success rate for cardiothoracic and vascular (CTV) surgeons compared to other specialties in converting K-level grants into R01 equivalents. All K (K08 and K23) grants awarded to surgeons by the NIH between 1992-2017 were identified through NIH RePORTER, an online database combining funding, publications, and patents. Only grants awarded to CTV surgeons were included. Grants active within the past year were excluded. Mann-Whitney U-tests and Chi-squared tests were used to compare groups. A total of 62 K grants awarded to CTV surgeons were identified during this period. Sixteen grants were still active within the last year and excluded from analysis. Twenty-two (48%) of the remaining K awardees successfully transitioned to an R01 or equivalent grant. Awardees with successful conversion published 9 publications per K grant compared to 4 publications for those who did not convert successfully (p=0.01). The median time for successful conversion to an R grant was 5.0 years after the K award start date. Importantly, the 10-year conversion rate to R01 was equal for CTV surgeons compared to other clinician-investigators (52.6% vs 42.5%). CTV surgeons have an equal 10-year conversion rate to first R01 award compared to other clinicians. These data suggest that NIH achieves a good return on investment when funding CTV surgeon-scientists with K-level funding. Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Showing R-Rated Videos in School.

ERIC Educational Resources Information Center

Zirkel, Perry A.

1999-01-01

Since 1990, there have been at least six published court decisions concerning teachers' use of controversial videos in public schools. A relevant district policy led the Colorado Supreme Court to uphold a teacher's termination for showing 12th graders an R-rated 1900 Bertolucci film on fascism. Implications are discussed. (MLH)

230Th and 231Pa: Tracers for Deep Water Circulation and Particle Fluxes in the Arctic Ocean

NASA Astrophysics Data System (ADS)

Valk, O.; Rutgers van der Loeff, M.; Puigcorbe Lacueva, V.; Paffrath, R.; Gdaniec, S.

2016-02-01

230Th and 231Pa data from the central Arctic Ocean is very limited. 230Th and 231Pa are produced at a constant rate in the water column by radioactive decay of Uranium isotopes (234U and 235U respectively) (e.g. Anderson et al., 1983). They are both particle reactive and are scavenged on settling particles. As 230Th is more particle reactive than 231Pa, their distribution in the water column and activity ratio give us information about particle fluxes and circulation patterns and -intensities (Henderson et al., 1999; Scholten et al., 2001). The Arctic Ocean is an almost landlocked ocean with limited connections to the Atlantic and Pacific and a high input of river water. About 10 % of the global river run-off is delivered to the Arctic Ocean. Due to climate change the Arctic Ocean will undergo dramatic changes in sea ice cover and supply of fresh water, while increasing coastal erosion will cause an increased input of terrestrial material (Peterson et al., 2002). This will influence the biogeochemical cycling and transport of carbon, nutrients and trace elements (IPCC, 2007). We expect that the distribution of 230Th and 231Pa will reflect changes in particle fluxes and shelf-basin exchange (Roy-Barman, 2009). We will present the first results of 230Th and 231Pa, in combination with on board measured particulate 234Th, collected during the 2015 Polarstern section (GEOTRACES section GN04 2015) through the Nansen, Amundsen, and Makarov Basins. Anderson, R. F., et al. (1983). EPSL 62: 7-23. Henderson, G. M., et al. (1999). DSR I 46: 1861-1893. IPCC, 2007. Climate Change 2007: The Physical Science Basis. Contribution of Working Group I to the Fourth Assessment Report of the Intergovernmental Panel on Climate Change [Solomon, S. et al.]. Cambridge University Press. Peterson, B. J., et al. (2002). Science 298: 2171-2173. Roy-Barman, M. (2009). Biogeosciences 6: 3091-3107. Scholten, J. C., et al. (2001). DSR II 48: 2383-2408.

Improved antimicrobial activities of synthetic-hybrid bacteriocins designed from enterocin E50-52 and pediocin PA-1.

PubMed

Tiwari, Santosh Kumar; Sutyak Noll, Katia; Cavera, Veronica L; Chikindas, Michael L

2015-03-01

Two hybrid bacteriocins, enterocin E50-52/pediocin PA-1 (EP) and pediocin PA-1/enterocin E50-52 (PE), were designed by combining the N terminus of enterocin E50-52 and the C terminus of pediocin PA-1 and by combining the C terminus of pediocin PA-1 and the N terminus of enterocin E50-52, respectively. Both hybrid bacteriocins showed reduced MICs compared to those of their natural counterparts. The MICs of hybrid PE and EP were 64- and 32-fold lower, respectively, than the MIC of pediocin PA-1 and 8- and 4-fold lower, respectively, than the MIC of enterocin E50-52. In this study, the effect of hybrid as well as wild-type (WT) bacteriocins on the transmembrane electrical potential (ΔΨ) and their ability to induce the efflux of intracellular ATP were investigated. Enterocin E50-52, pediocin PA-1, and hybrid bacteriocin PE were able to dissipate ΔΨ, but EP was unable to deplete this component. Both hybrid bacteriocins caused a loss of the intracellular concentration of ATP. EP, however, caused a faster efflux than PE and enterocin E50-52. Enterocin E50-52 and hybrids PE and EP were active against the Gram-positive and Gram-negative bacteria tested, such as Micrococcus luteus, Salmonella enterica serovar Enteritidis 20E1090, and Escherichia coli O157:H7. The hybrid bacteriocins designed and described herein are antimicrobial peptides with MICs lower those of their natural counterparts. Both hybrid peptides induce the loss of intracellular ATP and are capable of inhibiting Gram-negative bacteria, and PE dissipates the electrical potential. In this study, the MIC of hybrid bacteriocin PE decreased 64-fold compared to the MIC of its natural peptide counterpart, pediocin PA-1. Inhibition of Gram-negative pathogens confers an additional advantage for the application of these peptides in therapeutics. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Improved Antimicrobial Activities of Synthetic-Hybrid Bacteriocins Designed from Enterocin E50-52 and Pediocin PA-1

PubMed Central

Tiwari, Santosh Kumar; Sutyak Noll, Katia; Cavera, Veronica L.

2014-01-01

Two hybrid bacteriocins, enterocin E50-52/pediocin PA-1 (EP) and pediocin PA-1/enterocin E50-52 (PE), were designed by combining the N terminus of enterocin E50-52 and the C terminus of pediocin PA-1 and by combining the C terminus of pediocin PA-1 and the N terminus of enterocin E50-52, respectively. Both hybrid bacteriocins showed reduced MICs compared to those of their natural counterparts. The MICs of hybrid PE and EP were 64- and 32-fold lower, respectively, than the MIC of pediocin PA-1 and 8- and 4-fold lower, respectively, than the MIC of enterocin E50-52. In this study, the effect of hybrid as well as wild-type (WT) bacteriocins on the transmembrane electrical potential (ΔΨ) and their ability to induce the efflux of intracellular ATP were investigated. Enterocin E50-52, pediocin PA-1, and hybrid bacteriocin PE were able to dissipate ΔΨ, but EP was unable to deplete this component. Both hybrid bacteriocins caused a loss of the intracellular concentration of ATP. EP, however, caused a faster efflux than PE and enterocin E50-52. Enterocin E50-52 and hybrids PE and EP were active against the Gram-positive and Gram-negative bacteria tested, such as Micrococcus luteus, Salmonella enterica serovar Enteritidis 20E1090, and Escherichia coli O157:H7. The hybrid bacteriocins designed and described herein are antimicrobial peptides with MICs lower those of their natural counterparts. Both hybrid peptides induce the loss of intracellular ATP and are capable of inhibiting Gram-negative bacteria, and PE dissipates the electrical potential. In this study, the MIC of hybrid bacteriocin PE decreased 64-fold compared to the MIC of its natural peptide counterpart, pediocin PA-1. Inhibition of Gram-negative pathogens confers an additional advantage for the application of these peptides in therapeutics. PMID:25527560

The improved physical activity index for measuring physical activity in EPIC Germany.

PubMed

Wientzek, Angelika; Vigl, Matthäus; Steindorf, Karen; Brühmann, Boris; Bergmann, Manuela M; Harttig, Ulrich; Katzke, Verena; Kaaks, Rudolf; Boeing, Heiner

2014-01-01

In the European Investigation into Cancer and Nutrition study (EPIC), physical activity (PA) has been indexed as a cross-tabulation between PA at work and recreational activity. As the proportion of non-working participants increases, other categorization strategies are needed. Therefore, our aim was to develop a valid PA index for this population, which will also be able to express PA continuously. In the German EPIC centers Potsdam and Heidelberg, a clustered sample of 3,766 participants was re-invited to the study center. 1,615 participants agreed to participate and 1,344 participants were finally included in this study. PA was measured by questionnaires on defined activities and a 7-day combined heart rate and acceleration sensor. In a training sample of 433 participants, the Improved Physical Activity Index (IPAI) was developed. Its performance was evaluated in a validation sample of 911 participants and compared with the Cambridge Index and the Total PA Index. The IPAI consists of items covering five areas including PA at work, sport, cycling, television viewing, and computer use. The correlations of the IPAI with accelerometer counts in the training and validation sample ranged r = 0.40-0.43 and with physical activity energy expenditure (PAEE) r = 0.33-0.40 and were higher than for the Cambridge Index and the Total PA Index previously applied in EPIC. In non-working participants the IPAI showed higher correlations than the Cambridge Index and the Total PA Index, with r = 0.34 for accelerometer counts and r = 0.29 for PAEE. In conclusion, we developed a valid physical activity index which is able to express PA continuously as well as to categorize participants according to their PA level. In populations with increasing rates of non-working people the performance of the IPAI is better than the established indices used in EPIC.

Proteomic profiling of Pseudomonas aeruginosa AES-1R, PAO1 and PA14 reveals potential virulence determinants associated with a transmissible cystic fibrosis-associated strain

PubMed Central

2012-01-01

Background Pseudomonas aeruginosa is an opportunistic pathogen that is the major cause of morbidity and mortality in patients with cystic fibrosis (CF). While most CF patients are thought to acquire P. aeruginosa from the environment, person-person transmissible strains have been identified in CF clinics worldwide. The molecular basis for transmissibility and colonization of the CF lung remains poorly understood. Results A dual proteomics approach consisting of gel-based and gel-free comparisons were undertaken to analyse protein profiles in a transmissible, early (acute) isolate of the Australian epidemic strain 1 (AES-1R), the virulent burns/wound isolate PA14, and the poorly virulent, laboratory-associated strain PAO1. Over 1700 P. aeruginosa proteins were confidently identified. AES-1R protein profiles revealed elevated abundance of proteins associated with virulence and siderophore biosynthesis and acquisition, antibiotic resistance and lipopolysaccharide and fatty acid biosynthesis. The most abundant protein in AES-1R was confirmed as a previously hypothetical protein with sequence similarity to carbohydrate-binding proteins and database search revealed this gene is only found in the CF-associated strain PA2192. The link with CF infection may suggest that transmissible strains have acquired an ability to rapidly interact with host mucosal glycoproteins. Conclusions Our data suggest that AES-1R expresses higher levels of proteins, such as those involved in antibiotic resistance, iron acquisition and virulence that may provide a competitive advantage during early infection in the CF lung. Identification of novel proteins associated with transmissibility and acute infection may aid in deciphering new strategies for intervention to limit P. aeruginosa infections in CF patients. PMID:22264352

TMPRSS4 induces cancer cell invasion through pro-uPA processing.

PubMed

Min, Hye-Jin; Lee, Myung Kyu; Lee, Jung Weon; Kim, Semi

2014-03-28

TMPRSS4 is a novel type II transmembrane serine protease that is highly expressed on the cell surface in pancreatic, thyroid, colon, and other cancer tissues. Previously, we demonstrated that TMPRSS4 mediates cancer cell invasion, epithelial-mesenchymal transition, and metastasis and that increased TMPRSS4 expression correlates with colorectal cancer progression. We also demonstrated that TMPRSS4 upregulates urokinase-type plasminogen activator (uPA) gene expression to induce cancer cell invasion. However, it remains unknown how proteolytic activity of TMPRSS4 contributes to invasion. In this study, we report that TMPRSS4 directly converted inactive pro-uPA into the active form through its proteolytic activity. Analysis of conditioned medium from cells overexpressing TMPRSS4 demonstrated that the active TMPRSS4 protease domain is released from the cells and is associated with the plasma membrane. Furthermore, TMPRSS4 could increase pro-uPA-mediated invasion in a serine proteolytic activity-dependent manner. These observations suggest that TMPRSS4 is an upstream regulator of pro-uPA activation. This study provides valuable insights into the proteolytic function of TMPRSS4 as well as mechanisms for the control of invasion. Copyright © 2014 Elsevier Inc. All rights reserved.

Social safety, self-rated general health and physical activity: changes in area crime, area safety feelings and the role of social cohesion.

PubMed

Ruijsbroek, Annemarie; Droomers, Mariël; Groenewegen, Peter P; Hardyns, Wim; Stronks, Karien

2015-01-01

The aim of this study was to examine whether changes over time in reported area crime and perceived area safety were related to self-rated general health and physical activity (PA), in order to provide support for a causal relationship between social safety and health. Additionally, we investigated whether social cohesion protects the residents against the negative impact of unsafe areas on health and PA. Multilevel logistic regression analyses were performed on Dutch survey data, including 47,926 respondents living in 2974 areas. An increase in area level unsafety feelings between 2009 and 2011 was associated with more people reporting poor general health in 2012 in that area, but was not related to PA. Changes in reported area crime were not related to either poor general health or PA. The social cohesion in the area did not modify the effect of changes in social safety on health and PA. The results suggest that tackling feelings of unsafety in an area might contribute to the better general health of the residents. Because changes in area social safety were not associated with PA, we found no leads that such health benefits were achieved through an increase in physical activity. Copyright © 2014 Elsevier Ltd. All rights reserved.

Selective retension of active cells employing low centrifugal force at the medium change during suspension culture of Chinese hamster ovary cells producing tPA.

PubMed

Takagi, M; Ilias, M; Yoshida, T

2000-01-01

The effect of centrifugal force applied for cell separation at the medium change on the growth, metabolism and tissue plasminogen activator (tPA) productivity of Chinese hamster ovary (CHO) cells suspension culture was investigated. The viability of the precipitated cells increased exponentially as the centrifugal force decreased. However, the cell recovery was lower than 91% when centrifugal forces applied for 5 min was less than 67 x g. In cultures incubated for 474 h with 7 medium changes employing centrifugal forces ranging from 67 to 364 x g, a centrifugal force lower than 119 x g resulted in higher specific rates of growth, glucose consumption, and lactate and tPA production during the whole culture period. On the other hand, daily centrifugation at 67 to 537 x g without discarding the supernatant had no effect on the specific rates. The cultures inoculated with cells precipitated at a centrifugal force of 67 x g showed apparently higher specific rates of metabolism compared to those inoculated with cells in the supernatant. The cells in the supernatant and the precipitate obtained following centrifugation at 67 x g have average diameters of 15.5 and 17.4 microm, respectively. The intracellular contents of amino acids, especially nonessential amino acids, of the precipitated cells were markedly higher than those of the cells in the supernatant. These results indicate that large cells with high amino acid content and metabolic activity were selectively retained in the culture by means of centrifugation at low forces such as 67 x g. Consequently, application of a low centrifugal force is recommended for medium change in order to maintain higher specific productivity of suspended mammalian cells in perfusion culture.

RIVERBANK AND MEADOW, LOOKING SOUTHEAST. PA148 AND PA149 CAN BE ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

RIVERBANK AND MEADOW, LOOKING SOUTHEAST. PA-1-48 AND PA-1-49 CAN BE PAIRED TO FORM A PANORAMA SHOWING THE RELATIONSHIP BETWEEN THE RIVERBANK AND THE MEADOW - John Bartram House & Garden, 54th Street & Lindbergh Boulevard, Philadelphia, Philadelphia County, PA

How can we improve stroke thrombolysis rates? A review of health system factors and approaches associated with thrombolysis administration rates in acute stroke care.

PubMed

Paul, Christine L; Ryan, Annika; Rose, Shiho; Attia, John R; Kerr, Erin; Koller, Claudia; Levi, Christopher R

2016-04-08

Thrombolysis using intravenous (IV) tissue plasminogen activator (tPA) is one of few evidence-based acute stroke treatments, yet achieving high rates of IV tPA delivery has been problematic. The 4.5-h treatment window, the complexity of determining eligibility criteria and the availability of expertise and required resources may impact on treatment rates, with barriers encountered at the levels of the individual clinician, the social context and the health system itself. The review aimed to describe health system factors associated with higher rates of IV tPA administration for ischemic stroke and to identify whether system-focussed interventions increased tPA rates for ischemic stroke. Published original English-language research from four electronic databases spanning 1997-2014 was examined. Observational studies of the association between health system factors and tPA rates were described separately from studies of system-focussed intervention strategies aiming to increase tPA rates. Where study outcomes were sufficiently similar, a pooled meta-analysis of outcomes was conducted. Forty-one articles met the inclusion criteria: 7 were methodologically rigorous interventions that met the Cochrane Collaboration Evidence for Practice and Organization of Care (EPOC) study design guidelines and 34 described observed associations between health system factors and rates of IV tPA. System-related factors generally associated with higher IV tPA rates were as follows: urban location, centralised or hub and spoke models, treatment by a neurologist/stroke nurse, in a neurology department/stroke unit or teaching hospital, being admitted by ambulance or mobile team and stroke-specific protocols. Results of the intervention studies suggest that telemedicine approaches did not consistently increase IV tPA rates. Quality improvement strategies appear able to provide modest increases in stroke thrombolysis (pooled odds ratio = 2.1, p = 0.05). In order to improve IV tPA rates in

Physical Activity and Health Beliefs among Saudi Women

PubMed Central

Al-Eisa, Einas S.; Al-Sobayel, Hana I.

2012-01-01

Background. Physical activity (PA) is associated with health benefits and disease prevention and is often prescribed in managing many health conditions. Understanding the cultural influences is relevant in order to effectively promote PA. The objective of this study was to assess the level of PA among Saudi women, measured by daily step count, and the association between PA and health beliefs. Methods. A total of 161 eligible participants were asked to complete two questionnaires to assess health beliefs: Health Locus of Control (HLC) and Self-Efficacy Assessment Scale. Each participant was given a pedometer and a diary to record their daily PA for two weeks. Results. One hundred and five participants completed the two weeks pedometer data (mean age 26.3 ± 7.1 years, BMI 25 ± 4.2 kg/m2). The average pedometer score over two weeks was 5114 ± 2213 steps. Step count had strong correlation with self-efficacy (r s = 0.75), mild correlation with internal HLC (r s = 0.42), and mild negative correlation with external HLC (r s = −0.35). Conclusion. The study demonstrates high level of inactivity among Saudi females in reference to the international recommendation for minimum activity. The data also reveal an association between PA and health beliefs. Ultimately, such information can be used to design gender- and culture-sensitive interventions that could enhance adherence to PA. PMID:22523673

Crystal structure of the flavoenzyme PA4991 from Pseudomonas aeruginosa

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

Jacewicz, Agata; Schnell, Robert; Lindqvist, Ylva

PA4991 is a FAD-dependent oxidoreductase from the pathogen P. aeruginosa that is essential for virulence and survival in the infected host. The structure of this enzyme, determined to 2.4 Å resolution, reveals that PA4991 belongs to the GR{sub 2} family of flavoenzymes. The locus PA4991 in Pseudomonas aeruginosa encodes an open reading frame that has been identified as essential for the virulence and/or survival of this pathogenic organism in the infected host. Here, it is shown that this gene encodes a monomeric FAD-binding protein of molecular mass 42.2 kDa. The structure of PA4991 was determined by a combination of molecularmore » replacement using a search model generated with Rosetta and phase improvement by a low-occupancy heavy-metal derivative. PA4991 belongs to the GR{sub 2} family of FAD-dependent oxidoreductases, comprising an FAD-binding domain typical of the glutathione reductase family and a second domain dominated by an eight-stranded mixed β-sheet. Most of the protein–FAD interactions are via the FAD-binding domain, but the isoalloxazine ring is located at the domain interface and interacts with residues from both domains. A comparison with the structurally related glycine oxidase and glycerol-3-phosphate dehydrogenase shows that in spite of very low amino-acid sequence identity (<18%) several active-site residues involved in substrate binding in these enzymes are conserved in PA4991. However, enzymatic assays show that PA4991 does not display amino-acid oxidase or glycerol-3-phosphate dehydrogenase activities, suggesting that it requires different substrates for activity.« less

Examining the reliability and validity of a modified version of the International Physical Activity Questionnaire, long form (IPAQ-LF) in Nigeria: a cross-sectional study.

PubMed

Oyeyemi, Adewale L; Bello, Umar M; Philemon, Saratu T; Aliyu, Habeeb N; Majidadi, Rebecca W; Oyeyemi, Adetoyeje Y

2014-12-01

To investigate the reliability and an aspect of validity of a modified version of the long International Physical Activity Questionnaire (Hausa IPAQ-LF) in Nigeria. Cross-sectional study, examining the reliability and construct validity of the Hausa IPAQ-LF compared with anthropometric and biological variables. Metropolitan Maiduguri, the capital city of Borno State in Nigeria. 180 Nigerian adults (50% women) with a mean age of 35.6 (SD=10.3) years, recruited from neighbourhoods with diverse socioeconomic status and walkability. Domains (domestic physical activity (PA), occupational PA, leisure-time PA, active transportation and sitting time) and intensities of PA (vigorous, moderate and walking) were measured with the Hausa IPAQ-LF on two different occasions, 8 days apart. Outcomes for construct validity were measured body mass index (BMI), systolic blood pressure (SBP) and diastolic blood pressure (DBP). The Hausa IPAQ-LF demonstrated good test-retest reliability (intraclass correlation coefficient, ICC>75) for total PA (ICC=0.79, 95% CI 0.65 to 0.82), occupational PA (ICC=0.77, 95% CI 0.68 to 0.82), active transportation (ICC=0.82, 95% CI 0.75 to 0.87) and vigorous intensity activities (ICC=0.82, 95% CI 0.76 to 0.87). Reliability was substantially higher for total PA (ICC=0.80), occupational PA (ICC=0.78), leisure-time PA (ICC=0.75) and active transportation (ICC=0.80) in men than in women, but domestic PA (ICC=0.38) and sitting time (ICC=0.71) demonstrated more substantial reliability coefficients in women than in men. For the construct validity, domestic PA was significantly related mainly with SBP (r=-0.27) and DBP (r=-0.17), and leisure-time PA and total PA were significantly related only with SBP (r=-0.16) and BMI (r=-0.29), respectively. Similarly, moderate-intensity PA was mainly related with SBP (r=-0.16, p<0.05) and DBP (r=-0.21, p<0.01), but vigorous-intensity PA was only related with BMI (r=-0.11, p<0.05). The modified Hausa IPAQ-LF demonstrated

Screening Physical Activity in Family Practice: Validity of the Spanish Version of a Brief Physical Activity Questionnaire.

PubMed

Puig-Ribera, Anna; Martín-Cantera, Carlos; Puigdomenech, Elisa; Real, Jordi; Romaguera, Montserrat; Magdalena-Belio, José Félix; Recio-Rodríguez, Jose Ignacio; Rodriguez-Martin, Beatriz; Arietaleanizbeaskoa, Maria Soledad; Repiso-Gento, Irene; Garcia-Ortiz, Luis

2015-01-01

The use of brief screening tools to identify inactive patients is essential to improve the efficiency of primary care-based physical activity (PA) programs. However, the current employment of short PA questionnaires within the Spanish primary care pathway is unclear. This study evaluated the validity of the Spanish version of a Brief Physical Activity Assessment Tool (SBPAAT). A validation study was carried out within the EVIDENT project. A convenience sample of patients (n = 1,184; age 58.9±13.7 years; 60.5% female) completed the SBPAAT and the 7-day Physical Activity Recall (7DPAR) and, in addition, wore an accelerometer (ActiGraph GT3X) for seven consecutive days. Validity was evaluated by measuring agreement, Kappa correlation coefficients, sensitivity and specificity in achieving current PA recommendations with the 7DPAR. Pearson correlation coefficients with the number of daily minutes engaged in moderate and vigorous intensity PA according to the accelerometer were also assessed. Comparison with accelerometer counts, daily minutes engaged in sedentary, light, moderate, and vigorous intensity PA, total daily kilocalories, and total PA and leisure time expenditure (METs-hour-week) between the sufficiently and insufficiently active groups identified by SBPAAT were reported. The SBPAAT identified 41.3% sufficiently active (n = 489) and 58.7% insufficiently active (n = 695) patients; it showed moderate validity (k = 0.454, 95% CI: 0.402-0.505) and a specificity and sensitivity of 74.3% and 74.6%, respectively. Validity was fair for identifying daily minutes engaged in moderate (r = 0.215, 95% CI:0.156 to 0.272) and vigorous PA (r = 0.282, 95% CI:0.165 to 0.391). Insufficiently active patients according to the SBPAAT significantly reported fewer counts/minute (-22%), fewer minutes/day of moderate (-11.38) and vigorous PA (-2.69), spent fewer total kilocalories/day (-753), and reported a lower energy cost (METs-hour-week) of physical activities globally (-26

Peach MYB7 activates transcription of the proanthocyanidin pathway gene encoding leucoanthocyanidin reductase, but not anthocyanidin reductase

PubMed Central

Zhou, Hui; Lin-Wang, Kui; Liao, Liao; Gu, Chao; Lu, Ziqi; Allan, Andrew C.; Han, Yuepeng

2015-01-01

Proanthocyanidins (PAs) are a group of natural phenolic compounds that have a great effect on both flavor and nutritious value of fruit. It has been shown that PA synthesis is regulated by R2R3-MYB transcription factors (TFs) via activation of PA-specific pathway genes encoding leucoanthocyanidin reductase and anthocyanidin reductase. Here, we report the isolation and characterization of a MYB gene designated PpMYB7 in peach. The peach PpMYB7 represents a new group of R2R3-MYB genes regulating PA synthesis in plants. It is able to activate transcription of PpLAR1 but not PpANR, and has a broader selection of potential bHLH partners compared with PpMYBPA1. Transcription of PpMYB7 can be activated by the peach basic leucine-zipper 5 TF (PpbZIP5) via response to ABA. Our study suggests a transcriptional network regulating PA synthesis in peach, with the results aiding the understanding of the functional divergence between R2R3-MYB TFs in plants. PMID:26579158

tPA variant tPA-A296-299 Prevents impairment of cerebral autoregulation and necrosis of hippocampal neurons after stroke by inhibiting upregulation of ET-1.

PubMed

Armstead, William M; Hekierski, Hugh; Yarovoi, Serge; Higazi, Abd Al-Roof; Cines, Douglas B

2018-01-01

Tissue-type plasminogen activator (tPA) is neurotoxic and exacerbates uncoupling of cerebral blood flow (CBF) and metabolism after stroke, yet it remains the sole FDA-approved drug for treatment of ischemic stroke. Upregulation of c-Jun-terminal kinase (JNK) after stroke contributes to tPA-mediated impairment of autoregulation, but the role of endothelin-1 (ET-1) is unknown. Based on the Glasgow Coma Scale, impaired autoregulation is linked to adverse outcomes after TBI, but correlation with hippocampal histopathology after stroke has not been established. We propose that given after stroke, tPA activates N-Methyl-D-Aspartate receptors (NMDA-Rs) and upregulates ET-1 in a JNK dependent manner, imparing autoregulation and leading to histopathology. After stroke, CBF was reduced in the hippocampus and reduced further during hypotension, which did not occur in hypotensive sham pigs, indicating impairment of autoregulation. Autoregulation and necrosis of hippocampal CA1 and CA3 neurons were further impaired by tPA, but were preserved by the ET-1 antagonist BQ 123 and tPA-A, 296-299 a variant that is fibrinolytic but does not bind to NMDA-Rs. Expression of ET-1 was increased by stroke and potentiated by tPA but returned to sham levels by tPA-A 296-299 and the JNK antagonist SP600125. Results show that JNK releases ET-1 after stroke. Tissue-type plasminogen activator -A 296-299 prevents impairment of cerebral autoregulation and histopathology after stroke by inhibiting upregulation of ET-1. © 2017 Wiley Periodicals, Inc.

Selective vibration sensing: a new concept for activity-sensing rate-responsive pacing.

PubMed

Lau, C P; Stott, J R; Toff, W D; Zetlein, M B; Ward, D E; Camm, A J

1988-09-01

A clinically available model of an activity-sensing, rate-responsive pacemaker (Activitrax, Medtronic) utilizes body vibration during exercise as an indicator of the need for a rate increase. Although having the advantage of rapid onset of rate response, this system lacks specificity and the rate response does not closely correlate with the level of exertion. In addition, this pacemaker is susceptible to the effects of extraneous vibration. In this study involving 20 normal subjects fitted with an external Activitrax pacemaker, the rate responses to a variety of exercises were studied and were compared with the corresponding sinus rates. The vibration generated at the level of the pacemaker was also measured by accelerometers in three axes. Only a fair correlation (r = 0.51) was achieved between the pacemaker rate and the sinus rate. The total root mean square value of acceleration in either the anteroposterior or the vertical axes was found to have a better correlation (r = 0.8). As the main accelerations during physical activities were in the lower frequency range (0.1-4 Hz), a low-pass filter was used to reduce the influence of extraneous vibration. Selective sensing of the acceleration level may be usefully implemented in an algorithm for activity pacing.

32 CFR 701.123 - PA fees.

Code of Federal Regulations, 2010 CFR

2010-07-01

... duplication for free. (1) DON activities shall waive fees automatically if the direct cost for reproduction of... made on a case-to-case basis. (c) PA fee deposits. Checks or money orders shall be made payable to the...

32 CFR 701.123 - PA fees.

Code of Federal Regulations, 2012 CFR

2012-07-01

... duplication for free. (1) DON activities shall waive fees automatically if the direct cost for reproduction of... made on a case-to-case basis. (c) PA fee deposits. Checks or money orders shall be made payable to the...

32 CFR 701.123 - PA fees.

Code of Federal Regulations, 2013 CFR

2013-07-01

... duplication for free. (1) DON activities shall waive fees automatically if the direct cost for reproduction of... made on a case-to-case basis. (c) PA fee deposits. Checks or money orders shall be made payable to the...

32 CFR 701.123 - PA fees.

Code of Federal Regulations, 2014 CFR

2014-07-01

... duplication for free. (1) DON activities shall waive fees automatically if the direct cost for reproduction of... made on a case-to-case basis. (c) PA fee deposits. Checks or money orders shall be made payable to the...

32 CFR 701.123 - PA fees.

Code of Federal Regulations, 2011 CFR

2011-07-01

... duplication for free. (1) DON activities shall waive fees automatically if the direct cost for reproduction of... made on a case-to-case basis. (c) PA fee deposits. Checks or money orders shall be made payable to the...

A novel clot lysis assay for recombinant plasminogen activator.

PubMed

Jamialahmadi, Oveis; Fazeli, Ahmad; Hashemi-Najafabadi, Sameereh; Fazeli, Mohammad Reza

2015-03-01

Recombinant plasminogen activator (r-PA, reteplase) is an engineered variant of alteplase. When expressed in E. coli, it appears as inclusion bodies that require refolding to recover its biological activity. An important step following refolding is to determine the activity of refolded protein. Current methods for enzymatic activity of thrombolytic drugs are costly and complex. Here a straightforward and low-cost clot lysis assay was developed. It quantitatively measures the activity of the commercial reteplase and is also capable of screening refolding conditions. As evidence for adequate accuracy and sensitivity of the current assay, r-PA activity measurements are shown to be comparable to those obtained from chromogenic substrate assay.

Physical activity, stress, and metabolic risk score in 8- to 18-year-old boys.

PubMed

Holmes, Megan E; Eisenmann, Joey C; Ekkekakis, Panteleimon; Gentile, Douglas

2008-03-01

We examined whether physical activity modifies the relationship between stress and the metabolic risk score in 8- to 18-year-old males (n = 37). Physical activity (PA) and television (TV)/videogame (VG) use were assessed via accelerometer and questionnaire, respectively. Stress was determined from self-report measures. A metabolic risk score (MRS) was created by summing age-standardized residuals for waist circumference, mean arterial pressure, glycosylated hemoglobin, and high-density lipoprotein cholesterol. Correlations between PA and MRS were low (r < -.13), and TV and VG were moderately associated with MRS (r = .39 and .43, respectively). Correlations between stress-related variables and MRS ranged from r = .19 to .64. After partitioning by PA, significant correlations were observed in the low PA group between school- and sports-related self-esteem and anxiety with the MRS. The results provide suggestive evidence that PA might modify the relationship between stress and MRS in male adolescents.

Association of Smoking Onset With R-Rated Movie Restrictions and Adolescent Sensation Seeking

PubMed Central

Sargent, James D.; Stoolmiller, Mike; Scholte, Ron H. J.; Engels, Rutger C. M. E.; Tanski, Susanne E.

2011-01-01

OBJECTIVES: In this study, we examined how often US youths reported having complete parental restrictions on watching R-rated movies. In addition, we assessed the relationship between parental R-rated movie restrictions and adolescents' sensation seeking and how this interplay is related to smoking onset. METHODS: Data from a 4-wave longitudinal study of 6522 adolescents (10–14 years of age) who were recruited through a random-digit-dial telephone survey were used. At baseline, subjects were nationally representative of the US population. Subjects were monitored for 2 years and queried about their smoking status, their sensation-seeking propensity, and how often they were allowed to watch R-rated movies. A cross-lagged model combined with survival analysis was used to assess the relationships between parental R-rated movie restrictions, sensation-seeking propensity, and risk for smoking onset. RESULTS: Findings demonstrated that 32% of the US adolescents reported being completely restricted from watching R-rated movies by their parents. Model findings revealed that adolescents' sensation seeking was related to greater risk for smoking onset not only directly but also indirectly through their parents becoming more permissive of R-rated movie viewing. Parental R-rated movie restrictions were found to decrease the risk of smoking onset directly and indirectly by changing children's sensation seeking. CONCLUSIONS: These findings imply that, beyond direct influences, the relationship between adolescents' sensation seeking and parental R-rated movie restrictions in explaining smoking onset is bidirectional in nature. Finally, these findings highlight the relevance of motivating and supporting parents in limiting access to R-rated movies. PMID:21135004

Familial resemblance of body composition, physical activity, and resting metabolic rate in pre-school children

PubMed Central

Djafarian, Kurosh; Speakman, John R; Stewart, Joanne; M Jackson, Diane

2013-01-01

Background: Although parental obesity is a well-established predisposing factor for the development of obesity, associations between regional body compositions, resting metabolic rates (RMR), and physical activity (PA) of parents and their pre-school children remain unknown. The objective of this study was to investigate parent-child correlations for total and regional body compositions, resting energy expenditures, and physical activity. Methods: Participants were 89 children aged 2-6 years and their parents, consisting of 61 families. Resting metabolic rate was assessed using indirect calorimetry. Total and regional body compositions were measured by both dual energy X-ray absorptiometry (DXA) and deuterium dilution. Physical activity was assessed by an accelerometer. Results: There was a significant parent-offspring regression for total fat free mass (FFM) between children and their mothers (P=0.02), fathers (P=0.02), and mid-parent (average of father and mother value) (P=0.002) when measured by DXA. The same was true for fat mass (FM) between children and mothers (P<0.01), fathers (P=0.02), and mid-parent (P=0.001). There was no significant association between children and parents for physical activity during the entire week, weekend, weekdays, and different parts of days, except for morning activity, which was positively related to the mothers’ morning activities (P<0.01) and mid-parent (P=0.009). No association was found between RMR of children and parents before and after correction for FFM and FM. Conclusion: These data suggest a familial resemblance for total body composition between children and their parents. Our data showed no familial resemblance for PA and RMR between children and their parents. PMID:26989715

Effect of low frequency ultrasound on combined rt-PA and eptifibatide thrombolysis in human clots.

PubMed

Meunier, Jason M; Holland, Christy K; Pancioli, Arthur M; Lindsell, Christopher J; Shaw, George J

2009-01-01

Fibrinolytics such as recombinant tissue plasminogen activator (rt-PA) are used to treat thrombotic disease such as acute myocardial infarction (AMI) and ischemic stroke. Interest in increasing efficacy and reducing side effects has led to the study of adjuncts such as GP IIb-IIIa inhibitors and ultrasound (US) enhanced thrombolysis. Currently, GP IIb-IIIa inhibitor and fibrinolytic treatment are often used in AMI, and are under investigation for stroke treatment. However, little is known of the efficacy of combined GP IIb-IIIa inhibitor, fibrinolytic and ultrasound treatment. We measure the lytic efficacy of rt-PA, eptifibatide (Epf) and 120 kHz ultrasound treatment in an in-vitro human clot model. Blood was drawn from 15 subjects after IRB approval. Clots were made in 20 microL pipettes, and placed in a water tank for microscopic visualization during lytic treatment. Clots were exposed to control, rt-PA (rt-PA), eptifibatide (Epf), or rt-PA+eptifibatide (rt-PA + Epf), with (+US) or without (-US) ultrasound for 30 minutes at 37 degrees C in human plasma. Clot lysis was measured over time, using a microscopic imaging technique. The fractional clot loss (FCL) and initial lytic rate (LR) were used to quantify lytic efficacy. LR values for (- US) treated clots were 0.8+/-0.1(control), 1.8+/-0.3 (Epf), 1.5+/-0.2 (rt-PA), and 1.3+/-0.4 (rt-PA + Epf) (% clot width/minute) respectively. In comparison, the (+ US) group exhibited LR values of 1.6+/-0.2 (control), 4.3+/-0.4 (Epf), 6.3+/-0.4 (rt-PA), and 4.6+/-0.6 (rt-PA + Epf). For (- US) treated clots, FCL was 6.0+/-0.8 (control), 9.2+/-2.5 (Epf), 15.6+/-1.7 (rt-PA), and 28.0+/-2.2% (rt-PA + Epf) respectively. FCL for (+ US) clots was 13.5+/-2.4 (control), 20.7+/-6.4 (Epf), 44.4+/-3.6 (rt-PA) and 30.3+/-3.6% (rt-PA + Epf) respectively. Although the addition of eptifibatide enhances the in-vitro lytic efficacy of rt-PA in the absence of ultrasound, the efficacy of ultrasound and rt-PA is greater than that of combined

Regulated expression of a repressor protein: FadR activates iclR.

PubMed Central

Gui, L; Sunnarborg, A; LaPorte, D C

1996-01-01

The control of the glyoxylate bypass operon (aceBAK) of Escherichia coli is mediated by two regulatory proteins, IclMR and FadR. IclMR is a repressor protein which has previously been shown to bind to a site which overlaps the aceBAK promoter. FAR is a repressor/activator protein which participates in control of the genes of fatty acid metabolism. A sequence just upstream of the iclR promoter bears a striking resemblance to FadR binding sites found in the fatty acid metabolic genes. The in vitro binding specificity of FadR, determined by oligonucleotide selection, was in good agreement with the sequences of these sites. The ability of FadR to bind to the site associated with iclR was demonstrated by gel shift and DNase I footprint analyses. Disruption of FadR or inactivation of the FadR binding site of iclR decreased the expression of an iclR::lacZ operon fusion, indicating that FadR activates the expression of iclR. It has been reported that disruption of fadR increases the expression of aceBAK. We observed a similar increase when we inactivated the FadR binding site of an iclR+ allele. This result suggests that FadR regulates aceBAK indirectly by altering the expression of IclR. PMID:8755903

Acute Effects of a Therapeutic Mobility Device on Physical Activity and Heart Rate in Children with Down Syndrome

ERIC Educational Resources Information Center

Hauck, Janet L.; Ulrich, Dale A.

2015-01-01

Purpose: The purpose of this feasibility study was to provide an opportunity to increase physical activity (PA) and heart rate (HR) for children with Down syndrome (DS) during unstructured group exercise utilizing a riding device called the Power Pumper®. Method: Twenty-four children aged 5 to 7 years old participated in this case-control study,…

Physical activity in older adults in a combined functional circuit and walking program.

PubMed

Gallagher, Nancy Ambrose; Clarke, Philippa; Carr, Emily

Our study examined the impact of a 16-week functional circuit/walking program on physical activity (PA) in older adults in independent-living facilities. Exploratory goals included examination of associations among self-efficacy, neighborhood and mobility. Participants (N = 13) were female (M = 77.8, SD = 7.44, range = 65-85 years). One third were African-American; the remainder Caucasian; 1/3 used assistive devices. PA increased from 70 min/week (SD = 35.51) at baseline to 81.31 min/week (SD = 34.21) at 16 weeks. PA was associated with self-efficacy for overcoming neighborhood and facility barriers to walking at all measurement points (baseline r = .73, p < .05 and r = .68, p < .05, respectively). At eight weeks, PA was associated with self-efficacy for walking duration (r = .58, p < .05), self-efficacy for individual (r = .66, p < .05), facility (r = .58, p < .05) and neighborhood (r = .70, p < .05) barriers. At sixteen weeks, physical activity was associated with balance confidence (r = .72, p < .05), and self-efficacy for individual (r = .76, p < .05), facility (r = .71, p < .05), and neighborhood (r = .80, p < .01) barriers. Functional circuit/walking interventions can increase PA in older adults. Further examination of self-efficacy, mobility, neighborhoods and PA is needed. Copyright © 2016 Elsevier Inc. All rights reserved.

The Improved Physical Activity Index for Measuring Physical Activity in EPIC Germany

PubMed Central

Wientzek, Angelika; Vigl, Matthäus; Steindorf, Karen; Brühmann, Boris; Bergmann, Manuela M.; Harttig, Ulrich; Katzke, Verena; Kaaks, Rudolf; Boeing, Heiner

2014-01-01

In the European Investigation into Cancer and Nutrition study (EPIC), physical activity (PA) has been indexed as a cross-tabulation between PA at work and recreational activity. As the proportion of non-working participants increases, other categorization strategies are needed. Therefore, our aim was to develop a valid PA index for this population, which will also be able to express PA continuously. In the German EPIC centers Potsdam and Heidelberg, a clustered sample of 3,766 participants was re-invited to the study center. 1,615 participants agreed to participate and 1,344 participants were finally included in this study. PA was measured by questionnaires on defined activities and a 7-day combined heart rate and acceleration sensor. In a training sample of 433 participants, the Improved Physical Activity Index (IPAI) was developed. Its performance was evaluated in a validation sample of 911 participants and compared with the Cambridge Index and the Total PA Index. The IPAI consists of items covering five areas including PA at work, sport, cycling, television viewing, and computer use. The correlations of the IPAI with accelerometer counts in the training and validation sample ranged r = 0.40–0.43 and with physical activity energy expenditure (PAEE) r = 0.33–0.40 and were higher than for the Cambridge Index and the Total PA Index previously applied in EPIC. In non-working participants the IPAI showed higher correlations than the Cambridge Index and the Total PA Index, with r = 0.34 for accelerometer counts and r = 0.29 for PAEE. In conclusion, we developed a valid physical activity index which is able to express PA continuously as well as to categorize participants according to their PA level. In populations with increasing rates of non-working people the performance of the IPAI is better than the established indices used in EPIC. PMID:24642812

Range 7 Scanner Integration with PaR Robot Scanning System

NASA Technical Reports Server (NTRS)

Schuler, Jason; Burns, Bradley; Carlson, Jeffrey; Minich, Mark

2011-01-01

An interface bracket and coordinate transformation matrices were designed to allow the Range 7 scanner to be mounted on the PaR Robot detector arm for scanning the heat shield or other object placed in the test cell. A process was designed for using Rapid Form XOR to stitch data from multiple scans together to provide an accurate 3D model of the object scanned. An accurate model was required for the design and verification of an existing heat shield. The large physical size and complex shape of the heat shield does not allow for direct measurement of certain features in relation to other features. Any imaging devices capable of imaging the entire heat shield in its entirety suffers a reduced resolution and cannot image sections that are blocked from view. Prior methods involved tools such as commercial measurement arms, taking images with cameras, then performing manual measurements. These prior methods were tedious and could not provide a 3D model of the object being scanned, and were typically limited to a few tens of measurement points at prominent locations. Integration of the scanner with the robot allows for large complex objects to be scanned at high resolution, and for 3D Computer Aided Design (CAD) models to be generated for verification of items to the original design, and to generate models of previously undocumented items. The main components are the mounting bracket for the scanner to the robot and the coordinate transformation matrices used for stitching the scanner data into a 3D model. The steps involve mounting the interface bracket to the robot's detector arm, mounting the scanner to the bracket, and then scanning sections of the object and recording the location of the tool tip (in this case the center of the scanner's focal point). A novel feature is the ability to stitch images together by coordinates instead of requiring each scan data set to have overlapping identifiable features. This setup allows models of complex objects to be developed

Bridging Therapy with i. v. rtPA in MCA Occlusion Prior to Endovascular Thrombectomy: a Double-Edged Sword?

PubMed

Kaesmacher, Johannes; Kleine, Justus F

2018-03-01

Recent studies suggested that preinterventional intravenous (i. v.) recombinant tissue plasminogen activator (rtPA) as bridging therapy facilitates successful and fast vessel recanalization in endovascular stroke treatment (EST); however, data on this effect and the associated clinical value are discrepant. This study examined if this discrepancy could be related to an effect-modifying variable, specifically to the exact occlusion site. Retrospective analysis of 239 patients with acute occlusion of the middle cerebral artery (MCA) treated with up to date endovascular techniques. Effects of i. v.-rtPA bridging on clinical outcomes and safety/efficacy of EST, defined as the respective rates of successful, first pass and thrombolysis in cerebral infarction (TICI) scale 3 recanalization, were evaluated and stratified according to distal versus proximal occlusion sites. Overall, i. v.-rtPA bridging was associated with a significantly higher rate of successful recanalization (86.9 % vs. 75.7 %, p = 0.028). i. v.-rtPA bridging-related effects, however, were observable only in distal, but not in proximal MCA-occlusions. In distal occlusions, i. v.-rtPA clearly favored successful recanalization (adj. OR 4.6, 95 %-CI 1.5-13.6, p = 0.006) and first-pass successes (adj. OR 2.8, 95 %-CI 1.0-7.6, p = 0.042), but tended to be associated with lower rates of complete (TICI-3) reperfusion (adj. OR 0.4, 95 %-CI 0.2-1.1, p = 0.068). The net effect was a small clinical benefit, reflected in higher rates of strong neurological improvement (adj. OR: 2.8, 95 %-CI: 1.1-6.9, p = 0.03). i. v.-rtPA-bridging-related effects are occlusion site-dependent, paralleling similar effects of systemic i. v.-rtPA when applied without subsequent endovascular therapy. In distal occlusions, i. v.-rtPA facilitates thrombectomy, but may also promote distal embolization, with a small clinical benefit as overall net effect. Randomized trials assessing i.v-rtPA bridging need

Domain-Specific Self-Reported and Objectively Measured Physical Activity in Children.

PubMed

Sprengeler, Ole; Wirsik, Norman; Hebestreit, Antje; Herrmann, Diana; Ahrens, Wolfgang

2017-03-01

Little is known about the extent that different domains contribute to total sedentary (SED), light (LPA) and moderate-to-vigorous physical activity (MVPA). We aimed to identify domain-specific physical activity (PA) patterns in school-aged children who were assessed by questionnaire and accelerometry. For the study, 298 German school children and adolescents aged 6-17 years wore an accelerometer for one week and completed a PA recall-questionnaire for the same period. Spearman coefficients (r) were used to evaluate the agreement between self-reported and objectively measured PA in five domains (transport, school hours, physical education, leisure-time, organized sports activities). School hours mainly contributed to the total objectively measured SED, LPA and MVPA (55%, 53% and 46%, respectively), whilst sports activities contributed only 24% to total MVPA. Compared to accelerometry, the proportion of self-reported LPA and MVPA during school hours was substantially underestimated but overestimated during leisure-time. The agreement of self-reported and objectively measured PA was low for total LPA (r = 0.09, 95% CI (confidence interval): -0.03-0.20) and total MVPA (r = 0.21, 95% CI: 0.10-0.32), while moderate agreement was only found for total SED (r = 0.44, 95% CI: 0.34-0.53), LPA during transport (r = 0.59; 95% CI: 0.49-0.67) and MVPA during organized sports activities (r = 0.54; 95% CI: 0.38-0.67). Since school hours mainly contribute to total SED, LPA and MVPA and self-reported LPA and MVPA during school were importantly underestimated compared to objectively measured LPA and MVPA, the application of objective measurements is compulsory to characterize the entire activity pattern of school-aged children.

Protective activity and immunogenicity of two recombinant anthrax vaccines for veterinary use.

PubMed

Fasanella, A; Tonello, F; Garofolo, G; Muraro, L; Carattoli, A; Adone, R; Montecucco, C

2008-10-23

In this study, the efficacy of two experimental vaccines against Bacillus anthracis toxinaemia was evaluated in the rabbit model. A recombinant Protective Antigen (rPA) mutant and a trivalent vaccine (TV) composed by the rPA, a inactive mutant of Lethal Factor (mLF-Y728A; E735A) and a inactive mutant of Edema Factor (mEF-K346R), both emulsified with mineral oils, were evaluated for their immunogenicity and protective activity in New Zealand white rabbits. Rabbits vaccinated subcutaneously with rPA and TV rapidly produced high level of anti-PA, anti-LF and anti-EF antibodies, which were still present 6 months later. In the efficacy test, these vaccines protected 100% of rabbits challenged with B. anthracis virulent strain 0843 one week after the vaccination. Moreover, all animals vaccinated twice with rPA and TV, resisted B. anthracis infection 6 months later. Our data indicate that rPA and TV could be good vaccine candidates for inducing protection against B. anthracis infection in target animal host. They could successfully be used in an emergency with simultaneous long-acting antibiotics to halt incubating infections or during an anthrax epidemic.

Thrombolysis with Intravenous Tissue Plasminogen Activator (rt-PA) Predicts Favorable Discharge Disposition in Patients with Acute Ischemic Stroke

PubMed Central

Ifejika-Jones, Nneka L.; Harun, Nusrat; Mohammed-Rajput, Nareesa A.; Noser, Elizabeth A.; Grotta, James C.

2011-01-01

Background and Purpose Acute ischemic stroke patients receiving IV tissue plasminogen activator (rt-PA) within 3 hours of symptom onset are 30% more likely to have minimal disability at three months. During hospitalization, short-term disability is subjectively measured by discharge disposition, whether to home, Inpatient Rehabilitation (IR), Skilled Nursing Facility (SNF) or Subacute Care (Sub). There are no studies assessing the role of rt-PA use as a predictor of post-stroke disposition. Methods Retrospective analysis of all ischemic stroke patients admitted to the University of Texas Houston Medical School (UTHMS) Stroke Service between Jan 2004 and Oct 2009. Baseline demographics and National Institute of Health Stroke Scale (NIHSS) score were collected. Cerebrovascular disease risk factors were used for risk stratification. Results Home vs. IR, SNF, Sub Of 2225 acute ischemic stroke patients, 1019 were discharged home, 1206 to another level of care. Patients who received rt-PA therapy were 1.9 times more likely to be discharged home (P = <0.0001; OR 1.945, 95% CI 1.538 to 2.459). IR vs. SNF, Sub / SNF vs. Sub Of 1206 acute ischemic stroke patients, 719 patients were discharged to acute IR, 371 were discharged to SNF, 116 to Sub. There were no differences in disposition between patients who received rt-PA therapy. Conclusions Stroke patients who receive IV rt-PA for acute ischemic stroke are more 1.9 times more likely to be discharged directly home after hospitalization. This study is limited by its retrospective nature and the undetermined role of psychosocial factors related to discharge. PMID:21293014

Spermatozoa Expression of piR-31704, piR-39888, and piR-40349 and Their Correlation to Sperm Concentration and Fertilization Rate After ICSI.

PubMed

Cui, Long; Fang, Li; Shi, Biwei; Qiu, Sunquan; Ye, Yinghui

2018-05-01

To investigate the relationship between spermatozoa PIWI-interacting RNAs (piRNAs) levels and semen parameters and to evaluate the role of expression of piRNAs on fertilization and embryo development after intracytoplasmic sperm injection (ICSI) treatment. One hundred and eighty-six patients with idiopathic male infertility who had undergone first ICSI cycles were enrolled in our study. The levels of piRNAs in spermatozoa were measured by real-time polymerase chain reaction. Semen parameters, including sperm concentration, motility, and morphology, were evaluated. The rates of fertilization, early cleavage, and day 3 good-quality embryo were calculated to assess embryo development potential. Spermatozoa levels of piR-31704 and piR-39888 were decreased in male factor infertility group as compared with control group (for piR-31704, P = .027 and for piR-39888, P = .041, respectively). And these 2 piRNAs were expressed at higher levels in patients with normal sperm concentration compared with subnormal sperm concentration group (for piR-31704, P = .042; for piR-39888, P = .047, respectively), while there were no correlation between the 3 piRNAs expression levels in spermatozoa and the rates of sperm progressive motility and normal sperm morphology. There were significant increases in the levels of all 3 piRNAs in spermatozoa from the group with higher 2PN rates (for piR-31704, P = .002; for piR-39888, P < .001; for piR-40349, P < .001; respectively), but there was no correlation between spermatozoa levels of these 3 piRNAs and the rates of embryo early cleavage, day 3 good-quality embryos and pregnancy. Spermatozoa piRNA levels correlate with sperm concentration and fertilization rate after ICSI. Paternal piRNAs may play a role in fertilization process.

elPBN neurons regulate rVLM activity through elPBN-rVLM projections during activation of cardiac sympathetic afferent nerves

PubMed Central

Longhurst, John C.; Tjen-A-Looi, Stephanie C.; Fu, Liang-Wu

2016-01-01

The external lateral parabrachial nucleus (elPBN) within the pons and rostral ventrolateral medulla (rVLM) contributes to central processing of excitatory cardiovascular reflexes during stimulation of cardiac sympathetic afferent nerves (CSAN). However, the importance of elPBN cardiovascular neurons in regulation of rVLM activity during CSAN activation remains unclear. We hypothesized that CSAN stimulation excites the elPBN cardiovascular neurons and, in turn, increases rVLM activity through elPBN-rVLM projections. Compared with controls, in rats subjected to microinjection of retrograde tracer into the rVLM, the numbers of elPBN neurons double-labeled with c-Fos (an immediate early gene) and the tracer were increased after CSAN stimulation (P < 0.05). The majority of these elPBN neurons contain vesicular glutamate transporter 3. In cats, epicardial bradykinin and electrical stimulation of CSAN increased the activity of elPBN cardiovascular neurons, which was attenuated (n = 6, P < 0.05) after blockade of glutamate receptors with iontophoresis of kynurenic acid (Kyn, 25 mM). In separate cats, microinjection of Kyn (1.25 nmol/50 nl) into the elPBN reduced rVLM activity evoked by both bradykinin and electrical stimulation (n = 5, P < 0.05). Excitation of the elPBN with microinjection of dl-homocysteic acid (2 nmol/50 nl) significantly increased basal and CSAN-evoked rVLM activity. However, the enhanced rVLM activity induced by dl-homocysteic acid injected into the elPBN was reversed following iontophoresis of Kyn into the rVLM (n = 7, P < 0.05). These data suggest that cardiac sympathetic afferent stimulation activates cardiovascular neurons in the elPBN and rVLM sequentially through a monosynaptic (glutamatergic) excitatory elPBN-rVLM pathway. PMID:27225950

GSK-3β inhibitor TWS119 attenuates rtPA-induced hemorrhagic transformation and activates the Wnt/β-catenin signaling pathway after acute ischemic stroke in rats.

PubMed

Wang, Wei; Li, Mingchang; Wang, Yuefei; Li, Qian; Deng, Gang; Wan, Jieru; Yang, Qingwu; Chen, Qianxue; Wang, Jian

2016-12-01

Hemorrhagic transformation (HT) is a devastating complication for patients with acute ischemic stroke who are treated with tissue plasminogen activator (tPA). It is associated with high morbidity and mortality, but no effective treatments are currently available to reduce HT risk. Therefore, methods to prevent HT are urgently needed. In this study, we used TWS119, an inhibitor of glycogen synthase kinase 3β (GSK-3β), to evaluate the role of the Wnt/β-catenin signaling pathway in recombinant tPA (rtPA)-induced HT. Sprague-Dawley rats were subjected to a middle cerebral artery occlusion (MCAO) model of ischemic stroke and then were administered rtPA, rtPA combined with TWS119, or vehicle at 4 h. The animals were sacrificed 24 h after infarct induction. Rats treated with rtPA showed evident HT, had more severe neurologic deficit, brain edema, and blood-brain barrier breakdown, and had larger infarction volume than did the vehicle group. Rats treated with TWS119 had significantly improved outcomes compared with those of rats treated with rtPA alone. In addition, Western blot analysis showed that TWS119 increased the protein expression of β-catenin, claudin-3, and ZO-1 while suppressing the expression of GSK-3β. These results suggest that TWS119 reduces rtPA-induced HT and attenuates blood-brain barrier disruption, possibly through activation of the Wnt/β-catenin signaling pathway. This study provides a potential therapeutic strategy to prevent tPA-induced HT after acute ischemic stroke.

Ask Here PA: Large-Scale Synchronous Virtual Reference for Pennsylvania

ERIC Educational Resources Information Center

Mariner, Vince

2008-01-01

Ask Here PA is Pennsylvania's new statewide live chat reference and information service. This article discusses the key strategies utilized by Ask Here PA administrators to recruit participating libraries to contribute staff time to the service, the importance of centralized staff training, the main aspects of staff training, and activating the…

Effect of Low Frequency Ultrasound on Combined rt-PA and Eptifibatide Thrombolysis in Human Clots

PubMed Central

Meunier, Jason M.; Holland, Christy K.; Pancioli, Arthur M.; Lindsell, Christopher J.; Shaw, George J.

2009-01-01

Introduction Fibrinolytics such as recombinant tissue plasminogen activator (rt-PA) are used to treat thrombotic disease such as acute myocardial infarction (AMI) and ischemic stroke. Interest in increasing efficacy and reducing side effects has led to the study of adjuncts such as GP IIb-IIIa inhibitors and ultrasound (US) enhanced thrombolysis. Currently, GP IIb-IIIa inhibitor and fibrinolytic treatment are often used in AMI, and are under investigation for stroke treatment. However, little is known of the efficacy of combined GP IIb-IIIa inhibitor, fibrinolytic and ultrasound treatment. We measure the lytic efficacy of rt-PA, eptifibatide (Epf) and 120 kHz ultrasound treatment in an in-vitro human clot model. Materials and Methods Blood was drawn from 15 subjects after IRB approval. Clots were made in 20 μL pipettes, and placed in a water tank for microscopic visualization during lytic treatment. Clots were exposed to control, rt-PA (rt-PA), eptifibatide (Epf), or rt-PA+eptifibatide (rt-PA+Epf), with or without ultrasound for 30 minutes at 37°C in human plasma. Clot lysis was measured over time, using a microscopic imaging technique. The fractional clot loss (FCL) and initial lytic rate (LR) were used to quantify lytic efficacy. Results and Conclusions LR values for (−US) treated clots were 0.8±0.1(control), 1.8±0.3 (Epf), 1.5±0.2 (rt-PA), and 1.3±0.4 (rt-PA+Epf) (% clot width/minute) respectively. In comparison, the (+US) group exhibited LR values of 1.6±0.2 (control), 4.3±0.4 (Epf), 6.3±0.4 (rt-PA), and 4.6±0.6 (rt-PA+Epf). For (−US) treated clots, FCL was 6.0±0.8 (control), 9.2±2.5 (Epf), 15.6±1.7 (rt-PA), and 28.0±2.2% (rt-PA+Epf) respectively. FCL for (+US) clots was 13.5±2.4 (control), 20.7±6.4 (Epf), 44.4±3.6 (rt-PA) and 30.3±3.6% (rt-PA+Epf) respectively. Although the addition of eptifibatide enhances the in-vitro lytic efficacy of rt-PA in the absence of ultrasound, the efficacy of ultrasound and rt-PA is greater than that of

Subatmospheric vapor pressures for fluoromethane (R41), 1,1-difluoroethane (R152a), and 1,1,1-trifluoroethane (R143a) evaluated from internal-energy measurements

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

Duarte-Garza, H.A.; Magee, J.W.

1999-09-01

Vapor pressures were evaluated from measured internal-energy changes {Delta}U{sup (2)} in the vapor + liquid two-phase region. The method employed a thermodynamic relationship between the derivative quantity ({partial_derivative}U{sup (2)}/{partial_derivative}V){sub T}, the vapor pressure p{sub {sigma}}, and its temperature derivative ({partial_derivative}p/{partial_derivative}T){sub {sigma}}. This method was applied at temperatures between the triple point and the normal boiling point of three substances: fluoromethane (R41), 1,1-difluoroethane (R152a), and 1,1,1-trifluoroethane (R143a). In the case of R41, vapor pressures up to 1 MPa were calculated to validate the technique at higher pressures. For R152a, the calculated vapor pressure at the triple-point temperature differed from a directmore » experimental measurement by less than the claimed uncertainty (5 Pa) of the measurement. The calculated vapor pressures for R41 helped to resolve discrepancies in several published vapor pressure sources. Agreement with experimentally measured vapor pressures for R152a and for R143a near the normal boiling point (101.325 kPa) was within the experimental uncertainty of approximately 0.04 kPa (0.04%) for the published measurements.« less

Screening Physical Activity in Family Practice: Validity of the Spanish Version of a Brief Physical Activity Questionnaire

PubMed Central

Puig-Ribera, Anna; Martín-Cantera, Carlos; Puigdomenech, Elisa; Real, Jordi; Romaguera, Montserrat; Magdalena-Belio, José Félix; Recio-Rodríguez, Jose Ignacio; Rodriguez-Martin, Beatriz; Arietaleanizbeaskoa, Maria Soledad; Repiso–Gento, Irene; Garcia-Ortiz, Luis

2015-01-01

Objectives The use of brief screening tools to identify inactive patients is essential to improve the efficiency of primary care-based physical activity (PA) programs. However, the current employment of short PA questionnaires within the Spanish primary care pathway is unclear. This study evaluated the validity of the Spanish version of a Brief Physical Activity Assessment Tool (SBPAAT). Methods A validation study was carried out within the EVIDENT project. A convenience sample of patients (n = 1,184; age 58.9±13.7 years; 60.5% female) completed the SBPAAT and the 7-day Physical Activity Recall (7DPAR) and, in addition, wore an accelerometer (ActiGraph GT3X) for seven consecutive days. Validity was evaluated by measuring agreement, Kappa correlation coefficients, sensitivity and specificity in achieving current PA recommendations with the 7DPAR. Pearson correlation coefficients with the number of daily minutes engaged in moderate and vigorous intensity PA according to the accelerometer were also assessed. Comparison with accelerometer counts, daily minutes engaged in sedentary, light, moderate, and vigorous intensity PA, total daily kilocalories, and total PA and leisure time expenditure (METs-hour-week) between the sufficiently and insufficiently active groups identified by SBPAAT were reported. Results The SBPAAT identified 41.3% sufficiently active (n = 489) and 58.7% insufficiently active (n = 695) patients; it showed moderate validity (k = 0.454, 95% CI: 0.402–0.505) and a specificity and sensitivity of 74.3% and 74.6%, respectively. Validity was fair for identifying daily minutes engaged in moderate (r = 0.215, 95% CI:0.156 to 0.272) and vigorous PA (r = 0.282, 95% CI:0.165 to 0.391). Insufficiently active patients according to the SBPAAT significantly reported fewer counts/minute (-22%), fewer minutes/day of moderate (-11.38) and vigorous PA (-2.69), spent fewer total kilocalories/day (-753), and reported a lower energy cost (METs-hour-week) of physical

Using the social cognitive theory to understand physical activity among dialysis patients.

PubMed

Patterson, Megan S; Umstattd Meyer, M Renée; Beaujean, A Alexander; Bowden, Rodney G

2014-08-01

The purpose of this study was to use the social cognitive theory (SCT) constructs self-efficacy, outcome expectations, and self-regulation to better understand associations of physical activity (PA) behaviors among dialysis patients after controlling for demographic and health-related factors. This study was cross-sectional in design. Participants (N = 115; mean age = 61.51 years, SD = 14.01) completed self-report questionnaires during a regularly scheduled dialysis treatment session. Bivariate and hierarchical linear regression analyses were conducted to examine relationships among SCT constructs and PA. Significant relationships between PA and self-efficacy (r = .336), self-regulation (r = .280), and outcome expectations (r = .265) were detected among people on dialysis in bivariate analyses. Hierarchical linear regression revealed significant increases in variance explained for the addition of self-efficacy, self-regulation, and covariates (p < .01). Younger age, self-efficacy, and self-regulation were associated (p < .10) with greater participation in physical activity in the final model (R² = .272). Conclusion/Implication: This research supports the use of SCT in understanding PA among people undergoing dialysis treatment. The findings of this study can help health educators and health care practitioners better understand PA and how to promote it among this population. Future research should further investigate which activities dialysis patients participate in across the life span of their disease. Future PA programs should focus on increasing a patient's self-efficacy and self-regulation.

Domain-Specific Self-Reported and Objectively Measured Physical Activity in Children

PubMed Central

Sprengeler, Ole; Wirsik, Norman; Hebestreit, Antje; Herrmann, Diana; Ahrens, Wolfgang

2017-01-01

Little is known about the extent that different domains contribute to total sedentary (SED), light (LPA) and moderate-to-vigorous physical activity (MVPA). We aimed to identify domain-specific physical activity (PA) patterns in school-aged children who were assessed by questionnaire and accelerometry. For the study, 298 German school children and adolescents aged 6–17 years wore an accelerometer for one week and completed a PA recall-questionnaire for the same period. Spearman coefficients (r) were used to evaluate the agreement between self-reported and objectively measured PA in five domains (transport, school hours, physical education, leisure-time, organized sports activities). School hours mainly contributed to the total objectively measured SED, LPA and MVPA (55%, 53% and 46%, respectively), whilst sports activities contributed only 24% to total MVPA. Compared to accelerometry, the proportion of self-reported LPA and MVPA during school hours was substantially underestimated but overestimated during leisure-time. The agreement of self-reported and objectively measured PA was low for total LPA (r = 0.09, 95% CI (confidence interval): −0.03–0.20) and total MVPA (r = 0.21, 95% CI: 0.10–0.32), while moderate agreement was only found for total SED (r = 0.44, 95% CI: 0.34–0.53), LPA during transport (r = 0.59; 95% CI: 0.49–0.67) and MVPA during organized sports activities (r = 0.54; 95% CI: 0.38–0.67). Since school hours mainly contribute to total SED, LPA and MVPA and self-reported LPA and MVPA during school were importantly underestimated compared to objectively measured LPA and MVPA, the application of objective measurements is compulsory to characterize the entire activity pattern of school-aged children. PMID:28257046

PA-824 Kills Nonreplicating Mycobacterium tuberculosis by Intracellular NO Release

PubMed Central

Singh, Ramandeep; Manjunatha, Ujjini; Boshoff, Helena I. M.; Ha, Young Hwan; Niyomrattanakit, Pornwaratt; Ledwidge, Richard; Dowd, Cynthia S.; Lee, Ill Young; Kim, Pilho; Zhang, Liang; Kang, Sunhee; Keller, Thomas H.; Jiricek, Jan; Barry, Clifton E.

2009-01-01

Bicyclic nitroimidazoles, including PA-824, are exciting candidates for the treatment of tuberculosis. These prodrugs require intracellular activation for their biological function. We found that Rv3547 is a deazaflavin-dependent nitroreductase (Ddn) that converts PA-824 into three primary metabolites; the major one is the corresponding des-nitroimidazole (des-nitro). When derivatives of PA-824 were used, the amount of des-nitro metabolite formed was highly correlated with anaerobic killing of Mycobacterium tuberculosis (Mtb). Des-nitro metabolite formation generated reactive nitrogen species, including nitric oxide (NO), which are the major effectors of the anaerobic activity of these compounds. Furthermore, NO scavengers protected the bacilli from the lethal effects of the drug. Thus, these compounds may act as intracellular NO donors and could augment a killing mechanism intrinsic to the innate immune system. PMID:19039139

Anti-cancer, immunoregulatory, and antimicrobial activities of the frog skin host-defense peptides pseudhymenochirin-1Pb and pseudhymenochirin-2Pa.

PubMed

Mechkarska, Milena; Attoub, Samir; Sulaiman, Shahrazad; Pantic, Jelena; Lukic, Miodrag L; Conlon, J Michael

2014-11-01

Pseudhymenochirin-1Pb (Ps-1Pb) and pseudhymenochirin-2Pa (Ps-2Pa) are host-defense peptides, first isolated from skin secretions of the frog Pseudhymenochirus merlini (Pipidae). Ps-1Pb and Ps-2Pa are highly cytotoxic (LC50<12 μM) against non-small cell lung adenocarcinoma A549 cells, breast adenocarcinoma MDA-MB-231 cells, and colorectal adenocarcinoma HT-29 cells but are also hemolytic against human erythrocytes (LC50=28±2 μM for Ps-1Pb and LC50=6±1 μM for Ps-2Pa). Ps-2Pa shows selective cytotoxicity for tumor cells (LC50 against non-neoplastic human umbilical vein (HUVEC) cells=68±2 μM). Ps-1Pb and Ps-2Pa (5 μg/mL) significantly inhibit production of the anti-inflammatory cytokine IL-10 and the multifunctional cytokine IL-6 from lipopolysaccharide (LPS)-stimulated peritoneal macrophages from C57BL/6 mice and enhance the production of the pro-inflammatory cytokine IL-23 from both unstimulated and LPS-stimulated macrophages. Ps-1Pb potently (MIC≤10 μM) inhibits growth of multidrug-resistant clinical isolates of the Gram-positive bacteria methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis, and the Gram-negative bacteria Acinetobacter baumannii and Stenotrophomonas maltophilia. Ps-2Pa shows the same high potency (MIC≤10 μM) against the Gram-positive bacteria but is 2-4 fold less potent against the Gram-negative isolates. Ps-1Pb at 4×MIC kills 99.9% of Escherichia coli within 30 min and 99.9% of S. aureus within 180 min. In conclusion, cytotoxicity against tumor cells, cytokine-mediated immunomodulatory properties, and broad-spectrum antimicrobial activity suggest that the Ps-1Pb and Ps-2Pa represent templates for design of non-hemolytic analogs for tumor therapy and for treatment of infections in cancer patients produced by multidrug-resistant pathogens. Copyright © 2014 Elsevier B.V. All rights reserved.

Oxidative and ER stress-dependent ASK1 activation in steatotic hepatocytes and Kupffer cells sensitizes mice fatty liver to ischemia/reperfusion injury.

PubMed

Imarisio, Chiara; Alchera, Elisa; Bangalore Revanna, Chandrashekar; Valente, Guido; Follenzi, Antonia; Trisolini, Elena; Boldorini, Renzo; Carini, Rita

2017-11-01

Steatosis intensifies hepatic ischemia/reperfusion (I/R) injury increasing hepatocyte damage and hepatic inflammation. This study evaluates if this process is associated to a differential response of steatotic hepatocytes (HP) and Kupffer cells (KC) to I/R injury and investigates the molecular mechanisms involved. Control or steatotic (treated with 50 μmol palmitic acid, PA) mouse HP or KC were exposed to hypoxia/reoxygenation (H/R). C57BL/6 mice fed 9 week with control or High Fat diet underwent to partial hepatic IR. PA increased H/R damage of HP and further activated the ASK1-JNK axis stimulated by ER stress during H/R. PA also induced the production of oxidant species (OS), and OS prevention nullified the capacity of PA to increase H/R damage and ASK1/JNK stimulation. ASK1 inhibition prevented JNK activation and entirely protected HP damage. In KC, PA directly activated ER stress, ASK1 and p38 MAPK and increased H/R damage. However, in contrast to HP, ASK1 inhibition further increased H/R damage by preventing p38 MAPK activation. In mice liver, steatosis induced the expression of activated ASK1 in only KC, whereas I/R exposure of steatotic liver activated ASK1 expression also in HP. "In vivo", ASK1 inhibition prevented ASK1, JNK and p38 MAPK activation and protected I/R damage and expression of inflammatory markers. Lipids-induced ASK1 stimulation differentially affects HP and KC by promoting cytotoxic or protective signals. ASK1 increases H/R damage of HP by stimulating JNK and protects KC activating p38MAPK. These data support the potentiality of the therapeutic employment of ASK1 inhibitors that can antagonize the damaging effects of I/R upon fatty liver surgery by the contextual reduction of HP death and of KC-mediated reactions. Copyright © 2017 Elsevier Inc. All rights reserved.

Assessment of Physical Activity in Chronic Kidney Disease

PubMed Central

Robinson-Cohen, Cassianne; Littman, Alyson J; Duncan, Glen E; Roshanravan, Baback; Ikizler, T. Alp; Himmelfarb, Jonathan; Kestenbaum, Bryan R

2012-01-01

Background Physical activity (PA) plays important roles in the development of kidney disease and its complications; however, the validity of standard tools for measuring PA is not well understood. Study Design We investigated the performance of several readily-available and widely-used PA and physical function questionnaires, individually and in combination, against accelerometry among a cohort of CKD participants. Setting and Participants Forty-six participants from the Seattle Kidney Study, an observational cohort study of persons with CKD, completed the PA Scale for the Elderly, Human Activity Profile (HAP), Medical Outcomes Study SF-36 questionnaire, and the Four Week PA History Questionnaire (FWH). We simultaneously measured PA using an Actigraph GT3X accelerometer over a 14-day period. We estimated the validity of each instrument by testing its associations with log-transformed accelerometry counts. We used the Akaike information criterion to investigate the performance of combinations of questionnaires. Results All questionnaire scores were significantly associated with log-transformed accelerometry counts. The HAP correlated best with accelerometry counts (r2=0.32) followed by the SF-36 (r2=0.23). Forty-three percent of the variability in accelerometry counts data was explained by a model that combined the HAP, SF-36 and FWH. Conclusion A combination of measurement tools can account for a modest component of PA in patients with CKD; however, a substantial proportion of physical activity is not captured by standard assessments. PMID:22739659

Applications of neutron activation analysis in determination of natural and man-made radionuclides, including PA-231

NASA Astrophysics Data System (ADS)

Byrne, A. R.; Benedik, L.

1999-01-01

Neutron activation analysis (NAA), being essentially an isotopic and not an elemental method of analysis, is capable of determining a number of important radionuclides of radioecological interest by transformation into another, more easily quantifiable radionuclide. The nuclear characteristics which favour this technique may be summarized in an advantage factor relative to radiometric analysis of the original radioanalyte. Well known or hardly known examples include235U,238U,232Th,230Th,129I,99Tc,237Np and231Pa; a number of these are discussed and illustrated in analysis of real samples of environmental and biological origin. In particular, determination of231Pa by RNAA was performed using both postirradiation and preseparation methods. Application of INAA to enable the use of238U and232Th as endogenous (internal) radiotracers in alpha spectrometric analyses of uranium and thorium radioisotopes in radioecological studies is described, also allowing independent data sets to be obtained for quality control.

Sterilizing activity of R207910 (TMC207)-containing regimens in the murine model of tuberculosis.

PubMed

Ibrahim, Murad; Truffot-Pernot, Chantal; Andries, Koen; Jarlier, Vincent; Veziris, Nicolas

2009-09-15

The diarylquinoline R207910 (TMC207) has potent bactericidal activity in a murine model of tuberculosis (TB), but its sterilizing activity has not been determined. To evaluate the sterilizing activity of R207910-containing combinations in the murine model of TB. Swiss mice were intravenously inoculated with 6 log(10) of Mycobacterium tuberculosis strain H37Rv, treated with R207910-containing regimens, and followed for 3 months to determine relapse rates (modified Cornell model). Quantitative lung and spleen colony-forming unit counts and bacteriological relapse rates 3 months after the end of therapy were compared for the following regimens: 2, 3, or 4 months of R207910 (J) and pyrazinamide (Z) combined with rifampin (R) or isoniazid (H) or both and 3 or 4 months of a moxifloxacin (M)-containing regimen and 6 months of the standard WHO regimen RHZ. All J-treated mice were culture negative after 4 months of therapy. The relapse rate in the group treated with 4 months of JHRZ was similar to that of mice treated for 6 months with the RHZ regimen (6 vs. 17%; P = 0.54) and lower than that of RMZ (6 vs. 42%; P = 0,03), a moxifloxacin-containing regimen that was the most active in mice on once-daily basis. Four months of treatment with some J-containing regimens was as effective as the 6-month standard regimen and more effective than 4 months of treatment with M-containing regimens. Supplementation of standard regimen (RHZ) with J or substitution of J for H may shorten the treatment duration needed to cure TB in patients.

CRISPR Knockout of the HuR Gene Causes a Xenograft Lethal Phenotype

PubMed Central

Lal, Shruti; Cheung, Edwin C.; Zarei, Mahsa; Preet, Ranjan; Chand, Saswati N.; Mambelli-Lisboa, Nicole C.; Romeo, Carmella; Stout, Matthew C.; Londin, Eric; Goetz, Austin; Lowder, Cinthya Y.; Nevler, Avinoam; Yeo, Charles J.; Campbell, Paul M.; Winter, Jordan M.; Dixon, Dan A.; Brody, Jonathan R.

2017-01-01

Pancreatic ductal adenocarcinoma (PDA) is the third leading cause of cancer related deaths in the U.S., while colorectal cancer (CRC) is the third most common cancer. The RNA binding protein HuR (ELAVL1), supports a pro-oncogenic network in gastrointestinal (GI) cancer cells through enhanced HuR expression. Using a publically available database, HuR expression levels were determined to be increased in primary PDA and CRC tumor cohorts as compared to normal pancreas and colon tissues, respectively. CRISPR/Cas9 technology was successfully used to delete the HuR gene in both PDA (MIA PaCa-2 and Hs 766T) and CRC (HCT116) cell lines. HuR deficiency has a mild phenotype, in vitro, as HuR-deficient MIA PaCa-2 (MIA.HuR-KO(−/−)) cells had increased apoptosis when compared to isogenic wild-type (MIA.HuR-WT(+/+)) cells. Using this isogenic system, mRNAs were identified that specifically bound to HuR and were required for transforming a 2D culture into 3D (i.e., organoids). Importantly, HuR-deficient MIA PaCa-2 and Hs 766T cells were unable to engraft tumors in vivo compared to control HuR-proficient cells, demonstrating a unique xenograft lethal phenotype. While not as a dramatic phenotype, CRISPR knockout HuR HCT116 colon cancer cells (HCT.HuR-KO(−/−)) showed significantly reduced in vivo tumor growth compared to controls (HCT.HuR-WT(+/+)). Finally, HuR deletion affects KRAS activity and controls a subset of pro-oncogenic genes. Implications The work reported here supports the notion that targeting HuR is a promising therapeutic strategy to treat GI malignancies. PMID:28242812

CRISPR Knockout of the HuR Gene Causes a Xenograft Lethal Phenotype.

PubMed

Lal, Shruti; Cheung, Edwin C; Zarei, Mahsa; Preet, Ranjan; Chand, Saswati N; Mambelli-Lisboa, Nicole C; Romeo, Carmella; Stout, Matthew C; Londin, Eric; Goetz, Austin; Lowder, Cinthya Y; Nevler, Avinoam; Yeo, Charles J; Campbell, Paul M; Winter, Jordan M; Dixon, Dan A; Brody, Jonathan R

2017-06-01

Pancreatic ductal adenocarcinoma (PDA) is the third leading cause of cancer-related deaths in the United States, whereas colorectal cancer is the third most common cancer. The RNA-binding protein HuR (ELAVL1) supports a pro-oncogenic network in gastrointestinal (GI) cancer cells through enhanced HuR expression. Using a publically available database, HuR expression levels were determined to be increased in primary PDA and colorectal cancer tumor cohorts as compared with normal pancreas and colon tissues, respectively. CRISPR/Cas9 technology was successfully used to delete the HuR gene in both PDA (MIA PaCa-2 and Hs 766T) and colorectal cancer (HCT116) cell lines. HuR deficiency has a mild phenotype, in vitro , as HuR-deficient MIA PaCa-2 (MIA.HuR-KO (-/-) ) cells had increased apoptosis when compared with isogenic wild-type (MIA.HuR-WT (+/+) ) cells. Using this isogenic system, mRNAs were identified that specifically bound to HuR and were required for transforming a two-dimensional culture into three dimensional (i.e., organoids). Importantly, HuR-deficient MIA PaCa-2 and Hs 766T cells were unable to engraft tumors in vivo compared with control HuR-proficient cells, demonstrating a unique xenograft lethal phenotype. Although not as a dramatic phenotype, CRISPR knockout HuR HCT116 colon cancer cells (HCT.HuR-KO (-/-) ) showed significantly reduced in vivo tumor growth compared with controls (HCT.HuR-WT (+/+) ). Finally, HuR deletion affects KRAS activity and controls a subset of pro-oncogenic genes. Implications: The work reported here supports the notion that targeting HuR is a promising therapeutic strategy to treat GI malignancies. Mol Cancer Res; 15(6); 696-707. ©2017 AACR . ©2017 American Association for Cancer Research.

Relationship between habitual physical activity and gross motor skills is multifaceted in 5- to 8-year-old children.

PubMed

Laukkanen, A; Pesola, A; Havu, M; Sääkslahti, A; Finni, T

2014-04-01

Adequate motor skills are essential for children participating in age-related physical activities, and gross motor skills may play an important role for maintaining sufficient level of physical activity (PA) during life course. The purpose of this study was to examine the relationship between gross motor skills and PA in children when PA was analyzed by both metabolic- and neuromuscular-based methods. Gross motor skills (KTK--Körperkoordinationstest für Kinder and APM inventory--manipulative skill test) of 84 children aged 5-8 years (53 preschoolers, 28 girls; 31 primary schoolers, 18 girls) were measured, and accelerometer-derived PA was analyzed using in parallel metabolic counts and neuromuscular impact methods. The gross motor skills were associated with moderate-to-high neuromuscular impacts, PA of vigorous metabolic intensity, and mean level of PA in primary school girls (0.5 < r < 0.7, P < 0.05), and with high impacts in preschool girls (0.3 < r < 0.5, P < 0.05). In preschool boys, moderate impacts, light-to-vigorous PA, and mean level of PA were associated with gross motor skills (0.4 < r < 0.7, P < 0.05). In conclusion, the result emphasizes an important relationship between gross motor skills and PA stressing both metabolic and neuromuscular systems in children. Furthermore, PA highly stressing neuromuscular system interacts with gross motor proficiency in girls especially. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Combination of ultrasound and rtPA enhances fibrinolysis in an In Vitro clot system

PubMed Central

Winter, Philipp; Müller-Werkmeister, Hendrik; Strand, Susanne; König, Jochem; Kempski, Oliver; Ringel, Florian; Kantelhardt, Sven R.; Keric, Naureen

2017-01-01

Background Catheter-based lysis with recombinant tissue plasminogen activator (rtPA) is a well-established therapy for spontaneous intracerebral hemorrhage (ICH). The effectiveness of this therapy can be increased with ultrasound, but the optimal conditions are not yet clearly established. Using a novel in vitro system of blood clots previously developed by our group, we investigated various parameters of intralesional sonothrombolysis using an endosonography catheter in combination with rtPA. Methods Standardized human blood clots were equipped with a drainage catheter and weighed before and after 4 treatments: control (drainage only), rtPA only, ultrasound only and the combination of rtPA+ultrasound. The effectiveness of ultrasound was further analysed in terms of optimal frequency, duration and distance to the probe. Temperature and acoustic peak rarefaction pressure (APRP) were assessed to analyse potential adverse effects and quantify lysis. Histo-morphological analysis of the treated clots was performed by H&E staining and confocal laser scanning microscopy using fluorescent fibrinogen. Results The combined treatment rtPA+ultrasound achieved the highest lysis rates with a relative weight of 30.3%±5.5% (p≤0.0001) compared to all other groups. Similar results were observed when treating aged clots. Confocal fluorescent microscopy of the treated clots revealed a rarefied fibrin mesh without cavitations. No relevant temperature increase occurred (0.53±0.75°C). The optimal insonation treatment time was 1 hour. APRP measurements showed a lysis threshold of 515.5±113.4 kPa. Application of 10 MHz achieved optimal lysis and lysis radius, while simultaneously proving to be the best frequency for morphologic imaging of the clot and surrounding tissue. Conclusions These promising data provide the basis for an individualized minimal invasive ICH therapy by rtPA and sonothrombolysis independent of ICH age. PMID:29145482

Genistein modifies liver fibrosis and improves liver function by inducing uPA expression and proteolytic activity in CCl4-treated rats.

PubMed

Salas, Alfonso Leija; Montezuma, Tania Díaz; Fariña, German Garrido; Reyes-Esparza, Jorge; Rodríguez-Fragoso, Lourdes

2008-01-01

To evaluate the effect of genistein on the fibrosis and matrix degradation caused by experimentally induced fibrosis in rats. Hepatic fibrosis was brought about by chronic administration of carbon tetrachloride to rats. To evaluate the effect of genistein on liver fibrosis and function, total collagen content and proteolytic activity in the liver were quantified. Urokinase-type plasminogen activator (uPA) expression during experimental fibrosis was localized by immunohistochemistry. Histopathological changes were evaluated using light and electron microscopy. Animals with fibrosis and treated with genistein showed an important reduction (73%) in hepatic collagen content as well as an improvement in liver function (p < 0.001). Genistein increased the capacity of the liver to degrade type I collagen and Matrigel (3.1- and 3.7-fold, respectively; p < 0.001) in animals with liver fibrosis. Genistein increased the number of uPA-immunoreactive cells. The increase in the uPA expression correlated with an increase in proteolytic activity. Histological analysis revealed a reduction in the number of fiber septa in pericentral and perisinusoidal areas. Transmission electron micrographs of livers from animals with fibrosis and treated with genistein showed a reduction in the number of hepatic stellate cells activated and a smaller number of collagen fibers. Genistein is able to improve the liver after injury and fibrosis induced by chronic administration of carbon tetrachloride. This finding suggests that genistein has antifibrogenic potential and could therefore be useful for treating chronic liver disease. (c) 2008 S. Karger AG, Basel.

Observations of 231Pa/ 235U disequilibrium in volcanic rocks

NASA Astrophysics Data System (ADS)

Pickett, David A.; Murrell, Michael T.

1997-04-01

We present here the first survey of ( 231Pa/ 235U) ratios in volcanic rocks; such measurements are made possible by new mass spectrometric techniques. The data place new constraints on the timing and extent of magma source and evolutionary processes, particularly due to the sensitivity of the 231Pa- 235U pair and its intermediate time scale ( 231Pat 1/2 = 33 ky). ( 231Pa/ 235U) is found to vary widely, from 0.2 in carbonatites to 1.1-2.9 in basalts and 0.9-2.2 in arcs. Substantial Pa enrichment is nearly ubiquitous, suggestive of the relative incompatibility of Pa, qualitatively consistent with available partitioning data. The level of 231Pa- 235U disequilibrium typically far exceeds that of 230Th- 238U and is comparable to 226Ra- 230Th. The high ( 231Pa/ 235U) ratios in MORB and other basalts reflect a large degree of discrimination between two incompatible elements, posing challenges for modelling of melt generation and migration. Fundamental differences in ( 231Pa/ 235U) among different basaltic environments are likely related to contrasts in melting zone conditions (e.g., melting rate). Strong ( 231Pa/ 235U) disequilibria in continental basalts, for which ( 230Th/ 238U) disequilibria are small or absent, demonstrate that Pa-U fractionation is possible in both garnet and spinel mantle stability fields. In arcs, correlation of ( 231Pa/ 235U) and ( 230Th/ 238U) is consistent with U enrichment via slab-derived fluids, a process which is additional to the still dominant Pa enrichment. An important new constraint is provided by the observation that the near-equilibrium ( 230Th/ 238U) common to arcs and continental basalts is not typically accompanied by near-equilibrium ( 231Pa/ 235U), arguing against the influence of long magma history, crustal material, or equilibrium mantle sources in affecting decay-series ratios. Small sample sets from two silicic centers illustrate: (1) recent, rapid U enrichment in the magma chamber (El Chichón); and (2) the failure of

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

PubMed

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

2018-05-02

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

Overwhelming tPA Release, not PAI-1 Degradation, is Responsible for Hyperfibrinolysis in Severely Injured Trauma Patients

PubMed Central

Chapman, Michael P.; Moore, Ernest E.; Moore, Hunter B.; Gonzalez, Eduardo; Gamboni, Fabia; Chandler, James G.; Mitra, Sanchayita; Ghasabyan, Arsen; Chin, Theresa L.; Sauaia, Angela; Banerjee, Anirban; Silliman, Christopher C.

2015-01-01

Background Trauma induced coagulopathy (TIC) is associated with a four-fold increased risk of mortality. Hyperfibrinolysis is a component of TIC, but its mechanism is poorly understood. PAI-1 degradation by activated protein C has been proposed as mechanism for deregulation of the plasmin system in hemorrhagic shock, but in other settings of ischemia, tPA has been shown to be elevated. We hypothesized that the hyperfibrinolysis in TIC is not the result of PAI-1 degradation, but is driven by an increase in tPA, with resultant loss of PAI-1 activity through complexation with tPA. Methods 86 consecutive trauma activation patients had blood collected at the earliest time after injury, and were screened for hyperfibrinolysis using thrombelastography (TEG). Twenty-five hyperfibrinolytic patients were compared to 14 healthy controls using ELISAs for active tPA, active PAI-1 and PAI-1/tPA complex. Blood was also subjected to TEG with exogenous tPA-challenge as a functional assay for PAI-1 reserve. Results Total levels of PAI-1 (the sum of the active PAI-1 species and its covalent complex with tPA) are not significantly different between hyperfibrinolytic trauma patients and healthy controls: median 104 pM (IQR 48—201 pM) versus 115 pM (IQR 54—202 pM). The ratio of active to complexed PAI-1, however, was two orders of magnitude lower in hyperfibrinolysis than controls. Conversely, total tPA levels (active plus complex) were significantly higher in hyperfibrinolysis than controls: 139 pM (IQR 68—237 pM) versus 32 pM (IQR 16—37 pM). Hyperfibrinolytic trauma patients displayed increased sensitivity to exogenous challenge with tPA: median LY30 of 66.8% compared to 9.6% for controls. Conclusions Depletion of PAI-1 in TIC is driven by an increase in tPA, not PAI-1 degradation. The tPA-challenged TEG, based on this principle, is a functional test for PAI-1 reserves. Exploration of the mechanism of upregulation of tPA is critical to an understanding of hyperfibrinolysis in

Insulin promotes proliferation and fibrosing responses in activated pancreatic stellate cells

PubMed Central

Yang, Jiayue; Waldron, Richard T.; Su, Hsin-Yuan; Moro, Aune; Chang, Hui-Hua; Eibl, Guido; Ferreri, Kevin; Kandeel, Fouad R.; Lugea, Aurelia; Li, Ling

2016-01-01

Epidemiological studies support strong links between obesity, diabetes, and pancreatic disorders including pancreatitis and pancreatic adenocarcinoma (PDAC). Type 2 diabetes (T2DM) is associated with insulin resistance, hyperglycemia, and hyperinsulinemia, the latter due to increased insulin secretion by pancreatic beta-cells. We reported that high-fat diet-induced PDAC progression in mice is associated with hyperglycemia, hyperinsulinemia, and activation of pancreatic stellate cells (PaSC). We investigated here the effects of high concentrations of insulin and glucose on mouse and human PaSC growth and fibrosing responses. We found that compared with normal, pancreata from T2DM patients displayed extensive collagen deposition and activated PaSC in islet and peri-islet exocrine pancreas. Mice fed a high-fat diet for up to 12 mo similarly displayed increasing peri-islet fibrosis compared with mice fed control diet. Both quiescent and activated PaSC coexpress insulin (IR; mainly A type) and IGF (IGF-1R) receptors, and both insulin and glucose modulate receptor expression. In cultured PaSC, insulin induced rapid tyrosine autophosphorylation of IR/IGF-1R at specific kinase domain activation loop sites, activated Akt/mTOR/p70S6K signaling, and inactivated FoxO1, a transcription factor that restrains cell growth. Insulin did not promote activation of quiescent PaSC in either 5 mM or 25 mM glucose containing media. However, in activated PaSC, insulin enhanced cell proliferation and augmented production of extracellular matrix proteins, and these effects were abolished by specific inhibition of mTORC1 and mTORC2. In conclusion, our data support the concept that increased local glucose and insulin concentrations associated with obesity and T2DM promote PaSC growth and fibrosing responses. PMID:27609771

Assessment of physical activity in chronic kidney disease.

PubMed

Robinson-Cohen, Cassianne; Littman, Alyson J; Duncan, Glen E; Roshanravan, Baback; Ikizler, T Alp; Himmelfarb, Jonathan; Kestenbaum, Bryan R

2013-03-01

Physical inactivity plays an important role in the development of kidney disease and its complications; however, the validity of standard tools for measuring physical activity (PA) is not well understood. We investigated the performance of several readily available and widely used PA and physical function questionnaires, individually and in combination, against accelerometry among a cohort of chronic kidney disease (CKD) participants. Forty-six participants from the Seattle Kidney Study, an observational cohort study of persons with CKD, completed the Physical Activity Scale for the Elderly, Human Activity Profile (HAP), Medical Outcomes Study SF-36 questionnaire, and the Four-week Physical Activity History questionnaires. We simultaneously measured PA using an Actigraph GT3X accelerometer during a 14-day period. We estimated the validity of each instrument by testing its associations with log-transformed accelerometry counts. We used the Akaike information criterion to investigate the performance of combinations of questionnaires. All questionnaire scores were significantly associated with log-transformed accelerometry counts. The HAP correlated best with accelerometry counts (r(2) = 0.32) followed by SF-36 (r(2) = 0.23). Forty-three percent of the variability in accelerometry counts data was explained by a model that combined the HAP, SF-36, and Four-week Physical Activity History questionnaires. A combination of measurement tools can account for a modest component of PA in patients with CKD; however, a substantial proportion of PA is not captured by standard assessments. Copyright © 2013 National Kidney Foundation, Inc. All rights reserved.

The preparation of TiO2@rGO nanocomposite efficiently activated with UVA/LED and H2O2 for high rate oxidation of acetaminophen: Catalyst characterization and acetaminophen degradation and mineralization

NASA Astrophysics Data System (ADS)

Cheshme Khavar, Amir Hossein; Moussavi, Gholamreza; Mahjoub, Ali Reza

2018-05-01

The present work was focused on the preparation of TiO2@rGO nanocomposite using an innovative facile synthesis method and the investigation of its photocatalytic activity in a UVA/LED photoreactor. The XRD patterns indicated anatase structure for all samples. Presence of rGO in nanocomposites was confirmed by FT-IR and Raman spectra. Also, mono-dispersed TiO2 nanoparticles on rGO sheet were shown in the SEM and HRTEM images. The prepared TiO2@rGO nanocomposite was used as the photocatalyst for degradation of acetaminophen (ACT) in the photoreactor illuminated with UVA/LEDs having the intensity of 95 μW/cm2. The complete degradation of 50 mg/L ACT was attained within 50 min in the LED/TiO2@rGO process while P25/LED process only showed 17% ACT degradation under similar experimental conditions. The photocatalytic activity was strongly affected by the rGO to TiO2 ratio in the nanocomposites and the highest photocatalytic activity was observed at 3.0 wt.% of rGO. Reaction with free radOH was the main mechanism involved in the ACT photodegradation in the TiO2@rGO/LED process under the selected conditions. The performance of LED/TiO2@rGO process improved by four and three times in ACT degradation and mineralization, respectively, at the presence of H2O2. As made TiO2@rGO nanocompsite could preserve its catalytic activity during five consecutive recycles in the process. Accordingly, TiO2@rGO nanocomposite is an active and stable catalyst in the UVA/LED photoreactor for high rate degradation of pharmaceuticals in the contaminated water.

Plasmin-dependent modulation of the blood–brain barrier: a major consideration during tPA-induced thrombolysis?

PubMed Central

Niego, Be'eri; Medcalf, Robert L

2014-01-01

Plasmin, the principal downstream product of tissue-type plasminogen activator (tPA), is known for its potent fibrin-degrading capacity but is also recognized for many non-fibrinolytic activities. Curiously, plasmin has not been conclusively linked to blood–brain barrier (BBB) disruption during recombinant tPA (rtPA)-induced thrombolysis in ischemic stroke. This is surprising given the substantial involvement of tPA in the modulation of BBB permeability and the co-existence of tPA and plasminogen in both blood and brain throughout the ischemic event. Here, we review the work that argues a role for plasmin together with endogenous tPA or rtPA in BBB alteration, presenting the overall controversy around the topic yet creating a rational case for an involvement of plasmin in this process. PMID:24896566

23 CFR Appendix F to Part 1200 - Planning and Administration (P&A) Costs

Code of Federal Regulations, 2014 CFR

2014-04-01

... 23 Highways 1 2014-04-01 2014-04-01 false Planning and Administration (P&A) Costs F Appendix F to... HIGHWAY SAFETY GRANT PROGRAMS Pt. 1200, App. F Appendix F to Part 1200—Planning and Administration (P&A) Costs (a) Policy. Federal participation in P&A activities shall not exceed 50 percent of the total cost...

23 CFR Appendix F to Part 1200 - PLANNING AND ADMINISTRATION (P&A) COSTS

Code of Federal Regulations, 2013 CFR

2013-04-01

... 23 Highways 1 2013-04-01 2013-04-01 false PLANNING AND ADMINISTRATION (P&A) COSTS F APPENDIX F TO... HIGHWAY SAFETY GRANT PROGRAMS Pt. 1200, App. F APPENDIX F TO PART 1200—PLANNING AND ADMINISTRATION (P&A) COSTS (a) Policy. Federal participation in P&A activities shall not exceed 50 percent of the total cost...

TOWER STAIRHALL; SOUTH SOFFIT, SOUTH WEST (R). Glass plate stereopair ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

TOWER STAIRHALL; SOUTH SOFFIT, SOUTH WEST (R). Glass plate stereopair number PA-1430-139 LC-HABS-GS05-TS-D-26 (R) 157.4815. Left (printed) - Independence Hall Complex, Independence Hall, 500 Chestnut Street, Philadelphia, Philadelphia County, PA

1. Historic American Buildings Survey, Photocopy from P.R.R. General Library, ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

1. Historic American Buildings Survey, Photocopy from P.R.R. General Library, TRAIN SIDE FRONT (NORTH) c.1870 TRANSPORTATION BUILDING, 17TH STREET AND PENNSYLVANIA AVENUE, PHILADELPHIA, PENNSYLVANIA. - Pennsylvania Railroad Bryn Mawr Station, Bryn Mawr & Morris Avenues, Bryn Mawr, Montgomery County, PA

TOWER STAIRHALL; SOUTH SOFFIT, SOUTH WEST (R). Glass plate stereopair ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

TOWER STAIRHALL; SOUTH SOFFIT, SOUTH WEST (R). Glass plate stereopair number PA-1430-139 LC-HABS-GS05-TS-D-26 (R) 157.4815. Right (not printed) - Independence Hall Complex, Independence Hall, 500 Chestnut Street, Philadelphia, Philadelphia County, PA

Interrupted reperfusion reduces the activation of NADPH oxidase after cerebral I/R injury.

PubMed

Shen, Jia; Bai, Xiao-Yin; Qin, Yuan; Jin, Wei-Wei; Zhou, Jing-Yin; Zhou, Ji-Ping; Yan, Ying-Gang; Wang, Qiong; Bruce, Iain C; Chen, Jiang-Hua; Xia, Qiang

2011-06-15

Interrupted reperfusion reduces ischemia/reperfusion (I/R) injury. This study was designed to determine whether NADPH oxidase participates in the neural protection against global I/R injury after interrupted reperfusion. Mice were randomly divided into five groups: sham (sham-operated), I/R (20-min global I/R), RR (I/R+interrupted reperfusion), Apo (I/R+apocynin administration), and RR+Apo. Behavioral tests (pole test, beam walking, and Morris water maze) and Nissl staining were undertaken in all five groups; superoxide levels, expression of gp91(phox) and p47(phox), p47(phox) translocation, and Rac1 activation were measured in the sham, I/R, and RR groups. The motor coordination, bradykinesia, and spatial learning and memory, as well as the neuron survival rates, were better in the RR, Apo, and RR+Apo groups than in the I/R group. The NADPH oxidase-dependent superoxide levels, p47(phox) and gp91(phox) expression, p47(phox) translocation, and Rac1 activation were lower in the RR group than in the I/R group. In conclusion, the neural protective effect of interrupted reperfusion is at least partly mediated by decreasing the expression and assembly of NADPH oxidase and the levels of NADPH oxidase-derived superoxide. The most striking reduction Rac1-GTP in the RR group suggests that interrupted reperfusion also acts on the activation of assembled NADPH oxidase by reducing the availability of Rac1-GTP. Copyright © 2011 Elsevier Inc. All rights reserved.

Antiausterity activity of arctigenin enantiomers: importance of (2R,3R)-absolute configuration.

PubMed

Awale, Suresh; Kato, Mamoru; Dibwe, Dya Fita; Li, Feng; Miyoshi, Chika; Esumi, Hiroyasu; Kadota, Shigetoshi; Tezuka, Yasuhiro

2014-01-01

From a MeOH extract of powdered roots of Wikstroemia indica, six dibenzyl-gamma-butyrolactone-type lignans with (2S,3S)-absolute configuration [(+)-arctigenin (1), (+)-matairesinol (2), (+)-trachelogenin (3), (+)-nortrachelogenin (4), (+)-hinokinin (5), and (+)-kusunokinin (6)] were isolated, whereas three dibenzyl-gamma-butyrolactone-type lignans with (2R,3R)-absolute configuration [(-)-arctigenin (1*), (-)-matairesinol (2*), (-)-trachelogenin (3*)] were isolated from Trachelospermum asiaticum. The in vitro preferential cytotoxic activity of the nine compounds was evaluated against human pancreatic PANC-1 cancer cells in nutrient-deprived medium (NDM), but none of the six lignans (1-6) with (2S,3S)-absolute configuration showed preferential cytotoxicity. On the other hand, three lignans (1*-3*) with (2R,3R)-absolute configuration exhibited preferential cytotoxicity in a concentration-dependent manner with PC50 values of 0.54, 6.82, and 5.85 microM, respectively. Furthermore, the effect of (-)- and (+)-arctigenin was evaluated against the activation of Akt, which is a key process in the tolerance to nutrition starvation. Interestingly, only (-)-arctigenin (1*) strongly suppressed the activation of Akt. These results indicate that the (2R,3R)-absolute configuration of (-)-enantiomers should be required for the preferential cytotoxicity through the inhibition of Akt activation.

Process and Energy Optimization Assessment, Tobyhanna Army Depot, PA

DTIC Science & Technology

2006-04-17

assembly of electronic-communication components, different welding processes are performed at TYAD. It uses shielded arc, metal inert gas (MIG...tungsten inert gas ( TIG ), and silver braz- ing oxygen/acetylene cutting plasma arc methods to complete mission re- quirements. Major welding jobs are...ER D C/ CE R L TR -0 6 -1 1 Process and Energy Optimization Assessment Tobyhanna Army Depot, PA Mike C.J. Lin, Alexander M. Zhivov

Expression of the R2R3-MYB Transcription Factor TaMYB14 from Trifolium arvense Activates Proanthocyanidin Biosynthesis in the Legumes Trifolium repens and Medicago sativa1[W][OA

PubMed Central

Hancock, Kerry R.; Collette, Vern; Fraser, Karl; Greig, Margaret; Xue, Hong; Richardson, Kim; Jones, Chris; Rasmussen, Susanne

2012-01-01

Proanthocyanidins (PAs) are oligomeric flavonoids and one group of end products of the phenylpropanoid pathway. PAs have been reported to be beneficial for human and animal health and are particularly important in pastoral agricultural systems for improved animal production and reduced greenhouse gas emissions. However, the main forage legumes grown in these systems, such as Trifolium repens and Medicago sativa, do not contain any substantial amounts of PAs in leaves. We have identified from the foliar PA-accumulating legume Trifolium arvense an R2R3-MYB transcription factor, TaMYB14, and provide evidence that this transcription factor is involved in the regulation of PA biosynthesis in legumes. TaMYB14 expression is necessary and sufficient to up-regulate late steps of the phenylpropanoid pathway and to induce PA biosynthesis. RNA interference silencing of TaMYB14 resulted in almost complete cessation of PA biosynthesis in T. arvense, whereas Nicotiana tabacum, M. sativa, and T. repens plants constitutively expressing TaMYB14 synthesized and accumulated PAs in leaves up to 1.8% dry matter. Targeted liquid chromatography-multistage tandem mass spectrometry analysis identified foliar PAs up to degree of polymerization 6 in leaf extracts. Hence, genetically modified M. sativa and T. repens plants expressing TaMYB14 provide a viable option for improving animal health and mitigating the negative environmental impacts of pastoral animal production systems. PMID:22566493

SECOND FLOOR LOBBY; EAST WALL, UPPER LEFT (R). Glass plate ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

SECOND FLOOR LOBBY; EAST WALL, UPPER LEFT (R). Glass plate stereopair number PA-1430-139 LC-HABS-GS05-2L-E-2 (R) 157.4825. Right (not printed) - Independence Hall Complex, Independence Hall, 500 Chestnut Street, Philadelphia, Philadelphia County, PA

SECOND FLOOR LOBBY; EAST WALL, UPPER LEFT (R). Glass plate ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

SECOND FLOOR LOBBY; EAST WALL, UPPER LEFT (R). Glass plate stereopair number PA-1430-139 LC-HABS-GS05-2L-E-2 (R) 157.4825. Left (printed) - Independence Hall Complex, Independence Hall, 500 Chestnut Street, Philadelphia, Philadelphia County, PA

SECOND FLOOR LOBBY; EAST WALL, LOWER LEFT (R). Glass plate ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

SECOND FLOOR LOBBY; EAST WALL, LOWER LEFT (R). Glass plate stereopair number PA-1430-139 LC-HABS-GS05-2L-E-1 (R) 157.4824. Left (printed) - Independence Hall Complex, Independence Hall, 500 Chestnut Street, Philadelphia, Philadelphia County, PA

SECOND FLOOR LOBBY; EAST WALL, LOWER LEFT (R). Glass plate ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

SECOND FLOOR LOBBY; EAST WALL, LOWER LEFT (R). Glass plate stereopair number PA-1430-139 LC-HABS-GS05-2L-E-1 (R) 157.4824. Right (not printed) - Independence Hall Complex, Independence Hall, 500 Chestnut Street, Philadelphia, Philadelphia County, PA

SECOND FLOOR LOBBY; EAST WALL, LOWER RIGHT (R). Glass plate ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

SECOND FLOOR LOBBY; EAST WALL, LOWER RIGHT (R). Glass plate stereopair number PA-1430-139 LC-HABS-GS05-2L-E-3 (R) 157.4826. Left (printed) - Independence Hall Complex, Independence Hall, 500 Chestnut Street, Philadelphia, Philadelphia County, PA

SECOND FLOOR LOBBY; EAST WALL, LOWER RIGHT (R). Glass plate ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

SECOND FLOOR LOBBY; EAST WALL, LOWER RIGHT (R). Glass plate stereopair number PA-1430-139 LC-HABS-GS05-2L-E-3 (R) 157.4826. Right (not printed) - Independence Hall Complex, Independence Hall, 500 Chestnut Street, Philadelphia, Philadelphia County, PA

SECOND FLOOR LOBBY; EAST WALL, UPPER RIGHT (R). Glass plate ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

SECOND FLOOR LOBBY; EAST WALL, UPPER RIGHT (R). Glass plate stereopair number PA-1430-139 LC-HABS-GS05-2L-E-4 (R) 157.4827. Right (not printed) - Independence Hall Complex, Independence Hall, 500 Chestnut Street, Philadelphia, Philadelphia County, PA

SECOND FLOOR LOBBY; EAST WALL, UPPER RIGHT (R). Glass plate ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

SECOND FLOOR LOBBY; EAST WALL, UPPER RIGHT (R). Glass plate stereopair number PA-1430-139 LC-HABS-GS05-2L-E-4 (R) 157.4827. Left (printed) - Independence Hall Complex, Independence Hall, 500 Chestnut Street, Philadelphia, Philadelphia County, PA

Pharmacodynamic evaluation of clopidogrel plus PA32540: the Spaced PA32540 With Clopidogrel Interaction Gauging (SPACING) study.

PubMed

Gurbel, P A; Bliden, K P; Fort, J; Zhang, Y; Plachetka, J R; Antonino, M; Gesheff, M; Tantry, U S

2011-12-01

PA32540 combines 325 mg enteric-coated (EC) aspirin (ASA) with 40 mg immediate-release omeprazole; its influence on the antiplatelet effect of clopidogrel (C) is unknown. In this randomized, open-label study, subjects (n = 30) were treated with (i) 300 mg C + 325 mg ECASA followed by 75 mg C + 325 mg ECASA on days 2-7, (ii) 300 mg C + PA32540 followed by 75 mg C + PA32540 on days 2-7, or (iii) PA32540 in the morning + 300 mg C 10 h later on day 1 and PA32540 in the morning + 75 mg C 10 h later on days 2-7. We analyzed the noninferiority of PA32540 relative to ECASA, as defined by the upper bound of the 95% confidence interval ≤10% for the difference in least-square means of platelet inhibition between the treatments. As compared to ECASA+C, synchronous treatment of PA32540+C was not noninferior, whereas the spacing strategy of PA32540+C was noninferior. Spacing the administration of PA32540 and clopidogrel lessens the interaction observed with synchronous administration; PA32540 administration with clopidogrel may be associated with a different antiplatelet profile.

A cross-sectional study of the relationship between parents' and children's physical activity.

PubMed

Stearns, Jodie A; Rhodes, Ryan; Ball, Geoff D C; Boule, Normand; Veugelers, Paul J; Cutumisu, Nicoleta; Spence, John C

2016-10-28

Though parents' physical activity (PA) is thought to be a predictor of children's PA, findings have been mixed. The purpose of this study was to examine the relationship between pedometer-measured steps/day of parents' and their children and potential moderators of this relationship. We also assessed the parent-child PA relationship as measured by questionnaires. Six-hundred and twelve 7-8 year olds and one of their parents wore Steps Count (SC)-T2 pedometers for four consecutive days. Parents reported their PA from the last seven days and their child's usual PA. Hierarchical linear regressions were used to assess the parent-child PA relationships, controlling for covariates. Gender (parent, child), gender homogeneity, weight status (parent, child), weight status homogeneity, and socioeconomic status (SES) variables (parent education, household income, area-level SES) were tested as potential moderators of this relationship. Partial r's were used as an estimate of effect size. Parents' steps was significantly related to children's steps (r partial  = .24). For every 1,000 step increase in parents' steps, the children took 260 additional steps. None of the tested interactions were found to moderate this relationship. Using questionnaires, a relatively smaller parent-child PA relationship was found (r partial  = .14). Physically active parents tend to have physically active children. Interventions designed to get children moving more throughout the day could benefit from including a parent component. Future research should explore the mechanisms by which parents influence their children, and other parent attributes and styles as potential moderators.

Functionalization and Melt-compounding of MWCNTs in PA-6 for Tribological Applications

NASA Astrophysics Data System (ADS)

Chopra, Swamini; Deshmukh, Kavita A.; Deshmukh, Abhay D.; Peshwe, D. R.

2018-04-01

The present study focuses on the fabrication and mechanical property evaluation of PA-6/MWCNT nanocomposites reinforced with microwave-functionalized MWCNTs. The MWCNTs were subjected to microwave radiation in the solution of H2SO4 and HNO3 for 3 minutes, with the aim of achieving better and faster functionalization. The change observed in the crystal structure of PA-6 matrix after CNT addition suggested improved nucleation due to well-dispersed MWCNTs after functionalization. The tensile strength of PA-6 increased by approx. 12 % and 15 % after addition of pristine and functionalized MWCNTs, respectively. This was credited to improved interaction between CNTs and PA-6 matrix. The dispersion quality of CNTs in PA-6 matrix was verified by FEG-SEM, while the fractography of composites revealed polymer sheathing of PA-6 matrix around CNTs. This again contributed in improving the elongation of the composites by approx. 10 %. The wear resistance of the composites also improved appreciably, irrespective of the applied load. The specific wear rate of PA-6/CNT nanocomposite reinforced with functionalized MWCNTs increased by approx. 60 to 70 %, while coefficient of friction reduced by approx. 30 to 40%.

The impact of physical activity on endothelial function in middle-aged and elderly subjects: the Ikaria study.

PubMed

Siasos, Gerasimos; Chrysohoou, Christina; Tousoulis, Dimitris; Oikonomou, Evangelos; Panagiotakos, Demosthenes; Zaromitidou, Marina; Zisimos, Konstantinos; Marinos, Georgios; Mazaris, Savvas; Kampaksis, Manolis; Papavassiliou, Athanasios G; Pitsavos, Christos; Stefanadis, Christodoulos

2013-01-01

Exercise training and physical activity (PA) have substantial vascular and cardiac health benefits. Ikaria Island has been recognised as having one of the highest longevity rates worldwide and a high percentage of healthy ageing. We examined the relationship between endothelial function and levels of habitual PA to evaluate the factors related to healthy ageing in this population. The study was conducted on a subgroup population of the IKARIA study consisting of 185 middle-aged (40-65 years) and 142 elderly subjects (66-91 years). Endothelial function was evaluated by ultrasound measurement of flow-mediated dilatation (FMD). PA was evaluated using the shortened version of the self-reported International Physical Activity Questionnaire (IPAQ). Subjects in the low PA group (<500 MET/ min/week) were considered as physically inactive and the rest as active. In the overall study population FMD was inversely associated with age (r=-0.24, p<0.001) and middle-aged subjects had higher FMD compared with the elderly (6.26 ± 3.31% vs. 5.21 ± 2.95%, p=0.003). Multiple linear regression analysis revealed that among middle-aged subjects the physically active had higher FMD compared with the physically inactive. Physically active subjects in the middle-aged group showed higher FMD compared with the physically active elderly (p=0.008). However, there was no difference in FMD values between middle-aged inactive subjects and the elderly physically active (p=NS). The present study revealed that increased PA was associated with improved endothelial function in middle-aged subjects and that PA in elderly subjects can ameliorate the devastating effects of ageing on arterial wall properties.

[Disseminated intravascular coagulation induced by endotoxin in rabbits: effect of treatment with t-PA and urokinase].

PubMed

Paloma, M J; Páramo, J A; Rifón, J; Rocha, E

1992-12-01

To assess the therapeutic efficacy of agents capable of stimulating the fibrinolytic system, such as tissue plasminogen activator (t-PA) and urokinase (UK) on endotoxin-induced disseminated intravascular coagulation (DIC) in the rabbit. DIC was induced by intravenous administration of endotoxin, 20 micrograms/kg/hr during 6 hr. Four different groups were established: a) control group, receiving only saline solution; b) t-PA group receiving 0.2 mg/kg; c) t-PA group receiving 0.7 mg/kg, and d) UK group, which was given 3,000 IU/kg/hr for 6 hr. Blood samples were drawn before and after 2 hr and 6 hr of endotoxin administration. Platelet count, and fibrinogen, factor XII and antithrombin III concentrations, were assessed in each sample. Mean, standard deviation and percentage of increase or decrease with respect to the basal value, this considered 100%, were used to evaluate the findings. For comparison of values, Student's t and Mann Whitney's U were used; the Fisher test was used for mortality studies. No statistical differences appeared for any of the values in the rabbits under basal conditions. The rabbits in the control group developed DIC. No doses of t-PA modified the changes appearing in blood coagulation. UK reduced the fibrinogen and factor XII consumption induced by endotoxin. The mortality rate in the control group reached 70%. High-dose t-PA decreased such figure to 50%, while low-dose t-PA or UK failed to reduce mortality. High-dose t-PA has beneficial effects on endotoxin-induced DIC in rabbits. UK failed to achieve such effect at the doses given in this experimental DIC model.

231Pa and 230Th in the ocean model of the Community Earth System Model (CESM1.3)

NASA Astrophysics Data System (ADS)

Gu, Sifan; Liu, Zhengyu

2017-12-01

The sediment 231Pa / 230Th activity ratio is emerging as an important proxy for deep ocean circulation in the past. In order to allow for a direct model-data comparison and to improve our understanding of the sediment 231Pa / 230Th activity ratio, we implement 231Pa and 230Th in the ocean component of the Community Earth System Model (CESM). In addition to the fully coupled implementation of the scavenging behavior of 231Pa and 230Th with the active marine ecosystem module (particle-coupled: hereafter p-coupled), another form of 231Pa and 230Th have also been implemented with prescribed particle flux fields of the present climate (particle-fixed: hereafter p-fixed). The comparison of the two forms of 231Pa and 230Th helps to isolate the influence of the particle fluxes from that of ocean circulation. Under present-day climate forcing, our model is able to simulate water column 231Pa and 230Th activity and the sediment 231Pa / 230Th activity ratio in good agreement with available observations. In addition, in response to freshwater forcing, the p-coupled and p-fixed sediment 231Pa / 230Th activity ratios behave similarly over large areas of low productivity on long timescales, but can differ substantially in some regions of high productivity and on short timescales, indicating the importance of biological productivity in addition to ocean transport. Therefore, our model provides a potentially powerful tool to help the interpretation of sediment 231Pa / 230Th reconstructions and to improve our understanding of past ocean circulation and climate changes.

Testing Direct and Indirect Effects of Identity, Media Use, Cognitions, and Conversations on Self-Reported Physical Activity Among a Sample of Hispanic Adults.

PubMed

Wirtz, John G; Wang, Zongyuan; Kulpavarapos, Supathida

2017-03-01

This article presents the results of a study testing the direct and indirect effects of identity, media use, cognitions and conversations on physical activity (PA). The study was guided by the O-S-O-R model (Markus & Zajonc, 1985), and it used data collected from a sample of Hispanic adults (N = 268) living in the U.S. Southwest. Exercise identity and ethnic identity were defined as pre-orientations (O 1 ); use of PA-related media content was defined as the stimulus (S); reflective integration and conversations about PA-related media were post-orientations (O 2 ); and self-reported physical activity was the behavioral response (R). Structural equation modeling was used to analyze the data, and several compelling results emerged. Exercise identity had a significant positive direct effect on PA and PA-related media use, as well as a significant positive indirect effect on conversations about PA-related media. PA-related media use exerted a strong and significant positive effect on conversations about PA-related media, as well as a significant positive indirect effect on PA. Finally, conversations about PA-related media content had a significant positive direct effect on PA. The results indicate that identity acts as a filter influencing what media content are selected and that cognitions and conversations about media content can serve as a link between media use and health behavior. Key words: O-S-O-R model, physical activity, Hispanic adults, identity, media use, conversation.

Overestimation of physical activity level is associated with lower BMI: a cross-sectional analysis.

PubMed

Watkinson, Clare; van Sluijs, Esther Mf; Sutton, Stephen; Hardeman, Wendy; Corder, Kirsten; Griffin, Simon J

2010-09-20

Poor recognition of physical inactivity may be an important barrier to healthy behaviour change, but little is known about this phenomenon. We aimed to characterize a high-risk population according to the discrepancies between objective and self-rated physical activity (PA), defined as awareness. An exploratory cross-sectional analysis of PA awareness using baseline data collected from 365 ProActive participants between 2001 and 2003 in East Anglia, England. Self-rated PA was defined as 'active' or 'inactive' (assessed via questionnaire). Objective PA was defined according to achievement of guideline activity levels (≥30 minutes or <30 minutes spent at least moderate intensity PA, assessed by heart rate monitoring). Four awareness groups were created: 'Realistic Actives', 'Realistic Inactives', 'Overestimators' and 'Underestimators'. Logistic regression was used to assess associations between awareness group and 17 personal, social and biological correlates. 63.3% of participants (N = 231) were inactive according to objective measurement. Of these, 45.9% rated themselves as active ('Overestimators'). In a multiple logistic regression model adjusted for age and smoking, males (OR = 2.11, 95% CI = 1.12, 3.98), those with lower BMI (OR = 0.89, 95% CI = 0.84, 0.95), younger age at completion of full-time education (OR = 0.83, 95% CI = 0.74, 0.93) and higher general health perception (OR = 1.02 CI = 1.00, 1.04) were more likely to overestimate their PA. Overestimation of PA is associated with favourable indicators of relative slimness and general health. Feedback about PA levels could help reverse misperceptions.

Psychosocial and perceived environmental correlates of physical activity in rural and older african american and white women.

PubMed

Wilcox, Sara; Bopp, Melissa; Oberrecht, Larissa; Kammermann, Sandra K; McElmurray, Charles T

2003-11-01

African American and rural older women are among the least active segments of the population. This study, guided by social cognitive theory, examined the correlates of physical activity (PA) in 102 rural older women (41% African American; 70.6 +/- 9.2 years). In bivariate associations, education, marital status, self-efficacy, greater pros than cons, perceived stress, social support, and perceived neighborhood safety were positively associated with PA; age, depressive symptoms, perceived sidewalks, health care provider discussion of PA, and perceived traffic were negatively associated with PA. In a hierarchical regression analysis, the sociodemographic (R(2) = 23%), psychological (IR(2) = 9%), social (IR(2) = 6%), and perceived physical environmental (IR(2) = 9%) sets of variables were significant (p <.05) predictors of PA (model R(2) = 47%). In response to open-ended questions, most women cited individual and social factors as PA barriers and motivators; falls, injuries, and heart attacks were identified most often as risks. These findings support the importance of multilevel influences on PA in older rural women and are useful for informing PA interventions.

Palmitoylation-dependent activation of MC1R prevents melanomagenesis

PubMed Central

Chen, Shuyang; Zhu, Bo; Yin, Chengqian; Liu, Wei; Han, Changpeng; Chen, Baoen; Liu, Tongzheng; Li, Xin; Chen, Xiang; Li, Chunying; Hu, Limin; Zhou, Jun; Xu, Zhi-Xiang; Gao, Xiumei; Wu, Xu; Goding, Colin R.; Cui, Rutao

2017-01-01

The melanocortin-1 receptor (MC1R), a G protein-coupled receptor, plays a crucial role in human and mouse pigmentation1–8. Activation of MC1R in melanocytes by α-melanocyte-stimulating hormone (α-MSH)9 stimulates cAMP signaling and melanin production and enhances DNA repair after UV irradiation (UVR)10–16. Individuals carrying MC1R variants, especially those associated with red hair color, fair skin and poor tanning ability (RHC-variants), are associated with higher risk of melanoma5,17,18,19,20. However, how MC1R activity might be modulated by UV irradiation, why redheads are more prone to developing melanoma, and whether the activity of RHC variants might be restored for therapeutic benefit remain unresolved questions. Here we demonstrate a potential MC1R-targeted intervention strategy to rescue loss-of-function MC1R in MC1R RHC-variants for therapeutic benefit based on activating MC1R protein palmitoylation. Specifically, MC1R palmitoylation, primarily mediated by the protein-acyl transferase (PAT) ZDHHC13, is essential for activating MC1R signaling that triggers increased pigmentation, UVB-induced G1-like cell cycle arrest and control of senescence and melanomagenesis in vitro and in vivo. Using C57BL/6J-MC1Re/eJ mice expressing MC1R RHC-variants we show that pharmacological activation of palmitoylation rescues the defects of MC1R RHC-variants and prevents melanomagenesis. The results highlight a central role for MC1R palmitoylation in pigmentation and protection against melanoma. PMID:28869973

Anti-allodynic effect of intrathecal processed Aconitum jaluense is associated with the inhibition of microglial activation and P2X7 receptor expression in spinal cord.

PubMed

Yang, Jihoon; Park, Keun Suk; Yoon, Jae Joon; Bae, Hong-Beom; Yoon, Myung Ha; Choi, Jeong Il

2016-07-13

For their analgesic and anti-arthritic effects, Aconitum species have been used in folk medicine in some East Asian countries. Although their analgesic effect is attributed to its action on voltage-dependent sodium channels, they also suppress purinergic receptor expression in dorsal root ganglion neurons in rats with neuropathic pain. In vitro study also demonstrated that the Aconitum suppresses ATP-induced P2X7 receptor (P2X7R)-mediated inflammatory responses in microglial cell lines. Herein, we examined the effect of intrathecal administration of thermally processed Aconitum jaluense (PA) on pain behavior, P2X7R expression and microglial activation in a rat spinal nerve ligation (SNL) model. Mechanical allodynia induced by L5 SNL in Sprague-Dawley rats was measured using the von Frey test to evaluate the effect of intrathecal injection of PA. Changes in the expression of P2X7R in the spinal cord were examined using RT-PCR and Western blot analysis. In addition, the effect of intrathecal PA on microglial activation was evaluated by immunofluorescence. Intrathecal PA attenuated mechanical allodynia in a dose-dependent manner showing both acute and chronic effects with 65 % of the maximal possible effect. The expression and production of spinal P2X7R was increased five days after SNL, but daily intrathecal PA injection significantly inhibited the increase to the level of naïve animals. Immunofluorescence of the spinal cord revealed a significant increase in P2X7R expression and activation of microglia in the dorsal horn, which was inhibited by intrathecal PA treatment. P2X7R co-localized with microglia marker, but not neurons. Intrathecal PA exerts anti-allodynic effects in neuropathic pain, possibly by suppressing P2X7R production and expression as well as reducing microglial activation in the spinal cord.

Measuring stigma in children receiving mental health treatment: Validation of the Paediatric Self-Stigmatization Scale (PaedS).

PubMed

Kaushik, A; Papachristou, E; Dima, D; Fewings, S; Kostaki, E; Ploubidis, G B; Kyriakopoulos, M

2017-06-01

Research on the impact of stigma associated with mental illness in children is scarce. Considering the known negative effects of stigma associated with mental illness in adults, it is crucial to explore the stigma experienced by children who access mental health treatment. However, no scale measuring self-stigmatization in younger children is available to date. This study aimed to develop and validate such a scale, the Paediatric Self-Stigmatization Scale (PaedS). A total of 156 children (119 receiving outpatient and 37 receiving inpatient treatment), aged 8-12 years, completed the PaedS, the Self-Perception Profile for Children and the Pediatric Quality of Life Inventory (PedsQL - Child Report, ages 8-12). In addition, parents completed the PedsQL (Parent Report for Children, ages 8-12), the Strengths and Difficulties Questionnaire (SDQ) and a modified subscale of the PaedS measuring the children's rejection by others due to their mental health difficulties. A confirmatory factor analysis showed that a four-factor structure, comprising Societal Devaluation, Personal Rejection, Self-Stigma and Secrecy scales, had excellent fit to the data (CFI=0.95; TLI=0.95; RMSEA=0.05). Child-reported PaedS scores were positively correlated with parental-reported PaedS scores and negatively with PedsQL, the SDQ, and 5 out of 6 subscales of the Self-Perception Profile for Children, suggesting adequate convergent validity (all P-values<0.05). The PaedS is a valid instrument, which is hoped to advance the understanding of self-stigmatization in children with mental health difficulties and contribute to its prevention. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Beta-Decay Rates for Exotic Nuclei and R-Process Nucleosynthesis

NASA Astrophysics Data System (ADS)

Suzuki, Toshio; Yoshida, Takashi; Wanajo, Shinya; Kajino, Toshitaka; Otsuka, Takaharu

Beta-decay rates for exotic nuclei at N = 126 relevant to r-process nucleosynthesis are studied by shell-model calculations. The half-lives obtained are used to study r-process nucleosynthesis in core-collapse supernova explosions and binary neutron star mergers. The element abundances are obtained up to the third peak as well as beyond the peak region up to uranium.

Barriers to Physical Activity in Children With Autism Spectrum Disorders: Relationship to Physical Activity and Screen Time.

PubMed

Must, Aviva; Phillips, Sarah; Curtin, Carol; Bandini, Linda G

2015-04-01

Individual, social, and community barriers to physical activity (PA) experienced by children with autism spectrum disorder (ASD) make PA participation more difficult and may contribute to increased screen time. We compared the prevalence of parent-reported barriers to PA among 58 typically developing (TD) children and 53 children with an ASD, 3 to 11 years, and assessed the association between barriers and PA participation and screen time among children with ASD. Parents of children with ASD reported significantly more barriers than parents of TD children. Based on parent-report, 60% of children with ASD required too much supervision compared with no TD children (P < .001). Parents of children with ASD were more likely to report that adults lack skills needed to include their child (58%), that their child has few friends (45%), and that other children exclude their child (23%). The number of parent-reported barriers to PA was inversely correlated with the hours spent in PA per year (r = -0.27, P = .05) and positively related to total screen time (r = .32, P < .03). These findings underscore the need for community-based PA programs designed to meet the special requirements of this population and policies that compel schools and other government-supported organizations for inclusion and/or targeted programming.

tPA Prescription and Administration Errors within a Regional Stroke System

PubMed Central

Chung, Lee S; Tkach, Aleksander; Lingenfelter, Erin M; Dehoney, Sarah; Rollo, Jeannie; de Havenon, Adam; DeWitt, Lucy Dana; Grantz, Matthew Ryan; Wang, Haimei; Wold, Jana J; Hannon, Peter M; Weathered, Natalie R; Majersik, Jennifer J

2015-01-01

Background IV tPA utilization in acute ischemic stroke (AIS) requires weight-based dosing and a standardized infusion rate. In our regional network, we have tried to minimize tPA dosing errors. We describe the frequency and types of tPA administration errors made in our comprehensive stroke center (CSC) and at community hospitals (CHs) prior to transfer. Methods Using our stroke quality database, we extracted clinical and pharmacy information on all patients who received IV tPA from 2010–11 at the CSC or CH prior to transfer. All records were analyzed for the presence of inclusion/exclusion criteria deviations or tPA errors in prescription, reconstitution, dispensing, or administration, and analyzed for association with outcomes. Results We identified 131 AIS cases treated with IV tPA: 51% female; mean age 68; 32% treated at CSC, 68% at CH (including 26% by telestroke) from 22 CHs. tPA prescription and administration errors were present in 64% of all patients (41% CSC, 75% CH, p<0.001), the most common being incorrect dosage for body weight (19% CSC, 55% CH, p<0.001). Of the 27 overdoses, there were 3 deaths due to systemic hemorrhage or ICH. Nonetheless, outcomes (parenchymal hematoma, mortality, mRS) did not differ between CSC and CH patients nor between those with and without errors. Conclusion Despite focus on minimization of tPA administration errors in AIS patients, such errors were very common in our regional stroke system. Although an association between tPA errors and stroke outcomes was not demonstrated, quality assurance mechanisms are still necessary to reduce potentially dangerous, avoidable errors. PMID:26698642

Physical activity questionnaires for youth: a systematic review of measurement properties.

PubMed

Chinapaw, Mai J M; Mokkink, Lidwine B; van Poppel, Mireille N M; van Mechelen, Willem; Terwee, Caroline B

2010-07-01

Because of the diversity in available questionnaires, it is not easy for researchers to decide which instrument is most suitable for his or her specific demands. Therefore, we systematically summarized and appraised studies examining measurement properties of self-administered and proxy-reported physical activity (PA) questionnaires in youth. Literature was identified through searching electronic databases (PubMed, EMBASE using 'EMBASE only' and SportDiscus) until May 2009. Studies were included if they reported on the measurement properties of self-administered and proxy-reported PA questionnaires in youth (mean age <18 years) and were published in the English language. Methodological quality and results of included studies was appraised using a standardized checklist (qualitative attributes and measurement properties of PA questionnaires [QAPAQ]). We included 54 manuscripts examining 61 versions of questionnaires. None of the included questionnaires showed both acceptable reliability and validity. Only seven questionnaires received a positive rating for reliability. Reported validity varied, with correlations between PA questionnaires and accelerometers ranging from very low to high (previous day PA recall: correlation coefficient [r] = 0.77). In general, PA questionnaires for adolescents correlated better with accelerometer scores than did those for children. From this systematic review, we conclude that no questionnaires were available with both acceptable reliability and validity. Considerably more high-quality research is required to examine the validity and reliability of promising PA questionnaires for youth.

uPA/uPAR system activation drives a glycolytic phenotype in melanoma cells.

PubMed

Laurenzana, Anna; Chillà, Anastasia; Luciani, Cristina; Peppicelli, Silvia; Biagioni, Alessio; Bianchini, Francesca; Tenedini, Elena; Torre, Eugenio; Mocali, Alessandra; Calorini, Lido; Margheri, Francesca; Fibbi, Gabriella; Del Rosso, Mario

2017-09-15

In this manuscript, we show the involvement of the uPA/uPAR system in the regulation of aerobic glycolysis of melanoma cells. uPAR over-expression in human melanoma cells controls an invasive and glycolytic phenotype in normoxic conditions. uPAR down-regulation by siRNA or its uncoupling from integrins, and hence from integrin-linked tyrosine kinase receptors (IL-TKRs), by an antagonist peptide induced a striking inhibition of the PI3K/AKT/mTOR/HIF1α pathway, resulting into impairment of glucose uptake, decrease of several glycolytic enzymes and of PKM2, a checkpoint that controls metabolism of cancer cells. Further, binding of uPA to uPAR regulates expression of molecules that govern cell invasion, including extracellular matrix metallo-proteinases inducer (EMPPRIN) and enolase, a glycolytyc enzyme that also serves as a plasminogen receptor, thus providing a common denominator between tumor metabolism and phenotypic invasive features. Such effects depend on the α5β1-integrin-mediated uPAR connection with EGFR in melanoma cells with engagement of the PI3K-mTOR-HIFα pathway. HIF-1α trans-activates genes whose products mediate tumor invasion and glycolysis, thus providing the common denominator between melanoma metabolism and its invasive features. These findings unveil a unrecognized interaction between the invasion-related uPAR and IL-TKRs in the control of glycolysis and disclose a new pharmacological target (i.e., uPAR/IL-TKRs axis) for the therapy of melanoma. © 2017 UICC.

Wearable Activity Tracker Literature Review (January 2009 - July 2016)

DTIC Science & Technology

2017-03-14

heart rate. Step count was the most frequently reported metric (12 studies covering 26 devices) and had the highest correlations to actual steps taken...WAT-measured heart rate (five devices) was reviewed in two reports and correlations to reference measures were moderate (r = .67) to excellent (r...reliability data on HR or time spent in PA. Reliability tended to be assessed using correlational analyses. Criteria for interpreting the strength of the

15. 'Southern Pacific R.R., One 236'0' Bet. End Pins S. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

15. 'Southern Pacific R.R., One 236'-0' Bet. End Pins S. Tr. Thro'. Draw Bridge over Sacramento River at Tehama, The Phoenix Bridge Co., Phoenixville, Pa., Jan'y 19th 98, Dwg. 585.' - Southern Pacific Railroad Shasta Route, Bridge No. 210.52, Milepost 210.52, Tehama, Tehama County, CA

Measurement of Outgassing Rates of Steels.

PubMed

Park, Chongdo; Kim, Se-Hyun; Ki, Sanghoon; Ha, Taekyun; Cho, Boklae

2016-12-13

Steels are commonly used materials in the fabrication of vacuum systems because of their good mechanical, corrosion, and vacuum properties. A variety of steels meet the criterion of low outgassing required for high or ultrahigh vacuum applications. However, a given material can present different outgassing rates depending on its manufacturing process or the various pretreatment processes involved during the fabrication. Thus, the measurement of outgassing rates is highly desirable for a specific vacuum application. For this reason, the rate-of-pressure rise (RoR) method is often used to measure the outgassing of hydrogen after bakeout. In this article, a detailed description of the design and execution of the experimental protocol involved in the RoR method is provided. The RoR method uses a spinning rotor gauge to minimize errors that stem from outgassing or the pumping action of a vacuum gauge. The outgassing rates of two ordinary steels (stainless steel and mild steel) were measured. The measurements were made before and after the heat pretreatment of the steels. The heat pretreatment of steels was performed to reduce the outgassing. Extremely low rates of outgassing (on the order of 10 - 11 Pa m 3 sec - 1 m - 2 ) can be routinely measured using relatively small samples.

Variation in energy expenditure among black-legged kittiwakes: Effects of activity-specific metabolic rates and activity budgets

USGS Publications Warehouse

Jodice, P.G.R.; Roby, D.D.; Suryan, R.M.; Irons, D.B.; Kaufman, A.M.; Turco, K.R.; Visser, G. Henk

2003-01-01

We sought to determine the effect of variation in time-activity budgets (TABs) and foraging behavior on energy expenditure rates of parent black-legged kittiwakes (Rissa tridactyla). We quantified TABs using direct observations of radio-tagged adults and simultaneously measured field metabolic rates (FMR) of these same individuals (n = 20) using the doubly labeled water technique. Estimated metabolic rates of kittiwakes attending their brood at the nest or loafing near the colony were similar (ca. 1.3 x basal metabolic rate [BMR]), although loafing during foraging trips was more costly (2.9 x BMR). Metabolic rates during commuting flight (7.3 x BMR) and prey-searching flight (6.2 x BMR) were similar, while metabolic rates during plunge diving were much higher (ca. 47 x BMR). The proportion of the measurement interval spent foraging had a positive effect on FMR (R2 = 0.68), while the combined proportion of time engaged in nest attendance and loafing near the colony had a negative effect on FMR (R2 = 0.72). Thus, more than two-thirds of the variation in kittiwake FMR could be explained by the allocation of time among various activities. The high energetic cost of plunge diving relative to straight flight and searching flight suggests that kittiwakes can optimize their foraging strategy under conditions of low food availability by commuting long distances to feed in areas where gross foraging efficiency is high.

Passive avoidance and complex maze learning in the senescence accelerated mouse (SAM): age and strain comparisons of SAM P8 and R1.

PubMed

Spangler, Edward L; Patel, Namisha; Speer, Dorey; Hyman, Michael; Hengemihle, John; Markowska, Alicja; Ingram, Donald K

2002-02-01

Two strains of the senescence accelerated mouse, P8 and R1,were tested in footshock-motivated passive avoidance (PA; P8, 3-21 months; R1, 3-24 months) and 14-unit T-maze (P8 and R1, 9, and 15 months) tasks. For PA, entry to a dark chamber from a lighted chamber was followed by a brief shock. Latency to enter the dark chamber 24 hours later served as a measure of retention. Two days of active avoidance training in a straight runway preceded 2 days (8 trials/day) of testing in the 14-unit T-maze. For PA retention, older P8 mice entered the dark chamber more quickly than older R1 mice, whereas no differences were observed between young P8 or R1 mice. In the 14-unit T-maze, age-related learning performance deficits were reflected in higher error scores for older mice. P8 mice were actually superior learners; that is, they had lower error scores compared with those of age-matched R1 counterparts. Although PA learning results were in agreement with other reports, results obtained in the 14-unit T-maze were not consistent with previous reports of learning impairments in the P8 senescence accelerated mouse.

Associations of physical activity, fitness, and body composition with heart rate variability–based indicators of stress and recovery on workdays: a cross-sectional study

PubMed Central

2014-01-01

Background The purpose of this study was to investigate how physical activity (PA), cardiorespiratory fitness (CRF), and body composition are associated with heart rate variability (HRV)-based indicators of stress and recovery on workdays. Additionally, we evaluated the association of objectively measured stress with self-reported burnout symptoms. Methods Participants of this cross-sectional study were 81 healthy males (age range 26–40 y). Stress and recovery on workdays were measured objectively based on HRV recordings. CRF and anthropometry were assessed in laboratory conditions. The level of PA was based on a detailed PA interview (MET index [MET-h/d]) and self-reported activity class. Results PA, CRF, and body composition were significantly associated with levels of stress and recovery on workdays. MET index (P < 0.001), activity class (P = 0.001), and CRF (P = 0.019) were negatively associated with stress during working hours whereas body fat percentage (P = 0.005) was positively associated. Overall, 27.5% of the variance of total stress on workdays (P = 0.001) was accounted for by PA, CRF, and body composition. Body fat percentage and body mass index were negatively associated with night-time recovery whereas CRF was positively associated. Objective work stress was associated (P = 0.003) with subjective burnout symptoms. Conclusions PA, CRF, and body composition are associated with HRV-based stress and recovery levels, which needs to be taken into account in the measurement, prevention, and treatment of work-related stress. The HRV-based method used to determine work-related stress and recovery was associated with self-reported burnout symptoms, but more research on the clinical importance of the methodology is needed. PMID:24742265

Physicochemical properties influencing denitrification rate and microbial activity in denitrification bioreactors

NASA Astrophysics Data System (ADS)

Schmidt, C. A.

2012-12-01

The use of N-based fertilizer will need to increase to meet future demands, yet existing applications have been implicated as the main source of coastal eutrophication and hypoxic zones. Producing sufficient crops to feed a growing planet will require efficient production in combination with sustainable treatment solutions. The long-term success of denitrification bioreactors to effectively remove nitrate (NO¬3), indicates this technology is a feasible treatment option. Assessing and quantifying the media properties that affect NO¬3 removal rate and microbial activity can improve predictions on bioreactor performance. It was hypothesized that denitrification rates and microbial biomass would be correlated with total C, NO¬3 concentration, metrics of organic matter quality, media surface area and laboratory measures of potential denitrification rate. NO¬3 removal rates and microbial biomass were evaluated in mesocosms filled with different wood treatments and the unique influence of these predictor variables was determined using a multiple linear regression analysis. NO3 reduction rates were independent of NO¬3 concentration indicating zero order reaction kinetics. Temperature was strongly correlated with denitrification rate (r2=0.87; Q10=4.7), indicating the variability of bioreactor performance in differing climates. Fiber quality, and media surface area were strong (R>0.50), unique predictors of rates and microbial biomass, although C:N ratio and potential denitrification rate did not predict actual denitrification rate or microbial biomass. Utilizing a stepwise multiple linear regression, indicates that the denitrification rate can be effectively (r2=0.56;p<0.0001) predicted if the groundwater temperature, neutral detergent fiber and surface area alone are quantified. These results will assist with the widespread implementation of denitrification bioreactors to achieve significant N load reductions in large watersheds. The nitrate reduction rate as a

Enzyme-linked immunosorbent assay using a recombinant baculovirus-expressed Bacillus anthracis protective antigen (PA): measurement of human anti-PA antibodies.

PubMed Central

Iacono-Connors, L C; Novak, J; Rossi, C; Mangiafico, J; Ksiazek, T

1994-01-01

We developed an antigen capture enzyme-linked immunosorbent assay (ELISA) which does not require purified protective antigen (PA) for detection of human antibodies to Bacillus anthracis PA. Lysates of Spodoptera frugiperda (Sf-9) cells infected with recombinant baculovirus containing the PA gene were used as the source of PA to develop the ELISA. Recombinant PA from crude Sf-9 cell lysates or PA purified from B. anthracis Sterne strain was captured by an anti-PA monoclonal antibody coated onto microtiter plates. We demonstrated that human serum antibody titers to PA were identical in the ELISA whether we used crude Sf-9 cell lysates containing recombinant baculovirus-expressed PA or purified Sterne PA. Finally, false-positive results observed in a direct ELISA were eliminated with this antigen capture ELISA. Thus, the antigen capture ELISA with crude preparations of baculovirus-expressed PA is reliable, safe, and inexpensive for determining anti-PA antibody levels in human sera. PMID:7496927

How to catch a parasite: Parasite Niche Modeler (PaNic) meets Fishbase

USGS Publications Warehouse

Strona, Giovanni; Lafferty, Kevin D.

2012-01-01

Parasite Niche Modeler (PaNic) is a free online software tool that suggests potential hosts for fish parasites. For a particular parasite species from the major helminth groups (Acanthocephala, Cestoda, Monogenea, Nematoda, Trematoda), PaNic takes data from known hosts (maximum body length, growth rate, life span, age at first maturity, trophic level, phylogeny, and biogeography) and hypothesizes similar fish species that might serve as hosts to that parasite. Users can give varying weights to host attributes and create custom models. In addition to suggesting plausible hosts (with varying degrees of confidence), the models indicate known host species that appear to be outliers in comparison to other known hosts. These unique features make PaNic an innovative tool for addressing both theoretical and applied questions in fish parasitology. PaNic can be accessed at .

Pancreatic Fibroblasts Stimulate the Motility of Pancreatic Cancer Cells through IGF1/IGF1R Signaling under Hypoxia.

PubMed

Hirakawa, Toshiki; Yashiro, Masakazu; Doi, Yosuke; Kinoshita, Haruhito; Morisaki, Tamami; Fukuoka, Tatsunari; Hasegawa, Tsuyoshi; Kimura, Kenjiro; Amano, Ryosuke; Hirakawa, Kosei

2016-01-01

Pancreatic ductal adenocarcinoma (PDAC) is characterized by its hypovascularity, with an extremely poor prognosis because of its highly invasive nature. PDAC proliferates with abundant stromal cells, suggesting that its invasive activity might be controlled by intercellular interactions between cancer cells and fibroblasts. Using four PDAC cell lines and two pancreas cancer-associated fibroblasts (CAFs), the expression of insulin-like growth factor-1 (IGF1) and IGF1 receptor (IGF1R) was evaluated by RT-PCR, FACScan, western blot, or ELISA. Correlation between IGF1R and the hypoxia marker carbonic anhydrase 9 (CA9) was examined by immunohistochemical staining of 120 pancreatic specimens. The effects of CAFs, IGF1, and IGF1R inhibitors on the motility of cancer cells were examined by wound-healing assay or invasion assay under normoxia (20% O2) and hypoxia (1% O2). IGF1R expression was significantly higher in RWP-1, MiaPaCa-2, and OCUP-AT cells than in Panc-1 cells. Hypoxia increased the expression level of IGF1R in RWP-1, MiaPaCa-2, and OCUP-AT cells. CA9 expression was correlated with IGF1R expression in pancreatic specimens. CAFs produced IGF1 under hypoxia, but PDAC cells did not. A conditioned medium from CAFs, which expressed αSMA, stimulated the migration and invasion ability of MiaPaCa-2, RWP-1, and OCUP-AT cells. The motility of all PDAC cells was greater under hypoxia than under normoxia. The motility-stimulating ability of CAFs was decreased by IGF1R inhibitors. These findings might suggest that pancreas CAFs stimulate the invasion activity of PDAC cells through paracrine IGF1/IGF1R signaling, especially under hypoxia. Therefore the targeting of IGF1R signaling might represent a promising therapeutic approach in IGF1R-dependent PDAC.

A chronicle of PA journals.

PubMed

Hooker, Roderick S

2017-02-01

At its semicentennial mark, the PA profession appears to be flourishing. Over the past 50 years, a number of journals have emerged to highlight the development of the profession and offer observations on it. The Physician Associate Journal, launched in 1970, was the first foray into PA reporting. Following this small effort, a dozen journals or newspapers came into print, lasted for a while, and then were replaced or died. Of journals that survived to the present, four are in English and one in Dutch. Three of the five journals are association-based, and four produce clinical articles; publication is monthly, quarterly, or semiannually. Two journals produce original health services research or studies on the PA education process and have citable track records. Readership of all journals is growing, and collectively these periodicals produce a body of scholarly work that clarifies the PA as a healthcare professional growing on a world stage. This article describes the journalistic history of one aspect of PA development.

AhV_aPA-induced vasoconstriction involves the IP₃Rs-mediated Ca²⁺ releasing.

PubMed

Zeng, Fuxing; Zou, Zhisong; Niu, Liwen; Li, Xu; Teng, Maikun

2013-08-01

AhV_aPA, the acidic PLA₂ purified from Agkistrodon halys pallas venom, was previously reported to possess a strong enzymatic activity and can remarkably induce a further contractile response on the 60 mM K⁺-induced contraction with an EC₅₀ in 369 nM on mouse thoracic aorta rings. In the present study, we found that the p-bromo-phenacyl-bromide (pBPB), which can completely inhibit the enzymatic activity of AhV_aPA, did not significantly reduce the contractile response on vessel rings induced by AhV_aPA, indicating that the vasoconstrictor effects of AhV_aPA are independent of the enzymatic activity. The inhibitor experiments showed that the contractile response induced by AhV_aPA is mainly attributed to the Ca²⁺ releasing from Ca²⁺ store, especially sarcoplasmic reticulum (SR). Detailed studies showed that the Ca²⁺ release from SR is related to the activation of inositol trisphosphate receptors (IP₃Rs) rather than ryanodine receptors (RyRs). Furthermore, the vasoconstrictor effect could be strongly reduced by pre-incubation with heparin, indicating that the basic amino acid residues on the surface of AhV_aPA may be involved in the interaction between AhV_aPA and the molecular receptors. These findings offer new insights into the functions of snake PLA₂ and provide a novel pathogenesis of A. halys pallas venom. Copyright © 2013 Elsevier Ltd. All rights reserved.

Aviation Machinist's Mate R 1 and C: Rate Training Manual.

ERIC Educational Resources Information Center

Naval Education and Training Command, Pensacola, FL.

The profusely illustrated rate training manual is one of a series of training manuals prepared for enlisted personnel of the Navy and Naval Reserve who are studying for advancement in the Aviation Machinist's Mate R rating (ADR 1 and ADRC). Chapter one provides information helpful for use in advancement. Chapters two through ten consist of units…

Production and properties of the native Chromobacterium violaceum fucose-binding lectin (CV-IIL) compared to homologous lectins of Pseudomonas aeruginosa (PA-IIL) and Ralstonia solanacearum (RS-IIL).

PubMed

Zinger-Yosovich, Keren; Sudakevitz, Dvora; Imberty, Anne; Garber, Nachman C; Gilboa-Garber, Nechama

2006-02-01

Chromobacterium violaceum is a versatile, violet pigment (violacein)-producing beta-proteobacterium, confined to tropical and subtropical regions, dwelling in soil and water, like Pseudomonas aeruginosa and Ralstonia solanacearum. These three bacteria are saprophytes that occasionally become aggressive opportunistic pathogens virulently attacking animals (the first two) and plants (the third). The recent availability of their genome sequences enabled identification in the C. violaceum genome of an ORF (locus no. 1744) that is similar to those of P. aeruginosa and R. solanacearum lectins, PA-IIL and RS-IIL, respectively. A recombinant protein, CV-IIL, encoded by that ORF exhibited fucose>mannose-specific lectin activity resembling PA-IIL. This paper describes production and properties of the native CV-IIL, which, like PA-IIL and RS-IIL, is probably also a quorum-sensing-driven secondary metabolite, appearing concomitantly with violacein. Its formation is repressed in the CV026 mutant of C. violaceum, which lacks endogenous N-acylhomoserine lactone. The upstream extragenic sequence of its ORF contains a 20 bp sequence (5'-101-120) with partial similarities to the luxI-box and the related P. aeruginosa and R. solanacearum promoter boxes of quorum-sensing-controlled genes. The lectin level is augmented by addition of trehalose to the medium. The subunit size of CV-IIL (around 11.86 kDa) is similar to those of PA-IIL (11.73 kDa) and RS-IIL (11.60 kDa). Like PA-IIL, in the tetrameric form CV-IIL preferentially agglutinates alpha1-2 fucosylated H-positive human erythrocytes (regardless of their A, B or O type), as opposed to the O(h) Bombay type, but differs from it in having no interaction with rabbit erythrocytes and in displaying stronger affinity to l-galactose than to l-fucose. The greater similarity of CV-IIL to PA-IIL than to RS-IIL might be related to the selective adaptation of both C. violaceum and P. aeruginosa to animal tissues versus the preferential homing

Convergent validity of a questionnaire for assessing physical activity in Spanish adolescents with overweight.

PubMed

Martínez-Gómez, David; Gómez-Martínez, Sonia; Wärnberg, Julia; Welk, Gregory J; Marcos, Ascensión; Veiga, Oscar L

2011-01-15

To evaluate the convergent validity of the PAQ-A for assessing physical activity (PA) in overweight (including obese) adolescents. Two hundred and three Spanish adolescents (96 females), aged 13-17 years, were selected for this study. Levels of PA were self-reported by 3-day activity diary, activity rating and PAQ-A. Adolescents wore the ActiGraph accelerometer for 7 days. Overweight was classified according to International Obesity Task Force age- and sex-specific body mass index cut offs. Fifty-four (33 male and 21 female) adolescents (27%) were classified as overweight or obese. The PAQ-A was moderately related in the overweight adolescent group to an activity rating (ρ=0.52), total PA and moderate-to-vigorous PA assessed by activity monitor (ρ=0.52 and 0.43) and total PA and moderate-to-vigorous PA assessed by activity diary (ρ=0.32 and 0.47). There were no significant differences in the correlation coefficients between non-overweight and overweight adolescents. The PAQ-A shows a reasonable validity for assessing PA in Spanish overweight adolescents. Copyright © 2010 Elsevier España, S.L. All rights reserved.

Measuring physical activity during US Army Basic Combat Training: a comparison of 3 methods.

PubMed

Redmond, Jan E; Cohen, Bruce S; Simpson, Kathleen; Spiering, Barry A; Sharp, Marilyn A

2013-01-01

An understanding of the demands of physical activity (PA) during US Army Basic Combat Training (BCT) is necessary to support Soldier readiness and resilience. The purpose of this study was to determine the agreement among 3 different PA measurement instruments in the BCT environment. Twenty-four recruits from each of 11 companies wore an ActiGraph accelerometer (Actigraph, LLC, Pensacola, FL) and completed a daily PA log during 8 weeks of BCT at 2 different training sites. The PA of one recruit from each company was recorded using PAtracker, an Army-developed direct observation tool. Information obtained from the accelerometer, PA log, and PAtracker included time spent in various types of PA, body positions, PA intensities, and external loads carried. Pearson product moment correlations were run to determine the strength of association between the ActiGraph and PAtracker for measures of PA intensity and between the PAtracker and daily PA log for measures of body position and PA type. The Bland-Altman method was used to assess the limits of agreement (LoA) between the measurement instruments. Weak correlations (r=-0.052 to r=0.302) were found between the ActiGraph and PAtracker for PA intensity. Weak but positive correlations (r=0.033 to r=0.268) were found between the PAtracker and daily PA log for body position and type of PA. The 95% LoA for the ActiGraph and PAtracker for PA intensity were in disagreement. The 95% LoA for the PAtracker and daily PA log for standing and running and all PA types were in disagreement; sitting and walking were in agreement. The ActiGraph accelerometer provided the best measure of the recruits' PA intensity while the PAtracker and daily PA log were best for capturing body position and type of PA in the BCT environment. The use of multiple PA measurement instruments in this study was necessary to best characterize the physical demands of BCT.

A framework for establishing predictive relationships between specific bacterial 16S rRNA sequence abundances and biotransformation rates.

PubMed

Helbling, Damian E; Johnson, David R; Lee, Tae Kwon; Scheidegger, Andreas; Fenner, Kathrin

2015-03-01

The rates at which wastewater treatment plant (WWTP) microbial communities biotransform specific substrates can differ by orders of magnitude among WWTP communities. Differences in taxonomic compositions among WWTP communities may predict differences in the rates of some types of biotransformations. In this work, we present a novel framework for establishing predictive relationships between specific bacterial 16S rRNA sequence abundances and biotransformation rates. We selected ten WWTPs with substantial variation in their environmental and operational metrics and measured the in situ ammonia biotransformation rate constants in nine of them. We isolated total RNA from samples from each WWTP and analyzed 16S rRNA sequence reads. We then developed multivariate models between the measured abundances of specific bacterial 16S rRNA sequence reads and the ammonia biotransformation rate constants. We constructed model scenarios that systematically explored the effects of model regularization, model linearity and non-linearity, and aggregation of 16S rRNA sequences into operational taxonomic units (OTUs) as a function of sequence dissimilarity threshold (SDT). A large percentage (greater than 80%) of model scenarios resulted in well-performing and significant models at intermediate SDTs of 0.13-0.14 and 0.26. The 16S rRNA sequences consistently selected into the well-performing and significant models at those SDTs were classified as Nitrosomonas and Nitrospira groups. We then extend the framework by applying it to the biotransformation rate constants of ten micropollutants measured in batch reactors seeded with the ten WWTP communities. We identified phylogenetic groups that were robustly selected into all well-performing and significant models constructed with biotransformation rates of isoproturon, propachlor, ranitidine, and venlafaxine. These phylogenetic groups can be used as predictive biomarkers of WWTP microbial community activity towards these specific

Pharmacological evaluation of a novel cyclic phosphatidic acid derivative 3-S-cyclic phosphatidic acid (3-S-cPA).

PubMed

Nozaki, Emi; Gotoh, Mari; Tanaka, Ryo; Kato, Masaru; Suzuki, Takahiro; Nakazaki, Atsuo; Hotta, Harumi; Kobayashi, Susumu; Murakami-Murofushi, Kimiko

2012-05-15

Cyclic phosphatidic acid (cPA) is a naturally occurring phospholipid mediator possessing cyclic phosphate ring, which is necessary for its specific biological activities. To stabilize cyclic phosphate ring of cPA, we synthesized a series of cPA derivatives. We have shown that racemic 3-S-cPA, with a phosphate oxygen atom replaced with a sulfur atom at the sn-3, was a more effective autotaxin (ATX) inhibitor than cPA. In this study, we showed that racemic 3-S-cPA also had potent biological activities such as inhibition of cancer cell migration, suppression of the nociceptive reflex, and attenuation of ischemia-induced delayed neuronal cell death in the hippocampal CA1. Moreover, we synthesized both enantiomers of palmitoleoyl derivative of 3-S-cPA, and found that the chirality of 3-S-cPA is not involved in ATX inhibition. Based on these findings, racemic 3-S-cPA is suggested as an effective therapeutic compound like cPA. Copyright © 2012 Elsevier Ltd. All rights reserved.

Enterolactone Suppresses Proliferation, Migration and Metastasis of MDA-MB-231 Breast Cancer Cells Through Inhibition of uPA Induced Plasmin Activation and MMPs-Mediated ECM Remodeling

PubMed Central

Mali, Aniket V; Joshi, Asavari A; Hegde, Mahabaleshwar V; Kadam, Shivajirao S

2017-01-01

Background: To enhance their own survival, tumor cells can manipulate their microenvironment through remodeling of the extra cellular matrix (ECM). The urokinase-type plasminogen activator (uPA) system catalyzes plasmin production which further mediates activation of matrix metalloproteinases (MMPs) and plays an important role in breast cancer invasion and metastasis through ECM remodeling. This provides a potential target for therapeutic intervention of breast cancer treatment. Enterolactone (EL) is derived from dietary flax lignans in the human body and is known to have anti-breast cancer activity. We here investigated molecular and cellular mechanisms of EL action on the uPA-plasmin-MMPs system. Methods: MTT and trypan blue dye exclusion assays, anchorage-dependent clonogenic assays and wound healing assays were carried out to study effects on cell proliferation and viability, clonogenicity and migration capacity, respectively. Real-time PCR was employed to study gene expression and gelatin zymography was used to assess MMP-2 and MMP-9 activities. All data were statistically analysed and presented as mean ± SEM values. Results: All the findings collectively demonstrated anticancer and antimetastatic potential of EL with antiproliferative, antimigratory and anticlonogenic cellular mechanisms. EL was found to exhibit multiple control of plasmin activation by down-regulating uPA expression and also up-regulating its natural inhibitor, PAI-1, at the mRNA level. Further, EL was found to down-regulate expression of MMP-2 and MMP-9 genes, and up-regulate TIMP-1 and TIMP-2; natural inhibitors of MMP-2 and MMP-9, respectively. This may be as a consequence of inhibition of plasmin activation, resulting in robust control over migration and invasion of breast cancer cells during metastasis. Conclusions: EL suppresses proliferation, migration and metastasis of MDA-MB-231 breast cancer cells by inhibiting induced ECM remodeling by the ‘uPA-plasmin-MMPs system’. PMID

Comparison of methods to assess energy expenditure and physical activity in people with spinal cord injury.

PubMed

Tanhoffer, Ricardo A; Tanhoffer, Aldre I P; Raymond, Jacqueline; Hills, Andrew P; Davis, Glen M

2012-01-01

To compare different methods of assessing energy expenditure (EE) and physical activity (PA) in people with spinal cord injury (SCI) under community-dwelling conditions. A reference standard encompassing the doubly labelled water (DLW) technique, heart rate monitoring (FLEX-HR), a multi-sensor armband (SenseWear Armband (SWA)), and two PA recall questionnaires were employed in 14 people with SCI to estimate EE and leisure-time PA. Mean total daily energy expenditure (TDEE) assessed by DLW, FLEX-HR, and SWA were 9817 ± 2491 kJ/day, 8498 ± 1516 kJ/day, and 11414 ± 3242 kJ/day, respectively. Physical activity energy expenditure (PAEE) quantified by DLW was 2841 ± 1626 kJ/day, 2935 ± 1732 kJ/day estimated from FLEX-HR, and 2773 ± 2966 kJ/day derived from SWA. After converting the PA recall questionnaire data to EE in kJ/day, PAEE for the Physical Activity Recall Assessment for People with Spinal Cord Injury (PARA-SCI) was 2339 ± 1171 kJ/day and for Physical Activity Scale for Individuals with Physical Disabilities (PASIPD) 749 ± 1026 kJ/day. DLW-quantified PAEE was moderately associated with PARA-SCI (R(2) = 0.62, P < 0.05), but not with the other estimates of PAEE (R(2) ranged between 0.13 and 0.30, P > 0.05). Our findings revealed that the PARA-SCI recall questionnaire was the best estimate of PAEE compared to the reference standard DLW approach. Although the between-method variability for SWA, FLEX-HR, and PASIPD-derived PAEE was small, there was a weak association between these methods and the criterion DLW technique. The best estimate of DLW-quantified TDEE was by FLEX-HR. SWA significantly overestimated TDEE in this population.

SPoRT's Participation in the GOES-R Proving Ground Activity

NASA Astrophysics Data System (ADS)

Jedlovec, G.; Fuell, K.; Smith, M. R.; Stano, G. T.; Molthan, A.

2011-12-01

The next generation geostationary satellite, GOES-R, will carry two new instruments with unique atmospheric and surface observing capabilities, the Advanced Baseline Imager (ABI) and the Geostationary Lightning Mapper (GLM), to study short-term weather processes. The ABI will bring enhanced multispectral observing capabilities with frequent refresh rates for regional and full disk coverage to geostationary orbit to address many existing and new forecast challenges. The GLM will, for the first time, provide the continuous monitoring of total lightning flashes over a hemispherical region from space. NOAA established the GOES-R Proving Ground activity several years ago to demonstrate the new capabilities of these instruments and to prepare forecasters for their day one use. Proving Ground partners work closely with algorithm developers and the end user community to develop and transition proxy data sets representing GOES-R observing capabilities. This close collaboration helps to maximize refine algorithms leading to the delivery of a product that effectively address a forecast challenge. The NASA Short-term Prediction Research and Transition (SPoRT) program has been a participant in the NOAA GOES-R Proving Ground activity by developing and disseminating selected GOES-R proxy products to collaborating WFOs and National Centers. Established in 2002 to demonstrate the weather and forecasting application of real-time EOS measurements, the SPoRT program has grown to be an end-to-end research to operations activity focused on the use of advanced NASA modeling and data assimilation approaches, nowcasting techniques, and unique high-resolution multispectral data from EOS satellites to improve short-term weather forecasts on a regional and local scale. Participation in the Proving Ground activities extends SPoRT's activities and taps its experience and expertise in diagnostic weather analysis, short-term weather forecasting, and the transition of research and experimental

SPoRT's Participation in the GOES-R Proving Ground Activity

NASA Technical Reports Server (NTRS)

Jedlovec, Gary; Fuell, Kevin; Smith, Matthew; Stano, Geoffrey; Molthan, Andrew

2011-01-01

The next generation geostationary satellite, GOES-R, will carry two new instruments with unique atmospheric and surface observing capabilities, the Advanced Baseline Imager (ABI) and the Geostationary Lightning Mapper (GLM), to study short-term weather processes. The ABI will bring enhanced multispectral observing capabilities with frequent refresh rates for regional and full disk coverage to geostationary orbit to address many existing and new forecast challenges. The GLM will, for the first time, provide the continuous monitoring of total lightning flashes over a hemispherical region from space. NOAA established the GOES-R Proving Ground activity several years ago to demonstrate the new capabilities of these instruments and to prepare forecasters for their day one use. Proving Ground partners work closely with algorithm developers and the end user community to develop and transition proxy data sets representing GOES-R observing capabilities. This close collaboration helps to maximize refine algorithms leading to the delivery of a product that effectively address a forecast challenge. The NASA Short-term Prediction Research and Transition (SPoRT) program has been a participant in the NOAA GOES-R Proving Ground activity by developing and disseminating selected GOES-R proxy products to collaborating WFOs and National Centers. Established in 2002 to demonstrate the weather and forecasting application of real-time EOS measurements, the SPoRT program has grown to be an end-to-end research to operations activity focused on the use of advanced NASA modeling and data assimilation approaches, nowcasting techniques, and unique high-resolution multispectral data from EOS satellites to improve short-term weather forecasts on a regional and local scale. Participation in the Proving Ground activities extends SPoRT s activities and taps its experience and expertise in diagnostic weather analysis, short-term weather forecasting, and the transition of research and experimental

Age and gender differences in correlations of leisure-time, household, and work-related physical activity with physical performance in older Japanese adults.

PubMed

Tsunoda, Kenji; Soma, Yuki; Kitano, Naruki; Tsuji, Taishi; Mitsuishi, Yasuhiro; Yoon, Ji-Yeong; Okura, Tomohiro

2013-10-01

This study aimed to compare relationships of leisure-time, household, and work-related physical activity (PA) with physical performance by age and gender in older Japanese adults. This cross-sectional study included 525 community-dwelling older adults (73.3 ± 5.2 years) recruited in 2009-2011 in Kasama City, rural Japan. We used the Physical Activity Scale for the Elderly to assess PA variables. Physical performance was evaluated by 11 performance tests: grip strength, single-leg balance, functional reach, sit-and-reach, standing time from long sitting position, sit-to-stand, timed up and go, habitual walk, hand working, and simple and choice reaction times. After adjusting for potential confounders, leisure-time PA in young-old (≤ 74 years) men correlated significantly with eight performance tests (absolute value of Spearman's partial rank correlation coefficient: r = 0.18-0.39), whereas in old-old (≥ 75 years) men it correlated with three performance tests (r = 0.20-0.23). Although leisure-time PA correlated with six performance tests (r = 0.19-0.22) in young-old women, there were no significant correlations between leisure-time PA and performance tests in old-old women. Household PA of young-old men (r = 0.20-0.23) and old-old women (r = 0.26-0.34) correlated with four performance tests. In old-old men and young-old women, no significant correlation was found between household PA and performance tests. Work-related PA did not relate significantly to any performance tests in any groups. This study showed that leisure-time PA is related to physical performance, especially in young-old men and women, and household PA is especially related in young-old men and old-old women. Our findings suggest that supporting strategies for maintaining physical functions would differ by gender and age. © 2013 Japan Geriatrics Society.

rRNA Genes Are Not Fully Activated in Mouse Somatic Cell Nuclear Transfer Embryos*

PubMed Central

Zheng, Zhong; Jia, Jia-Lin; Bou, Gerelchimeg; Hu, Li-Li; Wang, Zhen-Dong; Shen, Xing-Hui; Shan, Zhi-Yan; Shen, Jing-Ling; Liu, Zhong-Hua; Lei, Lei

2012-01-01

The well known and most important function of nucleoli is ribosome biogenesis. However, the nucleolus showed delayed development and malfunction in somatic cell nuclear transfer (NT) embryos. Previous studies indicated that nearly half rRNA genes (rDNA) in somatic cells were inactive and not transcribed. We compared the rDNA methylation level, active nucleolar organizer region (NORs) numbers, nucleolar proteins (upstream binding factor (UBF), nucleophosmin (B23)) distribution, and nucleolar-related gene expression in three different donor cells and NT embryos. The results showed embryonic stem cells (ESCs) had the most active NORs and lowest rDNA methylation level (7.66 and 6.76%), whereas mouse embryonic fibroblasts (MEFs) were the opposite (4.70 and 22.57%). After the donor cells were injected into enucleated MII oocytes, cumulus cells and MEFs nuclei lost B23 and UBF signals in 20 min, whereas in ESC-NT embryos, B23 and UBF signals could still be detected at 60 min post-NT. The embryos derived from ESCs, cumulus cells, and MEFs showed the same trend in active NORs numbers (7.19 versus 6.68 versus 5.77, p < 0.05) and rDNA methylation levels (6.36 versus 9.67% versus 15.52%) at the 4-cell stage as that in donor cells. However, the MEF-NT embryos displayed low rRNA synthesis/processing potential at morula stage and had an obvious decrease in blastocyst developmental rate. The results presented clear evidences that the rDNA reprogramming efficiency in NT embryos was determined by the rDNA activity in donor cells from which they derived. PMID:22467869

Influence of extracurricular sport activities on body composition and physical fitness in boys: a 3-year longitudinal study.

PubMed

Ara, I; Vicente-Rodriguez, G; Perez-Gomez, J; Jimenez-Ramirez, J; Serrano-Sanchez, J A; Dorado, C; Calbet, J A L

2006-07-01

To analyse the effect of extracurricular physical activities on fat mass accumulation and physical fitness during growth in early pubertal males. Longitudinal study. A total of 42 male children (9.4+/-1.4 years, Tanner I-II and 12.7+/-1.5 years, Tanner III-IV, before and after the 3.3 years follow-up, respectively), randomly sampled from the population of Gran Canaria (Spain), 26 of them physically active (PA, at least 3 h per week during 3 years) and 16 non-physically active (non-PA). Body composition (dual-energy X-ray absorptiometry), anthropometrics (body circumferences and skinfolds) and physical fitness variables (dynamic and isometric force, anaerobic capacity and maximal aerobic power) were determined in all subjects. Both groups had comparable body sizes at the start and the end of the study. Body mass index increased with growth more in the PA than in the non-PA group (P<0.05). However, fat mass accumulation with growth was lower in the PA than in the non-PA (P<0.05). There was a positive relationship between the increment of total and trunkal fat mass, especially in non-active children (r2=0.93). In contrast, there was an inverse relationship between the total lean mass growth and the accumulation of total and regional fat mass (r=-0.37 to -0.41, all P<0.05). Physical fitness was maintained in the PA, while it worsened in the non-PA children. Without any dietary intervention, children who regularly participate in at least 3 h per week of sports activities are more protected against total and regional fat mass accumulation. They also increase their total lean and bone mass to a greater extent than children who do not participate in extracurricular sport activities. In addition, PA children maintain their physical fitness during growth, while it deteriorates in the non-PA children.

Using pedometers to estimate ambulatory physical activity in Vietnam.

PubMed

Thuy, Au Bich; Blizzard, Leigh; Schmidt, Michael; Magnussen, Costan; Hansen, Emily; Dwyer, Terence

2011-01-01

Pedometer measurement of physical activity (PA) has been shown to be reliable and valid in industrialized populations, but its applicability in economically developing Vietnam remains untested. This study assessed the feasibility, stability and validity of pedometer estimates of PA in Vietnam. 250 adults from a population-based survey were randomly selected to wear Yamax pedometers and record activities for 7 consecutive days. Stability and concurrent validity were assessed using intraclass correlation coefficients (ICC) and Spearman correlation coefficients. Overall, 97.6% of participants provided at least 1 day of usable recordings, and 76.2% wore pedometers for all 7 days. Only 5.2% of the sample participants were involved in work activities not measurable by pedometer. The number of steps increased with hours of wear. There was no significant difference between weekday and weekend in number of steps, and at least 3 days of recordings were required (ICC of the 3 days of recordings: men 0.96, women 0.97). Steps per hour were moderately correlated (men r = .42, women r = .26) with record estimates of total PA. It is feasible to use pedometers to estimate PA in Vietnam. The measure should involve at least 3 days of recording irrespective of day of the week. ©2011 Human Kinetics, Inc.

Effect of a Long-Term Physical Activity Intervention on Resting Pulse Rate in Older Persons: Results from the LIFE Study

PubMed Central

Hartaigh, Bríain ó; Lovato, Laura C.; Pahor, Marco; Buford, Thomas W.; Dodson, John A.; Forman, Daniel E.; Buman, Matthew P.; Demons, Jamehl L.; Santanasto, Adam J.; Liu, Christine; Miller, Michael E.; McDermott, Mary McGrae; Gill, Thomas M.

2016-01-01

Background High resting pulse rate (RPR) is often associated with adverse cardiovascular risk. Prior studies show that habitual exercise slows RPR, though most studies have focused primarily on persons younger than 65 years. Our objective was to assess the utility of a long-term physical activity (PA) intervention for reducing RPR in older persons. Design Lifestyle Interventions and Independence for Elders Study. Setting Community based. Participants A total 1,635 persons (67.2% women) aged 70–89 years were randomized to a moderate intensity PA intervention (n=818) or health education-based “successful aging” (SA) intervention (n=817). Measurements RPR was recorded at baseline, 6-, 18-, and 30-months. Longitudinal changes in RPR were evaluated between intervention groups using a mixed-effects analysis of covariance model for repeatedly measured outcomes, generating least squares means with standard errors (SE) or 95% confidence intervals (95% CI). Results Mean duration of the study was 2.6 years (median, 2.7 years; interquartile range, 2.3–3.1 years). The average effect of the PA intervention on RPR across follow-up visits was statistically significant but clinically small (Average Intervention Difference = 0.84 beats/min; 95% CI 0.17 to 1.51; Paverage =0.01), with the most pronounced effect observed at 18-months (PA: 66.5 [0.32] beats/min, SA: 67.8 [0.32] beats/min, Difference = 1.37 (95% CI 0.48 to 2.26). The relationship became somewhat weaker and was not statistically significant at 30-months. There were no significant differences across several pre-specified subgroups. Conclusion A long-term moderate-intensity physical activity program was associated with a small and clinically insignificant slowing of RPR in older persons. Whether physical activity can deliver a beneficial reduction in RPR requires further examination among older adults. PMID:27787876

Associations of objectively measured physical activity with daily mood ratings and psychophysiological stress responses in women.

PubMed

Poole, Lydia; Steptoe, Andrew; Wawrzyniak, Andrew J; Bostock, Sophie; Mitchell, Ellen S; Hamer, Mark

2011-08-01

The aim of this study was to examine associations of objectively measured physical activity with daily mood ratings and psychophysiological stress responses. We recruited 40 healthy females (aged 28.7 ± 6.1 yrs) who completed a once-a-day mood rating scale for 7 days, along with a 7-day assessment of physical activity using accelerometers and psychophysiological stress testing. The findings suggest that levels of physical activity as measured using an accelerometer are associated with both depressive symptoms over the past 2 weeks (CES-D) (r = - .33, p = .038) and with daily positive emotional style (r = .49, p = .001). The relationship between physical activity and positive emotional style remained after controlling for age, body mass index, and negative emotional style (t = 3.31, p = .002). Physical activity was not related to any psychophysiological stress responses. Copyright © 2011 Society for Psychophysiological Research.

The BPAQ: a bone-specific physical activity assessment instrument.

PubMed

Weeks, B K; Beck, B R

2008-11-01

A newly developed bone-specific physical activity questionnaire (BPAQ) was compared with other common measures of physical activity for its ability to predict parameters of bone strength in healthy, young adults. The BPAQ predicted indices of bone strength at clinically relevant sites in both men and women, while other measures did not. Only certain types of physical activity (PA) are notably osteogenic. Most methods to quantify levels of PA fail to account for bone relevant loading. Our aim was to examine the ability of several methods of PA assessment and a new bone-specific measure to predict parameters of bone strength in healthy adults. We recruited 40 men and women (mean age 24.5). Subjects completed the modifiable activity questionnaire, Bouchard 3-day activity record, a recently published bone loading history questionnaire (BLHQ), and wore a pedometer for 14 days. We also administered our bone-specific physical activity questionnaire (BPAQ). Calcaneal broadband ultrasound attenuation (BUA) (QUS-2, Quidel) and densitometric measures (XR-36, Norland) were examined. Multiple regression and correlation analyses were performed on the data. The current activity component of BPAQ was a significant predictor of variance in femoral neck bone mineral density (BMD), lumbar spine BMD, and whole body BMD (R(2) = 0.36-0.68, p < 0.01) for men, while the past activity component of BPAQ predicted calcaneal BUA (R(2) = 0.48, p = 0.001) for women. The BPAQ predicted indices of bone strength at skeletal sites at risk of osteoporotic fracture while other PA measurement tools did not.

[Validity of four questionnaires to assess physical activity in Spanish adolescents].

PubMed

Martínez-Gómez, David; Martínez-De-Haro, Vicente; Del-Campo, Juan; Zapatera, Belén; Welk, Gregory J; Villagra, Ariel; Marcos, Ascensión; Veiga, Oscar L

2009-01-01

The physical activity (PA) levels of Spanish adolescents must be determined to assess how the lack of PA may affect the increasing prevalence of obesity. Thus, to assess PA in this age range valid measurement instruments are essential. The aim of this study was to evaluate the validity of four easily applied questionnaires (the enKid and FITNESSGRAM questions, the Patient-Centered Assessment and Counselling [PACE] questionnaire, and an activity rating) to assess PA in Spanish adolescents by using an accelerometer as the criterion instrument. A total of 232 adolescents (113 girls) completed the questionnaires and wore an ActiGraph accelerometer for 7 consecutive days. Spearman's correlation coefficient (rho) was used to compare the questionnaires and total PA, moderate PA, vigorous PA and moderate-to-vigorous PA (MVPA) assessed by the accelerometer. All the questionnaires showed moderate correlations when compared against total PA (rho=0.36-0.43) and MVPA (rho=0.34-0.46) obtained by the accelerometer in the total sample. Higher correlations were found when comparing the questionnaires against vigorous PA (rho=0.42-0.51) than against moderate PA (rho=0.15-0.17). The FITNESSGRAM question and the PACE questionnaire obtained weak correlations in girls and the enKid question and activity rating were moderately correlated for boys and girls. The four questionnaires evaluated showed acceptable validity in the assessment of PA in the Spanish adolescent population.

Comparison of PA imaging by narrow beam scanning and one-shot broad beam excitation

NASA Astrophysics Data System (ADS)

Xia, Jinjun; Wei, Chen-Wei; Huang, Lingyun; Pelivanov, I. M.; O'Donnell, Matthew

2011-03-01

Current systems designed for deep photoacoustic (PA) imaging typically use a low repetition rate, high power pulsed laser to provide a ns-scale pulse illuminating a large tissue volume. Acoustic signals recorded on each laser firing can be used to reconstruct a complete 2-D (3-D) image of sources of heat release within that region. Using broad-beam excitation, the maximum frame rate of the imaging system is restricted by the pulse repetition rate of the laser. An alternate illumination approach is proposed based on fast scanning by a low energy (~ 1 mJ) high repetition rate (up to a few kHz) narrow laser beam (~1 mm) along the tissue surface over a region of interest. A final PA image is produced from the summation of individual PA images reconstructed at each laser beam position. This concept can take advantage of high repetition rate fiber lasers to create PA images with much higher frame rates than current systems, enabling true real-time integration of photoacoustics with ultrasound imaging. As an initial proof of concept, we compare conventional broad beam illumination to a scanned beam approach in a simple model system. Two transparent teflon tubes with diameters of 1.6 mm and 0.8 mm were filled with ink having an absorption coefficient of 5 cm-1. These tubes were buried inside chicken breast tissue acting as an optical scattering medium. They were separated by 3 mm or 10 mm to test spatial and contrast resolution for the two scan formats. The excitation wavelength was 700 nm. The excitation source is a traditional OPO pumped by a Q-switched Nd:YAG laser with doubler. Photoacoustic images were reconstructed using signals from a small, scanned PVDF transducer acting as an acoustic array. Two different illumination schemes were compared: one was 15 mm x 10 mm in cross section and acted as the broad beam; the other was 5 mm x 2 mm in cross section (15 times smaller than the broad beam case) and was scanned over an area equivalent to broad beam illumination

The role of daily physical activity and nutritional status on bone turnover in cystic fibrosis: a cross-sectional study.

PubMed

Tejero, Sergio; Cejudo, Pilar; Quintana-Gallego, E; Sañudo, Borja; Oliva-Pascual-Vaca, A

2016-03-18

Nutritional status and daily physical activity (PA) may be an excellent tool for the maintenance of bone health in patients with cystic fibrosis (CF). To evaluate the relationship between nutritional status, daily physical activity and bone turnover in cystic fibrosis patients. A cross-sectional study of adolescent and adult patients diagnosed with clinically stable cystic fibrosis was conducted. Total body, femoral neck, and lumbar spine bone mineral density (BMD) were determined by dual energy X-ray absorptiometry and bone metabolism markers ALP, P1NP, PICP, and ß-CrossLaps. PA monitoring was assessed for 5 consecutive days using a portable device. Exercise capacity was also determined. Serum 25-hydroxyvitamin D and vitamin K were also determined in all participants. Fifty patients (median age: 24.4 years; range: 16-46) were included. BMI had positive correlation with all BMD parameters, with Spearman's coefficients ranging from 0.31 to 0.47. Total hip bone mineral density and femoral neck BMD had positive correlation with the daily time spent on moderate PA (>4.8 metabolic equivalent-minutes/day; r=0.74, p<0.001 and r=0.72 p<0.001 respectively), daily time spent on vigorous PA (>7.2 metabolic equivalent-minutes/day; r=0.45 p<0.001), body mass index (r=0.44, p=0.001), and muscle mass in limbs (r=0.41, p=0.004). Levels of carboxy-terminal propeptide of type 1 collagen were positively associated with the daily time spent on moderate (r=0.33 p=0.023) and vigorous PA (r=0.53, p<0.001). BMI and the daily time spent on moderate PA were found to be correlated with femoral neck BMD in CF patients. The association between daily PA and biochemical markers of bone formation suggests that the level of daily PA may be linked to bone health in this patient group. Further research is needed to confirm these findings.

Prevalence of physical activity and sedentary-related behaviors among adolescents: data from the Qatar National School Survey.

PubMed

Al-Thani, M; Al-Thani, A; Alyafei, S; Al-Kuwari, M G; Al-Chetachi, W; Khalifa, S E; Ibrahim, I; Sayegh, S; Vinodson, B; Akram, H

2018-07-01

To investigate the prevalence of physical activity (PA) and sedentary behaviors among adolescents in Qatar by selected demographic characteristics. Cross-sectional study. A total of 5862 students (2938 boys and 2924 girls) in the age group 12-17 years were included in the analyses. PA and sedentary-related measures were obtained from the self-reported survey questions. Only 35.4% of students were performing 60 min of PA ≥3 days/week. The proportion of students with >2 hr screentime ranged from 43% to 57% (weekdays) and 50% to 62.5% (weekends). Girls had less odds of being physically active than the boys (odds ratio [OR] = 0.61, P < 0.001). Qatari students were less likely to be physically active than non-Qataris (OR = 0.79, P < 0.001). Age was inversely correlated with PA ([r = -0.113, P < 0.001 for participation with sports team] and [r = -0.139, P < 0.001 for school physical education classes]). Participation in sports teams positively correlated with 60 min of PA number of days in a week (r = 0.317, P < 0.001). The study describes insufficient PA among youth as a public health issue of concern in the State of Qatar that requires multipronged health promotion initiatives. Copyright © 2018 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

Neutron Capture Rates and the r-Process Abundance Pattern in Shocked Neutrino-Driven Winds

NASA Astrophysics Data System (ADS)

Barringer, Daniel; Surman, Rebecca

2009-10-01

The r-process is an important process in nucleosynthesis in which nuclei will undergo rapid neutron captures. Models of the r-process require nuclear data such as neutron capture rates for thousands of individual nuclei, many of which lie far from stability. Among the potential sites for the r-process, and the one that we investigate, is the shocked neutrino-driven wind in core-collapse supernovae. Here we examine the importance of the neutron capture rates of specific, individual nuclei in the second r-process abundance peak occurring at A ˜ 130 for a range of parameterized neutrino-driven wind trajectories. Of specific interest are the nuclei whose capture rates affect the abundances of nuclei outside of the A ˜ 130 peak. We found that increasing the neutron capture rate for a number of nuclei including ^135In, ^132Sn, ^133Sb, ^137Sb, and ^136Te can produce changes in the resulting abundance pattern of up to 13%.

78 FR 22285 - Notice of Inventory Completion: Carnegie Museum of Natural History, Pittsburgh, PA

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-15

....R50000] Notice of Inventory Completion: Carnegie Museum of Natural History, Pittsburgh, PA AGENCY: National Park Service, Interior. ACTION: Notice. SUMMARY: The Carnegie Museum of Natural History has... associated funerary objects should submit a written request to the Carnegie Museum of Natural History. If no...

Gain of function AMP-activated protein kinase γ3 mutation (AMPKγ3R200Q) in pig muscle increases glycogen storage regardless of AMPK activation.

PubMed

Scheffler, Tracy L; Park, Sungkwon; Roach, Peter J; Gerrard, David E

2016-06-01

Chronic activation of AMP-activated protein kinase (AMPK) increases glycogen content in skeletal muscle. Previously, we demonstrated that a mutation in the ryanodine receptor (RyR1(R615C)) blunts AMPK phosphorylation in longissimus muscle of pigs with a gain of function mutation in the AMPKγ3 subunit (AMPKγ3(R200Q)); this may decrease the glycogen storage capacity of AMPKγ3(R200Q) + RyR1(R615C) muscle. Therefore, our aim in this study was to utilize our pig model to understand how AMPKγ3(R200Q) and AMPK activation contribute to glycogen storage and metabolism in muscle. We selected and bred pigs in order to generate offspring with naturally occurring AMPKγ3(R200Q), RyR1(R615C), and AMPKγ3(R200Q) + RyR1(R615C) mutations, and also retained wild-type littermates (control). We assessed glycogen content and parameters of glycogen metabolism in longissimus muscle. Regardless of RyR1(R615C), AMPKγ3(R200Q) increased the glycogen content by approximately 70%. Activity of glycogen synthase (GS) without the allosteric activator glucose 6-phosphate (G6P) was decreased in AMPKγ3(R200Q) relative to all other genotypes, whereas both AMPKγ3(R200Q) and AMPKγ3(R200Q) + RyR1(R615C) muscle exhibited increased GS activity with G6P. Increased activity of GS with G6P was not associated with increased abundance of GS or hexokinase 2. However, AMPKγ3(R200Q) enhanced UDP-glucose pyrophosphorylase 2 (UGP2) expression approximately threefold. Although UGP2 is not generally considered a rate-limiting enzyme for glycogen synthesis, our model suggests that UGP2 plays an important role in increasing flux to glycogen synthase. Moreover, we have shown that the capacity for glycogen storage is more closely related to the AMPKγ3(R200Q) mutation than activity. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Predicting Activity Energy Expenditure Using the Actical[R] Activity Monitor

ERIC Educational Resources Information Center

Heil, Daniel P.

2006-01-01

This study developed algorithms for predicting activity energy expenditure (AEE) in children (n = 24) and adults (n = 24) from the Actical[R] activity monitor. Each participant performed 10 activities (supine resting, three sitting, three house cleaning, and three locomotion) while wearing monitors on the ankle, hip, and wrist; AEE was computed…

Validity of hip-mounted uniaxial accelerometry with heart-rate monitoring vs. triaxial accelerometry in the assessment of free-living energy expenditure in young children: the IDEFICS Validation Study.

PubMed

Ojiambo, Robert; Konstabel, Kenn; Veidebaum, Toomas; Reilly, John; Verbestel, Vera; Huybrechts, Inge; Sioen, Isabelle; Casajús, José A; Moreno, Luis A; Vicente-Rodriguez, German; Bammann, Karin; Tubic, Bojan M; Marild, Staffan; Westerterp, Klaas; Pitsiladis, Yannis P

2012-11-01

One of the aims of Identification and Prevention of Dietary- and Lifestyle-Induced Health Effects in Children and Infants (IDEFICS) validation study is to validate field measures of physical activity (PA) and energy expenditure (EE) in young children. This study compared the validity of uniaxial accelerometry with heart-rate (HR) monitoring vs. triaxial accelerometry against doubly labeled water (DLW) criterion method for assessment of free-living EE in young children. Forty-nine European children (25 female, 24 male) aged 4-10 yr (mean age: 6.9 ± 1.5 yr) were assessed by uniaxial ActiTrainer with HR, uniaxial 3DNX, and triaxial 3DNX accelerometry. Total energy expenditure (TEE) was estimated using DLW over a 1-wk period. The longitudinal axis of both devices and triaxial 3DNX counts per minute (CPM) were significantly (P < 0.05) associated with physical activity level (PAL; r = 0.51 ActiTrainer, r = 0.49 uniaxial-3DNX, and r = 0.42 triaxial Σ3DNX). Eight-six percent of the variance in TEE could be predicted by a model combining body mass (partial r(2) = 71%; P < 0.05), CPM-ActiTrainer (partial r(2) = 11%; P < 0.05), and difference between HR at moderate and sedentary activities (ModHR - SedHR) (partial r(2) = 4%; P < 0.05). The SE of TEE estimate for ActiTrainer and 3DNX models ranged from 0.44 to 0.74 MJ/days or ∼7-11% of the average TEE. The SE of activity-induced energy expenditure (AEE) model estimates ranged from 0.38 to 0.57 MJ/day or 24-26% of the average AEE. It is concluded that the comparative validity of hip-mounted uniaxial and triaxial accelerometers for assessing PA and EE is similar.

Biological age and sex-related declines in physical activity during adolescence.

PubMed

Cairney, John; Veldhuizen, Scott; Kwan, Matthew; Hay, John; Faught, Brent E

2014-04-01

Sex differences in the rate of decline in physical activity (PA) are most pronounced during adolescence. However, once boys and girls are aligned on biological age, sex differences in the patterns of PA become attenuated. The aim of this study was to test whether biological maturation can account for sex differences in participation in PA over time from late childhood to early adolescence. A prospective cohort of children (N = 2100; 1064 boys) was followed from ages 11 to 14 yr, with repeated assessments of PA and anthropometry. Self-reported participation in organized and free play activities was used to track participation in PA. Biological age was measured using an estimate of years to attainment of peak height velocity. Mixed-effects models were used to test whether controlling for biological age attenuates the effect of chronological age and sex on PA. As expected, the rate of decline in participation in PA was greater for girls than for boys (B = -1.18, P < 0.01). In multivariable analyses, adjusting for biological age completely attenuated the effect of sex and chronological age for participation in free play activities, but not for participation in organized play. Overall, biological age was a stronger predictor of participation than chronological age. The effect of biological age on sex by chronological age differences may be specific to certain types of PA participation. Given the importance of maturation to participation in activity, it is suggested that public health strategies target biological not chronological age to prevent declines in PA during adolescence particularly when promoting habitual or lifestyle activity.

Technical Insights for Saltstone PA Maintenance

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

Flach, G.; Sarkar, S.; Mahadevan, S.

2011-07-20

compatibility with existing CBP expertise and already-planned activities. Based on these criteria, the five original topics were down-selected to two: external sulfate attack and mechanistic geochemical prediction. For each of the selected topics, the CBP communicated with the PA analysts and subject matter experts at Savannah River to acquire input data specific to the Saltstone facility and related laboratory experiments. Simulations and analyses were performed for both topics using STADIUM (SIMCO 2008), LeachXS/ORCHESTRA (ECN 2007, Meeussen 2003), and other software tools. These supplemental CBP analyses produced valuable technical insights that can be used to strengthen the Saltstone PA using the ongoing PA maintenance process. This report in part summarizes key information gleaned from more comprehensive documents prepared by Sarkar et al. (2010), Samson (2010), and Sarkar (2010).« less

Sliding friction study of the oscillating translational motion for steel on PA66 and PA46 type materials

NASA Astrophysics Data System (ADS)

Lates, M. T.; Velicu, R. G.; Papuc, R.

2016-08-01

The paper presents the study of the friction, by using tests, in the sliding translational oscillating motion of the steel on PA46 relative to the steel on PA66 type materials by considering as variables the testing parameters as: the load, the velocity and the operating temperature. The paper starts with a study of the literature and, according to that, presents the main conclusions regarding the sliding friction of the steel on PA66 and PA46 type materials and identifies the lacks of the results. The tests are performed on an oscillating motion type tribometer module. First, it is made a running-in program, for each of the materials, at 25 and 90°C, a load of 5 N and a frequency of 1 Hz for one hour; after that, there are performed tests at 90°C and 120°C, at loads of 3 N, 5 N, 7 N and at frequencies at 0.25 Hz, 5 Hz and 1 Hz. The results are presented for the PA46 type material relative to the PA66 material. The conclusions indicate in which conditions and with which advantages are used the PA66 and PA46 polyamides in the case of oscillating translational motions.

Regional variation in rates of pediatric perforated appendicitis.

PubMed

Sarda, Samir; Short, Heather L; Hockenberry, Jason M; McCarthy, Ian; Raval, Mehul V

2017-09-01

While trends in perforated appendicitis (PA) rates have been studied, regional variability in pediatric admissions for PA remains unknown. A retrospective, cross-sectional analysis of the 2006-2012 Kids' Inpatient Database was conducted to examine variation in PA admission rates by region of the United States and insurance status. PA rates were calculated and reported as per 1000 admissions in accordance with national quality measure specifications. National PA rates per 1000 admissions for 2006, 2009, and 2012 were 313.9, 279.2, and 309.1, respectively. Similarly, all regions demonstrated a statistically significant decrease in PA rates between 2006 and 2009 (p<0.001), where the increase in rates between 2009 and 2012 was only statistically significant in the Midwest [Odds Ratio (OR) 1.07; 95% Confidence Interval (95%CI) 1.03-1.12] and West (OR 1.10; 95% CI 1.07-1.14). The Northeast consistently experienced the lowest PA rates. The odds of PA were highest among uninsured patients (OR 1.35; 95% CI 1.31-1.29). The South had the highest proportion of uninsured children, and these patients had the highest odds of perforation (OR 1.57; 95% CI 1.21-2.02). For children with appendicitis, geographic region and insurance status appear to be associated with perforation upon presentation. Understanding regional variation in pediatric PA rates may inform health policymakers in the constantly evolving insurance coverage landscape. Level III Treatment Study - Retrospective comparative study of appendicitis presentation in children by region of the country. Copyright © 2017 Elsevier Inc. All rights reserved.

Assessment of error rates in acoustic monitoring with the R package monitoR

USGS Publications Warehouse

Katz, Jonathan; Hafner, Sasha D.; Donovan, Therese

2016-01-01

Detecting population-scale reactions to climate change and land-use change may require monitoring many sites for many years, a process that is suited for an automated system. We developed and tested monitoR, an R package for long-term, multi-taxa acoustic monitoring programs. We tested monitoR with two northeastern songbird species: black-throated green warbler (Setophaga virens) and ovenbird (Seiurus aurocapilla). We compared detection results from monitoR in 52 10-minute surveys recorded at 10 sites in Vermont and New York, USA to a subset of songs identified by a human that were of a single song type and had visually identifiable spectrograms (e.g. a signal:noise ratio of at least 10 dB: 166 out of 439 total songs for black-throated green warbler, 502 out of 990 total songs for ovenbird). monitoR’s automated detection process uses a ‘score cutoff’, which is the minimum match needed for an unknown event to be considered a detection and results in a true positive, true negative, false positive or false negative detection. At the chosen score cut-offs, monitoR correctly identified presence for black-throated green warbler and ovenbird in 64% and 72% of the 52 surveys using binary point matching, respectively, and 73% and 72% of the 52 surveys using spectrogram cross-correlation, respectively. Of individual songs, 72% of black-throated green warbler songs and 62% of ovenbird songs were identified by binary point matching. Spectrogram cross-correlation identified 83% of black-throated green warbler songs and 66% of ovenbird songs. False positive rates were  for song event detection.

The Effect of an Active Transport to School Intervention at a Suburban Elementary School

ERIC Educational Resources Information Center

Bungum, Timothy J.; Clark, Sheila; Aguilar, Brenda

2014-01-01

Background: Many children do not meet physical activity (PA) guidelines. One strategy that may enhance PA is to increase active transport to school (ATS) rates. Purpose: To assess the effects of an ATS intervention. Methods: A quasi-experimental design was used to compare ATS and vehicle traffic rates at a school that participated in a statewide…

Effect of parental R-rated movie restriction on adolescent smoking initiation: a prospective study.

PubMed

Sargent, James D; Beach, Michael L; Dalton, Madeline A; Ernstoff, Linda Titus; Gibson, Jennifer J; Tickle, Jennifer J; Heatherton, Todd F

2004-07-01

To determine if young adolescents who report that their parents restrict viewing R-rated movies have a lower risk of trying smoking in the future. Prospective observational study. Students from 15 schools in New Hampshire and Vermont, randomly selected from all middle schools with >150 students, were surveyed in 1999. Baseline never-smokers were surveyed again by telephone 13 to 26 months later to determine smoking status. Trying smoking during the follow-up period. The majority of the 2596 students were white, with ages ranging from 10 to 14 years. Nineteen percent reported that their parents never allowed them to view R-rated movies, 29% were allowed once in a while, and 52% were allowed sometimes or all the time. Ten percent of students tried smoking during the follow-up period. Smoking-initiation rates increased as parental restriction of R-rated movies decreased (2.9% for adolescents reporting that their parents never allowed them to view R-rated movies, 7.0% for those allowed to view them once in a while, and 14.3% for those allowed to view them sometimes or all the time). There was a strong and statistically significant effect of parental R-rated movie restriction on adolescent smoking even after controlling for sociodemographics, social influences (friend smoking, receptivity to tobacco promotions), parenting style (maternal support and control, parental disapproval of smoking), and characteristics of the adolescent (school performance, sensation seeking, rebelliousness, self-esteem). Compared with adolescents whose parents never allowed them to view R-rated movies, the adjusted relative risk for trying smoking was 1.8 (95% confidence interval [CI]: 1.1, 3.1) for those allowed to watch them once in a while and 2.8 (95% CI: 1.6, 4.7) for those allowed to watch them sometimes or all the time. The effect was especially strong among adolescents not exposed to family (parent or sibling) smoking, among whom the adjusted relative risk for smoking was 4.3 (95% CI

Antiviral Activity of Bay 41-4109 on Hepatitis B Virus in Humanized Alb-uPA/SCID Mice

PubMed Central

Brezillon, Nicolas; Brunelle, Marie-Noëlle; Massinet, Hélène; Giang, Eric; Lamant, Céline; DaSilva, Lucie; Berissi, Sophie; Belghiti, Jacques; Hannoun, Laurent; Puerstinger, Gherard; Wimmer, Eva; Neyts, Johan; Hantz, Olivier; Soussan, Patrick; Morosan, Serban; Kremsdorf, Dina

2011-01-01

Current treatments for HBV chronic carriers using interferon alpha or nucleoside analogues are not effective in all patients and may induce the emergence of HBV resistant strains. Bay 41-4109, a member of the heteroaryldihydropyrimidine family, inhibits HBV replication by destabilizing capsid assembly. The aim of this study was to determine the antiviral effect of Bay 41-4109 in a mouse model with humanized liver and the spread of active HBV. Antiviral assays of Bay 41-4109 on HepG2.2.15 cells constitutively expressing HBV, displayed an IC50 of about 202 nM with no cell toxicity. Alb-uPA/SCID mice were transplanted with human hepatocytes and infected with HBV. Ten days post-infection, the mice were treated with Bay 41-4109 for five days. During the 30 days of follow-up, the HBV load was evaluated by quantitative PCR. At the end of treatment, decreased HBV viremia of about 1 log(10) copies/ml was observed. By contrast, increased HBV viremia of about 0.5 log(10) copies/ml was measured in the control group. Five days after the end of treatment, a rebound of HBV viremia occurred in the treated group. Furthermore, 15 days after treatment discontinuation, a similar expression of the viral capsid was evidenced in liver biopsies. Our findings demonstrate that Bay 41-4109 displayed antiviral properties against HBV in humanized Alb-uPA/SCID mice and confirm the usefulness of Alb-uPA/SCID mice for the evaluation of pharmaceutical compounds. The administration of Bay 41-4109 may constitute a new strategy for the treatment of patients in escape from standard antiviral therapy. PMID:22162746

Comparison of rSP-C surfactant with natural and synthetic surfactants after late treatment in a rat model of the acute respiratory distress syndrome

PubMed Central

Häfner, Dietrich; Germann, Paul-Georg; Hauschke, Dieter

1998-01-01

In a previous paper we showed that an SP-C containing surfactant preparation has similar activity as bovine-derived surfactants in a rat lung lavage model of the adult respiratory distress syndrome. In this study surfactant was given ten minutes after the last lavage (early treatment). In the present investigation we were interested how different surfactant preparations behave when they are administered 1 h after the last lavage (late treatment). Four protein containing surfactants (rSP-C surfactant, bLES, Infasurf and Survanta) were compared with three protein-free surfactants (ALEC, Exosurf and the phospholipid (PL) mixture of the rSP-C surfactant termed PL surfactant) with respect to their ability to improve gas exchange in this more stringent model when surfactant is given one hour after the last lavage. For better comparison of the surfactants the doses were related to phospholipids. The surfactants were given at doses of 25, 50 and 100 mg kg−1 body weight. The surfactants were compared to an untreated control group that was only ventilated for the whole experimental period. Tracheotomized rats (8–12 per dose and surfactant) were pressure-controlled ventilated (Siemens Servo Ventilator 900C) with 100% oxygen at a respiratory rate of 30 breaths min−1, inspiration expiration ratio of 1 : 2, peak inspiratory pressure of 28 cmH2O at positive endexpiratory pressure (PEEP) of 8 cmH2O. Animals were ventilated for one hour after the last lavage and thereafter the surfactants were intratracheally instilled. During the whole experimental period the ventilation was not changed. Partial arterial oxygen pressures (PaO2, mmHg) at 30 min and 120 min after treatment were used for statistical comparison. All protein containing surfactants caused a dose-dependent increase of the reduced PaO2 values at 30 min after treatment. The protein-free surfactants showed only weak dose-dependent increase in PaO2 values at this time. This difference between the

Jet activity in the symbiotic variable R Aquarii

NASA Technical Reports Server (NTRS)

Michalitsianos, A. G.; Hollis, J. M.; Kafatos, M.

1986-01-01

Low-resolution ultraviolet spectra of the R Aquarii jet have been obtained with the International Ultraviolet Explorer (IUE). The most recent IUE observations indicate the ionization state of the jet is increasing. Subarcsecond, Very Large Array observations of R Aquarii have resolved the radio-continuum structure into discrete parcels of emission that are extended and nearly collinear. R Aquarii provides evidence that indicates stellar jet activity is not unique to objects associated with high-energy emission processes alone. Rather, the nature of the aligned radio-optical features that comprise the R Aquarii jet indicate that directional mass expulsion, in the form of discrete-collimated ejecta, probably reflect a general, underlying, physical process associated with a wide variety of peculiar stellar objects. As such, the R Aquarii jet constitutes a prototype for jet activity in composite or peculiar emission stars.

Parent influences on preschoolers' objectively assessed physical activity.

PubMed

Oliver, Melody; Schofield, Grant M; Schluter, Philip J

2010-07-01

The purposes of this study were to examine the relationship between accelerometer-derived physical activity (PA) in preschoolers and their parents, and to investigate other potential child and parental associates of child PA. Families of children aged 2-5 yrs were recruited in Auckland, New Zealand, from October 2006 to July 2007. Consenting children and parents had their height, weight, and waist circumference measured and were asked to wear accelerometers over 7 consecutive days, measuring PA in 15s epochs. Accelerometer data were gathered from 78 children, 62 mothers and 20 fathers over a median of 6.5-7 days, and converted to estimated daily PA rates for each individual using negative binomial generalised estimating equation (GEE) modelling. Potential associates of children's daily PA rates were then assessed using normal GEE models with exchangeable correlation structures. After taking account of all factors in the final multivariable model, parental PA rates (coefficient 0.09, 95% CI 0.03, 0.16, P=0.01) and child age (coefficient 0.11, 95% CI 0.01, 0.21, P=0.03) were the only factors significantly associated with child PA rates. Younger children may stand to benefit from PA intervention, and encouraging parental involvement in preschool PA interventions may be useful for increasing PA levels in young children. More work in this field is needed to corroborate these findings, improve generalisability, and determine causality. Copyright 2009 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

A Retrospective Study of thrombolysis with 0.6 mg/kg Recombinant Tissue Plasminogen Activator (rt-PA) in Mild Stroke.

PubMed

Yang, Jie; Yu, Fei; Liu, Hong; An, Hedi; Xiong, Ran; Huang, Dongya

2016-08-11

We sought to assess the safety, effectiveness and cost of 0.6 mg/kg rt-PA treatment for patients with acute mild stroke and to compare that with 0.9 mg/kg. We retrospectively analyzed consecutive acute ischemic stroke patients who had a NIHSS score ≤5 at admission and who were treated with rt-PA within 4.5 hours of symptom onset. The demographic data, clinical outcomes and hospitalization cost were analyzed. A total of 108 patients were included. Forty six patients (42.6%) received a 0.6 mg/kg dosage of rt-PA. The baseline characteristics of the two groups were well matched (p > 0.05). Regarding the safety and effectiveness, the 0.6 mg/kg dosage group had a comparable proportion of symptomatic intracranial hemorrhage (sICH) (0.6 mg/kg, 4.3% vs 0.9 mg/kg, 4.8%; p > 0.05), early neurological deterioration (END) (19.6% vs 17.7%; p > 0.05), in-hospital mortality (4.3% vs 1.6%; p > 0.05), and a similar rate of favorable functional outcome (mRS score 0-1) at 3 months (73.9% vs 71.0%; p > 0.05) to those who received the standard dosage. However, the hospital cost was markedly lower in the 0.6 mg/kg group (0.6  mg/kg, 3,401.7 USD vs 0.9  mg/kg, 4,157.4 USD; p < 0.01). Our study suggest that 0.6 mg/kg rt-PA shared similar effectiveness and safety profile compared with that of 0.9 mg/kg in treating mild stroke, but cost less.

Sixty Minutes of Physical Activity per Day Included Within Preschool Academic Lessons Improves Early Literacy.

PubMed

Kirk, Stacie M; Kirk, Erik P

2016-03-01

The effects of increases in physical activity (PA) on early literacy skills in preschool children are not known. Fifty-four African-American preschool children from a low socioeconomic urban Head Start participated over 8 months. A 2-group, quasi-experimental design was used with one preschool site participating in the PA intervention and a second site participating as the control site. The PA program was designed to promote 300 minutes/week of moderate to vigorous PA academic lessons. Academic achievement related to early literacy and phonological awareness in the areas of rhyming and alliteration were assessed at baseline, 4 and 8 months. Over 8 months, rhyming significantly (p < .01) improved in the PA group (173 ± 12%) compared with the controls (28 ± 8%) resulting in between group differences at 8 months (p < .01). Alliteration significantly (p < .01) improved in the PA group (52 ± 16%) compared with controls (13 ± 5%), resulting in between group differences at 8 months (p < .01). As minutes of exposure to moderate to vigorous PA increased, the change in picture naming (R(2) = .35, p < .05), alliteration (R(2) = .38, p < .05), and rhyming (R(2) = .42, p < .05), increased. A teacher-directed PA program is effective at increasing PA and improving early literacy. © 2016, American School Health Association.

75 FR 69468 - Metlife Moosic, PA, Metlife Clarks Summit, PA; Notice of Affirmative Determination Regarding...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-12

... DEPARTMENT OF LABOR Employment and Training Administration [TA-W-73,210; TA-W-73,210A] Metlife Moosic, PA, Metlife Clarks Summit, PA; Notice of Affirmative Determination Regarding Application for Reconsideration By application dated August 2, 2010, the petitioners requested administrative reconsideration of...

Development and Validation of the Cognitive Behavioral Physical Activity Questionnaire.

PubMed

Schembre, Susan M; Durand, Casey P; Blissmer, Bryan J; Greene, Geoffrey W

2015-01-01

Develop and demonstrate preliminary validation of a brief questionnaire aimed at assessing social cognitive determinants of physical activity (PA) in a college population. Quantitative and observational. A midsized northeastern university. Convenience sample of 827 male and female college students age 18 to 24 years. International Physical Activity Questionnaire and a PA stage-of-change algorithm. A sequential process of survey development, including item generation and data reduction analyses by factor analysis, was followed with the goal of creating a parsimonious questionnaire. Structural equation modeling was used for confirmatory factor analysis and construct validation was confirmed against self-reported PA and stage of change. Validation analyses were replicated in a second, independent sample of 1032 college students. Fifteen items reflecting PA self-regulation, outcome expectations, and personal barriers explained 65% of the questionnaire data and explained 28.6% and 39.5% of the variance in total PA and moderate-to-vigorous-intensity PA, respectively. Scale scores were distinguishable across the stages of change. Findings were similar when the Cognitive Behavioral Physical Activity Questionnaire (CBPAQ) was tested in a similar and independent sample of college students (40%; R (2) moderate-to-vigorous-intensity PA = .40; p < .001). The CBPAQ successfully explains and predicts PA behavior in a college population, warranting its incorporation into future studies aiming at understanding and improving on PA behavior in college students.

The relationship between the built environment and habitual levels of physical activity in South African older adults: a pilot study.

PubMed

Kolbe-Alexander, Tracy L; Pacheco, Kyla; Tomaz, Simone A; Karpul, David; Lambert, Estelle V

2015-05-30

Previous research has shown that the built environment plays a role in habitual levels of physical activity (PA), however much of this research has been conducted in adults and higher income countries. The aim of this pilot study was to examine the strength of association between the built environment and PA in South African older adults. Participants were recruited (n = 44, mean age 65 ± 8.5 years) from two suburbs, representing either a high socioeconomic (HSA) or low socioeconomic area (LSA). Self-reported PA, and subjective assessments of neighborhood walkability (Neighborhood Environment Walkability Scale, NEWS) was measured. Participants wore Actigraph GT3x accelerometers to objectively quantify PA. HSA participants reported significantly more leisure-time and less transport PA. Objectively measured and self-reported MVPA was significantly higher in HSA participants. NEWS 'Land-use Mix' was negatively associated with leisure-time MVPA, (r(2) = 0.20; p < 0.02). In addition, neighborhood aesthetics was positively associated with leisure-time physical activity (r(2) = 0.33; p = 0.02). 'Safety from traffic' was inversely associated with travel-related PA (r(2) = 0.14, p = 0.01). None of the other NEWS scores were associated with PA for the total group. Leisure-time and transport-related PA was influenced by socio-economic status. Attributes of the perceived built environment associated with leisure-time and total MVPA in older South Africa adults were different in low- and high- income settings.

Temporal trends in physical activity: a systematic review.

PubMed

Knuth, Alan G; Hallal, Pedro C

2009-09-01

In spite of all accumulated scientific knowledge on the benefits of physical activity (PA) for health, high rates of sedentary lifestyle are still observed worldwide. The aim of this study was to systematically review articles on temporal trends of PA and fitness, with emphasis on differences between children/ adolescents and adults. An electronic search at the Medline/PubMed database was carried out using the following combination of keywords: temporal trends or trends or surveillance or monitoring and PA or exercise or physical fitness or motor activity or sedentary or fitness. By using this strategy, 23,088 manuscripts were detected. After examination, 41 articles fulfilled all inclusion criteria, and were, therefore, included. The data currently available in the literature for adults shows that leisure-time activity levels tend to be increasing over time, while occupational-related PA is decreasing over time. Youth PA seems to be decreasing over time, including a lower level of activity in physical education classes. As a consequence, fitness levels are also declining. PA surveillance must be strongly encouraged in all settings and age groups. Special attention must be paid to low and middle-income countries, where PA surveillance is virtually inexistent.

ULTRASOUND-ENHANCED rt-PA THROMBOLYSIS IN AN EX VIVO PORCINE CAROTID ARTERY MODEL

PubMed Central

Hitchcock, Kathryn E.; Ivancevich, Nikolas M.; Haworth, Kevin J.; Caudell Stamper, Danielle N.; Vela, Deborah C.; Sutton, Jonathan T.; Pyne-Geithman, Gail J.; Holland, Christy K.

2014-01-01

Ultrasound is known to enhance recombinant tissue plasminogen activator (rt-PA) thrombolysis. In this study, occlusive porcine whole blood clots were placed in flowing plasma within living porcine carotid arteries. Ultrasonically induced stable cavitation was investigated as an adjuvant to rt-PA thrombolysis. Aged, retracted clots were exposed to plasma alone, plasma containing rt-PA (7.1 ± 3.8 μg/mL) or plasma with rt-PA and Definity® ultrasound contrast agent (0.79 ± 0.47 μL/mL) with and without 120-kHz continuous wave ultrasound at a peak-to-peak pressure amplitude of 0.44 MPa. An insonation scheme was formulated to promote and maximize stable cavitation activity by incorporating ultrasound quiescent periods that allowed for the inflow of Definity®-rich plasma. Cavitation was measured with a passive acoustic detector throughout thrombolytic treatment. Thrombolytic efficacy was measured by comparing clot mass before and after treatment. Average mass loss for clots exposed to rt-PA and Definity® without ultrasound (n = 7) was 34%, and with ultrasound (n = 6) was 83%, which constituted a significant difference (p < 0.0001). Without Definity® there was no thrombolytic enhancement by ultrasound exposure alone at this pressure amplitude (n = 5, p < 0.0001). In the low-oxygen environment of the ischemic artery, significant loss of endothelium occurred but no correlation was observed between arterial tissue damage and treatment type. Acoustic stable cavitation nucleated by an infusion of Definity® enhances rt-PA thrombolysis without apparent treatment-related damage in this ex vivo porcine carotid artery model. PMID:21723448

PA1 Protein, a New Competitive Decelerator Acting at More than One Step to Impede Glucocorticoid Receptor-mediated Transactivation*

PubMed Central

Zhang, Zhenhuan; Sun, Yunguang; Cho, Young-Wook; Chow, Carson C.; Simons, S. Stoney

2013-01-01

Numerous cofactors modulate the gene regulatory activity of glucocorticoid receptors (GRs) by affecting one or more of the following three major transcriptional properties: the maximal activity of agonists (Amax), the potency of agonists (EC50), and the partial agonist activity of antisteroids (PAA). Here, we report that the recently described nuclear protein, Pax2 transactivation domain interaction protein (PTIP)-associated protein 1 (PA1), is a new inhibitor of GR transactivation. PA1 suppresses Amax, increases the EC50, and reduces the PAA of an exogenous reporter gene in a manner that is independent of associated PTIP. PA1 is fully active with, and strongly binds to, the C-terminal half of GR. PA1 reverses the effects of the coactivator TIF2 on GR-mediated gene induction but is unable to augment the actions of the corepressor SMRT. Analysis of competition assays between PA1 and TIF2 with an exogenous reporter indicates that the kinetic definition of PA1 action is a competitive decelerator at two sites upstream from where TIF2 acts. With the endogenous genes IGFBP1 and IP6K3, PA1 also represses GR induction, increases the EC50, and decreases the PAA. ChIP and re-ChIP experiments indicate that PA1 accomplishes this inhibition of the two genes via different mechanisms as follows: PA1 appears to increase GR dissociation from and reduce GR transactivation at the IGFBP1 promoter regions but blocks GR binding to the IP6K3 promoter. We conclude that PA1 is a new competitive decelerator of GR transactivation and can act at more than one molecularly defined step in a manner that depends upon the specific gene. PMID:23161582

PA1 protein, a new competitive decelerator acting at more than one step to impede glucocorticoid receptor-mediated transactivation.

PubMed

Zhang, Zhenhuan; Sun, Yunguang; Cho, Young-Wook; Chow, Carson C; Simons, S Stoney

2013-01-04

Numerous cofactors modulate the gene regulatory activity of glucocorticoid receptors (GRs) by affecting one or more of the following three major transcriptional properties: the maximal activity of agonists (A(max)), the potency of agonists (EC(50)), and the partial agonist activity of antisteroids (PAA). Here, we report that the recently described nuclear protein, Pax2 transactivation domain interaction protein (PTIP)-associated protein 1 (PA1), is a new inhibitor of GR transactivation. PA1 suppresses A(max), increases the EC(50), and reduces the PAA of an exogenous reporter gene in a manner that is independent of associated PTIP. PA1 is fully active with, and strongly binds to, the C-terminal half of GR. PA1 reverses the effects of the coactivator TIF2 on GR-mediated gene induction but is unable to augment the actions of the corepressor SMRT. Analysis of competition assays between PA1 and TIF2 with an exogenous reporter indicates that the kinetic definition of PA1 action is a competitive decelerator at two sites upstream from where TIF2 acts. With the endogenous genes IGFBP1 and IP6K3, PA1 also represses GR induction, increases the EC(50), and decreases the PAA. ChIP and re-ChIP experiments indicate that PA1 accomplishes this inhibition of the two genes via different mechanisms as follows: PA1 appears to increase GR dissociation from and reduce GR transactivation at the IGFBP1 promoter regions but blocks GR binding to the IP6K3 promoter. We conclude that PA1 is a new competitive decelerator of GR transactivation and can act at more than one molecularly defined step in a manner that depends upon the specific gene.

Reliability and Validity of the Early Childhood Environment Rating Scale, Revised Edition, ECERS-R in Arabic

ERIC Educational Resources Information Center

Hadeed, Julie

2014-01-01

The aim of this study was to test reliabilities and validations for the Arabic translation of the Early Childhood Environment Rating Scale, Revised (ECERS-R) scale [Harms, T., Clifford, R. M., & Cryer, D. (1998). "Early childhood environment rating scale, revised edition." New York: Teachers College Press]. ECERS-R mean scores were…

Physical activity and quality of life after radical prostatectomy

PubMed Central

Mina, Daniel Santa; Matthew, Andrew G.; Trachtenberg, John; Tomlinson, George; Guglietti, Crissa L.; Alibhai, Shabbir M.H.; Ritvo, Paul

2010-01-01

Background: There are significant post-surgical reductions in health-related quality of life (HRQOL) in prostate cancer (PCa) patients undergoing radical prostatectomy (RP). Physical activity (PA) interventions have improved treatment outcomes for PCa patients undergoing radiation and hormone therapy, but PA effects have not previously been examined in the RP setting. This study examined the relationship between preoperative PA levels and postoperative HRQOL outcomes in PCa patients treated with RP. Methods: Sixty patients were interviewed regarding lifetime PA and completed preoperative (2 weeks prior to surgery) and postoperative (4 weeks after surgery) HRQOL questionnaires. Aerobic fitness testing was conducted on a subsample of 22 patients. Results: Higher levels of total past-year PA and occupational PA significantly correlated with lesser HRQOL declines from presurgery to 4 weeks post-surgery (Beta = −0.364, p = 0.037 and Beta = −0.243, p = 0.089, respectively) in models adjusted for age, postoperative questionnaire completion date, Gleason score and education. Past-year occupational PA was highly positively correlated with past-year total PA (r = 0.785, p < 0.001). Lifetime total PA was correlated with estimated VO2 max (r = 0.486, p = 0.026) in the 22 patients who were aerobically tested. Lifetime and past-year PA volumes were not correlated with waist circumference or body mass index. Interpretation: Declines in HRQOL after RP may be reduced in patients with higher preoperative levels of self-reported PA. These findings require further study with larger samples to confirm results. If confirmed, findings suggest exercise preoperatively may improve HRQOL outcomes after RP. PMID:20514281

Physical Education Lesson Content and Teacher Style and Elementary Students' Motivation and Physical Activity Levels

ERIC Educational Resources Information Center

Erwin, Heather E.; Stellino, Megan Babkes; Beets, Michael W.; Beighle, Aaron; Johnson, Christine E.

2013-01-01

Obesity levels among American children are increasing at an alarming rate, due in part to a lack of regular physical activity (PA). Physical education (PE) is one way to facilitate student PA. The overarching PA goal for physical educators is 50% PA for students. Self-determination theory suggests that PA levels in PE and a variety of other…

Extracellular Collagen Promotes Interleukin-1β-Induced Urokinase-Type Plasminogen Activator Production by Human Corneal Fibroblasts.

PubMed

Sugioka, Koji; Kodama-Takahashi, Aya; Yoshida, Koji; Aomatsu, Keiichi; Okada, Kiyotaka; Nishida, Teruo; Shimomura, Yoshikazu

2017-03-01

Keratocytes maintain homeostasis of the corneal stroma through synthesis, secretion, and degradation of collagen fibrils of the extracellular matrix. Given that these cells are essentially embedded in a collagen matrix, keratocyte-collagen interactions may play a key role in regulation of the expression or activation of enzymes responsible for matrix degradation including urokinase-type plasminogen activator (uPA), plasmin, and matrix metalloproteinases (MMPs). We examined the effect of extracellular collagen on the production of uPA by corneal fibroblasts (activated keratocytes) stimulated with the proinflammatory cytokine interleukin-1β (IL-1β). Human corneal fibroblasts were cultured either on plastic or in a three-dimensional gel of type I collagen. Plasminogen activators were detected by fibrin zymography, whereas the IL-1 receptor (IL-1R) and MMPs were detected by immunoblot analysis. Collagen degradation by corneal fibroblasts was assessed by measurement of hydroxyproline in acid hydrolysates of culture supernatants. Collagen and IL-1β synergistically increased the synthesis and secretion of uPA in corneal fibroblasts. Collagen also upregulated IL-1R expression in the cells in a concentration-dependent manner. The conversion of extracellular plasminogen to plasmin, as well as the plasminogen-dependent activation of MMP-1 and MMP-3 and degradation of collagen apparent in three-dimensional cultures of corneal fibroblasts exposed to IL-1β, were all abolished by a selective uPA inhibitor. Collagen and IL-1β cooperate to upregulate uPA production by corneal fibroblasts. Furthermore, IL-1β-induced collagen degradation by these cells appears to be strictly dependent on uPA expression and mediated by a uPA-plasmin-MMP pathway.

Opportunities for Promoting Physical Activity in Rural Communities by Understanding the Interests and Values of Community Members.

PubMed

Park, Thomas; Eyler, Amy A; Tabak, Rachel G; Valko, Cheryl; Brownson, Ross C

2017-01-01

Physical activity (PA) has well-established health benefits, but most Americans do not meet national guidelines. In southeastern Missouri, trails have been developed to increase rates of PA. Although this has had success, broad-scale interventions will be needed to improve rates further. In this study, we surveyed residents of southeastern Missouri to identify ways to improve rates of PA. We conducted a telephone survey in 2015 of adults ( n = 524) from eight rural Missouri towns that had walking trails, regarding their activities and interests. Forty percent of respondents reported both walking and meeting PA recommendations, 29% reported walking but not meeting PA recommendations, and the remainder did not walk or did not answer. Respondents who used the trails were significantly more likely to meet PA recommendations (odds ratio = 2.7; 95% confidence interval = 1.7, 4.5). Certain values and interests that may encourage PA or draw people to trails were common. The group that walked but did not meet PA recommendations would be the ideal group to target for intervention, which could focus on their reported values and interests (e.g., personal relationships, being outdoors). Use of walking trails was associated with meeting PA recommendations.

A pilot lifestyle intervention study: effects of an intervention using an activity monitor and Twitter on physical activity and body composition.

PubMed

Nishiwaki, Masato; Nakashima, Nana; Ikegami, Yumi; Kawakami, Ryoko; Kurobe, Kazumichi; Matsumoto, Naoyuki

2017-04-01

This pilot study aimed to examine the effects of a lifestyle intervention comprising an activity monitor and the concurrent use of Twitter, on physical activity (PA) and body composition. Seventeen healthy volunteers (36±3 years) were randomly assigned to normal (N, N.=8) or Twitter (T, N.=9) intervention groups for six weeks. Participants in both groups wore an activity monitor but those in the T group also tweeted daily about their PA. An observer read the tweets from each participant and provided feedback. Body composition was determined using bioelectrical impedance analysis before and after the intervention. Significantly more daily steps and PA at an intensity of ≥3 metabolic equivalents (METs) were recorded by the T than the N during six weeks. The number of steps and PA did not significantly change over time in the N, but significantly increased in the T from weeks one to six (8170±1130 to 12,934±1400 steps/day and 2.6±0.5 to 5.0±0.8 METs·h/day). In addition, significantly more body fat was lost in the T, than in the N (-1.1±0.2 vs. -0.1±0.3 kg), and the changes in PA significantly correlated with the changes in body fat (r=-0.713). Lifestyle intervention can increase daily PA and reduce body fat more effectively when using an activity monitor and Twitter than an activity monitor alone.

Self-Efficacy versus Perceived Enjoyment as Predictors of Physical Activity Behavior

PubMed Central

Lewis, Beth A.; Williams, David M.; Frayeh, Amanda L.; Marcus, Bess H.

2015-01-01

Objective Self-efficacy and physical activity (PA) enjoyment are related to PA behavior, but it is unclear which is more important and how they interrelate. The purpose of this study was to examine how these two constructs interrelate to influence PA behavior. Design Participants were low active adults (n=448) participating in a RCT examining the effect of a PA promotion intervention. Participants completed physical activity, enjoyment, and self-efficacy measures at baseline, six, and 12 months. Results Self-efficacy and enjoyment at both baseline and six months predicted PA at 12 months. However, enjoyment was a stronger predictor than self-efficacy in that self-efficacy no longer predicted PA behavior when included alongside enjoyment. In follow-up mediation analyses, enjoyment at six months did not mediate the effect of baseline self-efficacy on 12-month PA; however, six-month self-efficacy mediated the effect of baseline enjoyment on 12-month PA. Conclusion Our results indicate that interventions should perhaps initially focus on increasing enjoyment of physical activity. Greater PA enjoyment appears to influence individuals’ self-reported ability to engage in regular PA (i.e., higher self-efficacy ratings). Additional research is needed to better understand the interrelationships between self-efficacy and enjoyment and how these constructs affect PA. PMID:26541890

Self-efficacy versus perceived enjoyment as predictors of physical activity behaviour.

PubMed

Lewis, Beth A; Williams, David M; Frayeh, Amanda; Marcus, Bess H

2016-01-01

Self-efficacy and physical activity (PA) enjoyment are related to PA behaviour, but it is unclear which is more important and how they interrelate. The purpose of this study was to examine how these two constructs interrelate to influence PA behaviour. Participants were low-active adults (n = 448) participating in a RCT examining the effect of a PA promotion intervention. Participants completed physical activity, enjoyment and self-efficacy measures at baseline, six and 12 months. Self-efficacy and enjoyment at both baseline and six months predicted PA at 12 months. However, enjoyment was a stronger predictor than self-efficacy, in that self-efficacy no longer predicted PA behaviour when included alongside enjoyment. In follow-up mediation analyses, enjoyment at six months did not mediate the effect of baseline self-efficacy on 12-month PA; however, six-month self-efficacy mediated the effect of baseline enjoyment on 12-month PA. Our results indicate that interventions should perhaps initially focus on increasing enjoyment of physical activity. Greater PA enjoyment appears to influence individuals' self-reported ability to engage in regular PA (i.e. higher self-efficacy ratings). Additional research is needed to better understand the interrelationships between self-efficacy and enjoyment and how these constructs affect PA.

R-rated movie viewing, growth in sensation seeking and alcohol initiation: reciprocal and moderation effects.

PubMed

Stoolmiller, Mike; Gerrard, Meg; Sargent, James D; Worth, Keilah A; Gibbons, Frederick X

2010-03-01

The current study employed parallel process and discrete time hazard regressions to examine the interplay among exposure to R-rated movies, sensation seeking, and initiation of alcohol use in a national U.S. sample (N = 6255) of adolescents, ages 10-14, who were followed over four waves spanning 2 years. There was a short-term reciprocal relation between watching R-rated movies and sensation seeking, but over the 2-year observation period, exposure to R-rated movies was associated with increases in sensation seeking and not vice versa. Sensation seeking also moderated the effect of watching R-rated movies on initiation of alcohol consumption such that exposure was associated with greater increases in initiation of alcohol use among low sensation than among high sensation seeking adolescents. The study provides empirical evidence of an environmental media effect on sensation seeking, and important new information about the relations among sensation seeking, media exposure, and adolescent alcohol use.

R-rated Movie Viewing, Growth in Sensation Seeking and Alcohol Initiation: Reciprocal and Moderation Effects

PubMed Central

Stoolmiller, Mike; Gerrard, Meg; Worth, Keilah A.; Gibbons, Frederick X.

2010-01-01

The current study employed parallel process and discrete time hazard regressions to examine the interplay among exposure to R-rated movies, sensation seeking, and initiation of alcohol use in a national U.S. sample (N=6255) of adolescents, ages 10–14, who were followed over four waves spanning 2 years. There was a short-term reciprocal relation between watching R-rated movies and sensation seeking, but over the 2-year observation period, exposure to R-rated movies was associated with increases in sensation seeking and not vice versa. Sensation seeking also moderated the effect of watching R-rated movies on initiation of alcohol consumption such that exposure was associated with greater increases in initiation of alcohol use among low sensation than among high sensation seeking adolescents. The study provides empirical evidence of an environmental media effect on sensation seeking, and important new information about the relations among sensation seeking, media exposure, and adolescent alcohol use. PMID:19655251

14-Day thawed plasma retains clot enhancing properties and inhibits tPA-induced fibrinolysis.

PubMed

Huebner, Benjamin R; Moore, Ernest E; Moore, Hunter B; Shepherd-Singh, Raymond; Sauaia, Angela; Stettler, Gregory R; Nunns, Geoffrey R; Silliman, Christopher C

2017-11-01

Plasma-first resuscitation attenuates trauma-induced coagulopathy (TIC); however, the logistics of plasma-first resuscitation require thawed plasma (TP) be readily available due to the obligatory thawing time of fresh frozen plasma (FFP). The current standard is storage of TP for up to 5 days at 4°C, based on factor levels at outdate, for use in patients at risk for TIC, but there remains a 2.2% outdated wastage rate. However, the multitude of plasma proteins in attenuating TIC remains unknown. We hypothesize that TP retains the ability to enhance clotting and reduce tPA-induced fibrinolysis at 14-day storage. FFP was thawed and stored at 4°C at the following intervals: 14, 10, 7, 5, 3, and 1-day prior to the experiment. Healthy volunteers underwent blood draws followed by 50% dilution with TP stored at previously mentioned intervals as well as FFP, normal saline (NS), albumin, and whole blood (WB) control. Samples underwent tPA-modified (75 ng/mL) thrombelastography (TEG) with analysis of R-time, angle, maximum amplitude (MA), and LY30. TEG properties did not change significantly over the thawed storage. 14-day TP retained the ability to inhibit tPA-induced hyperfibrinolysis (median LY30% 9.6%) similar to FFP (5.6%), WB (14.6%), and superior to albumin (59.3%) and NS (58.1%). 14-day TP also retained faster clot formation (median angle, 66.2°) and superior clot strength (MA, 61.5 mm) to albumin (34.8°, 21.6 mm) and NS (41.6°, 32.2 mm). TP plasma stored for 14 days retains clot-enhancing ability and resistance to clot degradation similar to FFP. A clinical trial is needed to validate these in vitro results. Copyright © 2017 Elsevier Inc. All rights reserved.

Teacher ratings of DSM-III-R symptoms for the disruptive behavior disorders.

PubMed

Pelham, W E; Gnagy, E M; Greenslade, K E; Milich, R

1992-03-01

Ratings were collected on a rating scale comprised of the DSM-III-R diagnostic criteria for disruptive behavior disorders. Teacher ratings were obtained for 931 boys in regular classrooms in grades K through 8 from around North America. Means and standard deviations for attention-deficit hyperactivity disorder (ADHD), oppositional-defiant disorder (ODD), and conduct disorder (CD) scales are reported by age. Frequencies of DSM-III-R symptoms are reported by age, and suggested diagnostic cutoffs are discussed. A factor analysis revealed three factors: one reflecting ODD and several CD symptoms, one on which ADHD symptoms of inattention loaded, and one comprised of ADHD impulsivity/overactivity symptoms. Conditional probability analyses revealed that several hallmark symptoms of ADHD had very poor predictive power, whereas combinations of symptoms from the two ADHD factors had good predictive power. Combinations of ODD symptoms also had very high predictive power. The limited utility of teacher ratings in assessing symptoms of conduct disorder in this age range is discussed.

Physical activity, bowel function, and quality of life among rectal cancer survivors.

PubMed

Krouse, Robert S; Wendel, Christopher S; Garcia, David O; Grant, Marcia; Temple, Larissa K F; Going, Scott B; Hornbrook, Mark C; Bulkley, Joanna E; McMullen, Carmit K; Herrinton, Lisa J

2017-11-01

Physical activity (PA) is positively associated with numerous health benefits among cancer survivors. This study examined insufficiently investigated relationships among PA, health-related quality of life (HRQOL), and bowel function (BF) in rectal cancer survivors. RC survivors (n = 1063) ≥5 years from diagnosis in two Kaiser permanente regions were mailed a multidimensional survey to assess HRQOL and BF. PA was assessed by a modified Godin Leisure-Time Exercise Questionnaire. PA minutes were categorized into weighted categories based on guidelines: (1) not active (zero PA minutes); (2) insufficiently active (1-149 PA minutes); (3) meeting guidelines (150-299 PA minutes); and (4) above guidelines (≥300 PA minutes). Relationships of PA with HRQOL and BF were evaluated using multiple linear regression, stratified by sex and ostomy status for BF. Types of PA identified as helpful for BF and symptoms addressed were summarized. Response rate was 60.5%. Of 557 participants, 40% met or exceeded PA guidelines, 34% were not active, and 26% were insufficiently active. Aerobic activities, specifically walking and cycling, were most commonly reported to help BF. Higher PA was associated with better psychological wellbeing and multiple SF12 scales, worse BF scores in men with ostomies, and better BF scores in women. Meeting or exceeding PA guidelines was associated with higher HRQOL. Although the BF findings are exploratory, they suggest women may benefit from increased PA, whereas men with ostomies may face challenges that require more study. Identifying PA strategies that will lead to improved patient compliance and benefit are needed.

Physical Activity as a Vital Sign: A Systematic Review

PubMed Central

Allen, Kelli D.; Ambrose, Kirsten R.; Stiller, Jamie L.; Evenson, Kelly R.; Voisin, Christiane; Hootman, Jennifer M.; Callahan, Leigh F.

2017-01-01

Introduction Physical activity (PA) is strongly endorsed for managing chronic conditions, and a vital sign tool (indicator of general physical condition) could alert providers of inadequate PA to prompt counseling or referral. This systematic review examined the use, definitions, psychometric properties, and outcomes of brief PA instruments as vital sign measures, with attention primarily to studies focused on arthritis. Methods Electronic databases were searched for English-language literature from 1985 through 2016 using the terms PA, exercise, vital sign, exercise referral scheme, and exercise counseling. Of the 838 articles identified for title and abstract review, 9 articles qualified for full text review and data extraction. Results Five brief PA measures were identified: Exercise Vital Sign (EVS), Physical Activity Vital Sign (PAVS), Speedy Nutrition and Physical Activity Assessment (SNAP), General Practice Physical Activity Questionnaire (GPPAQ), and Stanford Brief Activity Survey (SBAS). Studies focusing on arthritis were not found. Over 1.5 years of using EVS in a large hospital system, improvements occurred in relative weight loss among overweight patients and reduction in glycosylated hemoglobin among diabetic patients. On PAVS, moderate physical activity of 5 or more days per week versus fewer than 5 days per week was associated with a lower body mass index (−2.90 kg/m2). Compared with accelerometer-defined physical activity, EVS was weakly correlated (r = 0.27), had low sensitivity (27%–59%), and high specificity (74%–89%); SNAP showed weak agreement (κ = 0.12); GPPAQ had moderate sensitivity (46%) and specificity (50%), and SBAS was weakly correlated (r = 0.10–0.28), had poor to moderate sensitivity (18%–67%), and had moderate specificity (58%–79%). Conclusion Few studies have examined a brief physical activity tool as a vital sign measure. Initial investigations suggest the promise of these simple and quick assessment tools, and

Glucose-Sensing Receptor T1R3: A New Signaling Receptor Activated by Glucose in Pancreatic β-Cells.

PubMed

Kojima, Itaru; Nakagawa, Yuko; Hamano, Kunihisa; Medina, Johan; Li, Longfei; Nagasawa, Masahiro

2015-01-01

Subunits of the sweet taste receptors T1R2 and T1R3 are expressed in pancreatic β-cells. Compared with T1R3, mRNA expression of T1R2 is considerably lower. At the protein level, expression of T1R2 is undetectable in β-cells. Accordingly, a major component of the sweet taste-sensing receptor in β-cells may be a homodimer of T1R3 rather than a heterodimer of T1R2/T1R3. Inhibition of this receptor by gurmarin or deletion of the T1R3 gene attenuates glucose-induced insulin secretion from β-cells. Hence the T1R3 homodimer functions as a glucose-sensing receptor (GSR) in pancreatic β-cells. When GSR is activated by the T1R3 agonist sucralose, elevation of intracellular ATP concentration ([ATP]i) is observed. Sucralose increases [ATP]i even in the absence of ambient glucose, indicating that sucralose increases [ATP]i not simply by activating glucokinase, a rate-limiting enzyme in the glycolytic pathway. In addition, sucralose augments elevation of [ATP]i induced by methylsuccinate, suggesting that sucralose activates mitochondrial metabolism. Nonmetabolizable 3-O-methylglucose also increases [ATP]i and knockdown of T1R3 attenuates elevation of [ATP]i induced by high concentration of glucose. Collectively, these results indicate that the T1R3 homodimer functions as a GSR; this receptor is involved in glucose-induced insulin secretion by activating glucose metabolism probably in mitochondria.

The PA-Gene-Mediated Lethal Dissemination and Excessive Innate Immune Response Contribute to the High Virulence of H5N1 Avian Influenza Virus in Mice

PubMed Central

Hu, Jiao; Hu, Zenglei; Song, Qingqing; Gu, Min; Liu, Xiaowen; Wang, Xiaoquan; Hu, Shunlin; Chen, Chaoyang; Liu, Huimou; Liu, Wenbo; Chen, Sujuan; Peng, Daxin

2013-01-01

Highly pathogenic H5N1 influenza A virus remains a substantial threat to public health. To understand the molecular basis and host mechanism for the high virulence of H5N1 viruses in mammals, we compared two H5N1 isolates which have similar genetic backgrounds but greatly differ in their virulence in mice. A/Chicken/Jiangsu/k0402/2010 (CK10) is highly pathogenic, whereas A/Goose/Jiangsu/k0403/2010 (GS10) is nonpathogenic. We first showed that CK10 elicited a more potent innate immune response than did GS10 in mouse lungs by increasing the number and expression levels of activated genes. We then generated a series of reassortants between the two viruses and evaluated their virulence in mice. Inclusion of the CK10 PA gene in the GS10 background resulted in a dramatic increase in virulence. Conversely, expression of the GS10 PA gene in the CK10 background significantly attenuated the virulence. These results demonstrated that the PA gene mainly determines the pathogenicity discrepancy between CK10 and GS10 in mice. We further determined that arginine (R) at position 353 of the PA gene contributes to the high virulence of CK10 in mice. The reciprocal substitution at position 353 in PA or the exchange of the entire PA gene largely caused the transfer of viral phenotypes, including virus replication, polymerase activity, and manipulation of the innate response, between CK10 and GS10. We therefore defined a novel molecular marker associated with the high virulence of H5N1 influenza viruses, providing further insights into the pathogenesis of H5N1 viruses in mammals. PMID:23255810

Quorum sensing systems differentially regulate the production of phenazine-1-carboxylic acid in the rhizobacterium Pseudomonas aeruginosa PA1201

PubMed Central

Sun, Shuang; Zhou, Lian; Jin, Kaiming; Jiang, Haixia; He, Ya-Wen

2016-01-01

Pseudomonas aeruginosa strain PA1201 is a newly identified rhizobacterium that produces high levels of the secondary metabolite phenazine-1-carboxylic acid (PCA), the newly registered biopesticide Shenqinmycin. PCA production in liquid batch cultures utilizing a specialized PCA-promoting medium (PPM) typically occurs after the period of most rapid growth, and production is regulated in a quorum sensing (QS)-dependent manner. PA1201 contains two PCA biosynthetic gene clusters phz1 and phz2; both clusters contribute to PCA production, with phz2 making a greater contribution. PA1201 also contains a complete set of genes for four QS systems (LasI/LasR, RhlI/RhlR, PQS/MvfR, and IQS). By using several methods including gene deletion, the construction of promoter-lacZ fusion reporter strains, and RNA-Seq analysis, this study investigated the effects of the four QS systems on bacterial growth, QS signal production, the expression of phz1 and phz2, and PCA production. The possible mechanisms for the strain- and condition-dependent expression of phz1 and phz2 were discussed, and a schematic model was proposed. These findings provide a basis for further genetic engineering of the QS systems to improve PCA production. PMID:27456813

Structure and Function of PA4872 from Pseudomonas aeruginosa, a Novel Class of Oxaloacetate Decarboxylase from the PEP Mutase/Isocitrate Lyase Superfamily

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

Narayanan, Buvaneswari C.; Niu, Weiling; Han, Ying

2008-06-30

Pseudomonas aeruginosa PA4872 was identified by sequence analysis as a structurally and functionally novel member of the PEP mutase/isocitrate lyase superfamily and therefore targeted for investigation. Substrate screens ruled out overlap with known catalytic functions of superfamily members. The crystal structure of PA4872 in complex with oxalate (a stable analogue of the shared family R-oxyanion carboxylate intermediate/transition state) and Mg{sup 2+} was determined at 1.9 {angstrom} resolution. As with other PEP mutase/isocitrate lyase superfamily members, the protein assembles into a dimer of dimers with each subunit adopting an {alpha}/{beta} barrel fold and two subunits swapping their barrel's C-terminal {alpha}-helices. Mg2+more » and oxalate bind in the same manner as observed with other superfamily members. The active site gating loop, known to play a catalytic role in the PEP mutase and lyase branches of the superfamily, adopts an open conformation. The N{sup {epsilon}} of His235, an invariant residue in the PA4872 sequence family, is oriented toward a C(2) oxygen of oxalate analogous to the C(3) of a pyruvyl moiety. Deuterium exchange into {alpha}-oxocarboxylate-containing compounds was confirmed by {sup 1}H NMR spectroscopy. Having ruled out known activities, the involvement of a pyruvate enolate intermediate suggested a decarboxylase activity of an {alpha}-oxocarboxylate substrate. Enzymatic assays led to the discovery that PA4872 decarboxylates oxaloacetate (k{sub cat}) = 7500 s{sup -1} and K{sub m} = 2.2 mM) and 3-methyloxaloacetate (k{sub cat}) = 250 s{sup -1} and K{sub m} = 0.63 mM). Genome context of the fourteen sequence family members indicates that the enzyme is used by select group of Gram-negative bacteria to maintain cellular concentrations of bicarbonate and pyruvate; however the decarboxylation activity cannot be attributed to a pathway common to the various bacterial species.« less

Active α-macroglobulin is a reservoir for urokinase after fibrinolytic therapy in rabbits with tetracycline-induced pleural injury and in human pleural fluids

PubMed Central

Florova, Galina; Azghani, Ali; Karandashova, Sophia; Kurdowska, Anna K.; Idell, Steven

2013-01-01

Intrapleural processing of prourokinase (scuPA) in tetracycline (TCN)-induced pleural injury in rabbits was evaluated to better understand the mechanisms governing successful scuPA-based intrapleural fibrinolytic therapy (IPFT), capable of clearing pleural adhesions in this model. Pleural fluid (PF) was withdrawn 0–80 min and 24 h after IPFT with scuPA (0–0.5 mg/kg), and activities of free urokinase (uPA), plasminogen activator inhibitor-1 (PAI-1), and uPA complexed with α-macroglobulin (αM) were assessed. Similar analyses were performed using PFs from patients with empyema, parapneumonic, and malignant pleural effusions. The peak of uPA activity (5–40 min) reciprocally correlated with the dose of intrapleural scuPA. Endogenous active PAI-1 (10–20 nM) decreased the rate of intrapleural scuPA activation. The slow step of intrapleural inactivation of free uPA (t1/2β = 40 ± 10 min) was dose independent and 6.7-fold slower than in blood. Up to 260 ± 70 nM of αM/uPA formed in vivo [second order association rate (kass) = 580 ± 60 M−1·s−1]. αM/uPA and products of its degradation contributed to durable intrapleural plasminogen activation up to 24 h after IPFT. Active PAI-1, active α2M, and α2M/uPA found in empyema, pneumonia, and malignant PFs demonstrate the capacity to support similar mechanisms in humans. Intrapleural scuPA processing differs from that in the bloodstream and includes 1) dose-dependent control of scuPA activation by endogenous active PAI-1; 2) two-step inactivation of free uPA with simultaneous formation of αM/uPA; and 3) slow intrapleural degradation of αM/uPA releasing active free uPA. This mechanism offers potential clinically relevant advantages that may enhance the bioavailability of intrapleural scuPA and may mitigate the risk of bleeding complications. PMID:23997178

Ultrasound-enhanced rt-PA thrombolysis in an ex vivo porcine carotid artery model.

PubMed

Hitchcock, Kathryn E; Ivancevich, Nikolas M; Haworth, Kevin J; Caudell Stamper, Danielle N; Vela, Deborah C; Sutton, Jonathan T; Pyne-Geithman, Gail J; Holland, Christy K

2011-08-01

Ultrasound is known to enhance recombinant tissue plasminogen activator (rt-PA) thrombolysis. In this study, occlusive porcine whole blood clots were placed in flowing plasma within living porcine carotid arteries. Ultrasonically induced stable cavitation was investigated as an adjuvant to rt-PA thrombolysis. Aged, retracted clots were exposed to plasma alone, plasma containing rt-PA (7.1 ± 3.8 μg/mL) or plasma with rt-PA and Definity® ultrasound contrast agent (0.79 ± 0.47 μL/mL) with and without 120-kHz continuous wave ultrasound at a peak-to-peak pressure amplitude of 0.44 MPa. An insonation scheme was formulated to promote and maximize stable cavitation activity by incorporating ultrasound quiescent periods that allowed for the inflow of Definity®-rich plasma. Cavitation was measured with a passive acoustic detector throughout thrombolytic treatment. Thrombolytic efficacy was measured by comparing clot mass before and after treatment. Average mass loss for clots exposed to rt-PA and Definity® without ultrasound (n = 7) was 34%, and with ultrasound (n = 6) was 83%, which constituted a significant difference (p < 0.0001). Without Definity® there was no thrombolytic enhancement by ultrasound exposure alone at this pressure amplitude (n = 5, p < 0.0001). In the low-oxygen environment of the ischemic artery, significant loss of endothelium occurred but no correlation was observed between arterial tissue damage and treatment type. Acoustic stable cavitation nucleated by an infusion of Definity® enhances rt-PA thrombolysis without apparent treatment-related damage in this ex vivo porcine carotid artery model. Copyright © 2011. Published by Elsevier Inc.

PA28γ is a novel corepressor of HTLV-1 replication and controls viral latency

PubMed Central

Ko, Nga Ling; Taylor, John M.; Bellon, Marcia; Bai, Xue Tao; Shevtsov, Sergey P.; Dundr, Miroslav

2013-01-01

The establishment of a latent reservoir by human tumor viruses is a vital step in initiating cellular transformation and represents a major shortcoming to current therapeutic strategies and the ability to eradicate virus-infected cells. Human T-cell leukemia virus type 1 (HTLV-1) establishes a lifelong infection and is linked to adult T-cell leukemia lymphoma (ATLL). Here, we demonstrate that HTLV-1 p30 recruits the cellular proteasome activator PA28γ onto the viral tax/rex mRNA to prevent its nuclear export and suppress virus replication. Interaction of p30 with a PA28γ retaining fully functional proteasome activity is required for p30's ability to repress HTLV-1. Consistently, HTLV-1 molecular clones replicate better and produce more virus particles in PA28γ-deficient cells. These results define a unique and novel role for the cellular factor PA28γ in the control of nuclear RNA trafficking and HTLV-1–induced latency. Importantly, knockdown of PA28γ expression in ATLL cells latently infected with HTLV-1 reactivates expression of viral tax/rex RNA and the Tax protein. Because Tax is the most immunogenic viral antigen and triggers strong CTL responses, our results suggest that PA28γ-targeted therapy may reactivate virus expression from latently infected cells and allow their eradication from the host. PMID:23104922

Structure-based drug discovery for combating influenza virus by targeting the PA-PB1 interaction.

PubMed

Watanabe, Ken; Ishikawa, Takeshi; Otaki, Hiroki; Mizuta, Satoshi; Hamada, Tsuyoshi; Nakagaki, Takehiro; Ishibashi, Daisuke; Urata, Shuzo; Yasuda, Jiro; Tanaka, Yoshimasa; Nishida, Noriyuki

2017-08-25

Influenza virus infections are serious public health concerns throughout the world. The development of compounds with novel mechanisms of action is urgently required due to the emergence of viruses with resistance to the currently-approved anti-influenza viral drugs. We performed in silico screening using a structure-based drug discovery algorithm called Nagasaki University Docking Engine (NUDE), which is optimised for a GPU-based supercomputer (DEstination for Gpu Intensive MAchine; DEGIMA), by targeting influenza viral PA protein. The compounds selected by NUDE were tested for anti-influenza virus activity using a cell-based assay. The most potent compound, designated as PA-49, is a medium-sized quinolinone derivative bearing a tetrazole moiety, and it inhibited the replication of influenza virus A/WSN/33 at a half maximal inhibitory concentration of 0.47 μM. PA-49 has the ability to bind PA and its anti-influenza activity was promising against various influenza strains, including a clinical isolate of A(H1N1)pdm09 and type B viruses. The docking simulation suggested that PA-49 interrupts the PA-PB1 interface where important amino acids are mostly conserved in the virus strains tested, suggesting the strain independent utility. Because our NUDE/DEGIMA system is rapid and efficient, it may help effective drug discovery against the influenza virus and other emerging viruses.

Twenty Species of Hypobarophilic Bacteria Recovered from Diverse Soils Exhibit Growth under Simulated Martian Conditions at 0.7 kPa

NASA Astrophysics Data System (ADS)

Schuerger, Andrew C.; Nicholson, Wayne L.

2016-12-01

Bacterial growth at low pressure is a new research area with implications for predicting microbial activity in clouds and the bulk atmosphere on Earth and for modeling the forward contamination of planetary surfaces like Mars. Here, we describe experiments on the recovery and identification of 20 species of bacterial hypobarophiles (def., growth under hypobaric conditions of approximately 1-2 kPa) in 10 genera capable of growth at 0.7 kPa. Hypobarophilic bacteria, but not archaea or fungi, were recovered from diverse soils, and high numbers of hypobarophiles were recovered from Arctic and Siberian permafrost soils. Isolates were identified through 16S rRNA sequencing to belong to the genera Bacillus, Carnobacterium, Clostridium, Cryobacterium, Exiguobacterium, Paenibacillus, Rhodococcus, Streptomyces, and Trichococcus. The highest population of culturable hypobarophilic bacteria (5.1 × 104 cfu/g) was recovered from Colour Lake soils from Axel Heiberg Island in the Canadian Arctic. In addition, we extend the number of hypobarophilic species in the genus Serratia to six type-strains that include S. ficaria, S. fonticola, S. grimesii, S. liquefaciens, S. plymuthica, and S. quinivorans. Microbial growth at 0.7 kPa suggests that pressure alone will not be growth-limiting on the martian surface, or in Earth's atmosphere up to an altitude of 34 km.

Evaluation of ID-PaGIA syphilis antibody test.

PubMed

Naaber, Paul; Makoid, Ene; Aus, Anneli; Loivukene, Krista; Poder, Airi

2009-01-01

Laboratory diagnosis of syphilis is usually accomplished by serology. There are currently a large number of different commercial treponemal tests available that vary in format, sensitivity and specificity. To evaluate the ID-PaGIA Syphilis Antibody Test as an alternative to other specific treponemal tests for primary screening or confirmation of diagnosis. Serum samples from healthy adults (n = 100) were used for detection of specificity of ID-PaGIA. To evaluate sensitivity of ID-PaGIA serum samples (n = 101) from patients with confirmed or suspected syphilis were tested for syphilis antibodies with FTA-Abs IgM, ID-PaGIA, ELISA IgM and TPHA tests. No false-positive results were found with ID-PaGIA. Sensitivity of various treponemal tests was the following: FTA-Abs IgM: 95.5%, ID-PaGIA and ELISA IgM: 94%, and TPHA 75%. The positive and negative predictive values of ID-PaGIA were 100 and 89.5%, respectively. Compared with other treponemal tests ID-PaGIA has excellent sensitivity and specificity.

Comparison of the EPIC Physical Activity Questionnaire with combined heart rate and movement sensing in a nationally representative sample of older British adults.

PubMed

España-Romero, Vanesa; Golubic, Rajna; Martin, Kathryn R; Hardy, Rebecca; Ekelund, Ulf; Kuh, Diana; Wareham, Nicholas J; Cooper, Rachel; Brage, Soren

2014-01-01

To compare physical activity (PA) subcomponents from EPIC Physical Activity Questionnaire (EPAQ2) and combined heart rate and movement sensing in older adults. Participants aged 60-64y from the MRC National Survey of Health and Development in Great Britain completed EPAQ2, which assesses self-report PA in 4 domains (leisure time, occupation, transportation and domestic life) during the past year and wore a combined sensor for 5 consecutive days. Estimates of PA energy expenditure (PAEE), sedentary behaviour, light (LPA) and moderate-to-vigorous PA (MVPA) were obtained from EPAQ2 and combined sensing and compared. Complete data were available in 1689 participants (52% women). EPAQ2 estimates of PAEE and MVPA were higher than objective estimates and sedentary time and LPA estimates were lower [bias (95% limits of agreement) in men and women were 32.3 (-61.5 to 122.6) and 29.0 (-39.2 to 94.6) kJ/kg/day for PAEE; -4.6 (-10.6 to 1.3) and -6.0 (-10.9 to -1.0) h/day for sedentary time; -171.8 (-454.5 to 110.8) and -60.4 (-367.5 to 246.6) min/day for LPA; 91.1 (-159.5 to 341.8) and 55.4 (-117.2 to 228.0) min/day for MVPA]. There were significant positive correlations between all self-reported and objectively assessed PA subcomponents (rho= 0.12 to 0.36); the strongest were observed for MVPA (rho = 0.30 men; rho = 0.36 women) and PAEE (rho = 0.26 men; rho = 0.25 women). EPAQ2 produces higher estimates of PAEE and MVPA and lower estimates of sedentary and LPA than objective assessment. However, both methodologies rank individuals similarly, suggesting that EPAQ2 may be used in etiological studies in this population.

Cordyceps sinensis promotes immune regulation and enhances bacteriostatic activity of PA-824 via IL-10 in Mycobacterium tuberculosis disease

PubMed Central

Li, D.G.; Ren, Z.X.

2017-01-01

PA-824 is a novel bicyclic nitroimidazole anti-tuberculosis (TB) drug. Cordyceps sinensis (Berk.) Sacc. (CS) was proven to be a good immunomodulatory compound. This research aimed to investigate the effect of CS on PA-824 in Mycobacterium tuberculosis (M.tb) infected mice (female CBA/J mice, 6 to 8 weeks of age and 20±2 g of weight). Mice were randomly assigned to 4 groups: PA-824, CS, PA-824+CS, and control. To verify the effect of PA-824 and CS on M.tb, after drug administration, mice lungs were harvested and bacterial colony formations were measured. Cells were isolated from infected lungs and spleens to analyze the percentage of CD4+ T cells (CD11a positive). Lung cells were cultured to detect the secretion of interferon-γ (IFN-γ) and interleukin-10 (IL-10) by ELISA. IFN-γ and IL-10 double-positive CD4+ cells in peripheral blood were measured by flow cytometry. The expression levels of IL-2 and IL-10 in mice lungs were analyzed by real-time PCR and western blot. Results showed that PA-824 combined with CS led to the lowest lung colony-forming units (CFU) counts among treated groups. Furthermore, this beneficial outcome might be associated with the decreased CD11a on CD4+ cells in mice lungs and spleens. Moreover, the suppressed secretion of IFN-γ and IL-10, and IL-10 expressions, as well as the decreased IFN-γ and IL-10 double-positive CD4+ cells in blood, could also be associated with the positive effect. However, no significant effect on IL-2 production was found. The combination of PA-824 and CS had more effective bacteriostatic and immunomodulatory effects on M.tb infected mice than PA-824 alone. In conclusion, CS has the potential to be an effective adjuvant in TB treatment. PMID:28793052

Cordyceps sinensis promotes immune regulation and enhances bacteriostatic activity of PA-824 via IL-10 in Mycobacterium tuberculosis disease.

PubMed

Li, D G; Ren, Z X

2017-08-07

PA-824 is a novel bicyclic nitroimidazole anti-tuberculosis (TB) drug. Cordyceps sinensis (Berk.) Sacc. (CS) was proven to be a good immunomodulatory compound. This research aimed to investigate the effect of CS on PA-824 in Mycobacterium tuberculosis (M.tb) infected mice (female CBA/J mice, 6 to 8 weeks of age and 20±2 g of weight). Mice were randomly assigned to 4 groups: PA-824, CS, PA-824+CS, and control. To verify the effect of PA-824 and CS on M.tb, after drug administration, mice lungs were harvested and bacterial colony formations were measured. Cells were isolated from infected lungs and spleens to analyze the percentage of CD4+ T cells (CD11a positive). Lung cells were cultured to detect the secretion of interferon-γ (IFN-γ) and interleukin-10 (IL-10) by ELISA. IFN-γ and IL-10 double-positive CD4+ cells in peripheral blood were measured by flow cytometry. The expression levels of IL-2 and IL-10 in mice lungs were analyzed by real-time PCR and western blot. Results showed that PA-824 combined with CS led to the lowest lung colony-forming units (CFU) counts among treated groups. Furthermore, this beneficial outcome might be associated with the decreased CD11a on CD4+ cells in mice lungs and spleens. Moreover, the suppressed secretion of IFN-γ and IL-10, and IL-10 expressions, as well as the decreased IFN-γ and IL-10 double-positive CD4+ cells in blood, could also be associated with the positive effect. However, no significant effect on IL-2 production was found. The combination of PA-824 and CS had more effective bacteriostatic and immunomodulatory effects on M.tb infected mice than PA-824 alone. In conclusion, CS has the potential to be an effective adjuvant in TB treatment.

Comparison of methods to assess energy expenditure and physical activity in people with spinal cord injury

PubMed Central

Tanhoffer, Ricardo A.; Tanhoffer, Aldre I. P.; Raymond, Jacqueline; Hills, Andrew P.; Davis, Glen M.

2012-01-01

Objective To compare different methods of assessing energy expenditure (EE) and physical activity (PA) in people with spinal cord injury (SCI) under community-dwelling conditions. Methods A reference standard encompassing the doubly labelled water (DLW) technique, heart rate monitoring (FLEX-HR), a multi-sensor armband (SenseWear Armband (SWA)), and two PA recall questionnaires were employed in 14 people with SCI to estimate EE and leisure-time PA. Results Mean total daily energy expenditure (TDEE) assessed by DLW, FLEX-HR, and SWA were 9817 ± 2491 kJ/day, 8498 ± 1516 kJ/day, and 11414 ± 3242 kJ/day, respectively. Physical activity energy expenditure (PAEE) quantified by DLW was 2841 ± 1626 kJ/day, 2935 ± 1732 kJ/day estimated from FLEX-HR, and 2773 ± 2966 kJ/day derived from SWA. After converting the PA recall questionnaire data to EE in kJ/day, PAEE for the Physical Activity Recall Assessment for People with Spinal Cord Injury (PARA-SCI) was 2339 ± 1171 kJ/day and for Physical Activity Scale for Individuals with Physical Disabilities (PASIPD) 749 ± 1026 kJ/day. DLW-quantified PAEE was moderately associated with PARA-SCI (R2 = 0.62, P < 0.05), but not with the other estimates of PAEE (R2 ranged between 0.13 and 0.30, P > 0.05). Conclusion Our findings revealed that the PARA-SCI recall questionnaire was the best estimate of PAEE compared to the reference standard DLW approach. Although the between-method variability for SWA, FLEX-HR, and PASIPD-derived PAEE was small, there was a weak association between these methods and the criterion DLW technique. The best estimate of DLW-quantified TDEE was by FLEX-HR. SWA significantly overestimated TDEE in this population. PMID:22330189

Structure-activity correlations for organophosphorus ester anticholinesterases. Part 2: CNDO/2 calculations applied to ester hydrolysis rates

NASA Technical Reports Server (NTRS)

Johnson, H.; Kenley, R. A.; Rynard, C.; Golub, M. A.

1984-01-01

Quantitative structure-activity relationships are presented for the hydrolysis of organophosphorus esters, RR'P(O)X, where R and R' are alkyl and/or alkoxy groups and X is fluorine, chlorine or a phenoxy group. CNDO/2 calculations provide values for molecular parameters that correlate with alkaline hydrolysis rates. For each subset of esters with the same leaving group, X, the CNDO-derived net atomic charge at the central phosphorus atom correlates well with the alkaline hydrolysis rate constants. For the whole set of esters with different leaving groups, equations are derived that relate charge, orbital energy and bond order to the hydrolysis rate constants.

Temperature affects thrombolytic efficacy using rt-PA and eptifibatide, an in vitro study.

PubMed

Meunier, Jason M; Chang, Wan-Tsu W; Bluett, Brent; Wenker, Evan; Lindsell, Christopher J; Shaw, George J

2012-09-01

The potential for hypothermia as a neuroprotectant during stroke has led to its increase in clinical use. At the same time, combination pharmaceutical therapies for ischemic stroke using recombinant tissue plasminogen activator (rt-PA), and GP IIb-IIIa inhibitors, such as Eptifibatide (Epf ), are under study. However, there is little data on how the reactions triggered by these agents are impacted by temperature. Here, clot lysis during exposure to the combination of rt-PA and Epf is measured in an in vitro human clot model at hypothermic temperatures. The hypothesis is that lytic efficacy of rt-PA and Epf decreases with decreasing temperature. Whole blood clots from 31 volunteers were exposed to rt-PA (0.5 μg/mL) and Epf (0.63 μg/mL) in human fresh-frozen plasma (rt-PA+Epf ), rt-PA alone in plasma (rt-PA Alone), or to plasma alone (Control), at temperatures from 30°C to 37°C, for 30 minutes. Clot lysis was measured using a microscopic imaging technique; the mean fractional clot loss (FCL) at 30 minutes was used to determine lytic efficacy. Temperature had a significant impact on FCL in clots exposed to rt-PA+Epf, with the FCL being lower at 30°C to 36°C than at 37°C. The FCL remained significantly higher for rt-PA+Epf–treated clots than Controls regardless of temperature, with the exception of measurements made at 30°C when no significant differences in the FCL were observed between groups. The use of hypothermia as a neuroprotectant may negatively impact the therapeutic benefit of thrombolytic agents.

Temperature Affects Thrombolytic Efficacy Using rt-PA and Eptifibatide, an In Vitro Study

PubMed Central

Chang, Wan-Tsu W.; Bluett, Brent; Wenker, Evan; Lindsell, Christopher J.; Shaw, George J.

2012-01-01

The potential for hypothermia as a neuroprotectant during stroke has led to its increase in clinical use. At the same time, combination pharmaceutical therapies for ischemic stroke using recombinant tissue plasminogen activator (rt-PA), and GP IIb-IIIa inhibitors, such as Eptifibatide (Epf ), are under study. However, there is little data on how the reactions triggered by these agents are impacted by temperature. Here, clot lysis during exposure to the combination of rt-PA and Epf is measured in an in vitro human clot model at hypothermic temperatures. The hypothesis is that lytic efficacy of rt-PA and Epf decreases with decreasing temperature. Whole blood clots from 31 volunteers were exposed to rt-PA (0.5 μg/mL) and Epf (0.63 μg/mL) in human fresh-frozen plasma (rt-PA+Epf ), rt-PA alone in plasma (rt-PA Alone), or to plasma alone (Control), at temperatures from 30°C to 37°C, for 30 minutes. Clot lysis was measured using a microscopic imaging technique; the mean fractional clot loss (FCL) at 30 minutes was used to determine lytic efficacy. Temperature had a significant impact on FCL in clots exposed to rt-PA+Epf, with the FCL being lower at 30°C to 36°C than at 37°C. The FCL remained significantly higher for rt-PA+Epf–treated clots than Controls regardless of temperature, with the exception of measurements made at 30°C when no significant differences in the FCL were observed between groups. The use of hypothermia as a neuroprotectant may negatively impact the therapeutic benefit of thrombolytic agents. PMID:23667777

Socio-economic effects on meeting PA guidelines: comparisons among 32 countries

PubMed Central

Borraccino, A; Lemma, P; Iannotti, R; Zambon, A; Dalmasso, P; Lazzeri, G; Giacchi, M; Cavallo, F

2008-01-01

Purpose This study examined the relationship between age and gender with physical activity (PA) and how meeting of PA guidelines (PAGL) is related to socio-economic-status. Methods Data were collected from 11-, 13-, and 15-y.o. students in 32 countries participating in the Health Behaviour in School-aged Children (HBSC) survey 2001/2002. A self-completed questionnaire assessed moderate-to-vigorous physical activity (MVPA) for the past seven days and MVPA for a typical week. Socio-economic status (SES) was assessed using the Family Affluence Scale (FAS). Results None of the countries averaged enough MVPA to meet PAGL. The pattern of MVPA across gender and age was consistent among all countries. In all countries girls were significantly less active than boys (mean hours/week of MVPA 3.52 ±1.88 vs 4.13 ±1.95) and were more likely to not meet the PAGL; older children were less active when compared to the youngest. SES was significantly associated with the amount of reported MVPA. SES and PAGL were significantly related in seven countries and a significant decrease in the influence of age was observed in these countries compared to other countries. Conclusions Levels of MVPA during adolescence showed consistent patterns across countries in relation to age, gender and social-class. The limited effect of age on PA in countries where the influence of social class was less strong, suggesting the possibility of a moderating effect of context in the development of habits acquired in childhood PMID:19276860

Auto-phosphorylation Represses Protein Kinase R Activity.

PubMed

Wang, Die; de Weerd, Nicole A; Willard, Belinda; Polekhina, Galina; Williams, Bryan R G; Sadler, Anthony J

2017-03-10

The central role of protein kinases in controlling disease processes has spurred efforts to develop pharmaceutical regulators of their activity. A rational strategy to achieve this end is to determine intrinsic auto-regulatory processes, then selectively target these different states of kinases to repress their activation. Here we investigate auto-regulation of the innate immune effector protein kinase R, which phosphorylates the eukaryotic initiation factor 2α to inhibit global protein translation. We demonstrate that protein kinase R activity is controlled by auto-inhibition via an intra-molecular interaction. Part of this mechanism of control had previously been reported, but was then controverted. We account for the discrepancy and extend our understanding of the auto-inhibitory mechanism by identifying that auto-inhibition is paradoxically instigated by incipient auto-phosphorylation. Phosphor-residues at the amino-terminus instigate an intra-molecular interaction that enlists both of the N-terminal RNA-binding motifs of the protein with separate surfaces of the C-terminal kinase domain, to co-operatively inhibit kinase activation. These findings identify an innovative mechanism to control kinase activity, providing insight for strategies to better regulate kinase activity.

Opportunities for Promoting Physical Activity in Rural Communities by Understanding the Interests and Values of Community Members

PubMed Central

Eyler, Amy A.; Valko, Cheryl

2017-01-01

Purpose Physical activity (PA) has well-established health benefits, but most Americans do not meet national guidelines. In southeastern Missouri, trails have been developed to increase rates of PA. Although this has had success, broad-scale interventions will be needed to improve rates further. In this study, we surveyed residents of southeastern Missouri to identify ways to improve rates of PA. Methods We conducted a telephone survey in 2015 of adults (n = 524) from eight rural Missouri towns that had walking trails, regarding their activities and interests. Findings Forty percent of respondents reported both walking and meeting PA recommendations, 29% reported walking but not meeting PA recommendations, and the remainder did not walk or did not answer. Respondents who used the trails were significantly more likely to meet PA recommendations (odds ratio = 2.7; 95% confidence interval = 1.7, 4.5). Certain values and interests that may encourage PA or draw people to trails were common. Conclusions The group that walked but did not meet PA recommendations would be the ideal group to target for intervention, which could focus on their reported values and interests (e.g., personal relationships, being outdoors). Use of walking trails was associated with meeting PA recommendations. PMID:28932248

Relationships between transtheoretical model stages of change, decisional balance, self-efficacy, and physical activity level among Nigerian market vendors.

PubMed

Maruf, Fatai Adesina; Ibikunle, Peter Olanrewaju; Raji, Najim Olanrewaju

2014-01-01

This study explored decisional balance, self-efficacy, and physical activity (PA) level in relation to stages of change (SoC) for PA among Nigerian vendors. The study explored associations among decisional balance, self-efficacy, and PA level, and examined differences, by stage, in decisional balance, self-efficacy, and PA level. Cross-sectional survey. Outdoor markets located in Eke Amobi, Nkwo, and Okpuno Egbu in Nnewi, southeastern Nigeria. Participants were 499 market vendors (98 males and 401 females). Self-efficacy, perceived barrier and benefit, PA level, and SoC for PA. Spearman rank-order and partial correlations; analysis of variance by gender with Bonferroni post hoc adjustment. Self-efficacy (r = 0.69; p = 0.000), perceived benefit (r = .12; p = .007), and perceived barrier (r = -.11; p = .017) for PA were related to the SoC. Adjusting for age, gender, and marital status, only self-efficacy (r = .48; p = .000) remained correlated with the SoC. In males, significant differences in perceived barrier (p = .003) and benefit (p = .003) lay between stages of contemplation and preparation and between stages of precontemplation and contemplation for self-efficacy (p = .006). In females, there were significance differences in self-efficacy across stages of precontemplation and contemplation (p = .000) and preparation and action (p = .007). When designing PA interventions, age, gender, and marital status should be considered in explaining the relationships between outcome constructs of transtheoretical model (TTM) and SoC in vendors. It is also important to note that the stages at which outcome constructs of TTM change during PA interventions vary in males and females.

Experimental validation of a theoretical model of dual wavelength photoacoustic (PA) excitation in fluorophores

NASA Astrophysics Data System (ADS)

Märk, Julia; Theiss, Christoph; Schmitt, Franz-Josef; Laufer, Jan

2015-03-01

Fluorophores, such as exogenous dyes and genetically expressed proteins, exhibit radiative relaxation with long excited state lifetimes. This can be exploited for PA detection based on dual wavelength excitation using pump and probe wavelengths that coincide with the absorption and emission spectra, respectively. While the pump pulse raises the fluorophore to a long-lived excited state, simultaneous illumination with the probe pulse reduces the excited state lifetime due to stimulated emission (SE).This leads to a change in thermalized energy, and hence PA signal amplitude, compared to single wavelength illumination. By introducing a time delay between pump and probe pulses, the change in PA amplitude can be modulated. Since the effect is not observed in endogenous chromophores, it provides a contrast mechanism for the detection of fluorophores via PA difference imaging. In this study, a theoretical model of the PA signal generation in fluorophores was developed and experimentally validated. The model is based on a system of coupled rate equations, which describe the spatial and temporal changes in the population of the molecular energy levels of a fluorophore as a function of pump-probe energy and concentration. This allows the prediction of the thermalized energy distribution, and hence the time-resolved PA signal amplitude. The model was validated by comparing its predictions to PA signals measured in solutions of rhodamine 6G, a well-known laser dye, and Atto680, a NIR fluorophore.

Generation of Novel Chimeric Mice with Humanized Livers by Using Hemizygous cDNA-uPA/SCID Mice

PubMed Central

Tateno, Chise; Kawase, Yosuke; Tobita, Yoshimi; Hamamura, Satoko; Ohshita, Hiroki; Yokomichi, Hiroshi; Sanada, Harumi; Kakuni, Masakazu; Shiota, Akira; Kojima, Yuha; Ishida, Yuji; Shitara, Hiroshi; Wada, Naoko A.; Tateishi, Hiromi; Sudoh, Masayuki; Nagatsuka, Shin-ichiro; Jishage, Kou-ichi; Kohara, Michinori

2015-01-01

We have used homozygous albumin enhancer/promoter-driven urokinase-type plasminogen activator/severe combined immunodeficient (uPA/SCID) mice as hosts for chimeric mice with humanized livers. However, uPA/SCID mice show four disadvantages: the human hepatocytes (h-heps) replacement index in mouse liver is decreased due to deletion of uPA transgene by homologous recombination, kidney disorders are likely to develop, body size is small, and hemizygotes cannot be used as hosts as more frequent homologous recombination than homozygotes. To solve these disadvantages, we have established a novel host strain that has a transgene containing albumin promoter/enhancer and urokinase-type plasminogen activator cDNA and has a SCID background (cDNA-uPA/SCID). We applied the embryonic stem cell technique to simultaneously generate a number of transgenic lines, and found the line with the most appropriate levels of uPA expression—not detrimental but with a sufficiently damaged liver. We transplanted h-heps into homozygous and hemizygous cDNA-uPA/SCID mice via the spleen, and monitored their human albumin (h-alb) levels and body weight. Blood h-alb levels and body weight gradually increased in the hemizygous cDNA-uPA/SCID mice and were maintained until they were approximately 30 weeks old. By contrast, blood h-alb levels and body weight in uPA/SCID chimeric mice decreased from 16 weeks of age onwards. A similar decrease in body weight was observed in the homozygous cDNA-uPA/SCID genotype, but h-alb levels were maintained until they were approximately 30 weeks old. Microarray analyses revealed identical h-heps gene expression profiles in homozygous and hemizygous cDNA-uPA/SCID mice were identical to that observed in the uPA/SCID mice. Furthermore, like uPA/SCID chimeric mice, homozygous and hemizygous cDNA-uPA/SCID chimeric mice were successfully infected with hepatitis B virus and C virus. These results indicate that hemizygous cDNA-uPA/SCID mice may be novel and useful hosts for

Generation of Novel Chimeric Mice with Humanized Livers by Using Hemizygous cDNA-uPA/SCID Mice.

PubMed

Tateno, Chise; Kawase, Yosuke; Tobita, Yoshimi; Hamamura, Satoko; Ohshita, Hiroki; Yokomichi, Hiroshi; Sanada, Harumi; Kakuni, Masakazu; Shiota, Akira; Kojima, Yuha; Ishida, Yuji; Shitara, Hiroshi; Wada, Naoko A; Tateishi, Hiromi; Sudoh, Masayuki; Nagatsuka, Shin-Ichiro; Jishage, Kou-Ichi; Kohara, Michinori

2015-01-01

We have used homozygous albumin enhancer/promoter-driven urokinase-type plasminogen activator/severe combined immunodeficient (uPA/SCID) mice as hosts for chimeric mice with humanized livers. However, uPA/SCID mice show four disadvantages: the human hepatocytes (h-heps) replacement index in mouse liver is decreased due to deletion of uPA transgene by homologous recombination, kidney disorders are likely to develop, body size is small, and hemizygotes cannot be used as hosts as more frequent homologous recombination than homozygotes. To solve these disadvantages, we have established a novel host strain that has a transgene containing albumin promoter/enhancer and urokinase-type plasminogen activator cDNA and has a SCID background (cDNA-uPA/SCID). We applied the embryonic stem cell technique to simultaneously generate a number of transgenic lines, and found the line with the most appropriate levels of uPA expression-not detrimental but with a sufficiently damaged liver. We transplanted h-heps into homozygous and hemizygous cDNA-uPA/SCID mice via the spleen, and monitored their human albumin (h-alb) levels and body weight. Blood h-alb levels and body weight gradually increased in the hemizygous cDNA-uPA/SCID mice and were maintained until they were approximately 30 weeks old. By contrast, blood h-alb levels and body weight in uPA/SCID chimeric mice decreased from 16 weeks of age onwards. A similar decrease in body weight was observed in the homozygous cDNA-uPA/SCID genotype, but h-alb levels were maintained until they were approximately 30 weeks old. Microarray analyses revealed identical h-heps gene expression profiles in homozygous and hemizygous cDNA-uPA/SCID mice were identical to that observed in the uPA/SCID mice. Furthermore, like uPA/SCID chimeric mice, homozygous and hemizygous cDNA-uPA/SCID chimeric mice were successfully infected with hepatitis B virus and C virus. These results indicate that hemizygous cDNA-uPA/SCID mice may be novel and useful hosts for

PA-X protein decreases replication and pathogenicity of swine influenza virus in cultured cells and mouse models.

PubMed

Gong, Xiao-Qian; Sun, Ying-Feng; Ruan, Bao-Yang; Liu, Xiao-Min; Wang, Qi; Yang, Hai-Ming; Wang, Shuai-Yong; Zhang, Peng; Wang, Xiu-Hui; Shan, Tong-Ling; Tong, Wu; Zhou, Yan-Jun; Li, Guo-Xin; Zheng, Hao; Tong, Guang-Zhi; Yu, Hai

2017-06-01

Swine influenza viruses have been circulating in pigs throughout world and might be potential threats to human health. PA-X protein is a newly discovered protein produced from the PA gene by ribosomal frameshifting and the effects of PA-X on the 1918 H1N1, the pandemic 2009 H1N1, the highly pathogenic avian H5N1 and the avian H9N2 influenza viruses have been reported. However, the role of PA-X in the pathogenesis of swine influenza virus is still unknown. In this study, we rescued the H1N1 wild-type (WT) classical swine influenza virus (A/Swine/Guangdong/1/2011 (H1N1)) and H1N1 PA-X deficient virus containing mutations at the frameshift motif, and compared their replication properties and pathogenicity of swine influenza virus in vitro and in vivo. Our results show that the expression of PA-X inhibits virus replication and polymerase activity in cultured cells and decreases virulence in mouse models. Therefore, our study demonstrates that PA-X protein acts as a negative virulence regulator for classical H1N1 swine influenza virus and decreases virulence by inhibiting viral replication and polymerase activity, deepening our understanding of the pathogenesis of swine influenza virus. Copyright © 2017 Elsevier B.V. All rights reserved.

GOES-R active vibration damping controller design, implementation, and on-orbit performance

NASA Astrophysics Data System (ADS)

Clapp, Brian R.; Weigl, Harald J.; Goodzeit, Neil E.; Carter, Delano R.; Rood, Timothy J.

2018-01-01

GOES-R series spacecraft feature a number of flexible appendages with modal frequencies below 3.0 Hz which, if excited by spacecraft disturbances, can be sources of undesirable jitter perturbing spacecraft pointing. To meet GOES-R pointing stability requirements, the spacecraft flight software implements an Active Vibration Damping (AVD) rate control law which acts in parallel with the nadir point attitude control law. The AVD controller commands spacecraft reaction wheel actuators based upon Inertial Measurement Unit (IMU) inputs to provide additional damping for spacecraft structural modes below 3.0 Hz which vary with solar wing angle. A GOES-R spacecraft dynamics and attitude control system identified model is constructed from pseudo-random reaction wheel torque commands and IMU angular rate response measurements occurring over a single orbit during spacecraft post-deployment activities. The identified Fourier model is computed on the ground, uplinked to the spacecraft flight computer, and the AVD controller filter coefficients are periodically computed on-board from the Fourier model. Consequently, the AVD controller formulation is based not upon pre-launch simulation model estimates but upon on-orbit nadir point attitude control and time-varying spacecraft dynamics. GOES-R high-fidelity time domain simulation results herein demonstrate the accuracy of the AVD identified Fourier model relative to the pre-launch spacecraft dynamics and control truth model. The AVD controller on-board the GOES-16 spacecraft achieves more than a ten-fold increase in structural mode damping for the fundamental solar wing mode while maintaining controller stability margins and ensuring that the nadir point attitude control bandwidth does not fall below 0.02 Hz. On-orbit GOES-16 spacecraft appendage modal frequencies and damping ratios are quantified based upon the AVD system identification, and the increase in modal damping provided by the AVD controller for each structural mode is

GOES-R Active Vibration Damping Controller Design, Implementation, and On-Orbit Performance

NASA Technical Reports Server (NTRS)

Clapp, Brian R.; Weigl, Harald J.; Goodzeit, Neil E.; Carter, Delano R.; Rood, Timothy J.

2017-01-01

GOES-R series spacecraft feature a number of flexible appendages with modal frequencies below 3.0 Hz which, if excited by spacecraft disturbances, can be sources of undesirable jitter perturbing spacecraft pointing. In order to meet GOES-R pointing stability requirements, the spacecraft flight software implements an Active Vibration Damping (AVD) rate control law which acts in parallel with the nadir point attitude control law. The AVD controller commands spacecraft reaction wheel actuators based upon Inertial Measurement Unit (IMU) inputs to provide additional damping for spacecraft structural modes below 3.0 Hz which vary with solar wing angle. A GOES-R spacecraft dynamics and attitude control system identified model is constructed from pseudo-random reaction wheel torque commands and IMU angular rate response measurements occurring over a single orbit during spacecraft post-deployment activities. The identified Fourier model is computed on the ground, uplinked to the spacecraft flight computer, and the AVD controller filter coefficients are periodically computed on-board from the Fourier model. Consequently, the AVD controller formulation is based not upon pre-launch simulation model estimates but upon on-orbit nadir point attitude control and time-varying spacecraft dynamics. GOES-R high-fidelity time domain simulation results herein demonstrate the accuracy of the AVD identified Fourier model relative to the pre-launch spacecraft dynamics and control truth model. The AVD controller on-board the GOES-16 spacecraft achieves more than a ten-fold increase in structural mode damping of the fundamental solar wing mode while maintaining controller stability margins and ensuring that the nadir point attitude control bandwidth does not fall below 0.02 Hz. On-orbit GOES-16 spacecraft appendage modal frequencies and damping ratios are quantified based upon the AVD system identification, and the increase in modal damping provided by the AVD controller for each structural

Differential effects of efavirenz, lopinavir/r, and atazanavir/r on the initial viral decay rate in treatment naïve HIV-1-infected patients.

PubMed

Edén, Arvid; Andersson, Lars-Magnus; Andersson, Orjan; Flamholc, Leo; Josephson, Filip; Nilsson, Staffan; Ormaasen, Vidar; Svedhem, Veronica; Säll, Christer; Sönnerborg, Anders; Tunbäck, Petra; Gisslén, Magnus

2010-05-01

Initial viral decay rate may be useful when comparing the relative potency of antiretroviral regimens. Two hundred twenty-seven ART-naïve patients were randomized to receive efavirenz (EFV) (n = 74), lopinavir/ritonavir (LPV/r) (n = 77), or atazanavir/ritonavir (ATV/r) (n = 79) in combination with two NRTIs. The most frequently used NRTI combinations in the EFV and ATV/r groups were the nonthymidine analogues tenofovir and emtricitabine or lamivudine (70% and 68%, respectively) and, in the LPV/r group, lamivudine and the thymidine analogue zidovudine (89%). HIV-1 RNA was monitored during the first 28 days after treatment initiation. Phase 1 and 2 decay rate was estimated in a subset of 157 patients by RNA decrease from days 0 to 7, and days 14 to 28. One-way ANOVA and subsequent Tukey's post hoc tests were used for groupwise comparisons. Mean (95% CI) HIV-1 RNA reductions from days 0 to 28 were 2.59 (2.45-2.73), 2.42 (2.27-2.57), and 2.13 (2.01-2.25) log(10) copies/ml for the EFV-, LPV/r-, and ATV/r-based treatment groups, respectively, with a significantly larger decrease in the EFV-based group at all time points compared with ATV/r (p < 0.0001), and with LPV/r at days 7-21 (p < 0.0001-0.03). LPV/r gave a greater RNA decrease compared with ATV/r from day 14 (p = 0.02). Phase 1 decay rate was significantly higher in the EFV group compared with LPV/r (p = 0.003) or ATV/r (p < 0.0001). No difference was found in phase 2 decrease. EFV-based treatment gave a more rapid decline in HIV-1 RNA than did either of the boosted protease inhibitor-based regimens. The observed differences may reflect different inherent regimen potencies.

Association of outdoor recreation availability with physical activity and weight status in Minnesota youth.

PubMed

Wilhelm Stanis, Sonja A; Oftedal, Andrew; Schneider, Ingrid

2014-03-01

Examine macro-level associations of youth physical activity (PA) and weight status with availability of outdoor recreation resources (i.e., parkland, forestland, natural preserves, nonmotorized trails, and motorized trails) across counties in Minnesota. Hierarchical regression models examined if availability of recreation resources significantly improved prediction of PA and weight status of 9th and 12th grade boys and girls (2010) across Minnesota counties. The inclusion of county-level densities of recreational land variables did not produce a significant increase in R(2) for any of the models predicting 9th grade outcomes, yet county-level densities of recreational trails did significantly increase R(2) for both levels of PA and weight status. In contrast, the inclusion of recreational trails did not produce any significant increases in R(2) for 12th grade outcomes, although the inclusion of recreational land did significantly increase the R(2) for 12th grade girls achieving 30min of PA 5 or more days of the week. Findings indicate that various recreational land and trail types may have different impacts on and associations with PA and health outcomes. As such, it is important that future studies focus not only on parks, but also on other types of recreational lands and trails as well. Copyright © 2013 Elsevier Inc. All rights reserved.

Positioning Australia's Contemporary Health and Physical Education Curriculum to Address Poor Physical Activity Participation Rates by Adolescent Girls

ERIC Educational Resources Information Center

Usher, Wayne; Edwards, Allan; Cudmore, Laura

2016-01-01

Background: Given the wealth of research identifying how schools are in a strong position to promote physical activity (PA) among children, it would be reasonable to suggest that initial experiences of physical education and school sport are critical factors influencing whether a student will develop a healthy relationship to PA. However, research…

Mucosal priming of newborn mice with S. Typhi Ty21a expressing anthrax protective antigen (PA) followed by parenteral PA-boost induces B and T cell-mediated immunity that protects against infection bypassing maternal antibodies

PubMed Central

Ramirez, Karina; Ditamo, Yanina; Galen, James E.; Baillie, Les W. J.; Pasetti, Marcela F.

2010-01-01

The currently licensed anthrax vaccine has several limitations and its efficacy has been proven only in adults. Effective immunization of newborns and infants requires adequate stimulation of their immune system, which is competent but not fully activated. We explored the use of the licensed live attenuated S. Typhi vaccine strain Ty21a expressing Bacillus anthracis protective antigen [Ty21a(PA)] followed PA-alum as a strategy for immunizing the pediatric population. Newborn mice primed with a single dose of Ty21a(PA) exhibited high frequencies of mucosal IgA-secreting B cells and IFN-γ-secreting T cells during the neonatal period, none of which was detected in newborns immunized with a single dose of PA-alum. Priming with Ty21a(PA) followed by PA-boost resulted in high levels of PA-specific IgG, toxin-neutralizing and opsonophagocytic antibodies and increased frequency of bone marrow IgG plasma cells and memory B cells compared with repeated immunization with PA-alum alone. Robust B and T cell responses developed even in the presence of maternal antibodies. The prime-boost protected against systemic and respiratory infection. Mucosal priming with a safe and effective S. Typhi-based anthrax vaccine followed by PA-boost could serve as a practical and effective prophylactic approach to prevent anthrax early in life. PMID:20619377

Endovascular thrombectomy for acute ischemic stroke in failed intravenous tissue plasminogen activator versus non-intravenous tissue plasminogen activator patients: revascularization and outcomes stratified by the site of arterial occlusions.

PubMed

Shi, Zhong-Song; Loh, Yince; Walker, Gary; Duckwiler, Gary R

2010-06-01

Intracranial mechanical thrombectomy is a therapeutic option for acute ischemic stroke patients failing intravenous tissue plasminogen activator (IV tPA). We compared patients treated by mechanical embolus removal in cerebral ischemia (MERCI) thrombectomy after failed IV tPA with those treated with thrombectomy alone. We pooled MERCI and Multi MERCI study patients, grouped them either as failed IV tPA or non-IV tPA, and assessed revascularization rates, procedural complications, symptomatic hemorrhage rates, clinical outcomes, and mortality. We also evaluated outcomes stratified by the occlusion site and final revascularization. Among 305 patients, 48 failed, and 257 were ineligible for IV tPA. Nonresponders to IV tPA trended toward a higher revascularization rate (73% versus 63%) and less mortality (27.7% versus 40.1%) and had similar rates of symptomatic hemorrhage and procedural complications. Favorable 90-day outcomes were similar in failed and non-IV tPA patients (38% versus 31%), with no difference according to occlusion site. Among patients failing IV tPA, good outcomes tended to occur more frequently in revascularized patients (47.1% versus 15.4%), although this relationship was attributable solely to middle cerebral artery and not internal carotid artery occlusions, with no difference in mortality. Among IV tPA-ineligible patients, revascularization correlated with good outcome (47.4% versus 4.4%) and less mortality (28.5% versus 59.6%). The risks of hemorrhage and procedure-related complications after mechanical thrombectomy do not differ with respect to previous IV tPA administration. Thrombectomy after IV tPA achieves similar rates of good outcomes, a tendency toward lower mortality, and similar revascularization rates when stratified by clot location. Good outcomes correlate with successful revascularization except with internal carotid artery occlusions in tPA-nonresponders.

Direct and indirect measurement of physical activity in older adults: a systematic review of the literature

PubMed Central

2012-01-01

Background Due to physiological and cognitive changes that occur with aging, accurate physical activity (PA) measurement in older adults represents a unique challenge. The primary purpose of this study was to systematically review measures of PA and their use and appropriateness with older adults. A secondary aim was to determine the level of agreement between PA measures in older adults. Methods Literature was identified through electronic databases. Studies were eligible if they examined the correlation and/or agreement between at least 2 measures, either indirect and/or direct, of PA in older adults (> 65 years of age). Results Thirty-six studies met eligibility criteria. The indirect and direct measures of PA across the studies differed widely in their ability to address the key dimensions (i.e., frequency, intensity, time, type) of PA in older adults. The average correlation between indirect and direct measures was moderate (r=0.38). The correlation between indirect and other indirect measures (r=0.29) was weak, while correlations between direct measures with other direct measures were high (real world: r= 0.84; controlled settings: r=0.92). Agreement was strongest between direct PA measures with other direct measures in both real world and laboratory settings. While a clear trend regarding the agreement for mean differences between other PA measures (i.e., direct with indirect, indirect with indirect) did not emerge, there were only a limited number of studies that reported comparable units. Conclusions Despite the lack of a clear trend regarding the agreement between PA measures in older adults, the findings underscore the importance of valid, accurate and reliable measurement. To advance this field, researchers will need to approach the assessment of PA in older adults in a more standardized way (i.e., consistent reporting of results, consensus over cut-points and epoch lengths, using appropriate validation tools). Until then researchers should be cautious

Direct and indirect measurement of physical activity in older adults: a systematic review of the literature.

PubMed

Kowalski, Kristina; Rhodes, Ryan; Naylor, Patti-Jean; Tuokko, Holly; MacDonald, Stuart

2012-12-18

Due to physiological and cognitive changes that occur with aging, accurate physical activity (PA) measurement in older adults represents a unique challenge. The primary purpose of this study was to systematically review measures of PA and their use and appropriateness with older adults. A secondary aim was to determine the level of agreement between PA measures in older adults. Literature was identified through electronic databases. Studies were eligible if they examined the correlation and/or agreement between at least 2 measures, either indirect and/or direct, of PA in older adults (> 65 years of age). Thirty-six studies met eligibility criteria. The indirect and direct measures of PA across the studies differed widely in their ability to address the key dimensions (i.e., frequency, intensity, time, type) of PA in older adults. The average correlation between indirect and direct measures was moderate (r=0.38). The correlation between indirect and other indirect measures (r=0.29) was weak, while correlations between direct measures with other direct measures were high (real world: r= 0.84; controlled settings: r=0.92). Agreement was strongest between direct PA measures with other direct measures in both real world and laboratory settings. While a clear trend regarding the agreement for mean differences between other PA measures (i.e., direct with indirect, indirect with indirect) did not emerge, there were only a limited number of studies that reported comparable units. Despite the lack of a clear trend regarding the agreement between PA measures in older adults, the findings underscore the importance of valid, accurate and reliable measurement. To advance this field, researchers will need to approach the assessment of PA in older adults in a more standardized way (i.e., consistent reporting of results, consensus over cut-points and epoch lengths, using appropriate validation tools). Until then researchers should be cautious when choosing measures for PA that are

Gender differences in the predictors of physical activity among assisted living residents.

PubMed

Chen, Yuh-Min; Li, Yueh-Ping; Yen, Min-Ling

2015-05-01

To explore gender differences in the predictors of physical activity (PA) among assisted living residents. A cross-sectional design was adopted. A convenience sample of 304 older adults was recruited from four assisted living facilities in Taiwan. Two separate simultaneous multiple regression analyses were conducted to identify the predictors of PA for older men and women. Independent variables entered into the regression models were age, marital status, educational level, past regular exercise participation, number of chronic diseases, functional status, self-rated health, depression, and self-efficacy expectations. In older men, a junior high school or higher educational level, past regular exercise participation, better functional status, better self-rated health, and higher self-efficacy expectations predicted more PA, accounting for 61.3% of the total variance in PA. In older women, better self-rated health, lower depression, and higher self-efficacy expectations predicted more PA, accounting for 50% of the total variance in PA. Predictors of PA differed between the two genders. The results have crucial implications for developing gender-specific PA interventions. Through a clearer understanding of gender-specific predictors, healthcare providers can implement gender-sensitive PA-enhancing interventions to assist older residents in performing sufficient PA. © 2015 Sigma Theta Tau International.

The uPA/uPAR system regulates the bioavailability of PDGF-DD: implications for tumour growth.

PubMed

Ehnman, M; Li, H; Fredriksson, L; Pietras, K; Eriksson, U

2009-01-29

Members of the platelet-derived growth factor (PDGF) family are mitogens for cells of mesenchymal origin and have important functions during embryonic development, blood vessel maturation, fibrotic diseases and cancer. In contrast to the two classical PDGFs, the novel and less well-characterized members, PDGF-CC and PDGF-DD, are latent factors that need to be processed extracellularly by activating proteases, before they can mediate PDGF receptor activation. Here, we elucidate the structural requirements for urokinase plasminogen activator (uPA)-mediated activation of PDGF-DD, as well as the intricate interplay with uPA receptor (uPAR) signalling. Furthermore, we show that activated PDGF-DD, in comparison to latent, more potently transforms NIH/3T3 cells in vitro. Conversely, xenograft studies in nude mice demonstrate that cells expressing latent PDGF-DD are more tumorigenic than those expressing activated PDGF-DD. These findings imply that a fine-tuned proteolytic activation, in the local milieu, controls PDGF-DD bioavailability. Moreover, we suggest that proteolytic activation of PDGF-DD reveals a retention motif mediating interactions with pericellular components. Our proposed mechanism, where uPA not only generates active PDGF-DD, but also regulates its spatial distribution, provides novel insights into the biological function of PDGF-DD.

Sources of Variability in Physical Activity Among Inactive People with Multiple Sclerosis.

PubMed

Uszynski, Marcin K; Herring, Matthew P; Casey, Blathin; Hayes, Sara; Gallagher, Stephen; Motl, Robert W; Coote, Susan