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  1. Fasting Ghrelin Levels Are Decreased in Obese Subjects and Are Significantly Related With Insulin Resistance and Body Mass Index

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    Dimitrios Papandreou

    2017-10-01

    CONCLUSION: Obese subjects have low fasting ghrelin levels that they are significantly related to insulin resistance and body mass index. More prospective studies are needed to establish the role of ghrelin in the pathogenesis of human obesity.

  2. N- and C-terminal truncations of a GH10 xylanase significantly increase its activity and thermostability but decrease its SDS resistance.

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    Zheng, Fei; Huang, Jingxuan; Liu, Xingchen; Hu, Hang; Long, Liangkun; Chen, Kaixiang; Ding, Shaojun

    2016-04-01

    XynII from Volvariella volvacea has high sodium dodecyl sulfate (SDS) resistance, with the potential for industrial applications under harsh conditions. It consists of a single glycoside hydrolase family 10 (GH10) catalytic domain but contains an additional unique 10 and 4 amino acid residues at the N- and C-terminus, respectively. In this study, five XynII derivatives with N- and/or C-terminus deletions were constructed to determine the effects of these regions on enzyme activity, substrate specificity, thermostability, and SDS resistance. Our results revealed that N- and/or C-terminal truncations significantly increased enzyme activity and thermostability, but reduced SDS resistance. Specifically, the XynIIΔNC4 mutant had 2.53-fold more catalytic efficiency (k cat/K m) towards beechwood xylan than wild-type and 3.0-fold more thermostability (t 1/2 [55°C]). XynIIΔNC4 displayed 3.33-, 4.38-, 1.37-, and 1.98-fold more activity against xylotriose, xylotetraose, xylopentaose, and xylohexaose, respectively, than XynII did. However, its half-life (t 1/2) in 4 % SDS was only 1.72 h, while that of XynII was 4.65 h. Circular dichroism analysis revealed that deletion of N- and C-terminal segments caused minor changes in secondary structure. Our observations suggest that the extra N- and C-terminal segments in wild-type XynII evolved to strengthen the interaction between these regions of the protein, making the local structure more rigid and reducing structural flexibility. In this way, N- and C-terminal truncations increased the thermostability and activity of XynII on different xylans and linear xylooligosaccharides, but reduced its resistance to SDS.

  3. A significant reduction in the frequency of HIV-1 drug resistance in Québec from 2001 to 2011 is associated with a decrease in the monitored viral load.

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    Hugues Charest

    Full Text Available BACKGROUND: HIV drug resistance represents a major threat for effective treatment. We assessed the trends in the frequency of drug resistance mutations and the monitored viral load (VL in treatment-naïve (TN and treatment-experienced (TE individuals infected with HIV-1 in Québec, Canada, between 2001 and 2011. METHODS AND FINDINGS: Resistance data were obtained from 4,105 and 5,086 genotypic tests performed on TN and TE patients, respectively. Concomitantly, 274,161 VL tests were carried out in the Province. Changes over time in drug resistance frequency and in different categories of VL were assessed using univariate logistic regression. Multiple logistic regression was used to evaluate associations between the rates of certain mutations and antiretroviral prescriptions. From 2001 to 2011, the proportion of undetectable VL test results continually increased, from 42.1% to 75.9%, while a significant decrease in the frequency of resistance mutations associated with protease inhibitors [PI (from 54% to 16%], nucleoside [NRTI (from 78% to 37% and non-nucleoside reverse transcriptase inhibitors [NNRTI (from 44% to 31%] was observed in TE patients. In TN individuals, the overall frequency of transmitted drug resistance was 13.1%. A multiple logistic regression analysis indicated that the introduction of co-formulated emtricitabine/tenofovir or emtricitabine/tenofovir/efavirenz was positively associated with the decrease of the frequency of the M184I/V mutations observed overtime (p = 0.0004. CONCLUSIONS: We observed a significant decrease in the frequency of drug resistance mutations in TE patients, concomitant with a decrease in the proportion of patients with detectable viremia. These findings may be related to both the increased potencies and adherence to therapy associated with newer antiretroviral regimens. Nevertheless, our data demonstrate that broad use of antiretrovirals does not increase the level of circulating drug resistant

  4. Prognostic Significance of Preterm Isolated Decreased Fetal Movement

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    Ertuğrul Karahanoğlu

    2017-12-01

    Full Text Available Objective: Our aim is to evaluate the prognostic significance of isolated, preterm decreased fetal movement following normal initial full diagnostic workup. Study design: A retrospective observational study was conducted at a tertiary centre. The applied protocol was approved by the Medical Research Ethics Department of the hospital where the research was conducted. Obstetrics outcomes of preterm- and term-decreased fetal movement were compared following an initial, normal diagnostic work up. Evaluated outcomes were birth weight, mode of delivery, stillbirth rate, induction of labour, development of gestational hypertension, small for gestational age and oligohydramnios, polyhydramnios during the follow up period. Result: Obstetric complications related to placental insufficiency develops more frequently for decreased fetal movement in preterm cases with respect to that of in term cases. Following the diagnosis of decreased fetal movement, pregnancy hypertension occurred in 17% of preterm decreased fetal movement cases and in 4.7% of term decreased fetal movement cases. Fetal growth restriction developed in 6.6% of preterm decreased fetal movement and in 2.3% of term decreased fetal movement. Amniotic fluid abnormalities more frequently developed in preterm decreased fetal movement. Conclusion: Following an initial normal diagnostic workup, preterm decreased fetal movement convey a higher risk for the development of pregnancy complications associated with placental insufficiency. The patient should be monitored closely and management protocols must be developed for initial normal diagnostic workups in cases of preterm decreased fetal movement.

  5. Lateral Squats Significantly Decrease Sprint Time in Collegiate Baseball Athletes

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    Jason B. White

    2016-03-01

    Full Text Available The purpose was to examine the effect of prior performance of dumbbell lateral squats (DBLS on an agility movement-into-a-sprint (AMS test. Twelve collegiate, resistance-trained, baseball athletes participated in three sessions separated by three days. Session One consisted of AMS baseline test, DBLS 5-RM test, and experimental protocol familiarization. Subjects were randomly assigned the protocol order for Sessions Two and Three, which consisted of warm up followed by 1-min sitting (no-DBLS or performing the DBLS for 1 × 5 repetitions @ 5RM for each leg. Four minutes of slow recovery walking preceded the AMS test, which consisted of leading off a base and waiting for a visual stimulus. In reaction to stimulus, subjects exerted maximal effort while moving to the right by either pivoting or drop stepping and sprinting for 10 yards (yd. In Session Three, subjects switched protocols (DBLS, no-DBLS. Foot contact time (FCT, stride frequency (SF, stride length (SL, and 10-yd sprint time were measured. There were no differences between conditions for FCT, SF, or SL. Differences existed between DBLS (1.85 ± 0.09 s and no-DBLS (1.89 ± 0.10 s for AMS (p = 0.03. Results from the current study support the use of DBLS for performance enhancement prior to performing the AMS test.

  6. Decreased cisplatin uptake by resistant L1210 leukemia cells

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    Hromas, R.A.; North, J.A.; Burns, C.P.

    1987-01-01

    Cisplatin resistance remains poorly understood compared to other forms of anti-neoplastic drug resistance. In this report radiolabelled cisplatin and rapid separation techniques were used to compare drug uptake by L1210 leukemia cells that are sensitive (K25) or resistant (SCR9) to cisplatin. Uptake of cisplatin by both cell lines was linear without saturation kinetics up to 100 μM. The resistant ZCR9 cells had 36-60% reduced drug uptake as compared to its sensitive parent line, K25. In contrast, there was no difference in the rate of efflux. We conclude that a decreased rate of uptake is one possible mechanism of cellular cisplatin resistance. (Author)

  7. Dynamic resistance training decreases sympathetic tone in hypertensive ovariectomized rats

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    Shimojo, G.L.; Palma, R.K.; Brito, J.O.; Sanches, I.C. [Laboratório de Fisiologia Translacional, Programa de Ciências da Reabilitação, Universidade Nove de Julho, São Paulo, SP (Brazil); Irigoyen, M.C. [Instituto do Coração, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); De Angelis, K. [Laboratório de Fisiologia Translacional, Programa de Ciências da Reabilitação, Universidade Nove de Julho, São Paulo, SP (Brazil)

    2015-03-27

    The aim of this study was to investigate the effects of resistance exercise training on hemodynamics and cardiac autonomic control in ovariectomized spontaneously hypertensive rats. Female rats were divided into 4 groups: sedentary control (SC), sedentary hypertensive (SH), sedentary hypertensive ovariectomized (SHO), and resistance-trained hypertensive ovariectomized (RTHO). Resistance exercise training was performed on a vertical ladder (5 days/week, 8 weeks) at 40-60% maximal load. Direct arterial pressure was recorded. Vagal and sympathetic tones were measured by heart rate (HR) responses to methylatropine (3 mg/kg, iv) and propranolol (4 mg/kg, iv). Ovariectomy resulted in additional increases in blood pressure in hypertensive rats and was associated with decreased vagal tone. Resistance exercise trained rats had lower mean arterial pressure than untrained rats (RTHO: 159±2.2 vs SHO: 177±3.4 mmHg), as well as resting bradycardia (RTHO: 332±9.0 vs SHO: 356±5 bpm). Sympathetic tone was also lower in the trained group. Moreover, sympathetic tone was positively correlated with resting HR (r=0.7, P<0.05). The additional arterial pressure increase in hypertensive rats caused by ovarian hormone deprivation was attenuated by moderate-intensity dynamic resistance training. This benefit may be associated with resting bradycardia and reduced cardiac sympathetic tone after training, which suggests potential benefits of resistance exercise for the management of hypertension after ovarian hormone deprivation.

  8. Dynamic resistance training decreases sympathetic tone in hypertensive ovariectomized rats

    International Nuclear Information System (INIS)

    Shimojo, G.L.; Palma, R.K.; Brito, J.O.; Sanches, I.C.; Irigoyen, M.C.; De Angelis, K.

    2015-01-01

    The aim of this study was to investigate the effects of resistance exercise training on hemodynamics and cardiac autonomic control in ovariectomized spontaneously hypertensive rats. Female rats were divided into 4 groups: sedentary control (SC), sedentary hypertensive (SH), sedentary hypertensive ovariectomized (SHO), and resistance-trained hypertensive ovariectomized (RTHO). Resistance exercise training was performed on a vertical ladder (5 days/week, 8 weeks) at 40-60% maximal load. Direct arterial pressure was recorded. Vagal and sympathetic tones were measured by heart rate (HR) responses to methylatropine (3 mg/kg, iv) and propranolol (4 mg/kg, iv). Ovariectomy resulted in additional increases in blood pressure in hypertensive rats and was associated with decreased vagal tone. Resistance exercise trained rats had lower mean arterial pressure than untrained rats (RTHO: 159±2.2 vs SHO: 177±3.4 mmHg), as well as resting bradycardia (RTHO: 332±9.0 vs SHO: 356±5 bpm). Sympathetic tone was also lower in the trained group. Moreover, sympathetic tone was positively correlated with resting HR (r=0.7, P<0.05). The additional arterial pressure increase in hypertensive rats caused by ovarian hormone deprivation was attenuated by moderate-intensity dynamic resistance training. This benefit may be associated with resting bradycardia and reduced cardiac sympathetic tone after training, which suggests potential benefits of resistance exercise for the management of hypertension after ovarian hormone deprivation

  9. Parathyroidectomy Decreases Insulin Resistance Index in Patients with Primary Hyperparathyroidism.

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    Duran, Cevdet; Sevinc, Barıs; Kutlu, Orkide; Karahan, Omer

    2017-04-01

    Primary hyperparathyroidism (PHPT) has been considered a cause of insulin resistance (IR) and impaired glucose metabolism. However, there are conflicting results related with the recovery of insulin resistance in patients with PHPT following curative parathyroidectomy. Our aim is to evaluate the effects of curative parathyroidectomy on IR in patients with PHPT. This is a prospective interventional study. Twenty-one consecutive patients with symptomatic PHPT were included into the study. All patients underwent parathyroidectomy. Fasting serum glucose, calcium, phosphorous, parathormone, plasma insulin, and vitamin D levels were measured both at baseline and 2 months after parathyroidectomy. Insulin resistance was calculated by homeostasis of model assessment-insulin resistance (HOMA-IR). Two months after curative parathyroidectomy, serum levels of calcium ( p  = 0.001), PTH ( p  HOMA-IR ( p  = 0.003) decreased, while phosphorous levels increased ( p  = 0.001). During this period, no changes were observed at vitamin D and glucose levels. We concluded that curative parathyroidectomy decreases HOMA-IR index in patients with PHPT. Studies with larger population and longer follow-up period are required to confirm our results.

  10. Protease-resistant prions selectively decrease Shadoo protein.

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    Joel C Watts

    2011-11-01

    Full Text Available The central event in prion diseases is the conformational conversion of the cellular prion protein (PrP(C into PrP(Sc, a partially protease-resistant and infectious conformer. However, the mechanism by which PrP(Sc causes neuronal dysfunction remains poorly understood. Levels of Shadoo (Sho, a protein that resembles the flexibly disordered N-terminal domain of PrP(C, were found to be reduced in the brains of mice infected with the RML strain of prions [1], implying that Sho levels may reflect the presence of PrP(Sc in the brain. To test this hypothesis, we examined levels of Sho during prion infection using a variety of experimental systems. Sho protein levels were decreased in the brains of mice, hamsters, voles, and sheep infected with different natural and experimental prion strains. Furthermore, Sho levels were decreased in the brains of prion-infected, transgenic mice overexpressing Sho and in infected neuroblastoma cells. Time-course experiments revealed that Sho levels were inversely proportional to levels of protease-resistant PrP(Sc. Membrane anchoring and the N-terminal domain of PrP both influenced the inverse relationship between Sho and PrP(Sc. Although increased Sho levels had no discernible effect on prion replication in mice, we conclude that Sho is the first non-PrP marker specific for prion disease. Additional studies using this paradigm may provide insight into the cellular pathways and systems subverted by PrP(Sc during prion disease.

  11. Simulated Reflux Decreases Vocal Fold Epithelial Barrier Resistance

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    Erickson, Elizabeth; Sivasankar, Mahalakshmi

    2010-01-01

    Objectives/Hypothesis The vocal fold epithelium provides a barrier to the entry of inhaled and systemic challenges. However, the location of the epithelium makes it vulnerable to damage. Past research suggests, but does not directly demonstrate, that exposure to gastric reflux adversely affects the function of the epithelial barrier. Understanding the nature of reflux-induced epithelial barrier dysfunction is necessary to better recognize the mechanisms for vocal fold susceptibility to this disease. Therefore, we examined the effects of physiologically relevant reflux challenges on vocal fold transepithelial resistance and gross epithelial and subepithelial appearance. Study Design Ex vivo, mixed design with between-group and repeated-measures analyses. Methods Healthy, native porcine vocal folds (N = 52) were exposed to physiologically relevant acidic pepsin, acid-only, or pepsin-only challenges and examined with electrophysiology and light microscopy. For all challenges, vocal folds exposed to a neutral pH served as control. Results Acidic pepsin and acid-only challenges, but not pepsin-only or control challenges significantly reduced transepithelial resistance within 30 minutes. Reductions in transepithelial resistance were irreversible. Challenge exposure produced minimal gross changes in vocal fold epithelial or subepithelial appearance as evidenced by light microscopy. Conclusions These findings demonstrate that acidic environments characteristic of gastric reflux compromise epithelial barrier function without gross structural changes. In healthy, native vocal folds, reductions in transepithelial resistance could reflect reflux-related epithelial disruption. These results might guide the development of pharmacologic and therapeutic recommendations for patients with reflux, such as continued acid-suppression therapy and patient antireflux behavioral education. PMID:20564752

  12. Periapical lesions decrease insulin signal and cause insulin resistance.

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    Astolphi, Rafael Dias; Curbete, Mariane Machado; Colombo, Natalia Helena; Shirakashi, Daisy Jaqueline; Chiba, Fernando Yamamoto; Prieto, Annelise Katrine Carrara; Cintra, Luciano Tavares Angelo; Bomfim, Suely Regina Mogami; Ervolino, Edilson; Sumida, Doris Hissako

    2013-05-01

    Inflammatory cytokines are associated with decreased insulin signal transduction. Moreover, local oral inflammation, such as that accompanying periodontal disease, is associated with insulin resistance and type 2 diabetes mellitus. The aim of this study was to evaluate the effect of periapical lesions (PLs) on insulin signaling and insulin sensitivity in rats. We hypothesized that PLs alter systemic insulin signaling and insulin sensitivity via elevated plasmatic tumor necrosis factor α (TNF-α). Wistar rats were divided into control (CN) and PL groups. PLs were induced by exposing pulpal tissue to the oral environment. After 30 days, insulin sensitivity was measured using the insulin tolerance test. After euthanization, maxillae were processed for histopathology. Plasmatic concentrations of tumor necrosis factor α (TNF-α) were determined via the enzyme-linked immunosorbent assay. Insulin signal transduction was evaluated using insulin receptor substrate tyrosine phosphorylation status and serine phosphorylation status in periepididymal white adipose tissue via Western blotting. For insulin signaling and insulin tolerance tests, the analyses performed were analysis of variance followed by the Tukey post hoc test. For TNF-α analysis, the Student's t test was used. In all tests, P change in serine phosphorylation status in white adipose tissue after insulin stimulation. PLs can cause alterations to both insulin signaling and insulin sensitivity, probably because of elevation of plasmatic TNF-α. The results from this study emphasize the importance of the prevention of local inflammatory diseases, such as PLs, with regard to the prevention of insulin resistance. Copyright © 2013 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  13. Decreasing the Resistance of the Human Resources to Organizational Changes

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    Ovidiu NICOLESCU; Ciprian NICOLESCU

    2011-01-01

    One of the most difficult problems faced by the management of all organizations within innovation and change processes is the resistance to change. This study, dealing with this issue, has the following main objectives: to identify the main sources of resistance to change, to outline the directions for reducing chang’s resistance, to design essentially managerial approaches in order to counter the resistance to change. The first part presents the 14 most frequent and most important sources of...

  14. When Does Air Resistance Become Significant in Projectile Motion?

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    Mohazzabi, Pirooz

    2018-03-01

    In an article in this journal, it was shown that air resistance could never be a significant source of error in typical free-fall experiments in introductory physics laboratories. Since projectile motion is the two-dimensional version of the free-fall experiment and usually follows the former experiment in such laboratories, it seemed natural to extend the same analysis to this type of motion. We shall find that again air resistance does not play a significant role in the parameters of interest in a traditional projectile motion experiment.

  15. Empagliflozin decreases remnant-like particle cholesterol in type 2 diabetes patients with insulin resistance.

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    Hattori, Sachiko

    2017-11-28

    Remnant lipoproteins are thought to be atherogenic. Remnant-like particle cholesterol (RLP-C), which reflects the levels of various kinds of remnant lipoproteins in the blood, has a significant correlation with insulin resistance. In the present study, we measured the effect of empagliflozin (EMPA) on the levels of RLP-C, and investigated whether EMPA-mediated change in RLP-C is associated with a change in insulin resistance in type 2 diabetes patients who have insulin resistance. Patients were allocated to receive a placebo (n = 51) or EMPA (n = 58) as an add-on treatment. Fasting blood samples were collected before and 12 weeks after this intervention. EMPA significantly decreased glycated hemoglobin, bodyweight, systolic blood pressure, plasma triglycerides, liver transaminases and estimated glomerular filtration rate, and increased high-density lipoprotein cholesterol. Furthermore, EMPA decreased RLP-C and homeostatic model assessment of insulin resistance. In the placebo group, there were no significant changes in these factors except for slight increases in liver transaminases. Multiple regression analysis showed that the change in homeostatic model assessment of insulin resistance (P = 0.0102) and the change in alanine aminotransferase (P = 0.0301) were significantly associated with the change in RLP-C in the EMPA group. The change in RLP-C significantly correlated with the change in homeostatic model assessment of insulin resistance (Pearson correlation coefficient 0.503, 95% confidence interval 0.199-0.719; P = 0.00241). EMPA decreases RLP-C levels, which is closely associated with amelioration of insulin sensitivity in diabetes patients who have insulin resistance. © 2017 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

  16. When Does Air Resistance Become Significant in Projectile Motion?

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    Mohazzabi, Pirooz

    2018-01-01

    In an article in this journal, it was shown that air resistance could never be a significant source of error in typical free-fall experiments in introductory physics laboratories. Since projectile motion is the two-dimensional version of the free-fall experiment and usually follows the former experiment in such laboratories, it seemed natural to…

  17. Significant decrease in congenital malformations in newborn infants of an unselected population of diabetic women

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    Damm, P; Mølsted-Pedersen, L

    1989-01-01

    In an unselected and consecutive series of 1858 newborn infants of diabetic mothers, born in the Rigshospital, Copenhagen, in the period 1967 to 1986, congenital malformations were studied. The malformation rate in White Classes B to F was remarkably constant from 1967 to 1981, but a significant...... decrease in major congenital malformations was found in the period 1982 to 1986 versus 1977 to 1981 (2.7% vs. 7.4%, p less than 0.05). This decrease was mainly due to a fourfold decline in major congenital malformations in White Classes D and F (p less than 0.01), and consequently a correlation between...... the severity of maternal diabetes and the frequency of congenital malformations was no longer present. In the offspring of a control group of 1715 nondiabetic women, major congenital malformations were found in 1.7% (p greater than 0.05). Seventy-five percent of the diabetic pregnancies were planned...

  18. An Acute Lateral Ankle Sprain Significantly Decreases Physical Activity across the Lifespan

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    Tricia Hubbard-Turner, Erik A. Wikstrom, Sophie Guderian, Michael J. Turner

    2015-09-01

    Full Text Available We do not know the impact an ankle sprain has on physical activity levels across the lifespan. With the negative consequences of physical inactivity well established, understanding the effect of an ankle sprain on this outcome is critical. The objective of this study was to measure physical activity across the lifespan after a single ankle sprain in an animal model. Thirty male mice (CBA/J were randomly placed into one of three groups: the transected calcaneofibular ligament (CFL group, the transected anterior talofibular ligament (ATFL/CFL group, and a SHAM group. Three days after surgery, all of the mice were individually housed in a cage containing a solid surface running wheel. Physical activity levels were recorded and averaged every week across the mouse’s lifespan. The SHAM mice ran significantly more distance each day compared to the remaining two running groups (post hoc p = 0.011. Daily duration was different between the three running groups (p = 0.048. The SHAM mice ran significantly more minutes each day compared to the remaining two running groups (post hoc p=0.046 while the ATFL/CFL mice ran significantly less minutes each day (post hoc p = 0.028 compared to both the SHAM and CFL only group. The SHAM mice ran at a faster daily speed versus the remaining two groups of mice (post hoc p = 0.019 and the ATFL/CFL mice ran significantly slower each day compared to the SHAM and CFL group (post hoc p = 0.005. The results of this study indicate that a single ankle sprain significantly decreases physical activity across the lifespan in mice. This decrease in physical activity can potentially lead to the development of numerous chronic diseases. An ankle sprain thus has the potential to lead to significant long term health risks if not treated appropriately.

  19. Significant decrease of mortality due to anastomotic leaks following esophageal resection: management makes the difference.

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    Schaible, Anja; Brenner, Thorsten; Hinz, Ulf; Schmidt, Thomas; Weigand, Markus; Sauer, Peter; Büchler, Markus W; Ulrich, Alexis

    2017-12-01

    Anastomotic leakage is the most frequent cause of postoperative mortality following esophageal surgery. However, no gold standard for diagnosing and managing leakage has been established. Continuous clinical judgment is extremely important; therefore, to optimize the management of leakage, we established a special group for decision-making in cases of suspected leakage in the early postoperative period. Between January 2010 and December 2016, 234 consecutive patients underwent elective esophageal resection with a thoracoabdominal incision. In 2014, we established a group consisting of a surgeon, surgical endoscopist, and anesthesiologist for decision-making in cases of suspected leakage. They discussed emerging problems and decided on further diagnostics or therapy. The data were documented prospectively and compared to the years prior to 2014. Two hundred and thirty-four consecutive patients were enrolled in the study, 110 in the years 2010-2013 (group A), and 124 in the years 2014-2016 (group B). Neither patients' characteristics nor the rate of anastomotic leakage differed significantly between the two study groups. The hospital mortality rate was 10% (11 patients) in group A and 4.8% (six patients) in group B. Most interestingly, mortality due to anastomotic leakage was 35% in group A (9/26), whereas it decreased significantly to 6.5% (2/31 patients) (P < 0.001) in group B. Our data clearly demonstrated that optimizing the management of anastomotic leakage by making team decisions can lead to a significant decrease in mortality.

  20. Glyphosate Can Decrease Germination of Glyphosate-Resistant Soybeans.

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    Gomes, Marcelo Pedrosa; Bicalho, Elisa Monteze; Smedbol, Élise; Cruz, Fernanda Vieira da Silva; Lucotte, Marc; Garcia, Queila Souza

    2017-03-22

    We investigated the effects of different concentrations of glyphosate acid and one of its formulations (Roundup) on seed germination of two glyphosate-resistant (GR) and one non-GR variety of soybean. As expected, the herbicide affected the shikimate pathway in non-GR seeds but not in GR seeds. We observed that glyphosate can disturb the mitochondrial electron transport chain, leading to H 2 O 2 accumulation in soybean seeds, which was, in turn, related to lower seed germination. In addition, GR seeds showed increased activity of antioxidant systems when compared to non-GR seeds, making them less vulnerable to oxidative stress induced by glyphosate. The differences in the responses of GR varieties to glyphosate exposure corresponded to their differences in enzymatic activity related to H 2 O 2 scavenging and mitochondrial complex III (the proposed site of ROS induction by glyphosate). Our results showed that glyphosate ought to be used carefully as a pre-emergence herbicide in soybean field crop systems because this practice may reduce seed germination.

  1. Potential prognostic significance of decreased serum levels of TRAIL after acute myocardial infarction.

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    Paola Secchiero

    Full Text Available BACKGROUND: Since soluble TRAIL exhibits anti-inflammatory and anti-atherosclerotic activities both in vitro and in animal models, this study was designed to assess the relationship between the serum levels of TRAIL and clinical outcomes in patients with acute myocardial infarction (AMI. METHODOLOGY/PRINCIPAL FINDINGS: Levels of TRAIL were measured by ELISA in serial serum samples obtained from 60 patients admitted for AMI, both during hospitalization and in a follow-up of 12 months, as well as in 60 healthy control subjects. Serum levels of TRAIL were significantly decreased in patients with AMI at baseline (within 24 hours from admission, compared with healthy controls, and showed a significant inverse correlation with a series of negative prognostic markers, such as CK, CK-MB and BNP. TRAIL serum levels progressively increased at discharge, but normalized only at 6-12 months after AMI. Of note, low TRAIL levels at the patient discharge were associated with increased incidence of cardiac death and heart failure in the 12-month follow-up, even after adjustment for demographic and clinical risk parameters (hazard ratio [HR] of 0.93 [95% CI, 0.89 to 0.97]; p = 0.001. CONCLUSIONS/SIGNIFICANCE: Although the number of patients studied was limited, our findings indicate for the first time that circulating TRAIL might represent an important predictor of cardiovascular events, independent of conventional risk markers.

  2. Circulating Microparticles Decrease After Cardiac Stress in Patients With Significant Coronary Artery Stenosis.

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    Sinning, Jan-Malte; Jansen, Felix; Hammerstingl, Christoph; Meier, Arne; Losch, Jan; Rohwer, Katharina; Schmitz, Theresa; Paul, Kathrin; Sedaghat, Alexander; Schueler, Robert; Vasa-Nicotera, Mariuca; Müller, Cornelius; Nickenig, Georg; Werner, Nikos

    2016-10-01

    Cardiac stress leads to a dynamic increase of circulating microparticles (MPs) in healthy individuals that is diminished in individuals with vascular disease. The impact of coronary ischemia on circulating MP level is unknown. This study investigates the kinetics of circulating MPs during cardiac stress in patients with coronary artery stenosis. Patients with significant coronary stenosis show altered circulating MP levels after cardiac stress. Eighty patients with stable coronary artery disease underwent dobutamine stress echocardiography (DSE) on the day before coronary angiography. Before, immediately after, at 4 hours, and at 24 hours after DSE, blood was drawn to determine CD144 + endothelial microparticles (EMPs), CD14 + CD16 + monocyte-derived microparticles (MMPs), and CD31 + CD42b + platelet microparticles. A significant stenosis was defined as stenosis diameter ≥70% in a major native epicardial coronary artery with a diameter of ≥2.5 mm. Significant coronary artery stenoses were found in 41 patients. In these patients, CD144 + -EMP and CD14 + CD16 + -MMP concentrations decreased immediately after DSE. Stimulation of target endothelial cells with sera from patients with significant coronary artery stenoses significantly augmented endothelial capacity to take up EMPs, but not MMPs, in vitro. Serum-induced enhancement of endothelial phosphatidylserine receptor expression was found as a potential mechanism of increased endothelial EMP uptake and subsequently reduced circulating EMP levels after cardiac stress. Cardiac ischemia leads to reduced circulating MP levels under cardiac stress. Changes of endothelial MP uptake capacities could be one possible mechanism. © 2016 Wiley Periodicals, Inc.

  3. L-carnitine significantly decreased aging of rat adipose tissue-derived mesenchymal stem cells.

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    Mobarak, Halimeh; Fathi, Ezzatollah; Farahzadi, Raheleh; Zarghami, Nosratollah; Javanmardi, Sara

    2017-03-01

    Mesenchymal stem cells are undifferentiated cells that have the ability to divide continuously and tissue regeneration potential during the transplantation. Aging and loss of cell survival, is one of the main problems in cell therapy. Since the production of free radicals in the aging process is effective, the use of antioxidant compounds can help in scavenging free radicals and prevent the aging of cells. The aim of this study is evaluate the effects of L-carnitine (LC) on proliferation and aging of rat adipose tissue-derived mesenchymal stem cells (rADSC). rADSCs were isolated from inguinal region of 5 male Rattus rats. Oil red-O, alizarin red-S and toluidine blue staining were performed to evaluate the adipogenic, osteogenic and chondrogenic differentiation of rADSCs, respectively. Flow cytometric analysis was done for investigating the cell surface markers. The methyl thiazol tetrazolium (MTT) method was used to determine the cell proliferation of rADSCs following exposure to different concentrations of LC. rADSCs aging was evaluated by beta-galactosidase staining. The results showed significant proliferation of rADSCs 48 h after treatment with concentrations of 0.2 mM LC. In addition, in the presence of 0.2 mM LC, rADSCs appeared to be growing faster than control group and 0.2 mM LC supplementation could significantly decrease the population doubling time and aging of rADSCs. It seems that LC would be a good antioxidant to improve lifespan of rADSCs due to the decrease in aging.

  4. Resistance to antivirals in human cytomegalovirus: mechanisms and clinical significance.

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    Pérez, J L

    1997-09-01

    Long term therapies needed for managing human cytomegalovirus (HCMV) infections in immunosupressed patients provided the background for the emergence of the resistance to antivirals active against HCMV. In addition, laboratory selected mutants have also been readily achieved. Both clinical and laboratory resistant strains share the same determinants of resistance. Ganciclovir resistance may be due to a few mutations in the HCMV UL97 gene and/or viral DNA pol gene, the former being responsible for about 70% of clinical resistant isolates. Among them, V464, V594, S595 and F595 are the most frequent mutations. Because of their less extensive clinical use, much less is known about resistance to foscarnet and cidofovir (formerly, HPMPC) but in both cases, it has been associated to mutations in the DNA pol. Ganciclovir resistant strains showing DNA pol mutations are cross-resistant to cidofovir and their corresponding IC50 are normally higher than those from strains harboring only mutations at the UL97 gene. To date, foscarnet resistance seems to be independent of both ganciclovir and cidofovir resistance.

  5. Intravenous Iron Repletion Does Not Significantly Decrease Platelet Counts in CKD Patients with Iron Deficiency Anemia

    Directory of Open Access Journals (Sweden)

    Neville R. Dossabhoy

    2013-01-01

    Full Text Available Purpose. We sought to investigate the effect of IV iron repletion on platelet (PLT counts in CKD patients with iron deficiency anemia (IDA. Methods. We conducted a retrospective chart review, including all patients with CKD and IDA who were treated with iron dextran total dose infusion (TDI between 2002 and 2007. Patient demographics were noted, and laboratory values for creatinine, hemoglobin (Hgb, iron stores and PLT were recorded pre- and post-dose. Results. 153 patients received a total of 251 doses of TDI (mean ± SD = 971 ± 175 mg; age years and Creatinine  mg/dL. All CKD stages were represented (stage 4 commonest. Hgb and Fe stores improved post-TDI (. There was a very mild decrease in PLT (pre-TDI 255 versus post-TDI 244, . The mild reduction in PLT after TDI remained non-significant ( when data was stratified by molecular weight (MW of iron dextran used (low versus high, as well as by dose administered (<1000 versus ≥1000 mg. Linear regression analysis between pre-dose PLT and Tsat and Fe showed R2 of 0.01 and 0.04, respectively. Conclusion. Correction of iron deficiency did not significantly lower PLT in CKD patients, regardless of MW or dose used. Correlation of PLT to severity of iron deficiency was very weak.

  6. An overview of antimicrobial resistance and its public health significance.

    Science.gov (United States)

    Balsalobre, Livia Carminato; Dropa, Milena; Matté, Maria Helena

    2014-01-01

    Multiple papers have been published regarding the bacterial resistance theme over the last years. A variety of information has reached general and scientific public, daily bringing up data on new resistant microorganisms, new drugs, outbreaks, epidemiological news, resistance gene dissemination, and the lack of information in a particular field has caught our attention: the public health department. Most of researchers, physicians and government employees interpret the public health field as a separate department, not linked to this antibiotic resistance era that we are living nowadays. In this paper we carefully tried to fill in the blanks between public health and the bacteria resistance issue, also considering historical, social, economical and biological problematic that come with this possible pre-antibiotic era.

  7. An overview of antimicrobial resistance and its public health significance

    Directory of Open Access Journals (Sweden)

    Livia Carminato Balsalobre

    2014-01-01

    Full Text Available Multiple papers have been published regarding the bacterial resistance theme over the last years. A variety of information has reached general and scientific public, daily bringing up data on new resistant microorganisms, new drugs, outbreaks, epidemiological news, resistance gene dissemination, and the lack of information in a particular field has caught our attention: the public health department. Most of researchers, physicians and government employees interpret the public health field as a separate department, not linked to this antibiotic resistance era that we are living nowadays. In this paper we carefully tried to fill in the blanks between public health and the bacteria resistance issue, also considering historical, social, economical and biological problematic that come with this possible pre-antibiotic era.

  8. Overexpression of VOZ2 confers biotic stress tolerance but decreases abiotic stress resistance in Arabidopsis.

    Science.gov (United States)

    Nakai, Yusuke; Fujiwara, Sumire; Kubo, Yasuyuki; Sato, Masa H

    2013-03-01

    VOZ (vascular plant one zinc-finger protein) is a plant specific one-zinc finger type transcriptional activator, which is highly conserved through land plant evolution. We have previously shown that loss-of-function mutations in VOZ1 and VOZ2 showed increased cold and drought stress tolerances whereas decreased biotic stress resistance in Arabidopsis. Here, we demonstrate that transgenic plants overexpressing VOZ2 impairs freezing and drought stress tolerances but increases resistance to a fungal pathogen, Colletoricum higginsianum. Consistent with changes in the tolerance to biotic and abiotic stresses, the expression of marker genes for these stresses is significantly altered compared with those of the wild-type plant. These results indicate that a overexpression of VOZ2 confers biotic stress tolerance but impairs abiotic stress tolerances in Arabidopsis.

  9. Perioperative use of tamsulosin significantly decreases rates of urinary retention in men undergoing pelvic surgery.

    Science.gov (United States)

    Poylin, Vitaliy; Curran, Thomas; Cataldo, Thomas; Nagle, Deborah

    2015-09-01

    Urinary retention is a common complication of pelvic surgery, leading to urinary tract infection and prolonged hospital stays. Tamsulosin is an alpha blocker that works by relaxing bladder neck muscles. It is used to treat benign prostatic hypertrophy and retention. We aim to investigate the potential benefits of preemptive tamsulosin use on rates of urinary retention in men undergoing pelvic surgery. This is a retrospective review of an institutional colorectal database. All men undergoing pelvic surgery between 2004 and 2013 were included. Patients given 0.4 mg of tamsulosin 3 days prior and after surgery at discretion of surgeon starting in 2007 were compared with patients receiving expectant postoperative management. One hundred eighty-five patients were included in the study (study group: N = 30; control group: N = 155). Study group patients were older (56.8 vs. 50.1 years). Overall urinary retention rate was 22% with significantly lower rates in the study group compared with control (6.7 vs. 25%; p = 0.029). Study group had higher rates of minimally invasive surgery (61 vs. 29.7%); however, this did not impact urinary retention rate (20.6 vs. 22.7% for minimally invasive surgery vs. open surgery; p = 0.85). Independent predictors of urinary retention included lack of preemptive tamsulosin (odds ratio (OR), 7.67; 95% confidence interval (CI), 1.4-41.7) and cancer location in the distal third of the rectum (OR, 18.8; 95% CI, 2.1-172.8). Preemptive perioperative use of tamsulosin may significantly decrease the incidence of urinary retention in men undergoing pelvic surgery. This may play a role in avoidance of urinary retention, particularly in patients with distal rectal cancer.

  10. Treatment-resistant panic disorder: clinical significance, concept and management.

    Science.gov (United States)

    Chen, Mu-Hong; Tsai, Shih-Jen

    2016-10-03

    Panic disorder is commonly prevalent in the population, but the treatment response for panic disorder in clinical practice is much less effective than that in our imagination. Increasing evidence suggested existence of a chronic or remitting-relapsing clinical course in panic disorder. In this systematic review, we re-examine the definition of treatment-resistant panic disorder, and present the potential risk factors related to the treatment resistance, including the characteristics of panic disorder, other psychiatric and physical comorbidities, and psychosocial stresses. Furthermore, we summarize the potential pathophysiologies, such as genetic susceptibility, altered brain functioning, brain-derived neurotrophic factor, and long-term inflammation, to explain the treatment resistance. Finally, we conclude the current therapeutic strategies for treating treatment-resistant panic disorder from pharmacological and non-pharmacological views. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Quercetin Decreases Insulin Resistance in a Polycystic Ovary Syndrome Rat Model by Improving Inflammatory Microenvironment.

    Science.gov (United States)

    Wang, Zhenzhi; Zhai, Dongxia; Zhang, Danying; Bai, Lingling; Yao, Ruipin; Yu, Jin; Cheng, Wen; Yu, Chaoqin

    2017-05-01

    Insulin resistance (IR) is a clinical feature of polycystic ovary syndrome (PCOS). Quercetin, derived from Chinese medicinal herbs such as hawthorn, has been proven practical in the management of IR in diabetes. However, whether quercetin could decrease IR in PCOS is unknown. This study aims to observe the therapeutic effect of quercetin on IR in a PCOS rat model and explore the underlying mechanism. An IR PCOS rat model was established by subcutaneous injection with dehydroepiandrosterone. The body weight, estrous cycle, and ovary morphology of the quercetin-treated rats were observed. Serum inflammatory cytokines were analyzed using enzyme-linked immunosorbent assay. In ovarian tissues, the expression of key genes involved in the inflammatory signaling pathway was detected through Western blot, real-time polymerase chain reaction, or immunohistochemistry. The nuclear translocation of nuclear factor κB (NF-κB) was also observed by immunofluorescence. The estrous cycle recovery rate of the insulin-resistant PCOS model after quercetin treatment was 58.33%. Quercetin significantly reduced the levels of blood insulin, interleukin 1β, IL-6, and tumor necrosis factor α. Quercetin also significantly decreased the granulosa cell nuclear translocation of NF-κB in the insulin-resistant PCOS rat model. The treatment inhibited the expression of inflammation-related genes, including the nicotinamide adenine dinucleotide phosphate oxidase subunit p22phox, oxidized low-density lipoprotein, and Toll-like receptor 4, in ovarian tissue. Quercetin improved IR and demonstrated a favorable therapeutic effect on the PCOS rats. The underlying mechanism of quercetin potentially involves the inhibition of the Toll-like receptor/NF-κB signaling pathway and the improvement in the inflammatory microenvironment of the ovarian tissue of the PCOS rat model.

  12. Early antiretroviral therapy and potent second-line drugs could decrease HIV incidence of drug resistance.

    Science.gov (United States)

    Shen, Mingwang; Xiao, Yanni; Rong, Libin; Meyers, Lauren Ancel; Bellan, Steven E

    2017-06-28

    Early initiation of antiretroviral therapy (ART) reduces the risk of drug-sensitive HIV transmission but may increase the transmission of drug-resistant HIV. We used a mathematical model to estimate the long-term population-level benefits of ART and determine the scenarios under which earlier ART (treatment at 1 year post-infection, on average) could decrease simultaneously both total and drug-resistant HIV incidence (new infections). We constructed an infection-age-structured mathematical model that tracked the transmission rates over the course of infection and modelled the patients' life expectancy as a function of ART initiation timing. We fitted this model to the annual AIDS incidence and death data directly, and to resistance data and demographic data indirectly among men who have sex with men (MSM) in San Francisco. Using counterfactual scenarios, we assessed the impact on total and drug-resistant HIV incidence of ART initiation timing, frequency of acquired drug resistance, and second-line drug effectiveness (defined as the combination of resistance monitoring, biomedical drug efficacy and adherence). Earlier ART initiation could decrease the number of both total and drug-resistant HIV incidence when second-line drug effectiveness is sufficiently high (greater than 80%), but increase the proportion of new infections that are drug resistant. Thus, resistance may paradoxically appear to be increasing while actually decreasing. © 2017 The Author(s).

  13. Association of a Novel Mutation in the Plasmodium falciparum Chloroquine Resistance Transporter With Decreased Piperaquine Sensitivity.

    Science.gov (United States)

    Agrawal, Sonia; Moser, Kara A; Morton, Lindsay; Cummings, Michael P; Parihar, Ankita; Dwivedi, Ankit; Shetty, Amol C; Drabek, Elliott F; Jacob, Christopher G; Henrich, Philipp P; Parobek, Christian M; Jongsakul, Krisada; Huy, Rekol; Spring, Michele D; Lanteri, Charlotte A; Chaorattanakawee, Suwanna; Lon, Chanthap; Fukuda, Mark M; Saunders, David L; Fidock, David A; Lin, Jessica T; Juliano, Jonathan J; Plowe, Christopher V; Silva, Joana C; Takala-Harrison, Shannon

    2017-08-15

    Amplified copy number in the plasmepsin II/III genes within Plasmodium falciparum has been associated with decreased sensitivity to piperaquine. To examine this association and test whether additional loci might also contribute, we performed a genome-wide association study of ex vivo P. falciparum susceptibility to piperaquine. Plasmodium falciparum DNA from 183 samples collected primarily from Cambodia was genotyped at 33716 genome-wide single nucleotide polymorphisms (SNPs). Linear mixed models and random forests were used to estimate associations between parasite genotypes and piperaquine susceptibility. Candidate polymorphisms were evaluated for their association with dihydroartemisinin-piperaquine treatment outcomes in an independent dataset. Single nucleotide polymorphisms on multiple chromosomes were associated with piperaquine 90% inhibitory concentrations (IC90) in a genome-wide analysis. Fine-mapping of genomic regions implicated in genome-wide analyses identified multiple SNPs in linkage disequilibrium with each other that were significantly associated with piperaquine IC90, including a novel mutation within the gene encoding the P. falciparum chloroquine resistance transporter, PfCRT. This mutation (F145I) was associated with dihydroartemisinin-piperaquine treatment failure after adjusting for the presence of amplified plasmepsin II/III, which was also associated with decreased piperaquine sensitivity. Our data suggest that, in addition to plasmepsin II/III copy number, other loci, including pfcrt, may also be involved in piperaquine resistance. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  14. Depletion of arginine in yeast cells decreases the resistance to hydrostatic pressure

    Science.gov (United States)

    Nomura, Kazuki; Iwahashi, Hitoshi; Iguchi, Akinori; Shigematsu, Toru

    2015-07-01

    High hydrostatic pressure (HP) inhibits growth and inactivates microorganisms by destabilizing non-covalent molecular interactions. Arginine contributes to stress resistance because it has a guanidine side chain, which assists in the refolding of aggregated proteins. We attempted to analyze the contribution of arginine to high HP stress using a pressure-sensitive mutant strain of Saccharomyces cerevisiae and a metabolomics approach. Our results showed that the content of 136 out of 250 detected metabolites differed in the mutant and parent strains. Decreased metabolites were involved in the tricarboxylic acid cycle and arginine biosynthesis. The expression of genes contributing to arginine biosynthesis was significantly lower in the mutant strain than in the parent strain. When arginine was supplemented to the medium, the mutant strain showed more tolerance to pressure. These results suggest that yeast cells survived due to the contribution of arginine to high pressure resistance. This indicates that depletion of arginine caused by decreased activity of the biosynthesis pathway confers sensitivity to HP.

  15. Lipid metabolism disturbances contribute to insulin resistance and decrease insulin sensitivity by malathion exposure in Wistar rat.

    Science.gov (United States)

    Lasram, Mohamed Montassar; Bouzid, Kahena; Douib, Ines Bini; Annabi, Alya; El Elj, Naziha; El Fazaa, Saloua; Abdelmoula, Jaouida; Gharbi, Najoua

    2015-04-01

    Several studies showed that organophosphorus pesticides disturb glucose homeostasis and can increase incidence of metabolic disorders and diabetes via insulin resistance. The current study investigates the influence of malathion on glucose metabolism regulation, in vivo, during subchronic exposure. Malathion was administered orally (200 mg/kg), once a day for 28 consecutive days. Plasma glucose, insulin and Glycated hemoglobin levels were significantly increased while hepatic glycogen content was decreased in intoxicated animals compared with the control group. Furthermore, there was a significant disturbance of lipid content in subchronic treated and post-treated rats deprived of malathion for one month. In addition, we used the homeostasis model assessment (HOMA) to assess insulin resistance (HOMA-IR) and pancreatic β-cell function (HOMA-β). Our results show that malathion increases insulin resistance biomarkers and decreases insulin sensitivity indices. Statistical analysis demonstrates that there was a positive and strong significant correlation between insulin level and insulin resistance indices, HOMA-IR, HOMA-β. Similarly, a negative and significant correlation was also found between insulin level and insulin sensitivity indices. For the first time, we demonstrate that malathion induces insulin resistance in vivo using homeostasis model assessment and these changes were detectable one month after the end of exposure. To explain insulin resistance induced by malathion we focus on lipid metabolism disturbances and their interaction with many proteins involved in insulin signaling pathways.

  16. Significance of the factor analysis due to decreasing anthropogenic pollution--exemplified by river sediments.

    Science.gov (United States)

    Möller, Stefan; Einax, Jürgen W

    2015-05-01

    Environmental datasets often consist of numerous features analyzed in many investigated samples. Therefore, the evaluation of those datasets is difficult. Chemometric methods like the factor analysis are useful tools to handle big datasets. In this paper, we discussed the relation between the geogenic background (noise) and anthropogenic pollution (source) for the suitability of environmental datasets for factor analytical methods. Thus, computed test datasets with different sources, diverse maximum of the sources, and various geogenic backgrounds were generated. Afterward, the maximum of the source was decreased stepwise, a factor analysis was computed, and the corresponding results were investigated in respect of the credibility. The major impacts on the evaluation of a feature are the mean value of the noise and the standard deviation of the noise. With the help of these two parameters, a pollution index can be calculated. The maximum of the source has to exceed that index in order to be usefully evaluable with the factor analyses. The evaluation of the results of the factor analysis would become increasingly complicated if the variability of a dataset decreases due to reduced maximum values or geogenic/anthropogenic sources which correspond to increasing environmental quality.

  17. Angiogenic activity in patients with psoriasis is significantly decreased by Goeckerman's therapy

    Energy Technology Data Exchange (ETDEWEB)

    Andrys, C.; Borska, L.; Pohl, D.; Fiala, Z.; Hamakova, K.; Krejsek, J. [Faculty Hospital, Hradec Kralove (Czech Republic). Dept. of Clinical Immunology & Allergy

    2007-03-15

    Goeckerman's therapy (GT) of psoriasis is based on daily application of pharmacy grade coal tar on affected skin with subsequent exposure to UV light. Goeckerman's therapy is still the first line therapy of psoriasis in the Czech Republic because of its low cost and long-term efficacy. Disturbances in angiogenic activity are characteristic for the immunopathogenesis of psoriasis. An abnormal spectrum of cytokines, growth factors and proangiogenic mediators is produced by keratinocytes and inflammatory cells in patients suffering from the disease. The aim of this study was to evaluate the influence of GT of psoriasis on angiogenic activities by comparing serum levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in 44 patients with psoriasis in peripheral blood samples collected before and after therapy. It was found that the angiogenic potential which is abnormally increased in patients with psoriasis is significantly alleviated by GT.

  18. Oral contraceptive pills decrease pulmonary airway resistance in healthy north Indian women.

    Science.gov (United States)

    Kumar, Pradeep; Singh, Shraddha; Singh, Uma; Verma, Pratima

    2011-02-01

    Oral contraceptive pills (OCPs) are hormonal pills used by females to prevent conception; they are a combination of estrogen and progestin. There is, however, compelling evidence that throughout the reproductive life of a woman, her airways are subject to the influence of the cyclical variations in sex hormones which occur in relation to circadian rhythms. The present study has been designed to investigate the effects of OCPs on airway resistance in terms of spirometric parameters in OCP users and nonusers. A total of 100 women (age: 20-40 years) ware selected for the present study. The subjects were provided with a one-month supply of OCPs. The constituents per tablet of MALA-N used were levonorgestrel 0.15 mg and ethinylestradiol 0.03 mg. Peak expiratory flow rate (PEFR), forced expiratory flow in expiring 25-75% air (FEF 25-75), forced expiratory volume percentage in one second (FEV1% or FEV1/FVC), forced vital capacity (FVC), and forced expiratory volume in one second (FEV1) were recorded. In our study, the FEF 25-75and PEFR increased significantly in OCP users, showing that these hormone pills decrease the resistance offered by small bronchioles.

  19. Does nasal congestion have a role in decreased resistance to regular CPAP usage?

    Science.gov (United States)

    İriz, Ayşe; Düzlü, Mehmet; Köktürk, Oğuz; Kemaloğlu, Yusuf Kemal; Eravcı, Fakih Cihat; Zorlu, Mehmet Ekrem; Karamert, Recep

    2017-11-01

    Nasal obstruction is known to cause resistance to continuous positive airway pressure (CPAP) therapy in obstructive sleep apnea syndrome (OSAS). In this paper, short- and long-term nasal congestion in OSAS patients receiving CPAP treatment were evaluated with acoustic rhinometry (AR). A total of 36 patients with moderate-to-severe OSAS, diagnosed with polysomnography were included in the study. Ten healthy subjects without OSAS constituted the control group. Pre-treatment nasal patency were measured with AR in all participants. 26 patients used the recommended CPAP treatment. Ten patients did not accept CPAP treatment. The AR test was repeated for all the subjects after 1 and 3 months except the 3rd month's measurements of the control group. There was no statistically significant difference between the initial minimum cross-sectional area (MCA) measurements of OSAS patients, using or not using CPAP, and the control group (P > 0.05). However, the first month MCA measurements of patients receiving CPAP were found to be significantly decreased compared with the initial values (P CPAP (P > 0.05). No significant difference revealed in the 3rd month MCA measurements of the patients using CPAP compared with the initial values (P > 0.05). In this study, the increased nasal congestion, which is thought to be the cause of CPAP resistance, was objectively demonstrated in OSAS patients using CPAP. In addition, the nasal congestion developing at the first month was shown to disappear over time, supporting the opinion that patient compliance in CPAP treatment is expected to increase after regular device usage.

  20. Increased nature relatedness and decreased authoritarian political views after psilocybin for treatment-resistant depression.

    Science.gov (United States)

    Lyons, Taylor; Carhart-Harris, Robin L

    2018-01-01

    Previous research suggests that classical psychedelic compounds can induce lasting changes in personality traits, attitudes and beliefs in both healthy subjects and patient populations. Here we sought to investigate the effects of psilocybin on nature relatedness and libertarian-authoritarian political perspective in patients with treatment-resistant depression (TRD). This open-label pilot study with a mixed-model design studied the effects of psilocybin on measures of nature relatedness and libertarian-authoritarian political perspective in patients with moderate to severe TRD ( n=7) versus age-matched non-treated healthy control subjects ( n=7). Psilocybin was administered in two oral dosing sessions (10 mg and 25 mg) 1 week apart. Main outcome measures were collected 1 week and 7-12 months after the second dosing session. Nature relatedness and libertarian-authoritarian political perspective were assessed using the Nature Relatedness Scale (NR-6) and Political Perspective Questionnaire (PPQ-5), respectively. Nature relatedness significantly increased ( t(6)=-4.242, p=0.003) and authoritarianism significantly decreased ( t(6)=2.120, p=0.039) for the patients 1 week after the dosing sessions. At 7-12 months post-dosing, nature relatedness remained significantly increased ( t(5)=-2.707, p=0.021) and authoritarianism remained decreased at trend level ( t(5)=-1.811, p=0.065). No differences were found on either measure for the non-treated healthy control subjects. This pilot study suggests that psilocybin with psychological support might produce lasting changes in attitudes and beliefs. Although it would be premature to infer causality from this small study, the possibility of drug-induced changes in belief systems seems sufficiently intriguing and timely to deserve further investigation.

  1. Trends in Antimicrobial Resistance in 1,968 Invasive Streptococcus pneumoniae Strains Isolated in Spanish Hospitals (2001 to 2003): Decreasing Penicillin Resistance in Children's Isolates

    Science.gov (United States)

    Oteo, Jesús; Lázaro, Edurne; de Abajo, Francisco J.; Baquero, Fernando; Campos, José

    2004-01-01

    To address the public health problem of antibiotic resistance, the European Union (EU) founded the European Antimicrobial Resistance Surveillance System. A network of 40 hospitals that serve approximately 30% of the Spanish population (about 12 million) participated. Each laboratory reported data on antimicrobial susceptibility testing using standard laboratory procedures that were evaluated by an external quality control program. The antibiotic consumption data were obtained from the National Health System. We compared the antibiotic susceptibility of Spanish isolates of invasive Streptococcus pneumoniae (2001 to 2003) with antibiotic consumption. Invasive S. pneumoniae was isolated from 1,968 patients, 20% of whom were children at or below the age of 14 years. Of non-penicillin-susceptible strains (35.6%; 95% confidence interval, 34 to 37.2), 26.4% were considered intermediate and 9.2% were considered resistant. Between 2001 and 2003, penicillin resistance decreased from 39.5 to 33% overall and from 60.4 to 41.2% in children at or below the age of 14 years (P = 0.002). Resistance to erythromycin was at 26.6%, and coresistance with penicillin was at 19.1%. Of total isolates, the ciprofloxacin MIC was >2 μg/ml for 2.1%, with numbers increasing from 0.4% (2001) to 3.9% (2003). Total antibiotic use decreased from 21.66 to 19.71 defined daily doses/1,000 inhabitants/day between 1998 and 2002. While consumption of broad-spectrum penicillins, cephalosporins, and erythromycin declined, use of amoxicillin-clavulanate and quinolones increased by 17.5 and 27%, respectively. The frequency of antibiotic resistance in invasive S. pneumoniae in Spain was among the highest in the EU. However, a significant decrease in penicillin resistance was observed in children. This decrease coincided with the introduction of a heptavalent conjugate pneumoccocal vaccine (June 2001) and with a global reduction in antibiotic consumption levels. PMID:15583283

  2. Azithromycin Resistance and Decreased Ceftriaxone Susceptibility in Neisseria gonorrhoeae, Hawaii, USA.

    Science.gov (United States)

    Papp, John R; Abrams, A Jeanine; Nash, Evelyn; Katz, Alan R; Kirkcaldy, Robert D; O'Connor, Norman P; O'Brien, Pamela S; Harauchi, Derek H; Maningas, Eloisa V; Soge, Olusegun O; Kersh, Ellen N; Komeya, Alan; Tomas, Juval E; Wasserman, Glenn M; Kunimoto, Gail Y; Trees, David L; Whelen, A Christian

    2017-05-01

    During 2016, eight Neisseria gonorrhoeae isolates from 7 patients in Hawaii were resistant to azithromycin; 5 had decreased in vitro susceptibility to ceftriaxone. Genomic analysis demonstrated a distinct phylogenetic clade when compared with local contemporary strains. Continued evolution and widespread transmission of these strains might challenge the effectiveness of current therapeutic options.

  3. Dietary fructo-oligosaccharides and inulin decrease resistance of rats to salmonelle: protective role of calcium

    NARCIS (Netherlands)

    Bruggencate, ten S.J.M.; Bovee-Oudenhoven, I.M.J.; Lettink-Wissink, M.L.G.; Katan, M.B.; Meer, van der R.

    2004-01-01

    Background: We have shown recently that rapid fermentable fructo-oligosaccharides (FOS) decreased resistance of rats towards salmonella. It is not known whether inulin ( which is fermented more gradually) has similar effects or whether buffering nutrients can counteract the adverse effects of rapid

  4. Resistance Training Combined With Diet Decreases Body Fat While Preserving Lean Mass Independent of Resting Metabolic Rate: A Randomized Trial.

    Science.gov (United States)

    Miller, Todd; Mull, Stephanie; Aragon, Alan Albert; Krieger, James; Schoenfeld, Brad Jon

    2018-01-01

    The purpose of this study was to determine the effects of resistance training only (RT; n = 10), dietary intervention only (DIET; n = 10), resistance training plus diet (RT+DIET; n = 10), and control (CON; n = 10) on body composition and resting metabolic rate (RMR) in a cohort of 40 premenopausal female volunteers. Subjects in DIET and RT+DIET were provided with daily macronutrient and calorie goals based on DXA and RMR tests, with protein maintained at 3.1 g/kg/day. Subjects in the RT and RT+DIET groups performed a supervised progressive RT program consisting of exercises for all the major muscle groups of the body. Results showed a significant month-by-group interaction for change in fat mass with no significant linear trend for control. The three treatment groups all showed significant linear decreases in fat mass, but the slope of the decrease became progressively steeper from the RT, to DIET, to RT+DIET. A significant linear increase for lean mass was seen for resistance training only. There was a nonsignificant increase in RMR in all groups from Month 0 to Month 4 but no significant month by group interaction. In conclusion, significant reductions in fat mass were achieved by all experimental groups, but results were maximized by RT+DIET. Only the RT group showed significant increases in lean mass.

  5. Evaluation of the effectiveness of auxiliary features on resistance with decreased occluso-cervical height: An In Vitro study

    Directory of Open Access Journals (Sweden)

    Aman Arora

    2016-01-01

    Full Text Available Background: Fewer studies were conducted on resistance form. This study evaluated the effect of different auxiliary features on inadequate resistance form. Aim: The aim of the study is to evaluate the resistance at 22° taper with reduced occluso-cervical height with different auxiliary features. Methodology: An ivorine tooth was prepared with computer-aided design-computer-aided manufacturing with total occlusal convergence (TOC of 22°, shoulder finish line 0.9 mm wide, reduced occluso-cervical height, i.e., 2.5 mm, and reduced diameter. The crown preparation was subsequently modified to include interproximal grooves, interproximal boxes, and reduced TOC in the axial wall from 22° to 8° in the cervical 1.5 mm of the axial wall. A total of four groups with ten standardized metal dies were prepared for each design with the computer-aided milling machine. Standardized complete metal crowns using silicon mold were fabricated and cemented on metal dies with glass ionomer cement. The resistance of each specimen was evaluated when force was applied at a 45° angulation to the long axis of the die in a lingual to buccal direction by a universal testing machine. The values were then analyzed using one-way analysis of variance test and post hoc Bonferroni test. Results: The comparison of the mean resistance test values was done among all the groups, and there was a significant (P ≤ 0.001 difference found among the groups. Conclusion: The most effective method of enhancing resistance form preparation is to decrease the TOC of the cervical portion of the prepared axial walls. Two interproximal boxes significantly increased the resistance form. However, two interproximal grooves did not significantly increase the resistance form.

  6. Aging causes decreased resistance to multiple stresses and a failure to activate specific stress response pathways

    Science.gov (United States)

    Bergsma, Alexis L.; Senchuk, Megan M.; Van Raamsdonk, Jeremy M.

    2016-01-01

    In this work, we examine the relationship between stress resistance and aging. We find that resistance to multiple types of stress peaks during early adulthood and then declines with age. To dissect the underlying mechanisms, we use C. elegans transcriptional reporter strains that measure the activation of different stress responses including: the heat shock response, mitochondrial unfolded protein response, endoplasmic reticulum unfolded protein response, hypoxia response, SKN-1-mediated oxidative stress response, and the DAF-16-mediated stress response. We find that the decline in stress resistance with age is at least partially due to a decreased ability to activate protective mechanisms in response to stress. In contrast, we find that any baseline increase in stress caused by the advancing age is too mild to detectably upregulate any of the stress response pathways. Further exploration of how worms respond to stress with increasing age revealed that the ability to mount a hormetic response to heat stress is also lost with increasing age. Overall, this work demonstrates that resistance to all types of stress declines with age. Based on our data, we speculate that the decrease in stress resistance with advancing age results from a genetically-programmed inactivation of stress response pathways, not accumulation of damage. PMID:27053445

  7. Aging causes decreased resistance to multiple stresses and a failure to activate specific stress response pathways.

    Science.gov (United States)

    Dues, Dylan J; Andrews, Emily K; Schaar, Claire E; Bergsma, Alexis L; Senchuk, Megan M; Van Raamsdonk, Jeremy M

    2016-04-01

    In this work, we examine the relationship between stress resistance and aging. We find that resistance to multiple types of stress peaks during early adulthood and then declines with age. To dissect the underlying mechanisms, we use C. elegans transcriptional reporter strains that measure the activation of different stress responses including: the heat shock response, mitochondrial unfolded protein response, endoplasmic reticulum unfolded protein response, hypoxia response, SKN-1-mediated oxidative stress response, and the DAF-16-mediated stress response. We find that the decline in stress resistance with age is at least partially due to a decreased ability to activate protective mechanisms in response to stress. In contrast, we find that any baseline increase in stress caused by the advancing age is too mild to detectably upregulate any of the stress response pathways. Further exploration of how worms respond to stress with increasing age revealed that the ability to mount a hormetic response to heat stress is also lost with increasing age. Overall, this work demonstrates that resistance to all types of stress declines with age. Based on our data, we speculate that the decrease in stress resistance with advancing age results from a genetically-programmed inactivation of stress response pathways, not accumulation of damage.

  8. Resistance exercise decreases heroin self-administration and alters gene expression in the nucleus accumbens of heroin-exposed rats.

    Science.gov (United States)

    Smith, Mark A; Fronk, Gaylen E; Abel, Jean M; Lacy, Ryan T; Bills, Sarah E; Lynch, Wendy J

    2018-02-02

    Preclinical studies consistently report that aerobic exercise decreases drug self-administration and other forms of drug-seeking behavior; however, relatively few studies have examined other types of physical activity. The purpose of the present study was to examine the effects of resistance exercise (i.e., strength training) on heroin self-administration and mRNA expression of genes known to mediate opioid reinforcement and addictive behavior in the nucleus accumbens (NAc) of heroin-exposed rats. Female rats were obtained during late adolescence and divided into two groups. Resistance exercise rats were trained to climb a vertical ladder wearing a weighted vest; sedentary control rats were placed repeatedly on the ladder oriented horizontally on its side. All rats were implanted with intravenous catheters and trained to self-administer heroin on a fixed ratio (FR1) schedule of reinforcement. mRNA expression in the NAc core and shell was examined following behavioral testing. Resistance exercise significantly decreased heroin self-administration, resulting in a downward shift in the dose-effect curve. Resistance exercise also reduced mRNA expression for mu opioid receptors and dopamine D1, D2, and D3 receptors in the NAc core. Resistance exercise increased mRNA expression of dopamine D5 receptors in the NAc shell and increased mRNA expression of brain-derived neurotrophic factor (exons I, IIB, IIC, IV, VI, IX) in the NAc core. These data indicate that resistance exercise decreases the positive reinforcing effects of heroin and produces changes in opioid and dopamine systems in the NAc of heroin-exposed rats.

  9. Chronic Inhibition of 11β-Hydroxysteroid Dehydrogenase Type 1 Activity Decreases Hypertension, Insulin Resistance, and Hypertriglyceridemia in Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Christine G. Schnackenberg

    2013-01-01

    Full Text Available Metabolic syndrome is a constellation of risk factors including hypertension, dyslipidemia, insulin resistance, and obesity that promote the development of cardiovascular disease. Metabolic syndrome has been associated with changes in the secretion or metabolism of glucocorticoids, which have important functions in adipose, liver, kidney, and vasculature. Tissue concentrations of the active glucocorticoid cortisol are controlled by the conversion of cortisone to cortisol by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1. Because of the various cardiovascular and metabolic activities of glucocorticoids, we tested the hypothesis that 11β-HSD1 is a common mechanism in the hypertension, dyslipidemia, and insulin resistance in metabolic syndrome. In obese and lean SHR/NDmcr-cp (SHR-cp, cardiovascular, metabolic, and renal functions were measured before and during four weeks of administration of vehicle or compound 11 (10 mg/kg/d, a selective inhibitor of 11β-HSD1. Compound 11 significantly decreased 11β-HSD1 activity in adipose tissue and liver of SHR-cp. In obese SHR-cp, compound 11 significantly decreased mean arterial pressure, glucose intolerance, insulin resistance, hypertriglyceridemia, and plasma renin activity with no effect on heart rate, body weight gain, or microalbuminuria. These results suggest that 11β-HSD1 activity in liver and adipose tissue is a common mediator of hypertension, hypertriglyceridemia, glucose intolerance, and insulin resistance in metabolic syndrome.

  10. The introduction of sialendoscopy has significantly contributed to a decreased number of excised salivary glands in Denmark

    DEFF Research Database (Denmark)

    Rye Rasmussen, Eva; Lykke, Eva; Wagner, Niels

    2015-01-01

    surgical interventions on the major salivary glands due to benign non-tumorous disease. Nationally and regionally the total number of resected major salivary glands due to benign obstructive disease also decreased significantly during the study period. A positive outcome, like the ones described here...

  11. Habitual exercise decreases systolic blood pressure during low-intensity resistance exercise in healthy middle-aged and older individuals.

    Science.gov (United States)

    Otsuki, Takeshi; Kotato, Takahiro; Zempo-Miyaki, Asako

    2016-10-01

    Since aerobic exercise (e.g., walking) and resistance exercise (e.g., lifting objects and mopping) are both parts of the activities of daily living, an exaggerated elevation in systolic blood pressure (SBP) during aerobic and resistance exercise is an early marker of cardiovascular disease. This study investigated the effects of habitual exercise on SBP during low-intensity resistance exercise using both cross-sectional and interventional approaches. First, in 57 normotensive women (61.9 ± 1.0 yr of age), daily physical activity level, as assessed by triaxial accelerometry, was correlated with SBP during resistance exercise at 20 and 40% of the 1 repetition maximum (r = -0.408 and r = -0.348, respectively). Maximal oxygen uptake was correlated with SBP during exercise at 20% (r = -0.385) and 40% (r = -0.457). Physical activity level or maximal oxygen uptake was identified as a predictor of SBP during the exercise in stepwise regression analysis, independent of SBP at rest and other factors (R 2 = 0.729-0.781). Second, 66 men and women (64.6 ± 0.9 yr of age) participated in a 6-wk intervention as a part of the training (walking, 4.3 ± 0.3 days/wk, 55.6 ± 4.1 min/day, 70.7 ± 1.2% of maximal heart rate) or control group. SBP during resistance exercise in the training group decreased after the intervention (before vs. after: 20%, 143 ± 4 vs. 128 ± 4 mmHg; and 40%, 148 ± 5 vs. 134 ± 4 mmHg). In the control group, there were no significant differences in SBP before and after the intervention. SBP during resistance exercise after the intervention was lower in the training group relative to the control group. These results suggest that habitual exercise decreases SBP during low-intensity resistance exercise. Copyright © 2016 the American Physiological Society.

  12. Prognostic Significance of Decreased Expression of Six Large Common Fragile Site Genes in Oropharyngeal Squamous Cell Carcinomas

    Directory of Open Access Journals (Sweden)

    Ge Gao

    2014-12-01

    Full Text Available Common fragile sites (CFSs are large regions with profound genomic instability that often span extremely large genes a number of which have been found to be important tumor suppressors. RNA sequencing previously revealed that there was a group of six large CFS genes which frequently had decreased expression in oropharyngeal squamous cell carcinomas (OPSCCs and real-time reverse transcriptase polymerase chain reaction experiments validated that these six large CFS genes (PARK2, DLG2, NBEA, CTNNA3, DMD, and FHIT had decreased expression in most of the tumor samples. In this study, we investigated whether the decreased expression of these genes has any clinical significance in OPSCCs. We analyzed the six CFS large genes in 45 OPSCC patients and found that 27 (60% of the OPSCC tumors had decreased expression of these six genes. When we correlated the expression of these six genes to each patient’s clinical records, for 11 patients who had tumor recurrence, 10 of them had decreased expression of almost all 6 genes. When we divided the patients into two groups, one group with decreased expression of the six genes and the other group with either slight changes or increased expression of the six genes, we found that there is significant difference in the incidence of tumor recurrence between these two groups by Kaplan-Meier plot analysis (P < .05. Our results demonstrated that those OPSCC tumors with decreased expression of this select group of six large CFS genes were much more likely to be associated with tumor recurrence and these genes are potential prognostic markers for predicting tumor recurrence in OPSCC.

  13. ACh-induced hyperpolarization and decreased resistance in mammalian type II vestibular hair cells.

    Science.gov (United States)

    Poppi, Lauren A; Tabatabaee, Hessam; Drury, Hannah R; Jobling, Phillip; Callister, Robert J; Migliaccio, Americo A; Jordan, Paivi M; Holt, Joseph C; Rabbitt, Richard D; Lim, Rebecca; Brichta, Alan M

    2018-01-01

    In the mammalian vestibular periphery, electrical activation of the efferent vestibular system (EVS) has two effects on afferent activity: 1) it increases background afferent discharge and 2) decreases afferent sensitivity to rotational stimuli. Although the cellular mechanisms underlying these two contrasting afferent responses remain obscure, we postulated that the reduction in afferent sensitivity was attributed, in part, to the activation of α9- containing nicotinic acetylcholine (ACh) receptors (α9*nAChRs) and small-conductance potassium channels (SK) in vestibular type II hair cells, as demonstrated in the peripheral vestibular system of other vertebrates. To test this hypothesis, we examined the effects of the predominant EVS neurotransmitter ACh on vestibular type II hair cells from wild-type (wt) and α9-subunit nAChR knockout (α9 -/- ) mice. Immunostaining for choline acetyltransferase revealed there were no obvious gross morphological differences in the peripheral EVS innervation among any of these strains. ACh application onto wt type II hair cells, at resting potentials, produced a fast inward current followed by a slower outward current, resulting in membrane hyperpolarization and decreased membrane resistance. Hyperpolarization and decreased resistance were due to gating of SK channels. Consistent with activation of α9*nAChRs and SK channels, these ACh-sensitive currents were antagonized by the α9*nAChR blocker strychnine and SK blockers apamin and tamapin. Type II hair cells from α9 -/- mice, however, failed to respond to ACh at all. These results confirm the critical importance of α9nAChRs in efferent modulation of mammalian type II vestibular hair cells. Application of exogenous ACh reduces electrical impedance, thereby decreasing type II hair cell sensitivity. NEW & NOTEWORTHY Expression of α9 nicotinic subunit was crucial for fast cholinergic modulation of mammalian vestibular type II hair cells. These findings show a multifaceted

  14. Does a herniated nucleus pulposus contribute significantly to a decrease in height of the intervertebral disc? Quantitative volumetrich MRI

    Energy Technology Data Exchange (ETDEWEB)

    Holodny, A.I.; Kisza, P.S.; Contractor, S.; Liu, W.C. [Department of Radiology, UMDNJ-New Jersey Medical School, University Hospital C-320, 150 Bergen Street, Newark, NJ 07103-2714 (United States)

    2000-06-01

    A lumbar intervertebral disc with a herniated nucleus pulposus (HNP) often exhibits a decrease in the height of the intervertebral space. Our purpose was to ascertain whether the loss of volume of an HNP is sufficient to cause a perceptible decrease in the height of the intervertebral space. MRI of 44 patients with 51 HNPs were reviewed. The volumes of the herniated material and of the intervertebral discs were calculated for every level from L 1-2 to L 5-S 1. The average volume of the HNP was 503{+-}301 mm{sup 3}. The average volumes of all 220 intervertebral discs and of the 127 normal-appearing discs were 14442{+-}4200 mm{sup 3} and 17476{+-}2885 mm{sup 3} respectively. The average volume of the HNP represented 3.5% of the parent disc. An average HNP caused a decrease in intervertebral space height of 0.35 mm (0.56 pixels). Therefore, the loss of the volume of the HNP does not cause a significant decrease in the intervertebral space height. The average calculated decrease in the disc height is less than that reported in normal diurnal variation. (orig.)

  15. Effect of decreasing electrical resistance in Characeae cell membranes caused by the flow of alternating current

    Directory of Open Access Journals (Sweden)

    Edward Śpiewla

    2014-01-01

    Full Text Available By means of the techniques of external electrodes and microelectrodes, it was found that evanescent flow of an alternating current through plasmalemma of Characeae cells neutralises oscillatory change in their electrical resistance and reversibly diminishes its value. This effect is particularly significant in the case of "high resistance cells", but it weakens with increasing temperature. The value of the estimated activation energy indicates that, after flow of the alternating current through the membrane, a rapid increase in the conductivity may be caused by an increase in conductivity of potassium channels. This result seems to support the hypothesis of electroconformational feedback.

  16. Significant decrease in thermal conductivity of multi-walled carbon nanotube induced by inter-wall van der Waals interactions

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Xue; Zhou, Wu-Xing, E-mail: wuxingzhou@hnu.edu.cn; Chen, Xue-Kun; Liu, Yue-Yang; Chen, Ke-Qiu, E-mail: keqiuchen@hnu.edu.cn

    2016-05-06

    The thermal transport properties of multi-walled carbon nanotubes (MWCNTs) were investigated by using non-equilibrium molecular dynamics simulation. The results show that the thermal conductivity of MWCNTs decreases significantly comparing to that of single-walled carbon nanotubes (SWCNTs) due to the inter-wall van der Waals interactions. The more interesting is a fact that the thermal conductance of MWCNTs is significantly greater than the thermal conductance summation of each SWCNTs. This is because the thermal conductance of a carbon nanotube protected by an outer tube is much larger than that of one that is not protected. Moreover, we also studied the thermal flux distribution of MWCNTs, and found that the outer tube plays a dominant role in heat energy transfer. - Highlights: • Significant decrease in thermal conductivity of multi-walled carbon nanotube induced by inter-wall interactions. • The thermal conductivity of the inner tube is increased significantly due to protected by outer tube. • The outer tube plays a dominant role in heat energy transfer in multi-walled carbon nanotube.

  17. An ab initio investigation of how residual resistivity can decrease when an alloy is deformed

    Science.gov (United States)

    Lowitzer, S.; Ködderitzsch, D.; Ebert, H.; Tulip, P. R.; Marmodoro, A.; Staunton, J. B.

    2010-11-01

    For a class of transition metal materials residual resistivity is observed to decrease when the materials are deformed and short-range order is removed. We investigate this counter-intuitive behavior with an ab initio theoretical study of the residual resistivity of several late transition metal-rich disordered alloys. The calculations are performed using the Korringa-Kohn-Rostoker (KKR) method applied to the Kubo-Greenwood formalism. The electronic effects arising from short-range ordering and clustering within the disorder are described using the non-local coherent-potential approximation (NL-CPA). We find a simple, general explanation of this K-state-like effect in terms of changes to the amplitude for d-electron hopping between majority late transition metal nearest-neighbor atoms at the Fermi energy.

  18. Prevalence of Mupirocin Resistance Among Staphylococci, its Clinical Significance and Relationship to Clinical Use.

    Science.gov (United States)

    Rudresh, Manohar Shoorashetty; Ravi, Giriyapur Siddappa; Motagi, Aravind; Alex, Ann Mary; Sandhya, Parthasarathi; Navaneeth, Bangalore Viswanath

    2015-01-01

    Mupirocin competitively inhibits bacterial isoleucyl transfer-RNA synthetase and inhibit bacterial protein synthesis. Widespread usage and over the counter availability of the drug has resulted in resistance among Staphylococcus species. This study aimed to determine the overall prevalence of mupirocin resistance among staphylococci. Correlate clinical significance of mupirocin resistance and its relationship to clinical use. Consecutive, nonrepetitive, clinical isolates of Staphylococcus aureus (n = 98), and coagulase-negative staphylococci (CoNS) (n = 45) from skin and soft-tissue infections between January 2014 and June 2014 were studied. Antibiotic susceptibility testing was done according to Clinical and Laboratory Standards Institute guidelines. Low- and high-level mupirocin resistance was screened by using 5 µg and 200 µg discs respectively and confirmed by agar dilution. Annual consumption of mupirocin was studied and correlated with resistance. High-level mupirocin resistance was found in 8.2% S. aureus and 15.6% of CoNS, while low-level mupirocin resistance was found in 17% S. aureus and 8.9% CoNS. High-level mupirocin resistance was more common in methicillin-sensitive S. aureus isolates when compared with methicillin-resistant S. aureus isolates (P staphylococci demands the judicious use of the drug in the community.

  19. Decreases in left atrial compliance during early-stage exercise are related to exercise intolerance in asymptomatic significant mitral stenosis.

    Science.gov (United States)

    Jung, Mi-Hyang; Jung, Hae Ok; Lee, Jung-Won; Youn, Ho-Joong

    2017-11-01

    Doppler-driven net atrioventricular compliance (C n ), which represents left atrial (LA) compliance, is an important determinant of pulmonary hypertension in mitral stenosis (MS). We hypothesized that decreases in C n during early-stage exercise underlie exercise intolerance in patients with MS. Thirty-three asymptomatic patients with significant MS (valve area 1.24 ± 0.16 cm 2 ) underwent resting and bicycle exercise echocardiography. LA compliance and conventional parameters were assessed at each workload. The patients were classified into two groups based on whether they developed dyspnea during exercise: an exercise-intolerance group (n = 22) and an exercise-tolerance group (n = 11). Moreover, "50 W" was defined as an early exercise stage. Although the groups had similar resting characteristics, there were striking differences in their echocardiographic parameters from the early stages of exercise. The relative C n decrease at 50 W (expressed as a percentage of the resting C n ) was significantly greater in the exercise-intolerance group (70.3 ± 15.4% vs 49.7 ± 9.7%, P intolerance group (P = .0005). Furthermore, differences in the trends in this parameter were observed between the two groups (P intolerance (adjusted OR 1.105, 95% CI 1.030-1.184) after adjustment for other conventional parameters. Decreases in C n during early-stage exercise are an important mechanism underlying exercise intolerance in MS. © 2017, Wiley Periodicals, Inc.

  20. Flavonol-rich dark cocoa significantly decreases plasma endothelin-1 and improves cognitive responses in urban children.

    Directory of Open Access Journals (Sweden)

    Lilian eCalderon-Garciduenas

    2013-08-01

    Full Text Available Air pollution exposures are linked to systemic inflammation, cardiovascular and respiratory morbidity and mortality, neuroinflammation and neuropathology in young urbanites. In particular, most Mexico City Metropolitan Area (MCMA children exhibit subtle cognitive deficits, and neuropathology studies show 40% of them exhibiting frontal tau hyperphosphorylation and 51% amyloid-β diffuse plaques (compared to 0% in low pollution control children. We assessed whether a short cocoa intervention can be effective in decreasing plasma endothelin 1 (ET-1 and/or inflammatory mediators in MCMA children. Thirty g of dark cocoa with 680 mg of total flavonols were given daily for 10.11± 3.4 days (range 9 to 24 days to 18 children (10.55yrs, SD =1.45; 11F/7M. Key metabolite ratios in frontal white matter and in hippocampus pre and during cocoa intervention were quantified by magnetic resonance spectroscopy. ET-1 significantly decreased after cocoa treatment (p=0.0002. Fifteen children (83% showed a marginally significant individual improvement in one or both of the applied simple short memory tasks. Endothelial dysfunction is a key feature of exposure to particulate matter and decreased endothelin-1 bioavailability is likely useful for brain function in the context of air pollution. Our findings suggest that cocoa interventions may be critical for early implementation of neuroprotection of highly exposed urban children. Multi-domain nutraceutical interventions could limit the risk for endothelial dysfunction, cerebral hypoperfusion, neuroinflammation, cognitive deficits, structural volumetric detrimental brain effects, and the early development of the neuropathological hallmarks of Alzheimer’s and Parkinson’s diseases.

  1. New findings regarding the significance of pavement skid resistance for road safety on Swiss freeways.

    Science.gov (United States)

    Lindenmann, H P

    2006-01-01

    The significance of the influence of poor pavement skid resistance values on accident frequency in wet pavement conditions has been the object of many studies over several years. The various investigations have produced very diverse findings. Only seldom, however, has detailed consideration been given to the central question of whether pavement skid resistance is a decisive parameter in the occurrence of local accident "black spots." Until now, the focus has been more on describing a relationship between pavement skid resistance and accident frequency. In the course of the network-wide survey of the states of pavements and of accident occurrence on Switzerland's freeways from 1999 to 2003, it emerged that a relationship with inadequate pavement skid resistance was provable for only a small proportion of accident black spots. These findings were used to frame a guideline for authorities and highway operators about how to treat skid resistance when assessing pavements and accident occurrence on freeways.

  2. Antibiotic reduction campaigns do not necessarily decrease bacterial resistance: the example of methicillin-resistant Staphylococcus aureus.

    Science.gov (United States)

    Kardas-Sloma, Lidia; Boëlle, Pierre-Yves; Opatowski, Lulla; Guillemot, Didier; Temime, Laura

    2013-09-01

    Interventions designed to reduce antibiotic consumption are under way worldwide. While overall reductions are often achieved, their impact on the selection of antibiotic-resistant selection cannot be assessed accurately from currently available data. We developed a mathematical model of methicillin-sensitive and methicillin-resistant Staphylococcus aureus (MSSA and MRSA) transmission inside and outside the hospital. A systematic simulation study was then conducted with two objectives: to assess the impact of antibiotic class-specific changes during an antibiotic reduction period and to investigate the interactions between antibiotic prescription changes in the hospital and the community. The model reproduced the overall reduction in MRSA frequency in French intensive-care units (ICUs) with antibiotic consumption in France from 2002 to 2003 as an input. However, the change in MRSA frequency depended on which antibiotic classes changed the most, with the same overall 10% reduction in antibiotic use over 1 year leading to anywhere between a 69% decrease and a 52% increase in MRSA frequency in ICUs and anywhere between a 37% decrease and a 46% increase in the community. Furthermore, some combinations of antibiotic prescription changes in the hospital and the community could act in a synergistic or antagonistic way with regard to overall MRSA selection. This study shows that class-specific changes in antibiotic use, rather than overall reductions, need to be considered in order to properly anticipate the impact of an antibiotic reduction campaign. It also highlights the fact that optimal gains will be obtained by coordinating interventions in hospitals and in the community, since the effect of an intervention in a given setting may be strongly affected by exogenous factors.

  3. Decrease of CD4+ T lymphocytes in patients with H1N1 in early stage and its clinical significances

    International Nuclear Information System (INIS)

    Zuo Lingyun; Zhao Wei; Zhao Hong; Yu Haiying; Sun Weiwei

    2010-01-01

    Objective: To observe the change of CD4 + T Lymphocytes in patients with H1N1 at early stage and figure out its clinical significances on the progress and therapeutic selection of H1N1. Methods: The absolute counts of T lymphocyte subset from the peripheral blood samples of 48 H1N1 patients in first ten days' duration were detected by flow cytometry, and the serial chest CT examinations were performed. Results: In all 48 clinical cases, 28 cases were in normal range of CD4 + lymphocyte absolute count, whose pulmonary lesions were limited and illness condition stayed in the stability, they didn't need steroid. In the other 20 cases with low level of CD4 + , 4 cases' illness presented the progressive development and needed to be treated with steroid and 16 cases with lightly decreased CD4 + level which had a stable condition without treatment with steroid. The result of Pearson correlation analysis showed that there were negative correlations between absolute count of CD4 + cells and pulmonary lesions (r=-0.299, P + cell absolute count of H1N1 patients at early stage indicates the worse condition of pulmonary lesions. The patients with remarkable decrease of CD4 + lymphocytes are in need of treatment with steroid. (authors)

  4. The decreased expression of TIPE2 protein in the decidua of patients with missed abortion and possible significance.

    Science.gov (United States)

    Sun, Yingshuo; Wang, Xiaoyan; Li, Yue; Sun, Han; Wan, Lu; Wang, Xishuang; Zhang, Lining; Fang, Zhenghui; Wei, Zengtao

    2017-08-29

    Missed abortion is a common occurrence for otherwise healthy women. Immunological factor is one of the most important reasons. Tumor necrosis factor-α-induced protein-8 like-2 (TIPE2) is a novel negative immune regulator related to several human diseases. However, the expression level and clinical significance of TIPE2 in missed abortion remain unclear. The expression of TIPE2 mRNA and protein in decidua and chorion from 36 missed abortion patients and 36 healthy controls was detected using quantitative real-time PCR, western blot and immunohistochemistry. In addition, serum TNF-ɑ and IL-10 levels were measured using flow cytometry. Serum estradiol and progesterone levels were measured by radioimmunoassay test. The correlations of TIPE2 protein levels with TNF-ɑ, IL-10, estradiol and progesterone were further analyzed. TIPE2 protein levels were significantly lower in decidual tissues of missed abortion patients than those in healthy controls. The patients with missed abortion had significantly higher levels of serum TNF-ɑ, and lower levels of serum IL-10, estradiol and progesterone compared with healthy controls. The TIPE2 protein levels were positively related to serum IL-10 levels. Our data indicate TIPE2 could play important roles in maintaining the maternal-fetal tolerance and decreased TIPE2 expression in the decidua may be related to the development of missed abortion.

  5. Clinical and Epidemiological Significance of Carbapenem Resistance in Acinetobacter baumannii Infections.

    Science.gov (United States)

    Tal-Jasper, Ruthy; Katz, David E; Amrami, Nadav; Ravid, Dor; Avivi, Dori; Zaidenstein, Ronit; Lazarovitch, Tsilia; Dadon, Mor; Kaye, Keith S; Marchaim, Dror

    2016-05-01

    Carbapenems are considered the treatment of choice for Acinetobacter baumannii infections. Many facilities implement preventive measures toward only carbapenem-resistant A. baumannii (CRAB). However, the independent role of the carbapenem resistance determinant on patient outcomes remains controversial. In a 6-year analysis of adults with A. baumannii bloodstream infection (BSI), the outcomes of 149 CRAB isolates were compared to those of 91 patients with carbapenem-susceptible A. baumannii In bivariable analyses, CRAB BSIs were significantly associated with worse outcomes and with a delay in the initiation of appropriate antimicrobial therapy (DAAT). However, in multivariable analyses, carbapenem resistance status was no longer associated with poor outcomes, while DAAT remained an independent predictor. The epidemiological significance of A. baumannii should not be determined by its resistance to carbapenems. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  6. Online training on the safe use of fluoroscopy can result in a significant decrease in patient dose.

    Science.gov (United States)

    Frederick-Dyer, Katherine C; Faulkner, Austin R; Chang, Ted T; Heidel, R Eric; Pasciak, Alexander S

    2013-10-01

    Concerns over medical radiation exposure have received national press in recent years, and training in the appropriate use of radiation has become an essential component of every radiology residency program. Appropriate training is particularly important in fluoroscopy because it is commonly used by inexperienced radiology residents and has the potential to impart relatively high patient radiation doses. In an effort to minimize the radiation doses received by patients, our institution has recently initiated an online training program in the safe use of fluoroscopy. This course is required and must be completed by new radiology residents before their first fluoroscopy rotation. The goal of this study was to determine if the use of an online course in the safe use of fluoroscopy could result in decreased patient dose without affecting diagnostic quality. Four years of retrospective procedural data for residents performing gastrointestinal and genitourinary fluoroscopic procedures without specialized training were reviewed. Incoming residents took an American Medical Association-accredited online training program in the safe use of fluoroscopy the week before their first fluoroscopy rotation. Patient dose and diagnostic quality data, inferred from the frequency of attending physician intervention necessary to complete the procedure, were collected for all exams performed by the new group of residents after completion of the training course. This was then compared to data from prior classes and stratified by procedure type. Statistically significant reductions in both average fluoroscopy time (FT) or dose-area-product (DAP) were found for many of the fluoroscopic procedures performed by residents who participated in the online fluoroscopy training program. Specifically, statistically significant reductions in FT for barium enema, cystogram, defecogram, and esophagram procedures (P fluoroscopy rotation, decreasing patient dose without affecting diagnostic quality

  7. Deletion of the NMDA receptor GluN2A subunit significantly decreases dendritic growth in maturing dentate granule neurons.

    Directory of Open Access Journals (Sweden)

    Timal S Kannangara

    Full Text Available It is known that NMDA receptors can modulate adult hippocampal neurogenesis, but the contribution of specific regulatory GluN2 subunits has been difficult to determine. Here we demonstrate that mice lacking GluN2A (formerly NR2A do not show altered cell proliferation or neuronal differentiation, but present significant changes in neuronal morphology in dentate granule cells. Specifically, GluN2A deletion significantly decreased total dendritic length and dendritic complexity in DG neurons located in the inner granular zone. Furthermore, the absence of GluN2A also resulted in a localized increase in spine density in the middle molecular layer, a region innervated by the medial perforant path. Interestingly, alterations in dendritic morphology and spine density were never seen in dentate granule cells located in the outer granular zone, a region that has been hypothesized to contain older, more mature, neurons. These results indicate that although the GluN2A subunit is not critical for the cell proliferation and differentiation stages of the neurogenic process, it does appear to play a role in establishing synaptic and dendritic morphology in maturing dentate granule cells localized in the inner granular zone.

  8. Resistance exercise performed with repetitions until failure affects nocturnal blood pressure decreases in hypertensive women

    Directory of Open Access Journals (Sweden)

    Marilia de Almeida Correia

    2015-12-01

    Full Text Available Studies have shown that resistance exercise reduces 24-hour blood pressure to levels below resting values, although this is not a universal finding. The number of repetitions has been shown to influence this response. Thus, the aim of the study was to analyze the effects of resistance exercise performed until failure (UF on 24-hour blood pressure in hypertensive women. Thirteen hypertensive women underwent three experimental sessions in random order: UF, resistance exercise with repetitions before concentric failure (BF and control (C. Prior to and up to 24 hours after the sessions, cardiovascular variables, as well as the nocturnal fall in blood pressure, the morning surge, and the presence or absence of a blood pressure dip pattern were established using an ambulatory blood pressure monitor. In both wakefulness and sleep there was no significant difference among the three groups. However, after UF and C fewer patients presented a dip in blood pressure (46% and 38%, respectively compared BF (77%, p=0.047. In conclusion, the UF attenuated blood pressure dips at night in hypertensive patients.

  9. Biodiversity increases functional and compositional resistance, but decreases resilience in phytoplankton communities.

    Science.gov (United States)

    Baert, Jan M; De Laender, Frederik; Sabbe, Koen; Janssen, Colin R

    2016-12-01

    There is now ample evidence that biodiversity stabilizes aggregated ecosystem functions, such as primary production, in changing environments. In primary producer systems, this stabilizing effect is found to be driven by higher functional resistance (i.e., reduced changes in functions by environmental changes) rather than through higher functional resilience (i.e., rapid recovery following environmental changes) in more diverse systems. The stability of aggregated ecosystem functions directly depends on changes in species composition and by consequence their functional contributions to ecosystem functions. Still, it remains only theoretically explored how biodiversity can stabilize ecosystem functions by affecting compositional stability. Here, we demonstrate how biodiversity effects on compositional stability drive biodiversity effects on functional stability in diatom communities. In a microcosm experiment, we exposed 39 communities of five different levels of species richness (1, 2, 4, 6, and 8 species) to three concentrations of a chemical stressor (0, 25, and 250 μg/L atrazine) for four weeks, after which all communities were transferred to atrazine-free medium for three more weeks. Biodiversity simultaneously increased, increasing functional and compositional resistance, but decreased functional and compositional resilience. These results confirm the theoretically proposed link between biodiversity effects on functional and compositional stability in primary producer systems, and provide a mechanistic underpinning for observed biodiversity-stability relationships. Finally, we discuss how higher compositional stability can be expected to become increasingly important in stabilizing ecosystem functions under field conditions when multiple environmental stressors fluctuate simultaneously. © 2016 by the Ecological Society of America.

  10. Intensity-Modulated Radiotherapy Results in Significant Decrease in Clinical Toxicities Compared With Conventional Wedge-Based Breast Radiotherapy

    International Nuclear Information System (INIS)

    Harsolia, Asif; Kestin, Larry; Grills, Inga; Wallace, Michelle; Jolly, Shruti; Jones, Cortney; Lala, Moinaktar; Martinez, Alvaro; Schell, Scott; Vicini, Frank A.

    2007-01-01

    Purpose: We have previously demonstrated that intensity-modulated radiotherapy (IMRT) with a static multileaf collimator process results in a more homogenous dose distribution compared with conventional wedge-based whole breast irradiation (WBI). In the present analysis, we reviewed the acute and chronic toxicity of this IMRT approach compared with conventional wedge-based treatment. Methods and Materials: A total of 172 patients with Stage 0-IIB breast cancer were treated with lumpectomy followed by WBI. All patients underwent treatment planning computed tomography and received WBI (median dose, 45 Gy) followed by a boost to 61 Gy. Of the 172 patients, 93 (54%) were treated with IMRT, and the 79 patients (46%) treated with wedge-based RT in a consecutive fashion immediately before this cohort served as the control group. The median follow-up was 4.7 years. Results: A significant reduction in acute Grade 2 or worse dermatitis, edema, and hyperpigmentation was seen with IMRT compared with wedges. A trend was found toward reduced acute Grade 3 or greater dermatitis (6% vs. 1%, p = 0.09) in favor of IMRT. Chronic Grade 2 or worse breast edema was significantly reduced with IMRT compared with conventional wedges. No difference was found in cosmesis scores between the two groups. In patients with larger breasts (≥1,600 cm 3 , n = 64), IMRT resulted in reduced acute (Grade 2 or greater) breast edema (0% vs. 36%, p <0.001) and hyperpigmentation (3% vs. 41%, p 0.001) and chronic (Grade 2 or greater) long-term edema (3% vs. 30%, p 0.007). Conclusion: The use of IMRT in the treatment of the whole breast results in a significant decrease in acute dermatitis, edema, and hyperpigmentation and a reduction in the development of chronic breast edema compared with conventional wedge-based RT

  11. Slow recovery of the impaired fatigue resistance in postunloading mouse soleus muscle corresponding to decreased mitochondrial function and a compensatory increase in type I slow fibers

    Science.gov (United States)

    Feng, Han-Zhong; Chen, Xuequn; Malek, Moh H.

    2015-01-01

    Unloading or disuse rapidly results in skeletal muscle atrophy, switching to fast-type fibers, and decreased resistance to fatigue. The recovery process is of major importance in rehabilitation for various clinical conditions. Here we studied mouse soleus muscle during 60 days of reloading after 4 wk of hindlimb suspension. Unloading produced significant atrophy of soleus muscle with decreased contractile force and fatigue resistance, accompanied by switches of myosin isoforms from IIa to IIx and IIb and fast troponin T to more low-molecular-weight splice forms. The total mass, fiber size, and contractile force of soleus muscle recovered to control levels after 15 days of reloading. However, the fatigue resistance showed a trend of worsening during this period with significant infiltration of inflammatory cells at days 3 and 7, indicating reloading injuries that were accompanied by active regeneration with upregulations of filamin-C, αB-crystallin, and desmin. The fatigue resistance partially recovered after 30–60 days of reloading. The expression of peroxisome proliferator-activated receptor γ coactivator 1α and mitofusin-2 showed changes parallel to that of fatigue resistance after unloading and during reloading, suggesting a causal role of decreased mitochondrial function. Slow fiber contents in the soleus muscle were increased after 30–60 days of reloading to become significantly higher than the normal level, indicating a secondary adaption to compensate for the slow recovery of fatigue resistance. PMID:26447205

  12. An Inexpensive Modified Primary Closure Technique for Class IV (Dirty) Wounds Significantly Decreases Superficial and Deep Surgical Site Infection.

    Science.gov (United States)

    Kim, Bradford J; Aloia, Thomas A

    2016-11-01

    Despite the creation of several programs to decrease the incidence of surgical site infection, it remains a common complication that has a significant impact on patient recovery and medical costs. The following is a description and brief outcome report of a modified primary closure technique used for dirty (Class IV) wounds. There were 14 consecutive patients who had a laparotomy with Class IV wounds treated by a single surgeon (TAA) from 2011 to 2015. All patients had a history of cancer and either showed signs suggestive for an acute abdomen and required an emergent exploratory laparotomy or were found to have purulent intraabdominal infection at the time of elective surgery. The operation and "modified primary closure" technique (subcutaneous wound wicks with stapled skin closure) were performed in every case. The modified primary closure technique was utilized in 14 patients with a Class IV wound. There were no 30-day mortalities or readmissions. Wound wicks were slowly advanced out over a 7-day period, and only one patient required subsequent wound packing of a single-wicked area. There were no superficial or deep surgical site infections, or wound dehiscence during the hospital course, or 30-day postoperative period. The modified primary closure technique is efficient and inexpensive and was effective in a series of 14 patients with wounds classified as dirty.

  13. Significant Aerosol Influence on the Recent Decadal Decrease in Tropical Cyclone Activity Over the Western North Pacific

    Science.gov (United States)

    Takahashi, Chiharu; Watanabe, Masahiro; Mori, Masato

    2017-09-01

    Over the past two decades, the number of tropical cyclones (TCs) has decreased markedly in the southeastern part of the western North Pacific (WNP) as a component of the interdecadal variation. This decrease has partially been explained by an internal low-frequency variability of sea surface temperature (SST) in the Pacific, but influences of external forcing remain unclear. Here we show that past changes in sulfate aerosol emissions contributed approximately 60% of the observed decreasing trends in TC genesis frequency in the southeastern WNP for 1992-2011, using multiple simulations by a global climate model. This decrease was mainly attributed to the increased vertical wind shear and decreased low-level vorticity, associated with a trans-basin multidecadal SST change driven by aerosol forcing. The near-future projection shows that the aerosol forcing still has some potential influence on decadal TC change, but the projected decreasing frequency is mainly due to increasing greenhouse gases forcing.

  14. Modest Decrease in Pgc1α Results in TAG Accumulation but not in Insulin Resistance in L6 Myotubes

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    Bartlomiej Lukaszuk

    2015-03-01

    Full Text Available Background/Aims: PGC-1α is an important cellular protein (coactivator regulating myocyte mitochondria number and function, and therefore whole cellular energy status. The aim of this work was to investigate the effects of modest, temporary PGC-1α knock-down on L6 myotubes insulin resistance in a light of cellular lipid metabolism. Methods: Gas liquid chromatography was applied for assessing FAs content and composition. For the expression of mitochondrial enzymes, as well as FA and glucose transporters, Western Blot technique was adopted. Additionally, radiolabelled glucose and palmitic acid uptake was performed to estimate the nutrients cellular influx. Results: Modest (-24% PGC-1α protein ablation resulted in decreased mitochondrial activity in general (reduced Cyt C content and FAs oxidation in particular (diminished β-HAD expression without increased FAs cellular influx. The aforementioned intervention led to significantly increased TAG cellular level, but not DAG nor CER. Consequently, no changes in cellular insulin responsiveness were noticed. Conclusions: Modest (-24% PGC-1α protein depletion results in lipid accumulation, without causing insulin resistance. Importantly, it seems that this TAG loading is a result of decreased mitochondrial oxidative capacity and/or possibly increased lipid biosynthesis but not fatty acid cellular influx.

  15. Resistance or aerobic training decreases blood pressure and improves cardiovascular autonomic control and oxidative stress in hypertensive menopausal rats.

    Science.gov (United States)

    da Palma, Renata K; Moraes-Silva, Ivana C; da Silva Dias, Danielle; Shimojo, Guilherme L; Conti, Filipe F; Bernardes, Nathalia; Barboza, Catarina A; Sanches, Iris C; da Rosa Araújo, Alex Sander; Irigoyen, Maria-Cláudia; De Angelis, Kátia

    2016-10-01

    We investigated whether resistance training (RT) vs. aerobic training (AT) differentially impacts on arterial pressure and related mechanisms in ovariectomized spontaneously hypertensive rats (SHRs). Female SHRs were ovariectomized and assigned to one of the following groups: sedentary, AT, or RT; sham sedentary SHR were used as control group. AT was performed on a treadmill, whereas RT was performed on a vertical ladder. Both exercise protocols were performed for 8 wk, 5 days/wk. Arterial pressure, baroreflex sensitivity, autonomic modulation, and cardiac oxidative stress parameters (lipid peroxidation, protein oxidation, redox balance, NADPH oxidase, and antioxidant enzymes activities) were analyzed. Ovariectomy increased mean arterial pressure (∼9 mmHg), sympathetic modulation (∼40%), and oxidative stress in sedentary rats. Both RT and AT reduced mean arterial pressure (∼20 and ∼8 mmHg, respectively) and improved baroreflex sensitivity compared with sedentary ovariectomized rats. However, RT-induced arterial pressure decrease was significantly less pronounced than AT. Lipid peroxidation and protein oxidation were decreased while antioxidant enzymes were increased in both trained groups vs. sedentaries. The reduced gluthatione was higher after AT vs. other groups, whereas oxidized gluthatione was lower after RT vs. AT. Moreover, sympathetic and parasympathetic modulations were highly correlated with cardiac oxidative stress parameters. In conclusion, both RT and AT can decrease arterial pressure in a model of hypertension and menopause; although, at different magnitudes this decrease was related to attenuated autonomic dysfunction in association with cardiac oxidative stress improvement in both exercise protocols. Copyright © 2016 the American Physiological Society.

  16. Abundant rifampin resistance genes and significant correlations of antibiotic resistance genes and plasmids in various environments revealed by metagenomic analysis.

    Science.gov (United States)

    Ma, Liping; Li, Bing; Zhang, Tong

    2014-06-01

    In the present study, a newly developed metagenomic analysis approach was applied to investigate the abundance and diversity of antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs) in aquaculture farm sediments, activated sludge, biofilm, anaerobic digestion sludge, and river water. BLASTX analysis against the Comprehensive Antibiotic Resistance Database was conducted for the metagenomic sequence data of each sample and then the ARG-like sequences were sorted based on structured sub-database using customized scripts. The results showed that freshwater fishpond sediment had the highest abundance (196 ppm), and anaerobic digestion sludge possessed the highest diversity (133 subtypes) of ARGs among the samples in this study. Significantly, rifampin resistance genes were universal in all the diverse samples and consistently accounted for 26.9~38.6 % of the total annotated ARG sequences. Furthermore, a significant linear correlation (R (2) = 0.924) was found between diversities (number of subtypes) of ARGs and diversities of plasmids in diverse samples. This work provided a wide spectrum scan of ARGs and MGEs in different environments and revealed the prevalence of rifampin resistance genes and the strong correlation between ARG diversity and plasmid diversity for the first time.

  17. Decreased expression of LamB and Odp1 complex is crucial for antibiotic resistance in Escherichia coli.

    Science.gov (United States)

    Lin, Xiang-min; Yang, Man-jun; Li, Hui; Wang, Chao; Peng, Xuan-Xian

    2014-02-26

    We previously revealed a negative regulation of LamB in chlortetracycline-resistant Escherichia coli strain. In the present study, we first showed that the negative regulation, which was characterized by decreased abundance of LamB with elevated growth of its gene-deleted mutant in medium with antibiotics, was a general response in resistance to different classes of antibiotics using 2-DE based proteomics or/and genetically gene-deletion mutant of LamB. Then, we revealed the interaction of LamB and Odp1 which catalyzes the overall conversion of pyruvate to acetyl-CoA and CO2, and found the decrease of the complex in antibiotic-resistant strains with a minimum inhibitory concentration dose-dependent manner. Further spectrofluorometry assay indicated that LamB served as a porin to influx an antibiotic. Finally, we showed that the decreased expression of LamB and Odp1 was detected in almost of all 34 multidrug-resistant strains, which suggested that LamB and Odp1 were biomarkers for identification of antibiotic-resistant E. coli. Our results indicated that the interaction of an outer membrane protein with an energy metabolic enzyme constructed an efficient pathway to resist antibiotics. These findings provide novel insights into the mechanisms of antibiotic resistance. Our data indicate that the negative regulation by LamB is widely detected in antibiotic-resistant E. coli. LamB serves as a porin to influx an antibiotic and is interacted with Odp1. The complex decreases in antibiotic-resistant strains with a MIC dose-dependent manner. Our findings indicate that interaction of outer membrane protein with energy metabolic enzyme constructs an efficient pathway to resist antibiotics and provides novel insights into the mechanisms of antibiotic resistance. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. The expression and significance of P-glycoprotein, lung resistance protein and multidrug resistance-associated protein in gastric cancer

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    Li Yan

    2009-11-01

    Full Text Available Abstract Background To detect the expression of multidrug resistance molecules P-glycoprotein (P-gp, Lung resistnce protein (LRP and Multidrug resistance-associated protein (MRP and analyze the relationship between them and the clinico-pathological features. Methods The expressions of P-gp, LRP and MRP in formalin-fixed paraffin-embedded tissue sections from 59 gastric cancer patients were determined by a labbelled Streptavidin-Peroxidase (SP immunohistochemical technique, and the results were analyzed in correlation with clinicopathological data. None of these patients received chemotherapy prior to surgery. Results The positive rates of P-gp, LRP, MRP were 86.4%, 84.7% and 27.1%, respectively. The difference between the positive rate of P-gp and MRP was significant statistically, as well as the difference between the expression of MRP and LRP. No significant difference was observed between P-gp and LRP, but the positively correlation between the expression of P-gp and LRP had been found. No significant correlation between the expression of P-gp, LRP, MRP and the grade of differentiation were observed. The expression of P-gp was correlated with clinical stages positively (r = 0.742, but the difference with the expression of P-gp in different stages was not significant. Conclusion The expressions of P-gp, LRP and MRP in patients with gastric cancer without prior chemotherapy are high, indicating that innate drug resistance may exist in gastric cancer.

  19. On the in vivo significance of bacterial resistance to antimicrobial peptides.

    Science.gov (United States)

    Bauer, Margaret E; Shafer, William M

    2015-11-01

    Antimicrobial peptides (AMPs) are at the front-line of host defense during infection and play critical roles both in reducing the microbial load early during infection and in linking innate to adaptive immunity. However, successful pathogens have developed mechanisms to resist AMPs. Although considerable progress has been made in elucidating AMP-resistance mechanisms of pathogenic bacteria in vitro, less is known regarding the in vivo significance of such resistance. Nevertheless, progress has been made in this area, largely by using murine models and, in two instances, human models of infection. Herein, we review progress on the use of in vivo infection models in AMP research and discuss the AMP resistance mechanisms that have been established by in vivo studies to contribute to microbial infection. We posit that in vivo infection models are essential tools for investigators to understand the significance to pathogenesis of genetic changes that impact levels of bacterial susceptibility to AMPs. This article is part of a Special Issue entitled: Bacterial Resistance to Antimicrobial Peptides. Published by Elsevier B.V.

  20. Antimicrobial resistance in invasive non-typhoid Salmonella from the Democratic Republic of the Congo: emergence of decreased fluoroquinolone susceptibility and extended-spectrum beta lactamases.

    Directory of Open Access Journals (Sweden)

    Octavie Lunguya

    Full Text Available BACKGROUND: Co-resistance against the first-line antibiotics ampicillin, chloramphenicol and trimethoprim/sulphamethoxazole or multidrug resistance (MDR is common in non typhoid Salmonella (NTS. Use of alternative antibiotics, such as fluoroquinolones or third generation cephalosporins is threatened by increasing resistance, but remains poorly documented in Central-Africa. METHODOLOGY/PRINCIPAL FINDINGS: As part of a microbiological surveillance study in DR Congo, blood cultures were collected between 2007 and 2011. Isolated NTS were assessed for serotype and antimicrobial resistance including decreased ciprofloxacin susceptibility and extended-spectrum beta-lactamase (ESBL production. In total, 233 NTS isolates (representing 23.6% of clinically significant organisms were collected, mainly consisting of Salmonella Typhimurium (79% and Salmonella Enteritidis (18%. The majority of NTS were isolated in the rainy season, and recovered from children ≤2 years old. MDR, decreased ciprofloxacin susceptibility, azithromycin and cefotaxime resistance were 80.7%, 4.3%, 3.0% and 2.1% respectively. ESBL production was noted in three (1.3% isolates. Decreased ciprofloxacin susceptibility was associated with mutations in codon 87 of the gyrA gene, while ESBLs all belonged to the SHV-2a type. CONCLUSIONS/SIGNIFICANCE: Presence of almost full MDR among NTS isolates from blood cultures in Central Africa was confirmed. Resistance to fluoroquinolones, azithromycin and third generation cephalosporins is still low, but emerging. Increased microbiological surveillance in DR Congo is crucial for adapted antibiotic therapy and the development of treatment guidelines.

  1. Significant enhancement of the strength-to-resistivity ratio by using nanotwins in epitaxial Cu films

    Energy Technology Data Exchange (ETDEWEB)

    Misra, Amit [Los Alamos National Laboratory; Ronningh, Filip [Los Alamos National Laboratory; Anderoglu, Osman [TEXAS A& M; Zhang, X [TEXAS A& M

    2008-01-01

    Epitaxial nanotwinned Cu films, with an average twin spacing ranging from 7 to 16 nm, exhibit a high ratio of strength-to-electrical resisitivity, -400 MPa({mu}{Omega}cm){sup -1}. The hardness of these Cu films approaches 2.8 GPa, and their electrical resistivities are comparable to that of oxygen-free high-conductivity Cu. Compared to high-angle grain boundaries, coherent twin interfaces possess inherently high resistance to the transmission of single dislocations, and yet an order of magnitude lower electron scattering coefficient, determined to be 1.5-5 x 10{sup -7} {mu}{Omega}cm{sup 2} at room temperature. Analytical studies as well as experimental results show that, in polycrystalline Cu, grain refinement leads to a maximum of the strength-to-resistivity ratio, -250 MPa({mu}{Omega}cm){sup -1}, when grain size is comparable to the mean-free path of electrons. However, in twinned Cu, such a ratio increases continuously with decreasing twin spacing down to a few nanometers. Hence nanoscale growth twins are more effective to achieve a higher strength-to-resistivity ratio than high-angle grain boundaries.

  2. The golden root, Rhodiola rosea, prolongs lifespan but decreases oxidative stress resistance in yeast Saccharomyces cerevisiae.

    Science.gov (United States)

    Bayliak, Maria M; Lushchak, Volodymyr I

    2011-11-15

    The effect of aqueous extract from R. rosea root on lifespan and the activity of antioxidant enzymes in budding yeast Saccharomyces cerevisiae have been studied. The supplementation of the growth medium with R. rosea extract decreased survival of exponentially growing S. cerevisiae cells under H(2)O(2)-induced oxidative stress, but increased viability and reproduction success of yeast cells in stationary phase. The extract did not significantly affect catalase activity and decreased SOD activity in chronologically aged yeast population. These results suggest that R. rosea acts as a stressor for S. cerevisiae cells, what sensitizes yeast cells to oxidative stress at exponential phase, but induces adaptation in stationary phase cells demonstrating the positive effect on yeast survival without activation of major antioxidant enzymes. Copyright © 2011 Elsevier GmbH. All rights reserved.

  3. Aluminum exposure for one hour decreases vascular reactivity in conductance and resistance arteries in rats

    International Nuclear Information System (INIS)

    Schmidt, Patrícia Medeiros; Escobar, Alyne Goulart; Torres, João Guilherme Dini; Martinez, Caroline Silveira; Rizzetti, Danize Aparecida; Kunz, Simone Noremberg; Vassallo, Dalton Valentim; Alonso, María Jesús; Peçanha, Franck Maciel; Wiggers, Giulia Alessandra

    2016-01-01

    Aims: Aluminum (Al) is an important environmental contaminant; however, there are not enough evidences of Al-induced cardiovascular dysfunction. We investigated the effects of acute exposure to aluminum chloride (AlCl 3 ) on blood pressure, vascular reactivity and oxidative stress. Methods and results: Male Wistar rats were divided into two groups: Untreated: vehicle (ultrapure water, ip) and AlCl 3 : single dose of AlCl 3 (100 mg/kg,ip). Concentration-response curves to phenylephrine in the absence and presence of endothelium, the nitric oxide synthase inhibitor L-NAME, the potassium channel blocker tetraethylammonium, and the NADPH oxidase inhibitor apocynin were performed in segments from aortic and mesenteric resistance arteries. NO released was assessed in aorta and reactive oxygen species (ROS), malondialdehyde, non-protein thiol levels, antioxidant capacity and enzymatic antioxidant activities were investigated in plasma, aorta and/or mesenteric arteries. After one hour of AlCl 3 exposure serum Al levels attained 147.7 ± 25.0 μg/L. Al treatment: 1) did not affect blood pressure, heart rate and vasodilator responses induced by acetylcholine or sodium nitroprusside; 2) decreased phenylephrine-induced vasoconstrictor responses; 3) increased endothelial modulation of contractile responses, NO release and vascular ROS production from NADPH oxidase; 4) increased plasmatic, aortic and mesenteric malondialdehyde and ROS production, and 5) decreased antioxidant capacity and affected the antioxidant biomarkers non-protein thiol levels, glutathione peroxidase, glutathione-S-transferase, superoxide dismutase and catalase enzymatic activities. Conclusion: AlCl 3 -acute exposure reduces vascular reactivity. This effect is associated with increased NO production, probably acting on K + channels, which seems to occur as a compensatory mechanism against Al-induced oxidative stress. Our results suggest that Al exerts toxic effects to the vascular system. - Highlights:

  4. Growing Burkholderia pseudomallei in Biofilm Stimulating Conditions Significantly Induces Antimicrobial Resistance

    Science.gov (United States)

    Sawasdidoln, Chakrit; Taweechaisupapong, Suwimol; Sermswan, Rasana W.; Tattawasart, Unchalee; Tungpradabkul, Sumalee; Wongratanacheewin, Surasakdi

    2010-01-01

    Background Burkholderia pseudomallei, a Gram-negative bacterium that causes melioidosis, was reported to produce biofilm. As the disease causes high relapse rate when compared to other bacterial infections, it therefore might be due to the reactivation of the biofilm forming bacteria which also provided resistance to antimicrobial agents. However, the mechanism on how biofilm can provide tolerance to antimicrobials is still unclear. Methodology/Principal Findings The change in resistance of B. pseudomallei to doxycycline, ceftazidime, imipenem, and trimethoprim/sulfamethoxazole during biofilm formation were measured as minimum biofilm elimination concentration (MBEC) in 50 soil and clinical isolates and also in capsule, flagellin, LPS and biofilm mutants. Almost all planktonic isolates were susceptible to all agents studied. In contrast, when they were grown in the condition that induced biofilm formation, they were markedly resistant to all antimicrobial agents even though the amount of biofilm production was not the same. The capsule and O-side chains of LPS mutants had no effect on biofilm formation whereas the flagellin-defective mutant markedly reduced in biofilm production. No alteration of LPS profiles was observed when susceptible form was changed to resistance. The higher amount of N-acyl homoserine lactones (AHLs) was detected in the high biofilm-producing isolates. Interestingly, the biofilm mutant which produced a very low amount of biofilm and was sensitive to antimicrobial agents significantly resisted those agents when grown in biofilm inducing condition. Conclusions/Significance The possible drug resistance mechanism of biofilm mutants and other isolates is not by having biofilm but rather from some factors that up-regulated when biofilm formation genes were stimulated. The understanding of genes related to this situation may lead us to prevent B. pseudomallei biofilms leading to the relapse of melioidosis. PMID:20169199

  5. Expression and Significance of IKBKB in Pulmonary Adenocarcinoma A549 Cells and Its Cisplatin-resistant Variant A549/DDP

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    Kang QI

    2014-05-01

    Full Text Available Background and objective Cisplatin-resistance in Lung cancer cells is widespread in the clinical treatment, seriously affecting the effects of the treatment of lung cancer. Therefore, the research of mechanisms of cisplain-resistance has significant meaning for developing new chemotherapeutic drug and solving the cisplain-resistance in clinic treatment. IKBKB is one of the most important catalytic subunits of IKK complexes. It plays an important regulatory role in activation of NF-κB. The aim of this study is to investigate the differential expression of IKBKB gene in human lung adenocarcinoma cells line A549 and the cisplatin-resistant variant A549/DDP and the mechanisms of cisplain-resistance induced by IKBKB gene. Methods MTT assay was employed to determine the sensitivity of A549 and A549/DDP cells line to cisplatin and the effect of IKBKB gene on A549 cell lines’ sensitivity to cisplatin. The mRNA level of IKBKB was determined by real-time PCR. Dual luciferase reporter gene experiment was employed to determine the activity of the NF-κB. Apoptosis rate of lung adenocarcinoma cells was determined by flow cytometry. Results Apoptosis rate and IC50 were significantly different in A549 and A549/DDP cells, the expression of mRNA level of IKBKB gene in A549/DDP was significantly higher than that in A549. Compared with control group, IKBKB gene was able to reduce the cisplain sensitivity of A549 cells. After A549 was transfected with pcDNA3.1/IKBKB plasmid, mRNA level of IKBKB was significantly increased, the sensitivity of cisplain was decreased, the IC50 was increased 2.85 fold, the apoptosis rate was decreased 59%, the activity of NF-κB has been greatly increased. Conclusion IKBKB inhibits cisplatin-induced apoptosis via the activation of NF-κB pathway. It will be helpful in the development of new anticancer drug and solving the challenge of cisplatin-resistance.

  6. [Expression and significance of IKBKB in pulmonary adenocarcinoma A549 cells and its cisplatin-resistant variant A549/DDP].

    Science.gov (United States)

    Qi, Kang; Li, Yang; Li, Xuebing; Zhang, Fang; Shao, Yi; Zhou, Qinghua

    2014-05-01

    Cisplatin-resistance in Lung cancer cells is widespread in the clinical treatment, seriously affecting the effects of the treatment of lung cancer. Therefore, the research of mechanisms of cisplain-resistance has significant meaning for developing new chemotherapeutic drug and solving the cisplain-resistance in clinic treatment. IKBKB is one of the most important catalytic subunits of IKK complexes. It plays an important regulatory role in activation of NF-κB. The aim of this study is to investigate the differential expression of IKBKB gene in human lung adenocarcinoma cells line A549 and the cisplatin-resistant variant A549/DDP and the mechanisms of cisplain-resistance induced by IKBKB gene. MTT assay was employed to determine the sensitivity of A549 and A549/DDP cells line to cisplatin and the effect of IKBKB gene on A549 cell lines' sensitivity to cisplatin. The mRNA level of IKBKB was determined by real-time PCR. Dual luciferase reporter gene experiment was employed to determine the activity of the NF-κB. Apoptosis rate of lung adenocarcinoma cells was determined by flow cytometry. Apoptosis rate and IC50 were significantly different in A549 and A549/DDP cells, the expression of mRNA level of IKBKB gene in A549/DDP was significantly higher than that in A549. Compared with control group, IKBKB gene was able to reduce the cisplain sensitivity of A549 cells. After A549 was transfected with pcDNA3.1/IKBKB plasmid, mRNA level of IKBKB was significantly increased, the sensitivity of cisplain was decreased, the IC50 was increased 2.85 fold, the apoptosis rate was decreased 59%, the activity of NF-κB has been greatly increased. IKBKB inhibits cisplatin-induced apoptosis via the activation of NF-κB pathway. It will be helpful in the development of new anticancer drug and solving the challenge of cisplatin-resistance.

  7. Decreased drug accumulation and increased tolerance to DNA damage in tumor cells with a low level of cisplatin resistance.

    Science.gov (United States)

    Lanzi, C; Perego, P; Supino, R; Romanelli, S; Pensa, T; Carenini, N; Viano, I; Colangelo, D; Leone, R; Apostoli, P; Cassinelli, G; Gambetta, R A; Zunino, F

    1998-04-15

    In an attempt to examine the cellular changes associated with cisplatin resistance, we selected a cisplatin-resistant (A43 1/Pt) human cervix squamous cell carcinoma cell line following continuous in vitro drug exposure. The resistant subline was characterized by a 2.5-fold degree of resistance. In particular, we investigated the expression of cellular defence systems and other cellular factors probably involved in dealing with cisplatin-induced DNA damage. Resistant cells exhibited decreased platinum accumulation and reduced levels of DNA-bound platinum and interstrand cross-link frequency after short-term drug exposure. Analysis of the effect of cisplatin on cell cycle progression revealed a cisplatin-induced G2M arrest in sensitive and resistant cells. Interestingly, a slowdown in S-phase transit was found in A431/Pt cells. A comparison of the ability of sensitive and resistant cells to repair drug-induced DNA damage suggested that resistant cells were able to tolerate higher levels of cisplatin-induced DNA damage than their parental counterparts. Analysis of the expression of proteins involved in DNA mismatch repair showed a decreased level of MSH2 in resistant cells. Since MSH2 seems to be involved in recognition of drug-induced DNA damage, this change may account for the increased tolerance to DNA damage observed in the resistant subline. In conclusion, the involvement of accumulation defects and the increased tolerance to cisplatin-induced DNA damage in these cisplatin-resistant cells support the notion that multiple changes contribute to confer a low level of cisplatin resistance.

  8. Decreased prevalence of Plasmodium falciparum resistance markers to amodiaquine despite its wide scale use as ACT partner drug in Zanzibar.

    Science.gov (United States)

    Fröberg, Gabrielle; Jörnhagen, Louise; Morris, Ulrika; Shakely, Delér; Msellem, Mwinyi I; Gil, José P; Björkman, Anders; Mårtensson, Andreas

    2012-09-11

    Zanzibar has recently undergone a rapid decline in Plasmodium falciparum transmission following combined malaria control interventions with artemisinin-based combination therapy (ACT) and integrated vector control. Artesunate-amodiaquine (ASAQ) was implemented as first-line treatment for uncomplicated P. falciparum malaria in Zanzibar in 2003. Resistance to amodiaquine has been associated with the single nucleotide polymorphism (SNP) alleles pfcrt 76T, pfmdr1 86Y, 184Y and 1246Y. An accumulation of these SNP alleles in the parasite population over time might threaten ASAQ efficacy.The aim of this study was to assess whether prolonged use of ASAQ as first-line anti-malarial treatment selects for P. falciparum SNPs associated with resistance to the ACT partner drug amodiaquine. The individual as well as the combined SNP allele prevalence were compared in pre-treatment blood samples from patients with uncomplicated P. falciparum malaria enrolled in clinical trials conducted just prior to the introduction of ASAQ in 2002-2003 (n = 208) and seven years after wide scale use of ASAQ in 2010 (n = 122). There was a statistically significant decrease of pfcrt 76T (96-63%), pfmdr1 86Y (75-52%), 184Y (83-72%), 1246Y (28-16%) and the most common haplotypes pfcrt/pfmdr1 TYYD (46-26%) and TYYY (17-8%), while an increase of pfcrt/pfmdr1 KNFD (0.4-14%) and KNYD (1-12%). This is the first observation of a decreased prevalence of pfcrt 76T, pfmdr1 86Y, 184Y and 1246Y in an African setting after several years of extensive ASAQ use as first-line treatment for uncomplicated malaria. This may support sustained efficacy of ASAQ on Zanzibar, although it was unexpected considering that all these SNPs have previously been associated with amodiaquine resistance. The underlying factors of these results are unclear. Genetic dilution by imported P. falciparum parasites from mainland Tanzania, a de-selection by artesunate per se and/or an associated fitness cost might represent contributing

  9. Decreased prevalence of Plasmodium falciparum resistance markers to amodiaquine despite its wide scale use as ACT partner drug in Zanzibar

    Directory of Open Access Journals (Sweden)

    Fröberg Gabrielle

    2012-09-01

    Full Text Available Abstract Background Zanzibar has recently undergone a rapid decline in Plasmodium falciparum transmission following combined malaria control interventions with artemisinin-based combination therapy (ACT and integrated vector control. Artesunate-amodiaquine (ASAQ was implemented as first-line treatment for uncomplicated P. falciparum malaria in Zanzibar in 2003. Resistance to amodiaquine has been associated with the single nucleotide polymorphism (SNP alleles pfcrt 76T, pfmdr1 86Y, 184Y and 1246Y. An accumulation of these SNP alleles in the parasite population over time might threaten ASAQ efficacy. The aim of this study was to assess whether prolonged use of ASAQ as first-line anti-malarial treatment selects for P. falciparum SNPs associated with resistance to the ACT partner drug amodiaquine. Methods The individual as well as the combined SNP allele prevalence were compared in pre-treatment blood samples from patients with uncomplicated P. falciparum malaria enrolled in clinical trials conducted just prior to the introduction of ASAQ in 2002–2003 (n = 208 and seven years after wide scale use of ASAQ in 2010 (n = 122. Results There was a statistically significant decrease of pfcrt 76T (96–63%, pfmdr1 86Y (75–52%, 184Y (83–72%, 1246Y (28–16% and the most common haplotypes pfcrt/pfmdr1 TYYD (46–26% and TYYY (17–8%, while an increase of pfcrt/pfmdr1 KNFD (0.4–14% and KNYD (1–12%. Conclusions This is the first observation of a decreased prevalence of pfcrt 76T, pfmdr1 86Y, 184Y and 1246Y in an African setting after several years of extensive ASAQ use as first-line treatment for uncomplicated malaria. This may support sustained efficacy of ASAQ on Zanzibar, although it was unexpected considering that all these SNPs have previously been associated with amodiaquine resistance. The underlying factors of these results are unclear. Genetic dilution by imported P. falciparum parasites from mainland Tanzania, a de-selection by

  10. Gastroduodenal resistance and neural mechanisms involved in saline flow decrease elicited by acute blood volume expansion in anesthetized rats

    Directory of Open Access Journals (Sweden)

    Graça J.R.V.

    1997-01-01

    Full Text Available We have previously demonstrated that blood volume (BV expansion decreases saline flow through the gastroduodenal (GD segment in anesthetized rats (Xavier-Neto J, dos Santos AA & Rola FH (1990 Gut, 31: 1006-1010. The present study attempts to identify the site(s of resistance and neural mechanisms involved in this phenomenon. Male Wistar rats (N = 97, 200-300 g were surgically manipulated to create four gut circuits: GD, gastric, pyloric and duodenal. These circuits were perfused under barostatically controlled pressure (4 cmH2O. Steady-state changes in flow were taken to reflect modifications in circuit resistances during three periods of time: normovolemic control (20 min, expansion (10-15 min, and expanded (30 min. Perfusion flow rates did not change in normovolemic control animals over a period of 60 min. BV expansion (Ringer bicarbonate, 1 ml/min up to 5% body weight significantly (P<0.05 reduced perfusion flow in the GD (10.3 ± 0.5 to 7.6 ± 0.6 ml/min, pyloric (9.0 ± 0.6 to 5.6 ± 1.2 ml/min and duodenal (10.8 ± 0.4 to 9.0 ± 0.6 ml/min circuits, but not in the gastric circuit (11.9 ± 0.4 to 10.4 ± 0.6 ml/min. Prazosin (1 mg/kg and yohimbine (3 mg/kg prevented the expansion effect on the duodenal but not on the pyloric circuit. Bilateral cervical vagotomy prevented the expansion effect on the pylorus during the expansion but not during the expanded period and had no effect on the duodenum. Atropine (0.5 mg/kg, hexamethonium (10 mg/kg and propranolol (2 mg/kg were ineffective on both circuits. These results indicate that 1 BV expansion increases the GD resistance to liquid flow, 2 pylorus and duodenum are important sites of resistance, and 3 yohimbine and prazosin prevented the increase in duodenal resistance and vagotomy prevented it partially in the pylorus

  11. Antibiotic resistance in Haemophilus influenzae decreased, except for beta-lactamase-negative amoxicillin-resistant isolates, in parallel with community antibiotic consumption in Spain from 1997 to 2007.

    Science.gov (United States)

    García-Cobos, Silvia; Campos, José; Cercenado, Emilia; Román, Federico; Lázaro, Edurne; Pérez-Vázquez, María; de Abajo, Francisco; Oteo, Jesús

    2008-08-01

    The susceptibility to 14 antimicrobial agents and the mechanisms of aminopenicillin resistance were studied in 197 clinical isolates of Haemophilus influenzae--109 isolated in 2007 (study group) and 88 isolated in 1997 (control group). Community antibiotic consumption trends were also examined. H. influenzae strains were consecutively isolated from the same geographic area, mostly from respiratory specimens from children and adults. Overall, amoxicillin resistance decreased by 8.4% (from 38.6 to 30.2%). Beta-lactamase production decreased by 15.6% (from 33 to 17.4%, P = 0.01), but amoxicillin resistance without beta-lactamase production increased by 7.1% (from 5.7 to 12.8%). All beta-lactamase-positive isolates were TEM-1, but five different promoter regions were identified, with Pdel being the most prevalent in both years, and Prpt being associated with the highest amoxicillin resistance. A new promoter consisting of a double repeat of 54 bp was detected. Community consumption of most antibiotics decreased, as did the geometric means of their MICs, but amoxicillin-clavulanic acid and azithromycin consumption increased by ca. 60%. For amoxicillin-clavulanic acid, a 14.2% increase in the population with an MIC of 2 to 4 microg/ml (P = 0.02) was observed; for azithromycin, a 21.2% increase in the population with an MIC of 2 to 8 microg/ml (P = 0.0005) was observed. In both periods, the most common gBLNAR (i.e., H. influenzae isolates with mutations in the ftsI gene as previously defined) patterns were IIc and IIb. Community consumption of trimethoprim-sulfamethoxazole decreased by 54%, while resistance decreased from 50 to 34.9% (P = 0.04). Antibiotic resistance in H. influenzae decreased in Spain from 1997 to 2007, but surveillance should be maintained since new forms of resistances may be developing.

  12. Significance of MDR1 and multiple drug resistance in refractory human epileptic brain

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    Dini Gabriele

    2004-10-01

    Full Text Available Abstract Background The multiple drug resistance protein (MDR1/P-glycoprotein is overexpressed in glia and blood-brain barrier (BBB endothelium in drug refractory human epileptic tissue. Since various antiepileptic drugs (AEDs can act as substrates for MDR1, the enhanced expression/function of this protein may increase their active extrusion from the brain, resulting in decreased responsiveness to AEDs. Methods Human drug resistant epileptic brain tissues were collected after surgical resection. Astrocyte cell cultures were established from these tissues, and commercially available normal human astrocytes were used as controls. Uptake of fluorescent doxorubicin and radioactive-labeled Phenytoin was measured in the two cell populations, and the effect of MDR1 blockers was evaluated. Frozen human epileptic brain tissue slices were double immunostained to locate MDR1 in neurons and glia. Other slices were exposed to toxic concentrations of Phenytoin to study cell viability in the presence or absence of a specific MDR1 blocker. Results MDR1 was overexpressed in blood vessels, astrocytes and neurons in human epileptic drug-resistant brain. In addition, MDR1-mediated cellular drug extrusion was increased in human 'epileptic' astrocytes compared to 'normal' ones. Concomitantly, cell viability in the presence of cytotoxic compounds was increased. Conclusions Overexpression of MDR1 in different cell types in drug-resistant epileptic human brain leads to functional alterations, not all of which are linked to drug pharmacokinetics. In particular, the modulation of glioneuronal MDR1 function in epileptic brain in the presence of toxic concentrations of xenobiotics may constitute a novel cytoprotective mechanism.

  13. Deficiency of a glycogen synthase-associated protein, Epm2aip1, causes decreased glycogen synthesis and hepatic insulin resistance.

    Science.gov (United States)

    Turnbull, Julie; Tiberia, Erica; Pereira, Sandra; Zhao, Xiaochu; Pencea, Nela; Wheeler, Anne L; Yu, Wen Qin; Ivovic, Alexander; Naranian, Taline; Israelian, Nyrie; Draginov, Arman; Piliguian, Mark; Frankland, Paul W; Wang, Peixiang; Ackerley, Cameron A; Giacca, Adria; Minassian, Berge A

    2013-11-29

    Glycogen synthesis is a major component of the insulin response, and defective glycogen synthesis is a major portion of insulin resistance. Insulin regulates glycogen synthase (GS) through incompletely defined pathways that activate the enzyme through dephosphorylation and, more potently, allosteric activation. We identify Epm2aip1 as a GS-associated protein. We show that the absence of Epm2aip1 in mice impairs allosteric activation of GS by glucose 6-phosphate, decreases hepatic glycogen synthesis, increases liver fat, causes hepatic insulin resistance, and protects against age-related obesity. Our work identifies a novel GS-associated GS activity-modulating component of insulin resistance.

  14. Endogenous cytokinin overproduction modulates ROS homeostasis and decreases salt stress resistance in Arabidopsis thaliana

    Directory of Open Access Journals (Sweden)

    Yanping eWang

    2015-11-01

    Full Text Available Cytokinins in plants are crucial for numerous biological processes, including seed germination, cell division and differentiation, floral initiation and adaptation to abiotic stresses. The salt stress can promote reactive oxygen species (ROS production in plants which are highly toxic and ultimately results in oxidative stress. However, the correlation between endogenous cytokinin production and ROS homeostasis in responding to salt stress is poorly understood. In this study, we analyzed the correlation of overexpressing the cytokinin biosynthetic gene AtIPT8 (adenosine phosphate-isopentenyl transferase 8 and the response of salt stress in Arabidopsis. Overproduction of cytokinins, which was resulted by the inducible overexpression of AtIPT8, significantly inhibited the primary root growth and true leaf emergence, especially under the conditions of exogenous salt, glucose and mannitol treatments. Upon cytokinin overproduction, the salt stress resistance was declined, and resulted in less survival rates and chlorophyll content. Interestingly, ROS production was obviously increased with the salt treatment, accompanied by endogenously overproduced cytokinins. The activities of CAT and SOD, which are responsible for scavenging ROS, were also affected. Transcription profiling revealed that the differential expressions of ROS-producing and scavenging related genes, the photosynthesis-related genes and stress responsive genes were existed in transgenic plants of overproducing cytokinins. Our results suggested that broken in the homeostasis of cytokinins in plant cells could modulate the salt stress responses through a ROS-mediated regulation in Arabidopsis.

  15. Active surveillance for methicillin-resistant Staphylococcus aureus (MRSA) decreases the incidence of MRSA bacteremia.

    Science.gov (United States)

    Shitrit, Pnina; Gottesman, Bat-Sheva; Katzir, Michal; Kilman, Avi; Ben-Nissan, Yona; Chowers, Michal

    2006-10-01

    To evaluate the influence of performance of active surveillance cultures for methicillin-resistant Staphylococcus aureus (MRSA) on the incidence of nosocomial MRSA bacteremia in an endemic hospital. Before-after trial. A 700-bed hospital. All patients admitted to the hospital who were at high risk for MRSA bacteremia. Performance of surveillance cultures for detection of MRSA were recommended for all patients at high risk, and contact isolation was implemented for patients with positive results of culture. Each MRSA-positive patient received one course of eradication treatment. We compared the total number of surveillance cultures, the percentage of surveillance cultures with positive results, and the number of MRSA bacteremia cases before the intervention (from January 2002 through February 2003) after the start of the intervention (from July 2003 through October 2004). The number of surveillance cultures performed increased from a mean of 272.57 cultures/month before the intervention to 865.83 cultures/month after the intervention. The percentage of surveillance cultures with positive results increased from 3.13% before to 5.22% after the intervention (P hidden reservoirs of MRSA. Contact isolation can prevent new colonization and infection and lead to a significant reduction of morbidity and healthcare costs.

  16. Consumption of resistant starch decreases postprandial lipogenesis in white adipose tissue of the rat

    Directory of Open Access Journals (Sweden)

    Brown Marc A

    2006-09-01

    Full Text Available Abstract Chronic consumption of diets high in resistant starch (RS leads to reduced fat cell size compared to diets high in digestible starch (DS in rats and increases total and meal fat oxidation in humans. The aim of the present study was to examine the rate of lipogenesis in key lipogenic organs following a high RS or DS meal. Following an overnight fast, male Wistar rats ingested a meal with an RS content of 2% or 30% of total carbohydrate and were then administered an i.p bolus of 50 μCi 3H2O either immediately or 1 hour post-meal. One hour following tracer administration, rats were sacrificed, a blood sample collected, and the liver, white adipose tissue (WAT, and gastrocnemius muscle excised and frozen until assayed for total 3H-lipid and 3H-glycogen content. Plasma triglyceride and NEFA concentrations and 3H-glycogen content did not differ between groups. In all tissues, except the liver, there was a trend for the rate of lipogenesis to be higher in the DS group than the RS group which reached significance only in WAT at 1 h (p

  17. Circulating MOTS-c levels are decreased in obese male children and adolescents and associated with insulin resistance.

    Science.gov (United States)

    Du, Caiqi; Zhang, Cai; Wu, Wei; Liang, Yan; Wang, Anru; Wu, Shimin; Zhao, Yue; Hou, Ling; Ning, Qin; Luo, Xiaoping

    2018-04-25

    A novel bioactive peptide, mitochondrial-derived peptide (MOTS-c), has recently attracted attention as a potential prevention or therapeutic option for obesity and type 2 diabetes mellitus (T2DM). MOTS-c profiles have not yet been reported in human obesity and T2DM. We aimed to determine circulating MOTS-c levels in obesity and explore the association between MOTS-c levels and various metabolic parameters. In this case-control study, 40 obese children and adolescents (27 males) and 57 controls (40 males) were recruited in the Hubei Province of China in 2017. Circulating MOTS-c levels were measured, clinical data (e.g., glucose, insulin and lipid profile) were recorded, and anthropometric measurements were performed. Finally, we investigated correlations between MOTS-c levels and related variables. MOTS-c levels were significantly decreased in the obese group compared with the control group (472.61 ± 22.83 ng/mL vs. 561.64 ± 19.19 ng/mL, p c levels were significantly decreased in obese male children and adolescents compared to their counterparts (465.26 ± 24.53 ng/mL vs. 584.07 ± 21.18 ng/mL, p 0.05). Further, MOTS-c levels were negatively correlated with body mass index (BMI), BMI standard deviation score, waist circumference, waist-to-hip ratio, fasting insulin level, HOMA-IR, and HbA1c in the male cohort. Circulating MOTS-c levels were decreased in obese male children and adolescents and correlated with markers of insulin resistance and obesity. This article is protected by copyright. All rights reserved.

  18. Multidrug resistance in Botrytis cinerea associated with decreased accumulation of the azole fungicide oxpoconazole and increased transcription of the ABC transporter gene BcatrD

    NARCIS (Netherlands)

    Hayashi, K.; Schoonbeek, H.; Sugiura, H.; Waard, De M.A.

    2001-01-01

    Azole-resistant mutants of Botrytis cinerea have a multidrug resistance phenotype since they exhibit cross-resistance to unrelated chemicals. These mutants also display resistance to the new azole fungicide oxpoconazole. Resistance to oxpoconazole is associated with decreased accumulation of the

  19. Two distinct groups within the Bacillus subtilis group display significantly different spore heat resistance properties.

    Science.gov (United States)

    Berendsen, Erwin M; Zwietering, Marcel H; Kuipers, Oscar P; Wells-Bennik, Marjon H J

    2015-02-01

    The survival of bacterial spores after heat treatment and the subsequent germination and outgrowth in a food product can lead to spoilage of the food product and economical losses. Prediction of time-temperature conditions that lead to sufficient inactivation requires access to detailed spore thermal inactivation kinetics of relevant model strains. In this study, the thermal inactivation kinetics of spores of fourteen strains belonging to the Bacillus subtilis group were determined in detail, using both batch heating in capillary tubes and continuous flow heating in a micro heater. The inactivation data were fitted using a log linear model. Based on the spore heat resistance data, two distinct groups (p subtilis group could be identified. One group of strains had spores with an average D120 °C of 0.33 s, while the spores of the other group displayed significantly higher heat resistances, with an average D120 °C of 45.7 s. When comparing spore inactivation data obtained using batch- and continuous flow heating, the z-values were significantly different, hence extrapolation from one system to the other was not justified. This study clearly shows that heat resistances of spores from different strains in the B. subtilis group can vary greatly. Strains can be separated into two groups, to which different spore heat inactivation kinetics apply. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Quantitative contributions of target alteration and decreased drug accumulation to Pseudomonas aeruginosa fluoroquinolone resistance.

    Science.gov (United States)

    Bruchmann, Sebastian; Dötsch, Andreas; Nouri, Bianka; Chaberny, Iris F; Häussler, Susanne

    2013-03-01

    Quinolone antibiotics constitute a clinically successful and widely used class of broad-spectrum antibiotics; however, the emergence and spread of resistance increasingly limits the use of fluoroquinolones in the treatment and management of microbial disease. In this study, we evaluated the quantitative contributions of quinolone target alteration and efflux pump expression to fluoroquinolone resistance in Pseudomonas aeruginosa. We generated isogenic mutations in hot spots of the quinolone resistance-determining regions (QRDRs) of gyrA, gyrB, and parC and inactivated the efflux regulator genes so as to overexpress the corresponding multidrug resistance (MDR) efflux pumps. We then introduced the respective mutations into the reference strain PA14 singly and in various combinations. Whereas the combined inactivation of two efflux regulator-encoding genes did not lead to resistance levels higher than those obtained by inactivation of only one efflux regulator-encoding gene, the combination of mutations leading to increased efflux and target alteration clearly exhibited an additive effect. This combination of target alteration and overexpression of efflux pumps was commonly observed in clinical P. aeruginosa isolates; however, these two mechanisms were frequently found not to be sufficient to explain the level of fluoroquinolone resistance. Our results suggest that there are additional mechanisms, independent of the expression of the MexAB-OprM, MexCD-OprJ, MexEF-OprN, and/or MexXY-OprM efflux pump, that increase ciprofloxacin resistance in isolates with mutations in the QRDRs.

  1. Strategies for decreasing multidrug antibiotic resistance: role of ototopical agents for treatment of middle ear infections.

    Science.gov (United States)

    Klein, Jerome O

    2002-10-01

    Change in the susceptibility of bacterial pathogens to antimicrobial agents is constant. The efficacy of a new drug may change as it is used in clinical settings, and resistant bacterial clones result from the encounter of drug and organism. Soon after the introduction of the sulfonamides in the mid-1930s, the first effective agents of the antimicrobial era, resistance of pneumococci and group A streptococci was evident. In each of the following decades, a different problem in multidrug resistance occurred among common bacterial pathogens: beta-lactamase-producing staphylococci in the 1950s; highly resistant gram-negative enteric bacteria in the 1960s; beta-lactamase-producing Haemophilus influenzae and Moraxella catarrhalis in the 1970s; and multidrug-resistant pneumococci in the 1980s. Antimicrobial resistance among respiratory pathogens is now a common clinical problem throughout the world, and its management is a part of routine office practice. Currently in the United States, about 25% of pneumococci are resistant to penicillin, and 25% of H influenzae and 90% of M catarrhalis produce beta-lactamase and would be inactivated by organisms producing the enzyme. The emergence of penicillin and multidrug-resistant pneumococci and beta-lactamase-producing strains of H influenzae and M catarrhalis have special importance for the management of infections of the middle ear. The widespread use of oral and parenteral antimicrobial drugs for appropriate and inappropriate uses has driven the emergence and spread of resistant organisms. This article discusses current susceptibility patterns of organisms involved in middle ear infections, risk factors associated with development of resistant strains, strategies for limiting the incidence and spread of resistant organisms and, as part of the strategy, use of ototopical rather than systemic antimicrobial drugs for chronic suppurative otitis media (CSOM) and acute otitis media (AOM) in children with tympanostomy tubes. Although

  2. Aging causes decreased resistance to multiple stresses and a failure to activate specific stress response pathways

    OpenAIRE

    Dues, Dylan J.; Andrews, Emily K.; Schaar, Claire E.; Bergsma, Alexis L.; Senchuk, Megan M.; Van Raamsdonk, Jeremy M.

    2016-01-01

    In this work, we examine the relationship between stress resistance and aging. We find that resistance to multiple types of stress peaks during early adulthood and then declines with age. To dissect the underlying mechanisms, we use C. elegans transcriptional reporter strains that measure the activation of different stress responses including: the heat shock response, mitochondrial unfolded protein response, endoplasmic reticulum unfolded protein response, hypoxia response, SKN-1-mediated oxi...

  3. Emergence of decreased susceptibility and resistance to extended-spectrum cephalosporins in Neisseria gonorrhoeae in Korea.

    Science.gov (United States)

    Lee, Hyukmin; Unemo, Magnus; Kim, Hyo Jin; Seo, Younghee; Lee, Kyungwon; Chong, Yunsop

    2015-09-01

    Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a major concern globally; however, no comprehensive AMR data for gonococcal isolates cultured after 2006 in Korea have been published internationally. We determined the susceptibility of N. gonorrhoeae isolates cultured in 2011-13, the mechanism of extended-spectrum cephalosporin (ESC) resistance and the molecular epidemiology of gonococcal strains in Korea. In 2011-13, 210 gonococcal isolates were collected in Korea and their AMR profiles were examined by the agar dilution method. The penA, mtrR, penB, ponA and pilQ genes were sequenced in 25 isolates that were resistant to ESCs and 70 randomly selected isolates stratified by year. For molecular epidemiology, N. gonorrhoeae multiantigen sequence typing and MLST were performed. None of the N. gonorrhoeae isolates was susceptible to penicillin G and most were resistant to tetracycline (50%) and ciprofloxacin (97%). The rates of resistance to ceftriaxone, azithromycin, cefpodoxime and cefixime were 3%, 5%, 8% and 9%, respectively. However, all isolates were susceptible to spectinomycin. Twenty-one (84%) of the 25 ESC-resistant isolates contained the non-mosaic PBP2 XIII allele; however, the remaining 4 (16%) possessed the mosaic PBP2 X allele, which has been previously associated with ESC resistance including treatment failures. In Korea, susceptibility to spectinomycin remains high. However, the recent emergence of ESC-resistant N. gonorrhoeae strains, including strains possessing the PBP2 mosaic X and non-mosaic XIII alleles, is a major concern and enhanced AMR surveillance is necessary to prevent transmission of these strains. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  4. Hyoscine butylbromide significantly decreases motion artefacts and allows better delineation of anatomic structures in mp-MRI of the prostate

    Energy Technology Data Exchange (ETDEWEB)

    Ullrich, T.; Quentin, M.; Schmaltz, A.K.; Rubbert, C.; Blondin, D.; Antoch, G.; Schimmoeller, L. [University Dusseldorf, Medical Faculty, Department of Diagnostic and Interventional Radiology, Dusseldorf (Germany); Arsov, C.; Rabenalt, R.; Albers, P. [University Dusseldorf, Medical Faculty, Department of Urology, Dusseldorf (Germany)

    2018-01-15

    To prospectively evaluate the effect of hyoscine butylbromide (HBB) on visualisation of anatomical details and motion-related artefacts in mp-MRI of the prostate at 3.0 Tesla. One hundred and three consecutive patients (65 ± 10 years) were included in this trial, powered to demonstrate an improvement of image quality after HBB administration, assessed on a 5-point scale by two blinded readers. All patients received high-spatial resolution axial T2-weighted TSE sequences at 3.0 T without spasmolytic agent, repeated after application of 40 mg HBB and followed by routine mp-MRI. Secondary endpoints were (1) susceptibility to side effects, (2) dependence of spasmolytic effect on patients and acute; weight, and (3) prostate volume. In 68% of patients, HBB significantly improved the anatomic score (mean 3.4 ± 0.9 before and 4.4 ± 0.7 after HBB for both readers, p = <0.001). In 67%, HBB significantly enhanced the artefact score (mean 3.2 ± 1 before and 4.2 ± 0.8 after HBB for reader 1, p = <0.001; 3.2 ± 1 and 4.1 ± 0.8 for reader 2, p = <0.001). Subgroup analysis revealed no statistically significant difference between patients with different bodyweight or prostate volume. Inter-reader agreement was excellent (k = 0.95-0.98). Hyoscine butylbromide significantly improves image quality and reduces motion-related artefacts in mp-MRI of the prostate independent of bodyweight or prostate volume. No side effects were reported. (orig.)

  5. Bromocriptine increased operant responding for high fat food but decreased chow intake in both obesity-prone and resistant rats

    Energy Technology Data Exchange (ETDEWEB)

    Thanos, P.K.; Wang, G.; Thanos, P.K.; Cho, J. Kim, R.; Michaelides, M.; Primeaux, S.; Bray, G.; Wang, G.-J.; Volkow, N.D.

    2010-10-27

    Dopamine (DA) and DAD{sub 2} receptors (D2R) have been implicated in obesity and are thought to be involved in the rewarding properties of food. Osborne-Mendel (OM) rats are susceptible to diet induced obesity (DIO) while S5B/P (S5B) rats are resistant when given a high-fat diet. Here we hypothesized that the two strains would differ in high-fat food self-administration (FSA) and that the D2R agonist bromocriptine (BC) would differently affect their behavior. Ad-libitum fed OM and S5B/P rats were tested in a FSA operant chamber and were trained to lever press for high-fat food pellets under a fixed-ratio (FR1) and a progressive ratio (PR) schedule. After sixteen days of PR sessions, rats were treated with three different doses of BC (1, 10 and 20 mg/kg). No significant differences were found between the two strains in the number of active lever presses. BC treatment (10 mg/kg and 20 mg/kg) increased the number of active lever presses (10 mg/kg having the strongest effect) whereas it decreased rat chow intake in the home cage with equivalent effects in both strains. These effects were not observed on the day of BC administration but on the day following its administration. Our results suggest that these two strains have similar motivation for procuring high fat food using this paradigm. BC increased operant responding for high-fat pellets but decreased chow intake in both strains, suggesting that D2R stimulation may have enhanced the motivational drive to procure the fatty food while correspondingly decreasing the intake of regular food. These findings suggest that susceptibility to dietary obesity (prior to the onset of obesity) may not affect operant motivation for a palatable high fat food and that differential susceptibility to obesity may be related to differential sensitivity to D2R stimulation.

  6. Significant effect of Ca2+ on improving the heat resistance of lactic acid bacteria.

    Science.gov (United States)

    Huang, Song; Chen, Xiao Dong

    2013-07-01

    The heat resistance of lactic acid bacteria (LAB) has been extensively investigated due to its highly practical significance. Reconstituted skim milk (RSM) has been found to be one of the most effective protectant wall materials for microencapsulating microorganisms during convective drying, such as spray drying. In addition to proteins and carbohydrate, RSM is rich in calcium. It is not clear which component is critical in the RSM protection mechanism. This study investigated the independent effect of calcium. Ca(2+) was added to lactose solution to examine its influence on the heat resistance of Lactobacillus rhamnosus ZY, Lactobacillus casei Zhang, Lactobacillus plantarum P8 and Streptococcus thermophilus ND03. The results showed that certain Ca(2+) concentrations enhanced the heat resistance of the LAB strains to different extents, that is produced higher survival and shorter regrowth lag times of the bacterial cells. In some cases, the improvements were dramatic. More scientifically insightful and more intensive instrumental study of the Ca(2+) behavior around and in the cells should be carried out in the near future. In the meantime, this work may lead to the development of more cost-effective wall materials with Ca(2+) added as a prime factor. © 2013 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

  7. No effect on the short-term of a decrease in blood viscosity on insulin resistance.

    Science.gov (United States)

    Gnasso, Agostino; Cacia, Michele; Cortese, Claudio; Succurro, Elena; Andreozzi, Francesco; Carallo, Claudio; Irace, Concetta

    2018-01-01

    Blood viscosity (BV) might influence glucose delivery to peripheral tissues and play an important role in insulin resistance and diabetes mellitus. However, the exact relationship between BV and insulin resistance is not yet clear. Aim of the present study is to evaluate the effects of the acute reduction in BV on insulin resistance, in healthy male subjects. Fifteen healthy male blood donors have been studied before and 48 hours after blood donation. Blood and plasma viscosity have been measured at 37°C with a cone-plate viscometer. Insulin resistance has been evaluated by euglycemic/hyperinsulinemic clamp in eight subjects, and by iHOMA2 Index in further seven subjects. Blood viscosity was markedly reduced after blood donation (BV225 (cP) 4.53 ± 0.59 vs. 4.18 ± 0.31, p < 0.05). Insulin resistance was unchanged: MFFM clamp: 5.6 ± 4.5vs. 4.4 ± 2.2 and iHOMA2 Index 1.2 ± 0.6 vs. 1.2 ± 0.5, before vs. after respectively, p = NS. Blood pressure and lipids were unchanged after blood donation. The present results demonstrate that acute reduction of BV in healthy male subjects does not change the insulin resistance, measured using both euglycemic/hyperinsulinemic clamp and iHOMA2 Index. Further intervention studies are needed to assess the effect that the reduction in BV can have in subjects with insulin resistance.

  8. Evaporation of multicomponent chemical spills: When is liquid phase resistance significant?

    International Nuclear Information System (INIS)

    Berger, D.; Mackay, D.

    1993-01-01

    When chemicals are spilled on land or water, it is important to be able to estimate evaporation rates accurately. Conventional models used to predict evaporation rates of multicomponent spills assume that the entire resistance to evaporation lies in the vapor phase. Under certain conditions, an additional liquid phase resistance may be introduced, resulting in retarded evaporation rates. Existing models may thus fail to predict spill behavior accurately. A study is described whose objective is to elucidate the significance of the liquid phase resistance. Evaporation experiments were conducted in which a thin layer of synthetic oil (mineral oil enriched with compounds such as pentane, hexane, toluene, octane, and p-xylene) was exposed to prolonged evaporation in a metal tray at controlled wind speeds. Bulk samples of the spill layer were taken at specific time intervals and their composition was determined by gas chromatographic analysis. The results are compared to those from a theoretical model and to gas stripping experiments. The model is based on the evaporative flux equation incorporating Raoult's law; inputs are the air-oil partition coefficient for each component and the composition of the synthetic oil on a volume and mole fraction basis. The study has enabled the formation of vertical concentration profiles to be examined and liquid phase mass transfer coefficients to be estimated. The results imply that liquid-phase resistance effects are likely to be important for the most volatile components. Contaminated areas may thus continue to be hazardous, even though model predictions indicate otherwise. 7 refs., 3 figs., 2 tabs

  9. Aroclor 1248 exposure leads to immunomodulation, decreased disease resistance and endocrine disruption in the brown bullhead, Ameiurus nebulosus

    Science.gov (United States)

    Iwanowicz, L.R.; Blazer, V.S.; McCormick, S.D.; Van Veld, P.A.; Ottinger, C.A.

    2009-01-01

    The brown bullhead Ameiurus nebulosus is a species of the family Ictaluridae commonly used as a sentinel of environmental contamination. While these fish have been utilized for this purpose in areas contaminated with polychlorinated biphenyls (PCBs), few controlled, laboratory-based studies have been designed to document the effects of PCB mixtures in this species. Here, brown bullhead were exposed to the PCB mixture, Aroclor 1248, via intraperitoneal injection and the effects on immune function, plasma hormones and disease resistance were evaluated. Exposure to this mixture led to a decrease in bactericidal activity and circulating antibodies to Edwardsiella ictaluri present from a previous exposure to this pathogen. A subsequent E. ictaluri disease challenge led to significantly higher mortality in A1248 treated fish compared to vehicle-control fish. The mitogenic response to the T-cell mitogen, phytohemaglutinin-P, was increased compared to vehicle-control fish. The steroid hormone, cortisol, and the thyroid hormone, T3, were also significantly lower in A1248 exposed fish. In summary, we have validated a number of functional immune assays for application in brown bullhead immunotoxicity studies. Additionally, we have demonstrated that the PCB mixture (A1248) modulates both immune function and endocrine physiology in brown bullhead. Such data may compliment the interpretation of data yielded from applied field studies conducted in PCB contaminated aquatic ecosystems.

  10. Natural resistance to experimental feline infectious peritonitis virus infection is decreased rather than increased by positive genetic selection.

    Science.gov (United States)

    Pedersen, Niels C; Liu, Hongwei; Durden, Monica; Lyons, Leslie A

    2016-03-01

    A previous study demonstrated the existence of a natural resistance to feline infectious peritonitis virus (FIPV) among 36% of randomly bred laboratory cats. A genome wide association study (GWAS) on this population suggested that resistance was polygenic but failed to identify any strong specific associations. In order to enhance the power of GWAS or whole genome sequencing to identify strong genetic associations, a decision was made to positively select for resistance over three generations. The inbreeding experiment began with a genetically related parental (P) population consisting of three toms and four queens identified from among the survivors of the earlier study and belonging to a closely related subgroup (B). The subsequent effects of inbreeding were measured using 42 genome-wide STR markers. P generation cats produced 57 first filial (F1) kittens, only five of which (9.0%) demonstrated a natural resistance to FIPV infection. One of these five F1 survivors was then used to produce six F1/P-backcrosses kittens, only one of which proved resistant to FIP. Six of eight of the F1 and F1/P survivors succumbed to a secondary exposure 4-12 months later. Therefore, survival after both primary and secondary infection was decreased rather than increased by positive selection for resistance. The common genetic factor associated with this diminished resistance was a loss of heterozygosity. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  11. A New Ala-122-Asn Amino Acid Change Confers Decreased Fitness to ALS-Resistant Echinochloa crus-galli.

    Science.gov (United States)

    Panozzo, Silvia; Scarabel, Laura; Rosan, Valentina; Sattin, Maurizio

    2017-01-01

    Gene mutations conferring herbicide resistance may cause pleiotropic effects on plant fitness. Knowledge of these effects is important for managing the evolution of herbicide-resistant weeds. An Echinochloa crus-galli population resistant to acetolactate synthase (ALS) herbicides was collected in a maize field in north-eastern Italy and the cross-resistance pattern, resistance mechanism and fitness costs associated to mutant-resistant plants under field conditions in the presence or absence of intra-specific competition were determined. The study reports for the first time the Ala-122-Asn amino-acid change in the ALS gene that confers high levels of cross-resistance to all ALS inhibitors tested. Results of 3-year growth analysis showed that mutant resistant E. crus-galli plants had a delayed development in comparison with susceptible plants and this was registered in both competitive (3, 7, and 20 plants m -2 ) and non-competitive (spaced plants) situations. The number of panicles produced by resistant plants was also lower (about 40% fewer panicles) than susceptible plants under no-intraspecific competition. Instead, with the increasing competition level, the difference in panicle production at harvest time decreased until it became negligible at 20 plants m -2 . Evaluation of total dry biomass as well as biomass allocation in vegetative parts did not highlight any difference between resistant and susceptible plants. Instead, panicle dry weight was higher in susceptible plants indicating that they allocated more biomass than resistant ones to the reproductive organs, especially in no-competition and in competition situations at lower plant densities. The different fitness between resistant and susceptible phenotypes suggests that keeping the infestation density as low as possible can increase the reproduction success of the susceptible phenotype and therefore contribute to lowering the ratio between resistant and susceptible alleles. If adequately embedded in a

  12. A New Ala-122-Asn Amino Acid Change Confers Decreased Fitness to ALS-Resistant Echinochloa crus-galli

    Directory of Open Access Journals (Sweden)

    Silvia Panozzo

    2017-11-01

    Full Text Available Gene mutations conferring herbicide resistance may cause pleiotropic effects on plant fitness. Knowledge of these effects is important for managing the evolution of herbicide-resistant weeds. An Echinochloa crus-galli population resistant to acetolactate synthase (ALS herbicides was collected in a maize field in north-eastern Italy and the cross-resistance pattern, resistance mechanism and fitness costs associated to mutant-resistant plants under field conditions in the presence or absence of intra-specific competition were determined. The study reports for the first time the Ala-122-Asn amino-acid change in the ALS gene that confers high levels of cross-resistance to all ALS inhibitors tested. Results of 3-year growth analysis showed that mutant resistant E. crus-galli plants had a delayed development in comparison with susceptible plants and this was registered in both competitive (3, 7, and 20 plants m-2 and non-competitive (spaced plants situations. The number of panicles produced by resistant plants was also lower (about 40% fewer panicles than susceptible plants under no-intraspecific competition. Instead, with the increasing competition level, the difference in panicle production at harvest time decreased until it became negligible at 20 plants m-2. Evaluation of total dry biomass as well as biomass allocation in vegetative parts did not highlight any difference between resistant and susceptible plants. Instead, panicle dry weight was higher in susceptible plants indicating that they allocated more biomass than resistant ones to the reproductive organs, especially in no-competition and in competition situations at lower plant densities. The different fitness between resistant and susceptible phenotypes suggests that keeping the infestation density as low as possible can increase the reproduction success of the susceptible phenotype and therefore contribute to lowering the ratio between resistant and susceptible alleles. If adequately

  13. Paradoxical resistance of multiple myeloma to proteasome inhibitors by decreased levels of 19S proteasomal subunits

    DEFF Research Database (Denmark)

    Acosta-Alvear, Diego; Cho, Min Y; Wild, Thomas

    2015-01-01

    Hallmarks of cancer, including rapid growth and aneuploidy, can result in non-oncogene addiction to the proteostasis network that can be exploited clinically. The defining example is the exquisite sensitivity of multiple myeloma (MM) to 20S proteasome inhibitors, such as carfilzomib. However, MM...... patients invariably acquire resistance to these drugs. Using a next-generation shRNA platform, we found that proteostasis factors, including chaperones and stress-response regulators, controlled the response to carfilzomib. Paradoxically, 19S proteasome regulator knockdown induced resistance to carfilzomib...

  14. Decreased Resistance to Broad-Spectrum Cephalosporin in Escherichia coli from Healthy Broilers at Farms in Japan After Voluntary Withdrawal of Ceftiofur.

    Science.gov (United States)

    Hiki, Mototaka; Kawanishi, Michiko; Abo, Hitoshi; Kojima, Akemi; Koike, Ryoji; Hamamoto, Shuichi; Asai, Tetsuo

    2015-07-01

    The high prevalence of broad-spectrum cephalosporin (BSC) resistance in Escherichia coli isolates from healthy broilers at farms is a source of grave concern in Japan. In an effort to solve this problem, the off-label use of ceftiofur (CTF) at hatcheries was voluntarily withdrawn around March 2012. The objective of this study was to assess the effect of the voluntary withdrawal on the prevalence of BSC resistance in E. coli from healthy broilers at farms. A total of 693 E. coli isolates collected from 362 fecal samples of healthy broilers at farms between 2010 and 2013 were examined to determine their antimicrobial resistance profiles and β-lactamase genes. β-Lactamase genes were characterized by polymerase chain reaction and sequencing. BSC resistance was detected in 84 of the 693 E. coli isolates (12.1%) from healthy broilers between 2010 and 2013. The percentage of BSC-resistant E. coli isolates was significantly decreased: from 16.4% (32/195) in 2010 and 16.8% (27/161) in 2011 to 9.2% (19/206) in 2012 and 4.6% (6/131) in 2013 (2010 versus 2012: p=0.024, 2010 versus 2013: p=0.001, 2011 versus 2012: p=0.038, and 2011 versus 2013: p=0.001). Regarding ß-lactamase genes, 58 of the 84 BSC-resistant E. coli isolates (69.0%) harbored blaCMY-2. The prevalence of BSC resistance in E. coli isolated from healthy broilers at farms was markedly decreased within a year after the voluntary withdrawal from CTF use at hatcheries. This indicates that BSC resistance in E. coli isolates from broilers could be controlled by restricting the use of CTF at the hatchery level.

  15. Managing Instructor Cyberanxiety: The Role of Self-Efficacy in Decreasing Resistance to Change.

    Science.gov (United States)

    George, Gerard; Camarata, M. R.

    1996-01-01

    Discussion of educational technology innovations focuses on some of the behavioral challenges facing the drive toward multimedia instruction and suggests a method by which instructor resistance to technological change can be lessened or eliminated based on the concept of self-efficacy. A typology of instructors is explained. (Author/LRW)

  16. Mitochondrial-Targeted Catalase Protects Against High-Fat Diet-Induced Muscle Insulin Resistance by Decreasing Intramuscular Lipid Accumulation.

    Science.gov (United States)

    Lee, Hui-Young; Lee, Jae Sung; Alves, Tiago; Ladiges, Warren; Rabinovitch, Peter S; Jurczak, Michael J; Choi, Cheol Soo; Shulman, Gerald I; Samuel, Varman T

    2017-08-01

    We explored the role of reactive oxygen species (ROS) in the pathogenesis of muscle insulin resistance. We assessed insulin action in vivo with a hyperinsulinemic-euglycemic clamp in mice expressing a mitochondrial-targeted catalase (MCAT) that were fed regular chow (RC) or a high-fat diet (HFD) or underwent an acute infusion of a lipid emulsion. RC-fed MCAT mice were similar to littermate wild-type (WT) mice. However, HFD-fed MCAT mice were protected from diet-induced insulin resistance. In contrast, an acute lipid infusion caused muscle insulin resistance in both MCAT and WT mice. ROS production was decreased in both HFD-fed and lipid-infused MCAT mice and cannot explain the divergent response in insulin action. MCAT mice had subtly increased energy expenditure and muscle fat oxidation with decreased intramuscular diacylglycerol (DAG) accumulation, protein kinase C-θ (PKCθ) activation, and impaired insulin signaling with HFD. In contrast, the insulin resistance with the acute lipid infusion was associated with increased muscle DAG content in both WT and MCAT mice. These studies suggest that altering muscle mitochondrial ROS production does not directly alter the development of lipid-induced insulin resistance. However, the altered energy balance in HFD-fed MCAT mice protected them from DAG accumulation, PKCθ activation, and impaired muscle insulin signaling. © 2017 by the American Diabetes Association.

  17. Chronic intermittent hypoxia from pedo-stage decreases glucose transporter 4 expression in adipose tissue and causes insulin resistance.

    Science.gov (United States)

    Chen, Lin; Cao, Zhao-long; Han, Fang; Gao, Zhan-cheng; He, Quan-ying

    2010-02-20

    The persistence of sleep disordered breathing (SDB) symptoms after tonsil and/or adenoid (T&A) surgery are common in children with obstructive sleep apnea (OSA). We tested the hypothesis that disturbances of glucose transporters (GLUTs) in intraabdominal adipose tissue caused by chronic intermittent hypoxia (CIH) from the pedo-period could facilitate the appearance of periphery insulin resistance in Sprague-Dawley (SD) rats. We tested the hypothesis that the changes of GLUTs in adipose tissue may be one of the reasons for persistent SDB among clinical OSA children after T&A surgery. Thirty 21-day-old SD rats were randomly divided into a CIH group, a chronic continuous hypoxia (CCH) group, and a normal oxygen group (control group) and exposed for 40 days. The changes of weight, fasting blood glucose and fasting blood insulin levels were measured. Hyperinsulinemic-euglycemic clamp techniques were used to measure insulin resistance in each animal. Real-time quantitative PCR and Western blotting were used to measure GLUT mRNA and proteins in intraabdominal adipose tissue. Additional intraabdomial white adipose tissue (WAT) was also processed into paraffin sections and directly observed for GLUTs1-4 expression. When compared with control group, CIH increased blood fasting insulin levels, (245.07 +/- 53.89) pg/ml vs. (168.63 +/- 38.70) pg/ml, P = 0.038, and decreased the mean glucose infusion rate (GIR), (7.25 +/- 1.29) mg x kg(-1) x min(-1) vs. (13.34 +/- 1.54) mg x kg(-1) x min(-1), P < 0.001. GLUT-4 mRNA and protein expression was significantly reduced after CIH compared with CCH or normal oxygen rats, 0.002 +/- 0.002 vs. 0.039 +/- 0.009, P < 0.001; 0.642 +/- 0.073 vs. 1.000 +/- 0.103, P = 0.035. CIH in young rats could induce insulin resistance via adverse effects on glycometabolism. These findings emphasize the importance of early detection and treatment of insulin insensitivity in obese childhood OSA.

  18. Cranberry juice concentrate does not significantly decrease the incidence of acquired bacteriuria in female hip fracture patients receiving urine catheter: a double-blind randomized trial

    Directory of Open Access Journals (Sweden)

    Gunnarsson AK

    2017-01-01

    Full Text Available Anna-Karin Gunnarsson,1 Lena Gunningberg,2 Sune Larsson,1 Kenneth B Jonsson1 1Institution of Surgical Sciences, Uppsala University, Uppsala, Sweden; 2Institution of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden Background: Urinary tract infection (UTI is a common complication among patients with hip fractures. Receiving an indwelling urinary catheter is a risk factor for developing UTIs. Treatment of symptomatic UTIs with antibiotics is expensive and can result in the development of antimicrobial resistance. Cranberries are thought to prevent UTI. There is no previous research on this potential effect in patients with hip fracture who receive urinary catheters. Aim: The aim of this study is to investigate whether intake of cranberry juice concentrate preoperatively decreases the incidence of postoperative UTIs in hip fracture patients that received a urinary catheter. Design: This study employed a randomized, placebo-controlled double-blind trial. Method: Female patients, aged 60 years and older, with hip fracture (n=227 were randomized to receive cranberry or placebo capsules daily, from admission, until 5 days postoperatively. Urine cultures were obtained at admission, 5 and 14 days postoperatively. In addition, Euro Qual five Dimensions assessments were performed and patients were screened for UTI symptoms. Result: In the intention-to-treat analysis, there was no difference between the groups in the proportion of patients with hospital-acquired postoperative positive urine cultures at any time point. When limiting the analysis to patients that ingested at least 80% of the prescribed capsules, 13 of 33 (39% in the placebo group and 13 of 47 (28% in the cranberry group (P=0.270 had a positive urine culture at 5 days postoperatively. However, this difference was not statistically significant (P=0.270. Conclusion: Cranberry concentrate does not seem to effectively prevent UTIs in female patients with hip fracture and

  19. Aggressive regimens for multidrug-resistant tuberculosis decrease all-cause mortality.

    Directory of Open Access Journals (Sweden)

    Carole D Mitnick

    Full Text Available A better understanding of the composition of optimal treatment regimens for multidrug-resistant tuberculosis (MDR-TB is essential for expanding universal access to effective treatment and for developing new therapies for MDR-TB. Analysis of observational data may inform the definition of an optimized regimen.This study assessed the impact of an aggressive regimen-one containing at least five likely effective drugs, including a fluoroquinolone and injectable-on treatment outcomes in a large MDR-TB patient cohort.This was a retrospective cohort study of patients treated in a national outpatient program in Peru between 1999 and 2002. We examined the association between receiving an aggressive regimen and the rate of death.In total, 669 patients were treated with individualized regimens for laboratory-confirmed MDR-TB. Isolates were resistant to a mean of 5.4 (SD 1.7 drugs. Cure or completion was achieved in 66.1% (442 of patients; death occurred in 20.8% (139. Patients who received an aggressive regimen were less likely to die (crude hazard ratio [HR]: 0.62; 95% CI: 0.44,0.89, compared to those who did not receive such a regimen. This association held in analyses adjusted for comorbidities and indicators of severity (adjusted HR: 0.63; 95% CI: 0.43,0.93.The aggressive regimen is a robust predictor of MDR-TB treatment outcome. TB policy makers and program directors should consider this standard as they design and implement regimens for patients with drug-resistant disease. Furthermore, the aggressive regimen should be considered the standard background regimen when designing randomized trials of treatment for drug-resistant TB.

  20. Mechanisms of quinolone resistance in Escherichia coli: characterization of nfxB and cfxB, two mutant resistance loci decreasing norfloxacin accumulation.

    Science.gov (United States)

    Hooper, D C; Wolfson, J S; Souza, K S; Ng, E Y; McHugh, G L; Swartz, M N

    1989-03-01

    Two genetic loci selected for norfloxacin (nfxB) and ciprofloxacin (cfxB) resistance were characterized. Both mutations have previously been shown to confer pleiotropic resistance to quinolones, chloramphenicol, and tetracycline and to decrease expression of porin outer-membrane protein OmpF. nfxB was shown to map at about 19 min and thus to be genetically distinct from ompF (21 min), and cfxB was shown to be very closely linked to marA (34 min). cfxB was dominant over cfxB+ in merodiploids, in contrast to other quinolone resistance mutations. The two loci appear to interact functionally, because nfxB was not expressed in the presence of marA::Tn5. Both nfxB and cfxB decreased the expression of ompF up to 50-fold at the posttranscriptional level as determined in strains containing ompF-lacZ operon and protein fusions. Both mutations also decreased norfloxacin accumulation in intact cells. This decrease in accumulation was abolished by energy inhibitors and by removal of the outer membrane. These findings, in conjunction with those of Cohen et al. (S. P. Cohen, D. C. Hooper, J. S. Wolfson, K. S. Souza, L. M. McMurry, and S. B. Levy, Antimicrob. Agents Chemother. 32:1187-1191, 1988), suggest a model for quinolone resistance by decreased permeation in which decreased diffusion through porin channels in the outer membrane interacts with a saturable drug efflux system at the inner membrane.

  1. Reversible lysine-specific demethylase 1 antagonist HCI-2509 inhibits growth and decreases c-MYC in castration- and docetaxel-resistant prostate cancer cells.

    Science.gov (United States)

    Gupta, S; Weston, A; Bearrs, J; Thode, T; Neiss, A; Soldi, R; Sharma, S

    2016-12-01

    Lysine-specific demethylase 1 (LSD1 or KDM1A) overexpression correlates with poor survival and castration resistance in prostate cancer. LSD1 is a coregulator of ligand-independent androgen receptor signaling promoting c-MYC expression. We examined the antitumor efficacy of LSD1 inhibition with HCI-2509 in advanced stages of prostate cancer. Cell survival, colony formation, histone methylation, c-MYC level, c-MYC expression, cell cycle changes and in vivo efficacy were studied in castration-resistant prostate cancer cells upon treatment with HCI-2509. In vitro combination studies, using HCI-2509 and docetaxel, were performed to assess the synergy. Cell survival, colony formation, histone methylation and c-myc levels were studied in docetaxel-resistant prostate cancer cells treated with HCI-2509. HCI-2509 is cytotoxic and inhibits colony formation in castration-resistant prostate cancer cells. HCI-2509 treatment causes a dose-dependent increase in H3K9me2 (histone H3lysine 9) levels, a decrease in c-MYC protein, inhibition of c-MYC expression and accumulation in the G0/G1 phase of the cell cycle in these cells. PC3 xenografts in mice have a significant reduction in tumor burden upon treatment with HCI-2509 with no associated myelotoxicity or weight loss. More synergy is noted at sub-IC 50 (half-maximal inhibitory concentration) doses of docetaxel and HCI-2509 in PC3 cells than in DU145 cells. HCI-2509 has growth-inhibitory efficacy and decreases the c-myc level in docetaxel-resistant prostate cancer cells. LSD1 inhibition with HCI-2509 decreases the c-MYC level in poorly differentiated prostate cancer cell lines and has a therapeutic potential in castration- and docetaxel-resistant prostate cancer.

  2. Decreased nuclear matrix DNA topoisomerase II in human leukemia cells resistant to VM-26 and m-AMSA

    International Nuclear Information System (INIS)

    Fernandes, D.J.; Danks, M.K.; Beck, W.T.

    1990-01-01

    CEM leukemia cells selected for resistance to VM-26 (CEM/VM-1) are cross-resistant to various other DNA topoisomerase II inhibitors but not to Vinca alkaloids. Since DNA topoisomerase II is a major protein of the nuclear matrix, the authors asked if alterations in nuclear matrix topoisomerase II might be important in this form of multidrug resistance. Pretreatment of drug-sensitive CEM cells for 2 h with either 5 μM VM-26 or 3 μM m-AMSA reduced the specific activity of newly replicated DNA on the nuclear matrix by 75 and 50%, respectively, relative to that of the bulk DNA. The decatenating and unknotting activities of DNA topoisomerase II were 6- and 7-fold lower, respectively, in the nuclear matrix preparations from the CEM/VM-1 cells compared to parental CEM cells. Western blot analysis revealed that the amount of immunoreactive topoisomerase II in the nuclear matrices of the CEM/VM-1 cells decreased 3.2-fold relative to that in CEM cells. Increasing the NaCl concentration used in the matrix isolation procedure from 0.2 to 1.8 M resulted in a progressive decrease in the specific activity of topoisomerase II in matrices of CEM/VM-1 but not CEM cells, which suggested that the association of the enzyme with the matrix is altered in the resistant cells. These data support the hypothesis that resistance to VM-26 and m-AMSA is directly related to the decreased activity of nuclear matrix topoisomerase II. In CEM/VM-1 cells the interaction of either VM-26 or m-AMSA with nuclear matrix topoisomerase II is specifically diminished

  3. Mechanisms of quinolone resistance in Escherichia coli: characterization of nfxB and cfxB, two mutant resistance loci decreasing norfloxacin accumulation.

    OpenAIRE

    Hooper, D C; Wolfson, J S; Souza, K S; Ng, E Y; McHugh, G L; Swartz, M N

    1989-01-01

    Two genetic loci selected for norfloxacin (nfxB) and ciprofloxacin (cfxB) resistance were characterized. Both mutations have previously been shown to confer pleiotropic resistance to quinolones, chloramphenicol, and tetracycline and to decrease expression of porin outer-membrane protein OmpF. nfxB was shown to map at about 19 min and thus to be genetically distinct from ompF (21 min), and cfxB was shown to be very closely linked to marA (34 min). cfxB was dominant over cfxB+ in merodiploids, ...

  4. Alkaline fermentation of waste sludge causes a significant reduction of antibiotic resistance genes in anaerobic reactors.

    Science.gov (United States)

    Huang, Haining; Zheng, Xiong; Chen, Yinguang; Liu, Hui; Wan, Rui; Su, Yinglong

    2017-02-15

    Alkaline fermentation has been reported to be an effective method to recover valuable products from waste sludge. However, to date, the potential effect of alkaline pH on the fate of antibiotic resistance genes (ARGs) during anaerobic fermentation of sludge has never been documented. In this study, the target ARGs in sludge was observed to be removed effectively and stably when sludge was anaerobically fermented at pH10. Compared with the control (without pH adjustment), the abundances of target ARGs at pH10 were reduced by 0.87 (sulI), 1.36 (sulII), 0.42 (tet(O)), 1.11 (tet(Q)), 0.79 (tet(C)) and 1.04 (tet(X)) log units. Further investigations revealed that alkaline fermentation shifted the community structures of potential ARGs hosts. Moreover, alkaline fermentation remarkably decreased the quantities and the ARGs-possessing ability of genetic vectors (plasmid DNA, extracellular DNA and phage DNA), which might limit the transfer of ARGs via conjugation, transformation and transduction. These results suggest that the shifted compositions of gene hosts and restricted gene transfer potential might be the critical reasons for the attenuation of ARGs at pH10. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Horizontal infection control strategy decreases methicillin-resistant Staphylococcus aureus infection and eliminates bacteremia in a surgical ICU without active surveillance.

    Science.gov (United States)

    Traa, Maria X; Barboza, Lorena; Doron, Shira; Snydman, David R; Noubary, Farzad; Nasraway, Stanley A

    2014-10-01

    Methicillin-resistant Staphylococcus aureus infection is a significant contributor to morbidity and mortality in hospitalized patients worldwide. Numerous healthcare bodies in Europe and the United States have championed active surveillance per the "search and destroy" model. However, this strategy is associated with significant economic, logistical, and patient costs without any impact on other hospital-acquired pathogens. We evaluated whether horizontal infection control strategies could decrease the prevalence of methicillin-resistant S. aureus infection in the ICU, without the need for active surveillance. Retrospective, observational study in the surgical ICU of a tertiary care medical center in Boston, MA, from 2005 to 2012. A total of 6,697 patients in the surgical ICU. Evidence-based infection prevention strategies were implemented in an iterative fashion, including 1) hand hygiene program with refresher education campaign, 2) chlorhexidine oral hygiene program, 3) chlorhexidine bathing, 4) catheter-associated bloodstream infection program, and 5) daily goals sheets. The prevalence of methicillin-resistant S. aureus infection fell from 2.66 to 0.69 per 1,000 patient days from 2005 to 2012, an average decrease of 21% per year. The biggest decline in rate of infection was detected in 2008, which may suggest that the catheter-associated bloodstream infection prevention program was particularly effective. Among 4,478 surgical ICU admissions over the last 5 years, not a single case of methicillin-resistant S. aureus bacteremia was observed. Aggressive multifaceted horizontal infection control is an effective strategy for reducing the prevalence of methicillin-resistant S. aureus infection and eliminating methicillin-resistant S. aureus bacteremia in the ICU without the need for active surveillance and decontamination.

  6. Early-life disruption of amphibian microbiota decreases later-life resistance to parasites.

    Science.gov (United States)

    Knutie, Sarah A; Wilkinson, Christina L; Kohl, Kevin D; Rohr, Jason R

    2017-07-20

    Changes in the early-life microbiota of hosts might affect infectious disease risk throughout life, if such disruptions during formative times alter immune system development. Here, we test whether an early-life disruption of host-associated microbiota affects later-life resistance to infections by manipulating the microbiota of tadpoles and challenging them with parasitic gut worms as adults. We find that tadpole bacterial diversity is negatively correlated with parasite establishment in adult frogs: adult frogs that had reduced bacterial diversity as tadpoles have three times more worms than adults without their microbiota manipulated as tadpoles. In contrast, adult bacterial diversity during parasite exposure is not correlated with parasite establishment in adult frogs. Thus, in this experimental setup, an early-life disruption of the microbiota has lasting reductions on host resistance to infections, which is possibly mediated by its effects on immune system development. Our results support the idea that preventing early-life disruption of host-associated microbiota might confer protection against diseases later in life.Early-life microbiota alterations can affect infection susceptibility later in life, in animal models. Here, Knutie et al. show that manipulating the microbiota of tadpoles leads to increased susceptibility to parasitic infection in adult frogs, in the absence of substantial changes in the adults' microbiota.

  7. Decrease of the surface resistance in superconducting niobium resonator cavities by the microwave field

    Energy Technology Data Exchange (ETDEWEB)

    Ciovati, Gianluigi [Thomas Jefferson National Accelerator Facility, Newport News, VA (United States); Dhakal, Pashupati [Thomas Jefferson National Accelerator Facility, Newport News, VA (United States); Gurevich, Alexander V. [Old Dominion University, Norfolk, VA (United States)

    2014-03-03

    Measurements of the quality factor, Q, of Nb superconducting microwave resonators often show that Q increases by {approx_equal} 10%–30% with increasing radio-frequency (rf) field, H, up to {approx} 15-20 mT. Recent high temperature heat treatments can amplify this rf field-induced increase of Q up to {approx_equal} 50%–100% and extend it to much higher fields, but the mechanisms of the enhancement of Q(H) remain unclear. Here, we suggest a method to reveal these mechanisms by measuring temperature dependencies of Q at different rf field amplitudes. We show that the increase of Q(H) does not come from a field dependent quasi-particles activation energy or residual resistance, but rather results from the smearing of the density of state by the rf field.

  8. Decreased Time to Treatment Initiation for Multidrug-Resistant Tuberculosis Patients after Use of Xpert MTB/RIF Test, Latvia.

    Science.gov (United States)

    Stagg, Helen R; White, Peter J; Riekstiņa, Vija; Cīrule, Andra; Šķenders, Ģirts; Leimane, Vaira; Kuksa, Liga; Dravniece, Gunta; Brown, James; Jackson, Charlotte

    2016-03-01

    Few studies have examined whether the Xpert MTB/RIF test improves time to treatment initiation for persons with multidrug-resistant tuberculosis (MDR TB). We determined the impact of this test in Latvia, where it was introduced in 2010. After descriptive analyses of pulmonary MDR TB patients in Latvia during 2009-2012, time to treatment initiation was calculated, and univariate and multivariable accelerated failure time models were constructed. Univariate results showed strong evidence of an association between having rifampin-resistant TB detected by Xpert MTB/RIF and reduced time to treatment initiation versus the test not being used. A multivariable model stratifying by previous TB showed similar results. Our finding that in Latvia, time to treatment initiation was decreased for MDR TB cases that were rifampin-resistant TB by XpertMTB/RIF has implications for the use of this test in other settings with a high burden of MDR TB in which rifampin resistance is highly predictive of MDR TB.

  9. The small molecule triclabendazole decreases the intracellular level of cyclic AMP and increases resistance to stress in Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Yong Joo Lee

    Full Text Available The Ras-adenylyl cyclase-protein kinase A nutrient-sensing pathway controls metabolism, proliferation and resistance to stress in Saccharomyces cerevisiae. The genetic disruption of this pathway increases resistance to a variety of stresses. We show here that the pharmacological inhibition of this pathway by the drug triclabendazole increases resistance to oxidants, heat stress and extends the chronological life. Evidence is presented that triclabendazole decreases the intracellular level of cyclic AMP by inhibiting adenylyl cyclase and triggers the parallel rapid translocation of the stress-resistance transcription factor Msn2 from the cytosol into the nucleus, as deduced from experiments employing a strain in which MSN2 is replaced with MSN2-GFP (GFP, green fluorescent protein. Msn2 and Msn4 are responsible for activating the transcription of numerous genes that encode proteins that protect cells from stress. The results are consistent with triclabendazole either inhibiting the association of Ras with adenylyl cyclase or directly inhibiting adenylyl cyclase, which in turn triggers Msn2/4 to enter the nucleus and activate stress-responsible element gene expression.

  10. Models and Mechanisms of Acquired Antihormone Resistance in Breast Cancer: Significant Clinical Progress Despite Limitations

    Science.gov (United States)

    Sweeney, Elizabeth E.; McDaniel, Russell E.; Maximov, Philipp Y.; Fan, Ping; Jordan, V. Craig

    2012-01-01

    Translational research for the treatment and prevention of breast cancer depends upon the four Ms: models, molecules, and mechanisms in order to create medicines. The process, to target the estrogen receptor (ER) in estrogen-dependent breast cancer, has yielded significant advances in patient survivorship and the first approved medicines (tamoxifen and raloxifene) to reduce the incidence of any cancer in high- or low-risk women. This review focuses on the critical role of the few ER-positive cell lines (MCF-7, T47D, BT474, ZR-75) that continue to advance our understanding of the estrogen-regulated biology of breast cancer. More importantly, the model cell lines have provided an opportunity to document the development and evolution of acquired antihormone resistance. The description of this evolutionary process that occurs in micrometastatic disease during up to a decade of adjuvant therapy would not be possible in the patient. The use of the MCF-7 breast cancer cell line in particular has been instrumental in discovering a vulnerability of ER-positive breast cancer exhaustively treated with antihormone therapy. Physiologic estradiol acts as an apoptotic trigger to cause tumor regression. These unanticipated findings in the laboratory have translated to clinical advances in our knowledge of the paradoxical role of estrogen in the life and death of breast cancer. PMID:23308083

  11. [Role of SPHK1 regulates multi-drug resistance of small cell lung cancer 
and its clinical significance].

    Science.gov (United States)

    Yang, Lan; Hu, Honglin; Deng, Ying; Bai, Yifeng

    2014-11-01

    Lung cancer is the leading cause of cancer-related deaths worldwide. Approximately 15% of all histological types consist of small cell lung cancer (SCLC). Chemotherapy is one of the major treatment method. Though the current first-line standard chemotherapy regimen for SCLC is active in most SCLC cases, however the disease recurs shortly after the first successful treatment with multi-drug resistance (MDR) phenotype. Our previously study showed that SPHK1 was associated with MDR in SCLC. The aim of this study is to investigate the role of sphingosine kinase 1 (SPHK1) showed in small cell lung multi-drug resistance. Firstly, the analysis of QRT-PCR and Western blot were used to study differential expression of SPHK1 from mRNA and protein levels in both the H69 and H69AR cell lines. Then, Downregulation of SPHK1 by transfection with siRNA in H69AR. Moreover, the sensitivities of cells to chemotherapy drugs such as ADM, DDP, VP-16 were detected by CCK8 assay. The change of cell cycle and apoptosis rate were detected by flow cytometry. Meanwhile, expression of SPHK1 in clinical specimens were detected by QT-PCR and immunohistochemistry. Relation of SPHK1 expression with clinicopathological features and prognosis of patients was studied. The expression of SPHK1 was significantly decreased in H69AR cells that in the H69 cells. The sensitivities of H69AR cells to chemotherapy drugs were increased when up-regulated the expression of SPHK1, enforced SPHK1 expression increased cell apoptosis and the cell cycle arrest in G0/G1 phase in H69AR cells, the expression of SPHK1 was not associated with gender, age, but significantly correlated with clinical stage, chemosensitivity and overall survival (Presistance, SPHK1 may be as potentialtarget gene to evaluate the chemosensitivity and clinical prognostic for SCLC.

  12. Deregulation of apoptotic volume decrease and ionic movements in multidrug-resistant tumor cells: role of chloride channels

    DEFF Research Database (Denmark)

    Poulsen, Kristian Arild; Andersen, E C; Hansen, C F

    2010-01-01

    Changes in cell volume and ion gradients across the plasma membrane play a pivotal role in the initiation of apoptosis. Here we explore the kinetics of apoptotic volume decrease (AVD) and ion content dynamics in wild-type (WT) and multidrug-resistant (MDR) Ehrlich ascites tumor cells (EATC). In WT...... EATC, induction of apoptosis with cisplatin (5 muM) leads to three distinctive AVD stages: an early AVD(1) (4-12 h), associated with a 30% cell water loss; a transition stage AVD(T) ( approximately 12 to 32 h), where cell volume is partly recovered; and a secondary AVD(2) (past 32 h), where cell volume...... was further reduced. AVD(1) and AVD(2) were coupled to net loss of Cl(-), K(+), Na(+), and amino acids (ninhydrin-positive substances), whereas during AVD(T), Na(+) and Cl(-) were accumulated. MDR EATC was resistant to cisplatin, showing increased viability and less caspase 3 activation. Compared with WT EATC...

  13. Increased intracellular Ca2+decreases cisplatin resistance by regulating iNOS expression in human ovarian cancer cells.

    Science.gov (United States)

    Yu, Yang; Xie, Qi; Liu, Weimin; Guo, Yuting; Xu, Na; Xu, Lu; Liu, Shibing; Li, Songyan; Xu, Ye; Sun, Liankun

    2017-02-01

    Previous studies have reported that intracellular Ca 2+ signals and inducible nitric oxide synthase (iNOS) are involved in cell apoptosis. However, the role of iNOS in cisplatin resistance in ovarian cancer remains unclear. Here, we demonstrate that SKOV3/DDP ovarian cancer cells were more resistant to cisplatin than were SKOV3 ovarian cancer cells. The expression of intracellular Ca 2+ and iNOS was more strongly induced by cisplatin in SKOV3 cells than in SKOV3/DDP cells. TAT-conjugated IP3R-derived peptide (TAT-IDP S ) increased cisplatin-induced iNOS expression and apoptosis in SKOV3/DDP cells. 2-Aminoethoxydiphenyl borate (2-APB) decreased cisplatin-induced iNOS expression and apoptosis in SKOV3 cells. Thus, iNOS induction may be a valuable strategy for improving the anti-tumor efficacy of cisplatin in ovarian cancer. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  14. Cluster of Neisseria gonorrhoeae Isolates With High-level Azithromycin Resistance and Decreased Ceftriaxone Susceptibility, Hawaii, 2016.

    Science.gov (United States)

    Katz, Alan R; Komeya, Alan Y; Kirkcaldy, Robert D; Whelen, A Christian; Soge, Olusegun O; Papp, John R; Kersh, Ellen N; Wasserman, Glenn M; O'Connor, Norman P; O'Brien, Pamela S; Sato, Douglas T; Maningas, Eloisa V; Kunimoto, Gail Y; Tomas, Juval E

    2017-09-15

    The Centers for Disease Control and Prevention (CDC) currently recommends dual therapy with ceftriaxone and azithromycin for gonorrhea to ensure effective treatment and slow emergence of antimicrobial resistance. Since 2013, the prevalence of reduced azithromycin susceptibility increased in the United States; however, these strains were highly susceptible to cephalosporins. We identified a cluster of Neisseria gonorrhoeae isolates with high-level azithromycin resistance, several of which also demonstrated decreased ceftriaxone susceptibility. Eight N. gonorrhoeae isolates collected from 7 patients on Oahu, Hawaii, seen 21 April 2016 through 10 May 2016 underwent routine Etest antimicrobial susceptibility testing by the Hawaii Department of Health. All demonstrated elevated azithromycin minimum inhibitory concentrations (MICs) >256 μg/mL and elevated ceftriaxone MICs (≥0.125 μg/mL). Isolates were sent to the University of Washington and CDC for confirmatory agar dilution testing; sequence data were sent to CDC for analysis. All patients were interviewed and treated, and when possible, partners were interviewed, tested, and treated. All isolates had azithromycin MICs >16 µg/mL and 5 had ceftriaxone MICs = 0.125 µg/mL by agar dilution. All isolates were β-lactamase positive and were resistant to penicillin, tetracycline, and ciprofloxacin. Genomic analysis revealed genetic relatedness. No patients reported recent travel or antibiotic use, and no male patients reported male sex partners. All patients were successfully treated. This cluster of genetically related gonococcal isolates with decreased ceftriaxone susceptibility and high-level azithromycin resistance may bring the threat of treatment failure in the United States with the current recommended dual therapy one step closer. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  15. Significance of steel electrical resistance method in the evaluation of reinforcement corrosion in cementitious systems

    Directory of Open Access Journals (Sweden)

    Krajci, L.

    2004-06-01

    Full Text Available The suitable detection system of steel reinforcement corrosion in concrete structures contributes to the reduction of their maintenance costs. Method of steel electrical resistance represents non-destructive monitoring of steel in cementitious systems. Specially prepared and arranged test specimen of steel as a corrosion sensor is embedded in mortar specimen. Verification tests of this method based on chloride corrosion of steel in mortars as well as its visual inspection are introduced. Significance of steel electrical resistance method lies in the expression of steel corrosion by these quantitative parameters: reduction of cross-section of steel, thickness of corroded layer and loss of weight of steel material. This method is an integral method that allows the indirect determination of mentioned corrosion characteristics. The comparison of verified method with gravimetric evaluation of steel corrosion gives a good correspondence. Test results on mortars with calcium chloride dosages between 0.5% and 4.0% by weight of cement prove high sensitiveness and reliability of steel electrical resistance method.

    La utilización de un sistema de detección de la corrosión de las armaduras en estructuras de hormigón puede contribuir a la reducción de sus costes de mantenimiento. El método de la resistencia eléctrica del acero consiste en la monitorización no-destructiva realizada sobre el acero en sistemas cementantes. Dentro de la muestra de mortero se coloca el sistema de detección, especialmente preparado y fijado, actuando como un sensor de la corrosión. En este trabajo se presentan ensayos de verificación de este método, junto con inspecciones visuales, en morteros sometidos a corrosión de armaduras por efecto de los cloruros. La efectividad de este método de la resistencia eléctrica del acero se expresa, en la corrosión de armaduras, de acuerdo a los siguientes parámetros cuantitativos: reducción de la sección transversal del

  16. Significance of insulin resistance and oxidative stress in dairy cattle with subclinical ketosis during the transition period.

    Science.gov (United States)

    Youssef, Mohamed; El-Ashker, Maged

    2017-02-01

    Health problems occurring during the transition period in dairy cattle are of utmost importance as they can decrease the animal's reproductive performance and favor the development of various metabolic diseases with resultant significant reproductive disorders. Among the commonly reported metabolic diseases occurring during that time, hyperketonemia is the most prevalent and could provoke a significant economic impact. The failing of a dairy cow to transit optimally between pregnancy and lactation is economically very relevant and should be considered. Until now, the role of insulin resistance (IR) in the etiology of subclinical ketosis (SCK) in dairy cattle is not clearly understood. This review aims to shed some light on the role of IR and oxidative stress in dairy cows with SCK during the transition period. The data presented in this review demonstrates that dairy cows could be vulnerable to the development of negative energy balance during transition. Moreover, the transitional cows could succumb to both IR and oxidative stress; however, the exact role of IR in cows with SCK needs further investigations. It is imperative to elaborate a suitable nutritional strategy to facilitate an easy transit of cows through this critical period and to minimize health problems and improve productivity during lactation.

  17. Clinical significance of intronic variants in BRAF inhibitor resistant melanomas with altered BRAF transcript splicing

    OpenAIRE

    Pupo, Gulietta M.; Boyd, Suzanah C.; Fung, Carina; Carlino, Matteo S.; Menzies, Alexander M.; Pedersen, Bernadette; Johansson, Peter; Hayward, Nicholas K.; Kefford, Richard F.; Scolyer, Richard A.; Long, Georgina V.; Rizos, Helen

    2017-01-01

    Alternate BRAF splicing is the most common mechanism of acquired resistance to BRAF inhibitor treatment in melanoma. Recently, alternate BRAF exon 4?8 splicing was shown to involve an intronic mutation, located 51 nucleotides upstream of BRAF exon 9 within a predicted splicing branch point. This intronic mutation was identified in a single cell line but has not been examined in vivo. Herein we demonstrate that in three melanomas biopsied from patients with acquired resistance to BRAF inhibito...

  18. Rice Bran Protein Hydrolysates Improve Insulin Resistance and Decrease Pro-inflammatory Cytokine Gene Expression in Rats Fed a High Carbohydrate-High Fat Diet.

    Science.gov (United States)

    Boonloh, Kampeebhorn; Kukongviriyapan, Veerapol; Kongyingyoes, Bunkerd; Kukongviriyapan, Upa; Thawornchinsombut, Supawan; Pannangpetch, Patchareewan

    2015-08-03

    A high carbohydrate-high fat (HCHF) diet causes insulin resistance (IR) and metabolic syndrome (MS). Rice bran has been demonstrated to have anti-dyslipidemic and anti-atherogenic properties in an obese mouse model. In the present study, we investigated the beneficial effects of rice bran protein hydrolysates (RBP) in HCHF-induced MS rats. After 12 weeks on this diet, the HCHF-fed group was divided into four subgroups, which were orally administered RBP 100 or 500 mg/kg, pioglitazone 10 mg/kg, or tap water for a further 6 weeks. Compared with normal diet control group, the MS rats had elevated levels of blood glucose, lipid, insulin, and HOMA-IR. Treatment with RBP significantly alleviated all those changes and restored insulin sensitivity. Additionally, RBP treatment increased adiponectin and suppressed leptin levels. Expression of Ppar-γ mRNA in adipose tissues was significantly increased whereas expression of lipogenic genes Srebf1 and Fasn was significantly decreased. Levels of mRNA of proinflammatory cytokines, Il-6, Tnf-α, Nos-2 and Mcp-1 were significantly decreased. In conclusion, the present findings support the consumption of RBP as a functional food to improve insulin resistance and to prevent the development of metabolic syndrome.

  19. Short-chained oligo(ethylene oxide)-functionalized gold nanoparticles: realization of significant protein resistance.

    Science.gov (United States)

    Riley, Kathryn R; Sims, Christopher M; Wood, Imani T; Vanderah, David J; Walker, Marlon L

    2018-01-01

    Protein corona formed on nanomaterial surfaces play an important role in the bioavailability and cellular uptake of nanomaterials. Modification of surfaces with oligoethylene glycols (OEG) are a common way to improve the resistivity of nanomaterials to protein adsorption. Short-chain ethylene oxide (EO) oligomers have been shown to improve the protein resistance of planar Au surfaces. We describe the application of these EO oligomers for improved protein resistance of 30 nm spherical gold nanoparticles (AuNPs). Functionalized AuNPs were characterized using UV-Vis spectroscopy, dynamic light scattering (DLS), and zeta potential measurements. Capillary electrophoresis (CE) was used for separation and quantitation of AuNPs and AuNP-protein mixtures. Specifically, nonequilibrium capillary electrophoresis of equilibrium mixtures (NECEEM) was employed for the determination of equilibrium and rate constants for binding between citrate-stabilized AuNPs and two model proteins, lysozyme and fibrinogen. Semi-quantitative CE analysis was carried out for mixtures of EO-functionalized AuNPs and proteins, and results demonstrated a 2.5-fold to 10-fold increase in protein binding resistance to lysozyme depending on the AuNP surface functionalization and a 15-fold increase in protein binding resistance to fibrinogen for both EO oligomers examined in this study. Graphical abstract Using capillary electrophoresis, the addition of short-chained oligo(ethylene oxide) ligands to gold nanoparticles was shown to improve protein binding resistance up to 15-fold.

  20. Significance of Coexisting Mutations on Determination of the Degree of Isoniazid Resistance in Mycobacterium tuberculosis Strains.

    Science.gov (United States)

    Karunaratne, Galbokka Hewage Roshanthi Eranga; Wijesundera, Sandhya Sulochana; Vidanagama, Dhammika; Adikaram, Chamila Priyangani; Perera, Jennifer

    2018-04-23

    The emergence and spread of drug-resistant tuberculosis (TB) pose a threat to TB control in Sri Lanka. Isoniazid (INH) is a key element of the first-line anti-TB treatment regimen. Resistance to INH is mainly associated with point mutations in katG, inhA, and ahpC genes. The objective of this study was to determine mutations of these three genes in INH-resistant Mycobacterium tuberculosis (MTb) strains in Sri Lanka. Complete nucleotide sequence of the three genes was amplified by polymerase chain reaction and subjected to DNA sequencing. Point mutations in the katG gene were identified in 93% isolates, of which the majority (78.6%) were at codon 315. Mutations at codons 212 and 293 of the katG gene have not been reported previously. Novel mutations were recognized in the promoter region of the inhA gene (C deletion at -34), fabG1 gene (codon 27), and ahpC gene (codon 39). Single S315T mutation in the katG gene led to a high level of resistance, while a low level of resistance with high frequency (41%) was observed when katG codon 315 coexisted with the mutation at codon 463. Since most of the observed mutations of all three genes coexisted with the katG315 mutation, screening of katG315 mutations will be a useful marker for molecular detection of INH resistance of MTb in Sri Lanka.

  1. [Insulin resistance in chronic kidney disease: its clinical characteristics and prognosis significance].

    Science.gov (United States)

    Caravaca, F; Cerezo, I; Macías, R; García de Vinuesa, E; Martínez del Viejo, C; Villa, J; Martínez Gallardo, R; Ferreira, F; Hernández-Gallego, R

    2010-01-01

    Insulin resistance (IR) increases significantly the risk for cardiovascular disease (CV) in the general population. IR is a common metabolic disorder in patients with chronic kidney disease (CKD). However, the influence of IR on the evolution of CKD patients has scarcely been studied. This study aims to determine whether IR is associated with the progression of CKD, the development of new CV events, or all-cause mortality of non-diabetic patients with CKD stage 4 or 5 not yet on dialysis. The study group consisted of 365 non-diabetic patients (63 ± 16 year, 169 females) with GFR < 30 ml/min. The degree of IR was estimated by the Homeostasis Model Assessment parameter (HOMA). The outcome measures were: progression of CKD (composite of initiation of dialysis or doubling of baseline serum creatinine level), new cardiovascular events, and all-cause mortality. Unadjusted and multivariable-adjusted relative risks were calculated for HOMA either as a continuous or qualitative variable (tertiles), using Cox proportional hazards models. Mean HOMA value (± SD) was 4.28 ± 2.07. HOMA values correlated significantly with body mass index (beta = 0.37; p < 0.0001), plasma triglycerides (beta = 0.22; p < 0.0001), plasma albumin (beta = 0.19; p = 0.007), and serum phosphate (beta = 0.17; p = 0.031). Progression of CKD was observed in 234 patients (64%) with a median follow-up of 542 days. Patients with HOMA values in the lower tertile (< 3.13) showed a slower progression of CKD than that of the rest of study patients (log rank 4.16, p < 0.05). In adjusted models for age, sex, baseline GFR, body mass index, and proteinuria, HOMA values in the lower tertile entered as an independent variable in the best predictive equation for progression of CKD (HR 0.72, p < 0.03). Fifty-one patients developed a new CV event and 103 patients died during the study period (median follow-up of 1,103 days). HOMA did not relate to the development of new CV events or all-cause mortality in unadjusted

  2. Decreased abundance of type III secretion system-inducing signals in Arabidopsis mkp1 enhances resistance against Pseudomonas syringae

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, Jeffrey C.; Wan, Ying; Kim, Young-Mo; Pasa-Tolic, Ljiljana; Metz, Thomas O.; Peck, Scott C.

    2014-04-21

    Many phytopathogenic bacteria use a type III secretion system (T3SS) to inject defense-suppressing effector proteins into host cells. Genes encoding the T3SS are induced at the start of infection, yet host signals that initiate T3SS gene expression are poorly understood. Here we identify several plant-derived metabolites that induce the T3SS in the bacterial pathogen Pseudomonas syringae pv tomato DC3000. In addition, we report that mkp1 (mapk phosphatase 1), an Arabidopsis mutant that is more resistant to bacterial infection, produces decreased levels of these T3SS-inducing metabolites. Consistent with the observed decrease in these metabolites, T3SS effector delivery by DC3000 was impaired in mkp1. Addition of the bioactive metabolites to the mkp1-DC3000 interaction fully restored T3SS effector delivery and suppressed enhanced resistance in mkp1. Together, these results demonstrate that DC3000 perceives multiple signals derived from plants to initiate their virulence program, and reveal a new layer of molecular communication between plants and these pathogenic bacteria.

  3. Increased Nitric Oxide Bioavailability and Decreased Sympathetic Modulation Are Involved in Vascular Adjustments Induced by Low-Intensity Resistance Training

    Science.gov (United States)

    Macedo, Fabrício N.; Mesquita, Thassio R. R.; Melo, Vitor U.; Mota, Marcelo M.; Silva, Tharciano L. T. B.; Santana, Michael N.; Oliveira, Larissa R.; Santos, Robervan V.; Miguel dos Santos, Rodrigo; Lauton-Santos, Sandra; Santos, Marcio R. V.; Barreto, Andre S.; Santana-Filho, Valter J.

    2016-01-01

    Resistance training is one of the most common kind of exercise used nowadays. Long-term high-intensity resistance training are associated with deleterious effects on vascular adjustments. On the other hand, is unclear whether low-intensity resistance training (LI-RT) is able to induce systemic changes in vascular tone. Thus, we aimed to evaluate the effects of chronic LI-RT on endothelial nitric oxide (NO) bioavailability of mesenteric artery and cardiovascular autonomic modulation in healthy rats. Wistar animals were divided into two groups: exercised (Ex) and sedentary (SED) rats submitted to the resistance (40% of 1RM) or fictitious training for 8 weeks, respectively. After LI-RT, hemodynamic measurements and cardiovascular autonomic modulation by spectral analysis were evaluated. Vascular reactivity, NO production and protein expression of endothelial and neuronal nitric oxide synthase isoforms (eNOS and nNOS, respectively) were evaluated in mesenteric artery. In addition, cardiac superoxide anion production and ventricle morphological changes were also assessed. In vivo measurements revealed a reduction in mean arterial pressure and heart rate after 8 weeks of LI-RT. In vitro studies showed an increased acetylcholine (ACh)-induced vasorelaxation and greater NOS dependence in Ex than SED rats. Hence, decreased phenylephrine-induced vasoconstriction was found in Ex rats. Accordingly, LI-RT increased the NO bioavailability under basal and ACh stimulation conditions, associated with upregulation of eNOS and nNOS protein expression in mesenteric artery. Regarding autonomic control, LI-RT increased spontaneous baroreflex sensitivity, which was associated to reduction in both, cardiac and vascular sympathetic modulation. No changes in cardiac superoxide anion or left ventricle morphometric parameters after LI-RT were observed. In summary, these results suggest that RT promotes beneficial vascular adjustments favoring augmented endothelial NO bioavailability and

  4. Strong decrease in streptomycin-resistance and absence of XDR 12 years after the Reorganization of the National Tuberculosis Control Program in the Central Region of Cameroon.

    Science.gov (United States)

    Sidze, Larissa Kamgue; Mouafo Tekwu, Emmanuel; Kuaban, Christopher; Assam Assam, Jean-Paul; Tedom, Jean-Claude; Eyangoh, Sara; Fouda, François-Xavier; Nolna, Désiré; Ntoumi, Francine; Frank, Matthias; Penlap Beng, Véronique N

    2014-01-01

    In the 1990s, resistance rates of 15% for streptomycin-resistance and 0.6% for multidrug-resistance (MDR) were reported from the Central Region of Cameroon. This work assesses drug resistant tuberculosis in this region 12 years after reorganization of the National Tuberculosis Control Program (NTCP). This cross-sectional study was conducted from April 2010 to March 2011 in Jamot Hospital in Yaoundé, Cameroon. Only patients with smear positive pulmonary tuberculosis were included. Sputa were cultured and subsequently underwent drug susceptibility testing (DST). All consenting individuals were tested for their HIV status. A total of 665 smear positive pulmonary tuberculosis patients were enrolled. The HIV prevalence was 28.5% (95%CI [25.2-32.1]). Of the 582 sputa that grew Mycobacterium tuberculosis complex species, DST results were obtained for 576. The overall resistance rate was 10.9% (63/576). The overall resistance rates for single drug resistance were: isoniazid-resistance 4.7% (27/576), streptomycin-resistance 3.3% (19/576), rifampicin-resistance 0.2% (1/576), kanamycin-resistance 0.2% (1/576) and ofloxacin-resistance 0.2% (1/576). The MDR rate was 1.1% (6/576) and no extensively drug resistant tuberculosis (XDR) was detected. The data show that reorganization of the NTCP resulted in a strong decrease in streptomycin-resistance and suggest that it prevented the emergence of XDR in the Central Region of Cameroon.

  5. Clinical Significance of HER-2 Splice Variants in Breast Cancer Progression and Drug Resistance

    Directory of Open Access Journals (Sweden)

    Claire Jackson

    2013-01-01

    Full Text Available Overexpression of human epidermal growth factor receptor (HER-2 occurs in 20–30% of breast cancers and confers survival and proliferative advantages on the tumour cells making HER-2 an ideal therapeutic target for drugs like Herceptin. Continued delineation of tumour biology has identified splice variants of HER-2, with contrasting roles in tumour cell biology. For example, the splice variant 16HER-2 (results from exon 16 skipping increases transformation of cancer cells and is associated with treatment resistance; conversely, Herstatin (results from intron 8 retention and p100 (results from intron 15 retention inhibit tumour cell proliferation. This review focuses on the potential clinical implications of the expression and coexistence of HER-2 splice variants in cancer cells in relation to breast cancer progression and drug resistance. “Individualised” strategies currently guide breast cancer management; in accordance, HER-2 splice variants may prove valuable as future prognostic and predictive factors, as well as potential therapeutic targets.

  6. Effects of cigarette smoke and chronic hypoxia on airways remodeling and resistance. Clinical significance

    OpenAIRE

    Olea, Elena; Prieto-Lloret, Jesús; Gonzalez-Martin, Carmen; Vega Agapito, Victoria; Gonzalez-Obeso, Elvira; Agapito, Teresa; Obeso, Ana; González, Constancio

    2011-01-01

    Previously we have reported that association of cigarette smoke (CS) and chronic hypoxia (CH) interact positively to physiopathologically remodel pulmonary circulation. In present study we have exposed guinea pigs to CS smoke (four cigarettes/day; 3 months; CS) and to chronic hypoxia (12% O2, 15 days; CH) alone or in combination (CSCH animals) and evaluated airways remodeling and resistance assessed as Penh (enhance pause). We measured Penh while animals breathe air, 10% O2 and 5% CO2 and fou...

  7. Clinical significance of methicillin-resistant coagulase-negative staphylococci obtained from sterile specimens.

    Science.gov (United States)

    Tashiro, Masato; Izumikawa, Koichi; Ashizawa, Nobuyuki; Narukawa, Munetoshi; Yamamoto, Yoshihiro

    2015-01-01

    Distinguishing true coagulase-negative staphylococci bacteremia from contamination remains a challenge. We conducted a retrospective analysis of 183 patients with methicillin-resistant coagulase-negative staphylococci (MR-CoNS)-positive and methicillin-resistant Staphylococcus aureus-positive cultures obtained from sterile sites such as blood, synovial fluid, ascitic fluid, and cerebrospinal fluid. Of the 209 MR-CoNS isolates, 83 (39.7%) were considered infection associated, and 126 (60.3%) were considered contamination. MR-CoNS isolates cultured from synovial fluid were more likely to be infection associated (P = 0.009). The median interval from insertion of a central venous catheter to onset of infection tended to be longer in MR-CoNS infection cases than in methicillin-resistant S. aureus infection cases (41 days versus 14 days, P = 0.055). In conclusion, our results suggest that the proportion of cases of true MR-CoNS infection may be higher than previously reported. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Deletion of C7L and K1L genes leads to significantly decreased virulence of recombinant vaccinia virus TianTan.

    Directory of Open Access Journals (Sweden)

    Zheng Liu

    Full Text Available The vaccinia virus TianTan (VTT has been modified as an HIV vaccine vector in China and has shown excellent performance in immunogenicity and safety. However, its adverse effects in immunosuppressed individuals warrant the search for a safer vector in the following clinic trails. In this study, we deleted the C7L and K1L genes of VTT and constructed six recombinant vaccinia strains VTT△C7L, VTT△K1L, VTT△C7LK1L, VTKgpe△C7L, VTKgpe△K1L and VTT△C7LK1L-gag. The pathogenicity and immunogenicity of these recombinants were evaluated in mouse and rabbit models. Comparing to parental VTT, VTT△C7L and VTT△K1L showed significantly decreased replication capability in CEF, Vero, BHK-21 and HeLa cell lines. In particular, replication of VTT△C7LK1L decreased more than 10-fold in all four cell lines. The virulence of all these mutants were decreased in BALB/c mouse and rabbit models; VTT△C7LK1L once again showed the greatest attenuation, having resulted in no evident damage in mice and erythema of only 0.4 cm diameter in rabbits, compared to 1.48 cm for VTT. VTKgpe△C7L, VTKgpe△K1L and VTT△C7LK1L-gag elicited as strong cellular and humoral responses against HIV genes as did VTKgpe, while humoral immune response against the vaccinia itself was reduced by 4-8-fold. These data show that deletion of C7L and K1L genes leads to significantly decreased virulence without compromising animal host immunogenicity, and may thus be key to creating a more safe and effective HIV vaccine vector.

  9. 5-Episinuleptolide Decreases the Expression of the Extracellular Matrix in Early Biofilm Formation of Multi-Drug Resistant Acinetobacter baumannii

    Directory of Open Access Journals (Sweden)

    Sung-Pin Tseng

    2016-07-01

    Full Text Available Nosocomial infections and increasing multi-drug resistance caused by Acinetobacter baumannii have been recognized as emerging problems worldwide. Moreover, A. baumannii is able to colonize various abiotic materials and medical devices, making it difficult to eradicate and leading to ventilator-associated pneumonia, and bacteremia. Development of novel molecules that inhibit bacterial biofilm formation may be an alternative prophylactic option for the treatment of biofilm-associated A. baumannii infections. Marine environments, which are unlike their terrestrial counterparts, harbor an abundant biodiversity of marine organisms that produce novel bioactive natural products with pharmaceutical potential. In this study, we identified 5-episinuleptolide, which was isolated from Sinularia leptoclados, as an inhibitor of biofilm formation in ATCC 19606 and three multi-drug resistant A. baumannii strains. In addition, the anti-biofilm activities of 5-episinuleptolide were observed for Gram-negative bacteria but not for Gram-positive bacteria, indicating that the inhibition mechanism of 5-episinuleptolide is effective against only Gram-negative bacteria. The mechanism of biofilm inhibition was demonstrated to correlate to decreased gene expression from the pgaABCD locus, which encodes the extracellular polysaccharide poly-β-(1,6-N-acetylglucosamine (PNAG. Scanning electron microscopy (SEM indicated that extracellular matrix of the biofilm was dramatically decreased by treatment with 5-episinuleptolide. Our study showed potentially synergistic activity of combination therapy with 5-episinuleptolide and levofloxacin against biofilm formation and biofilm cells. These data indicate that inhibition of biofilm formation via 5-episinuleptolide may represent another prophylactic option for solving the persistent problem of biofilm-associated A. baumannii infections.

  10. Significantly enhanced creep resistance of low volume fraction in-situ TiBw/Ti6Al4V composites by architectured network reinforcements

    Science.gov (United States)

    Wang, S.; Huang, L. J.; Geng, L.; Scarpa, F.; Jiao, Y.; Peng, H. X.

    2017-01-01

    We present a new class of TiBw/Ti6Al4V composites with a network reinforcement architecture that exhibits a significant creep resistance compared to monolithic Ti6Al4V alloys. Creep tests performed at temperatures between 773 K and 923 K and stress range of 100 MPa-300 MPa indicate both a significant improvement of the composites creep resistance due to the network architecture made by the TiB whiskers (TiBw), and a decrease of the steady-state creep rates by augmenting the local volume fractions of TiBw in the network region. The deformation behavior is driven by a diffusion-controlled dislocation climb process. Moreover, the activation energies of these composites are significantly higher than that of Ti6Al4V alloys, indicating a higher creep resistance. The increase of the activation energy can be attributed to the TiBw architecture that severely impedes the movements of dislocation and grain boundary sliding and provides a tailoring of the stress transfer. These micromechanical mechanisms lead to a remarkable improvement of the creep resistance of these networked TiBw/Ti6Al4V composites featuring the special networked architecture.

  11. Using resistivity to measure H/Pd and D/Pd loading. Method and significance

    International Nuclear Information System (INIS)

    Mckubre, M.C.H.; Tanzella, F.L.

    2006-01-01

    The resistance ratio method is the most frequent technique used to determine the extent of interstitial loading of hydrogen or deuterium atoms into palladium electrodes, or extended structures used in electrolytic or gas phase cold fusion experiments. Specifically, advantage is taken of an empirical relationship between the measured resistance, R, normalized to that of the same body at the same temperature in the absence of hydrogen isotope, R 0 , hence R/R 0 , and the atomic fraction occupancy of octahedral interstitials, x=H/Pd or D/Pd. This method was first suggested and employed in cold fusion studies by the present authors, and received immediate and widespread acceptance because of the ease with which this experimental technique could be used to make in situ, real-time measurements of a parameter, D/Pd, anticipated or hypothesized at that time to relate to cold fusion heat excess or nuclear production. We take up this topic again 15 years later in an attempt to clear up some errors and misunderstandings regarding the resistance ratio method and its application in cold fusion studies. The relationship between R/R 0 and x is empirical. That is, calibrations are only as good as the experiments that support the shape of the curve and cannot be used outside the range (P, T, x) in which data are taken. The original calibration (unaccountably and erroneously immortalized as the 'famous Baranowski curve') involved an extrapolation of known data into the region of cold fusion interest in the D-Pd system, at x > 0.6. Present theory and results focus new attention on the very high loading region as x approaches or even exceeds unity, where double occupation of octahedral sites, tetrahedral site occupancy, new phase formation or new electrical states, may be relevant to the underlying physical process of excess heat and nuclear production. Rather than simply using the resistance ratio as a qualitative tool to determine whether an electrode is better or lesser loaded, it

  12. Plasma sterol evidence for decreased absorption and increased synthesis of cholesterol in insulin resistance and obesity1234

    Science.gov (United States)

    Knopp, Robert H; Kahn, Steven E; Retzlaff, Barbara M; Fish, Brian; Ma, Lina; Ostlund, Richard E

    2011-01-01

    Background: The rise in LDL with egg feeding in lean insulin-sensitive (LIS) participants is 2- and 3-fold greater than in lean insulin-resistant (LIR) and obese insulin-resistant (OIR) participants, respectively. Objective: We determined whether differences in cholesterol absorption, synthesis, or both could be responsible for these differences by measuring plasma sterols as indexes of cholesterol absorption and endogenous synthesis. Design: Plasma sterols were measured by gas chromatography–mass spectrometry in a random subset of 34 LIS, 37 LIR, and 37 OIR participants defined by the insulin sensitivity index (SI) and by BMI criteria selected from a parent group of 197 participants. Cholestanol and plant sterols provide a measure of cholesterol absorption, and lathosterol provides a measure of cholesterol synthesis. Results: The mean (±SD) ratio of plasma total absorption biomarker sterols to cholesterol was 4.48 ± 1.74 in LIS, 3.25 ± 1.06 in LIR, and 2.82 ± 1.08 in OIR participants. After adjustment for age and sex, the relations of the absorption sterol–cholesterol ratios were as follows: LIS > OIR (P LIR (P OIR (P = 0.11). Lathosterol-cholesterol ratios were 0.71 ± 0.32 in the LIS participants, 0.95 ± 0.47 in the LIR participants, and 1.29 ± 0.55 in the OIR participants. After adjustment for age and sex, the relations of lathosterol-cholesterol ratios were as follows: LIS Cholesterol absorption was highest in the LIS participants, whereas cholesterol synthesis was highest in the LIR and OIR participants. Therapeutic diets for hyperlipidemia should emphasize low-cholesterol diets in LIS persons and weight loss to improve SI and to decrease cholesterol overproduction in LIR and OIR persons. PMID:21940599

  13. Hydroxypropyl methylcellulose, a viscous soluble fiber, reduces insulin resistance and decreases fatty liver in Zucker Diabetic Fatty rats

    Directory of Open Access Journals (Sweden)

    Brockman David A

    2012-11-01

    fatty acid oxidation by HPMC. Conclusions Consumption of the viscous non-fermentable fiber HPMC decreased diabetic wasting, improved glucose control and reduced insulin resistance and fatty liver in a model of obesity with diabetes.

  14. Clinical significance of acquired activated protein C resistance in patients with systemic lupus erythematosus.

    Science.gov (United States)

    Muñoz-Rodríguez, F J; Reverter, J C; Font, J; Tàssies, D; Espinosa, G; Cervera, R; Carmona, F; Balsch, J; Ingelmo, M; Ordinas, A

    2002-01-01

    Antiphospholipid antibodies (aPL) may induce acquired activated protein C resistance (acquired APCR). The role of acquired APCR in patients with systemic lupus erythematosus (SLE) is not well known. To evaluate the prevalence of acquired APCR and its association with clinical manifestations we studied 103 consecutive SLE patients and 103 matched controls. APCR in the undiluted test and after dilution in factor V deficient plasma, factor V Leiden, protein C and S, lupus anticoagulant, and anti-cardiolipin, anti-beta2-glycoprotein I and anti-prothrombin antibodies were determined. Factor V Leiden was found in 4% in both patients and controls. The prevalence of acquired APCR was 22% for the undiluted assay and 17% in the diluted test. In SLE patients, acquired APCR was associated with aPL (39 vs 13% in undiluted assay, P = 0.007; and 33 vs 7% in the diluted test, P = 0.001). Arterial thromboses were found in 24% of patients with acquired APCR and in 6% of patients without (P = 0.04). However, no relationship was found with venous thrombosis. Acquired APCR was also associated with pregnancy losses: miscarriages in 70% of women with acquired APCR vs 32% in those without (P=0.03). Thus, in SLE patients acquired APCR seems to be associated with increased prevalence of arterial thrombosis and pregnancy losses.

  15. Expression of chicken interleukin-2 by a highly virulent strain of Newcastle disease virus leads to decreased systemic viral load but does not significantly affect mortality in chickens.

    Science.gov (United States)

    Susta, Leonardo; Diel, Diego G; Courtney, Sean; Cardenas-Garcia, Stivalis; Sundick, Roy S; Miller, Patti J; Brown, Corrie C; Afonso, Claudio L

    2015-08-08

    In mammals, interleukin 2 (IL-2) has been shown to decrease replication or attenuate pathogenicity of numerous viral pathogens (herpes simplex virus, vaccinia virus, human respiratory syncytial virus, human immunodeficiency virus) by activating natural killer cells (NK), cytotoxic T lymphocytes and expanding subsets of memory cells. In chickens, IL-2 has been shown to activate T cells, and as such it might have the potential to affect replication and pathogenesis of Newcastle disease virus (NDV). To assess the effect of IL-2 during NDV infection in chickens, we produced a recombinant virulent NDV strain expressing chicken IL-2 (rZJ1-IL2). The effects of IL-2 expression were investigated in vivo using the intracerebral pathogenicity index (ICPI) in day-old chicks and pathogenesis experiments in 4-week-old chickens. In these studies, rZJ1-IL2 was compared to a control virus expressing the green fluorescent protein (rZJ1-GFP). Assessed parameters included survival curves, detailed histological and immunohistochemical grading of lesions in multiple organs, and virus isolation in blood, spleen and mucosal secretions of infected birds. At the site of infection (eyelid), expression of IL-2 was demonstrated in areas of rZJ-IL2 replication, confirming IL-2 production in vivo. Compared to rZJ1-GFP strain, rZJ1-IL2 caused milder lesions and displayed decreased viral load in blood, spleen and mucosal secretions of infected birds. In the rZJ1-IL2-infected group, virus level in the blood peaked at day 4 post-infection (pi) (10(3.46) EID50 /0.1 ml) and drastically decreased at day 5 pi (10(0.9) EID50/0.1 ml), while in the rZJ1-GFP-infected group virus levels in the blood reached 10(5.35) EID50/0.1 ml at day 5. However, rZJ1-IL2-infected groups presented survival curves similar to control birds infected with rZJ1-GFP, with comparable clinical signs and 100 % mortality. Further, expression of IL-2 did not significantly affect the ICPI scores, compared to rZJ1-GFP strain. Increased

  16. Treated domestic sewage irrigation significantly decreased the CH4, N2O and NH3 emissions from paddy fields with straw incorporation

    Science.gov (United States)

    Xu, Shanshan; Hou, Pengfu; Xue, Lihong; Wang, Shaohua; Yang, Linzhang

    2017-11-01

    Straw incorporation and domestic sewage irrigation have been recommended as an environmentally friendly agricultural practice and are widely used not only in China but also in other countries. The individual effects on yield and environmental impacts have been studied extensively, but the comprehensive effect when straw returning and domestic sewage irrigation are combined together has seldom been reported. This study was conducted to examine the effects of straw returning and domestic sewage irrigation on rice yields, greenhouse gas emissions (GHGs) and ammonia (NH3) volatilization from paddy fields from 2015 to 2016. The results showed that the rice yield was not affected by the irrigation water sources and straw returning under the same total N input, which was similar in both years. Due to the rich N in the domestic sewage, domestic sewage irrigation could reduce approximately 45.2% of chemical nitrogen fertilizer input without yield loss. Compared to straw removal treatments, straw returning significantly increased the CH4 emissions by approximately 7-9-fold under domestic sewage irrigation and 13-14-fold under tap water irrigation. Straw returning also increased the N2O emissions under the two irrigation water types. In addition, the seasonal NH3 volatilization loss was significantly increased by 88.8% and 61.2% under straw returning compared to straw removal in 2015 and 2016, respectively. However, domestic sewage irrigation could decrease CH4 emissions by 24.5-26.6%, N2O emissions by 37.0-39.0% and seasonal NH3 volatilization loss by 27.2-28.3% under straw returning compared to tap water irrigation treatments. Global warming potentials (GWP) and greenhouse gas intensities (GHGI) were significantly increased with straw returning compared with those of straw removal, while they were decreased by domestic sewage irrigation under straw returning compared to tap water irrigation. Significant interactions between straw returning and domestic sewage irrigation on

  17. Restrictive Streptomycin Resistance Mutations Decrease the Formation of Attaching and Effacing Lesions in Escherichia coli O157:H7 Strains.

    Science.gov (United States)

    Chen, Chun; Blumentritt, Carla A; Curtis, Meredith M; Sperandio, Vanessa; Torres, Alfredo G; Dudley, Edward G

    2013-09-01

    Streptomycin binds to the bacterial ribosome and disrupts protein synthesis by promoting misreading of mRNA. Restrictive mutations on the ribosomal subunit protein S12 confer a streptomycin resistance (Str r ) phenotype and concomitantly increase the accuracy of the decoding process and decrease the rate of translation. Spontaneous Str r mutants of Escherichia coli O157:H7 have been generated for in vivo studies to promote colonization and to provide a selective marker for this pathogen. The locus of enterocyte effacement (LEE) of E. coli O157:H7 encodes a type III secretion system (T3SS), which is required for attaching and effacing to the intestinal epithelium. In this study, we observed decreases in both the expression and secretion levels of the T3SS translocated proteins EspA and EspB in E. coli O157:H7 Str r restrictive mutants, which have K42T or K42I mutations in S12. However, mildly restrictive (K87R) and nonrestrictive (K42R) mutants showed slight or indistinguishable changes in EspA and EspB secretion. Adherence and actin staining assays indicated that restrictive mutations compromised the formation of attaching and effacing lesions in E. coli O157:H7. Therefore, we suggest that E. coli O157:H7 strains selected for Str r should be thoroughly characterized before in vivo and in vitro experiments that assay for LEE-directed phenotypes and that strains carrying nonrestrictive mutations such as K42R make better surrogates of wild-type strains than those carrying restrictive mutations. Copyright © 2013, American Society for Microbiology. All Rights Reserved.

  18. Combining Cue-Lure and Methyl Eugenol in Traps Significantly Decreases Catches of Most Bactrocera, Zeugodacus and Dacus Species (Diptera: Tephritidae: Dacinae) in Australia and Papua New Guinea.

    Science.gov (United States)

    Royer, Jane E; Mayer, David G

    2018-02-09

    Male fruit fly attractants, cue-lure (CL) and methyl eugenol (ME), are important in the monitoring and control of pest fruit fly species. Species respond to CL or ME but not both, and there are conflicting reports on whether combining CL (or its hydroxy analogue raspberry ketone) and ME decreases their attractiveness to different species. Fruit fly monitoring programs expend significant effort using separate CL and ME traps and avoiding lure cross-contamination, and combining the two lures in one trap would create substantial savings. To determine if combining lures has an inhibitory effect on trap catch, CL and ME wicks placed in the same Steiner trap were field tested in comparison to CL alone and ME alone in Australia and Papua New Guinea (PNG). In Australia, 24 out of 27 species trapped were significantly more attracted to CL or ME alone than the combination ME/CL lure, including the pests Bactrocera bryoniae (Tryon), B. frauenfeldi (Schiner), B. kraussi (Hardy), B. neohumeralis (Hardy), B. tryoni (Froggatt) (CL-responsive), and B. musae (Tryon) (ME-responsive). In PNG, 13 out of 16 species trapped were significantly more attracted to CL or ME alone than the ME/CL combination, including the pests B. bryoniae, B. frauenfeldi, B. neohumeralis, B. trivialis (Drew), Zeugodacus cucurbitae (Coquillett) (CL-responsive) and B. dorsalis (Hendel), B. musae, and B. umbrosa (Fabricius) (ME-responsive). This study shows that combining CL and ME in the one trap in equal parts significantly reduces catches of most species of Dacini fruit flies in Australia and PNG. © The Author(s) 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  19. Variations of insulin resistance and associated hormone levels in elderly and middle-aged male persons and their clinical significance

    International Nuclear Information System (INIS)

    Zhuo Liankun; Yan Daochun; Chen Xiumei; Liu Peng; Zhang Aihua

    2005-01-01

    To study the relationship between age and insulin resistance and the variation of associated hormones in elderly and middle-aged males, blood levels of LH, FSH, T, SHBG, TSH, INS were determined by RIA, FBG by GPO, IR by HOMA in 268 healthy male persons aged 41 to 60 years and in 80 normal control male persions of 35 to 40 years old. The results showed that levels of IR, LH, FSH, SHBG were increasing and T, TSH were decreasing along with the increase of age except for TSH. Therefore, analyzing these changes could evaluate the conditions of elderly and middle-aged males. (authors)

  20. Decreased antimicrobial resistance and defined daily doses after implementation of a clinical culture-guided antimicrobial stewardship program in a local hospital

    Directory of Open Access Journals (Sweden)

    Chang-Teng Wu

    2017-12-01

    Full Text Available Background: We aimed to report the implementation of an antimicrobial stewardship program (ASP guided by clinically significant cultures in a hospital to assess its pharmaceutical, microbiological, financial, and outcome effects. Methods: A 3-year cohort study of an antimicrobial restriction policy implementation was performed. The ASP with culture-guided de-escalation of antibiotics was instituted in a local hospital since January 1, 2012. The cost of antimicrobials, defined daily dose (DDD, susceptibility to antimicrobials, and outcome of all admitted patients were calculated and evaluated before and after the ASP implementation. Results: Average monthly length of stay of admitted patients decreased from 7.8 ± 0.5 days in 2011 to 6.9 ± 0.3 days in 2013 (p < 0.001. The average monthly cost of antimicrobials decreased 46.9% from US$30,146.8 in 2011 to US$16,021.3 in 2013 (p < 0.001. Total intravenous antimicrobial DDDs per 100 bed-days of the inpatients were 66.9, 54.1 and 48.4 in 2011, 2012 and 2013, respectively. A total of 18.6 DDDs per 100 bed-days of inpatients (27.7% decreased from 2011 to 2013. By comparing data in 2013 to those in 2011, the ASP reduced antimicrobial resistance of Gram-positive bacteria (p = 0.013, Gram-negative bacteria (p < 0.001, and predominant species (all p < 0.05. The yearly mortality also decreased from 1.3% in 2011 to 1.1% in 2012 and 1.0% in 2013. Conclusions: The ASP with a culture-guided de-escalation of antibiotics successfully reduced length of stay, mortality, the cost of antimicrobials, DDDs, and antimicrobial resistance rate, and that is highly recommended for local hospitals. Keywords: antimicrobial resistance, antimicrobial restriction policy, antimicrobial stewardship program, defined daily dose

  1. An Antimicrobial Metabolite from Bacillus sp.: Significant activity against pathogenic bacteria including multidrug-resistant clinical strains

    Directory of Open Access Journals (Sweden)

    AJAY GHOSH CHALASANI

    2015-12-01

    Full Text Available In this study, the cell free modified trypticase soya broth (pH 7.4+0.2 of Bacillus subtilis URID 12.1 showed significant antimicrobial activity against multidrug-resistant strains of Staphylococcus aureus, S. epidermidis, Streptococcus pyogenes and Enterococcus faecalis. The partially purified antimicrobial molecule was found to be resistant to extremes of pH and temperatures and also to higher concentrations of trypsin and proteinase K. The antimicrobial molecule was purified by a three-step method that included reverse-phased high performance liquid chromatography (RP-HPLC. The minimum inhibitory concentration (MIC values were determined for 11 species of bacteria using a microbroth dilution technique. The HPLC-purified fraction showed the MICs ranging from 0.5 to 1 µg/ml for methicillin and vancomycin resistant Staphylococcus aureus (MVRSA and methicillin-resistant Staphylococcus epidermidis (MRSE strains. The molecular mass of the antimicrobial compound was determined to be 842.37 Da. The same antimicrobial fraction showed negligible haemolytic activity against human red blood cells even at a concentration as high as 100µg/ml. Because of its significant antimicrobial activity at low MIC values coupled with its non-haemolytic property, it may prove to be a novel antimicrobial lead molecule.

  2. Moderate Intensity Resistance Training Significantly Elevates Testosterone following Upper Body and Lower Body Bouts When Total Volume is Held Constant

    Directory of Open Access Journals (Sweden)

    Robert Rietjens

    2015-10-01

    Full Text Available Introduction: It is unknown whether resistance training intensity or total volume of work affects the acute testosterone response to a greater extent. Purpose: Therefore, the circulating testosterone response was investigated following four resistance training protocols where total volume of work was held constant: moderate intensity (70% 1RM upper body (bench press, bent barbell row, and military press, moderate intensity lower body (squat and deadlift, high intensity (90% 1RM upper body, high intensity lower body. Methods: Total volume of work performed by each participant between protocols was maintained by adjusting the number of sets and or repetitions performed. Ten healthy, resistance trained men volunteered, and performed exercise protocols on separate days in a counterbalanced order. Capillary blood was obtained via finger stick at baseline (pre, immediately following the exercise session (post, and 1h post for the determination of testosterone concentration. Data were analyzed using a factorial ANOVA and significance was accepted at p≤ 0.05. Results: Both moderate intensity resistance protocols (upper and lower body significantly increased testosterone concentration (p=0.026, and p=0.024 respectively, whereas the high intensity protocols elevated testosterone but failed to achieve significance (upper p=0.272, lower p=0.658. No difference was noted in post session testosterone concentration between upper and lower body protocols for either moderate (p=0.248 or high intensity (p=0.990. Conclusion: This may be useful for novice resistance trained individuals because it provides evidence that moderate intensity is sufficient to increase testosterone compared to high intensity protocols that could be associated with a greater risk of injury. Keywords: hormone response, equal total work, high intensity protocol

  3. Human circulating plasma DNA significantly decreases while lymphocyte DNA damage increases under chronic occupational exposure to low-dose gamma-neutron and tritium β-radiation

    Energy Technology Data Exchange (ETDEWEB)

    Korzeneva, Inna B., E-mail: inna.korzeneva@molgen.vniief.ru [Russian Federal Nuclear Center – All-Russian Research Institute of Experimental Physics (RFNC-VNIIEF) 607190, Sarov, 37 Mira ave., Nizhniy Novgorod Region (Russian Federation); Kostuyk, Svetlana V.; Ershova, Liza S. [Research Centre for Medical Genetics, Russian Academy of Medical Sciences, 115478 Moscow, 1 Moskvorechye str. (Russian Federation); Osipov, Andrian N. [Federal Medial and Biological Center named after Burnazyan of the Federal Medical and Biological Agency (FMBTz named after Burnazyan of FMBA), Moscow (Russian Federation); State Research Center - Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency, Zhivopisnaya, 46, Moscow, 123098 (Russian Federation); Zhuravleva, Veronika F.; Pankratova, Galina V. [Russian Federal Nuclear Center – All-Russian Research Institute of Experimental Physics (RFNC-VNIIEF) 607190, Sarov, 37 Mira ave., Nizhniy Novgorod Region (Russian Federation); Porokhovnik, Lev N.; Veiko, Natalia N. [Research Centre for Medical Genetics, Russian Academy of Medical Sciences, 115478 Moscow, 1 Moskvorechye str. (Russian Federation)

    2015-09-15

    Highlights: • The chronic exposure to low-dose IR induces DSBs in human lymphocytes (TM index). • Exposure to IR decreases the level of human circulating DNA (cfDNA index). • IR induces an increase of DNase1 activity (DNase1 index) in plasma. • IR induces an increase of the level of antibodies to DNA (Ab DNA index) in plasma. • The ratio cfDNA/(DNase 1 × Ab DNA × TM) is a potential marker of human exposure to IR. - Abstract: The blood plasma of healthy people contains cell-fee (circulating) DNA (cfDNA). Apoptotic cells are the main source of the cfDNA. The cfDNA concentration increases in case of the organism’s cell death rate increase, for example in case of exposure to high-dose ionizing radiation (IR). The objects of the present research are the blood plasma and blood lymphocytes of people, who contacted occupationally with the sources of external gamma/neutron radiation or internal β-radiation of tritium N = 176). As the controls (references), blood samples of people, who had never been occupationally subjected to the IR sources, were used (N = 109). With respect to the plasma samples of each donor there were defined: the cfDNA concentration (the cfDNA index), DNase1 activity (the DNase1 index) and titre of antibodies to DNA (the Ab DNA index). The general DNA damage in the cells was defined (using the Comet assay, the tail moment (TM) index). A chronic effect of the low-dose ionizing radiation on a human being is accompanied by the enhancement of the DNA damage in lymphocytes along with a considerable cfDNA content reduction, while the DNase1 content and concentration of antibodies to DNA (Ab DNA) increase. All the aforementioned changes were also observed in people, who had not worked with the IR sources for more than a year. The ratio cfDNA/(DNase1 × Ab DNA × TM) is proposed to be used as a marker of the chronic exposure of a person to the external low-dose IR. It was formulated the assumption that the joint analysis of the cfDNA, DNase1, Ab

  4. Major Pathophysiology in Prediabetes and Type 2 Diabetes: Decreased Insulin in Lean and Insulin Resistance in Obese.

    Science.gov (United States)

    Kabadi, Udaya M

    2017-06-01

    Lowering of body mass index (BMI) to ≥25 kg/m 2 as obesity by ADA suggests insulin resistance as a major mechanism of impaired glucose metabolism (IGM) in Asians. However, glimepiride, an insulin secretagogue, delayed onset of type 2 diabetes (DM2) from prediabetes (PreDM), indicating decreased insulin secretion (IS) as a major factor in lean (L; BMI DM2. Seventy-five men and 45 women ages 36 to 75 years were divided into six groups: LN, LPreDM, LDM2, ObN, ObPreDM, and ObDM2. Determination of IS by insulinogenic indices (I/G) at fasting (FI/FG), first phase (∆I/∆G), and cumulative responses over 2 hours of OGTT (CRI/CRG), and IR by FIXFG, ∆IX∆G, and CRIXCRG. Changes in IS and IR for PreDM and DM2 were calculated as % fall and % rise, respectively, from levels in N. All indices of IS and IR were lower ( P DM2 ( P < 0.05) in both groups. However, the declines in IS were greater ( P < 0.05) than rises in IR in LPreDM and LDM2. Whereas, the rises in IR were higher ( P < 0.05) than declines in IS in ObPreDM and ObDM2. In L, major mechanism of IGM is declining IS and not rising IR documented among Ob.

  5. [Multiparameter analysis of the ergometric test. Significance of the failure of systolic blood pressure to decrease during recovery phase as an index of coronary disease].

    Science.gov (United States)

    Doria, G; Scaccianoce, G; Artale, S; Francaviglia, B; Platania, F; Circo, A

    1990-10-01

    Ergometric tests were performed in 27 patients who had previously undergone coronarography following instrumental findings and/or symptoms which seemed highly indicative of ischemic cardiopathy. The aim of the study was to assess the diagnostic importance of the failure of systolic blood pressure to decrease during the third minute of the recovery phase of the test as an index of coronary disease. In particular, as reported by other studies, the ratio between systolic blood pressure at the third minute of recovery and maximum systolic blood pressure during the test was also assessed values above 0.7 were considered pathological. Sixteen out the 27 patients examined showed lesions which were hemodynamically significant, whereas 11 patients were free of lesions and 9 had previous myocardial necrosis. The level of the above ratio in subjects without significant coronary lesions was 0.66 +/- 0.05, whereas it was 0.85 +/- 0.04 (p less than 0.01) in patients with coronary disease. Sensitivity, specificity, and positive and negative prognostic values were respectively 91.6%, 62%, 64.7% and 90.9%. In patients with lesions to the three main arteries both the sensitivity and the specificity were 100%. In the same patients, the ST criteria were 85.7%, 50%, 81.8% and 74.3%.

  6. Assessment of the role of fibular fixation in distal-third tibia-fibula fractures and its significance in decreasing malrotation and malalignment.

    Science.gov (United States)

    Prasad, Manish; Yadav, Sanjay; Sud, Ajaydeep; Arora, Naresh C; Kumar, Narender; Singh, Shambhu

    2013-12-01

    In the treatment of distal-third tibia/fibula fractures treated by interlocking nailing, the role of fibular fixation is not clearly defined. This study aimed to assess the benefits of fibular fixation in such fractures. Sixty patients with fractures of the lower third of the leg were enrolled into the study and divided into two groups based on whether the fibula was fixed (group A) or not (group B). Fracture tibia was treated with interlocked intramedullary nailing and fibular fixation was done using a 3.5-mm Limited Contact Dynamic Compression Plate (LC-DCP). The two groups were compared for differences in rotation at ankle, angulation at the fracture site, time of union and complications. Clinical and functional outcomes were assessed regularly. Merchant-Dietz criteria were used to assess ankle function. The demographics of the two groups were similar. Average valgus angulation was significantly less in group A (average 5°) versus group B (average 9°). The degree of rotational malalignment at the ankle in group A was average 7° versus average 15° in group B. The outcome of two groups for clinical ankle score, time of union and complications showed no significant differences. Fixation of the fibula along with interlocking nailing of the tibia decreases the malalignment of the tibia and malrotation of the ankle in distal-third fractures of the tibia and fibula as compared with only interlocking nailing. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Resistant Maltodextrin Decreases Micellar Solubility of Lipids and Diffusion of Bile Salt Micelles and Suppresses Incorporation of Micellar Fatty Acids into Caco-2 Cells.

    Science.gov (United States)

    Ikeda, Ikuo; Tamakuni, Kyouhei; Sakuma, Tomomi; Ozawa, Ran; Inoue, Nao; Kishimoto, Yuka

    2016-01-01

    Several studies have suggested that resistant maltodextrin (RMD) suppresses intestinal lipid absorption in experimental animals and humans. However, possible mechanisms underlying this effect are not known. In this study, effects of RMD on processes of the absorption of various lipids were investigated in vitro. RMD dose-dependently suppressed the solubility of various lipid components, including 1-mono-oleoylglycerol, oleic acid, and phosphatidylcholine in bile salt micelles in vitro. When the diffusion rate of bile salt micelles through a filter membrane was investigated in vitro, bile salt micelles containing RMD diffused more slowly than those without RMD. Incorporation of [1- 14 C] oleic acid into Caco-2 cells from the RMD-containing bile salt micelles was significantly smaller than that from the control micelles (without RMD). These results show that RMD suppresses intestinal absorption of lipids by decreasing their micellar solubility and the diffusion rate of bile salt micelles.

  8. Strong Decrease in Streptomycin-Resistance and Absence of XDR 12 Years after the Reorganization of the National Tuberculosis Control Program in the Central Region of Cameroon

    Science.gov (United States)

    Kuaban, Christopher; Assam Assam, Jean-Paul; Tedom, Jean-Claude; Eyangoh, Sara; Fouda, François-Xavier; Nolna, Désiré; Ntoumi, Francine; Frank, Matthias; Penlap Beng, Véronique N.

    2014-01-01

    Background In the 1990s, resistance rates of 15% for streptomycin-resistance and 0.6% for multidrug-resistance (MDR) were reported from the Central Region of Cameroon. This work assesses drug resistant tuberculosis in this region 12 years after reorganization of the National Tuberculosis Control Program (NTCP). Methods This cross-sectional study was conducted from April 2010 to March 2011 in Jamot Hospital in Yaoundé, Cameroon. Only patients with smear positive pulmonary tuberculosis were included. Sputa were cultured and subsequently underwent drug susceptibility testing (DST). All consenting individuals were tested for their HIV status. Results A total of 665 smear positive pulmonary tuberculosis patients were enrolled. The HIV prevalence was 28.5% (95%CI [25.2–32.1]). Of the 582 sputa that grew Mycobacterium tuberculosis complex species, DST results were obtained for 576. The overall resistance rate was 10.9% (63/576). The overall resistance rates for single drug resistance were: isoniazid-resistance 4.7% (27/576), streptomycin-resistance 3.3% (19/576), rifampicin-resistance 0.2% (1/576), kanamycin-resistance 0.2% (1/576) and ofloxacin-resistance 0.2% (1/576). The MDR rate was 1.1% (6/576) and no extensively drug resistant tuberculosis (XDR) was detected. Conclusions The data show that reorganization of the NTCP resulted in a strong decrease in streptomycin-resistance and suggest that it prevented the emergence of XDR in the Central Region of Cameroon. PMID:24901982

  9. Possible Influence of Resistance to Malaria in Clinical Presentation of Rheumatoid Arthritis: Biological Significance of Natural Selection

    Directory of Open Access Journals (Sweden)

    Fabio Bonilla-Abadía

    2012-01-01

    Full Text Available Rheumatoid arthritis (RA is a common autoimmune disease that affects all ethnic groups. Genetic factors, mainly HLA alleles, are highly associated with increased risk to develop RA. However, there are few available data about the role of these genetic polymorphisms in the prevalence or severity of RA in the Afrodescendant population, who have evolutionarily and by natural selection developed mutations that allowed them to acquire resistance to infectious diseases like malaria. Some of the mechanisms, by which this resistance was developed as a product of natural selection, are involved in different forms of immunological response, many of them of a well-known importance in the pathophysiology of RA. This paper focuses on presenting the known mechanisms of resistance to malaria and their possible contribution to the pathophysiology of RA, including “loss-of-function” mutations, lack of expression of chemokine receptors, decrease of immune complexes clearance by asplenia, or increase of immune reactivity mediated by B cells, among other mechanisms in this special group of patients.

  10. A Novel Hands-Free Abdominal Compression Device for Colonoscopy Significantly Decreases Cecal Intubation Time: A Prospective Single-Blinded Pilot Study.

    Science.gov (United States)

    Schulman, Allison R; Ryou, Marvin; Chan, Walter W

    2017-06-01

    Colonoscopy outcome is limited by endoscope looping, which leads to patient discomfort, prolonged procedure, and increased sedation requirement. Traditional manual abdominal pressure is imprecise and manually intensive. A hands-free abdominal compression device (ACD) may improve colonoscopy outcome. We aimed to assess the effect of a novel ACD on colonoscopy outcomes compared to manual pressure. This was a prospective single-blinded study of patients undergoing outpatient colonoscopy. The ACD (N-Doe Pillow™) was applied on 50 consecutive patients. Endoscopists were blinded to device usage. Control cases using manual pressure were randomly selected in a 2:1 manner. Primary outcome was cecal intubation time. Secondary outcomes included sedation requirement and complications. Subgroup analyses evaluated ACD effect on endoscopists with different experiences and patients at higher risk of difficult colonoscopy. Fisher's exact and Student's t-tests were performed for univariate analyses. Multivariate analysis was performed using generalized linear regression. Fifty patients undergoing colonoscopy with ACD assistance were compared to 100 matched controls. Mean cecal intubation time was significantly reduced in the ACD group compared to controls (6.38 minutes versus 11.8 minutes, P ACD use was independently associated with reduction in cecal intubation time (β-coeff: -4.11, P = .007). Subgroup analyses revealed a trend toward increased improvement in cecal intubation time among junior endoscopists and obese patients. A novel, hands-free ACD significantly decreased cecal intubation time in this prospective, single-blinded, match-controlled study. A trend toward more improvement was seen among junior faculty, suggesting an application for trainees and/or endoscopists with smaller case volumes.

  11. Pre-operative antiseptic shower and bath policy decreases the rate of S. aureus and methicillin-resistant S. aureus surgical site infections in patients undergoing joint arthroplasty.

    Science.gov (United States)

    Colling, Kristin; Statz, Catherine; Glover, James; Banton, Kaysie; Beilman, Greg

    2015-04-01

    Surgical site infection (SSI) following joint arthroplasty increases length of stay, hospital cost, and leads to patient and healthcare provider dissatisfaction. Due to the presence of non-biologic implants (the prosthetic joint) in these procedures, infection is often devastating and treatment of the infection is more difficult. For this reason, prevention of SSI is of crucial importance in this population. Staphylococcus aureus colonizes the nares of approximately 30-40% of the population, is the most common pathogen causing SSI, and is associated with high morbidity and mortality rate. A pre-operative shower or bath with an antiseptic is an inexpensive and effective method of removal of these transient skin pathogens prior to the procedure and may be used to decrease SSI. We hypothesize that a preoperative antiseptic shower or bath will decrease the rate of SSI. A retrospective review was performed at two affiliated hospitals within the same system, one with a hospital-wide policy enforcing pre-operative antiseptic shower or bath and the other with no policy, with cases included from January 2010 to June 2012. International Classification of Disease-Ninth Revision-Clinical Modification (ICD-9-CM) codes and chart review were used to identify patients undergoing joint arthroplasty and to identify those with SSI. Two thousand three-hundred forty-nine arthroplasties were performed at the University of Minnesota Medical Center, a tertiary-care hospital with a pre-operative antiseptic shower or bath policy in place. An additional 1,693 procedures were performed at Fairview Ridges Hospital, a community hospital with no pre-operative policy. There was no difference in the rate of SSI between the two hospitals (1.96% vs. 1.95%; p=1.0). However, the rate of SSI caused by S. aureus was significantly decreased by pre-operative antiseptic shower/bath (17% vs. 61%; p=0.03), as was the rate of methicillin-resistant S. aureus (MRSA) infections (2% vs. 24% p=0.002). A pre

  12. Zygosaccharomyces lentus: a significant new osmophilic, preservative-resistant spoilage yeast, capable of growth at low temperature.

    Science.gov (United States)

    Steels, H; James, S A; Roberts, I N; Stratford, M

    1999-10-01

    Zygosaccharomyces lentus is a yeast species recently identified from its physiology and 18S ribosomal sequencing (Steels et al. 1999).The physiological characteristics of five strains of this new yeast so far isolated were investigated, particularly those of technical significance for a spoilage yeast, namely temperature range, pH range, osmotolerance, sugar fermentation, resistance to food preservatives such as sorbic acid, benzoic acid and dimethyldicarbonate (DMDC; Velcorin). Adaptation to benzoic acid, and growth in shaking and static culture were also investigated. Zygosaccharomyces lentus strains grew over a wide range of temperature (4-25 degrees C) and pH 2.2-7.0. Growth at 4 degrees C was significant. Zygosaccharomyces lentus strains grew at 25-26 degrees C in static culture but were unable to grow in aerobic culture close to their temperature maximum. All Z. lentus strains grew in 60% w/v sugar and consequently, are osmotolerant. Zygosaccharomyces lentus strains could utilize sucrose, glucose or fructose as a source of fermentable sugar, but not galactose. Zygosaccharomyces lentus strains were resistant to food preservatives, growing in sorbic acid up to 400 mg l-1 and benzoic acid to 900 mg l-1 at pH 4.0. Adaptation to higher preservative concentrations was demonstrated with benzoic acid. Resistance to DMDC was shown to be greater than that of Z. bailii and Saccharomyces cerevisiae. This study confirms that Z. lentus is an important food spoilage organism potentially capable of growth in a wide range of food products, particularly low pH, high sugar foods and drinks. It is likely to be more significant than Z. bailii in the spoilage of chilled products.

  13. A non-traditional model of the metabolic syndrome: the adaptive significance of insulin resistance in fasting-adapted seals

    Directory of Open Access Journals (Sweden)

    Dorian S Houser

    2013-11-01

    Full Text Available Insulin resistance in modern society is perceived as a pathological consequence of excess energy consumption and reduced physical activity. Its presence in relation to the development of cardiovascular risk factors has been termed the metabolic syndrome, which produces increased mortality and morbidity and which is rapidly increasing in human populations. Ironically, insulin resistance likely evolved to assist animals during food shortages by increasing the availability of endogenous lipid for catabolism while protecting protein from use in gluconeogenesis and eventual oxidation. Some species that incorporate fasting as a predictable component of their life history demonstrate physiological traits similar to the metabolic syndrome during prolonged fasts. One such species is the northern elephant seal (Mirounga angustirostris, which fasts from food and water for periods of up to three months. During this time, ~90% of the seals metabolic demands are met through fat oxidation and circulating non-esterified fatty acids are high (0.7-3.2 mM. All life history stages of elephant seal studied to date demonstrate insulin resistance and fasting hyperglycemia as well as variations in hormones and adipocytokines that reflect the metabolic syndrome to some degree. Elephant seals demonstrate some intriguing adaptations with the potential for medical advancement; for example, ketosis is negligible despite significant and prolonged fatty acid oxidation and investigation of this feature might provide insight into the treatment of diabetic ketoacidosis. The parallels to the metabolic syndrome are likely reflected to varying degrees in other marine mammals, most of which evolved on diets high in lipid and protein content but essentially devoid of carbohydrate. Utilization of these natural models of insulin resistance may further our understanding of the pathophysiology of the metabolic syndrome in humans and better assist the development of preventative measures

  14. A non-traditional model of the metabolic syndrome: the adaptive significance of insulin resistance in fasting-adapted seals.

    Science.gov (United States)

    Houser, Dorian S; Champagne, Cory D; Crocker, Daniel E

    2013-11-01

    Insulin resistance in modern society is perceived as a pathological consequence of excess energy consumption and reduced physical activity. Its presence in relation to the development of cardiovascular risk factors has been termed the metabolic syndrome, which produces increased mortality and morbidity and which is rapidly increasing in human populations. Ironically, insulin resistance likely evolved to assist animals during food shortages by increasing the availability of endogenous lipid for catabolism while protecting protein from use in gluconeogenesis and eventual oxidation. Some species that incorporate fasting as a predictable component of their life history demonstrate physiological traits similar to the metabolic syndrome during prolonged fasts. One such species is the northern elephant seal (Mirounga angustirostris), which fasts from food and water for periods of up to 4 months. During this time, ∼90% of the seals metabolic demands are met through fat oxidation and circulating non-esterified fatty acids are high (0.7-3.2 mM). All life history stages of elephant seal studied to date demonstrate insulin resistance and fasting hyperglycemia as well as variations in hormones and adipocytokines that reflect the metabolic syndrome to some degree. Elephant seals demonstrate some intriguing adaptations with the potential for medical advancement; for example, ketosis is negligible despite significant and prolonged fatty acid oxidation and investigation of this feature might provide insight into the treatment of diabetic ketoacidosis. The parallels to the metabolic syndrome are likely reflected to varying degrees in other marine mammals, most of which evolved on diets high in lipid and protein content but essentially devoid of carbohydrate. Utilization of these natural models of insulin resistance may further our understanding of the pathophysiology of the metabolic syndrome in humans and better assist the development of preventative measures and therapies.

  15. Significance of multi-drug-resistant proteins in predicting chemotherapy response and prognosis in epithelial ovarian cancer.

    Science.gov (United States)

    Yokoyama, Y; Sato, S; Fukushi, Y; Sakamoto, T; Futagami, M; Saito, Y

    1999-12-01

    To clarify the expression of multi-drug-resistant (MDR) markers, GST-pi, c-Jun, P-glycoprotein (Pgp), and MDR-associated protein (MRP) in epithelial ovarian cancer, and to determine whether their expression is predictive of chemotherapy response and patient prognosis. Specimens of 58 epithelial ovarian cancer cases obtained at initial surgery were studied immunohistochemically using antibodies. Overall positive rates in the 58 specimens were 58.6% for GST-pi, 44.8% for c-Jun, 27.6% for Pgp, and 22.4% for MRP. The 5-year disease-free survival rate was 26.0% for patients with MRP-positive tumors and 75.2% for those with MRP-negative tumors. The prognosis for those with MRP-positive tumors was significantly poorer (p < 0.05). Patients with GST-pi-positive tumors had a significantly worse prognosis than those with GST-pi-negative tumors (51.9% vs 79.2%, p < 0.05). Multivariate analysis showed that residual tumors 2 cm or larger and MRP expression were independent prognostic factors for chemotherapy resistance. The relative risk of chemotherapy resistance in a patient with a residual tumor 2 cm or larger, positive MRP, and positive GST-pi was 10.6 times greater than the risk in a patient without these factors. MRP and GST-pi expression might be potential predictors of the response to standard chemotherapy in epithelial ovarian cancer. Their expression also might contribute to individualizing clinical trials of postoperative chemotherapy.

  16. Expression of chicken interleukin-2 by a highly virulent strain of Newcastle disease virus leads to decreased systemic viral load but does not significantly affect mortality in chickens

    Science.gov (United States)

    In mammals, interleukin 2 (IL-2) has been shown to decrease replication or attenuate pathogenicity of numerous viral pathogens by activating natural killer cells (NK), cytotoxic T lymphocytes, and expanding subsets of memory cells. In chickens, IL-2 has been shown to activate T cells, and as such i...

  17. Significant association of TREM-1 with HMGB1, TLRs and RAGE in the pathogenesis of insulin resistance in obese diabetic populations.

    Science.gov (United States)

    Subramanian, Saravanan; Pallati, Pradeep K; Sharma, Poonam; Agrawal, Devendra K; Nandipati, Kalyana C

    2017-01-01

    Activated cell surface and intracellular receptors lead to insulin resistance in obesity. Among these receptors, triggering receptors expressed on myeloid cells (TREM)-1, toll like receptors (TLRs), and receptors for advanced glycation end products (RAGE) play a significant role in the induction of inflammatory response in innate immunity. TREM-1 potentially amplifies TLRs and RAGE synergistically with DNA-binding high-mobility group box 1 (HMGB-1). The objective of the study was to analyze the association between TREM-1/DAP12 and HMGB-1, RAGE and TLRs in obesity-induced insulin resistance. We examined the mRNA expression by RT-PCR and protein expression by Western blotting and immunofluorescence for TREM-1, TREM-2, DAP-12, HMGB-1, RAGE, TLR-4 and TLR-2 in omentum, subcutaneous and liver biopsy tissues of obese diabetic (n=22) and non-diabetic subjects (n=24) and compared with the non-obese non-diabetic controls (n=5). There was a significantly increased expression of TREM-1, DAP-12, HMGB-1, RAGE, TLR-4 and TLR-2 and decreased expression of TREM-2 in the omentum, subcutaneous and liver biopsy of obese diabetic subjects compared to obese non-diabetics and the non-obese population. Overall, obese diabetic subjects had high expression of TREM-1 in association with HMGB1 (100% vs 58.3%, P=0.003), RAGE (77.3% vs 41.7%, P=0.045), TLR4 (100% vs 58.3%, P=0.003), and TLR2 (100% vs 50%, P=0.003) in liver biopsy samples in comparison to obese non-diabetic subjects. Obese diabetics have significantly increased TREM-1, HMGB1, RAGE, and TLRs compared to obese non-diabetics. Our findings suggest a potential pathophysiological role of TREM-1 in conjunction with HMGB1 and inflammatory cell receptors (RAGE, TLR-4 and TLR-2) in obesity-induced insulin resistance.

  18. Resolving cognitive dissonance by acquisition of self-organizational skills may decrease drug-resistant seizures - A case report.

    Science.gov (United States)

    Michaelis, Rosa; Andrews, Donna J; Reiter, Joel M; von Schoen-Angerer, Tido

    2014-01-01

    A recent review of psychobehavioral therapy for epilepsy recommends case reports as a research design to explore specific psychological mediators of psychobehavioral interventions for epilepsy that address the bidirectional relationship between psychological states and seizures. The report was prepared according to the consensus-based CARE guidelines for standardized clinical case reporting. This is a case of a 16-year-old male individual with a diagnosed seizure disorder and learning disability who continued to have daytime and nighttime seizures on a regular basis despite exhausting of available conventional treatment options. A psychological assessment led to the working hypothesis that cognitive dissonance between fear of failure and high expectations of self had led to a "broken" self-image and active avoidance of responsibility that resulted in intense emotional distress which correlated with the occurrence of seizures. This working hypothesis resulted in a treatment plan that employed the acquisition of self-organizational skills and relaxation techniques as the main therapeutic strategy. Motivational strategies were employed to facilitate the regulation of lifestyle-related seizure precipitants. In this case, the acquisition of self-organizational skills and the development of seizure interruption techniques correlated with a clinically significant decrease of seizures. Methodological limitations of the interpretation of the presented data are discussed.

  19. Antibiotic Resistance in Haemophilus influenzae Decreased, except for β-Lactamase-Negative Amoxicillin-Resistant Isolates, in Parallel with Community Antibiotic Consumption in Spain from 1997 to 2007▿

    Science.gov (United States)

    García-Cobos, Silvia; Campos, José; Cercenado, Emilia; Román, Federico; Lázaro, Edurne; Pérez-Vázquez, María; de Abajo, Francisco; Oteo, Jesús

    2008-01-01

    The susceptibility to 14 antimicrobial agents and the mechanisms of aminopenicillin resistance were studied in 197 clinical isolates of Haemophilus influenzae—109 isolated in 2007 (study group) and 88 isolated in 1997 (control group). Community antibiotic consumption trends were also examined. H. influenzae strains were consecutively isolated from the same geographic area, mostly from respiratory specimens from children and adults. Overall, amoxicillin resistance decreased by 8.4% (from 38.6 to 30.2%). β-Lactamase production decreased by 15.6% (from 33 to 17.4%, P = 0.01), but amoxicillin resistance without β-lactamase production increased by 7.1% (from 5.7 to 12.8%). All β-lactamase-positive isolates were TEM-1, but five different promoter regions were identified, with Pdel being the most prevalent in both years, and Prpt being associated with the highest amoxicillin resistance. A new promoter consisting of a double repeat of 54 bp was detected. Community consumption of most antibiotics decreased, as did the geometric means of their MICs, but amoxicillin-clavulanic acid and azithromycin consumption increased by ca. 60%. For amoxicillin-clavulanic acid, a 14.2% increase in the population with an MIC of 2 to 4 μg/ml (P = 0.02) was observed; for azithromycin, a 21.2% increase in the population with an MIC of 2 to 8 μg/ml (P = 0.0005) was observed. In both periods, the most common gBLNAR (i.e., H. influenzae isolates with mutations in the ftsI gene as previously defined) patterns were IIc and IIb. Community consumption of trimethoprim-sulfamethoxazole decreased by 54%, while resistance decreased from 50 to 34.9% (P = 0.04). Antibiotic resistance in H. influenzae decreased in Spain from 1997 to 2007, but surveillance should be maintained since new forms of resistances may be developing. PMID:18505850

  20. Decreased PARP and procaspase-2 protein levels are associated with cellular drug resistance in childhood acute lymphoblastic leukemia

    NARCIS (Netherlands)

    A. Holleman (Amy); M.L. den Boer (Monique); K.M. Kazemier (Karin); H.B. Beverloo (Berna); A.R.M. von Bergh (Anne); G.E. Janka-Schaub (Gritta); R. Pieters (Rob)

    2005-01-01

    textabstractDrug resistance in childhood acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) is associated with impaired ability to induce apoptosis. To elucidate causes of apoptotic defects, we studied the protein expression of Apaf-1, procaspases-2, -3, -6, -7,

  1. The proteomic signature of insulin-resistant human skeletal muscle reveals increased glycolytic and decreased mitochondrial enzymes

    DEFF Research Database (Denmark)

    Giebelstein, J; Poschmann, G; Højlund, K

    2012-01-01

    The molecular mechanisms underlying insulin resistance in skeletal muscle are incompletely understood. Here, we aimed to obtain a global picture of changes in protein abundance in skeletal muscle in obesity and type 2 diabetes, and those associated with whole-body measures of insulin action....

  2. Resistance to oxidative stress induced by paraquat correlates well with both decreased and increased lifespan in Drosophila melanogaster

    NARCIS (Netherlands)

    Vermeulen, CJ; Van De Zande, L; Bijlsma, R

    2005-01-01

    There is increasing support for the notion that genetic variation for lifespan, both within and between species, is correlated with variation in the efficiency of the free radical scavenging system and the ability to withstand oxidative stress. In Drosophila, resistance to dietary paraquat, a free

  3. No significant role for beta tubulin mutations and mismatch repair defects in ovarian cancer resistance to paclitaxel/cisplatin

    International Nuclear Information System (INIS)

    Mesquita, Bárbara; Veiga, Isabel; Pereira, Deolinda; Tavares, Ana; Pinto, Isabel M; Pinto, Carla; Teixeira, Manuel R; Castedo, Sérgio

    2005-01-01

    The mechanisms of chemoresistance in ovarian cancer patients remain largely to be elucidated. Paclitaxel/cisplatin combination is the standard chemotherapeutic treatment for this disease, although some patients do not respond to therapy. Our goals were to investigate whether TUBB mutations and mismatch repair defects underlie paclitaxel and cisplatin resistance. Thirty-four patients with primary ovarian carcinomas (26 serous and eight clear cell carcinomas) treated with paclitaxel/cisplatin were analysed. TUBB exon 4 was analysed by nested PCR after a first round PCR using intronic primers. Microsatellite analysis was performed with the quasimonomorphic markers BAT 26 and BAT 34. Twenty-two of the 34 ovarian cancers (64.7%) presented residual tumour after surgery, seven of which (7/22; 31.8%) were shown to be chemoresistant (five serous and two clear cell tumours). Sequence analysis did not find any mutation in TUBB exon 4. Microsatellite instability was not detected in any of the ovarian carcinomas. We conclude that TUBB exon 4 mutations and mismatch repair defects do not play a significant role in paclitaxel/cisplatin resistance

  4. An exception to the rule "no association between antibiotic resistance and decreased disinfectant microbicidal efficacy": Orthophthalaldehyde (OPA) andPseudomonas aeruginosaisolated from ICU and paraplegic patients.

    Science.gov (United States)

    Herruzo, R; Vizcaíno, M J; Herruzo, I

    2017-03-01

    Antibiotic resistance and decreased susceptibility to disinfectants are not usually associated in microorganisms, but we have found an exception to this rule: P. aeruginosa versus orthophthalaldehyde (OPA). Bactericidal effect of OPA was measured at 10 minutes on endodoncy files contaminated with an ATCC strain (control) or 206 strains of P. aeruginosa recently isolated from 206 ICU and paraplegic patients in a tertiary university hospital, in two consecutive years. Differences in bactericidal effect of OPA were found between the strains isolated each year (decreased susceptibility in the first period), but in both years the statistical differences (p OPA susceptibility in parallel to an increase of their antibiotic resistance. In contrast, there were no differences depending on the type of sample (sputum, urine, faeces, pharynx) or of patient (paraplegic or ICU: adult, newborn, burn). Finally we selected 15 strains with an OPA effect below 3.5 log10 at 10 minutes and repeated the study with an OPA exposure of 15 minutes. In these conditions OPA showed a total bactericidal effect on these P. aeruginosa strains. There was an association between antibiotic resistance and decreased OPA susceptibility. This normally does not require an increase in disinfection time, but, for endoscope disinfection or instruments from colonized/infected patients with resistant/multiresistant P. aeruginosa, we consider it better to use 15 min of OPA. Regular tests (e.g., once every 12 months) with germ-carriers, should be performed to assess ecological changes in susceptibility to high level disinfectants and must include not only ATCC strains, but also recently isolated microorganisms with different antibiotic sensitivities (susceptible, resistant and multi-resistant).

  5. Soluble CD36 and risk markers of insulin resistance and atherosclerosis are elevated in polycystic ovary syndrome and significantly reduced during pioglitazone treatment

    DEFF Research Database (Denmark)

    Glintborg, Dorte; Højlund, Kurt; Andersen, Marianne

    2007-01-01

    Objective: We investigated the relation between soluble CD36 (sCD36), risk markers of atherosclerosis and body composition, and glucose and lipid metabolism in polycystic ovary syndrome (PCOS) Research Design and Methods: Thirty PCOS patients were randomized to pioglitazone, 30 mg/day or placebo...... independent predictors of glucose, and lipid metabolism, whereas hsCRP and IL-6 showed no significant contribution. Following pioglitazone treatment, insulin sensitivity increased, whereas sCD36 (3.21(0.76 - 13.6) vs. 2.33 (0.84 - 6.46) relative units) and hsCRP decreased (p... measured in body composition. Conclusions: sCD36 and oxLDL correlated with measures of insulin sensitivity independent of central fat mass. Pioglitazone treatment reduced sCD36 while improving insulin-stimulated glucose metabolism, further supporting the association between sCD36 and insulin resistance...

  6. In nondiabetic, human immunodeficiency virus-infected patients with lipodystrophy, hepatic insulin extraction and posthepatic insulin clearance rate are decreased in proportion to insulin resistance

    DEFF Research Database (Denmark)

    Haugaard, Steen B; Andersen, Ove; Hansen, Birgitte R

    2005-01-01

    In healthy, nondiabetic individuals with insulin resistance, fasting insulin is inversely correlated to the posthepatic insulin clearance rate (MCRi) and the hepatic insulin extraction (HEXi). We investigated whether similar early mechanisms to facilitate glucose homeostasis exist in nondiabetic...... > .1). Our data suggest that HEXi and MCRi are decreased in proportion to the degree of insulin resistance in nondiabetic HIV-infected patients with lipodystrophy....... insulin clearance rate was estimated as the ratio of posthepatic insulin appearance rate to steady-state plasma insulin concentration during a euglycemic hyperinsulinemic clamp (40 mU.m-2 .min-1). Posthepatic insulin appearance rate during the clamp was calculated, taking into account the remnant...

  7. Lipid-induced insulin resistance in cultured hepatoma cells is associated with a decreased insulin receptor tyrosine kinase activity.

    OpenAIRE

    Hubert, P; Bruneau-Wack, C; Cremel, G; Le Marchand-Brustel, Y; Staedel, C

    1991-01-01

    We have shown previously that experimental modifications of the cellular lipid composition of an insulin-sensitive rat hepatoma cell line (Zajdela Hepatoma Culture, ZHC) affect both binding and biological actions of insulin. Discrepancies between insulin binding and actions implied a postbinding defect, responsible for the observed insulin resistance in lipid-treated cells. To elucidate the mechanism for this defect, we have studied insulin binding and insulin receptor kinase activity in part...

  8. GLUT4 content decreases along with insulin resistance and high levels of inflammatory markers in rats with metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Leguisamo Natalia M

    2012-08-01

    Full Text Available Abstract Background Metabolic syndrome is characterized by insulin resistance, which is closely related to GLUT4 content in insulin-sensitive tissues. Thus, we evaluated the GLUT4 expression, insulin resistance and inflammation, characteristics of the metabolic syndrome, in an experimental model. Methods Spontaneously hypertensive neonate rats (18/group were treated with monosodium glutamate (MetS during 9 days, and compared with Wistar-Kyoto (C and saline-treated SHR (H. Blood pressure (BP and lipid levels, C-reactive protein (CRP, interleukin 6 (IL-6, TNF-α and adiponectin were evaluated. GLUT4 protein was analysed in the heart, white adipose tissue and gastrocnemius. Studies were performed at 3 (3-mo, 6 (6-mo and 9 (9-mo months of age. Results MetS rats were more insulin resistant (pvs H, but adiponectin was lower in MetS at 9 months (MetS: 32 ± 2, H: 42 ± 2, C: 45 ± 2 pg/mL; p Conclusions MSG-treated SHR presented all metabolic syndrome characteristics, as well as reduced GLUT4 content, which must play a key role in the impaired glycemic homeostasis of the metabolic syndrome.

  9. Decreased emergence of HIV-1 drug resistance mutations in a cohort of Ugandan women initiating option B+ for PMTCT.

    Directory of Open Access Journals (Sweden)

    Patrycja Machnowska

    Full Text Available Since 2012, WHO guidelines for the prevention of mother-to-child transmission (PMTCT of HIV-1 in resource-limited settings recommend the initiation of lifelong antiretroviral combination therapy (cART for all pregnant HIV-1 positive women independent of CD4 count and WHO clinical stage (Option B+. However, long-term outcomes regarding development of drug resistance are lacking until now. Therefore, we analysed the emergence of drug resistance mutations (DRMs in women initiating Option B+ in Fort Portal, Uganda, at 12 and 18 months postpartum (ppm.124 HIV-1 positive pregnant women were enrolled within antenatal care services in Fort Portal, Uganda. Blood samples were collected at the first visit prior starting Option B+ and postpartum at week six, month six, 12 and 18. Viral load was determined by real-time RT-PCR. An RT-PCR covering resistance associated positions in the protease and reverse transcriptase HIV-1 genomic region was performed. PCR-positive samples at 12/18 ppm and respective baseline samples were analysed by next generation sequencing regarding HIV-1 drug resistant variants including low-frequency variants. Furthermore, vertical transmission of HIV-1 was analysed. 49/124 (39.5% women were included into the DRM analysis. Virological failure, defined as >1000 copies HIV-1 RNA/ml, was observed in three and seven women at 12 and 18 ppm, respectively. Sequences were obtained for three and six of these. In total, DRMs were detected in 3/49 (6.1% women. Two women displayed dual-class resistance against all recommended first-line regimen drugs. Of 49 mother-infant-pairs no infant was HIV-1 positive at 12 or 18 ppm.Our findings suggest that the WHO-recommended Option B+ for PMTCT is effective in a cohort of Ugandan HIV-1 positive pregnant women with regard to the low selection rate of DRMs and vertical transmission. Therefore, these results are encouraging for other countries considering the implementation of lifelong cART for all pregnant

  10. Human circulating plasma DNA significantly decreases while lymphocyte DNA damage increases under chronic occupational exposure to low-dose gamma-neutron and tritium β-radiation.

    Science.gov (United States)

    Korzeneva, Inna B; Kostuyk, Svetlana V; Ershova, Liza S; Osipov, Andrian N; Zhuravleva, Veronika F; Pankratova, Galina V; Porokhovnik, Lev N; Veiko, Natalia N

    2015-09-01

    The blood plasma of healthy people contains cell-fee (circulating) DNA (cfDNA). Apoptotic cells are the main source of the cfDNA. The cfDNA concentration increases in case of the organism's cell death rate increase, for example in case of exposure to high-dose ionizing radiation (IR). The objects of the present research are the blood plasma and blood lymphocytes of people, who contacted occupationally with the sources of external gamma/neutron radiation or internal β-radiation of tritium N = 176). As the controls (references), blood samples of people, who had never been occupationally subjected to the IR sources, were used (N = 109). With respect to the plasma samples of each donor there were defined: the cfDNA concentration (the cfDNA index), DNase1 activity (the DNase1 index) and titre of antibodies to DNA (the Ab DNA index). The general DNA damage in the cells was defined (using the Comet assay, the tail moment (TM) index). A chronic effect of the low-dose ionizing radiation on a human being is accompanied by the enhancement of the DNA damage in lymphocytes along with a considerable cfDNA content reduction, while the DNase1 content and concentration of antibodies to DNA (Ab DNA) increase. All the aforementioned changes were also observed in people, who had not worked with the IR sources for more than a year. The ratio cfDNA/(DNase1×Ab DNA × TM) is proposed to be used as a marker of the chronic exposure of a person to the external low-dose IR. It was formulated the assumption that the joint analysis of the cfDNA, DNase1, Ab DNA and TM values may provide the information about the human organism's cell resistivity to chronic exposure to the low-dose IR and about the development of the adaptive response in the organism that is aimed, firstly, at the effective cfDNA elimination from the blood circulation, and, secondly - at survival of the cells, including the cells with the damaged DNA. Copyright © 2015. Published by Elsevier B.V.

  11. The HIV-1 reverse transcriptase M184I mutation enhances the E138K-associated resistance to rilpivirine and decreases viral fitness.

    Science.gov (United States)

    Kulkarni, Rima; Babaoglu, Kerim; Lansdon, Eric B; Rimsky, Laurence; Van Eygen, Veerle; Picchio, Gaston; Svarovskaia, Evguenia; Miller, Michael D; White, Kirsten L

    2012-01-01

    The registrational phase III clinical trials of the nonnucleoside reverse transcriptase (RT) inhibitor (NNRTI) rilpivirine (RPV) in combination with two nucleoside/nucleotide RT inhibitors (NRTIs) found a unique genotypic resistance pattern involving the NNRTI mutation E138K with the NRTI mutation M184I. Eighty percent of subjects used emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF); a single tablet regimen of FTC/RPV/TDF is in development. HIV-1 with E138K and/or M184V or I mutations were constructed and phenotyped in MT-2 cells and the PhenoSense and Antivirogram assays. Viral fitness was determined using growth competitions. Molecular models of the mutants were constructed from the RT-RPV crystal structure. The E138K mutant showed low-level reduced susceptibility to RPV (2.4-fold), but full susceptibility to FTC and tenofovir (TFV). Viruses with M184V or M184I showed high-level resistance to FTC and full susceptibility to RPV and TFV. Addition of M184I, but not M184V, to E138K, further decreased susceptibility to RPV and maintained FTC resistance. The E138K and M184V or I single and double mutants showed decreased replication fitness compared with wild type. M184V outcompeted M184I when compared directly and in the background of E138K. E138K + M184I was less fit than either E138K or M184I alone. Removing a salt bridge between E138/K101 is implicated in resistance to RPV. The higher frequency of E138K and M184I among RPV + FTC/TDF virologic failures is due to reduced susceptibility of the single mutants to RPV and FTC and the enhanced resistance to RPV for the double mutant at the cost of decreased viral fitness.

  12. Macrophytes may not contribute significantly to removal of nutrients, pharmaceuticals, and antibiotic resistance in model surface constructed wetlands.

    Science.gov (United States)

    Cardinal, Pascal; Anderson, Julie C; Carlson, Jules C; Low, Jennifer E; Challis, Jonathan K; Beattie, Sarah A; Bartel, Caitlin N; Elliott, Ashley D; Montero, Oscar F; Lokesh, Sheetal; Favreau, Alex; Kozlova, Tatiana A; Knapp, Charles W; Hanson, Mark L; Wong, Charles S

    2014-06-01

    Outdoor shallow wetland mesocosms, designed to simulate surface constructed wetlands to improve lagoon wastewater treatment, were used to assess the role of macrophytes in the dissipation of wastewater nutrients, selected pharmaceuticals, and antibiotic resistance genes (ARGs). Specifically, mesocosms were established with or without populations of Typha spp. (cattails), Myriophyllum sibiricum (northern water milfoil), and Utricularia vulgaris (bladderwort). Following macrophyte establishment, mesocosms were seeded with ARG-bearing organisms from a local wastewater lagoon, and treated with a single pulse of artificial municipal wastewater with or without carbamazepine, clofibric acid, fluoxetine, and naproxen (each at 7.6μg/L), as well as sulfamethoxazole and sulfapyridine (each at 150μg/L). Rates of pharmaceutical dissipation over 28d ranged from 0.073 to 3.0d(-1), corresponding to half-lives of 0.23 to 9.4d. Based on calculated rate constants, observed dissipation rates were consistent with photodegradation driving clofibric acid, naproxen, sulfamethoxazole, and sulfapyridine removal, and with sorption also contributing to carbamazepine and fluoxetine loss. Of the seven gene determinants assayed, only two genes for both beta-lactam resistance (blaCTX and blaTEM) and sulfonamide resistance (sulI and sulII) were found in sufficient quantity for monitoring. Genes disappeared relatively rapidly from the water column, with half-lives ranging from 2.1 to 99d. In contrast, detected gene levels did not change in the sediment, with the exception of sulI, which increased after 28d in pharmaceutical-treated systems. These shallow wetland mesocosms were able to dissipate wastewater contaminants rapidly. However, no significant enhancement in removal of nutrients or pharmaceuticals was observed in mesocosms with extensive aquatic plant communities. This was likely due to three factors: first, use of naïve systems with an unchallenged capacity for nutrient assimilation and

  13. Effectiveness of a low-fructose and/or low-sucrose diet in decreasing insulin resistance (DISFRUTE study): study protocol for a randomized controlled trial

    OpenAIRE

    Dom?nguez Coello, Santiago; Carrillo Fern?ndez, Lourdes; Gobierno Hern?ndez, Jes?s; M?ndez Abad, Manuel; Borges ?lamo, Carlos; Garc?a Dopico, Jos? Antonio; Aguirre Jaime, Armando; Cabrera de Le?n, Antonio

    2017-01-01

    Background Research published to date on the relationship between insulin resistance (IR) and fructose consumption is scarce, has used different methods, and has yielded sometimes contradictory results. This study aims to determine whether a low-fructose and/or low-sucrose diet supervised by a physician or nurse decreases IR compared to a standard diet. Methods/design This field trial is located at primary care centers. The participants are adults aged 29 to 66?years, with a Body mass Index (...

  14. Vancomycin-resistant enterococci colonization among dialysis patients: a meta-analysis of prevalence, risk factors, and significance.

    Science.gov (United States)

    Zacharioudakis, Ioannis M; Zervou, Fainareti N; Ziakas, Panayiotis D; Rice, Louis B; Mylonakis, Eleftherios

    2015-01-01

    Vancomycin-resistant enterococci (VRE) have become important nosocomial pathogens causing outbreaks worldwide. Patients undergoing dialysis represent a vulnerable population due to their comorbid conditions, frequent use of antibacterial agents, and frequent contact with health care settings. Systematic review and meta-analysis of cross-sectional studies of screening for VRE colonization. Patients receiving long-term dialysis treatment. We performed a systematic literature search of PubMed and EMBASE databases to identify studies performing screening for VRE colonization among dialysis patients. Region, recent use of vancomycin or other antibiotics, previous hospitalization. (1) VRE colonization and (2) rate of VRE infection among colonized and noncolonized individuals. Relative effects were expressed as ORs and 95% CIs. We identified 23 studies that fulfilled the inclusion criteria and provided data for 4,842 dialysis patients from 100 dialysis centers. The pooled prevalence of VRE colonization was 6.2% (95% CI, 2.8%-10.8%), with significant variability between centers. The corresponding number for North American centers was 5.2% (95% CI, 2.8%-8.2%). Recent use of any antibiotic (OR, 3.62; 95% CI, 1.22-10.75), particularly vancomycin (OR, 5.15; 95% CI, 1.56-17.02), but also use of antibiotics other than vancomycin (OR, 2.92; 95% CI, 0.99-8.55) and recent hospitalization (OR, 4.55; 95% CI, 1.93-10.74) significantly increased the possibility of a VRE-positive surveillance culture. Colonized patients had a significantly higher risk of VRE infection (OR, 21.62; 95% CI, 5.33-87.69) than their noncolonized counterparts. In 19 of 23 studies, a low percentage of dialysis patients (vancomycin, and recent hospitalization are important predicting factors of colonization, whereas the risk of VRE infection is significantly higher for colonized patients. Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  15. Changes in T-cell subpopulations and cytokine network during early period of ibrutinib therapy in chronic lymphocytic leukemia patients: the significant decrease in T regulatory cells number.

    Science.gov (United States)

    Podhorecka, Monika; Goracy, Aneta; Szymczyk, Agnieszka; Kowal, Malgorzata; Ibanez, Blanca; Jankowska-Lecka, Olga; Macheta, Arkadiusz; Nowaczynska, Aleksandra; Drab-Urbanek, Elzbieta; Chocholska, Sylwia; Jawniak, Dariusz; Hus, Marek

    2017-05-23

    B cell receptor (BCR) stimulation signal plays an important role in the pathogenesis of chronic lymphocytic leukemia (CLL), and kinase inhibitors directed toward the BCR pathway are now the promising anti-leukemic drugs. Ibrutinib, a Bruton tyrosine kinase inhibitor, demonstrates promising clinical activity in CLL. It is reported that ibrutinib, additionally to directly targeting leukemic cells, also inhibits the interactions of these cells with T cells, macrophages and accessory cells. Assessment of these mechanisms is important because of their non -direct anti-leukemic effects and to identify possible side effects connected with long-term drug administration.The aim of this study was to assess the in vivo effects of ibrutinib on T-cell subpopulations and cytokine network in CLL. The analysis was performed on a group of 19 patients during first month of ibrutinib therapy. The standard multicolor flow cytometry and cytometric bead array methods were used for assessment of T-cell subsets and cytokines/chemokines, respectively.The data obtained indicates that Ibrutinib treatment results in changes in T-cell subpopulations and cytokine network in CLL patients. Particularly, a significant reduction of T regulatory cells in peripheral blood was observed. By targeting these populations of T cells Ibrutinib can stimulate rejection of tumor cells by the immune system.

  16. Bone stroma-derived cells change coregulators recruitment to androgen receptor and decrease cell proliferation in androgen-sensitive and castration-resistant prostate cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Villagran, Marcelo A.; Gutierrez-Castro, Francisco A.; Pantoja, Diego F.; Alarcon, Jose C.; Fariña, Macarena A.; Amigo, Romina F.; Muñoz-Godoy, Natalia A. [Molecular Endocrinology and Oncology Laboratory, University of Concepcion, Concepcion (Chile); Pinilla, Mabel G. [Department of Medical Specialties, School of Medicine, University of Concepcion, Concepcion (Chile); Peña, Eduardo A.; Gonzalez-Chavarria, Ivan; Toledo, Jorge R.; Rivas, Coralia I.; Vera, Juan C. [Department of Physiopathology, School of Biological Sciences, University of Concepcion, Concepcion (Chile); McNerney, Eileen M. [Molecular Endocrinology and Oncology Laboratory, University of Concepcion, Concepcion (Chile); Onate, Sergio A., E-mail: sergio.onate@udec.cl [Molecular Endocrinology and Oncology Laboratory, University of Concepcion, Concepcion (Chile); Department of Medical Specialties, School of Medicine, University of Concepcion, Concepcion (Chile); Department of Urology, State University of New York at Buffalo, NY (United States)

    2015-11-27

    Prostate cancer (CaP) bone metastasis is an early event that remains inactive until later-stage progression. Reduced levels of circulating androgens, due to andropause or androgen deprivation therapies, alter androgen receptor (AR) coactivator expression. Coactivators shift the balance towards enhanced AR-mediated gene transcription that promotes progression to androgen-resistance. Disruptions in coregulators may represent a molecular switch that reactivates latent bone metastasis. Changes in AR-mediated transcription in androgen-sensitive LNCaP and androgen-resistant C4-2 cells were analyzed for AR coregulator recruitment in co-culture with Saos-2 and THP-1. The Saos-2 cell line derived from human osteosarcoma and THP-1 cell line representing human monocytes were used to display osteoblast and osteoclast activity. Increased AR activity in androgen-resistant C4-2 was due to increased AR expression and SRC1/TIF2 recruitment and decreased SMRT/NCoR expression. AR activity in both cell types was decreased over 90% when co-cultured with Saos-2 or THP-1 due to dissociation of AR from the SRC1/TIF2 and SMRT/NCoR coregulators complex, in a ligand-dependent and cell-type specific manner. In the absence of androgens, Saos-2 decreased while THP-1 increased proliferation of LNCaP cells. In contrast, both Saos-2 and THP-1 decreased proliferation of C4-2 in absence and presence of androgens. Global changes in gene expression from both CaP cell lines identified potential cell cycle and androgen regulated genes as mechanisms for changes in cell proliferation and AR-mediated transactivation in the context of bone marrow stroma cells. - Highlights: • Decreased corepressor expression change AR in androgen-resistance prostate cancer. • Bone stroma-derived cells change AR coregulator recruitment in prostate cancer. • Bone stroma cells change cell proliferation in androgen-resistant cancer cells. • Global gene expression in CaP cells is modified by bone stroma cells in co

  17. Bone stroma-derived cells change coregulators recruitment to androgen receptor and decrease cell proliferation in androgen-sensitive and castration-resistant prostate cancer cells

    International Nuclear Information System (INIS)

    Villagran, Marcelo A.; Gutierrez-Castro, Francisco A.; Pantoja, Diego F.; Alarcon, Jose C.; Fariña, Macarena A.; Amigo, Romina F.; Muñoz-Godoy, Natalia A.; Pinilla, Mabel G.; Peña, Eduardo A.; Gonzalez-Chavarria, Ivan; Toledo, Jorge R.; Rivas, Coralia I.; Vera, Juan C.; McNerney, Eileen M.; Onate, Sergio A.

    2015-01-01

    Prostate cancer (CaP) bone metastasis is an early event that remains inactive until later-stage progression. Reduced levels of circulating androgens, due to andropause or androgen deprivation therapies, alter androgen receptor (AR) coactivator expression. Coactivators shift the balance towards enhanced AR-mediated gene transcription that promotes progression to androgen-resistance. Disruptions in coregulators may represent a molecular switch that reactivates latent bone metastasis. Changes in AR-mediated transcription in androgen-sensitive LNCaP and androgen-resistant C4-2 cells were analyzed for AR coregulator recruitment in co-culture with Saos-2 and THP-1. The Saos-2 cell line derived from human osteosarcoma and THP-1 cell line representing human monocytes were used to display osteoblast and osteoclast activity. Increased AR activity in androgen-resistant C4-2 was due to increased AR expression and SRC1/TIF2 recruitment and decreased SMRT/NCoR expression. AR activity in both cell types was decreased over 90% when co-cultured with Saos-2 or THP-1 due to dissociation of AR from the SRC1/TIF2 and SMRT/NCoR coregulators complex, in a ligand-dependent and cell-type specific manner. In the absence of androgens, Saos-2 decreased while THP-1 increased proliferation of LNCaP cells. In contrast, both Saos-2 and THP-1 decreased proliferation of C4-2 in absence and presence of androgens. Global changes in gene expression from both CaP cell lines identified potential cell cycle and androgen regulated genes as mechanisms for changes in cell proliferation and AR-mediated transactivation in the context of bone marrow stroma cells. - Highlights: • Decreased corepressor expression change AR in androgen-resistance prostate cancer. • Bone stroma-derived cells change AR coregulator recruitment in prostate cancer. • Bone stroma cells change cell proliferation in androgen-resistant cancer cells. • Global gene expression in CaP cells is modified by bone stroma cells in co

  18. Spaces for smoking in a psychiatric hospital: social capital, resistance to control, and significance for 'therapeutic landscapes'.

    Science.gov (United States)

    Wood, Victoria J; Curtis, Sarah E; Gesler, Wil; Spencer, Ian H; Close, Helen J; Mason, James M; Reilly, Joe G

    2013-11-01

    This paper reports on research framed by theories of therapeutic landscapes and the ways that the social, physical and symbolic dimensions of landscapes relate to wellbeing and healing. We focus especially on the question of how attributes of therapeutic landscapes are constructed in different ways according to the variable perspectives of individuals and groups. Through an ethnographic case study in a psychiatric hospital in the North of England we explore the perceived significance for wellbeing of 'smoking spaces' (where tobacco smoking is practiced in ways that may, or may not be officially sanctioned). We interpret our findings in light of literature on how smoking spaces are linked to the socio-geographical power relations that determine how smoking is organised within the hospital and how this is understood by different groups using the hospital building. We draw on qualitative research findings from discussion groups, observations, and interviews with patients, carers and staff. These focused on their views about the building design and setting of the new psychiatric hospital in relation to their wellbeing, and issues relating to smoking spaces emerged as important for many participants. Creating and managing smoking spaces as a public health measure in psychiatric hospitals is shown to be a controversial issue involving conflicting aims for health and wellbeing of patients and staff. Our findings indicate that although from a physical health perspective, smoking is detrimental, the spaces in which patients and staff smoke have social and psychological significance, providing a forum for the creation of social capital and resistance to institutional control. While the findings relate to one case study setting, the paper illustrates issues of wider relevance and contributes to an international literature concerning the tensions between perceived psychological and psychosocial benefits of smoking vs. physical harm that smoking is likely to cause. We consider

  19. Protein Supplementation Does Not Significantly Augment the Effects of Resistance Exercise Training in Older Adults: A Systematic Review.

    Science.gov (United States)

    Thomas, Danielle K; Quinn, Marcus A; Saunders, David H; Greig, Carolyn A

    2016-10-01

    Physical activity and nutritional supplementation interventions may be used to ameliorate age-related loss of skeletal muscle mass and function. Previous reviews have demonstrated the beneficial effects of resistance exercise training (RET) combined with protein or essential amino acids (EAA) in younger populations. Whether or not older adults also benefit is unclear. The aim of this review was to determine whether regular dietary supplementation with protein/EAA during a RET regimen augments the effects of RET on skeletal muscle in older adults. A literature search was conducted in August 2015 using MEDLINE, EMBASE, SPORTDiscus, and CINAHL Plus to identify all controlled trials using a RET regimen with and without protein/EAA supplementation. Outcome variables included muscle strength, muscle size, functional ability, and body composition. Fifteen studies fulfilled the eligibility criteria, including 917 participants with a mean age of 77.4 years. Studies involving both healthy participants and those described as frail or sarcopenic were included. Overall, results indicated that protein supplementation did not significantly augment the effects of RET on any of the specified outcomes. Exceptions included some measures of muscle strength (3 studies) and body composition (2 studies). Meta-analyses were conducted but were limited because of methodologic differences between studies, and results were inconclusive. Systematic review and meta-analysis of controlled trials reveal that protein/EAA supplementation does not significantly augment the effects of progressive RET in older adults. Copyright © 2016 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

  20. Efflux system overexpression and decreased OprD contribute to the carbapenem resistance among extended-spectrum beta-lactamase-producing Pseudomonas aeruginosa isolates from a Chinese university hospital.

    Science.gov (United States)

    Liu, Yang; Li, Xiang-Yang; Wan, La-Gen; Jiang, Wei-Yan; Li, Fang-Qu; Yang, Jing-Hong

    2013-12-01

    The aim of this study was to investigate, for the first time, the combinations of carbapenem resistance mechanisms in clinical isolates of extended-spectrum beta-lactamase (ESBL)-producing Pseudomonas aeruginosa in a Chinese hospital. Pulsed-field gel electrophoresis revealed the presence of eight clonal types among the 15 ESBL producers. Multilocus sequence typing of two isolates harboured blaIMP-1 identified the clonal strain as ST325. All these genes were found either alone or simultaneously in the strains in the following five different arrangements:; ; ; ; . Regarding mutation-driven resistance, all, but four of the isolates had a relevant decrease of oprD expression. In addition, 73.3% of the isolates overexpressed mexB, 40% mexD, and 33.3% mexY. A specific combination of overexpressed mexB or mexY and alteration in loop L710 of OprD were significantly associated with meropenem resistance. In conclusion, combination of several mutation-driven mechanisms leading to OprD inactivation and overexpression of efflux systems was the main carbapenem resistance mechanism among the ESBL-producing P. aeruginosa isolates, but acquisition of a transferable resistance determinant such as metallo-β-lactamase could be problematic in clinical settings in China.

  1. Oxacillin-susceptible methicillin-resistant Staphylococcus aureus (OS-MRSA), a hidden resistant mechanism among clinically significant isolates in the Wessex region/UK.

    Science.gov (United States)

    Saeed, K; Ahmad, N; Dryden, M; Cortes, N; Marsh, P; Sitjar, A; Wyllie, S; Bourne, S; Hemming, J; Jeppesen, C; Green, S

    2014-10-01

    Methicillin-resistant Staphylococcus aureus (MRSA) is defined as S. aureus genetically having the mecA or mecC genes or phenotypically showing minimum inhibitory concentration (MIC) of oxacillin higher than 2 mg/L. However, recently, cefoxitin/oxacillin-susceptible mecA-positive S. aureus (OS-MRSA) has been reported worldwide. Little is known about the prevalence and virulence of these strains among clinically significant isolates in the UK. The aims were to (1) investigate the prevalence of OS-MRSA in seven major hospitals in the Wessex region/UK from a cohort of 500 clinically significant phenotypically identified MSSA isolates, (2) genetically characterise OS-MRSA strains by pulsed-field gel electrophoresis (PFGE) and compare these to common UK epidemic strains; and (3) to determine Panton-Valentine leukocidin (PVL; lukFS) gene carriage rates among these isolates. OS-MRSA was found in six isolates (1.2 %) of phenotypically identified and reported MSSA isolates by conventional methods. PFGE showed OS-MRSA strains to be genetically diverse and distinct from the common UK epidemic strains EMRSA-15 and EMRSA-16. None of these OS-MRSA stains carried the genes encoding PVL; however, overall positivity rate for PVL was 4.4 %, much higher than the nationally reported rates of 2 % in the UK. There are still many unknowns regarding phenotypic and/or genetic characterization of the emerging OS-MRSA isolates in the UK and worldwide. Data regarding their epidemiology and optimal therapy for infection are limited and need further investigation not only in the UK, but also worldwide, as it is likely to have an impact on the empirical treatment of S. aureus infections.

  2. Can ultraviolet light C decrease the environmental burden of antimicrobial-resistant and -sensitive bacteria on textiles?

    Science.gov (United States)

    Bentley, Jennifer J; Santoro, Domenico; Gram, Dunbar W; Dujowich, Mauricio; Marsella, Rosanna

    2016-12-01

    The environment is important in transmission of bacteria. Textiles are difficult and time consuming to clean; ultraviolet light C (UVC) is germicidal and may be an effective disinfection method for textile surfaces. This study evaluated the efficacy of UVC, a commercial quaternary ammonium compound antimicrobial spray (FAS) and UVC+FAS combined for reducing bacterial colonization on experimentally contaminated textiles. Microfibre, cotton and polyester were inoculated with meticillin-sensitive and -resistant Staphylococcus aureus (MSSA and MRSA), Staphylococcus pseudintermedius (MSSP and MRSP), Pseudomonas aeruginosa or Escherichia coli. ATCC ® strains were used except for MRSP, for which ten canine clinical isolates were collected. Textiles were treated with three doses of UVC (13 mJ/cm 2 , 54 mJ/cm 2 or 270 mJ/cm 2 ), FAS or both (FAS and UVC at 270 mJ/cm 2 ). UVC was delivered using a modified mercury-based lamp. Bleach (8.25%) was used as a positive control. Negative controls received no treatment. Surface bacterial counts were determined 24 h post-treatment. The lower dosages (13 mJ/cm 2 and 54 mJ/cm 2 ) of UVC had >90% colony forming unit (CFU) reduction, 270 mJ/cm 2 had >99% CFU reduction and combined UVC+FAS had 100% CFU reduction against all bacterial strains on all surfaces (P < 0.05). Ten experiments showed that treatment with UVC had a greater CFU reduction when compared to FAS alone (P < 0.05). A majority of those experiments (seven of 10) involved Gram-negative species (P. aeruginosa or E. coli). UVC quickly reduced the bacterial burden on textiles to greater than 90%; UVC may be a better disinfecting agent than FAS for Gram-negative species. © 2016 ESVD and ACVD.

  3. Genome sequencing of a Neisseria gonorrhoeae isolate of a successful international clone with decreased susceptibility and resistance to extended-spectrum cephalosporins.

    Science.gov (United States)

    Hess, David; Wu, Abel; Golparian, Daniel; Esmaili, Sarah; Pandori, Will; Sena, Emilee; Klausner, Jeffrey D; Barry, Pennan; Unemo, Magnus; Pandori, Mark

    2012-11-01

    The recent emergence of Neisseria gonorrhoeae strains with decreased susceptibility to extended-spectrum cephalosporins is a major concern globally. We sequenced the genome of an N. gonorrhoeae multiantigen sequence typing (NG-MAST) ST1407 isolate (SM-3) with decreased susceptibility and resistance to oral extended-spectrum cephalosporins. The isolate was cultured in 2008 in San Francisco, CA, and possessed mosaic penA allele XXXIV, which is associated with an international clone that possesses decreased susceptibility as well as resistance to oral extended-spectrum cephalosporins globally. The genome sequence of strain NCCP11945 was used as a scaffold, and our assembly resulted in 91 contigs covering 2,029,064 bp (91%; >150× coverage) of the genome. Numerous instances of suspected horizontal genetic transfer events with other Neisseria species were identified, and two genes, opa and txf, acquired from nongonococcal Neisseria species, were identified. Strains possessing mosaic penA alleles (n = 108) and nonmosaic penA alleles (n = 169) from the United States and Europe (15 countries), cultured in 2002 to 2009, were screened for the presence of these genes. The opa gene was detected in most (82%) penA mosaic-containing isolates (mainly from 2007 to 2009) but not in any penA nonmosaic isolates. The txf gene was found in all strains containing opa but also in several (18%) penA nonmosaic strains. Using opa and txf as genetic markers, we identified a strain that possesses mosaic penA allele XXXIV, but the majority of its genome is not genetically related to strain SM-3. This implies that penA mosaic allele XXXIV was transferred horizontally. Such isolates also possessed decreased susceptibility and resistance to oral extended-spectrum cephalosporins. These findings support that genetic screening for particular penA mosaic alleles can be a valuable method for tracking strains with decreased susceptibility as well as resistance to oral extended-spectrum cephalosporins

  4. CO{sub 2} emissions by installations submitted to quotas have significantly decreased in 2009; Les emissions de CO{sub 2} des installations soumises a quotas ont fortement baisse en 2009

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2011-07-01

    This document comments the significant decrease of CO{sub 2} emissions by installations submitted to quotas in the European Union. It outlines that French installations are among the most over-the-target ones. They notice that this decrease occurred in all the main emitting sectors, notably in iron and steel industry. However, this decrease is reduced by an increase of production's carbon intensity almost in all sectors, and more particularly in small and medium enterprises. As the economic recession is the main reason for the emission decrease, the price per ton of CO{sub 2} should be the incentive for further emission reductions

  5. A PGC-1α- and muscle fibre type-related decrease in markers of mitochondrial oxidative metabolism in skeletal muscle of humans with inherited insulin resistance

    DEFF Research Database (Denmark)

    Kristensen, Jonas M; Skov, Vibe; Petersson, Stine J

    2014-01-01

    with biological pathway analysis. Findings were validated by quantitative real-time PCR, immunoblotting and activity assays. RESULTS: In INSR mutation carriers, insulin resistance was associated with a coordinated downregulation of OxPhos genes in skeletal muscle. This was related to a 46% decrease in mRNA levels...... synthase activity (p = 0.025). Moreover, mutation carriers showed a marked reduction in type 1 muscle fibres (35% vs 62%, p = 0.0005) and increased type 2a fibres (53% vs 32%; p = 0.002) compared with controls. There were no differences in protein content and phosphorylation of 5' AMP-activated protein...... kinase, p38 mitogen-activated protein kinase, Erk1 and Erk2. CONCLUSIONS/INTERPRETATION: These data indicate that inherited insulin resistance coincides with reduced mitochondrial oxidative capacity in a PGC-1α- and muscle fibre type-related manner. Whether this co-existence is directly or indirectly...

  6. Decreased susceptibility to cephalosporins among gonococci: data from the Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP) in England and Wales, 2007-2011.

    Science.gov (United States)

    Ison, Catherine A; Town, Katy; Obi, Chinelo; Chisholm, Stephanie; Hughes, Gwenda; Livermore, David M; Lowndes, Catherine M

    2013-09-01

    Effective treatment of gonorrhoea is fundamental to public health control; however, the ability of Neisseria gonorrhoeae to successively develop resistance to different treatments has hampered control efforts. The extended-spectrum cephalosporins--cefixime and ceftriaxone--have been recommended in the UK for treatment of gonorrhoea since 2005. We looked at surveillance data from England and Wales to ascertain the current usefulness of these drugs and to inform changes to national treatment guidelines. We obtained data from the Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP) for patients attending 26 genitourinary medicine clinics in England and Wales between 2007 and 2011. We did analyses with univariate and multivariable logistic regression methods to identify trends in susceptibility to cephalosporins and risk factors associated with infection with isolates with decreased susceptibility to cefixime, and we assessed changes in prescribing practices. We did molecular typing to investigate genetic relatedness of non-susceptible isolates. The prevalence of decreased susceptibility to both cefixime and ceftriaxone rose between 2007 and 2010 but was more noticeable for cefixime (an increase from 1·5% in 2007 to 17·1% in 2010), with a bimodal distribution of minimum inhibitory concentration recorded between 2009 and 2010. By multivariable analysis, isolates with decreased susceptibility to cefixime were associated with infection in men who have sex with men (odds ratio 5·47, 95% CI 3·99-7·48; pWales was changed in 2010 to prolong the use of cephalosporins. The decline in prevalence of isolates with decreased cefixime susceptibility cannot be attributed unequivocally to this change in prescribing practice; however, the association is striking. Department of Health (England), Public Health England. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Drug resistance in cortical and hippocampal slices from resected tissue of epilepsy patients: no significant impact of P-glycoprotein and Multidrug resistance associated proteins.

    Directory of Open Access Journals (Sweden)

    Nora eSandow

    2015-02-01

    Full Text Available Drug resistant patients undergoing epilepsy surgery have a good chance to become sensitive to anticonvulsant medication, suggesting that the resected brain tissue is responsible for drug resistance. Here, we address the question whether P-glycoprotein (Pgp and multidrug resistance associated proteins (MRPs expressed in the resected tissue contribute to drug resistance in vitro. Effects of anti-epileptic drugs (carbamazepine, sodium valproate, phenytoin and two unspecific inhibitors of Pgp and MRPs (verapamil and probenecid on seizure-like events induced in slices from 35 hippocampal and 35 temporal cortex specimens of altogether 51 patients (161 slices were studied. Although in slice preparations the blood brain barrier is not functional, we found that seizure-like events predominantly persisted in the presence of anticonvulsant drugs (90% and also in the presence of verapamil and probenecid (86%. Following subsequent co-administration of antiepileptic drugs and drug transport inhibitors, seizure-like events continued in 63% of 143 slices. Drug sensitivity in slices was recognized either as transition to recurrent epileptiform transients (30% or as suppression (7%, particularly by perfusion with carbamazepine in probenecid containing solutions (43%, 9%. Summarizing responses to co-administration from more than one slice per patient revealed that suppression of seizure-like activity in all slices was only observed in 7 % of patients. Patients whose tissue was completely or partially sensitive (65 % presented with higher seizure frequencies than those with resistant tissue (35 %. However, corresponding subgroups of patients don’t differ with respect to expression rates of drug transporters. Our results imply that parenchymal MRPs and Pgp are not responsible for drug resistance in resected tissue.

  8. Resisting majesty: Apis cerana, has lower antennal sensitivity and decreased attraction to queen mandibular pheromone than Apis mellifera

    Science.gov (United States)

    Dong, Shihao; Wen, Ping; Zhang, Qi; Li, Xinyu; Tan, Ken; Nieh, James

    2017-03-01

    In highly social bees, queen mandibular pheromone (QMP) is vital for colony life. Both Apis cerana (Ac) and Apis mellifera (Am) share an evolutionarily conserved set of QMP compounds: (E)-9-oxodec-2-enoic acid (9-ODA), (E)-9-hydroxydec-2-enoic acid (9-HDA), (E)-10-hydroxy-dec-2-enoic acid (10-HDA), 10-hydroxy-decanoic acid (10-HDAA), and methyl p-hydroxybenzoate (HOB) found at similar levels. However, evidence suggests there may be species-specific sensitivity differences to QMP compounds because Ac workers have higher levels of ovarian activation than Am workers. Using electroantennograms, we found species-specific sensitivity differences for a blend of the major QMP compounds and three individual compounds (9-HDA, 10-HDAA, and 10-HDA). As predicted, Am was more sensitive than Ac in all cases (1.3- to 2.7- fold higher responses). There were also species differences in worker retinue attraction to three compounds (9-HDA, HOB, and 10-HDA). In all significantly different cases, Am workers were 4.5- to 6.2-fold more strongly attracted than Ac workers were. Thus, Ac workers responded less strongly to QMP than Ac workers, and 9-HDA and 10-HDA consistently elicited stronger antennal and retinue formation responses.

  9. A one-year resistance training program following weight loss has no significant impact on body composition and energy expenditure in postmenopausal women living with overweight and obesity.

    Science.gov (United States)

    Hintze, Luzia Jaeger; Messier, Virginie; Lavoie, Marie-Ève; Brochu, Martin; Lavoie, Jean-Marc; Prud'homme, Denis; Rabasa-Lhoret, Rémi; Doucet, Éric

    2018-03-13

    Resistance training (RT) has been shown to decrease fat mass (FM), and increase fat-free mass (FFM), which can be a useful for weight loss maintenance. To examine the effects of a 1-year RT intervention on weight loss maintenance following a 6-month dietary weight loss intervention. Following a 6-month dietary weight loss intervention (-6% ± 5.8; 5.05 kg ± 4.45), 70 postmenopausal women living with overweight or obesity were randomized to a control group (n = 34) or a RT group (n = 36) (3×/week first 6 months, 2×/week last 6 months, 70-80% of 1-repetition maximum). Body composition (DXA), abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) (CT scan), resting energy expenditure (EE) (indirect calorimetry), physical activity EE and total daily EE were measured (doubly-labelled water). A total of 54 participants completed the study (control group n = 29; RT group n = 25) and compliance to the RT program was on average 64%. Significant regains were noted for body weight 0.98 (3.71) kg vs. 1.33 (3.94) kg and FM regain 1.32 (2.69) kg vs. 0.81 (3.26) kg in control and RT groups after the 1-year weight maintenance phase. No group differences were noted. Resting EE and total daily EE did not change after the weight maintenance phase, and no differences were observed between groups. Both groups had significantly greater than predicted decrease in resting EE after the 6-month dietary intervention and at the end of the 1-year weight-loss maintenance phase. Our results suggest that a 1-year RT intervention following a 6-month dietary weight loss intervention does not improve weight loss maintenance, body composition or EE in post-menopausal women living with overweight or obesity. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. Decreased Libido

    Science.gov (United States)

    ... causes decreased libido? Decreased libido often accompanies other sexual disorders. Although most men with erectile dysfunction do not complain of decreased libido, after time, persistent failure with erections and sexual performance can lead to reduced sex drive in ...

  11. Significant ecological impact on the progression of fluoroquinolone resistance in Escherichia coli with increased community use of moxifloxacin, levofloxacin and amoxicillin/clavulanic acid.

    Science.gov (United States)

    Cuevas, Oscar; Oteo, Jesús; Lázaro, Edurne; Aracil, Belén; de Abajo, Francisco; García-Cobos, Silvia; Ortega, Adriana; Campos, José

    2011-03-01

    To determine trends in ciprofloxacin resistance and co-resistance to other antibiotic classes in blood isolates of Escherichia coli, and to investigate if there is an ecological relationship to the community use of fluoroquinolones and other antibiotics. Forty-two Spanish hospitals of the European Antimicrobial Resistance Surveillance Network collected ciprofloxacin and other antibiotic susceptibility data for non-duplicate consecutive E. coli isolates from patients with bacteraemia between 2001 and 2009. The nationwide ambulatory use of antibiotics between 1997 and 2008 was determined by WHO methods, and the co-evolution of both parameters was further analysed. Of the 28 307 E. coli blood isolates, 27.9% were ciprofloxacin non-susceptible (CIPNS), increasing from 17.6% in 2001 to 32.7% in 2009. A continuous increase was observed between CIPNS and other resistances, including cephalosporin resistance due to the production of extended-spectrum β-lactamases (ESBLs) and non-susceptibility to both amoxicillin/clavulanic acid and tobramycin. Although the total use of antibiotics did not increase, community use of levofloxacin, moxifloxacin and amoxicillin/clavulanic acid increased by 307.2%, 62.6% and 70.1%, respectively. Yearly rates of CIPNS E. coli strongly correlated with the use of levofloxacin, moxifloxacin and amoxicillin/clavulanic acid (r(2 )> 0.80; P resistance to amoxicillin/clavulanic acid, production of ESBLs and resistance to aminoglycosides. Community use of fluoroquinolones (mainly moxifloxacin and levofloxacin) and of amoxicillin/clavulanic acid represents a significant driver in the progression of fluoroquinolone resistance in bacteraemic E. coli.

  12. Inhibition of Intestinal OATP2B1 by the Calcium Receptor Antagonist Ronacaleret Results in a Significant Drug-Drug Interaction by Causing a 2-Fold Decrease in Exposure of Rosuvastatin.

    Science.gov (United States)

    Johnson, Marta; Patel, Dipal; Matheny, Christopher; Ho, May; Chen, Liangfu; Ellens, Harma

    2017-01-01

    Rosuvastatin is a widely prescribed antihyperlipidemic which undergoes limited metabolism, but is an in vitro substrate of multiple transporters [organic anion transporting polypeptide 1B1 (OATP1B1), OATP1B3, OATP1A2, OATP2B1, sodium-taurocholate cotransporting polypeptide, breast cancer resistance protein (BCRP), multidrug resistance protein 2 (MRP2), MRP4, organic anion transporter 3]. It is therefore frequently used as a probe substrate in clinical drug-drug interaction (DDI) studies to investigate transporter inhibition. Although each of these transporters is believed to play a role in rosuvastatin disposition, multiple pharmacogenetic studies confirm that OATP1B1 and BCRP play an important role in vivo. Ronacaleret, a drug-development candidate for treatment of osteoporosis (now terminated), was shown to inhibit OATP1B1 in vitro (IC 50 = 11 µM), whereas it did not inhibit BCRP. Since a DDI risk through inhibition of OATP1B1 could not be discharged, a clinical DDI study was performed with rosuvastatin before initiation of phase II trials. Unexpectedly, coadministration with ronacaleret decreased rosuvastatin exposure by approximately 50%, whereas time of maximal plasma concentration and terminal half-life remained unchanged, suggesting decreased absorption and/or enhanced first-pass elimination of rosuvastatin. Of the potential in vivo rosuvastatin transporter pathways, two might explain the observed results: intestinal OATP2B1 and hepatic MRP4. Further investigations revealed that ronacaleret inhibited OATP2B1 (in vitro IC 50 = 12 µM), indicating a DDI risk through inhibition of absorption. Ronacaleret did not inhibit MRP4, discharging the possibility of enhanced first-pass elimination of rosuvastatin (reduced basolateral secretion from hepatocytes into blood). Therefore, a likely mechanism of the observed DDI is inhibition of intestinal OATP2B1, demonstrating the in vivo importance of this transporter in rosuvastatin absorption in humans. Copyright © 2016

  13. A Case of Inoperable Malignant Insulinoma with Resistant Hypoglycemia Who Experienced the Most Significant Clinical Improvement with Everolimus

    Directory of Open Access Journals (Sweden)

    Emre Bozkirli

    2013-01-01

    Full Text Available Metastatic insulinomas may sometimes present with recurrent life-threatening hypoglycemia episodes. Such patients usually fail to respond to various therapeutic agents which causes constant dextrose infusion requirement. Herein, we present a resistant case of inoperable malignant insulinoma who was treated with many therapeutic agents and interventions including somatostatin analogues, Yttrium-90 radioembolization, everolimus, radiotherapy, and chemoembolization. Close blood sugar monitorization during these therapies showed the most favourable response with everolimus. Everolimus treatment resulted in rapid improvement of hypoglycemia episodes, letting us discontinue dextrose infusion and discharge the patient. However, experience with everolimus in such patients is still limited, and more precise data can be obtained with the increasing use of this agent for neuroendocrine tumours.

  14. Significant interaction between activated charcoal and antiretroviral therapy leading to subtherapeutic drug concentrations, virological breakthrough and development of resistance.

    Science.gov (United States)

    Tseng, Alice L; la Porte, Charles; Salit, Irving E

    2013-01-01

    A 42-year-old, treatment-experienced woman, virologically suppressed on tenofovir/emtricitabine and boosted atazanavir, experienced virological breakthrough, drop in CD4(+) T-cell count and undetectable drug concentrations. Adherence to treatment was confirmed, but repeat testing yielded similar results. After 2 months, the patient stated that she had been taking activated charcoal to manage gastrointestinal symptoms associated with her combination antiretroviral therapy, but she had recently discontinued the charcoal. Atazanavir concentrations were therapeutic but the patient's viral load rebounded and genotype testing revealed new reverse transcriptase mutations. The patient was changed to zidovudine, lamivudine, and boosted darunavir and achieved viral suppression. At 1 year follow-up, her viral load remained activated charcoal and atazanavir/ritonavir leading to virological breakthrough and development of resistance.

  15. Appropriateness of gram-negative agent use at a tertiary care hospital in the setting of significant antimicrobial resistance.

    Science.gov (United States)

    Vora, Neil M; Kubin, Christine J; Furuya, E Yoko

    2015-01-01

    Background.  Practicing antimicrobial stewardship in the setting of widespread antimicrobial resistance among gram-negative bacilli, particularly in urban areas, is challenging. Methods.  We conducted a retrospective cross-sectional study at a tertiary care hospital with an established antimicrobial stewardship program in New York, New York to determine appropriateness of use of gram-negative antimicrobials and to identify factors associated with suboptimal antimicrobial use. Adult inpatients who received gram-negative agents on 2 dates, 1 June 2010 or 1 December 2010, were identified through pharmacy records. Clinical data were collected for each patient. Use of gram-negative agents was deemed optimal or suboptimal through chart review and according to hospital guidelines. Data were compared using χ(2) or Fischer's exact test for categorical variables and Student t test or Mann-Whitney U test for continuous variables. Results.  A total of 356 patients were included who received 422 gram-negative agents. Administration was deemed suboptimal in 26% of instances, with the most common reason being spectrum of activity too broad. In multivariable analysis, being in an intensive care unit (adjusted odds ratio [aOR], .49; 95% confidence interval [CI], .29-.84), having an infectious diseases consultation within the previous 7 days (aOR, .52; 95% CI, .28-.98), and having a history of multidrug-resistant gram-negative bacilli within the past year (aOR, .24; 95% CI, .09-.65) were associated with optimal gram-negative agent use. Beta-lactam/beta-lactamase inhibitor combination drug use (aOR, 2.6; 95% CI, 1.35-5.16) was associated with suboptimal use. Conclusions.  Gram-negative agents were used too broadly despite numerous antimicrobial stewardship program activities.

  16. Arabidopsis and Brachypodium distachyon Transgenic Plants Expressing Aspergillus nidulans Acetylesterases Have Decreased Degree of Polysaccharide Acetylation and Increased Resistance to Pathogens1[C][W][OA

    Science.gov (United States)

    Pogorelko, Gennady; Lionetti, Vincenzo; Fursova, Oksana; Sundaram, Raman M.; Qi, Mingsheng; Whitham, Steven A.; Bogdanove, Adam J.; Bellincampi, Daniela; Zabotina, Olga A.

    2013-01-01

    The plant cell wall has many significant structural and physiological roles, but the contributions of the various components to these roles remain unclear. Modification of cell wall properties can affect key agronomic traits such as disease resistance and plant growth. The plant cell wall is composed of diverse polysaccharides often decorated with methyl, acetyl, and feruloyl groups linked to the sugar subunits. In this study, we examined the effect of perturbing cell wall acetylation by making transgenic Arabidopsis (Arabidopsis thaliana) and Brachypodium (Brachypodium distachyon) plants expressing hemicellulose- and pectin-specific fungal acetylesterases. All transgenic plants carried highly expressed active Aspergillus nidulans acetylesterases localized to the apoplast and had significant reduction of cell wall acetylation compared with wild-type plants. Partial deacetylation of polysaccharides caused compensatory up-regulation of three known acetyltransferases and increased polysaccharide accessibility to glycosyl hydrolases. Transgenic plants showed increased resistance to the fungal pathogens Botrytis cinerea and Bipolaris sorokiniana but not to the bacterial pathogens Pseudomonas syringae and Xanthomonas oryzae. These results demonstrate a role, in both monocot and dicot plants, of hemicellulose and pectin acetylation in plant defense against fungal pathogens. PMID:23463782

  17. 12 weeks' aerobic and resistance training without dietary intervention did not influence oxidative stress but aerobic training decreased atherogenic index in middle-aged men with impaired glucose regulation.

    Science.gov (United States)

    Venojärvi, Mika; Korkmaz, Ayhan; Wasenius, Niko; Manderoos, Sirpa; Heinonen, Olli J; Lindholm, Harri; Aunola, Sirkka; Eriksson, Johan G; Atalay, Mustafa

    2013-11-01

    Our aim was to determine whether 12 weeks' aerobic Nordic walking (NW) or resistance exercise training (RT) without diet-induced weight loss could decrease oxidative stress and atherogenic index of plasma (AIP), prevalence of metabolic syndrome (MetS) and MetS score in middle-aged men with impaired glucose regulation (IGR) (n=144. 54.5 ± 6.5 years). In addition, we compared effects of intervention between overweight and obese subgroups. Prevalence of MetS and AIP index decreased only in NW group and MetS score in both NW and RT groups but not in control group. The changes in AIP index correlated inversely with changes in plasma antioxidant capacity. The change in AIP index remained a significant independent predictor of the changes in MetS score after the model was adjusted for age, BMI and volume of exercise (MET h/week) in NW group. There were no changes in the other measured markers of oxidative stress and related cytokines (e.g. osteopontin and osteoprotegerin) in any of the groups. Nordic walking decreased prevalence of MetS and MetS score. Improved lipid profile remained a predictor of decreased MetS score only in NW group and it seems that Nordic walking has more beneficial effects on cardiovascular disease risks than RT training. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Significant Tic Reduction in An Otherwise Treatment-Resistant Patient with Gilles de la Tourette Syndrome Following Treatment with Nabiximols

    Directory of Open Access Journals (Sweden)

    Ahmad Seif Kanaan

    2017-04-01

    Full Text Available Early anecdotal reports and preliminary studies suggested that cannabinoid-based medicines such as delta-9-tetrahydrocannabinol (THC are effective in the treatment of Gilles de la Tourette syndrome (TS. We report a single case study of a patient with otherwise treatment-resistant TS successfully treated with nabiximols. Our patient was a 22-year-old male suffering from severe and complex TS. Treatment with nabiximols was commenced at a dose of 1 puff/day (= 100 μL containing 2.7 mg THC and 2.5 mg cannabidiol (CBD and slowly increased up to a dosage of 3 × 3 puffs/day (= 24.3 mg THC and 22.5 mg CBD. Several clinical measures for tics, premonitory urges, and global impairment were acquired before and after two weeks of treatment. Treatment with nabiximols resulted in major improvements of both tics and premonitory urges, but also global impairment and health-related quality of life according to all used measurements without causing relevant adverse effects. Our results provide further evidence that treatment with nabiximols may be effective in the treatment of patients with TS. Given the positive response exhibited by the patient highlighted in this report, further investigation of the effects of nabiximols is proposed on a larger group of patients in a clinical trial setting.

  19. Clinical significance of methicillin-resistant Staphylococcus aureus colonization in residents in community long-term-care facilities in Spain.

    Science.gov (United States)

    Manzur, A; De Gopegui, E Ruiz; Dominguez, M; Mariscal, D; Gavalda, L; Perez, J L; Segura, F; Pujol, M

    2012-03-01

    Methicillin-resistant Staphylococcus aureus (MRSA) is highly prevalent in Spanish hospitals and community long-term-care facilities (LTCFs). This longitudinal study was performed in community LTCFs to determine whether MRSA colonization is associated with MRSA infections and overall mortality. Nasal and decubitus ulcer cultures were performed every 6 months for an 18-month period on 178 MRSA-colonized residents (86 490 patient-days) and 196 non-MRSA carriers (97 470 patient-days). Fourteen residents developed MRSA infections and 10 of these were skin and soft tissue infections. Two patients with respiratory infections required hospitalization. The incidence rate of MRSA infection was 0·12/1000 patient-days in MRSA carriers and 0·05/1000 patient-days in non-carriers (P=0·46). No difference in MRSA infection rate was found according to the duration of MRSA colonization (P=0·69). The mortality rate was 20·8% in colonized residents and 16·8% in non-carriers; four residents with MRSA infection died. Overall mortality was statistically similar in both cohorts. Our results suggest that despite a high prevalence of MRSA colonization in LTCFs, MRSA infections are neither frequent nor severe while colonized residents remain at the facility. The epidemiological impact of an MRSA reservoir is more relevant than the clinical impact of this colonization for an individual resident and supports current recommendations to control MRSA spread in community LTCFs.

  20. A circle dance in a psychiatric setting : can a circle dance intervention decrease levels of depressed affect among patients with mental health illnesses and, if so, what aspect of this dance is most significant?

    OpenAIRE

    Beard, Ella King

    2016-01-01

    This study investigates the role of the circle dance in decreasing depressed affect amongst a group of 45 patients with severe mental health illnesses and highlights the most significant aspect of that dance. Patients participated in one of four conditions: a group performing a regular traditional upbeat Irish circle dance holding hands and with a jump step [jump+hands]; a group performing the same dance holding hands with no jump step [hands]; a group performing the same dance without holdin...

  1. The retardation of vasculopathy induced by attenuation of insulin resistance in the corpulent JCR:LA-cp rat is reflected by decreased vascular smooth muscle cell proliferation in vivo.

    Science.gov (United States)

    Absher, P M; Schneider, D J; Baldor, L C; Russell, J C; Sobel, B E

    1999-04-01

    Proliferation in vivo of vascular smooth muscle cells occurs early in the course of atherosclerosis. Cultured smooth muscle cells (SMCs) explanted from aortas of JCR:LA-cp corpulent rats known to exhibit metabolic derangements and insulin resistance typical of type II diabetes early in life and to develop atherosclerosis later in life exhibit increased proliferation compared with SMCs from lean, normal rats. Vascular smooth muscle proliferation in vitro was found to be positively and significantly correlated with plasma insulin levels in vivo. Proliferation of aortic SMCs from JCR:LA-cp cp/cp corpulent rats cultured in vitro exhibited increased proliferation in the presence of exogenous insulin. Exercise and diet, selected as interventions designed to ameliorate the insulin resistance and hyperinsulinemia in the JCR:LA-cp cp/cp rat, effectively lowered blood insulin levels and decreased subsequent proliferation in vitro of aortic SMCs explanted from these animals. The results indicate that assessment of proliferation of vascular smooth muscle cells ex vivo may provide insight into the presence and severity of atherogenicity in association with insulin resistance in diverse species under diverse circumstances. Accordingly, with appropriate controls, it may be possible to use SMC proliferation ex vivo as a marker of the extent to which an intervention such as administration of insulin sensitizers to experimental animals and human subjects results in a change in behavior of vessel wall elements potentially indicative of amelioration of atherogenicity and detectable as judged from reduced proliferative rates of the cells ex vivo when they have been harvested from vessels exposed to a milieu in which insulin resistance has been attenuated.

  2. Sixteen weeks of resistance training decrease plasma heat shock protein 72 (eHSP72) and increase muscle mass without affecting high sensitivity inflammatory markers' levels in sarcopenic men.

    Science.gov (United States)

    Perreault, K; Courchesne-Loyer, A; Fortier, M; Maltais, M; Barsalani, R; Riesco, E; Dionne, Isabelle J

    2016-04-01

    Sarcopenia has been associated with increased systemic inflammation and risk of physical disability in older adults. Recently, extracellular heat shock protein 72 (eHSP72) was proposed as a biomarker of sarcopenia but its response to interventions designed to increase muscle mass has never been evaluated. The present study was designed to (1) assess eHSP72 levels following resistance training and, (2) determine whether changes in eHSP72 correlate to changes in muscle mass and inflammatory markers. A total of 26 sarcopenic men participated in a 16-week resistance training program. The following variables were measured pre-post-intervention: plasma HSP72, serum high sensitivity (hs) inflammatory markers: interleukin-6 (hsIL-6), C-reactive protein (hsCRP), and tumor necrosis factor alpha (hsTNF-α), lean body mass (LBM) and appendicular muscle mass index (appMMI). eHSP72 was detected in 47 % of our participants and its level significantly decreased (P = 0.04) after the intervention, with a concomitant increase in several LBM variables and appMMI (all P < 0.035). Serum hsIL-6, hsCRP and hsTNF-α changes did not reach significance. Baseline hsIL-6 and hsCRP levels were negatively correlated with several LBM variables but solely baseline hsIL-6 was associated with changes in appLBM. No correlations were found between changes in measured variables. Attenuation of eHSP72 following resistance training in parallel with increase in LBM variables showed a concordance between the evolution of this biomarker and a clinical outcome relevant to sarcopenia. Nevertheless, the low bloodstream detection rate of eHSP72 in a sarcopenic otherwise healthy population might limit its use in clinical settings for now.

  3. Human circulating ribosomal DNA content significantly increases while circulating satellite III (1q12) content decreases under chronic occupational exposure to low-dose gamma- neutron and tritium beta-radiation.

    Science.gov (United States)

    Korzeneva, Inna B; Kostuyk, Svetlana V; Ershova, Elizaveta S; Skorodumova, Elena N; Zhuravleva, Veronika F; Pankratova, Galina V; Volkova, Irina V; Stepanova, Elena V; Porokhovnik, Lev N; Veiko, Natalia N

    A single exposure to ionizing radiation (IR) results in an elevated cell-free DNA (cfDNA) content in the blood plasma. In this case, the cfDNA concentration can be a marker of the cell death in the organism. However, a chronic exposure to a low-dose IR enhances both the endonuclease activity and titer of antibodies to DNA in blood plasma, resulting in a decrease of the total concentration of circulating cfDNA in exposed people. In this case, the total cfDNA concentration should not be considered as a marker of the cell death in an exposed body. We assumed that a pool of the cfDNA circulating in the exposed people contains DNA fragments, which are resistant to a double-strand break formation in the environment of the elevated plasma endonuclease activity, and can be accumulated in the blood plasma. In order to test this hypothesis, we studied the content of GC-rich sequences (69%GC) of the transcribed region of human ribosomal repeat (rDNA), as well as the content of AT-rich repeat (63%AT) of satellite III (1q12) in the cfDNA samples obtained from 285 individuals. We have found that a chronic exposure to gamma-neutron radiation (N=88) and tritium β-radiation (N=88) evokes an increase of the rDNA content (RrDNA index) and a decrease of the satellite III content (RsatIII index) in the circulating cfDNA as compared with the cfDNA of non-exposed people (N=109). Such index that simultaneously displays both the increase of rDNA content and decrease of satellite III content in the cfDNA (RrDNA/RsatIII) can be recommended as a marker of chronic processes in the body that involve the elevated cell death rate and/or increased blood plasma endonuclease activity. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Suction against resistance: a new breathing technique to significantly improve the blood flow ratio of the superior and inferior vena cava

    Energy Technology Data Exchange (ETDEWEB)

    Gutzeit, Andreas [Clinical Research Unit of St. Anna Hospital Luzern, Institute of Radiology and Nuclear Medicine, Luzern (Switzerland); Paracelsus Medical University Salzburg, Department of Radiology, Salzburg (Austria); Cantonal Hospital, Department of Radiology, Winterthur (Switzerland); Roos, Justus E. [Duke University, Department of Radiology, Durham, NC (United States); Hergan, Klaus [Paracelsus Medical University Salzburg, Department of Radiology, Salzburg (Austria); Weymarn, Constantin von; Reischauer, Carolin; Froehlich, Johannes M. [Clinical Research Unit of St. Anna Hospital Luzern, Institute of Radiology and Nuclear Medicine, Luzern (Switzerland); Cantonal Hospital, Department of Radiology, Winterthur (Switzerland); Waelti, Stephan [Cantonal Hospital, Department of Radiology, Winterthur (Switzerland)

    2014-12-15

    Optimal contrast within the pulmonary artery is achieved by the maximum amount of contrast-enhanced blood flowing through the superior vena cava (SVC), while minimum amounts of non-contrasted blood should originate from the inferior vena cava (IVC). This study aims to clarify whether ''suction against resistance'' might optimise this ratio. Phase-contrast pulse sequences on a 1.5T MRI magnet were used for flow quantification mean flow (mL/s), stroke volume (Vol) in the SVC and IVC in volunteers. Different breathing manoeuvers were analysed repeatedly: free breathing; inspiration; expiration; suction against resistance, and Valsalva. To standardise breathing commands, volunteers performed suction and Valsalva manoeuvers with an MR-compatible manometer.??Suction against resistance was associated with a significant drop of the IVC/SVC flow quotient (1.63 [range 1.3-2.0] p < 0.05 at -10 mmHg and 1.48 [1.1-1.9] p < 0.01 at -20 mmHg) corresponding to increased blood flow from SVC and diminished flow originating from the IVC. The remaining breathing commands (free breathing 2.2; inspiration 2.4; expiration 2.4; Valsalva 10 mmHg 2.3; Valsalva 20 mmHg 2.6; and Valsalva 30 mmHg 2.2) showed no differences (p > 0.05).??Suction against resistance caused a significant drop in the IVC/SVC quotient. Theoretically, this breathing manoeuver might significantly improve the enhancement characteristics of CT angiography. (orig.)

  5. Centrally administered urocortin 2 decreases gorging on high-fat diet in in both diet induced obesity-prone and -resistant rats

    Science.gov (United States)

    Cottone, Pietro; Sabino, Valentina; Nagy, Tim R.; Coscina, Donald V.; Levin, Barry E.; Zorrilla, Eric P.

    2013-01-01

    Objective Obesity is a costly, deadly public health problem for which new treatments are needed. Individual differences in meal pattern have been proposed to play a role in obesity risk. The present study tested the hypothesis that i) the microstructure of chronic high-fat diet intake differs between genetically selected Diet-Induced Obesity (DIO) and Diet Resistant (DR) rats, and ii) central administration of urocortin 2 (Ucn 2), a corticotropin-releasing factor type 2 (CRF2) agonist, decreases high-fat diet intake not only in lean DR rats, but also in obese DIO rats. Design Male, selectively bred DIO and DR rats (n=10/genotype) were chronically fed a high-fat diet. Food and water intake as well as ingestion microstructure were then compared under baseline conditions and following third intracerebroventricular injection of Ucn 2 (0, 0.1, 0.3, 1, 3 µg). Results Irrespective of genotype, Ucn 2 reduced nocturnal food intake with a minimum effective dose of 0.3 µg, suppressing high-fat diet intake by ~40% at the 3 µg dose. Ucn 2 also made rats of both genotypes eat smaller and briefer meals, including at doses that did not reduce drinking. Obese DIO rats ate fewer but larger meals than DR rats, which they ate more quickly and consumed with 2/3rd less water. Conclusions Unlike leptin and insulin, Ucn 2 retains its full central anorectic efficacy to reduce high-fat diet intake even in obese, genetically-prone DIO rats, which otherwise show a “gorging” meal pattern. These results open new opportunities of investigation towards treating some forms of diet-induced obesity. PMID:23478425

  6. Upregulation of ERK1/2-eNOS via AT2 receptors decreases the contractile response to angiotensin II in resistance mesenteric arteries from obese rats.

    Directory of Open Access Journals (Sweden)

    Graziela N Hagihara

    Full Text Available It has been clearly established that mitogen-activated protein kinases (MAPKS are important mediators of angiotensin II (Ang II signaling via AT1 receptors in the vasculature. However, evidence for a role of these kinases in changes of Ang II-induced vasoconstriction in obesity is still lacking. Here we sought to determine whether vascular MAPKs are differentially activated by Ang II in obese animals. The role of AT2 receptors was also evaluated. Male monosodium glutamate-induced obese (obese and non-obese Wistar rats (control were used. The circulating concentrations of Ang I and Ang II, determined by HPLC, were increased in obese rats. Ang II-induced isometric contraction was decreased in endothelium-intact resistance mesenteric arteries from obese compared with control rats and exhibited a retarded AT1 receptor antagonist response. Blocking of AT2 receptors and inhibition of either endothelial nitric oxide synthase (eNOS or extracellular signal-regulated protein kinases 1 and 2 (ERK1/2 restored Ang II-induced contraction in obese rats. Western blot analysis revealed increased protein expression of AT2 receptors in arteries from obese rats. Basal and Ang II-induced ERK1/2 phosphorylation was also increased in obese rats. Blockade of either AT1 or AT2 receptors corrected the increased ERK1/2 phosphorylation in arteries from obese rats to levels observed in control preparations. Phosphorylation of eNOS was increased in obese rats. Incubation with the ERK1/2 inhibitor before Ang II stimulation did not affect eNOS phosphorylation in control rats; however, it corrected the increased phosphorylation of eNOS in obese rats. These results clearly demonstrate that enhanced AT2 receptor and ERK1/2-induced, NO-mediated vasodilation reduces Ang II-induced contraction in an endothelium-dependent manner in obese rats.

  7. CCR5Δ32 (rs333) polymorphism is associated with decreased risk of chronic and aggressive periodontitis: A case-control analysis based in disease resistance and susceptibility phenotypes.

    Science.gov (United States)

    Cavalla, Franco; Biguetti, Claudia C; Dionisio, Thiago J; Azevedo, Michelle C S; Martins, Walter; Santos, Carlos F; Trombone, Ana Paula F; Silva, Renato M; Letra, Ariadne; Garlet, Gustavo P

    2018-03-01

    Chronic and aggressive periodontitis are infectious diseases characterized by the irreversible destruction of periodontal tissues, which is mediated by the host inflammatory immune response triggered by periodontal infection. The chemokine receptor CCR5 play an important role in disease pathogenesis, contributing to pro-inflammatory response and osteoclastogenesis. CCR5Δ32 (rs333) is a loss-of-function mutation in the CCR5 gene, which can potentially modulate the host response and, consequently periodontitis outcome. Thus, we investigated the effect of the CCR5Δ32 mutation over the risk to suffer periodontitis in a cohort of Brazilian patients (total N=699), representative of disease susceptibility (chronic periodontitis, N=197; and aggressive periodontitis, N=91) or resistance (chronic gingivitis, N=193) phenotypes, and healthy subjects (N=218). Additionally, we assayed the influence of CCR5Δ32 in the expression of the biomarkers TNFα, IL-1β, IL-10, IL-6, IFN-γ and T-bet, and key periodontal pathogens P. gingivalis, T. forsythia, and T. denticola. In the association analysis of resistant versus susceptible subjects, CCR5Δ32 mutant allele-carriers proved significantly protected against chronic (OR 0.49; 95% CI 0.29-0.83; p-value 0.01) and aggressive (OR 0.46; 95% CI 0.22-0.94; p-value 0.03) periodontitis. Further, heterozygous subjects exhibited significantly decreased expression of TNFα in periodontal tissues, pointing to a functional effect of the mutation in periodontal tissues during the progression of the disease. Conversely, no significant changes were observed in the presence or quantity of the periodontal pathogens P. gingivalis, T. forsythia, and T. denticola in the subgingival biofilm that could be attributable to the mutant genotype. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Significant Need for a French Network of Expert Centers Enabling a Better Characterization and Management of Treatment-Resistant Depression (Fondation FondaMental).

    Science.gov (United States)

    Yrondi, Antoine; Bennabi, Djamila; Haffen, Emmanuel; Garnier, Marion; Bellivier, Frank; Bourgerol, Thierry; Camus, Vincent; D'Amato, Thierry; Doumy, Olivier; Haesebaert, Frédéric; Holtzmann, Jérôme; Lançon, Christophe; Vignaud, Philippe; Moliere, Fanny; Nieto, Isabel; Richieri, Raphaëlle Marie; Domenech, Philippe; Rabu, Corentin; Mallet, Luc; Yon, Liova; Schmitt, Laurent; Stephan, Florian; Vaiva, Guillaume; Walter, Michel; Llorca, Pierre-Michel; Courtet, Philippe; Leboyer, Marion; El-Hage, Wissam; Aouizerate, Bruno

    2017-01-01

    Major depression is characterized by (i) a high lifetime prevalence of 16-17% in the general population; (ii) a high frequency of treatment resistance in around 20-30% of cases; (iii) a recurrent or chronic course; (iv) a negative impact on the general functioning and quality of life; and (v) a high level of comorbidity with various psychiatric and non-psychiatric disorders, high occurrence of completed suicide, significant burden along with the personal, societal, and economic costs. In this context, there is an important need for the development of a network of expert centers for treatment-resistant depression (TRD), as performed under the leadership of the Fondation FondaMental. The principal mission of this national network is to establish a genuine prevention, screening, and diagnosis policy for TRD to offer a systematic, comprehensive, longitudinal, and multidimensional evaluation of cases. A shared electronic medical file is used referring to a common exhaustive and standardized set of assessment tools exploring psychiatric, non-psychiatric, metabolic, biological, and cognitive dimensions of TRD. This is paralleled by a medico-economic evaluation to examine the global economic burden of the disease and related health-care resource utilization. In addition, an integrated biobank has been built by the collection of serum and DNA samples for the measurement of several biomarkers that could further be associated with the treatment resistance in the recruited depressed patients. A French observational long-term follow-up cohort study is currently in progress enabling the extensive assessment of resistant depressed patients. In those unresponsive cases, each expert center proposes relevant therapeutic options that are classically aligned to the international guidelines referring to recognized scientific societies. This approach is expected to improve the overall clinical assessments and to provide evidence-based information to those clinicians most closely

  9. Significant Need for a French Network of Expert Centers Enabling a Better Characterization and Management of Treatment-Resistant Depression (Fondation FondaMental

    Directory of Open Access Journals (Sweden)

    Antoine Yrondi

    2017-11-01

    Full Text Available BackgroundMajor depression is characterized by (i a high lifetime prevalence of 16–17% in the general population; (ii a high frequency of treatment resistance in around 20–30% of cases; (iii a recurrent or chronic course; (iv a negative impact on the general functioning and quality of life; and (v a high level of comorbidity with various psychiatric and non-psychiatric disorders, high occurrence of completed suicide, significant burden along with the personal, societal, and economic costs. In this context, there is an important need for the development of a network of expert centers for treatment-resistant depression (TRD, as performed under the leadership of the Fondation FondaMental.MethodsThe principal mission of this national network is to establish a genuine prevention, screening, and diagnosis policy for TRD to offer a systematic, comprehensive, longitudinal, and multidimensional evaluation of cases. A shared electronic medical file is used referring to a common exhaustive and standardized set of assessment tools exploring psychiatric, non-psychiatric, metabolic, biological, and cognitive dimensions of TRD. This is paralleled by a medico-economic evaluation to examine the global economic burden of the disease and related health-care resource utilization. In addition, an integrated biobank has been built by the collection of serum and DNA samples for the measurement of several biomarkers that could further be associated with the treatment resistance in the recruited depressed patients. A French observational long-term follow-up cohort study is currently in progress enabling the extensive assessment of resistant depressed patients. In those unresponsive cases, each expert center proposes relevant therapeutic options that are classically aligned to the international guidelines referring to recognized scientific societies.DiscussionThis approach is expected to improve the overall clinical assessments and to provide evidence

  10. Resting salivary levels of IgA and cortisol are significantly affected during intensive resistance training periods in elite male weightlifters.

    Science.gov (United States)

    Tsai, Min-Lung; Li, Tzai-Li; Chou, Li-Wei; Chang, Chen-Kang; Huang, Shu-Yi; Fang, Shih-Hua

    2012-08-01

    The aim of this study was to investigate the cumulative effects of intensive resistance training on salivary immunoglobulin A (SIgA) and cortisol responses in elite male weightlifters. Eleven elite male Taiwanese weightlifters were trained through 3 training stages before a national weightlifting competition, and this was followed by a 2-week recovery stage. Resting saliva samples were collected once in each of the 4 stages. Salivary concentrations of total protein (TP), SIgA, lactoferrin, and cortisol were measured. The results showed that (a) salivary TP concentrations were not significantly affected; (b) resting levels of SIgA, the ratio of SIgA to TP (SIgA/TP), cortisol, and the ratio of cortisol to TP (cortisol/TP) were significantly higher in the training stages than in the recovery stage; (c) a positive correlation was revealed between the ratios of SIgA/TP and cortisol/TP; and (d) the resting salivary lactoferrin concentrations and the ratio of lactoferrin to TP (lactoferrin/TP) were significantly lower in stage 1 than in the recovery stage. The findings in this study suggest that prolonged, intensive resistance training exerts cumulative effects on SIgA and cortisol responses in elite weightlifters.

  11. Decrease in electrical contact resistance of Sb-doped n+-BaSi2 layers and spectral response of an Sb-doped n+-BaSi2/undoped BaSi2 structure for solar cells

    Science.gov (United States)

    Kodama, Komomo; Takabe, Ryota; Yachi, Suguru; Toko, Kaoru; Suemasu, Takashi

    2018-03-01

    We investigated how the electron concentration n in a 300-nm-thick Sb-doped n+-BaSi2 layer grown by molecular beam epitaxy affected the contact resistance R C to surface electrodes (Al, indium-tin-oxide). As the n of n-BaSi2 increased, R C decreased and reached a minimum of 0.019 Ω cm2 at n = 2.4 × 1018 cm-3 for the Al electrodes. This value was more than 1 order of magnitude smaller than that obtained for Al/B-doped p-BaSi2. We believe that this significant decrease in R C came from Sb segregation. Furthermore, the internal quantum efficiency (IQE) spectrum was evaluated for an Sb-doped n+-BaSi2 (20 nm)/undoped BaSi2 (500 nm)/n+-Si(111) structure. Its IQE reached as high as ˜50% over a wide wavelength range under a small bias voltage of 0.1 V applied between the top and bottom electrodes.

  12. Detecting Mutations in the Mycobacterium tuberculosis Pyrazinamidase Gene pncA to Improve Infection Control and Decrease Drug Resistance Rates in Human Immunodeficiency Virus Coinfection

    Science.gov (United States)

    Dudley, Matthew Z.; Sheen, Patricia; Gilman, Robert H.; Ticona, Eduardo; Friedland, Jon S.; Kirwan, Daniela E.; Caviedes, Luz; Rodriguez, Richard; Cabrera, Lilia Z.; Coronel, Jorge; Grandjean, Louis; Moore, David A. J.; Evans, Carlton A.; Huaroto, Luz; Chávez-Pérez, Víctor; Zimic, Mirko

    2016-01-01

    Hospital infection control measures are crucial to tuberculosis (TB) control strategies within settings caring for human immunodeficiency virus (HIV)–positive patients, as these patients are at heightened risk of developing TB. Pyrazinamide (PZA) is a potent drug that effectively sterilizes persistent Mycobacterium tuberculosis bacilli. However, PZA resistance associated with mutations in the nicotinamidase/pyrazinamidase coding gene, pncA, is increasing. A total of 794 patient isolates obtained from four sites in Lima, Peru, underwent spoligotyping and drug resistance testing. In one of these sites, the HIV unit of Hospital Dos de Mayo (HDM), an isolation ward for HIV/TB coinfected patients opened during the study as an infection control intervention: circulating genotypes and drug resistance pre- and postintervention were compared. All other sites cared for HIV-negative outpatients: genotypes and drug resistance rates from these sites were compared with those from HDM. HDM patients showed high concordance between multidrug resistance, PZA resistance according to the Wayne method, the two most common genotypes (spoligotype international type [SIT] 42 of the Latino American-Mediterranean (LAM)-9 clade and SIT 53 of the T1 clade), and the two most common pncA mutations (G145A and A403C). These associations were absent among community isolates. The infection control intervention was associated with 58–92% reductions in TB caused by SIT 42 or SIT 53 genotypes (odds ratio [OR] = 0.420, P = 0.003); multidrug-resistant TB (OR = 0.349, P < 0.001); and PZA-resistant TB (OR = 0.076, P < 0.001). In conclusion, pncA mutation typing, with resistance testing and spoligotyping, was useful in identifying a nosocomial TB outbreak and demonstrating its resolution after implementation of infection control measures. PMID:27928075

  13. VP-16 resistance in the NCI-H460 human lung cancer cell line is significantly associated with glucose-regulated protein78 (GRP78) induction.

    Science.gov (United States)

    Wang, Qi; Wang, Tao; Wang, Yingyan; Wang, Wei; Wang, Yanyan; Hu, Xiujuan; Shao, Shujuan; Zhang, Jinhui; Suo, Zhenhe

    2007-01-01

    To investigate the relationship between the expression of glucose-regulated protein (GRP78) and resistance to VP-16 in the NCI-H460 cell line. RT-PCR, real-time RT-PCR and Western blotting were used in analyzing the expression of GRP78 at mRNA and protein levels in the NCI-H460 cell line induced by A23187 at different concentrations. Cell survival with VP-16 was determined using a colony-formation assay with the account of IC50. The expression of GRP78 at both the mRNA and protein levels was higher in the NCI-H460 cell line induced by A23187. A23187 treatment resulted in up to 4.8-fold elevation of GRP78 mRNA and up to 3.2-fold elevation of GRP78 protein in the experimental cells compared to the controls, all in a dose-dependent manner. The IC50s for VP-16 in the cells pretreated with different concentrations of A23187 (0, 1, 2, 4 and 6 microM) were: 12.11 +/- 0.83, 12.68 +/- 1.04, 25.82 +/- 1.83, 37.46 +/- 1.89 and 45.19 +/- 2.34 microM, respectively. Compared to the control, there was a significant elevation of IC50 for VP-16 in the cells pretreated with A23187. Survival curve analysis also showed that the induction of A23187 caused a significantly longer survival for the cells subjected to VP-16 treatment (p VP-16 in the human lung cancer NCI-H460 cell line. Based on the trend of the change in IC50 and the expression of GRP78 in differently exposed cells, we conclude that the induction of GRP78 by A23187 is significantly associated with the resistance to VP-16.

  14. Hormone resistance in two MCF-7 breast cancer cell lines is associated with reduced mTOR signaling, decreased glycolysis and increased sensitivity to cytotoxic drugs

    Directory of Open Access Journals (Sweden)

    Euphemia Yee Leung

    2014-09-01

    Full Text Available The mTOR pathway is a key regulator of multiple cellular signaling pathways and is a potential target for therapy. We have previously developed two hormone-resistant sub-lines of the MCF-7 human breast cancer line, designated TamC3 and TamR3, which were characterized by reduced mTOR signaling, reduced cell volume and resistance to mTOR inhibition. Here we show that these lines exhibit increased sensitivity to carboplatin, oxaliplatin, 5-fluorouracil, camptothecin, doxorubicin, paclitaxel, docetaxel and hydrogen peroxide. The mechanisms underlying these changes have not yet been characterized but may include a shift from glycolysis to mitochondrial respiration. If this phenotype is found in clinical hormone-resistant breast cancers, conventional cytotoxic therapy may be a preferred option for treatment.

  15. Multiple efflux pumps are involved in the transepithelial transport of colchicine: combined effect of p-glycoprotein and multidrug resistance-associated protein 2 leads to decreased intestinal absorption throughout the entire small intestine.

    Science.gov (United States)

    Dahan, Arik; Sabit, Hairat; Amidon, Gordon L

    2009-10-01

    The purpose of this study was to thoroughly characterize the efflux transporters involved in the intestinal permeability of the oral microtubule polymerization inhibitor colchicine and to evaluate the role of these transporters in limiting its oral absorption. The effects of P-glycoprotein (P-gp), multidrug resistance-associated protein 2 (MRP2), and breast cancer resistance protein (BCRP) inhibitors on colchicine bidirectional permeability were studied across Caco-2 cell monolayers, inhibiting one versus multiple transporters simultaneously. Colchicine permeability was then investigated in different regions of the rat small intestine by in situ single-pass perfusion. Correlation with the P-gp/MRP2 expression level throughout different intestinal segments was investigated by immunoblotting. P-gp inhibitors [N-(4-[2-(1,2,3,4-tetrahydro-6,7-dimethoxy-2-isoquinolinyl)ethyl]-phenyl)-9,10-dihydro-5-methoxy-9-oxo-4-acridine carboxamide (GF120918), verapamil, and quinidine], and MRP2 inhibitors [3-[[3-[2-(7-chloroquinolin-2-yl)vinyl]phenyl]-(2-dimethylcarbamoylethylsulfanyl)methylsulfanyl] propionic acid (MK571), indomethacin, and p-aminohippuric acid (p-AH)] significantly increased apical (AP)-basolateral (BL) and decreased BL-AP Caco-2 transport in a concentration-dependent manner. No effect was obtained by the BCRP inhibitors fumitremorgin C (FTC) and pantoprazole. P-gp/MRP2 inhibitors combinations greatly reduced colchicine mucosal secretion, including complete abolishment of efflux (GF120918/MK571). Colchicine displayed low (versus metoprolol) and constant permeability along the rat small-intestine. GF120918 significantly increased colchicine permeability in the ileum with no effect in the jejunum, whereas MK571 augmented jejunal permeability without changing the ileal transport. The GF120918/MK571 combination caused an effect similar to that of MK571 alone in the jejunum and to that of GF120918 alone in the ileum. P-gp expression followed a gradient increasing from

  16. Knowing prior methicillin-resistant Staphylococcus aureus (MRSA) infection or colonization status increases the empirical use of glycopeptides in MRSA bacteraemia and may decrease mortality.

    Science.gov (United States)

    Robinson, J O; Phillips, M; Christiansen, K J; Pearson, J C; Coombs, G W; Murray, R J

    2014-06-01

    To compare the management and outcome of methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia in patients known to be MRSA-colonized/infected (C-patients) with the management and outcome in those not known to be colonized/infected (NC-patients), we conducted a 10-year retrospective review of MRSA bacteraemia in an adult tertiary hospital. Clinical data were obtained by chart review, and mortality data from linked databases. Prior MRSA colonization/infection status was available to treating clinicians at the time of the bacteraemia as a 'Micro-Alert' tag on the patient's labels, in medical charts, and in electronic information systems. C-patients accounted for 35.4% of all MRSA bacteraemia episodes. C-patients were more likely to be indigenous, to be diabetic, or to have a history of previous S. aureus infection. Markers of illness severity (Simplified Acute Physiology Score (SAPS)-II, need for admission to the intensive-care unit, length of stay, and metastatic seeding) were similar in both groups. Empirical therapy included a glycopeptide in 49.3% of C-patients vs. 18.9% of NC-patients (p MRSA isolate tested susceptible in vitro in 56.7% of C-patients vs. 45.1% of NC-patients (p 0.13). All-cause 7-day and 30-day mortality were 7.5% vs. 18.9% (p 0.04), and 22.4% vs. 31.1% (p 0.20), in the C-patient and NC-patient groups, respectively. Knowing MRSA colonization status was significantly associated with lower 30-day mortality in Cox regression analysis (p MRSA bacteraemia is lower in C-patients, which may reflect the earlier use of glycopeptides. The low use of empirical glycopeptides in septic patients known to be previously MRSA-colonized/infected may represent a missed opportunity for infection control to positively impact on clinical management. © 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.

  17. Cafeteria diet-induced insulin resistance is not associated with decreased insulin signaling or AMPK activity and is alleviated by physical training in rats

    DEFF Research Database (Denmark)

    Brandt, Nina; De Bock, Katrien; Richter, Erik

    2010-01-01

    Excess energy intake via a palatable low-fat diet (cafeteria diet) is known to induce obesity and glucose intolerance in rats. However, the molecular mechanisms behind this adaptation are not known, and it is also not known whether exercise training can reverse it. Male Wistar rats were assigned...... was counteracted by training. In the perfused hindlimb, insulin-stimulated glucose transport in red gastrocnemius muscle was completely abolished in CAF and rescued by exercise training. Apart from a tendency toward an approximately 20% reduction in both basal and insulin-stimulated Akt Ser(473) phosphorylation (P......) among the groups. In conclusion, surplus energy intake of a palatable but low-fat cafeteria diet resulted in obesity and insulin resistance that was rescued by exercise training. Interestingly, insulin resistance was not accompanied by major defects in the insulin-signaling cascade or in altered AMPK...

  18. Reduction of sitting time has a positive effect on the decrease of insulin resistance in patients with non-alcoholic fatty liver disease

    OpenAIRE

    Sabinicz, Anna; Maciejewska, Dominika; Kaczorowska, Ma?gorzata; Ryterska, Karina; Jamio?-Milc, Dominika; Wyszomirska-Raszeja, Joanna; Gutowska, Izabela; Stachowska, Ewa

    2016-01-01

    Introduction Non-alcoholic fatty liver disease (NAFLD) affects a large part of the human population. One of the major environmental factors associated with the risk of NAFLD is the lack of physical activity. Aim To compare the level of physical activity and the insulin resistance in NAFLD patients. Material and methods Thirty patients with NAFLD underwent a six-month dietary intervention based on the principles of classical dietetics. Data about diet and physical activity was based on 72-hour...

  19. An asthma patient with steroid-resistant decrease in peak expiratory flow after the Great East Japan earthquake showing spontaneous recovery after 1 month.

    Science.gov (United States)

    Yanagimoto, Shintaro; Haida, Michiko; Suko, Matsunobu

    2012-01-01

    People living in Japan were affected in various ways after the Great East Japan earthquake of March 11, 2011. A 52-year-old female asthma patient not directly affected by the disaster experienced a decrease in peak expiratory flow (PEF) immediately after the earthquake. Despite increasing the inhaled and oral corticosteroid doses, her PEF did not recover. One month later, her PEF level abruptly returned to normal with minimal medications, which were previously ineffective, and the asthma-related symptoms vanished. The stabilization of her state of mind and actual social state seemed to be a part of the reason for the patient's recovery.

  20. Eight years of decreased methicillin-resistant Staphylococcus aureus health care-associated infections associated with a Veterans Affairs prevention initiative.

    Science.gov (United States)

    Evans, Martin E; Kralovic, Stephen M; Simbartl, Loretta A; Jain, Rajiv; Roselle, Gary A

    2017-01-01

    Declines in methicillin-resistant Staphylococcus aureus (MRSA) health care associated infections (HAIs) were previously reported in Veterans Affairs acute care (2012), spinal cord injury (SCIU) (2011), and long-term-care facilities (LTCFs) (2012). Here we report continuing declines in infection rates in these settings through September 2015. Monthly data entered into a national database from 127 acute care facilities, 22 SCIUs, and 133 LTCFs were evaluated for trends using negative binomial regression. There were 23,153,240 intensive care unit (ICU) and non-ICU, and 1,794,234 SCIU patient-days from October 2007-September 2015, and 22,262,605 LTCF resident-days from July 2009-September 2015. Admission nasal swabbing remained >92% in all 3 venues. Admission prevalence changed from 13.2%-13.5% in acute care, from 35.1%-32.0% in SCIUs, and from 23.1%-25.0% in LTCFs during the analysis periods. Monthly HAI rates fell 87.0% in ICUs, 80.1% in non-ICUs, 80.9% in SCIUs, and 49.4% in LTCFs (all P values Prevention Initiative. Published by Elsevier Inc.

  1. Decrease of fear avoidance beliefs following person-centered progressive resistance exercise contributes to reduced pain disability in women with fibromyalgia: secondary exploratory analyses from a randomized controlled trial.

    Science.gov (United States)

    Palstam, Annie; Larsson, Anette; Löfgren, Monika; Ernberg, Malin; Bjersing, Jan; Bileviciute-Ljungar, Indre; Gerdle, Björn; Kosek, Eva; Mannerkorpi, Kaisa

    2016-05-21

    Fibromyalgia (FM) is characterized by persistent widespread pain, increased pain sensitivity and tenderness. Women with FM also report disability, in terms of negative consequences on activities of daily living. Our recent randomized controlled trial (RCT) is the first study of resistance exercise to show positive effects on pain disability. The resistance exercise program of our RCT emphasized active involvement of participants in planning and progression of the exercise, using the principles of person-centeredness, to support each participant's ability to manage the exercise and the progress of it. The aim of this sub-study was to investigate explanatory factors for reduced pain disability in women with FM participating in a 15-week person-centered progressive resistance exercise program. A total of 67 women with FM were included in this sub-study of an RCT examining the effects of person-centered progressive resistance exercise performed twice a week for 15 weeks. Tests of physical capacity and health-related questionnaires were assessed at baseline and after the intervention period. Multivariable stepwise regression was used to analyze explanatory factors for improvements in pain disability. Reduced pain disability was explained by higher pain disability at baseline together with decreased fear avoidance beliefs about physical activity (R (2) = 28, p = 0.005). The improvements in the disability domains of recreation and social activity were explained by decreased fear avoidance beliefs about physical activity together with higher baseline values of each disability domain respectively (R (2) = 32, p = 0.025 and R (2) = 30, p = 0.017). The improvement in occupational disability was explained by higher baseline values of occupational disability (R (2) = 19, p = 0.001). The person-centered resistance exercise intervention, based on principles of self-efficacy, had a positive effect on recreational, social and occupational disability

  2. A decrease in ubiquitination and resulting prolonged life-span of KIT underlies the KIT overexpression-mediated imatinib resistance of KIT mutation-driven canine mast cell tumor cells.

    Science.gov (United States)

    Kobayashi, Masato; Kuroki, Shiori; Kurita, Sena; Miyamoto, Ryo; Tani, Hiroyuki; Tamura, Kyoichi; Bonkobara, Makoto

    2017-10-01

    Overexpression of KIT is one of the mechanisms that contributes to imatinib resistance in KIT mutation-driven tumors. Here, the mechanism underlying this overexpression of KIT was investigated using an imatinib-sensitive canine mast cell tumor (MCT) line CoMS, which has an activating mutation in KIT exon 11. A KIT-overexpressing imatinib-resistant subline, rCoMS1, was generated from CoMS cells by their continuous exposure to increasing concentrations of imatinib. Neither a secondary mutation nor upregulated transcription of KIT was detected in rCoMS1 cells. A decrease in KIT ubiquitination, a prolonged KIT life-span, and KIT overexpression were found in rCoMS1 cells. These events were suppressed by withdrawal of imatinib and were re-induced by re‑treatment with imatinib. These findings suggest that imatinib elicited overexpression of KIT via suppression of its ubiquitination. These results also indicated that imatinib-induced overexpression of KIT in rCoMS1 cells was not a permanently acquired feature but was a reversible response of the cells. Moreover, the pan deubiquitinating enzyme inhibitor PR619 prevented imatinib induction of KIT overexpression, suggesting that the imatinib-induced decrease in KIT ubiquitination could be mediated by upregulation and/or activation of deubiquitinating enzyme(s). It may be possible that a similar mechanism of KIT overexpression underlies the acquisition of imatinib resistance in some human tumors that are driven by KIT mutation.

  3. The major aminoglycoside-modifying enzyme AAC(3)-II found in Escherichia coli determines a significant disparity in its resistance to gentamicin and amikacin in China.

    Science.gov (United States)

    Xiao, Yonghong; Hu, Yunjian

    2012-02-01

    The aim of this study was to investigate the prevalence of aminoglycoside-modifying enzymes in Escherichia coli in different areas of China and to explore the relationship between pandemic enzyme type and bacterial resistance to antimicrobial agents in China. Gentamicin- or etimicin-resistant clinical isolates of E. coli were collected from different areas of China, and the in vitro antibacterial activity of 11 aminoglycoside agents was determined using standard (Clinical and Laboratory Standards Institute) agar dilution methods. Twelve aminoglycoside-modifying enzyme genes were detected by PCR and confirmed by DNA sequencing. A total of 205 E. coli strains were collected from nine hospitals in seven cities. All strains were highly resistant to gentamicin or etimicin, whereas resistance to tobramycin, netilmicin, and kanamycin was slightly lower. However, less than 15% of isolates were resistant to amikacin and isepamicin. Of the gentamicin-resistant strains, 88.2% and 86.7% were sensitive to isepamicin and amikacin, respectively. Five aminoglycoside-modifying enzyme genes were detected in 191 strains, whereas the remaining 14 strains were negative. The most common gene type was aac(3)-II (162 strains), followed by aac(6')-I (50 strains), ant(3″)-I (28 strains), aph(3')-II (20 strains), and ant(2″)-I (20 strains). Ninety-five strains yielded aac(3)-II only, whereas the others contained two or three genes. The three main gene combinations were aac(6')-I/aac(3)-II (28 strains), aac(3)-II/ant(3″)-I (11 strains), and aac(3)-II/aac(6')-I (10 strains). Regional bacterial resistance and enzyme distribution were roughly similar, although minor differences were found in Guangzhou, Jinan, and Dalian, which were the sources of most of the amikacin- or isepamicin-resistant strains. Chinese clinical isolates of E. coli remain highly resistant to gentamicin and etimicin, but are susceptible to amikacin and isepamicin. The dominant type of aminoglycoside-modifying enzyme

  4. Botrytis pseudocinerea Is a Significant Pathogen of Several Crop Plants but Susceptible to Displacement by Fungicide-Resistant B. cinerea Strains.

    Science.gov (United States)

    Plesken, Cecilia; Weber, Roland W S; Rupp, Sabrina; Leroch, Michaela; Hahn, Matthias

    2015-10-01

    Botrytis cinerea is one of the most important pathogens worldwide, causing gray mold on a large variety of crops. Botrytis pseudocinerea has been found previously to occur together with B. cinerea in low abundance in vineyards and strawberry fields. Here, we report B. pseudocinerea to be common and sometimes dominant over B. cinerea on several fruit and vegetable crops in Germany. On apples with calyx end rot and on oilseed rape, it was the major gray mold species. Abundance of B. pseudocinerea was often negatively correlated with fungicide treatments. On cultivated strawberries, it was frequently found in spring but was largely displaced by B. cinerea following fungicide applications. Whereas B. cinerea strains with multiple-fungicide resistance were common in these fields, B. pseudocinerea almost never developed resistance to any fungicide even though resistance mutations occurred at similar frequencies in both species under laboratory conditions. The absence of resistance to quinone outside inhibitors in B. pseudocinerea was correlated with an intron in cytB preventing the major G143A resistance mutation. Our work indicates that B. pseudocinerea has a wide host range similar to that of B. cinerea and that it can become an important gray mold pathogen on cultivated plants. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  5. Botrytis pseudocinerea Is a Significant Pathogen of Several Crop Plants but Susceptible to Displacement by Fungicide-Resistant B. cinerea Strains

    Science.gov (United States)

    Plesken, Cecilia; Weber, Roland W. S.; Rupp, Sabrina; Leroch, Michaela

    2015-01-01

    Botrytis cinerea is one of the most important pathogens worldwide, causing gray mold on a large variety of crops. Botrytis pseudocinerea has been found previously to occur together with B. cinerea in low abundance in vineyards and strawberry fields. Here, we report B. pseudocinerea to be common and sometimes dominant over B. cinerea on several fruit and vegetable crops in Germany. On apples with calyx end rot and on oilseed rape, it was the major gray mold species. Abundance of B. pseudocinerea was often negatively correlated with fungicide treatments. On cultivated strawberries, it was frequently found in spring but was largely displaced by B. cinerea following fungicide applications. Whereas B. cinerea strains with multiple-fungicide resistance were common in these fields, B. pseudocinerea almost never developed resistance to any fungicide even though resistance mutations occurred at similar frequencies in both species under laboratory conditions. The absence of resistance to quinone outside inhibitors in B. pseudocinerea was correlated with an intron in cytB preventing the major G143A resistance mutation. Our work indicates that B. pseudocinerea has a wide host range similar to that of B. cinerea and that it can become an important gray mold pathogen on cultivated plants. PMID:26231644

  6. Co-existence of bla OXA-23 and bla NDM-1 genes of Acinetobacter baumannii isolated from Nepal: antimicrobial resistance and clinical significance

    Directory of Open Access Journals (Sweden)

    Prabhu Raj Joshi

    2017-02-01

    Full Text Available Abstract Background Molecular analysis of carbapenem-resistant genes in Acinetobacter baumannii, an emerging pathogen, is less commonly reported from Nepal. In this study we determined the antibiotic susceptibility profile and genetic mechanism of carbapenem resistance in clinical isolates of A. baumannii. Methods A. baumannii were isolated from various clinical specimens and identified based on Gram staining, biochemical tests, and PCR amplification of organism specific 16S rRNA and bla OXA-51 genes. The antibiotic susceptibility testing was performed using disc diffusion and E-test method. Multiplex PCR assays were used to detect the following β-lactamase genes: four class D carbapenem hydrolyzing oxacillinases (bla OXA-51, bla OXA-23, bla OXA-24 and bla OXA-58. Uniplex PCRs were used to detect three class B metallo-β-lactamases genes (bla IMP, bla VIM and bla NDM-1, class C cephalosporin resistance genes (bla ADC, aminoglycoside resistance gene (aphA6, and ISAba1 of all isolates. Insertion sequence ISAba125 among NDM-1 positive strains was detected. Clonal relatedness of all isolates were analyzed using repetitive sequence-based PCR (rep-PCR. Results Of total 44 analyzed isolates, 97.7% (n = 43 were carbapenem-resistant A. baumannii (CR-AB and 97.7% (n = 43 were multidrug resistant A. baumannii (MDR-AB. One isolate was detected to be extremely drug resistant A. baumannii (XDR-AB. All the isolates were fully susceptible to colistin (MICs < 2 μg/ml. The bla OXA-23 gene was detected in all isolates, while bla NDM-1 was detected in 6 isolates (13.6%. Insertion sequence, ISAba1 was detected in all of bla OXA-23 positive isolates. ISAba125 was detected in all bla NDM-1 positive strains. The bla ADC and aphA6 genes were detected in 90.1 and 40.1%, respectively. The rep-PCR of all isolates represented 7 different genotypes. Conclusion We found high prevalence of CR-AB and MDR-AB with bla OXA-23 gene in a tertiary care hospital in

  7. Brain Insulin Signaling Is Increased in Insulin-Resistant States and Decreases in FOXOs and PGC-1α and Increases in Aβ1-40/42 and Phospho-Tau May Abet Alzheimer Development.

    Science.gov (United States)

    Sajan, Mini; Hansen, Barbara; Ivey, Robert; Sajan, Joshua; Ari, Csilla; Song, Shijie; Braun, Ursula; Leitges, Michael; Farese-Higgs, Margaret; Farese, Robert V

    2016-07-01

    Increased coexistence of Alzheimer disease (AD) and type 2 diabetes mellitus (T2DM) suggests that insulin resistance abets neurodegenerative processes, but linkage mechanisms are obscure. Here, we examined insulin signaling factors in brains of insulin-resistant high-fat-fed mice, ob/ob mice, mice with genetically impaired muscle glucose transport, and monkeys with diet-dependent long-standing obesity/T2DM. In each model, the resting/basal activities of insulin-regulated brain protein kinases, Akt and atypical protein kinase C (aPKC), were maximally increased. Moreover, Akt hyperactivation was accompanied by hyperphosphorylation of substrates glycogen synthase kinase-3β and mammalian target of rapamycin and FOXO proteins FOXO1, FOXO3A, and FOXO4 and decreased peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) expression. Akt hyperactivation was confirmed in individual neurons of anterocortical and hippocampal regions that house cognition/memory centers. Remarkably, β-amyloid (Aβ1-40/42) peptide levels were as follows: increased in the short term by insulin in normal mice, increased basally in insulin-resistant mice and monkeys, and accompanied by diminished amyloid precursor protein in monkeys. Phosphorylated tau levels were increased in ob/ob mice and T2DM monkeys. Importantly, with correction of hyperinsulinemia by inhibition of hepatic aPKC and improvement in systemic insulin resistance, brain insulin signaling normalized. As FOXOs and PGC-1α are essential for memory and long-term neuronal function and regeneration and as Aβ1-40/42 and phospho-tau may increase interneuronal plaques and intraneuronal tangles, presently observed aberrations in hyperinsulinemic states may participate in linking insulin resistance to AD. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  8. Brain Insulin Signaling Is Increased in Insulin-Resistant States and Decreases in FOXOs and PGC-1α and Increases in Aβ1–40/42 and Phospho-Tau May Abet Alzheimer Development

    Science.gov (United States)

    Sajan, Mini; Hansen, Barbara; Ivey, Robert; Sajan, Joshua; Ari, Csilla; Song, Shijie; Braun, Ursula; Leitges, Michael; Farese-Higgs, Margaret

    2016-01-01

    Increased coexistence of Alzheimer disease (AD) and type 2 diabetes mellitus (T2DM) suggests that insulin resistance abets neurodegenerative processes, but linkage mechanisms are obscure. Here, we examined insulin signaling factors in brains of insulin-resistant high-fat–fed mice, ob/ob mice, mice with genetically impaired muscle glucose transport, and monkeys with diet-dependent long-standing obesity/T2DM. In each model, the resting/basal activities of insulin-regulated brain protein kinases, Akt and atypical protein kinase C (aPKC), were maximally increased. Moreover, Akt hyperactivation was accompanied by hyperphosphorylation of substrates glycogen synthase kinase-3β and mammalian target of rapamycin and FOXO proteins FOXO1, FOXO3A, and FOXO4 and decreased peroxisome proliferator–activated receptor γ coactivator-1α (PGC-1α) expression. Akt hyperactivation was confirmed in individual neurons of anterocortical and hippocampal regions that house cognition/memory centers. Remarkably, β-amyloid (Aβ1–40/42) peptide levels were as follows: increased in the short term by insulin in normal mice, increased basally in insulin-resistant mice and monkeys, and accompanied by diminished amyloid precursor protein in monkeys. Phosphorylated tau levels were increased in ob/ob mice and T2DM monkeys. Importantly, with correction of hyperinsulinemia by inhibition of hepatic aPKC and improvement in systemic insulin resistance, brain insulin signaling normalized. As FOXOs and PGC-1α are essential for memory and long-term neuronal function and regeneration and as Aβ1–40/42 and phospho-tau may increase interneuronal plaques and intraneuronal tangles, presently observed aberrations in hyperinsulinemic states may participate in linking insulin resistance to AD. PMID:26895791

  9. Increased detection of clinically significant antibodies and decreased incidence of delayed haemolytic transfusion reaction with the indirect antiglobulin test potentiated by polyethylene glycol compared to albumin: a Japanese study

    Science.gov (United States)

    Okutsu, Miho; Ohto, Hitoshi; Yasuda, Hiroyasu; Kawabata, Kinuyo; Ono, Satoshi; Saito, Shunnichi; Sugawara, Akiko; Kikuchi, Masami; Miura, Saori; Ishii, Youko; Watanabe, Kazuya; Tohyama, Yuriko; Nollet, Kenneth E.

    2011-01-01

    Background The indirect antiglobulin test (IAT) can be potentiated by agents such as polyethylene glycol (PEG-IAT) and albumin (Alb-IAT). PEG-IAT is generally regarded as superior to Alb-IAT for the detection of clinically significant red blood cell (RBC) antibodies. However, supporting data come from Caucasian-dominant populations. Non-Caucasian populations should be investigated as well. Material and methods In this single-centre, retrospective, sequential study, Alb-IAT was used from 1989 to 1996 (8 years) and PEG-IAT from 1997 to 2008 (12 years). Pre-transfusion RBC alloantibody detection rates and specificity, post-transfusion alloantibody production, and the incidence of delayed haemolytic transfusion reaction were assessed and compared for the two periods. Results Although overall RBC alloantibody detection rates were comparable, PEG-IAT more frequently detected clinically significant antibodies such as anti-E, anti-Fyb, and anti-Jka, and less frequently detected insignificant antibodies such as anti-Leb and anti-P1. New alloantibodies emerged comparably during the two periods. Delayed haemolytic transfusion reaction was less frequent during the PEG-IAT period (0.30% versus 0.12%, ptransfusion reaction better than Alb-IAT among Japanese transfusion recipients in this retrospective survey of limited power. PMID:21251459

  10. Near infra-red photoimmunotherapy with anti-CEA-IR700 results in extensive tumor lysis and a significant decrease in tumor burden in orthotopic mouse models of pancreatic cancer.

    Directory of Open Access Journals (Sweden)

    Ali A Maawy

    Full Text Available Photoimmunotherapy (PIT of cancer utilizes tumor-specific monoclonal antibodies conjugated to a photosensitizer phthalocyanine dye IR700 which becomes cytotoxic upon irradiation with near infrared light. In this study, we aimed to evaluate the efficacy of PIT on human pancreatic cancer cells in vitro and in vivo in an orthotopic nude mouse model. The binding capacity of anti-CEA antibody to BxPC-3 human pancreatic cancer cells was determined by FACS analysis. An in vitro cytotoxicity assay was used to determine cell death following treatment with PIT. For in vivo determination of PIT efficacy, nude mice were orthotopically implanted with BxPC-3 pancreatic tumors expressing green fluorescent protein (GFP. After tumor engraftment, the mice were divided into two groups: (1 treatment with anti-CEA-IR700 + 690 nm laser and (2 treatment with 690 nm laser only. Anti-CEA-IR700 (100 μg was administered to group (1 via tail vein injection 24 hours prior to therapy. Tumors were then surgically exposed and treated with phototherapy at an intensity of 150 mW/cm2 for 30 minutes. Whole body imaging was done subsequently for 5 weeks using an OV-100 small animal imaging system. Anti-CEA-IR700 antibody bound to the BxPC3 cells to a high degree as shown by FACS analysis. Anti-CEA-IR700 caused extensive cancer cell killing after light activation compared to control cells in cytotoxicity assays. In the orthotopic models of pancreatic cancer, the anti-CEA-IR700 group had significantly smaller tumors than the control after 5 weeks (p<0.001. There was no significant difference in the body weights of mice in the anti-CEA-IR700 and control groups indicating that PIT was well tolerated by the mice.

  11. Significant Corrosion Resistance in an Ultrafine-Grained Al6063 Alloy with a Bimodal Grain-Size Distribution through a Self-Anodic Protection Mechanism

    Directory of Open Access Journals (Sweden)

    Mahdieh Shakoori Oskooie

    2016-12-01

    Full Text Available The bimodal microstructures of Al6063 consisting of 15, 30, and 45 vol. % coarse-grained (CG bands within the ultrafine-grained (UFG matrix were synthesized via blending of high-energy mechanically milled powders with unmilled powders followed by hot powder extrusion. The corrosion behavior of the bimodal specimens was assessed by means of polarization, steady-state cyclic polarization and impedance tests, whereas their microstructural features and corrosion products were examined using optical microscopy (OM, scanning transmission electron microscopy (STEM, field emission scanning electron microscopy (FE-SEM, electron backscattered diffraction (EBSD, energy dispersive spectroscopy (EDS, and X-ray diffraction (XRD techniques. The bimodal Al6063 containing 15 vol. % CG phase exhibits the highest corrosion resistance among the bimodal microstructures and even superior electrochemical behavior compared with the plain UFG and CG materials in the 3.5% NaCl solution. The enhanced corrosion resistance is attributed to the optimum cathode to anode surface area ratio that gives rise to the formation of an effective galvanic couple between CG areas and the UFG matrix. The operational galvanic coupling leads to the domination of a “self-anodic protection system” on bimodal microstructure and consequently forms a uniform thick protective passive layer over it. In contrast, the 45 vol. % CG bimodal specimen shows the least corrosion resistance due to the catastrophic galvanic corrosion in UFG regions. The observed results for UFG Al6063 suggest that metallurgical tailoring of the grain structure in terms of bimodal microstructures leads to simultaneous enhancement in the electrochemical behavior and mechanical properties of passivable alloys that are usually inversely correlated. The mechanism of self-anodic protection for passivable metals with bimodal microstructures is discussed here for the first time.

  12. High proportions of Staphylococcus epidermidis in dental caries harbor multiple classes of antibiotics resistance, significantly increase inflammatory interleukins in dental pulps.

    Science.gov (United States)

    Devang Divakar, Darshan; Muzaheed; Aldeyab, Sultan Salem; Alfawaz, Sara A; AlKheraif, Abdulaziz Abdullah; Ahmed Khan, Aftab

    2017-08-01

    Staphylococcus epidermidis is one of most prevalent in dental caries or dental pulp which has the capability of horizontal genetic transfer between different bacterial species in the oropharynx, suggesting that it may evolve with the dissemination of resistant determinants, This study was performed to molecularly characterize and differentiate S. epidermidis isolated from dental caries and healthy individual. Also, two important cytokines in inflammation were assayed caused due to S. epidermidis of health and dental caries sources. Dental caries strains were more resistant with high MIC 50 and MIC 90 value. These isolates also showed the presence of mecA gene and another virulence gene i. e sea and seb comparatively more than healthy individual isolates. SCCmec types, III and IV was more prevalent in dental caries isolates where an as healthy individual was more non-typable. Additionally, the quantity of IL-1β and IL-8 caused due to dental caries isolates was seen more which indicate dental caries isolates are able to induce. This study showed that S. epidermidis a normal flora of oropharyngeal are more diverse to those strains which cause dental caries. S. epidermidis owns a prodigious genetic plasticity that permits to obtain, lose or regulate genetic elements that provide compensations to improve its colonization in the host. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Consecutive Acupuncture Stimulations Lead to Significantly Decreased Neural Responses

    NARCIS (Netherlands)

    Yeo, S.; Choe, I.H.; Noort, M.W.M.L. van den; Bosch, M.P.C.; Lim, S.

    2010-01-01

    Objective: Functional magnetic resonance imaging (fMRI), in combination with block design paradigms with consecutive acupuncture stimulations, has often been used to investigate the neural responses to acupuncture. In this study, we investigated whether previous acupuncture stimulations can affect

  14. Significant spread of extensively drug-resistant Acinetobacter baumannii genotypes of clonal complex 92 among intensive care unit patients in a university hospital in southern Iran.

    Science.gov (United States)

    Saffari, Fereshteh; Monsen, Tor; Karmostaji, Afsaneh; Azimabad, Fahimeh Bahadori; Widerström, Micael

    2017-11-01

    Infections associated with Acinetobacter baumannii represent an increasing threat in healthcare settings. Therefore, we investigated the epidemiological relationship between clinical isolates of A. baumannii obtained from patients in a university hospital in Bandar Abbas in southern Iran. Sixty-four consecutive non-duplicate clinical isolates collected during 2014-2015 were subjected to susceptibility testing, clonal relationship analysis using PFGE, multilocus variable-number tandem-repeat analysis (MLVA) and multilocus sequence typing (MLST), and examined for the presence of carbapenemases and integrons. Almost all A. baumannii isolates were extensively drug-resistant (XDR; 98 %) and carried an OXA carbapenemase gene (blaOXA-23-like; 98 %) and class 1 integrons (48 %). PFGE and MLST analysis identified three major genotypes, all belonging to clonal complex 92 (CC92): sequence type 848 (ST848) (n=23), ST451 (n=16) and ST195 (n=8). CC92 has previously been documented in the hospital setting in northern Iran, and ST195 has been reported in Arab States of the Persian Gulf. These data suggest national and global transmission of A. baumannii CC92. This report demonstrates the occurrence and potential spread of closely related XDR genotypes of A. baumannii CC92 within a university hospital in southern Iran. These genotypes were found in the majority of the investigated isolates, showed high prevalence of blaOXA-23 and integron class 1, and were associated with stay in the intensive care unit. Very few treatment options remain for healthcare-adapted XDR A. baumannii, and hence effective measures are desperately needed to reduce the spread of these strains and resultant infections in the healthcare setting.

  15. Emergence of resistant pathogens against colistin

    OpenAIRE

    Rakesh Kumar; Baljit Jassal; Bhupinder Kumar

    2015-01-01

    Emergence of resistant strain to antimicrobials is a growing problem worldwide. Here, we report a case of multidrug-resistant Klebsiella pneumoniae and Acinectobacter baumannii, Gram-negative bacilli, which was only intermediate sensitive to colistin; a polymyxin E. Colistin has attracted more interest recently because of its significant activity against multi-resistant Pseudomonas aeruginosa, A. baumannii and K. pneumoniae, and the low resistance rates to it. The decrease in sensitivity of c...

  16. Resistance-resistant antibiotics.

    Science.gov (United States)

    Oldfield, Eric; Feng, Xinxin

    2014-12-01

    New antibiotics are needed because drug resistance is increasing while the introduction of new antibiotics is decreasing. We discuss here six possible approaches to develop 'resistance-resistant' antibiotics. First, multitarget inhibitors in which a single compound inhibits more than one target may be easier to develop than conventional combination therapies with two new drugs. Second, inhibiting multiple targets in the same metabolic pathway is expected to be an effective strategy owing to synergy. Third, discovering multiple-target inhibitors should be possible by using sequential virtual screening. Fourth, repurposing existing drugs can lead to combinations of multitarget therapeutics. Fifth, targets need not be proteins. Sixth, inhibiting virulence factor formation and boosting innate immunity may also lead to decreased susceptibility to resistance. Although it is not possible to eliminate resistance, the approaches reviewed here offer several possibilities for reducing the effects of mutations and, in some cases, suggest that sensitivity to existing antibiotics may be restored in otherwise drug-resistant organisms. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. THE MORAL SIGNIFICANCE OF ANTIMICROBIAL RESISTANCE.

    Science.gov (United States)

    Johnstone, Megan-Jane

    2016-08-01

    On 14 April 2016, ABC News and The 7:30 Report both reported the case of a 46 year old man who died from hepatitis B believed to have been contracted from another patient while on dialysis at a Melbourne hospital (http://www.abc.net.au/7:30/content/2015/s4443575.htm).

  18. Gestational Diabetes Mellitus Worsens the Profile of Cardiometabolic Risk Markers and Decrease Indexes of Beta-Cell Function Independently of Insulin Resistance in Nondiabetic Women with a Parental History of Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Alina Sokup

    2014-01-01

    Full Text Available Background. Women with a history of both parental type 2 diabetes (pt2DM and previous gestational diabetes (pGDM represent a group at high risk of cardiovascular events. We hypothesized that pGDM changes cardiometabolic risk markers levels as well as theirs associations with glucose indices in nondiabetic pt2DM women. Methods. Anthropometric parameters, glucose regulation (OGTT, insulin resistance (HOMA-IR, beta-cell function, lipid levels, parameters of endothelial dysfunction, and inflammation were evaluated in 55 women with pt2DM, 40 with both pt2DM and pGDM 2–24 months postpartum, and 35 controls. Results. Prediabetes was diagnosed more frequently in women with both pt2DM and pGDM in comparison with women with only pt2DM (10 versus 8, P=0.04. The pGDM group had higher LDL-cholesterol, sICAM-1, tPa Ag, fibrinogen, and lower beta-cell function after adjustment for HOMA-IR, in comparison with pt2DM group. In pt2DM group postchallenge glucose correlated independently with hsCRP and in pGDM group fasting glucose with HOMA-IR. Conclusions. pGDM exerts a combined effect on cardiometabolic risk markers in women with pt2DM. In these women higher LDL-cholesterol, fibrinogen, sICAM-1, tPa Ag levels and decreased beta cell function are associated with pGDM independently of HOMA-IR index value. Fasting glucose is an important cardiometabolic risk marker and is independently associated with HOMA-IR.

  19. Decreased insulin secretion and increased risk of type 2 diabetes associated with allelic variations of the WFS1 gene: the Data from Epidemiological Study on the Insulin Resistance Syndrome (DESIR) prospective study.

    Science.gov (United States)

    Cheurfa, N; Brenner, G M; Reis, A F; Dubois-Laforgue, D; Roussel, R; Tichet, J; Lantieri, O; Balkau, B; Fumeron, F; Timsit, J; Marre, M; Velho, G

    2011-03-01

    We investigated associations of allelic variations in the WFS1 gene with insulin secretion and risk of type 2 diabetes in a general population prospective study. We studied 5,110 unrelated French men and women who participated in the prospective Data from Epidemiological Study on the Insulin Resistance Syndrome (DESIR) study. Additional cross-sectional analyses were performed on 4,472 French individuals with type 2 diabetes and 3,065 controls. Three single nucleotide polymorphisms (SNPs) were genotyped: rs10010131, rs1801213/rs7672995 and rs734312. We observed statistically significant associations between the major alleles of the three variants and prevalent type 2 diabetes in the DESIR cohort at baseline. Cox analyses showed an association between the G-allele of rs10010131 and incident type 2 diabetes (HR 1.34, 95% CI 1.08-1.70, p = 0.007). Similar results were observed for the G-allele of rs1801213 and the A-allele of rs734312. The GGA haplotype was associated with an increased risk of diabetes as compared with the ACG haplotype (HR 1.26, 95% CI 1.04-1.42, p = 0.02). We also observed statistically significant associations of the three SNPs with plasma glucose, HbA(1c) levels and insulin secretion at baseline and throughout the study in individuals with type 2 diabetes or at risk of developing diabetes. However, no association was observed in those who remained normoglycaemic at the end of the follow-up. Associations between the three variants and type 2 diabetes were replicated in cross-sectional studies of type 2 diabetic patients in comparison with a non-diabetic control group. The most frequent haplotype at the haplotype block containing the WFS1 gene modulated insulin secretion and was associated with an increased risk of type 2 diabetes.

  20. Decreasing relative risk premium

    DEFF Research Database (Denmark)

    Hansen, Frank

    2007-01-01

    such that the corresponding relative risk premium is a decreasing function of present wealth, and we determine the set of associated utility functions. We find a new characterization of risk vulnerability and determine a large set of utility functions, closed under summation and composition, which are both risk vulnerable...... and have decreasing relative risk premium. We finally introduce the notion of partial risk neutral preferences on binary lotteries and show that partial risk neutrality is equivalent to preferences with decreasing relative risk premium...

  1. Resistance Versus Aerobic Exercise

    Science.gov (United States)

    Yardley, Jane E.; Kenny, Glen P.; Perkins, Bruce A.; Riddell, Michael C.; Balaa, Nadia; Malcolm, Janine; Boulay, Pierre; Khandwala, Farah; Sigal, Ronald J.

    2013-01-01

    OBJECTIVE In type 1 diabetes, small studies have found that resistance exercise (weight lifting) reduces HbA1c. In the current study, we examined the acute impacts of resistance exercise on glycemia during exercise and in the subsequent 24 h compared with aerobic exercise and no exercise. RESEARCH DESIGN AND METHODS Twelve physically active individuals with type 1 diabetes (HbA1c 7.1 ± 1.0%) performed 45 min of resistance exercise (three sets of seven exercises at eight repetitions maximum), 45 min of aerobic exercise (running at 60% of Vo2max), or no exercise on separate days. Plasma glucose was measured during and for 60 min after exercise. Interstitial glucose was measured by continuous glucose monitoring 24 h before, during, and 24 h after exercise. RESULTS Treatment-by-time interactions (P exercise. Plasma glucose decreased from 8.4 ± 2.7 to 6.8 ± 2.3 mmol/L (P = 0.008) during resistance exercise and from 9.2 ± 3.4 to 5.8 ± 2.0 mmol/L (P = 0.001) during aerobic exercise. No significant changes were seen during the no-exercise control session. During recovery, glucose levels did not change significantly after resistance exercise but increased by 2.2 ± 0.6 mmol/L (P = 0.023) after aerobic exercise. Mean interstitial glucose from 4.5 to 6.0 h postexercise was significantly lower after resistance exercise versus aerobic exercise. CONCLUSIONS Resistance exercise causes less initial decline in blood glucose during the activity but is associated with more prolonged reductions in postexercise glycemia than aerobic exercise. This might account for HbA1c reductions found in studies of resistance exercise but not aerobic exercise in type 1 diabetes. PMID:23172972

  2. A decrease in bulk water and mannitol and accumulation of trehalose and trehalose-based oligosaccharides define a two-stage maturation process towards extreme stress resistance in ascospores of Neosartorya fischeri (Aspergillus fischeri)

    NARCIS (Netherlands)

    Wyatt, Timon T; Golovina, Elena A; van Leeuwen, Richard; Hallsworth, John E; Wösten, Han A B; Dijksterhuis, Jan

    Fungal propagules survive stresses better than vegetative cells. Neosartorya fischeri, an Aspergillus teleomorph, forms ascospores that survive high temperatures or drying followed by heat. Not much is known about maturation and development of extreme stress resistance in fungal cells. This study

  3. Decreasing Relative Risk Premium

    DEFF Research Database (Denmark)

    Hansen, Frank

    We consider the risk premium demanded by a decision maker with wealth x in order to be indifferent between obtaining a new level of wealth y1 with certainty, or to participate in a lottery which either results in unchanged present wealth or a level of wealth y2 > y1. We define the relative risk...... premium as the quotient between the risk premium and the increase in wealth y1–x which the decision maker puts on the line by choosing the lottery in place of receiving y1 with certainty. We study preferences such that the relative risk premium is a decreasing function of present wealth, and we determine...... relative risk premium in the small implies decreasing relative risk premium in the large, and decreasing relative risk premium everywhere implies risk aversion. We finally show that preferences with decreasing relative risk premium may be equivalently expressed in terms of certain preferences on risky...

  4. Decreasing serial cost sharing

    DEFF Research Database (Denmark)

    Hougaard, Jens Leth; Østerdal, Lars Peter Raahave

    2009-01-01

    The increasing serial cost sharing rule of Moulin and Shenker (Econometrica 60:1009-1037, 1992) and the decreasing serial rule of de Frutos (J Econ Theory 79:245-275, 1998) are known by their intuitive appeal and striking incentive properties. An axiomatic characterization of the increasing serial...... rule was provided by Moulin and Shenker (J Econ Theory 64:178-201, 1994). This paper gives an axiomatic characterization of the decreasing serial rule....

  5. Decreasing Serial Cost Sharing

    DEFF Research Database (Denmark)

    Hougaard, Jens Leth; Østerdal, Lars Peter

    The increasing serial cost sharing rule of Moulin and Shenker [Econometrica 60 (1992) 1009] and the decreasing serial rule of de Frutos [Journal of Economic Theory 79 (1998) 245] have attracted attention due to their intuitive appeal and striking incentive properties. An axiomatic characterization...... of the increasing serial rule was provided by Moulin and Shenker [Journal of Economic Theory 64 (1994) 178]. This paper gives an axiomatic characterization of the decreasing serial rule...

  6. Expression of the cytochrome P450s, CYP6P3 and CYP6M2 are significantly elevated in multiple pyrethroid resistant populations of Anopheles gambiae s.s. from Southern Benin and Nigeria

    Directory of Open Access Journals (Sweden)

    Ranson Hilary

    2008-11-01

    Full Text Available Abstract Background Insecticide resistance in Anopheles mosquitoes is threatening the success of malaria control programmes. This is particularly true in Benin where pyrethroid resistance has been linked to the failure of insecticide treated bed nets. The role of mutations in the insecticide target sites in conferring resistance has been clearly established. In this study, the contribution of other potential resistance mechanisms was investigated in Anopheles gambiae s.s. from a number of localities in Southern Benin and Nigeria. The mosquitoes were sampled from a variety of breeding sites in a preliminary attempt to investigate the role of contamination of mosquito breeding sites in selecting for resistance in adult mosquitoes. Results All mosquitoes sampled belonged to the M form of An. gambiae s.s. There were high levels of permethrin resistance in an agricultural area (Akron and an urban area (Gbedjromede, low levels of resistance in mosquito samples from an oil contaminated site (Ojoo and complete susceptibility in the rural Orogun location. The target site mutation kdrW was detected at high levels in two of the populations (Akron f = 0.86 and Gbedjromede f = 0.84 but was not detected in Ojoo or Orogun. Microarray analysis using the Anopheles gambiae detox chip identified two P450s, CYP6P3 and CYP6M2 up regulated in all three populations, the former was expressed at particularly high levels in the Akron (12.4-fold and Ojoo (7.4-fold populations compared to the susceptible population. Additional detoxification and redox genes were also over expressed in one or more populations including two cuticular pre-cursor genes which were elevated in two of the three resistant populations. Conclusion Multiple resistance mechanisms incurred in the different breeding sites contribute to resistance to permethrin in Benin. The cytochrome P450 genes, CYP6P3 and CYP6M2 are upregulated in all three resistant populations analysed. Several additional potential

  7. Hydraulic resistance of biofilms

    KAUST Repository

    Dreszer, C.

    2013-02-01

    after 4 days at a flux of 100Lm-2h-1 (97μm) was in the same order of magnitude as the thickness of a biofilm at a flux of 20Lm-2h-1 (114μm). An increase of flux caused an increased biofilm resistance while a decrease of flux caused a decreased resistance. The effect was reversible. It is suggested that the biofilm resistance is mainly attributed to EPS, probably due to the tortuosity ("hair-in-sink-effect") of the biopolymers to water molecules travelling across the biofilm. The data show clearly that biofilm resistance (6×1012m-1) was high compared to the intrinsic resistance of the employed MF membrane (5×1011m-1). However, in nanofiltration (intrinsic membrane resistance ca. 2×1013m-1) and reverse osmosis membranes (intrinsic resistance ca. 9×1013m-1), the biofilm will not contribute significantly to the overall resistance. © 2012 Elsevier B.V.

  8. Decreasing asthma morbidity

    African Journals Online (AJOL)

    1994-12-12

    Dec 12, 1994 ... Apart from the optimal use of drugs, various supplementary methods have been tested to decrease asthma morbidity, usually in patients from reiatively affluent socio-economic backgrounds. A study of additional measures taken in a group of moderate to severe adult asthmatics from very poor socio- ...

  9. Camptothecin resistance

    DEFF Research Database (Denmark)

    Brangi, M; Litman, Thomas; Ciotti, M

    1999-01-01

    The mitoxantrone resistance (MXR) gene encodes a recently characterized ATP-binding cassette half-transporter that confers multidrug resistance. We studied resistance to the camptothecins in two sublines expressing high levels of MXR: S1-M1-80 cells derived from parental S1 colon cancer cells...... and MCF-7 AdVp3,000 isolated from parental MCF-7 breast cancer cells. Both cell lines were 400- to 1,000-fold more resistant to topotecan, 9-amino-20(S)-camptothecin, and the active metabolite of irinotecan, 7-ethyl-10-hydroxycamptothecin (SN-38), than their parental cell lines. The cell lines...... demonstrated much less resistance to camptothecin and to several camptothecin analogues. Reduced accumulation and energy-dependent efflux of topotecan was demonstrated by confocal microscopy. A significant reduction in cleavable complexes in the resistant cells could be observed after SN-38 treatment...

  10. Glucocorticoid receptor knockdown decreases the antioxidant protection of B16 melanoma cells: an endocrine system-related mechanism that compromises metastatic cell resistance to vascular endothelium-induced tumor cytotoxicity.

    Science.gov (United States)

    Obrador, Elena; Valles, Soraya L; Benlloch, María; Sirerol, J Antoni; Pellicer, José A; Alcácer, Javier; Coronado, Javier Alcácer-F; Estrela, José M

    2014-01-01

    We previously reported an interorgan system in which stress-related hormones (corticosterone and noradrenaline), interleukin-6, and glutathione (GSH) coordinately regulate metastatic growth of highly aggressive B16-F10 melanoma cells. Corticosterone, at levels measured in tumor-bearing mice, also induces apoptotic cell death in metastatic cells with low GSH content. In the present study we explored the potential role of glucocorticoids in the regulation of metastatic cell death/survival during the early stages of organ invasion. Glucocorticoid receptor (GCR) knockdown decreased the expression and activity of γ-glutamylcysteine synthetase (γ-GCS), the rate-limiting step in GSH synthesis, in metastatic cells in vivo independent of the tumor location (liver, lung, or subcutaneous). The decrease in γ-GCS activity was associated with lower intracellular GSH levels. Nrf2- and p53-dependent down-regulation of γ-GCS was associated with a decrease in the activities of superoxide dismutase 1 and 2, catalase, glutathione peroxidase, and glutathione reductase, but not of the O2--generating NADPH oxidase. The GCR knockdown-induced decrease in antioxidant protection caused a drastic decrease in the survival of metastatic cells during their interaction with endothelial cells, both in vitro and in vivo; only 10% of cancer cells attached to the endothelium survived compared to 90% survival observed in the controls. This very low rate of metastatic cell survival was partially increased (up to 52%) in vivo by inoculating B16-F10 cells preloaded with GSH ester, which enters the cell and delivers free GSH. Taken together, our results indicate that glucocorticoid signaling influences the survival of metastatic cells during their interaction with the vascular endothelium.

  11. Characterization of CTX-M-140, a Variant of CTX-M-14 Extended-Spectrum β-Lactamase with Decreased Cephalosporin Hydrolytic Activity, from Cephalosporin-Resistant Proteus mirabilis.

    Science.gov (United States)

    Tian, Guo-Bao; Jiang, Yi-Qi; Huang, Ying-Min; Qin, Yun; Feng, Lian-Qiang; Zhang, Xue-Fei; Li, Hong-Yu; Zhong, Lan-Lan; Zeng, Kun-Jiao; Patil, Sandip; Xing, Yong; Huang, Xi

    2016-10-01

    CTX-M-140, a novel CTX-M-type extended-spectrum β-lactamase (ESBL), was identified in cephalosporin-resistant clinical isolates of Proteus mirabilis CTX-M-140 contained an alanine-to-threonine substitution at position 109 compared to its putative progenitor, CTX-M-14. When it was expressed in an Escherichia coli isogenic background, CTX-M-140 conferred 4- to 32-fold lower MICs of cephalosporins than those with CTX-M-14, indicating that the phenotype was attributable to this single substitution. For four mutants of CTX-M-14 that were constructed by site-directed mutagenesis (A109E, A109D, A109K, and A109R mutants), MICs of cephalosporins were similar to those for the E. coli host strain, which suggested that the alanine at position 109 was essential for cephalosporin hydrolysis. The kinetic properties of native CTX-M-14 and CTX-M-140 were consistent with the MICs for the E. coli clones. Compared with that of CTX-M-14, a lower hydrolytic activity against cephalosporins was observed for CTX-M-140. blaCTX-M-140 is located on the chromosome as determined by I-CeuI pulsed-field gel electrophoresis (I-CeuI-PFGE) and Southern hybridization. The genetic environment surrounding blaCTX-M-140 is identical to the sequence found in different plasmids with blaCTX-M-9-group genes among the Enterobacteriaceae Genome sequencing and analysis showed that P. mirabilis strains with blaCTX-M-140 have a genome size of ∼4 Mbp, with a GC content of 38.7% and 23 putative antibiotic resistance genes. Our results indicate that alanine at position 109 is critical for the hydrolytic activity of CTX-M-14 against oxyimino-cephalosporins. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  12. Insulin decreases atherosclerosis by inducing endothelin receptor B expression

    DEFF Research Database (Denmark)

    Park, Kyoungmin; Mima, Akira; Li, Qian

    2016-01-01

    Endothelial cell (EC) insulin resistance and dysfunction, caused by diabetes, accelerates atherosclerosis. It is unknown whether specifically enhancing EC-targeted insulin action can decrease atherosclerosis in diabetes. Accordingly, overexpressing insulin receptor substrate-1 (IRS1......) in the endothelia of Apoe(-/-) mice (Irs1/Apoe(-/-)) increased insulin signaling and function in the aorta. Atherosclerosis was significantly reduced in Irs1/ApoE(-/-) mice on diet-induced hyperinsulinemia and hyperglycemia. The mechanism of insulin's enhanced antiatherogenic actions in EC was related to remarkable...... overexpression in the endothelia of Aki/ApoE(-/-) mice significantly decreased atherosclerosis. Interestingly, endothelial EDNRB expression was selectively reduced in intima of arteries from diabetic patients and rodents. However, endothelial EDNRB expression was upregulated by insulin via P13K/Akt pathway...

  13. Antimicrobial resistance among Campylobacter jejuni isolated from raw poultry meat at retail level in Denmark

    DEFF Research Database (Denmark)

    Andersen, S. R.; Saadbye, P.; Shukri, Naseer Mahmoud

    2006-01-01

    of resistance among C. jejuni were observed for tetracycline, nalidixic acid and ciprofloxacin, whereas macrolide resistance was rarely detected. C. jejuni originating from other poultry meat (mainly duck and turkey meat) exhibited the highest occurrences of antimicrobial resistance monitored; approximately one...... third of the isolates were tetracycline resistant (N=100). Among chicken meat isolates, the occurrence of tetracycline resistance was significantly higher (P ... for chloramphenicol, nalidixic acid and ciprofloxacin (P resistance in the period 1996-2003 among C jejuni isolates from chicken meat indicate a decrease in the occurrence of resistance towards fluoroquinolones. This may be due to reduced application of fluoroquinolones for food animals...

  14. Mechanisms of drought resistance in grain: II Stomatal regulation ...

    African Journals Online (AJOL)

    Earlier research works conducted to identify mechanisms of drought resistance in grain legumes under soil water stress of -0.6 MPa showed that drought resistance (maintenace of turgor) in chick pea was due to a significant decrease in osmotic potential (osmotic adjustment) while in common bean it was due to ...

  15. Ten-year decrease of acquired methicillin-resistant Staphylococcus aureus (MRSA bacteremia at a single institution: the result of a multifaceted program combining cross-transmission prevention and antimicrobial stewardship

    Directory of Open Access Journals (Sweden)

    Chalfine Annie

    2012-05-01

    Full Text Available Abstract Background In France, the proportion of MRSA has been over 25% since 2000. Prevention of hospital-acquired (HA MRSA spread is based on isolation precautions and antibiotic stewardship. At our institution, before 2000, the Infection Disease and the Infection Control teams had failed to reduce HA-MRSA rates. Objectives and methods We implemented a multifaceted hospital-wide prevention program and measured the effects on HA-MRSA colonization and bacteremia rates between 2000 and 2009. From 2000 to 2003, active screening and decontamination of ICU patients, hospital wide alcohol based hand rubs (ABHR use, control of specific classes of antibiotics, compliance audits, and feed-backs to the care providers were successively implemented. The efficacy of the program was assessed by HA-MRSA colonized and bacteremic patient rates per 1000 patient-days in patients hospitalized for more than twenty-four hours. Results Compliance with the isolation practices increased between 2000 and 2009. Consumption of ABHR increased from 6.8 L to 27.5 L per 1000 patient-days. The use of antibiotic Defined Daily Doses (DDD per 1000 patient-days decreased by 31%. HA-MRSA colonization decreased by 84% from 1.09 to 0.17 per 1000 patient-days and HA-MRSA bacteremia by 93%, from 0.15 to 0.01 per 1000 patient-days (p −7 for each rate. Conclusions In an area highly endemic for MRSA, a multifaceted prevention program allows for sustainable reduction in HA-MRSA bacteremia rates.

  16. Calbindins decreased after space flight.

    Science.gov (United States)

    Sergeev, I N; Rhoten, W B; Carney, M D

    1996-12-01

    Exposure of the body to microgravity during space flight causes a series of well-documented changes in Ca2+ metabolism, yet the cellular and molecular mechanisms leading to these changes are poorly understood. Calbindins, vitamin D-dependent Ca2+ binding proteins, are believed to have a significant role in maintaining cellular Ca2+ homeostasis. In this study, we used biochemical and immunocytochemical approaches to analyze the expression of calbindin-D28k and calbindin-D9k in kidneys, small intestine, and pancreas of rats flown for 9 d aboard the space shuttle. The effects of microgravity on calbindins in rats from space were compared with synchronous Animal Enclosure Module controls, modeled weightlessness animals (tail suspension), and their controls. Exposure to microgravity resulted in a significant and sustained decrease in calbindin-D28k content in the kidney and calbindin-D9k in the small intestine of flight animals, as measured by enzyme-linked immunosorbent assay (ELISA). Modeled weightlessness animals exhibited a similar decrease in calbindins by ELISA. Immunocytochemistry (ICC) in combination with quantitative computer image analysis was used to measure in situ the expression of calbindins in the kidney and the small intestine, and the expression of insulin in pancreas. There was a large decrease of immunoreactivity in renal distal tubular cell-associated calbindin-D28k and in intestinal absorptive cell-associated calbindin-D9k of space flight and modeled weightlessness animals compared with matched controls. No consistent difference in pancreatic insulin immunoreactivity between space flight, modeled weightlessness, and controls was observed. Regression analysis of results obtained by quantitative ICC and ELISA for space flight, modeled weightlessness animals, and their controls demonstrated a significant correlation. These findings after a short-term exposure to microgravity or modeled weightlessness suggest that a decreased expression of calbindins

  17. Awareness of bacterial resistance among physicians, pharmacists and nurses.

    Science.gov (United States)

    Alzoubi, Karem; Ayoub, Nehad; Al-Sakaji, Suehair; Al-Azzam, Sayer; Mhaidat, Nizar; Masadeh, Majed

    2009-01-01

    To assess the level of medical staff awareness of bacterial resistance and characterize the most common resistant bacterial species, the factors contributing to the development of such resistance, and the possible measures to limit the increasing rate of resistance to current antibacterial therapies. A questionnaire was administered to 352 health care professionals including physicians, pharmacists and nurses at four central university hospitals in Jordan. Our results indicate that most of the responding physicians and pharmacists considered Pseudomonas aeruginosa and methicilin-resistant Staphylococcus aureus the most frequently encountered resistant bacterial species. However, nurses recognized both methicilin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE) as the most prevalent resistant species. Physicians and nurses (50.0% and 61.6%, respectively) reported prolonged hospitalization as a factor likely to contribute to the increased incidence of bacterial resistance. About 58% of pharmacists indicated the use of antibiotics without prescription as a significant reason for the development of bacterial resistance. Most of physicians (61.2%) reported that appropriate infection control is the most important measure to reduce bacterial resistance. Pharmacists (58.1%) recognized better adherence to the infection control guidelines as the most important factor that could reduce the risk of bacterial resistance. The findings of this study indicate a varying level of awareness of bacterial resistance among the health care professionals. Thus, serious efforts are still needed to develop and implement strategies to decrease the future risk of bacterial resistance to antibiotics.

  18. Significance of ERBB2 Overexpression in Therapeutic Resistance and Cancer-Specific Survival in Muscle-Invasive Bladder Cancer Patients Treated With Chemoradiation-Based Selective Bladder-Sparing Approach

    International Nuclear Information System (INIS)

    Inoue, Masaharu; Koga, Fumitaka; Yoshida, Soichiro; Tamura, Tomoki; Fujii, Yasuhisa; Ito, Eisaku; Kihara, Kazunori

    2014-01-01

    Purpose: To investigate the associations of ERBB 2 overexpression with chemoradiation therapy (CRT) resistance and cancer-specific survival (CSS) in muscle-invasive bladder cancer (MIBC) patients treated with the CRT-based bladder-sparing protocol. Methods and Materials: From 1997 to 2012, 201 patients with cT2-4aN0M0 bladder cancer were treated with CRT (40 Gy with concurrent cisplatin) following transurethral resection of bladder tumor (TURBT). Basically, patients with tumors that showed good CRT response and were amenable to segmental resection underwent partial cystectomy (PC) with pelvic lymph node dissection for bladder preservation; otherwise, radical cystectomy (RC) was recommended. Included in this study were 119 patients in whom TURBT specimens were available for immunohistochemical analysis of ERBB 2 expression. Following CRT, 30 and 65 patients underwent PC or RC, respectively; the remaining 24 patients did not undergo cystectomy. Tumors were defined as CRT-resistant when patients did not achieve complete response after CRT. Associations of ERBB 2 overexpression with CRT resistance and CSS were evaluated. Results: CRT resistance was observed clinically in 56% (67 of 119 patients) and pathologically (in cystectomy specimens) in 55% (52 of 95 patients). ERBB 2 overexpression was observed in 45 patients (38%). On multivariate analysis, ERBB 2 overexpression was an independent predictor for CRT resistance clinically (odds ratio, 3.6; P=.002) and pathologically (odds ratio, 2.9; P=.031). ERBB 2 overexpression was associated with shorter CSS (5-year CSS rates, 56% vs 87% for the ERBB 2 overexpression group vs the others; P=.001). ERBB 2 overexpression was also an independent risk factor for bladder cancer death at all time points of our bladder-sparing protocol (pre-CRT, post-CRT, and post-cystectomy). Conclusions: ERBB 2 overexpression appears relevant to CRT resistance and unfavorable CSS in MIBC patients treated with the CRT-based bladder

  19. Significance of ERBB2 Overexpression in Therapeutic Resistance and Cancer-Specific Survival in Muscle-Invasive Bladder Cancer Patients Treated With Chemoradiation-Based Selective Bladder-Sparing Approach

    Energy Technology Data Exchange (ETDEWEB)

    Inoue, Masaharu [Department of Urology, Tokyo Medical and Dental University, Graduate School, Tokyo (Japan); Koga, Fumitaka, E-mail: f-koga@cick.jp [Department of Urology, Tokyo Medical and Dental University, Graduate School, Tokyo (Japan); Yoshida, Soichiro [Department of Urology, Tokyo Medical and Dental University, Graduate School, Tokyo (Japan); Tamura, Tomoki [Department of Pathology, Tokyo Medical and Dental University, Graduate School, Tokyo (Japan); Fujii, Yasuhisa [Department of Urology, Tokyo Medical and Dental University, Graduate School, Tokyo (Japan); Ito, Eisaku [Department of Pathology, Tokyo Medical and Dental University, Graduate School, Tokyo (Japan); Kihara, Kazunori [Department of Urology, Tokyo Medical and Dental University, Graduate School, Tokyo (Japan)

    2014-10-01

    Purpose: To investigate the associations of ERBB 2 overexpression with chemoradiation therapy (CRT) resistance and cancer-specific survival (CSS) in muscle-invasive bladder cancer (MIBC) patients treated with the CRT-based bladder-sparing protocol. Methods and Materials: From 1997 to 2012, 201 patients with cT2-4aN0M0 bladder cancer were treated with CRT (40 Gy with concurrent cisplatin) following transurethral resection of bladder tumor (TURBT). Basically, patients with tumors that showed good CRT response and were amenable to segmental resection underwent partial cystectomy (PC) with pelvic lymph node dissection for bladder preservation; otherwise, radical cystectomy (RC) was recommended. Included in this study were 119 patients in whom TURBT specimens were available for immunohistochemical analysis of ERBB 2 expression. Following CRT, 30 and 65 patients underwent PC or RC, respectively; the remaining 24 patients did not undergo cystectomy. Tumors were defined as CRT-resistant when patients did not achieve complete response after CRT. Associations of ERBB 2 overexpression with CRT resistance and CSS were evaluated. Results: CRT resistance was observed clinically in 56% (67 of 119 patients) and pathologically (in cystectomy specimens) in 55% (52 of 95 patients). ERBB 2 overexpression was observed in 45 patients (38%). On multivariate analysis, ERBB 2 overexpression was an independent predictor for CRT resistance clinically (odds ratio, 3.6; P=.002) and pathologically (odds ratio, 2.9; P=.031). ERBB 2 overexpression was associated with shorter CSS (5-year CSS rates, 56% vs 87% for the ERBB 2 overexpression group vs the others; P=.001). ERBB 2 overexpression was also an independent risk factor for bladder cancer death at all time points of our bladder-sparing protocol (pre-CRT, post-CRT, and post-cystectomy). Conclusions: ERBB 2 overexpression appears relevant to CRT resistance and unfavorable CSS in MIBC patients treated with the CRT-based bladder

  20. Significance of ERBB2 overexpression in therapeutic resistance and cancer-specific survival in muscle-invasive bladder cancer patients treated with chemoradiation-based selective bladder-sparing approach.

    Science.gov (United States)

    Inoue, Masaharu; Koga, Fumitaka; Yoshida, Soichiro; Tamura, Tomoki; Fujii, Yasuhisa; Ito, Eisaku; Kihara, Kazunori

    2014-10-01

    To investigate the associations of ERBB 2 overexpression with chemoradiation therapy (CRT) resistance and cancer-specific survival (CSS) in muscle-invasive bladder cancer (MIBC) patients treated with the CRT-based bladder-sparing protocol. From 1997 to 2012, 201 patients with cT2-4aN0M0 bladder cancer were treated with CRT (40 Gy with concurrent cisplatin) following transurethral resection of bladder tumor (TURBT). Basically, patients with tumors that showed good CRT response and were amenable to segmental resection underwent partial cystectomy (PC) with pelvic lymph node dissection for bladder preservation; otherwise, radical cystectomy (RC) was recommended. Included in this study were 119 patients in whom TURBT specimens were available for immunohistochemical analysis of ERBB 2 expression. Following CRT, 30 and 65 patients underwent PC or RC, respectively; the remaining 24 patients did not undergo cystectomy. Tumors were defined as CRT-resistant when patients did not achieve complete response after CRT. Associations of ERBB 2 overexpression with CRT resistance and CSS were evaluated. CRT resistance was observed clinically in 56% (67 of 119 patients) and pathologically (in cystectomy specimens) in 55% (52 of 95 patients). ERBB 2 overexpression was observed in 45 patients (38%). On multivariate analysis, ERBB 2 overexpression was an independent predictor for CRT resistance clinically (odds ratio, 3.6; P=.002) and pathologically (odds ratio, 2.9; P=.031). ERBB 2 overexpression was associated with shorter CSS (5-year CSS rates, 56% vs 87% for the ERBB 2 overexpression group vs the others; P=.001). ERBB 2 overexpression was also an independent risk factor for bladder cancer death at all time points of our bladder-sparing protocol (pre-CRT, post-CRT, and post-cystectomy). ERBB 2 overexpression appears relevant to CRT resistance and unfavorable CSS in MIBC patients treated with the CRT-based bladder-sparing protocol. ERBB 2-targeting treatment may improve the outcomes

  1. Fate of antibiotic resistance genes and metal resistance genes during thermophilic aerobic digestion of sewage sludge.

    Science.gov (United States)

    Jang, Hyun Min; Lee, Jangwoo; Kim, Young Beom; Jeon, Jong Hun; Shin, Jingyeong; Park, Mee-Rye; Kim, Young Mo

    2018-02-01

    This study examines the fate of twenty-three representative antibiotic resistance genes (ARGs) encoding tetracyclines, sulfonamides, quinolones, β-lactam antibiotics, macrolides, florfenicol and multidrug resistance during thermophilic aerobic digestion (TAD) of sewage sludge. The bacterial community, class 1 integrons (intI1) and four metal resistance genes (MRGs) were also quantified to determine the key drivers of changes in ARGs during TAD. At the end of digestion, significant decreases in the quantities of ARGs, MRGs and intI1 as well as 16S rRNA genes were observed. Partial redundancy analysis (RDA) showed that shifts in temperature were the key factors affecting a decrease in ARGs. Shifts in temperature led to decreased amounts of ARGs by reducing resistome and bacterial diversity, rather than by lowering horizontal transfer potential via intI1 or co-resistance via MRGs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Progesterone resistance in endometriosis

    DEFF Research Database (Denmark)

    Patel, Bansari G; Rudnicki, Martin; Yu, Jie

    2017-01-01

    Endometriosis is a common cause of pelvic pain and affects up to 10% of women of reproductive age. Aberrant progesterone signaling in the endometrium plays a significant role in impaired decidualization and establishment of ectopic endometrial implants. Eutopic endometrial cells from women...... with endometriosis fail to downregulate genes needed for decidualization, such as those involved in cell cycle regulation, leading to unbridled proliferation. Several causes of progesterone resistance in the endometrium have been postulated, including congenital "preconditioning", whereby the in utero environment...... renders infants susceptible to neonatal uterine bleeding and endometriosis. Progesterone action is crucial to decreasing inflammation in the endometrium, and deviant progesterone signaling results in a proinflammatory phenotype. Conversely, chronic inflammation can induce a progesterone resistant state...

  3. Hyperhomocysteinemia decreases bone blood flow

    Directory of Open Access Journals (Sweden)

    Neetu T

    2011-01-01

    Full Text Available Neetu Tyagi*, Thomas P Vacek*, John T Fleming, Jonathan C Vacek, Suresh C TyagiDepartment of Physiology and Biophysics, School of Medicine, University of Louisville, Louisville, KY, USA *These authors have equal authorshipAbstract: Elevated plasma levels of homocysteine (Hcy, known as hyperhomocysteinemia (HHcy, are associated with osteoporosis. A decrease in bone blood flow is a potential cause of compromised bone mechanical properties. Therefore, we hypothesized that HHcy decreases bone blood flow and biomechanical properties. To test this hypothesis, male Sprague–Dawley rats were treated with Hcy (0.67 g/L in drinking water for 8 weeks. Age-matched rats served as controls. At the end of the treatment period, the rats were anesthetized. Blood samples were collected from experimental or control rats. Biochemical turnover markers (body weight, Hcy, vitamin B12, and folate were measured. Systolic blood pressure was measured from the right carotid artery. Tibia blood flow was measured by laser Doppler flow probe. The results indicated that Hcy levels were significantly higher in the Hcy-treated group than in control rats, whereas vitamin B12 levels were lower in the Hcy-treated group compared with control rats. There was no significant difference in folate concentration and blood pressure in Hcy-treated versus control rats. The tibial blood flow index of the control group was significantly higher (0.78 ± 0.09 flow unit compared with the Hcy-treated group (0.51 ± 0.09. The tibial mass was 1.1 ± 0.1 g in the control group and 0.9 ± 0.1 in the Hcy-treated group. The tibia bone density was unchanged in Hcy-treated rats. These results suggest that Hcy causes a reduction in bone blood flow, which contributes to compromised bone biomechanical properties.Keywords: homocysteine, tibia, bone density

  4. HYDROGEOLOGICAL SIGNIFICANCE OF GEOELECTRIC ...

    African Journals Online (AJOL)

    ... basement complex rock and the sedimentary rock of Abeokuta formation. Thus for Ijebu-ode and its environs, a thorough geophysical survey is required before citing a borehole to guide against failure or dry hole. KEY WORDS: Aquifer, Coarse sand, Resistivity, Compacted Clay, Borehole. Global Jnl Geological Sciences.

  5. Tamoxifen induces resistance to activated protein C.

    Science.gov (United States)

    Rühl, Heiko; Schröder, Lars; Müller, Jens; Fimmers, Rolf; Sukhitashvili, Shorena; Welz, Julia; Kuhn, Walther C; Oldenburg, Johannes; Rudlowski, Christian; Pötzsch, Bernd

    2014-05-01

    The estrogen antagonist tamoxifen (TAM) increases the thrombotic risk similar to estrogen containing oral contraceptives (OC). In OC users this risk is attributed to alterations of hemostasis resulting in acquired resistance to activated protein C (APC). TAM-induced APC resistance has not been reported yet. Blood samples were collected prospectively from women with breast cancer before (n=25) and monthly after start of adjuvant TAM treatment (n=75). APC resistance was evaluated on basis of the effect of APC on the endogenous thrombin generation potential. To detect increased in vivo APC generation APC plasma levels were measured using a highly sensitive oligonucleotide-based enzyme capture assay. Routine hemostasis parameters were measured additionally. APC sensitivity decreased by 41% (p=0.001) compared to baseline after one month of TAM application and remained significantly decreased during the study period. Free protein S increased (p=0.008) while other analyzed procoagulant factors, inhibitors, and activation markers of coagulation decreased or did not change significantly. In five patients the APC concentration increased to non-physiological levels but an overall significant increase of APC was not observed. This is the first study showing acquired APC resistance under TAM therapy. Acquired APC resistance might explain the increased thrombotic risk during TAM treatment. Observed changes of hemostasis parameters suggest different determinants of TAM-induced APC resistance than in OC-induced APC resistance. The presence of acquired APC resistance in TAM patients warrants further evaluation if these patients may benefit from antithrombotic prophylaxis in the presence of additional thrombotic risk factors. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Intralipid decreases apolipoprotein M levels and insulin sensitivity in rats.

    Directory of Open Access Journals (Sweden)

    Lu Zheng

    Full Text Available BACKGROUND: Apolipoprotein M (ApoM is a constituent of high-density lipoproteins (HDL. It plays a crucial role in HDL-mediated reverse cholesterol transport. Insulin resistance is associated with decreased ApoM levels. AIMS: To assess the effects of increased free fatty acids (FFAs levels after short-term Intralipid infusion on insulin sensitivity and hepatic ApoM gene expression. METHODS: Adult male Sprague-Dawley (SD rats infused with 20% Intralipid solution for 6 h. Glucose infusion rates (GIR were determined by hyperinsulinemic-euglycemic clamp during Intralipid infusion and plasma FFA levels were measured by colorimetry. Rats were sacrificed after Intralipid treatment and livers were sampled. Human embryonic kidney 293T cells were transfected with a lentivirus mediated human apoM overexpression system. Goto-Kakizaki (GK rats were injected with the lentiviral vector and insulin tolerance was assessed. Gene expression was assessed by real-time RT-PCR and PCR array. RESULTS: Intralipid increased FFAs by 17.6 folds and GIR was decreased by 27.1% compared to the control group. ApoM gene expression was decreased by 40.4% after Intralipid infusion. PPARβ/δ expression was not changed by Intralipid. Whereas the mRNA levels of Acaca, Acox1, Akt1, V-raf murine sarcoma 3611 viral oncogene homolog, G6pc, Irs2, Ldlr, Map2k1, pyruvate kinase and RBC were significantly increased in rat liver after Intralipid infusion. The Mitogen-activated protein kinase 8 (MAPK8 was significantly down-regulated in 293T cells overexpressing ApoM. Overexpression of human ApoM in GK rats could enhance the glucose-lowering effect of exogenous insulin. CONCLUSION: These results suggest that Intralipid could decrease hepatic ApoM levels. ApoM overexpression may have a potential role in improving insulin resistance in vivo and modulating apoM expression might be a future therapeutic strategy against insulin resistance in type 2 diabetes.

  7. Effects of Pavement Skid Resistance on Traffic Accidents

    Directory of Open Access Journals (Sweden)

    Abdullah I. Al-Mansour

    2006-12-01

    Full Text Available The Ministry of Transport (MOT in the Kingdom of Saudi Arabia had collected a massive amount of friction measurements using a Mu-meter covering most of the major highway network in the kingdom. Traffic accident data of 89 high accident rate locations from four main different highway classes were extracted from the MOT accident records. Pavement skid resistance for the selected locations was determined from the pavement skid resistance records. The objective of this paper is to utilize these data to investigate the effects of pavement skid resistance on traffic accidents. The analysis included establishing relationships between skid resistance and accident number, accident significance and accident density. It was determined that a decreasing skid resistance leads to an increase in traffic accidents. Acritical value of skid resistance was also established based on number, significance and density of accidents.

  8. Characterization of a novel arginine catabolic mobile element (ACME) and staphylococcal chromosomal cassette mec composite island with significant homology to Staphylococcus epidermidis ACME type II in methicillin-resistant Staphylococcus aureus genotype ST22-MRSA-IV.

    LENUS (Irish Health Repository)

    Shore, Anna C

    2011-05-01

    The arginine catabolic mobile element (ACME) is prevalent among methicillin-resistant Staphylococcus aureus (MRSA) isolates of sequence type 8 (ST8) and staphylococcal chromosomal cassette mec (SCCmec) type IVa (USA300) (ST8-MRSA-IVa isolates), and evidence suggests that ACME enhances the ability of ST8-MRSA-IVa to grow and survive on its host. ACME has been identified in a small number of isolates belonging to other MRSA clones but is widespread among coagulase-negative staphylococci (CoNS). This study reports the first description of ACME in two distinct strains of the pandemic ST22-MRSA-IV clone. A total of 238 MRSA isolates recovered in Ireland between 1971 and 2008 were investigated for ACME using a DNA microarray. Twenty-three isolates (9.7%) were ACME positive, and all were either MRSA genotype ST8-MRSA-IVa (7\\/23, 30%) or MRSA genotype ST22-MRSA-IV (16\\/23, 70%). Whole-genome sequencing and comprehensive molecular characterization revealed the presence of a novel 46-kb ACME and staphylococcal chromosomal cassette mec (SCCmec) composite island (ACME\\/SCCmec-CI) in ST22-MRSA-IVh isolates (n=15). This ACME\\/SCCmec-CI consists of a 12-kb DNA region previously identified in ACME type II in S. epidermidis ATCC 12228, a truncated copy of the J1 region of SCCmec type I, and a complete SCCmec type IVh element. The composite island has a novel genetic organization, with ACME located within orfX and SCCmec located downstream of ACME. One PVL locus-positive ST22-MRSA-IVa isolate carried ACME located downstream of SCCmec type IVa, as previously described in ST8-MRSA-IVa. These results suggest that ACME has been acquired by ST22-MRSA-IV on two independent occasions. At least one of these instances may have involved horizontal transfer and recombination events between MRSA and CoNS. The presence of ACME may enhance dissemination of ST22-MRSA-IV, an already successful MRSA clone.

  9. Decreasing Human Trafficking through Sex Work Decriminalization.

    Science.gov (United States)

    Albright, Erin; D'Adamo, Kate

    2017-01-01

    In order to decrease human trafficking, health care workers should support the full decriminalization of prostitution. Similar to trafficking in other forms of labor, preventing trafficking in the sex trade requires addressing the different forms of marginalization that create vulnerable communities. By removing punitive laws that prevent reporting of exploitation and abuse, decriminalization allows sex workers to work more safely, thereby reducing marginalization and vulnerability. Decriminalization can also help destigmatize sex work and help resist political, social, and cultural marginalization of sex workers. © 2017 American Medical Association. All Rights Reserved.

  10. Resistance in psychotherapy with adolescents.

    Science.gov (United States)

    Graafsma, T; Anbeek, M

    1984-03-01

    Resistances are of considerable significance in psychoterapy with adolescents. In this article, that significance is investigated further, because the way in which resistances are valued is very important in treatment. The forms in which it appears and, the source and intention of resistances are discussed. It is proposed that the investigation of resistances should not be aimed primarily at their removal.

  11. Drug-resistant tuberculosis

    African Journals Online (AJOL)

    The epidemic of drug-resistant tuberculosis. (DR-TB) is a public health emergency that threatens to destabilise global TB control. Although TB incidence and mortality are decreasing in several parts of the world, the overall prevalence of multidrug-resistant tuberculosis (MDR-TB) is increasing in many high-burden countries, ...

  12. Decreased Azithromycin Susceptibility of Neisseria gonorrhoeae Isolates in Patients Recently Treated with Azithromycin

    NARCIS (Netherlands)

    Wind, Carolien M.; de Vries, Esther; Schim van der Loeff, Maarten F.; van Rooijen, Martijn S.; van Dam, Alje P.; Demczuk, Walter H. B.; Martin, Irene; de Vries, Henry J. C.

    2017-01-01

    Background. Increasing azithromycin usage and resistance in Neisseria gonorrhoeae threatens current dual treatment. Because antimicrobial exposure influences resistance, we analyzed the association between azithromycin exposure and decreased susceptibility of N. gonorrhoeae. Methods. We included N.

  13. [Resistance mechanisms and cross-resistance of phoxim-resistant Frankliniella occidentalis Pergande population].

    Science.gov (United States)

    Wang, Sheng-Yin; Zhou, Xian-Hong; Zhang, An-Sheng; Li, Li-Li; Men, Xing-Yuan; Zhang, Si-Cong; Liu, Yong-Jie; Yu, Yi

    2012-07-01

    To understand the resistance risks of Frankliniella occidentalis Pergande against phoxim, this paper studied the resistance mechanisms of phoxim-resistant F. occidentalis population against phoxim and the cross-resistance of the population against other insecticides. The phoxim-resistant population had medium level cross-resistance to chlorpyrifos, lambda-cyhalothrin, and methomyl, low level cross-resistance to chlorfenapyr, imidacloprid, emamectin-benzoate, and spinosad, but no cross-resistance to acetamiprid and abamectin. The synergists piperonyl butoxide (PBO), s, s, s-tributyl phosphorotrithioate (DEF), and triphenyl phosphate (TPP) had significant synergism (P occidentalis could play an important role in the resistance of the plant against phoxim.

  14. Detecting Novelty and Significance

    Science.gov (United States)

    Ferrari, Vera; Bradley, Margaret M.; Codispoti, Maurizio; Lang, Peter J.

    2013-01-01

    Studies of cognition often use an “oddball” paradigm to study effects of stimulus novelty and significance on information processing. However, an oddball tends to be perceptually more novel than the standard, repeated stimulus as well as more relevant to the ongoing task, making it difficult to disentangle effects due to perceptual novelty and stimulus significance. In the current study, effects of perceptual novelty and significance on ERPs were assessed in a passive viewing context by presenting repeated and novel pictures (natural scenes) that either signaled significant information regarding the current context or not. A fronto-central N2 component was primarily affected by perceptual novelty, whereas a centro-parietal P3 component was modulated by both stimulus significance and novelty. The data support an interpretation that the N2 reflects perceptual fluency and is attenuated when a current stimulus matches an active memory representation and that the amplitude of the P3 reflects stimulus meaning and significance. PMID:19400680

  15. Significant NRC Enforcement Actions

    Data.gov (United States)

    Nuclear Regulatory Commission — This dataset provides a list of Nuclear Regulartory Commission (NRC) issued significant enforcement actions. These actions, referred to as "escalated", are issued by...

  16. Obesity Decreases Perioperative Tissue Oxygenation

    Science.gov (United States)

    Kabon, Barbara; Nagele, Angelika; Reddy, Dayakar; Eagon, Chris; Fleshman, James W.; Sessler, Daniel I.; Kurz, Andrea

    2005-01-01

    Background: Obesity is an important risk factor for surgical site infections. The incidence of surgical wound infections is directly related to tissue perfusion and oxygenation. Fat tissue mass expands without a concomitant increase in blood flow per cell, which might result in a relative hypoperfusion with decreased tissue oxygenation. Consequently, we tested the hypotheses that perioperative tissue oxygen tension is reduced in obese surgical patients. Furthermore, we compared the effect of supplemental oxygen administration on tissue oxygenation in obese and non-obese patients. Methods: Forty-six patients undergoing major abdominal surgery were assigned to one of two groups according to their body mass index (BMI): BMI < 30 kg/m2 (non-obese) and BMI ≥ 30 kg/m2 (obese). Intraoperative oxygen administration was adjusted to arterial oxygen tensions of ≈150 mmHg and ≈300 mmHg in random order. Anesthesia technique and perioperative fluid management were standardized. Subcutaneous tissue oxygen tension was measured with a polarographic electrode positioned within a subcutaneous tonometer in the lateral upper arm during surgery, in the recovery room, and on the first postoperative day. Postoperative tissue oxygen was also measured adjacent to the wound. Data were compared with unpaired two tailed t-tests and Wilcoxon rank-sum tests; P < 0.05 was considered statistically significant. Results: Intraoperative subcutaneous tissue oxygen tension was significantly less in the obese patients at baseline (36 vs. 57 mmHg, P = 0.002) and with supplemental oxygen administration (47 vs. 76 mmHg, P = 0.014). Immediate postoperative tissue oxygen tension was also significantly less in subcutaneous tissue of the upper arm (43 vs. 54 mmHg, P = 0.011) as well as near the incision (42 vs. 62 mmHg, P = 0.012) in obese patients. In contrast, tissue oxygen tension was comparable in each group on the first postoperative morning. Conclusion: Wound and tissue hypoxia were common in obese

  17. Antibiotic Resistance in Foodborne Pathogens

    OpenAIRE

    Walsh, Ciara; Duffy, Geraldine

    2013-01-01

    Wide-spread antibiotic resistance among bacterial pathogens is now a serious public health issue and multi-antibiotic resistance has been reported in many foodborne pathogens including Salmonella and E. coli. A study to determine antibiotic resistance profiles of a range of Salmonella and Verocytotoxigenic E.coli (VTEC) isolated from Irish foods revealed significant levels of antibiotic resistance in the strains. S. typhimurium DT104 were multiantibiotic resistant with 97% resistant to 7 anti...

  18. The changes in plasma endothelin after dosing intervention in type 2 diabetes and its clinical significance

    International Nuclear Information System (INIS)

    Yang Xixiu; Sun Jinfeng; Li Lusheng; Wang Shufang; Zhao Xin

    2002-01-01

    To explore the correlation of endothelin (ET), insulin resistance and microvascular complications in type 2 diabetes, the serum concentrations of OGTT, INS, C-P and plasma ET were measured by radioimmunoassay in 30 normal subjects and 82 patients with type 2 diabetes. ET level had a linear negative correlationship with IAI. The level of ET were significantly greater in group with microangiopathy than in group without microangiopathy (P<0.01). Insulin sensitivity are strongly correlated with vascular endothelial cells. The intervention may play an important role in decreasing insulin resistance of type 2 diabetes, and it is a vascular complications

  19. Significant decrease in yield under future climate conditions: Stability and production of 138 spring barley accessions

    DEFF Research Database (Denmark)

    Ingvordsen, Cathrine Heinz; Backes, Gunter; Lyngkjær, Michael Foged

    2015-01-01

    The response in production parameters to projected future levels of temperature, atmospheric carbondioxide ([CO2]), and ozone ([O3]) was investigated in 138 spring barley accessions. The comprehensive setof landraces, cultivars, and breeder-lines, were during their entire life cycle exposed...

  20. Russian wheat aphid, Diuraphis noxia in the Czech Republic – cause of the significant population decrease

    Czech Academy of Sciences Publication Activity Database

    Havelka, Jan; Žurovcová, Martina; Rychlý, S.; Starý, Petr

    2014-01-01

    Roč. 138, č. 4 (2014), s. 273-280 ISSN 0931-2048 R&D Projects: GA ČR GA522/09/ 1940 Institutional support: RVO:60077344 Keywords : alien aphid species * anholocyclic populations * aphids overwintering mortality Subject RIV: EH - Ecology, Behaviour Impact factor: 1.650, year: 2014 http://onlinelibrary.wiley.com/doi/10.1111/jen.12068/pdf

  1. Variation and importance of aspirin resistance in patients with known cardiovascular disease

    DEFF Research Database (Denmark)

    Poulsen, Tina Svenstrup; Kristensen, Søren Risom; Korsholm, Lars

    2007-01-01

    AIM: To investigate whether aspirin resistance is a persistent condition, and to evaluate if aspirin resistance affects one-year clinical outcome. METHODS AND RESULTS: Previously we studied 298 patients admitted to hospital with symptoms suggestive of an acute myocardial infarction (MI) despite...... treatment with aspirin, and 70 patients (23.5%) were aspirin resistant. In the present study, platelet function was reassessed by use of a Platelet Function Analyzer-100 one year later. A total of 187 patients were re-examined, and 17 (9.1%) demonstrated aspirin resistance. Of these 17 patients, 12 also...... exhibited aspirin resistance at baseline resulting in a 6% (12/187) prevalence of persistent aspirin resistance. A total of 34 patients had changed from aspirin resistant at baseline to aspirin sensitive at follow-up. We found a significant decrease in the prevalence of aspirin resistance from baseline (43...

  2. Airplane radiation dose decrease during a strong Forbush decrease

    Czech Academy of Sciences Publication Activity Database

    Spurný, František; Kudela, K.; Dachev, T.

    2004-01-01

    Roč. 2, S05001 (2004), s. 1-4 ISSN 1542-7390 Grant - others:EC project(XE) FIGM-CT2000-00068 Institutional research plan: CEZ:AV0Z1048901 Keywords : airplane dose * Forbush decrease * cosmic rays Subject RIV: BG - Nuclear, Atomic and Molecular Physics, Colliders

  3. Mechanism and clinical significance of metronidazole resistance in Helicobacter pylori

    NARCIS (Netherlands)

    van der Wouden, EJ; Thijs, JC; Kusters, JG; van Zwet, AA; Kleibeuker, JH

    2001-01-01

    Metronidazole was introduced in 1959 for the treatment of Trichomonas vaginalis, but was subsequently shown to be active against anaerobic and some micro-aerophilic bacteria as well. In anaerobic microorganisms with their low redox potential, metronidazole is reduced to its active metabolite by a

  4. Cancer cachexia decreases specific force and accelerates fatigue in limb muscle

    Energy Technology Data Exchange (ETDEWEB)

    Roberts, B.M. [1225 Center Drive, HPNP Building Room 1142, Department of Physical Therapy, University of Florida, Gainesville, FL 32610 (United States); Frye, G.S.; Ahn, B.; Ferreira, L.F. [1864 Stadium Road, Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL 32610 (United States); Judge, A.R., E-mail: arjudge@phhp.ufl.edu [1225 Center Drive, HPNP Building Room 1142, Department of Physical Therapy, University of Florida, Gainesville, FL 32610 (United States)

    2013-06-07

    Highlights: •C-26 cancer cachexia causes a significant decrease in limb muscle absolute force. •C-26 cancer cachexia causes a significant decrease in limb muscle specific force. •C-26 cancer cachexia decreases fatigue resistance in the soleus muscle. •C-26 cancer cachexia prolongs time to peak twitch tension in limb muscle. •C-26 cancer cachexia prolongs one half twitch relaxation time in limb muscle. -- Abstract: Cancer cachexia is a complex metabolic syndrome that is characterized by the loss of skeletal muscle mass and weakness, which compromises physical function, reduces quality of life, and ultimately can lead to mortality. Experimental models of cancer cachexia have recapitulated this skeletal muscle atrophy and consequent decline in muscle force generating capacity. However, more recently, we provided evidence that during severe cancer cachexia muscle weakness in the diaphragm muscle cannot be entirely accounted for by the muscle atrophy. This indicates that muscle weakness is not just a consequence of muscle atrophy but that there is also significant contractile dysfunction. The current study aimed to determine whether contractile dysfunction is also present in limb muscles during severe Colon-26 (C26) carcinoma cachexia by studying the glycolytic extensor digitorum longus (EDL) muscle and the oxidative soleus muscle, which has an activity pattern that more closely resembles the diaphragm. Severe C-26 cancer cachexia caused significant muscle fiber atrophy and a reduction in maximum absolute force in both the EDL and soleus muscles. However, normalization to muscle cross sectional area further demonstrated a 13% decrease in maximum isometric specific force in the EDL and an even greater decrease (17%) in maximum isometric specific force in the soleus. Time to peak tension and half relaxation time were also significantly slowed in both the EDL and the solei from C-26 mice compared to controls. Since, in addition to postural control, the oxidative

  5. Cancer cachexia decreases specific force and accelerates fatigue in limb muscle

    International Nuclear Information System (INIS)

    Roberts, B.M.; Frye, G.S.; Ahn, B.; Ferreira, L.F.; Judge, A.R.

    2013-01-01

    Highlights: •C-26 cancer cachexia causes a significant decrease in limb muscle absolute force. •C-26 cancer cachexia causes a significant decrease in limb muscle specific force. •C-26 cancer cachexia decreases fatigue resistance in the soleus muscle. •C-26 cancer cachexia prolongs time to peak twitch tension in limb muscle. •C-26 cancer cachexia prolongs one half twitch relaxation time in limb muscle. -- Abstract: Cancer cachexia is a complex metabolic syndrome that is characterized by the loss of skeletal muscle mass and weakness, which compromises physical function, reduces quality of life, and ultimately can lead to mortality. Experimental models of cancer cachexia have recapitulated this skeletal muscle atrophy and consequent decline in muscle force generating capacity. However, more recently, we provided evidence that during severe cancer cachexia muscle weakness in the diaphragm muscle cannot be entirely accounted for by the muscle atrophy. This indicates that muscle weakness is not just a consequence of muscle atrophy but that there is also significant contractile dysfunction. The current study aimed to determine whether contractile dysfunction is also present in limb muscles during severe Colon-26 (C26) carcinoma cachexia by studying the glycolytic extensor digitorum longus (EDL) muscle and the oxidative soleus muscle, which has an activity pattern that more closely resembles the diaphragm. Severe C-26 cancer cachexia caused significant muscle fiber atrophy and a reduction in maximum absolute force in both the EDL and soleus muscles. However, normalization to muscle cross sectional area further demonstrated a 13% decrease in maximum isometric specific force in the EDL and an even greater decrease (17%) in maximum isometric specific force in the soleus. Time to peak tension and half relaxation time were also significantly slowed in both the EDL and the solei from C-26 mice compared to controls. Since, in addition to postural control, the oxidative

  6. Significant Tsunami Events

    Science.gov (United States)

    Dunbar, P. K.; Furtney, M.; McLean, S. J.; Sweeney, A. D.

    2014-12-01

    Tsunamis have inflicted death and destruction on the coastlines of the world throughout history. The occurrence of tsunamis and the resulting effects have been collected and studied as far back as the second millennium B.C. The knowledge gained from cataloging and examining these events has led to significant changes in our understanding of tsunamis, tsunami sources, and methods to mitigate the effects of tsunamis. The most significant, not surprisingly, are often the most devastating, such as the 2011 Tohoku, Japan earthquake and tsunami. The goal of this poster is to give a brief overview of the occurrence of tsunamis and then focus specifically on several significant tsunamis. There are various criteria to determine the most significant tsunamis: the number of deaths, amount of damage, maximum runup height, had a major impact on tsunami science or policy, etc. As a result, descriptions will include some of the most costly (2011 Tohoku, Japan), the most deadly (2004 Sumatra, 1883 Krakatau), and the highest runup ever observed (1958 Lituya Bay, Alaska). The discovery of the Cascadia subduction zone as the source of the 1700 Japanese "Orphan" tsunami and a future tsunami threat to the U.S. northwest coast, contributed to the decision to form the U.S. National Tsunami Hazard Mitigation Program. The great Lisbon earthquake of 1755 marked the beginning of the modern era of seismology. Knowledge gained from the 1964 Alaska earthquake and tsunami helped confirm the theory of plate tectonics. The 1946 Alaska, 1952 Kuril Islands, 1960 Chile, 1964 Alaska, and the 2004 Banda Aceh, tsunamis all resulted in warning centers or systems being established.The data descriptions on this poster were extracted from NOAA's National Geophysical Data Center (NGDC) global historical tsunami database. Additional information about these tsunamis, as well as water level data can be found by accessing the NGDC website www.ngdc.noaa.gov/hazard/

  7. Elevated plasma homocysteine in association with decreased ...

    African Journals Online (AJOL)

    Conclusion: This study showed a significant increase in plasma tHcy coexisting with a decrease in plasma vitamin B12 TC, LDLC and HDLC, in depressed patients. Increased plasma homocysteine could be a sensitive indicator of plasma B vitamin deficiency. Keywords: Cholesterol; Depression; Homocysteine; Tryptophan; ...

  8. Smoking decreases structural and functional resilience in the subgingival ecosystem.

    Science.gov (United States)

    Joshi, Vinayak; Matthews, Chad; Aspiras, Marcelo; de Jager, Marko; Ward, Marilyn; Kumar, Purnima

    2014-11-01

    Dysbiotic microbial communities underlie the aetiology of several oral diseases, especially in smokers. The ability of an ecosystem to rebound from the dysbiotic state and re-establish a health-compatible community, a characteristic known as resilience, plays an important role in susceptibility to future disease. The present investigation was undertaken to examine the effects of smoking on colonization dynamics and resilience in marginal and subgingival biofilms. Marginal and subgingival plaque and gingival crevicular fluid samples were collected from 25 current and 25 never smokers with pre-existing gingivitis at baseline, following resolution, after 1, 2 4, 7, 14 and 21 days of undisturbed plaque formation and following resolution. 16S cloning and sequencing was used for bacterial identification and multiplexed bead-based flow cytometry was used to quantify the levels of 27 immune mediators. Smokers demonstrated an early pathogenic colonization that led to sustained pathogen enrichment with periodontal and respiratory pathogens, eliciting a florid immune response. Smokers also demonstrated greater abundance of pathogenic species, poor compositional correlation between marginal and subgingival ecosystems, and significantly greater pro-inflammatory responses following resolution of the second episode of disease. The ability of the subgingival microbiome to "reset" itself following episodes of disease is decreased in smokers, thereby lowering the resilience of the ecosystem and decreasing its resistance to future disease. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Decreasing incidence rates of bacteremia

    DEFF Research Database (Denmark)

    Nielsen, Stig Lønberg; Pedersen, C; Jensen, T G

    2014-01-01

    BACKGROUND: Numerous studies have shown that the incidence rate of bacteremia has been increasing over time. However, few studies have distinguished between community-acquired, healthcare-associated and nosocomial bacteremia. METHODS: We conducted a population-based study among adults with first......-acquired, 50.0 for healthcare-associated and 66.7 for nosocomial bacteremia. During 2000-2008, the overall incidence rate decreased by 23.3% from 254.1 to 198.8 (3.3% annually, p ...) and the incidence rate of nosocomial bacteremia decreased by 28.9% from 82.2 to 56.0 (4.2% annually, p

  10. Significant engineering developments

    International Nuclear Information System (INIS)

    Pon, G.A.

    1987-01-01

    The CANDU nuclear power system is a successful product of creative intelligence combined with the tenacious pursuit of practical solutions to complex engineering challenges. Outstanding engineering developments have transformed a demanding technology into a safe, economic and reliable one. Among the noteworthy developments that have been made CANDU the world's best performing reactor system are those relating to fuel, pressure tubes, heavy water production and management, steam generators, live-load valve packing, pump seals, on-power refuelling and computer control. In addition to pragmatic engineering accomplishments, there has been significant engineering input to guide the direction and shaping of the unique form of safety design and regulation of the CANDU system

  11. Aluminum-induced testosterone decrease results in physiological ...

    African Journals Online (AJOL)

    A significant decrease in both serotonin and dopamine levels was simultaneously obtained with the decrease of testosterone level especially at the high dose of aluminum. In contrast, at the high dose, acetylcholine recorded significantly high value. In conclusion, aluminum-induced testosterone decrease resulted in a ...

  12. Forbush decreases registered onboard aircraft

    Czech Academy of Sciences Publication Activity Database

    Spurný, František; Kudela, K.; Dachev, T.

    2005-01-01

    Roč. 36, č. 9 (2005), s. 1634-1637 ISSN 0273-1177 Institutional research plan: CEZ:AV0Z10480505 Keywords : Forbush decrease * aircraft exposure * Si-detector Subject RIV: DN - Health Impact of the Environment Quality Impact factor: 0.706, year: 2005

  13. Safety significance evaluation system

    International Nuclear Information System (INIS)

    Lew, B.S.; Yee, D.; Brewer, W.K.; Quattro, P.J.; Kirby, K.D.

    1991-01-01

    This paper reports that the Pacific Gas and Electric Company (PG and E), in cooperation with ABZ, Incorporated and Science Applications International Corporation (SAIC), investigated the use of artificial intelligence-based programming techniques to assist utility personnel in regulatory compliance problems. The result of this investigation is that artificial intelligence-based programming techniques can successfully be applied to this problem. To demonstrate this, a general methodology was developed and several prototype systems based on this methodology were developed. The prototypes address U.S. Nuclear Regulatory Commission (NRC) event reportability requirements, technical specification compliance based on plant equipment status, and quality assurance assistance. This collection of prototype modules is named the safety significance evaluation system

  14. Anthropological significance of phenylketonuria.

    Science.gov (United States)

    Saugstad, L F

    1975-01-01

    The highest incidence rates of phenylketonuria (PKU) have been observed in Ireland and Scotlant. Parents heterozygous for PKU in Norway differ significantly from the general population in the Rhesus, Kell and PGM systems. The parents investigated showed an excess of Rh negative, Kell plus and PGM type 1 individuals, which makes them similar to the present populations in Ireland and Scotlant. It is postulated that the heterozygotes for PKU in Norway are descended from a completely assimilated sub-population of Celtic origin, who came or were brought here, 1ooo years ago. Bronze objects of Western European (Scottish, Irish) origin, found in Viking graves widely distributed in Norway, have been taken as evidence of Vikings returning with loot (including a number of Celts) from Western Viking settlements. The continuity of residence since the Viking age in most habitable parts of Norway, and what seems to be a nearly complete regional relationship between the sites where Viking graves contain western imported objects and the birthplaces of grandparents of PKUs identified in Norway, lend further support to the hypothesis that the heterozygotes for PKU in Norway are descended from a completely assimilated subpopulation. The remarkable resemblance between Iceland and Ireland, in respect of several genetic markers (including the Rhesus, PGM and Kell systems), is considered to be an expression of a similar proportion of people of Celtic origin in each of the two countries. Their identical, high incidence rates of PKU are regarded as further evidence of this. The significant decline in the incidence of PKU when one passes from Ireland, Scotland and Iceland, to Denmark and on to Norway and Sweden, is therefore explained as being related to a reduction in the proportion of inhabitants of Celtic extraction in the respective populations.

  15. Tumor significant dose

    International Nuclear Information System (INIS)

    Supe, S.J.; Nagalaxmi, K.V.; Meenakshi, L.

    1983-01-01

    In the practice of radiotherapy, various concepts like NSD, CRE, TDF, and BIR are being used to evaluate the biological effectiveness of the treatment schedules on the normal tissues. This has been accepted as the tolerance of the normal tissue is the limiting factor in the treatment of cancers. At present when various schedules are tried, attention is therefore paid to the biological damage of the normal tissues only and it is expected that the damage to the cancerous tissues would be extensive enough to control the cancer. Attempt is made in the present work to evaluate the concent of tumor significant dose (TSD) which will represent the damage to the cancerous tissue. Strandquist in the analysis of a large number of cases of squamous cell carcinoma found that for the 5 fraction/week treatment, the total dose required to bring about the same damage for the cancerous tissue is proportional to T/sup -0.22/, where T is the overall time over which the dose is delivered. Using this finding the TSD was defined as DxN/sup -p/xT/sup -q/, where D is the total dose, N the number of fractions, T the overall time p and q are the exponents to be suitably chosen. The values of p and q are adjusted such that p+q< or =0.24, and p varies from 0.0 to 0.24 and q varies from 0.0 to 0.22. Cases of cancer of cervix uteri treated between 1978 and 1980 in the V. N. Cancer Centre, Kuppuswamy Naidu Memorial Hospital, Coimbatore, India were analyzed on the basis of these formulations. These data, coupled with the clinical experience, were used for choice of a formula for the TSD. Further, the dose schedules used in the British Institute of Radiology fraction- ation studies were also used to propose that the tumor significant dose is represented by DxN/sup -0.18/xT/sup -0.06/

  16. Effects of an Intensive Resistant Training Sessions and Green Tea

    Directory of Open Access Journals (Sweden)

    Mohammad Esmaeil Afzalpour

    2014-03-01

    Full Text Available Background: Intensive and acute exercise trainings may induce oxidative stress, but antioxidant supplements may attenuate its degenerative consequences. The aim of this research was to examine the effect of green tea supplementation on the oxidative stress indices after an intensive resistance training session. Materials and Methods: 40 non-athletes (without regular physical activity women were randomly divided into 4 equal (n=10 groups including green tea supplementation, green tea supplementation plus resistance training, resistance training, and control groups. After supplementation period (600 mg/day, 14 days, resistance training and green tea supplementation plus resistance training groups performed an intensive resistance training session at 75-85 % of one repetition maximum. The malondialdehyde and total thiol were measured as oxidative stress indices. Data were analyzed by using of repeated measure ANOVA and LSD tests at p<0.056T. Results: Results showed that after 14 days of green tea consumption, malondialdehyde significantly decreased in green tea supplementation (p=0.03 and green tea supplementation plus resistance training (p=0.01 groups, while total thiol increased significantly (p=0.01 in two green tea supplementation groups. However, an intensive resistance training session increased malondialdehyde (p=0.01 without any significantly changes in total thiol (p=0.426T. Conclusion: It seems that green tea supplementation can inhibit exercise-induced protein and lipid oxidation in non-athletes women via enhancement of antioxidant defense system of the body6T.6T

  17. Metalloproteins during development of Walker-256 carcinosarcoma resistant phenotype

    Directory of Open Access Journals (Sweden)

    V. F. Chekhun

    2015-04-01

    Full Text Available The study was focused on the detection of changes in serum and tumor metal-containing proteins in animals during development of doxorubicin-resistant phenotype in malignant cells after 12 courses of chemotherapy. We found that on every stage of resistance development there was a significant increase in content of ferritin and transferrin proteins (which take part in iron traffick and storage in Walker-256 carcinosarcoma tissue. We observed decreased serum ferritin levels at the beginning stage of the resistance development and significant elevation of this protein levels in the cases with fully developed resistance phenotype. Transferrin content showed changes opposite to that of ferritin. During the development of resistance phenotype the tumor tissue also exhibited increased ‘free iron’ concentration that putatively correlate with elevation of ROS generation and levels of MMP-2 and MMP-9 active forms. The tumor non-protein thiol content increases gradually as well. The serum of animals with early stages of resistance phenotype development showed high ceruloplasmin activity and its significant reduction after loss of tumor sensitivity to doxorubicin. Therefore, the development of resistance phenotype in Walker-256 carcinosarcoma is accompanied by both the deregulation of metal-containing proteins in serum and tumor tissue and by the changes in activity of antioxidant defense system. Thus, the results of this study allow us to determine the spectrum of metal-containing proteins that are involved in the development of resistant tumor phenotype and that may be targeted for methods for doxorubicin sensitivity correction therapy.

  18. In Vitro screening of tomato genotypes for drought resistance using ...

    African Journals Online (AJOL)

    Drought resistant mutant derivatives and hybrid produced using mutant derivative as female parent performed significantly superior for root characters. Decrease in seedling growth was worth notice with increasing concentration of PEG indicating precise nature of the in vitro screening. Mutant hybrid and its derivatives were ...

  19. Fungi producing significant mycotoxins.

    Science.gov (United States)

    2012-01-01

    Mycotoxins are secondary metabolites of microfungi that are known to cause sickness or death in humans or animals. Although many such toxic metabolites are known, it is generally agreed that only a few are significant in causing disease: aflatoxins, fumonisins, ochratoxin A, deoxynivalenol, zearalenone, and ergot alkaloids. These toxins are produced by just a few species from the common genera Aspergillus, Penicillium, Fusarium, and Claviceps. All Aspergillus and Penicillium species either are commensals, growing in crops without obvious signs of pathogenicity, or invade crops after harvest and produce toxins during drying and storage. In contrast, the important Fusarium and Claviceps species infect crops before harvest. The most important Aspergillus species, occurring in warmer climates, are A. flavus and A. parasiticus, which produce aflatoxins in maize, groundnuts, tree nuts, and, less frequently, other commodities. The main ochratoxin A producers, A. ochraceus and A. carbonarius, commonly occur in grapes, dried vine fruits, wine, and coffee. Penicillium verrucosum also produces ochratoxin A but occurs only in cool temperate climates, where it infects small grains. F. verticillioides is ubiquitous in maize, with an endophytic nature, and produces fumonisins, which are generally more prevalent when crops are under drought stress or suffer excessive insect damage. It has recently been shown that Aspergillus niger also produces fumonisins, and several commodities may be affected. F. graminearum, which is the major producer of deoxynivalenol and zearalenone, is pathogenic on maize, wheat, and barley and produces these toxins whenever it infects these grains before harvest. Also included is a short section on Claviceps purpurea, which produces sclerotia among the seeds in grasses, including wheat, barley, and triticale. The main thrust of the chapter contains information on the identification of these fungi and their morphological characteristics, as well as factors

  20. Helicobacter pylori Antibiotic Resistance: Trends Over Time

    Directory of Open Access Journals (Sweden)

    Raymond G Lahaie

    2000-01-01

    Full Text Available Resistance to antibiotics can be a major problem in the treatment of bacterial infections. As the use of antibiotics increases, bacterial resistance to these agents is rising and in many cases is responsible for the failure of treatment regimens. Although the treatment of Helicobacter pylori infection requires the use of more than one antibiotic to obtain adequate eradication rates, the efficacy of the currently used antibiotic combinations has been shown to be decreased by resistance to one of the antibiotics. The use of antibiotics in regimens for the treatment of H pylori is increasing in many countries, including Canada. This increase is both in the use of these antibiotics alone for the treatment of nongastrointestinal infections and in their use in association with proton pump inhibitors for the treatment of H pylori infection. In several European and Asian countries, where resistance to antibiotics is being monitored, it has been demonstrated that H pylori resistance to metronidazole and to clarithromycin increased throughout the 1990s. Thus far, the data available in Canada do not show increased resistance to either of these antibiotics. As for other antibiotics used in the treatment of H pylori infection, such as tetracycline and amoxicillin, the rate of resistance to these agents is still very low and does not constitute a significant problem. Because the efficacy of the regimens used in the treatment of H pylori infection is compromised by resistance to the antibiotics used, it is important that H pylori resistance rates in Canada and throughout the world continue to be monitored. Only with such reliable data can the most optimal regimens be recommended.

  1. Decreasing Fires in Mediterranean Europe.

    Directory of Open Access Journals (Sweden)

    Marco Turco

    Full Text Available Forest fires are a serious environmental hazard in southern Europe. Quantitative assessment of recent trends in fire statistics is important for assessing the possible shifts induced by climate and other environmental/socioeconomic changes in this area. Here we analyse recent fire trends in Portugal, Spain, southern France, Italy and Greece, building on a homogenized fire database integrating official fire statistics provided by several national/EU agencies. During the period 1985-2011, the total annual burned area (BA displayed a general decreasing trend, with the exception of Portugal, where a heterogeneous signal was found. Considering all countries globally, we found that BA decreased by about 3020 km2 over the 27-year-long study period (i.e. about -66% of the mean historical value. These results are consistent with those obtained on longer time scales when data were available, also yielding predominantly negative trends in Spain and France (1974-2011 and a mixed trend in Portugal (1980-2011. Similar overall results were found for the annual number of fires (NF, which globally decreased by about 12600 in the study period (about -59%, except for Spain where, excluding the provinces along the Mediterranean coast, an upward trend was found for the longer period. We argue that the negative trends can be explained, at least in part, by an increased effort in fire management and prevention after the big fires of the 1980's, while positive trends may be related to recent socioeconomic transformations leading to more hazardous landscape configurations, as well as to the observed warming of recent decades. We stress the importance of fire data homogenization prior to analysis, in order to alleviate spurious effects associated with non-stationarities in the data due to temporal variations in fire detection efforts.

  2. Limited fitness costs of herbicide-resistance traits in Amaranthus tuberculatus facilitate resistance evolution.

    Science.gov (United States)

    Wu, Chenxi; Davis, Adam S; Tranel, Patrick J

    2018-02-01

    The fitness cost of herbicide resistance (HR) in the absence of herbicide selection plays a key role in HR evolution. Quantifying the fitness cost of resistance, however, is challenging, and there exists a knowledge gap in this area. A synthetic (artificially generated) Amaranthus tuberculatus population segregating for five types of HR was subjected to competitive growth conditions in the absence of herbicide selection for six generations. Fitness costs were quantified by using a combination of phenotyping and genotyping to monitor HR frequency changes over generations. In the absence of herbicide selection, a significant fitness cost was observed for resistance to acetolactate synthase-inhibiting herbicides, but not for resistances to atrazine (non-target-site resistance mechanism), protoporphyrinogen oxidase inhibitors, 4-hydroxyphenylpryuvate dioxygenase inhibitors or glyphosate. Glyphosate resistance was conferred by multiple mechanisms in the synthetic population, and further analysis revealed that one mechanism, amplification of the 5-enolypyruvylshikimate-3-phosphate synthase gene, did decrease in frequency. Our results indicate that herbicide-resistance mitigation strategies (e.g. herbicide rotation) that rely on the existence of fitness costs in the absence of herbicide selection likely will be largely ineffective in many cases. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  3. Clonal Evolution Leading to Maintenance of Antibiotic Resistance Rates among Colonizing Pneumococci in the PCV7 Era in Portugal ▿

    OpenAIRE

    Simões, Alexandra S.; Pereira, Liliana; Nunes, Sónia; Brito-Avô, António; de Lencastre, Hermínia; Sá-Leão, Raquel

    2011-01-01

    The introduction of the seven-valent pneumococcal conjugate vaccine (PCV7) in Portugal led to extensive serotype replacement among carriers of pneumococci, with a marked decrease of PCV7 types. Although antimicrobial resistance was traditionally associated with PCV7 types, no significant changes in the rates of nonsusceptibility to penicillin, resistance to macrolides, or multidrug resistance were observed. This study aimed to investigate the mechanisms leading to maintenance of antimicrobial...

  4. Resistance of green lacewing, Chrysoperla carnea Stephens to nitenpyram: Cross-resistance patterns, mechanism, stability, and realized heritability.

    Science.gov (United States)

    Mansoor, Muhammad Mudassir; Raza, Abu Bakar Muhammad; Abbas, Naeem; Aqueel, Muhammad Anjum; Afzal, Muhammad

    2017-01-01

    The green lacewing, Chrysoperla carnea Stephens (Neuroptera: Chrysopidae) is a major generalist predator employed in integrated pest management (IPM) plans for pest control on many crops. Nitenpyram, a neonicotinoid insecticide has widely been used against the sucking pests of cotton in Pakistan. Therefore, a field green lacewing strain was exposed to nitenpyram for five generations to investigate resistance evolution, cross-resistance pattern, stability, realized heritability, and mechanisms of resistance. Before starting the selection with nitenpyram, a field collected strain showed 22.08-, 23.09-, 484.69- and 602.90-fold resistance to nitenpyram, buprofezin, spinosad and acetamiprid, respectively compared with the Susceptible strain. After continuous selection for five generations (G1-G5) with nitenpyram in the laboratory, the Field strain (Niten-SEL) developed a resistance ratio of 423.95 at G6. The Niten-SEL strain at G6 showed no cross-resistance to buprofezin and acetamiprid and negative cross-resistance to spinosad compared with the Field strain (G1). For resistance stability, the Niten-SEL strain was left unexposed to any insecticide for four generations (G6-G9) and bioassay results at G10 showed that resistance to nitenpyram, buprofezin and spinosad was stable, while resistance to acetamiprid was unstable. The realized heritability values were 0.97, 0.16, 0.03, and -0.16 to nitenpyram, buprofezin, acetamiprid and spinosad, respectively, after five generations of selection. Moreover, the enzyme inhibitors (PBO or DEF) significantly decreased the nitenpyram resistance in the resistant strain, suggesting that resistance was due to microsomal oxidases and esterases. These results are very helpful for integration of green lacewings in IPM programs. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Individual’s Resistance Regarding BPM Initiative: Case Study of the Insurance Company

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    Pejić Bach Mirjana

    2017-12-01

    Full Text Available Though the individual’s resistance is very often considered a significant barrier to BPM success, the literature on that topic is quite scarce. With the aim to shed light on this topic, we have conducted research of a Croatian insurance company. We examined the impact of individual’s resistance regarding BPM initiative using the theory of reasoned action. Structural equation model was developed using the data collected by the survey among company employees. The results indicate that subjective norms are positively related to the individual’s resistance regarding BPM initiative, while positive initial belief regarding BPM initiative tends to decrease the probability of resistance to change.

  6. Ubiquitin-specific protease 2 decreases p53-dependent apoptosis in cutaneous T-cell lymphoma

    Science.gov (United States)

    Wei, Tianling; Biskup, Edyta; Rahbek Gjerdrum, Lise Mette; Niazi, Omid; Ødum, Niels; Gniadecki, Robert

    2016-01-01

    Treatment of advanced cutaneous T-cell lymphomas (CTCL) is challenging because they are resistant to conventional chemotherapy. USP2 has been shown to promote resistance to chemotherapeutic agents in several cancer models. We show here USP2 is expressed in quiescent and activated T-cells and its expression is 50% lower in CTCL cell lines (MyLa2000, SeAx and Hut-78) than in normal T-cells. USP2 is expressed in neoplastic cells in early, plaque-stage mycosis fungoides (MF) and is downregulated in advanced tumor stages. Upon treatment with psoralen with UVA (PUVA) or a p53 activator, nutlin3a, USP2 expression is significantly increased in MyLa2000 (p53wt/wt), but not in SeAx (p53mut) or Hut-78 (p53−/−). USP2 knockdown decreases MyLa2000 cell viability after PUVA by 50% but not Hut-78, suggesting that the function of USP2 in CTCL cells is p53-dependent. Furthermore, USP2 knockdown results in a decreased Mdm2 expression and upregulation of p53. Taken together, our findings suggest that USP2 stabilizes Mdm2 which antagonizes pro-apoptotic activity of p53 and possibly contributes to therapeutic resistance in CTCL. PMID:27351221

  7. Effect of Endophyte infection and clipping treatment on resistance and tolerance of Achnatherum sibiricum

    Directory of Open Access Journals (Sweden)

    Junhua Qin

    2016-12-01

    Full Text Available It is well-documented that endophytes can enhance the resistance of agronomical grasses, such as tall fescue and perennial ryegrass to herbivory. For native grasses, however, the related reports are limited, and the conclusions are variable. Achnatherum sibiricum is a grass native to the Inner Mongolian steppe. This grass is highly infected by endophytes but does not produce detectable endophyte-related alkaloids known under normal conditions. In this study, the contributions of endophytes to the resistance of A. sibiricum to Locusta migratoria were studied. We found that locusts preferred EF (endophyte-free plants to EI (endophyte-infected plants, and the weight of locusts fed on EI plants was significantly lower than those fed on EF plants. Hence, endophyte infection significantly enhanced the resistance of the host to L. migratoria. Endophyte infection significantly decreased the concentration of soluble sugar and amino acids while significantly increasing the concentration of total phenolic content, and these metabolites may contribute to herbivore resistance of the host. The clipping treatment further strengthened the locust resistance advantage of EI over EF plants. After clipping, the weight of the locusts fed on EI plants significantly decreased compared with those fed on unclipped plants, whereas the weight of the locusts fed on EF plants increased significantly. The results suggested that endophyte infection could increase herbivore resistance while decreasing the tolerance of the host grass by mechanisms apart from endophyte-conferred alkaloid defense.

  8. Legionella pneumophila decreases velocity of Acanthamoeba castellanii.

    Science.gov (United States)

    Mengue, Luce; Richard, Freddie-Jeanne; Caubet, Yves; Rolland, Steven; Héchard, Yann; Samba-Louaka, Ascel

    2017-12-01

    Acanthamoeba castellanii is a free-living amoeba commonly found in aquatic environment. It feeds on bacteria even if some bacteria resist amoebal digestion. Thus, A. castellanii is described as a Trojan horse able to harbor pathogenic bacteria. L. pneumophila is one of the amoeba-resisting bacteria able to avoid host degradation by phagocytosis and to multiply inside the amoeba. When infecting its host, L. pneumophila injects hundreds of effectors via a type IV secretion system that change physiology of the amoeba to its profit. In this study, we assess mobility of A. castellanii upon infection with L. pneumophila. Electron-microscopy analysis of amoebae revealed a reduction of acanthopodia on cells infected with L. pneumophila. Analysis of velocity showed that migration of A. castellanii infected with L. pneumophila was significantly impaired compare to uninfected cells. Taken together, infection with L. pneumophila could prevent formation of cytoplasmic extensions such as acanthopodia with consequences on the shape, adherence and mobility of A. castellanii. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Wrist Resistance Training Improves Motor Control and Strength.

    Science.gov (United States)

    Chu, Edward; Kim, You-Sin; Hill, Genevieve; Kim, Yoon Hyuk; Kim, Chang Kook; Shim, Jae Kun

    2018-04-01

    Chu, E, Kim, Y-S, Hill, G, Kim, YH, Kim, CK, and Shim, JK. Wrist resistance training improves motor control and strength. J Strength Cond Res 32(4): 962-969, 2018-The aim of this study was to investigate the effects of a 6-week direction-specific resistance training program on isometric torque control and isokinetic torque strength of the wrist joint. Nineteen subjects were randomly assigned to either the wrist training group (n = 9) or the control group (n = 10). The training group performed wrist exercises in 6 directions (flexion, extension, pronation, supination, radial deviation, and ulnar deviation), whereas the control group did not. Data were collected on the isometric torque control, 1-repetition maximum (1RM) strength, and isokinetic maximum torque (angular velocity of 60° per second wrist movements) before and after 6 weeks of resistance training and at 2-week intervals during training. The training group showed significant decreases in isometric torque control error in all 6 directions after 2 weeks of resistance training, whereas the control group did not show significant increase or decrease. After 4 weeks of training, the training group showed significant increases in maximum strength in all 6 directions as assessed by 1RM strength and isokinetic strength tests, whereas the control group did not show any statistically significant changes. This study shows that motor control significantly improves within the first 2 weeks of resistance training, whereas the wrist strength significantly improves within the first 4 weeks of resistance training. Based on the findings of this study, coaches and trainers should consider wrist resistance training to improve athletes' muscular strength and control of the wrist muscles.

  10. Loss of LPS is involved in the virulence and resistance to colistin of colistin-resistant Acinetobacter nosocomialis mutants selected in vitro.

    Science.gov (United States)

    Vila-Farrés, Xavier; Ferrer-Navarro, Mario; Callarisa, Anna Elena; Martí, Sara; Espinal, Paula; Gupta, Sushim; Rolain, Jean-Marc; Giralt, Ernest; Vila, Jordi

    2015-11-01

    Acinetobacter nosocomialis has increasingly been reported as an opportunistic pathogen causing nosocomial infections. Although it is more susceptible to all antimicrobial agents than Acinetobacter baumannii, MDR clinical isolates have also been described. In addition, several studies have shown a high percentage of resistance to colistin. Therefore, in the present study we investigated the mechanism of resistance to colistin in this microorganism. Colistin-resistant strains were selected from the original colistin-susceptible A. nosocomialis strain following multi-step mutant selection. Comparative genomic and proteomic analyses of both colistin-susceptible and colistin-resistant A. nosocomialis strains were performed. In addition, virulence was investigated using the Caenorhabditis elegans assay. The colistin-resistant mutants selected showed a lower resistance profile for other types of antibacterial agents together with a significant decrease in virulence. The LT50 (i.e. time required to kill 50% of the nematodes) for the colistin-susceptible strain (WT) was 7 days compared with 9 days for the colistin-resistant strain (256) (P colistin-resistant strains. The proteomic studies showed several up- and down-regulated proteins that may be involved in colistin resistance or in a decrease in the resistance profile for several antibiotics. This study shows that the mechanism of resistance to colistin by A. nosocomialis is mainly associated with the loss of LPS due to mutations in the lpxD gene, although changes in the expression of some proteins cannot be ruled out. In addition, the acquisition of colistin resistance is related to a decrease in virulence. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  11. Corticosteroids decrease glomerular angiotensin receptors

    Energy Technology Data Exchange (ETDEWEB)

    Douglas, J.G.

    1987-03-01

    Angiotensin II (ANG II) receptors of glomerular mesangial cells are regulated in vivo by changes in Na balance, effects that are presumed to be secondary to changes in circulating ANG II. However, since changes in ANG II were accompanied by parallel changes in plasma aldosterone in all models tested, it is possible that aldosterone may have also participated in the modulation of glomerular ANG II receptors. To test this hypothesis, short-term aldosterone infusions within the physiological range were employed to favor actions that would be mediated through a high-affinity mineralocorticoid receptor. The glucocorticoid, dexamethasone, was also tested to determine the mineralocorticoid specificity of the response. Two infusion rates were associated with a decrease in glomerular /sup 125/I ANG II receptor density of 33 and 45%, respectively. Serum potassium and urinary Na/K ratio were lower in the aldosterone group. Spironolactone abolished the effect of aldosterone consistent with an action mediated through a specific mineralocorticoid receptor. These studies support the hypothesis that corticosteroids modulate glomerular ANG II receptors and validate the complexity of glomerular receptor modulation. The downregulation observed would be expected to diminish the ability of ANG II to influence glomerular hemodynamics in models such as mineralocorticoid and glucocorticoid-induced hypertension.

  12. Management of insecticide resistance in Oriental fruit moth (Grapholita molesta; Lepidoptera: Tortricidae) populations from Ontario.

    Science.gov (United States)

    Kanga, Lambert H B; Pree, David J; van Lier, Jennifer L; Walker, Gerald M

    2003-08-01

    The development of resistance in the Oriental fruit moth, Grapholita molesta (Busck) to organophosphorus (OP) insecticides (azinphos-methyl and phosmet) is a serious threat to the tender fruit industry in Ontario (50% crop losses in 1994). Resistance to carbamate insecticides and increased survival of field-collected moths at diagnostic concentrations of pyrethroids were widespread. As a result, four different treatment regimes were tested to manage resistance in G molesta, and the changes in resistance frequencies under each treatment regime were monitored from 1996 to 1999. The data indicated that the levels of resistance were significantly influenced by the various treatment regimes. The seasonal pattern of resistance was similar for all treatment regimes, in that resistance peaked in mid-season and declined in the late season. Levels of resistance in G molesta to OPs decreased from 55% to 14% and that to pyrethroids declined from 30% to 10% from 1996 to 1999 under a treatment regime consisting of endosulfan-organophosphate-pyrethroid rotation. Similarly, under a treatment regime implemented in commercial orchards (organophosphate-pyrethroid rotation), resistance to OP insecticides declined from 50% to 12% and resistance to pyrethroids evolved to around 16%. The overall data indicated that resistance was unstable; a strategy based on rotation of insecticides by class for each generation of G molesta was successful in managing resistance to both OP and pyrethroid insecticides. The rotational strategy has been widely adopted by growers and is applied to ca 85% of the acreage.

  13. Antimicrobial Resistance

    Science.gov (United States)

    ... least 10 countries (Australia, Austria, Canada, France, Japan, Norway, Slovenia, South Africa, Sweden and the United Kingdom ... plan Global report on surveillance Country situation analysis Policy to combat antimicrobial resistance More on antimicrobial resistance ...

  14. Comparison of the effects of endurance, resistance and concurrent training on insulin resistance and adiponectin-leptin ratio in diabetic rat

    Directory of Open Access Journals (Sweden)

    A. Saremi

    2017-08-01

    Full Text Available Background: The obesity-related hormones leptin and adiponectin are independently and oppositely associated with insulin resistance. Objective: The aim of the present study was to investigate the effect of endurance, resistance and concurrent training on insulin resistance and adiponectin-leptin ratio in diabetic rats. Methods: Ten out of 50 male Wistar rats were separated as healthy subjects. Then diabetes was induced in the remaining rats by the injection of streptozotocin. Diabetic rats divided into 4 groups: Control, resistance training (5 sessions/week, 4 reps/3 sets, endurance training (5 sets per week of treadmill running and concurrent training. The resistance training protocol consisted of ten weeks climbing up the ladder, while endurance training performed on treadmill for ten weeks. Concurrent training group completed a combination of both resistances and endurance treadmill training. Blood samples were taken to assess leptin, adiponectin and insulin resistance. Findings: Endurance, resistance and concurrent training significantly decreased insulin resistance and glucose (P0.05. On the one hand, adiponctin level and adiponctin-leptin ratio significantly increased in all of training groups (P<0.05. Conclusion: Exercise training, as defined in this study, leads to improvements in adiponectin-leptin ratio and concurrent training has more impact on insulin resistance index in diabetic rats.

  15. Enzymatically synthesized glycogen inhibits colitis through decreasing oxidative stress.

    Science.gov (United States)

    Mitani, Takakazu; Yoshioka, Yasukiyo; Furuyashiki, Takashi; Yamashita, Yoko; Shirai, Yasuhito; Ashida, Hitoshi

    2017-05-01

    Inflammatory bowel diseases are a group of chronic inflammation conditions of the gastrointestinal tract. Disruption of the mucosal immune response causes accumulation of oxidative stress, resulting in the induction of inflammatory bowel disease. In this study, we investigated the effect of enzymatically synthesized glycogen (ESG), which is produced from starch, on dextran sulfate sodium (DSS)- and 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in C57BL/6 mice. Oral administration of ESG suppressed DSS- and TNBS-induced shortening of large intestine in female mice and significant decreased DSS-induced oxidative stress and TNBS-induced pro-inflammatory cytokine expression in the large intestine. ESG increase in the expression levels of heme oxygenase-1 (HO-1) and NF-E2-related factor-2 (Nrf2), a transcription factor for HO-1 expressed in the large intestine. Furthermore, ESG-induced HO-1 and Nrf2 were expressed mainly in intestinal macrophages. ESG is considered to be metabolized to resistant glycogen (RG) during digestion with α-amylase in vivo. In mouse macrophage RAW264.7 cells, RG, but not ESG decreased 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH)-induced reactive oxygen species (ROS). Knockdown of Nrf2 inhibited RG-induced HO-1 expression and negated the decrease in AAPH-induced ROS brought about by RG. RG up-regulated the protein stability of Nrf2 to decrease the formation of Nrf2-Keap1 complexes. RG-induced phosphorylation of Nrf2 at Ser40 was suppressed by ERK1/2 and JNK inhibitors. Our data indicate that ESG, digested with α-amylase to RG, suppresses DSS- and TNBS-induced colitis by increasing the expression of HO-1 in the large intestine of mice. Furthermore, we demonstrate that RG induces HO-1 expression by promoting phosphorylation of Nrf2 at Ser40 through activation of the ERK1/2 and JNK cascade in macrophages. Copyright © 2017. Published by Elsevier Inc.

  16. Antibiotic-Impregnated Central Venous Catheters Do Not Change Antibiotic Resistance Patterns.

    Science.gov (United States)

    Turnbull, Isaiah R; Buckman, Sara A; Horn, Christopher B; Bochicchio, Grant V; Mazuski, John E

    2018-01-01

    Antibiotic-impregnated central venous catheters (CVCs) decrease the incidence of infection in high-risk patients. However, use of these catheters carries the hypothetical risk of inducing antibiotic resistance. We hypothesized that routine use of minocycline and rifampin-impregnated catheters (MR-CVC) in a single intensive care unit (ICU) would change the resistance profile for Staphylococcus aureus. We reviewed antibiotic susceptibilities of S. aureus isolates obtained from blood cultures in a large urban teaching hospital from 2002-2015. Resistance patterns were compared before and after implementation of MR-CVC use in the surgical ICU (SICU) in August 2006. We also compared resistance patterns of S. aureus obtained in other ICUs and in non-ICU patients, in whom MR-CVCs were not used. Data for rifampin, oxacillin, and clindamycin were available for 9,703 cultures; tetracycline resistance data were available for 4,627 cultures. After implementation of MR-CVC use in the SICU, rifampin resistance remained unchanged, with rates the same as in other ICU and non-ICU populations (3%). After six years of use of MR-CVCs in the SICU, the rate of tetracycline resistance was unchanged in all facilities (1%-3%). The use of MR-CVCs was not associated with any change in S. aureus oxacillin-resistance rates in the SICU (66% vs. 60%). However, there was a significant decrease in S. aureus clindamycin resistance (59% vs. 34%; p resistance of S. aureus isolates to rifampin or tetracyclines.

  17. Are urban noise pollution levels decreasing?

    Science.gov (United States)

    Arana, M

    2010-04-01

    The majority of acoustic impact studies developed over the last 50 years have used a similar acoustic parameter (L(eq), L(dn)) but the noise mapping methodology has been very uneven. The selection of the measurement points, the measurement periods, or the evaluation indices have not followed a unique criterion. Therefore, it is not possible to compare the sound pollution levels between different cities from those studies, at least in a rigorous sense. Even more, different studies carried out in the same city by different researchers during different years and using different methodologies are not conclusive whether the acoustic pollution increases or decreases. The present paper shows results, with statistical significance, about the evolution of the acoustic pollution obtained for two Spanish cities, Pamplona and Madrid. In both cases, it can be concluded that noise pollution decreases over time (P<0.01).

  18. Impact and fracture resistance of an experimental acrylic polymer with elastomer in different proportions

    Directory of Open Access Journals (Sweden)

    Fernanda de Carvalho Panzeri Pires-de-Souza

    2009-01-01

    Full Text Available The purpose of this study was to evaluate the impact and fracture resistance of acrylic resins: a heat-polymerized resin, a high-impact resin and an experimental polymethyl methacrylate with elastomer in different proportions (10, 20, 40 and 60%. 120 specimens were fabricated and submitted to conventional heat-polymerization. For impact test, a Charpy-type impact tester was used. Fracture resistance was assessed with a 3-point bending test by using a mechanical testing machine. Ten specimens were used for each test. Fracture (MPa and impact resistance values (J.m-1 were submitted to ANOVA - Bonferroni's test - 5% significance level. Materials with higher amount of elastomer had statistically significant differences regarding to impact resistance (p < 0.05. Fracture resistance was superior (p < 0.01 for high-resistance acrylic resin. The increase in elastomer concentration added to polymethyl methacrylate raised the impact resistance and decreased the fracture resistance. Processing the material by injection decreased its resistance to impact and fracture.

  19. Intracellular diminazene aceturate content and adenosine incorporation in diminazene aceturate-resistant Babesia gibsoni isolate in vitro.

    Science.gov (United States)

    Yamasaki, Masahiro; Watanabe, Nao; Idaka, Natsuki; Yamamori, Tohru; Otsuguro, Ken-Ichi; Uchida, Naohiro; Iguchi, Aiko; Ohta, Hiroshi; Takiguchi, Mitsuyoshi

    2017-12-01

    The mechanism of the development of diminazene aceturate (DA) resistance in Babesia gibsoni is still unknown even though DA-resistant B. gibsoni isolate was previously developed in vitro. To clarify the mechanisms of DA-resistance in B. gibsoni, we initially examined the intracellular DA content in the DA-resistant isolate using high-performance liquid chromatography, and compared it with that in the wild-type. As a result, the intracellular DA content in the DA-resistant isolate was significantly lower than that in the wild-type, suggesting that the decreased DA content may contribute to DA-resistance. Additionally, the glucose consumption of the DA-resistant isolate was significantly higher than that of the wild-type, indicating that a large amount of glucose is utilized to maintain DA-resistance. It is possible that a large amount of energy is utilized to maintain the mechanisms of DA-resistance. It was reported that as the structure of DA is similar with that of adenosine, DA may be taken up by the P2 transporter, which contributes to the uptake of adenosine, in Trypanosoma brucei brucei, and that the uptake of adenosine is decreased in DA-resistant T. brucei brucei. In the present study, the adenosine incorporation in the DA-resistant B. gibsoni isolate was higher than in the wild-type. Moreover, the adenosine incorporation in the wild-type was not inhibited by the presence of DA. These results suggest that adenosine transport in B. gibsoni is not affected by DA and may not mediate DA-resistance. To clarify the mechanism of the development of DA resistance in B. gibsoni, we should investigate the cause of the decreased DA content in the DA-resistant isolate in the future. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. A whey protein supplement decreases post-prandial glycemia

    Directory of Open Access Journals (Sweden)

    Jenkins Alexandra L

    2009-10-01

    Full Text Available Abstract Background Incidence of diabetes, obesity and insulin resistance are associated with high glycemic load diets. Identifying food components that decrease post-prandial glycemia may be beneficial for developing low glycemic foods and supplements. This study explores the glycemic impact of adding escalating doses of a glycemic index lowering peptide fraction (GILP from whey to a glucose drink. Methods Ten healthy subjects (3M, 7F, 44.4 ± 9.3 years, BMI 33.6 ± 4.8 kg/m2 participated in an acute randomised controlled study. Zero, 5, 10 and 20 g of protein from GILP were added to a 50 g glucose drink. The control (0 g of GILP meal was repeated 2 times. Capillary blood samples were taken fasting (0 min and at 15, 30, 45, 60, 90 and 120 minutes after the start of the meal and analyzed for blood glucose concentration. Results Increasing doses of GILP decreased the incremental areas under the curve in a dose dependant manner (Pearson's r = 0.48, p = 0.002. The incremental areas (iAUC under the glucose curve for the 0, 5, 10, and 20 g of protein from GILP were 231 ± 23, 212 ± 23, 196 ± 23, and 138 ± 13 mmol.min/L respectively. The iAUC of the 20 g GILP was significantly different from control, 5 g GILP and 10 g GILP (p Conclusion Addition of GILP to a oral glucose bolus reduces blood glucose iAUC in a dose dependent manner and averages 4.6 ± 1.4 mmol.min/L per gram of GILP. These data are consistent with previous research on the effect of protein on the glycemic response of a meal.

  1. Physical activity decreases diverticular complications

    Science.gov (United States)

    Strate, Lisa L.; Liu, Yan L.; Aldoori, Walid H.; Giovannucci, Edward L.

    2011-01-01

    Objectives Little is known about the effect of physical activity on diverticular complications. This study examined prospectively the association between physical activity and diverticular bleeding and diverticulitis. Methods We studied 47,230 US males in the Health Professionals Follow-up Study cohort who were aged 40–75 years and free of diverticular disease, gastrointestinal cancer and inflammatory bowel disease at baseline in 1986. Men reporting newly diagnosed diverticular disease on biennial follow-up questionnaires were sent supplemental questionnaires outlining details of diagnosis and treatment. Physical activity was assessed every 2 years. Men recorded the average time per week spent in 8 recreational activities, and flights of stairs climbed per day. Cox proportional hazards regression was used to calculate relative risks. Results During 18 years of follow-up, 800 cases of diverticulitis, and 383 cases of diverticular bleeding were identified. Total cumulative physical activity was associated with a decreased risk of diverticulitis and diverticular bleeding. After adjustment for potential confounders, the relative risk (RR) for men in the highest quintile of total activity (≥57.4 Metabolic Equivalent (MET h/wk) was 0.75 (95% CI 0.58–0.95) for diverticulitis, and 0.54 (95% CI, 0.38–0.77) for bleeding when compared to men in the lowest quintile (≤8.2 MET h/wk). Vigorous activity was inversely related to diverticulitis (multivariable RR 0.66, 95% CI, 0.51–0.86), and bleeding (multivariable RR 0.61, 95% CI, 0.41 – 0.90) in a high vs. low comparison, whereas non-vigorous activity was not. These results were similar for recent (simple updated) and baseline activity. Conclusions Data from this large prospective cohort suggest that physical activity lowers the risk of diverticulitis and diverticular bleeding. Vigorous activity appears to account for this association. PMID:19367267

  2. The Mediterranean Diet decreases LDL atherogenicity in high cardiovascular risk individuals: a randomized controlled trial.

    Science.gov (United States)

    Hernáez, Álvaro; Castañer, Olga; Goday, Alberto; Ros, Emilio; Pintó, Xavier; Estruch, Ramón; Salas-Salvadó, Jordi; Corella, Dolores; Arós, Fernando; Serra-Majem, Lluis; Martínez-González, Miguel Ángel; Fiol, Miquel; Lapetra, José; de la Torre, Rafael; López-Sabater, M Carmen; Fitó, Montserrat

    2017-09-01

    Traditional Mediterranean diet (TMD) protects against cardiovascular disease through several mechanisms such as decreasing LDL cholesterol levels. However, evidence regarding TMD effects on LDL atherogenic traits (resistance against oxidation, size, composition, cytotoxicity) is scarce. We assessed the effects of a 1-year intervention with a TMD on LDL atherogenic traits in a random sub-sample of individuals from the PREDIMED study (N = 210). We compared two TMDs: one enriched with virgin olive oil (TMD-VOO, N = 71) and another with nuts (TMD-Nuts, N = 68), versus a low-fat control diet (N = 71). After the TMD-VOO intervention, LDL resistance against oxidation increased (+6.46%, p = 0.007), the degree of LDL oxidative modifications decreased (-36.3%, p<0.05), estimated LDL particle size augmented (+3.06%, p = 0.021), and LDL particles became cholesterol-rich (+2.41% p = 0.013) relative to the low-fat control diet. LDL lipoproteins became less cytotoxic for macrophages only relative to baseline (-13.4%, p = 0.019). No significant effects of the TMD-Nuts intervention on LDL traits were observed versus the control diet. Adherence to a TMD, particularly when enriched with virgin olive oil, decreased LDL atherogenicity in high cardiovascular risk individuals. The development of less atherogenic LDLs could contribute to explaining some of the cardioprotective benefits of this dietary pattern. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Drug Resistance

    Science.gov (United States)

    ... infected with a drug-resistant strain of HIV. Drug-resistance testing results are used to decide which HIV medicines to include in a person’s first HIV regimen. After treatment is started, drug-resistance testing is repeated if ...

  4. PP2A inhibition overcomes acquired resistance to HER2 targeted therapy.

    Science.gov (United States)

    McDermott, Martina Sj; Browne, Brigid C; Conlon, Neil T; O'Brien, Neil A; Slamon, Dennis J; Henry, Michael; Meleady, Paula; Clynes, Martin; Dowling, Paul; Crown, John; O'Donovan, Norma

    2014-06-24

    HER2 targeted therapies including trastuzumab and more recently lapatinib have significantly improved the prognosis for HER2 positive breast cancer patients. However, resistance to these agents is a significant clinical problem. Although several mechanisms have been proposed for resistance to trastuzumab, the mechanisms of lapatinib resistance remain largely unknown. In this study we generated new models of acquired resistance to HER2 targeted therapy and investigated mechanisms of resistance using phospho-proteomic profiling. Long-term continuous exposure of SKBR3 cells to low dose lapatinib established a cell line, SKBR3-L, which is resistant to both lapatinib and trastuzumab. Phospho-proteomic profiling and immunoblotting revealed significant alterations in phospho-proteins involved in key signaling pathways and molecular events. In particular, phosphorylation of eukaryotic elongation factor 2 (eEF2), which inactivates eEF2, was significantly decreased in SKBR3-L cells compared to the parental SKBR3 cells. SKBR3-L cells exhibited significantly increased activity of protein phosphatase 2A (PP2A), a phosphatase that dephosphorylates eEF2. SKBR3-L cells showed increased sensitivity to PP2A inhibition, with okadaic acid, compared to SKBR3 cells. PP2A inhibition significantly enhanced response to lapatinib in both the SKBR3 and SKBR3-L cells. Furthermore, treatment of SKBR3 parental cells with the PP2A activator, FTY720, decreased sensitivity to lapatinib. The alteration in eEF2 phosphorylation, PP2A activity and sensitivity to okadaic acid were also observed in a second HER2 positive cell line model of acquired lapatinib resistance, HCC1954-L. Our data suggests that decreased eEF2 phosphorylation, mediated by increased PP2A activity, contributes to resistance to HER2 inhibition and may provide novel targets for therapeutic intervention in HER2 positive breast cancer which is resistant to HER2 targeted therapies.

  5. Decreased Emotional Perception in Obesity.

    Science.gov (United States)

    Giel, Katrin Elisabeth; Hartmann, Armin; Zeeck, Almut; Jux, Anna; Vuck, Alexander; Gierthmuehlen, Petra C Guess; Wetzler-Burmeister, Edda; Sandholz, Angelika; Marjanovic, Goran; Joos, Andreas

    2016-07-01

    There is hardly any empirical evidence on emotion processing by controlled studies in obesity. Participants rated their emotions in response to visual emotional stimuli from the International Affective Picture System. Study 1 compared obese women with normal-weight controls and women with eating disorders. Study 2 compared obese men with normal-weight controls. Obese women had reduced emotional intensity scores for all basic emotions and the mixed emotion sadness-fear. Obese men had reduced scores for all emotions except happiness and disgust; anger showed a trend towards significance. The results were mainly based on ratings from non-depressed obese individuals. Obese men and women scored significantly lower on most basic and mixed emotions. Non-depressed obese subjects seem particularly affected. These new findings must be validated by further study, and longitudinal evaluation after weight loss, e.g. by bariatric surgery, will be of interest. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association.

  6. Interplay in the selection of fluoroquinolone resistance and bacterial fitness.

    Directory of Open Access Journals (Sweden)

    Linda L Marcusson

    2009-08-01

    Full Text Available Fluoroquinolones are antibacterial drugs that inhibit DNA Gyrase and Topoisomerase IV. These essential enzymes facilitate chromosome replication and RNA transcription by regulating chromosome supercoiling. High-level resistance to fluoroquinolones in E. coli requires the accumulation of multiple mutations, including those that alter target genes and genes regulating drug efflux. Previous studies have shown some drug-resistance mutations reduce bacterial fitness, leading to the selection of fitness-compensatory mutations. The impact of fluoroquinolone-resistance on bacterial fitness was analyzed in constructed isogenic strains carrying up to 5 resistance mutations. Some mutations significantly decreased bacterial fitness both in vitro and in vivo. We identified low-fitness triple-mutants where the acquisition of a fourth resistance mutation significantly increased fitness in vitro and in vivo while at the same time dramatically decreasing drug susceptibility. The largest effect occurred with the addition of a parC mutation (Topoisomerase IV to a low-fitness strain carrying resistance mutations in gyrA (DNA Gyrase and marR (drug efflux regulation. Increased fitness was accompanied by a significant change in the level of gyrA promoter activity as measured in an assay of DNA supercoiling. In selection and competition experiments made in the absence of drug, parC mutants that improved fitness and reduced susceptibility were selected. These data suggest that natural selection for improved growth in bacteria with low-level resistance to fluoroquinolones could in some cases select for further reductions in drug susceptibility. Thus, increased resistance to fluoroquinolones could be selected even in the absence of further exposure to the drug.

  7. Interplay in the selection of fluoroquinolone resistance and bacterial fitness.

    Science.gov (United States)

    Marcusson, Linda L; Frimodt-Møller, Niels; Hughes, Diarmaid

    2009-08-01

    Fluoroquinolones are antibacterial drugs that inhibit DNA Gyrase and Topoisomerase IV. These essential enzymes facilitate chromosome replication and RNA transcription by regulating chromosome supercoiling. High-level resistance to fluoroquinolones in E. coli requires the accumulation of multiple mutations, including those that alter target genes and genes regulating drug efflux. Previous studies have shown some drug-resistance mutations reduce bacterial fitness, leading to the selection of fitness-compensatory mutations. The impact of fluoroquinolone-resistance on bacterial fitness was analyzed in constructed isogenic strains carrying up to 5 resistance mutations. Some mutations significantly decreased bacterial fitness both in vitro and in vivo. We identified low-fitness triple-mutants where the acquisition of a fourth resistance mutation significantly increased fitness in vitro and in vivo while at the same time dramatically decreasing drug susceptibility. The largest effect occurred with the addition of a parC mutation (Topoisomerase IV) to a low-fitness strain carrying resistance mutations in gyrA (DNA Gyrase) and marR (drug efflux regulation). Increased fitness was accompanied by a significant change in the level of gyrA promoter activity as measured in an assay of DNA supercoiling. In selection and competition experiments made in the absence of drug, parC mutants that improved fitness and reduced susceptibility were selected. These data suggest that natural selection for improved growth in bacteria with low-level resistance to fluoroquinolones could in some cases select for further reductions in drug susceptibility. Thus, increased resistance to fluoroquinolones could be selected even in the absence of further exposure to the drug.

  8. Antimicrobial resistance trends among Salmonella isolates obtained from horses in the northeastern United States (2001-2013).

    Science.gov (United States)

    Cummings, Kevin J; Perkins, Gillian A; Khatibzadeh, Sarah M; Warnick, Lorin D; Aprea, Victor A; Altier, Craig

    2016-05-01

    OBJECTIVE To describe the antimicrobial resistance patterns of Salmonella isolates obtained from horses in the northeastern United States and to identify trends in resistance to select antimicrobials over time. SAMPLE 462 Salmonella isolates from horses. PROCEDURES Retrospective data were collected for all Salmonella isolates obtained from equine specimens that were submitted to the Cornell University Animal Health Diagnostic Center between January 1, 2001, and December 31, 2013. Temporal trends in the prevalence of resistant Salmonella isolates were investigated for each of 13 antimicrobials by use of the Cochran-Armitage trend test. RESULTS The prevalence of resistant isolates varied among antimicrobials and ranged from 0% (imipenem) to 51.5% (chloramphenicol). During the observation period, the prevalence of resistant isolates decreased significantly for amoxicillin-clavulanic acid, ampicillin, cefazolin, cefoxitin, ceftiofur, chloramphenicol, and tetracycline and remained negligible for amikacin and enrofloxacin. Of the 337 isolates for which the susceptibility to all 13 antimicrobials was determined, 138 (40.9%) were pansusceptible and 192 (57.0%) were multidrug resistant (resistant to ≥ 3 antimicrobial classes). The most common serovar isolated was Salmonella Newport, and although the annual prevalence of that serovar decreased significantly over time, that decrease had only a minimal effect on the observed antimicrobial resistance trends. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that current antimicrobial use in horses is not promoting the emergence and dissemination of antimicrobial-resistant Salmonella strains in the region served by the laboratory.

  9. Linezolid Resistance in Staphylococci

    Directory of Open Access Journals (Sweden)

    Stefania Stefani

    2010-06-01

    Full Text Available Linezolid, the first oxazolidinone to be used clinically, is effective in the treatment of infections caused by various Gram-positive pathogens, including multidrug resistant enterococci and methicillin-resistant Staphylococus aureus. It has been used successfully for the treatment of patients with endocarditis and bacteraemia, osteomyelitis, joint infections and tuberculosis and it is often used for treatment of complicated infections when other therapies have failed. Linezolid resistance in Gram-positive cocci has been encountered clinically as well as in vitro, but it is still a rare phenomenon. The resistance to this antibiotic has been, until now, entirely associated with distinct nucleotide substitutions in domain V of the 23S rRNA genes. The number of mutated rRNA genes depends on the dose and duration of linezolid exposure and has been shown to influence the level of linezolid resistance. Mutations in associated ribosomal proteins also affect linezolid activity. A new phenicol and clindamycin resistance phenotype has recently been found to be caused by an RNA methyltransferase designated Cfr. This gene confers resistance to lincosamides, oxazolidinones, streptogramin A, phenicols and pleuromutilins, decrease the susceptibility of S. aureus to tylosin, to josamycin and spiramycin and thus differs from erm rRNA methylase genes. Research into new oxazolidinones with improved characteristics is ongoing. Data reported in patent applications demonstrated that some oxazolidinone derivatives, also with improved characteristics with respect to linezolid, are presently under study: at least three of them are in an advanced phase of development.

  10. Antibiotic Resistance

    DEFF Research Database (Denmark)

    Munck, Christian

    of antimicrobial resistance: (1) adaptive mutations and (2) horizontal acquisition of resistance genes from antibiotic gene reservoirs. By studying the geno- and phenotypic changes of E. coli in response to single and drug-pair exposures, I uncover the evolutionary trajectories leading to adaptive resistance. I......Bacteria can avoid extinction during antimicrobial exposure by becoming resistant. They achieve this either via adaptive mutations or horizontally acquired resistance genes. If resistance emerges in clinical relevant species, it can lead to treatment failure and ultimately result in increasing...... morbidity and mortality as well as an increase in the cost of treatment. Understanding how bacteria respond to antibiotic exposure gives the foundations for a rational approach to counteract antimicrobial resistance. In the work presented in this thesis, I explore the two fundamental sources...

  11. Insulin Resistance in Liver Diseases

    OpenAIRE

    Irshad, M

    2011-01-01

    Present report gives a brief and consolidated review of insulin resistance developed in chronic liver diseases. Insulin resistance remains an important feature of chronic liver diseases and progresses disease towards fibrogenesis. Of hepatitis viral infections, hepatitis C virus (HCV) was reported to have a significant role in inducing insulin resistance. Both viral particles as such, as well its structural components induce insulin resistance. Hepatitis C virus core protein, specially, cause...

  12. Decreased prefrontal cortical dopamine transmission in alcoholism.

    Science.gov (United States)

    Narendran, Rajesh; Mason, Neale Scott; Paris, Jennifer; Himes, Michael L; Douaihy, Antoine B; Frankle, W Gordon

    2014-08-01

    Basic studies have demonstrated that optimal levels of prefrontal cortical dopamine are critical to various executive functions such as working memory, attention, inhibitory control, and risk/reward decisions, all of which are impaired in addictive disorders such as alcoholism. Based on this and imaging studies of alcoholism that have demonstrated less dopamine in the striatum, the authors hypothesized decreased dopamine transmission in the prefrontal cortex in persons with alcohol dependence. To test this hypothesis, amphetamine and [11C]FLB 457 positron emission tomography were used to measure cortical dopamine transmission in 21 recently abstinent persons with alcohol dependence and 21 matched healthy comparison subjects. [11C]FLB 457 binding potential, specific compared to nondisplaceable uptake (BPND), was measured in subjects with kinetic analysis using the arterial input function both before and after 0.5 mg kg-1 of d-amphetamine. Amphetamine-induced displacement of [11C]FLB 457 binding potential (ΔBPND) was significantly smaller in the cortical regions in the alcohol-dependent group compared with the healthy comparison group. Cortical regions that demonstrated lower dopamine transmission in the alcohol-dependent group included the dorsolateral prefrontal cortex, medial prefrontal cortex, orbital frontal cortex, temporal cortex, and medial temporal lobe. The results of this study, for the first time, unambiguously demonstrate decreased dopamine transmission in the cortex in alcoholism. Further research is necessary to understand the clinical relevance of decreased cortical dopamine as to whether it is related to impaired executive function, relapse, and outcome in alcoholism.

  13. Resistant Hypertension and Obstructive Sleep Apnea

    Directory of Open Access Journals (Sweden)

    Akram Khan

    2013-01-01

    Full Text Available Hypertension (HTN is a modifiable, highly prevalent risk factor for cardiovascular morbidity and renal dysfunction worldwide. In the United States, HTN affects one in three adults, contributes to one out of every seven deaths and to nearly half of all cardiovascular disease-related deaths. HTN is considered resistant when the blood pressure remains above goal despite lifestyle modification and administration of three antihypertensive agents of different classes including a diuretic. Large population-based studies have suggested that obstructive sleep apnea (OSA is a risk factor for resistant HTN. The mechanism proposed is a pattern of intermittent hypoxia associated with hyperaldosteronism, increased sympathetic tone, endothelial dysfunction, and inflammation. In this review we discuss the association between OSA and resistant HTN, the physiologic mechanisms linking OSA with resistant HTN, and the effect of continuous positive airway pressure therapy (CPAP on blood pressure in patients with resistant HTN. While the reduction in blood pressure with CPAP is usually modest in patients with OSA, a decrease of only a few mmHg in blood pressure can significantly reduce cardiovascular risk. Patients presenting to a center specializing in management of hypertension should be screened and treated for OSA as a potentially modifiable risk factor.

  14. Strength and hypertrophy responses to constant and decreasing rest intervals in trained men using creatine supplementation.

    Science.gov (United States)

    Souza-Junior, Tácito P; Willardson, Jeffrey M; Bloomer, Richard; Leite, Richard D; Fleck, Steven J; Oliveira, Paulo R; Simão, Roberto

    2011-10-27

    The purpose of the current study was to compare strength and hypertrophy responses to resistance training programs that instituted constant rest intervals (CI) and decreasing rest intervals (DI) between sets over the course of eight weeks by trained men who supplemented with creatine monohydrate (CR). Twenty-two recreationally trained men were randomly assigned to a CI group (n = 11; 22.3 ± 1 years; 77.7 ± 5.4 kg; 180 ± 2.2 cm) or a DI group (n = 11; 22 ± 2.5 years; 75.8 ± 4.9 kg; 178.8 ± 3.4 cm). Subjects in both groups supplemented with CR; the only difference between groups was the rest interval instituted between sets; the CI group used 2 minutes rest intervals between sets and exercises for the entire 8-weeks of training, while the DI group started with a 2 minute rest interval the first two weeks; after which the rest interval between sets was decreased 15 seconds per week (i.e. 2 minutes decreasing to 30 seconds between sets). Pre- and post-intervention maximal strength for the free weight back squat and bench press exercises and isokinetic peak torque were assessed for the knee extensors and flexors. Additionally, muscle cross-sectional area (CSA) of the right thigh and upper arm was measured using magnetic resonance imaging. Both groups demonstrated significant increases in back squat and bench press maximal strength, knee extensor and flexor isokinetic peak torque, and upper arm and right thigh CSA from pre- to post-training (p ≤ 0.0001); however, there were no significant differences between groups for any of these variables. The total volume for the bench press and back squat were significantly greater for CI group versus the DI group. We report that the combination of CR supplementation and resistance training can increase muscular strength, isokinetic peak torque, and muscle CSA, irrespective of the rest interval length between sets. Because the volume of training was greater for the CI group versus the DI group, yet strength gains were

  15. Strength and hypertrophy responses to constant and decreasing rest intervals in trained men using creatine supplementation

    Directory of Open Access Journals (Sweden)

    Fleck Steven J

    2011-10-01

    Full Text Available Abstract Background The purpose of the current study was to compare strength and hypertrophy responses to resistance training programs that instituted constant rest intervals (CI and decreasing rest intervals (DI between sets over the course of eight weeks by trained men who supplemented with creatine monohydrate (CR. Methods Twenty-two recreationally trained men were randomly assigned to a CI group (n = 11; 22.3 ± 1 years; 77.7 ± 5.4 kg; 180 ± 2.2 cm or a DI group (n = 11; 22 ± 2.5 years; 75.8 ± 4.9 kg; 178.8 ± 3.4 cm. Subjects in both groups supplemented with CR; the only difference between groups was the rest interval instituted between sets; the CI group used 2 minutes rest intervals between sets and exercises for the entire 8-weeks of training, while the DI group started with a 2 minute rest interval the first two weeks; after which the rest interval between sets was decreased 15 seconds per week (i.e. 2 minutes decreasing to 30 seconds between sets. Pre- and post-intervention maximal strength for the free weight back squat and bench press exercises and isokinetic peak torque were assessed for the knee extensors and flexors. Additionally, muscle cross-sectional area (CSA of the right thigh and upper arm was measured using magnetic resonance imaging. Results Both groups demonstrated significant increases in back squat and bench press maximal strength, knee extensor and flexor isokinetic peak torque, and upper arm and right thigh CSA from pre- to post-training (p ≤ 0.0001; however, there were no significant differences between groups for any of these variables. The total volume for the bench press and back squat were significantly greater for CI group versus the DI group. Conclusions We report that the combination of CR supplementation and resistance training can increase muscular strength, isokinetic peak torque, and muscle CSA, irrespective of the rest interval length between sets. Because the volume of training was greater for the

  16. Sarcopenia in older mice is characterized by a decreased anabolic response to a protein meal.

    Science.gov (United States)

    van Dijk, Miriam; Nagel, Jolanda; Dijk, Francina J; Salles, Jerôme; Verlaan, Sjors; Walrand, Stephane; van Norren, Klaske; Luiking, Yvette

    Ageing is associated with sarcopenia, a progressive decline of skeletal muscle mass, muscle quality and muscle function. Reduced sensitivity of older muscles to respond to anabolic stimuli, i.e. anabolic resistance, is part of the underlying mechanisms. Although, muscle parameters have been studied in mice of various ages/strains; the aim was to study if mice display similar deteriorating processes as human ageing. Therefore, 10,16,21 and 25 months-old C57BL6/6J male mice were studied to measure parameters of sarcopenia and factors contributing to its pathophysiology, with the aim of characterizing sarcopenia in old mice. Muscle mass of the hind limb was lower in 25 as compared to 10 month-old mice. A significant decrease in physical daily activity, muscle grip strength and ex vivo muscle maximal force production was observed in 25 compared to 10 month-old mice. The muscle anabolic response to a single protein meal showed increased muscle protein synthesis in young, but not in old mice, indicative to anabolic resistance. However, by increasing the protein content in meals, anabolic resistance could be overcome, similar as in human elderly. Additionally, aged mice showed higher fasted insulin and hepatic malondialdehyde (MDA) levels (=marker oxidative stress). This study shows clear characteristics of sarcopenia that coincide with anabolic resistance, insulin resistance and oxidative stress in 25 month-old C57/BL6 male mice, similar to human ageing. Furthermore, similar decline in muscle mass, strength and function was observed in this aged-mice-model. These observations offer potential for the future to explore in old mice the effects of interventions targeting sarcopenia. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  17. Serum Soluble Corin is Decreased in Stroke.

    Science.gov (United States)

    Peng, Hao; Zhu, Fangfang; Shi, Jijun; Han, Xiujie; Zhou, Dan; Liu, Yan; Zhi, Zhongwen; Zhang, Fuding; Shen, Yun; Ma, Juanjuan; Song, Yulin; Hu, Weidong

    2015-07-01

    Soluble corin was decreased in coronary heart disease. Given the connections between cardiac dysfunction and stroke, circulating corin might be a candidate marker of stroke risk. However, the association between circulating corin and stroke has not yet been studied in humans. Here, we aimed to examine the association in patients wtith stroke and community-based healthy controls. Four hundred eighty-one patients with ischemic stroke, 116 patients with hemorrhagic stroke, and 2498 healthy controls were studied. Serum soluble corin and some conventional risk factors of stroke were examined. Because circulating corin was reported to be varied between men and women, the association between serum soluble corin and stroke was evaluated in men and women, respectively. Patients with ischemic and hemorrhagic stroke had a significantly lower level of serum soluble corin than healthy controls in men and women (all P values, stroke than men in the highest quartile. Women in the lowest quartile of serum soluble corin were also more likely to have ischemic (OR, 3.10; 95% confidence interval, 1.76-5.44) and hemorrhagic (OR, 8.54; 95% confidence interval, 2.35-31.02) stroke than women in the highest quartile. ORs of ischemic and hemorrhagic stroke were significantly increased with the decreasing levels of serum soluble corin in men and women (all P values for trend, stroke compared with healthy controls. Our findings raise the possibility that serum soluble corin may have a pathogenic role in stroke. © 2015 American Heart Association, Inc.

  18. Lymphedema treatment decreases pain intensity in lipedema.

    Science.gov (United States)

    Szolnoky, G; Varga, E; Varga, M; Tuczai, M; Dósa-Rácz, E; Kemény, L

    2011-12-01

    Lipedema is a disproportional obesity featuring light pressure-induced or spontaneous pain. On the basis of our clinical observations, lymphedema therapy, as practiced in our clinic, reduces the perception of pain beyond leg volume reduction. We therefore aimed to measure pain intensity prior and subsequent to treatment. 38 women with lipedema were enrolled in the study with 19 patients undergoing treatment and 19 serving as the control group using exclusively moisturizers. Treatment consisted of once daily manual lymph drainage (MLD), intermittent pneumatic compression (IPC), and multilayered short-stretch bandaging performed throughout a 5-day-course. Pain was evaluated with a 10-item questionnaire, a pain rating scale (PRS), and the Wong-Baker Faces scale. Treatment resulted in a significant reduction of pain with a decrease in mean scores of all three measures. In the control group, only PRS showed significant decrease. Our study results indicate that this treatment regimen not only reduces leg volume and capillary fragility, but also improves pain intensity in patients with lipedema.

  19. Regional, seasonal, and temporal variations in the prevalence of antimicrobial-resistant Escherichia coli isolated from pigs at slaughter in Denmark (1997-2005).

    Science.gov (United States)

    Abatih, E N; Emborg, H D; Jensen, V F; Lo Fo Wong, D M A; Ersbøll, A K

    2009-04-01

    The aim of this study was to analyze and discuss regional, seasonal, and temporal trends in the occurrence of antimicrobial-resistant Escherichia coli isolated from pigs at slaughter in Denmark between 1997 and 2005. Data on antimicrobial-resistant E. coli were obtained from the Danish Integrated Antimicrobial Resistance Monitoring and Research Programme database. The Cochran-Armitage trend test was used to detect the presence and evaluate the significance of regional, seasonal, and annual trends in the occurrence of antimicrobial-resistant E. coli for four drugs. Associations between resistance and explanatory variables region, season, and the year of isolate sampling were analyzed using a logistic regression model. The Cochran-Armitage test provided evidence of significant temporal trends for ampicillin-resistant E. coli (an increasing trend, p streptomycin-resistant E. coli (a decreasing trend, p E. coli increased over time for all seasons (p E. coli were captured over time. On the other hand, a significant decreasing trend in prevalence of streptomycin-resistant E. coli was observed for the spring, summer, and winter months (p 0.05). The prevalence of ampicillin-resistant E. coli was observed to increase over time for the various regions, whereas that for streptomycin-resistant E. coli presented an overall significant decrease over time. The estimated odds ratios from the logistic regression model indicated varying risks for the occurrence of resistance by season and by region. The winter months were associated with an increased risk for the occurrence of resistant E. coli as compared to the other seasons of the year. Our study provides evidence of statistically significant regional, seasonal, and temporal variations for ampicillin- and streptomycin-resistant E. coli isolated from pigs at slaughter in Denmark between 1997 and 2005.

  20. Effect of thiazolidinedione treatment on resistin levels in insulin resistant sprague dawley rats

    International Nuclear Information System (INIS)

    Yousaf, I.; Hameed, W.; Rajput, T.A.

    2015-01-01

    Insulin resistance is manifested by decreased effect of fixed quantity of insulin on glucose metabolism leading to type 2 diabetes mellitus. Visceral obesity has been positively correlated with insulin resistance but its mechanism is not fully defined. Insulin resistance may be the consequence of adipocytokines including visfatin and resistin. This study was designed to see the effect of thiazolidinediones on levels of resistin in insulin resistant rats. Methods: Ninety Sprague Dawley rats were randomly divided into three groups. Group I served as control. Rats in Group II and III were made insulin resistant diabetics. Group III was treated with rosiglitazone after development of diabetes. Plasma glucose, serum triglycerides, HDL, TG:HDL ratio and serum resistin levels were analysed. Results: Body weight and plasma glucose were significantly increased (p<0.05) along with TG:HDL ratio (p<0.05) in group II and group III at the end of 4th week. Serum resistin levels also increased significantly (p<0.05) in group II and III at the end of 4th week. Treatment of group III with rosiglitazone led to improvement in insulin resistance with decrease in serum resistin levels (p<0.05). Conclusion: Increased serum resistin level indicates insulin resistance and impending hyperglycaemia. Thiazolidinediones augment sensitivity of insulin to restore normoglycaemia by decreasing serum resistin level. (author)

  1. Prevalence of Antibiotic-Resistant Escherichia coli in Drinking Water Sources in Hangzhou City

    Directory of Open Access Journals (Sweden)

    Zhaojun Chen

    2017-06-01

    Full Text Available This study investigated the distribution of antibiotic resistant Escherichia coli (E. coli and examined the possible relationship between water quality parameters and antibiotic resistance from two different drinking water sources (the Qiantang River and the Dongtiao Stream in Hangzhou city of China. E. coli isolates were tested for their susceptibility to 18 antibiotics. Most of the isolates were resistant to tetracycline (TE, followed by ampicillin (AM, piperacillin (PIP, trimethoprim/sulfamethoxazole (SXT, and chloramphenicol (C. The antibiotic resistance rate of E. coli isolates from two water sources was similar; For E. coli isolates from the Qiantang River, their antibiotic resistance rates decreased from up- to downstream. Seasonally, the dry and wet season had little impact on antibiotic resistance. Spearman's rank correlation revealed significant correlation between resistance to TE and phenicols or ciprofloxacin (CIP, as well as quinolones (ciprofloxacin and levofloxacin and cephalosporins or gentamicin (GM. Pearson's chi-square tests found certain water parameters such as nutrient concentration were strongly associated with resistance to some of the antibiotics. In addition, tet genes were detected from all 82 TE-resistant E. coli isolates, and most of the isolates (81.87% contained multiple tet genes, which displayed 14 different combinations. Collectively, this study provided baseline data on antibiotic resistance of drinking water sources in Hangzhou city, which indicates drinking water sources could be the reservoir of antibiotic resistance, potentially presenting a public health risk.

  2. Re-sensitizing drug-resistant bacteria to antibiotics by designing Antisense Therapeutics

    Science.gov (United States)

    Courtney, Colleen; Chatterjee, Anushree

    2014-03-01

    ``Super-bugs'' or ``multi-drug resistant organisms'' are a serious international health problem, with devastating consequences to patient health care. The Center for Disease Control has identified antibiotic resistance as one of the world's most pressing public health problems as a significant fraction of bacterial infections contracted are drug resistant. Typically, antibiotic resistance is encoded by ``resistance-genes'' which express proteins that carryout the resistance causing functions inside the bacterium. We present a RNA based therapeutic strategy for designing antimicrobials capable of re-sensitizing resistant bacteria to antibiotics by targeting labile regions of messenger RNAs encoding for resistance-causing proteins. We perform in silico RNA secondary structure modeling to identify labile target regions in an mRNA of interest. A synthetic biology approach is then used to administer antisense nucleic acids to our model system of ampicillin resistant Escherichia coli. Our results show a prolonged lag phase and decrease in viability of drug-resistant E. colitreated with antisense molecules. The antisense strategy can be applied to alter expression of other genes in antibiotic resistance pathways or other pathways of interest.

  3. Unsaturated fatty acids and insulin resistance in childhood obesity.

    Science.gov (United States)

    Toledo, Karen; Aranda, Mario; Asenjo, Sylvia; Sáez, Katia; Bustos, Paulina

    2014-05-01

    Obesity is characterized by increased levels of plasma free fatty acids (FFAs) that interfere with insulin signaling. The aim of our study was to assess the FFA profile in obese children and adolescents and to determine their relation with different degrees of insulin resistance. A transversal study was conducted of 51 children and adolescents (mean age, 11.7±1.6 years; 47% males) with obesity (body mass index ≥95 percentile). Anthropometric, clinical, and biochemical parameters were assessed. Insulin resistance was determined using the homeostasis model assessment of insulin resistance (HOMA-IR) index. Plasma fatty acids were quantified by high-performance liquid chromatography with heptadecanoic acid as the internal standard. The mean concentration of myristic acid, linoleic acid, palmitic acid, oleic acid, stearic acid, and total fatty acids was 9.3±2.2, 86.5±38.3, 93.0±35.5, 177.0±83.6, 48.5±14.9, and 414.3±160.9 μmol/L, respectively. Total fatty acids and unsaturated fatty acids such as oleic acid and linoleic acid showed an inverse significant correlation with insulin resistance. Children with high insulin resistance (HOMA-IR >2.5) showed a decrease in unsaturated fatty acids compared with children having a HOMA-IR of fatty acid concentrations between those groups. A decrease in unsaturated fatty acids was correlated with insulin resistance in childhood obesity.

  4. Engineered plant virus resistance.

    Science.gov (United States)

    Galvez, Leny C; Banerjee, Joydeep; Pinar, Hasan; Mitra, Amitava

    2014-11-01

    Virus diseases are among the key limiting factors that cause significant yield loss and continuously threaten crop production. Resistant cultivars coupled with pesticide application are commonly used to circumvent these threats. One of the limitations of the reliance on resistant cultivars is the inevitable breakdown of resistance due to the multitude of variable virus populations. Similarly, chemical applications to control virus transmitting insect vectors are costly to the farmers, cause adverse health and environmental consequences, and often result in the emergence of resistant vector strains. Thus, exploiting strategies that provide durable and broad-spectrum resistance over diverse environments are of paramount importance. The development of plant gene transfer systems has allowed for the introgression of alien genes into plant genomes for novel disease control strategies, thus providing a mechanism for broadening the genetic resources available to plant breeders. Genetic engineering offers various options for introducing transgenic virus resistance into crop plants to provide a wide range of resistance to viral pathogens. This review examines the current strategies of developing virus resistant transgenic plants. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  5. Effect of Ultrasonic Waves on the Heat Resistance of Bacillus cereus and Bacillus licheniformis Spores

    Science.gov (United States)

    Burgos, J.; Ordóñez, J. A.; Sala, F.

    1972-01-01

    Heat resistance of Bacillus cereus and Bacillus licheniformis spores in quarter-strength Ringer solution decreases markedly after ultrasonic treatments which are unable to kill a significant proportion of the spore population. This effect does not seem to be caused by a loss of Ca2+ or dipicolinic acid. The use of ultrasonics to eliminate vegetative cells or to break aggregates in Bacillus spore suspensions to be used subsequently in heat resistance experiments appears to be unadvisable. PMID:4627969

  6. Radiation-resistant characteristics of epoxyresins

    International Nuclear Information System (INIS)

    Saito, Toshio; Seguchi, Tadao.

    1985-01-01

    For the evaluation of radiation resistivity under the condition of low level irradiation in the atmospheric environment, oxidation and deterioration of several kinds of epoxy resins were examined by the acceleration method with 2.7 kGy/h, 2 MGy of 60 Co-γ irradiation and 3 MPa of oxygen pressure, and with 0.88 kGy/h, 2 MGy of irradiation and 4 MPa of oxygen pressure, to simulate 18 Gy/h, 12 years and 4.5 Gy/h, 50 years of atmospheric deterioration respectively. Bending strength emitted gas component, diffusion and solubility coefficients, oxidized layer thickness, gel fraction and dynamic visco-elasticity were determined for the irradiated epoxy resins. As for the radiation resistivity, epoxy resins of acid anhydride hardening agent showed superior quality to those of amine-type hardening agent, and the former showed no deterioration enen after irradiation in vacuum. From the above-mentioned understandings and also from data of exhausted gas analysis, gel fraction determination and visco-elasticity testing, it was clarified that the radiation resistivity of main components of epoxy resins were superior for Epikote 828, ether radical, tertiary amine to ester radical followed by hydroxyl radical. It was also clarified that heat resitivity was significantly lowered in the deteriorated resins and that thickness of oxidized layer was decreased with radiation dose. It was concluded that radiation resistivity of epoxy resins depended on their hardening agent significantly. (Takagi, S.)

  7. Hydrogen Sulfide Alleviates Aluminum Toxicity via Decreasing Apoplast and Symplast Al Contents in Rice

    Directory of Open Access Journals (Sweden)

    Chun Q. Zhu

    2018-03-01

    Full Text Available Hydrogen sulfide (H2S plays a vital role in Al3+ stress resistance in plants, but the underlying mechanism is unclear. In the present study, pretreatment with 2 μM of the H2S donor NaHS significantly alleviated the inhibition of root elongation caused by Al toxicity in rice roots, which was accompanied by a decrease in Al contents in root tips under 50 μM Al3+ treatment. NaHS pretreatment decreased the negative charge in cell walls by reducing the activity of pectin methylesterase and decreasing the pectin and hemicellulose contents in rice roots. This treatment also masked Al-binding sites in the cell wall by upregulating the expression of OsSATR1 and OsSTAR2 in roots and reduced Al binding in the cell wall by stimulating the expression of the citrate acid exudation gene OsFRDL4 and increasing the secretion of citrate acid. In addition, NaHS pretreatment decreased the symplasmic Al content by downregulating the expression of OsNRAT1, and increasing the translocation of cytoplasmic Al to the vacuole via upregulating the expression of OsALS1. The increment of antioxidant enzyme [superoxide dismutase (SOD, ascorbate peroxidase (APX, catalase (CAT, and peroxidase (POD] activity with NaHS pretreatment significantly decreased the MDA and H2O2 content in rice roots, thereby reducing the damage of Al3+ toxicity on membrane integrity in rice. H2S exhibits crosstalk with nitric oxide (NO in response to Al toxicity, and through reducing NO content in root tips to alleviate Al toxicity. Together, this study establishes that H2S alleviates Al toxicity by decreasing the Al content in the apoplast and symplast of rice roots.

  8. Contrasting effects of specialist and generalist herbivores on resistance evolution in invasive plants.

    Science.gov (United States)

    Zhang, Zhijie; Pan, Xiaoyun; Blumenthal, Dana; van Kleunen, Mark; Liu, Mu; Li, Bo

    2018-04-01

    Invasive alien plants are likely to be released from specialist herbivores and at the same time encounter biotic resistance from resident generalist herbivores in their new ranges. The Shifting Defense hypothesis predicts that this will result in evolution of decreased defense against specialist herbivores and increased defense against generalist herbivores. To test this, we performed a comprehensive meta-analysis of 61 common garden studies that provide data on resistance and/or tolerance for both introduced and native populations of 32 invasive plant species. We demonstrate that introduced populations, relative to native populations, decreased their resistance against specialists, and increased their resistance against generalists. These differences were significant when resistance was measured in terms of damage caused by the herbivore, but not in terms of performance of the herbivore. Furthermore, we found the first evidence that the magnitude of resistance differences between introduced and native populations depended significantly on herbivore origin (i.e., whether the test herbivore was collected from the native or non-native range of the invasive plant). Finally, tolerance to generalists was found to be higher in introduced populations, while neither tolerance to specialists nor that to simulated herbivory differed between introduced and native plant populations. We conclude that enemy release from specialist herbivores and biotic resistance from generalist herbivores have contrasting effects on resistance evolution in invasive plants. Our results thus provide strong support for the Shifting Defense hypothesis. © 2018 by the Ecological Society of America.

  9. Altered membrane permeability in multidrug resistant Escherichia ...

    African Journals Online (AJOL)

    PRECIOUS

    2009-11-02

    Nov 2, 2009 ... involvement during the transport of β - lactams in multidrug resistant Escherichia coli isolated from extra-intestinal infections. Also, the ... lactam resistance in multidrug resistant E. coli in ESBL and non-ESBL isolates. .... and decreased susceptibility to carbapenems, particularly ertapenem (Perez et al.,.

  10. Effect of Resistance Training on Serum Meteorin-like Hormone Level and Insulin Resistance Index in Overweight Adolescent Boys

    Directory of Open Access Journals (Sweden)

    Hamid Alizadeh

    2017-10-01

    Full Text Available Abstract Background: Adipose tissue's phenotypic alteration due to exercise training is a new theory. However, the cellular–molecular mechanisms for these phenotypic alterations are not yet clearly understood. The aim of this study was to investigate the effects of six weeks resistance training on Meteorin-like hormone level and insulin resistance index in overweight adolescent boys. Materials and Methods: Twenty overweight adolescent boys (average age 18.5±1 years old, average weight 81.1±4.5 kg, and BMI 27.7±0.7 kg/m2 participated in this study. The subjects were randomly assigned into two groups: control (N=10 and resistance training (N=10. Subjects in training group performed six-week resistance training program 3 days/week. Anthropometrics parameters and fasting serum of Meteorin-like hormone levels, insulin and glucose were measured at the baseline and at the end of study. Results: The level of Meteorin-like hormone was significantly decreased in control group (p=0.008, but that of Meteorin-like hormone in resistance training was increased insignificantly (p=0.311. The variations of Meteorin-like hormone levels between two groups were significant (p=0.004. The changes of insulin resistance were increased in both groups which were statistically significant (p=0.032 and insignificant (p=0.632 for control and training groups respectively. We found a negative and insignificant correlation between changes in Meteorin-like hormone levels and changes in insulin resistance index (p=0.273. Conclusion: The results showed that six weeks’ resistance training has no effect on increasing Meteorin-like hormone serum level and improving insulin resistance index and body composition in overweight adolescent boys.

  11. Impact of restricted amoxicillin/clavulanic acid use on Escherichia coli resistance--antibiotic DU90% profiles with bacterial resistance rates: a visual presentation.

    Science.gov (United States)

    Mimica Matanovic, Suzana; Bergman, Ulf; Vukovic, Dubravka; Wettermark, Björn; Vlahovic-Palcevski, Vera

    2010-10-01

    High use of amoxicillin/clavulanic acid (AMC) at the University Hospital Osijek (Croatia) contributed to high rates of resistance in Enterobacteriaceae, in particular Escherichia coli (50%). Thus, in order to decrease bacterial resistance, AMC use was restricted. We present results of the restriction on resistance amongst antibiotics accounting for 90% of antibiotic use [drug utilisation 90% (DU90%)]. Data were analysed on antibiotic use and microbiological susceptibility of E. coli during two 9-month periods, before and after the restriction of AMC use. Drug use was presented as numbers of defined daily doses (DDDs) and DDDs/100 bed-days. Resistance of E. coli to antibiotics was presented as percentages of isolated strains in the DU90% segment. Use of AMC was 16 DDDs/100 bed-days or 30% of all antibiotics before the intervention. Use of AMC fell to 2 DDDs/100 bed-days or 4% after the intervention, and resistance of E. coli fell from 37% to 11%. In conclusion, restricted use of AMC resulted in a significant decrease of E. coli resistance. DU90% resistance profiles are simple and useful tools in highlighting problems in antibiotic use and resistance but may also be useful in long-term follow-up of antibiotic policy. Copyright 2010 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  12. A single-amino-acid substitution in the TvbS1 receptor results in decreased susceptibility to infection by avian sarcoma and leukosis virus subgroups B and D and resistance to infection by subgroup E in vitro and in vivo

    Czech Academy of Sciences Publication Activity Database

    Reinišová, Markéta; Šenigl, Filip; Yin, X.; Plachý, Jiří; Geryk, Josef; Elleder, Daniel; Svoboda, Jan; Federspiel, M. J.; Hejnar, Jiří

    2008-01-01

    Roč. 82, č. 5 (2008), s. 2097-2105 ISSN 0022-538X R&D Projects: GA ČR GA523/07/1171; GA ČR GA523/07/1282 Grant - others:NIH(US) AI48682 Institutional research plan: CEZ:AV0Z50520514 Keywords : retrovirus receptors * avian sarcoma and leukosis virus * resistance to retrovirus Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.308, year: 2008

  13. The depressed central carbon and energy metabolisms is associated to the acquisition of levofloxacin resistance in Vibrio alginolyticus.

    Science.gov (United States)

    Cheng, Zhi-Xue; Yang, Man-Jun; Peng, Bo; Peng, Xuan-Xian; Lin, Xiang-Min; Li, Hui

    2018-04-05

    The overuse and misuse of antibiotics lead to bacterial antibiotic resistance, challenging human health and intensive cultivation. It is especially required to understand for the mechanism of antibiotic resistance to control antibiotic-resistant pathogens. The present study characterized the differential proteome of levofloxacin-resistant Vibrio alginolyticus with the most advanced iTRAQ quantitative proteomics technology. A total of 160 proteins of differential abundance were identified, where 70 were decreased and 90 were increased. Further analysis demonstrated that crucial metabolic pathways like TCA cycle were significantly down-regulated. qRT-PCR analysis demonstrated the decreased gene expression of glycolysis/gluconeogenesis, the TCA cycle, and fatty acid biosynthesis. Moreover, Na(+)-NQR complex gene expression, membrane potential and the adenylate energy charge ratio were decreased, indicating that the decreased central carbon metabolism is associated to the acquisition of levofloxacin resistance. Therefore, the reduced central carbon and energy metabolisms form a characteristic feature as fitness costs of V. alginolyticus in resistance to levofloxacin. The overuse and misuse of antibiotics lead to bacterial antibiotic resistance, challenging human health and intensive cultivation. Understanding for the antibiotic resistance mechanisms is especially required to control these antibiotic-resistant pathogens. The present study characterized the differential proteome of levofloxacin-resistant Vibrio alginolyticus using the most advanced iTRAQ quantitative proteomics technology. A total of 160 differential abundance of proteins were identified with 70 decreases and 90 increases by liquid chromatography matrix assisted laser desorption ionization mass spectrometry. Most interestingly, crucial metabolic pathways such as the TCA cycle sharply fluctuated. This is the first report that the reduced central carbon and energy metabolisms form a characteristic feature

  14. Electrical resistivities of rocks from Chalk River

    International Nuclear Information System (INIS)

    Katsube, T.J.; Hume, J.P.

    1989-01-01

    Bulk rock resistivity and bulk surface resistivity measurements have been obtained for 40 gneissic rock samples from Chalk River, Ontario. Though bulk rock resistivity is a function of pore structure, pore-fluid resistivity and pore-surface resistivity, the amount of data documented for pore-surface resistivity is small compared to that for pore structure and pore-fluid resistivity. This study indicates that pore-surface resistivity has a significant effect on bulk rock resistivity. It is important that this fact be considered when interpreting resistivity data obtained by geophysical methods. In addition, a group of mafic gneiss samples had pore-surface resistivity values that were much lower than those reported for clays, glass beads or petroleum reservoir rocks. This is thought to be due to metallic minerals lining the pore walls. Other rock samples collected from the same area showed pore-surface resistivity value similar to those reported in the literature

  15. The effects of bending on the resistance of elastically stretchable metal conductors, and a comparison with stretching

    Science.gov (United States)

    Graudejus, O.; Li, T.; Cheng, J.; Keiper, N.; Ponce Wong, R. D.; Pak, A. B.; Abbas, J.

    2017-05-01

    Microcracked gold films on elastomeric substrates can function as stretchable and deformable interconnects and sensors. In response to stretch or deformation, the design would seek to minimize the change in resistance for stretchable or deformable interconnects; if used as resistive sensors, a large change in resistance would be desired. This research examines the change in resistance upon bending of a microcracked conductor and compares the results with stretching such a conductor. The resistance depends on the strain in the film, which, for bending, is a function of the bending radius and the location of the film within the structure with respect to the neutral plane. The resistance decreases when the gold conductor is under compression and increases when it is under tension. The decrease in resistance under compression is small compared to the increase in resistance under tension, marginally depending on the bending radius. In contrast, the resistance under tension significantly increases with decreasing bending radius. The mechanics model presented here offers a mechanistic understanding of these observations. These results provide guidance for the design of interconnects for flexible and stretchable electronics and for flexible sensors to monitor the magnitude and direction of bending or stretching.

  16. Resistant Hypertension.

    Science.gov (United States)

    Doroszko, Adrian; Janus, Agnieszka; Szahidewicz-Krupska, Ewa; Mazur, Grzegorz; Derkacz, Arkadiusz

    2016-01-01

    Resistant hypertension is a severe medical condition which is estimated to appear in 9-18% of hypertensive patients. Due to higher cardiovascular risk, this disorder requires special diagnosis and treatment. The heterogeneous etiology, risk factors and comorbidities of resistant hypertension stand in need of sophisticated evaluation to confirm the diagnosis and select the best therapeutic options, which should consider lifestyle modifications as well as pharmacological and interventional treatment. After having excluded pseudohypertension, inappropriate blood pressure measurement and control as well as the white coat effect, suspicion of resistant hypertension requires an analysis of drugs which the hypertensive patient is treated with. According to one definition - ineffective treatment with 3 or more antihypertensive drugs including diuretics makes it possible to diagnose resistant hypertension. A multidrug therapy including angiotensin - converting enzyme inhibitors, angiotensin II receptor blockers, beta blockers, diuretics, long-acting calcium channel blockers and mineralocorticoid receptor antagonists has been demonstrated to be effective in resistant hypertension treatment. Nevertheless, optional, innovative therapies, e.g. a renal denervation or baroreflex activation, may create a novel pathway of blood pressure lowering procedures. The right diagnosis of this disease needs to eliminate the secondary causes of resistant hypertension e.g. obstructive sleep apnea, atherosclerosis and renal or hormonal disorders. This paper briefly summarizes the identification of the causes of resistant hypertension and therapeutic strategies, which may contribute to the proper diagnosis and an improvement of the long term management of resistant hypertension.

  17. Managing Resistance.

    Science.gov (United States)

    Maag, John W.

    2000-01-01

    This article presents some considerations and ideas for managing students' resistance. They are organized around four topics: the impact of context on behavior, the importance of being comprehensive and nonrestrictive in behavior, the adaptive function of resistant behavior, and the benefit of joining children in their frame of reference.…

  18. Does antifouling paint select for antibiotic resistance?

    Science.gov (United States)

    Flach, Carl-Fredrik; Pal, Chandan; Svensson, Carl Johan; Kristiansson, Erik; Östman, Marcus; Bengtsson-Palme, Johan; Tysklind, Mats; Larsson, D G Joakim

    2017-07-15

    There is concern that heavy metals and biocides contribute to the development of antibiotic resistance via co-selection. Most antifouling paints contain high amounts of such substances, which risks turning painted ship hulls into highly mobile refuges and breeding grounds for antibiotic-resistant bacteria. The objectives of this study were to start investigate if heavy-metal based antifouling paints can pose a risk for co-selection of antibiotic-resistant bacteria and, if so, identify the underlying genetic basis. Plastic panels with one side painted with copper and zinc-containing antifouling paint were submerged in a Swedish marina and biofilms from both sides of the panels were harvested after 2.5-4weeks. DNA was isolated from the biofilms and subjected to metagenomic sequencing. Biofilm bacteria were cultured on marine agar supplemented with tetracycline, gentamicin, copper sulfate or zinc sulfate. Biofilm communities from painted surfaces displayed lower taxonomic diversity and enrichment of Gammaproteobacteria. Bacteria from these communities showed increased resistance to both heavy metals and tetracycline but not to gentamicin. Significantly higher abundance of metal and biocide resistance genes was observed, whereas mobile antibiotic resistance genes were not enriched in these communities. In contrast, we found an enrichment of chromosomal RND efflux system genes, including such with documented ability to confer decreased susceptibility to both antibiotics and biocides/heavy metals. This was paralleled by increased abundances of integron-associated integrase and ISCR transposase genes. The results show that the heavy metal-based antifouling paint exerts a strong selection pressure on marine bacterial communities and can co-select for certain antibiotic-resistant bacteria, likely by favoring species and strains carrying genes that provide cross-resistance. Although this does not indicate an immediate risk for promotion of mobile antibiotic resistance, the

  19. Optical imaging of radiation-induced metabolic changes in radiation-sensitive and resistant cancer cells

    Science.gov (United States)

    Alhallak, Kinan; Jenkins, Samir V.; Lee, David E.; Greene, Nicholas P.; Quinn, Kyle P.; Griffin, Robert J.; Dings, Ruud P. M.; Rajaram, Narasimhan

    2017-06-01

    Radiation resistance remains a significant problem for cancer patients, especially due to the time required to definitively determine treatment outcome. For fractionated radiation therapy, nearly 7 to 8 weeks can elapse before a tumor is deemed to be radiation-resistant. We used the optical redox ratio of FAD/(FAD+NADH) to identify early metabolic changes in radiation-resistant lung cancer cells. These radiation-resistant human A549 lung cancer cells were developed by exposing the parental A549 cells to repeated doses of radiation (2 Gy). Although there were no significant differences in the optical redox ratio between the parental and resistant cell lines prior to radiation, there was a significant decrease in the optical redox ratio of the radiation-resistant cells 24 h after a single radiation exposure (p=0.01). This change in the redox ratio was indicative of increased catabolism of glucose in the resistant cells after radiation and was associated with significantly greater protein content of hypoxia-inducible factor 1 (HIF-1α), a key promoter of glycolytic metabolism. Our results demonstrate that the optical redox ratio could provide a rapid method of determining radiation resistance status based on early metabolic changes in cancer cells.

  20. A passive quantitative measurement of airway resistance using depth data.

    Science.gov (United States)

    Ostadabbas, Sarah; Bulach, Christoph; Ku, David N; Anderson, Larry J; Ghovanloo, Maysam

    2014-01-01

    The Respiratory Syncytial Virus (RSV) is the most common cause of serious lower respiratory tract infections in infants and young children. RSV often causes increased airway resistance, clinically detected as wheezing by chest auscultation. In this disease, expiratory flows are significantly reduced due to the high resistance in patient's airway passages. A quantitative method for measuring resistance can have a great benefit to diagnosis and management of children with RSV infections as well as with other lung diseases. Airway resistance is defined as the lung pressure divided by the airflow. In this paper, we propose a method to quantify resistance through a simple, non-contact measurement of chest volume that can act as a surrogate measure of the lung pressure and volumetric airflow. We used depth data collected by a Microsoft Kinect camera for the measurement of the lung volume over time. In our experimentation, breathing through a number of plastic straws induced different airway resistances. For a standard spirometry test, our volume/flow estimation using Kinect showed strong correlation with the flow data collected by a commercially-available spirometer (five subjects, each performing 20 breathing trials, correlation coefficient = 0.88, with 95% confidence interval). As the number of straws decreased, emulating a higher airway obstruction, our algorithm was sufficient to distinguish between several levels of airway resistance.

  1. Total peripheral resistance changes in dogs during aversive classical conditioning.

    Science.gov (United States)

    Anderson, D E; Yingling, J E

    1978-01-01

    The arterial pressure, heart rate, stroke volume, cardiac output and total peripheral resistance of laboratory dogs were monitored continuously before and during a 30 min period in which aversive classical conditioning procedures were applied. The experimental stimulation generated inhibition of behavioral activity ("freezing") together with sustained increases in arterial pressure averaging 30%, and increases in heart rate anc cardiac output of 60-70%. The calculated total peripheral resistance decreased by an average of 20%. The behavioral and cardiovascular responses were sustained during the aversive conditioning period. The results suggest that significant peripheral vasodilation occurred under these conditions which was probably not due to metabolic byproducts of behavioral activity, but probably reflected sympathetic cholinergic effects upon blood vessels in the skeletal muscles. These data document the significance of the skeletal muscle circulation in the total peripheral resistance to blood flow in unanesthetized animals.

  2. The Effect of Eight Weeks Resistance Training on Leptin and Insulin Resistance in Obese Female

    Directory of Open Access Journals (Sweden)

    S. Khalili

    2013-04-01

    Full Text Available Introduction & Objective: Leptin , the main peptide secreted by adipose tissue, is considered an alarming factor in the regulation of body fat content . With regard to the physiological effect of exercise as one of the potential regulators of leptin secretion from adipose tissue , this study was performed to examine the effects of resistance exercise on leptin. Materials & Methods: Twenty inactive and obese female students (10 controls and 10 experi-mentals participated in this study. The subjects in the experimental group performed an 8 week resistance training program (chest press, leg press, lat pull down, leg curl, bicep curl, leg extension with 60 - 70 percent of 1RM. ELISA was used to measure leptin. Results: The results of this study showed that 8 weeks of resistance training significantly decreased BMI (31.32 kg/m2 versus 29.73 kg/m2 , P=0.0001, weight body (80.5kg versus 76.25kg, P=0.0001, WHR (0.93 ver-sus0.89, P=0.0001 and body fat percent (27.48 versus 24.85, P=0.0001 in EG. Statistically significant differ-ences were not seen in leptin (P=0.939, insulin (P=0.336, glucose (P=0.264 and insulin resistance (P=0.306 between CG and EG. Conclusion: The results of this study showed that , there was no significant difference in leptin levels and insulin resistance between the control and experimental groups, after 8 weeks of resistance training. (Sci J Hamadan Univ Med Sci 2013; 20 (1:59-65

  3. Periodontal Disease and Decreased Kidney Function in Japanese Elderly

    NARCIS (Netherlands)

    Iwasaki, Masanori; Taylor, George W.; Nesse, Willem; Vissink, Arjan; Yoshihara, Akihiro; Miyazaki, Hideo

    Background: Early detection of decreased kidney function can help prevent the progression of kidney disease to kidney failure and cardiovascular events. Potentially significant associations between kidney function and periodontal disease have been reported in cross-sectional studies. However, no

  4. Insulin and Insulin Resistance

    Science.gov (United States)

    2005-01-01

    As obesity and diabetes reach epidemic proportions in the developed world, the role of insulin resistance and its consequences are gaining prominence. Understanding the role of insulin in wide-ranging physiological processes and the influences on its synthesis and secretion, alongside its actions from the molecular to the whole body level, has significant implications for much chronic disease seen in Westernised populations today. This review provides an overview of insulin, its history, structure, synthesis, secretion, actions and interactions followed by a discussion of insulin resistance and its associated clinical manifestations. Specific areas of focus include the actions of insulin and manifestations of insulin resistance in specific organs and tissues, physiological, environmental and pharmacological influences on insulin action and insulin resistance as well as clinical syndromes associated with insulin resistance. Clinical and functional measures of insulin resistance are also covered. Despite our incomplete understanding of the complex biological mechanisms of insulin action and insulin resistance, we need to consider the dramatic social changes of the past century with respect to physical activity, diet, work, socialisation and sleep patterns. Rapid globalisation, urbanisation and industrialisation have spawned epidemics of obesity, diabetes and their attendant co-morbidities, as physical inactivity and dietary imbalance unmask latent predisposing genetic traits. PMID:16278749

  5. [Effects of planting density and spraying PP333 on winter wheat lodging-resistance and grain yield].

    Science.gov (United States)

    Chen, Xiao-Guang; Wang, Zhen-Lin; Peng, Dian-Liang; Li, Yong; Cai, Tie; Wang, Ping; Chen, Er-Ying

    2011-06-01

    Taking two winter wheat varieties Gaocheng 8901 and Yannong 21 with different end-use qualities as test objects, a field experiment was conducted in the experimental farm of Shandong Agricultural University from 2008 to 2010, aimed to study the effects of different planting density and spraying PP333 on the basal stem morphological characteristics, snapping-resistance, lodging-resistant index, and grain yield. Gaocheng 8901 had higher lodging-resistance but lower grain yield than Yannong 21. Comparing with low planting density (180 x 10(4) basic seedlings per hm2), high planting density (240 x 10(4) basic seedlings per hm2) decreased the culm snapping-resistance and lodging-resistant index of the two varieties, especially Yannong 21. Spraying PP333 decreased the plant height and the basal internodes length, increased the snapping-resistance and lodging-resistant index, strengthened the lodging-resistance, and improved the spike number and grain yield. Correlation analysis showed that the second internode length, percentage of basal internodes (1 + 2) length to total internode length, and apparent lodging ratio were significantly negatively correlated with culm lodging resistant index. Therefore, to adopt an appropriate planting density combined with spraying PP333 could improve the lodging-resistance of winter wheat and its grain yield, being an important high-yielding cultivation technique for wheat production in sub-humid zone.

  6. Failure of Homeostatic Model Assessment of Insulin Resistance to Detect Marked Diet-Induced Insulin Resistance in Dogs

    Science.gov (United States)

    Ader, Marilyn; Stefanovski, Darko; Richey, Joyce M.; Kim, Stella P.; Kolka, Cathryn M.; Ionut, Viorica; Kabir, Morvarid; Bergman, Richard N.

    2014-01-01

    Accurate quantification of insulin resistance is essential for determining efficacy of treatments to reduce diabetes risk. Gold-standard methods to assess resistance are available (e.g., hyperinsulinemic clamp or minimal model), but surrogate indices based solely on fasting values have attractive simplicity. One such surrogate, the homeostatic model assessment of insulin resistance (HOMA-IR), is widely applied despite known inaccuracies in characterizing resistance across groups. Of greater significance is whether HOMA-IR can detect changes in insulin sensitivity induced by an intervention. We tested the ability of HOMA-IR to detect high-fat diet–induced insulin resistance in 36 healthy canines using clamp and minimal model analysis of the intravenous glucose tolerance test (IVGTT) to document progression of resistance. The influence of pancreatic function on HOMA-IR accuracy was assessed using the acute insulin response during the IVGTT (AIRG). Diet-induced resistance was confirmed by both clamp and minimal model (P HOMA-IR ([fasting insulin (μU/mL) × fasting glucose (mmol)]/22.5) did not detect reduced sensitivity induced by fat feeding (P = 0.22). In fact, 13 of 36 animals showed an artifactual decrease in HOMA-IR (i.e., increased sensitivity). The ability of HOMA-IR to detect diet-induced resistance was particularly limited under conditions when insulin secretory function (AIRG) is less than robust. In conclusion, HOMA-IR is of limited utility for detecting diet-induced deterioration of insulin sensitivity quantified by glucose clamp or minimal model. Caution should be exercised when using HOMA-IR to detect insulin resistance when pancreatic function is compromised. It is necessary to use other accurate indices to detect longitudinal changes in insulin resistance with any confidence. PMID:24353184

  7. Fluoroquinolone resistance in the rectal carriage of men in an active surveillance cohort: longitudinal analysis.

    Science.gov (United States)

    Cohen, Jason E; Landis, Patricia; Trock, Bruce J; Patel, Hiten D; Ball, Mark W; Auwaerter, Paul G; Schaeffer, Edward; Carter, H Ballentine

    2015-02-01

    Rectal swabs can identify men with fluoroquinolone resistant bacteria and decrease the infection rate after transrectal ultrasound guided prostate biopsy by targeted antimicrobial prophylaxis. We evaluated the rate of fluoroquinolone resistance in an active surveillance cohort with attention to factors associated with resistance and changes in resistance with time. We evaluated 416 men with prostate cancer on active surveillance who underwent rectal swabs to assess the rate of fluoroquinolone resistance compared to that in men undergoing diagnostic transrectal ultrasound guided prostate biopsy. The chi-square test and Student t-test were used to compare categorical and continuous variables, respectively. Poisson regression analysis was used for multivariate analysis. On the initial swab fluoroquinolone resistance was found in 95 of 416 men (22.8%) on active surveillance compared to 54 of 221 (24.4%) in the diagnostic biopsy cohort (p = 0.675). Diabetes was found in 4.0% of the fluoroquinolone sensitive group vs 14.7% of the resistant group (p fluoroquinolone. Resistance is significantly associated with diabetes but the number of prior biopsies is not. Men with fluoroquinolone resistant flora tend to remain resistant with time. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  8. Inflammation-induced microvascular insulin resistance is an early event in diet-induced obesity

    Science.gov (United States)

    Zhao, Lina; Fu, Zhuo; Wu, Jing; Aylor, Kevin W.; Barrett, Eugene J.; Cao, Wenhong

    2015-01-01

    Endothelial dysfunction and vascular insulin resistance usually coexist and chronic inflammation engenders both. In the present study, we investigate the temporal relationship between vascular insulin resistance and metabolic insulin resistance. We assessed insulin responses in all arterial segments, including aorta, distal saphenous artery and the microvasculature, as well as the metabolic insulin responses in muscle in rats fed on a high-fat diet (HFD) for various durations ranging from 3 days to 4 weeks with or without sodium salicylate treatment. Compared with controls, HFD feeding significantly blunted insulin-mediated Akt (protein kinase B) and eNOS [endothelial nitric oxide (NO) synthase] phosphorylation in aorta in 1 week, blunted vasodilatory response in small resistance vessel in 4 weeks and microvascular recruitment in as early as 3 days. Insulin-stimulated whole body glucose disposal did not begin to progressively decrease until after 1 week. Salicylate treatment fully inhibited vascular inflammation, prevented microvascular insulin resistance and significantly improved muscle metabolic responses to insulin. We conclude that microvascular insulin resistance is an early event in diet-induced obesity and insulin resistance and inflammation plays an essential role in this process. Our data suggest microvascular insulin resistance contributes to the development of metabolic insulin resistance in muscle and muscle microvasculature is a potential therapeutic target in the prevention and treatment of diabetes and its related complications. PMID:26265791

  9. Inflammation-induced microvascular insulin resistance is an early event in diet-induced obesity.

    Science.gov (United States)

    Zhao, Lina; Fu, Zhuo; Wu, Jing; Aylor, Kevin W; Barrett, Eugene J; Cao, Wenhong; Liu, Zhenqi

    2015-12-01

    Endothelial dysfunction and vascular insulin resistance usually coexist and chronic inflammation engenders both. In the present study, we investigate the temporal relationship between vascular insulin resistance and metabolic insulin resistance. We assessed insulin responses in all arterial segments, including aorta, distal saphenous artery and the microvasculature, as well as the metabolic insulin responses in muscle in rats fed on a high-fat diet (HFD) for various durations ranging from 3 days to 4 weeks with or without sodium salicylate treatment. Compared with controls, HFD feeding significantly blunted insulin-mediated Akt (protein kinase B) and eNOS [endothelial nitric oxide (NO) synthase] phosphorylation in aorta in 1 week, blunted vasodilatory response in small resistance vessel in 4 weeks and microvascular recruitment in as early as 3 days. Insulin-stimulated whole body glucose disposal did not begin to progressively decrease until after 1 week. Salicylate treatment fully inhibited vascular inflammation, prevented microvascular insulin resistance and significantly improved muscle metabolic responses to insulin. We conclude that microvascular insulin resistance is an early event in diet-induced obesity and insulin resistance and inflammation plays an essential role in this process. Our data suggest microvascular insulin resistance contributes to the development of metabolic insulin resistance in muscle and muscle microvasculature is a potential therapeutic target in the prevention and treatment of diabetes and its related complications. © 2015 Authors; published by Portland Press Limited.

  10. Antibiotic resistance in triclosan tolerant fecal coliforms isolated from surface waters near wastewater treatment plant outflows (Morris County, NJ, USA).

    Science.gov (United States)

    Middleton, June H; Salierno, James D

    2013-02-01

    , Serratia and Citrobacter. There was no correlation between river water quality and resistance of isolates to TCS. Presence of isolates not resistant to TCS, but resistant to other antibiotics, were significantly correlated to increased river flow, precipitation, and decreased nutrient levels, suggesting that observed resistance is due to run-off events. This study demonstrates that TCS resistant FC are common in river systems receiving WWTP effluent and display multiple drug resistance. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Shading Contributes to the Reduction of Stem Mechanical Strength by Decreasing Cell Wall Synthesis in Japonica Rice (Oryza sativa L.

    Directory of Open Access Journals (Sweden)

    Longmei Wu

    2017-05-01

    Full Text Available Low solar radiation caused by industrial development and solar dimming has become a limitation in crop production in China. It is widely accepted that low solar radiation influences many aspects of plant development, including slender, weak stems and susceptibility to lodging. However, the underlying mechanisms are not well understood. To clarify how low solar radiation affects stem mechanical strength formation and lodging resistance, the japonica rice cultivars Wuyunjing23 (lodging-resistant and W3668 (lodging-susceptible were grown under field conditions with normal light (Control and shading (the incident light was reduced by 60% with a black nylon net. The yield and yield components, plant morphological characteristics, the stem mechanical strength, cell wall components, culm microstructure, gene expression correlated with cellulose and lignin biosynthesis were measured. The results showed that shading significantly reduced grain yield attributed to reduction of spikelets per panicles and grain weight. The stem-breaking strength decreased significantly under shading treatment; consequently, resulting in higher lodging index in rice plant in both varieties, as revealed by decreased by culm diameter, culm wall thickness and increased plant height, gravity center height. Compared with control, cell wall components including non-structural carbohydrate, sucrose, cellulose, and lignin reduced quite higher. With histochemical straining, shading largely reduced lignin deposition in the sclerenchyma cells and vascular bundle cells compared with control, and decreased cellulose deposition in the parenchyma cells of culm tissue in both Wuyunjing23 and W3668. And under shading condition, gene expression involved in secondary cell wall synthesis, OsPAL, OsCOMT, OsCCoAOMT, OsCCR, and OsCAD2, and primary cell wall synthesis, OsCesA1, OsCesA3, and OsCesA8 were decreased significantly. These results suggest that gene expression involved in the reduction of

  12. Piggyback resistive Micromegas

    CERN Document Server

    Attié, D; Durand, D; Desforge, D; Ferrer-Ribas, E; Galán, J; Giomataris, Y; Gongadze, A; Iguaz, F J; Jeanneau, F; de Oliveira, R; Papaevangelou, T; Peyaud, A; Teixeira, A

    2013-01-01

    Piggyback Micromegas consists in a novel readout architecture where the anode element is made of a resistive layer on a ceramic substrate. The resistive layer is deposited on the thin ceramic substrate by an industrial process which provides large dynamic range of resistivity (10$^6$ to 10$^{10}$\\,M$\\Omega$/square). The particularity of this new structure is that the active part is entirely dissociated from the read-out element. This gives a large flexibility on the design of the anode structure and the readout scheme. Without significant loss, signals are transmitted by capacitive coupling to the read-out pads. The detector provides high gas gain, good energy resolution and the resistive layer assures spark protection for the electronics. This assembly could be combined with modern pixel array electronic ASICs. First tests with different Piggyback detectors and configurations will be presented. This structure is adequate for cost effective fabrication and low outgassing detectors. It was designed to perform ...

  13. Decreased chewing activity during mouth breathing.

    Science.gov (United States)

    Hsu, H-Y; Yamaguchi, K

    2012-08-01

    This study examined the effect of mouth breathing on the strength and duration of vertical effect on the posterior teeth using related functional parameters during 3 min of gum chewing in 39 nasal breathers. A CO(2) sensor was placed over the mouth to detect expiratory airflow. When no airflow was detected from the mouth throughout the recording period, the subject was considered a nasal breather and enrolled in the study. Electromyographic (EMG) activity was recorded during 3 min of gum chewing. The protocol was repeated with the nostrils occluded. The strength of the vertical effect was obtained as integrated masseter muscle EMG activity, and the duration of vertical effect was also obtained as chewing stroke count, chewing cycle variation and EMG activity duration above baseline. Baseline activity was obtained from the isotonic EMG activity during jaw movement at 1.6 Hz without making tooth contact. The duration represented the percentage of the active period above baseline relative to the 3-min chewing period. Paired t-test and repeated analysis of variance were used to compare variables between nasal and mouth breathing. The integrated EMG activity and the duration of EMG activity above baseline, chewing stroke count and chewing cycle significantly decreased during mouth breathing compared with nasal breathing (Pbreathing was significantly greater than nasal breathing (Pbreathing reduces the vertical effect on the posterior teeth, which can affect the vertical position of posterior teeth negatively, leading to malocclusion. © 2012 Blackwell Publishing Ltd.

  14. COGNITIVE THERAPY DECREASE THE LEVEL OF DEPRESSION

    Directory of Open Access Journals (Sweden)

    Ah. Yusuf

    2017-07-01

    Full Text Available Introduction: Aging is a natural process in individuals. Most of the elderly have problems in dealing with this natural process. Lost of occupation, friends and loneliness may result in depression in this age group. Cognitive therapy changes pessimistic idea, unrealistic hopes and excessive self evaluation may result and justify depression. Cognitive therapy may help elderly to recognize the problem in life, to develop positive objective of life and to create more positive personality. The aimed of this study was to analyze the effect of cognitive therapy to reduce the level of depression. Method: This study was used a pre experimental pre post test design. Sample were 10 elderly people who met to the inclusion criteria. The independent variable was cognitive therapy and dependent variable was the level of depression in elderly. Data were collected by using Geriatric Depression Scale (GDS 15, then analyzed by using Wilcoxon Signed Rank Test with significance levelα≤0.05. Result: The result showed that cognitive therapy has an effect on reducing depression with significance level p=0.005. Discussion: It can be concluded that cognitive therapy was effective in reducing depression level in elderly. Further studies are recommended to analyze the effect of cognitive therapy on decreasing anxiety in elderly by measuring cathecolamin.

  15. Lower skin temperature decreases maximal cycling performance.

    Science.gov (United States)

    Imai, Daiki; Okazaki, Kazunobu; Matsumura, Shinya; Suzuki, Takashi; Miyazawa, Taiki; Suzuki, Akina; Takeda, Ryosuke; Hamamoto, Takeshi; Zako, Tetsuo; Kawabata, Takashi; Miyagawa, Toshiaki

    2011-12-01

    It is known that external cooling of body regions involved in exercise, prior to exercise, decreases anaerobic performance. However, there have been no studies reporting the effects of whole body skin surface cooling before exercise on maximal anaerobic capacity. In order to clarify the effects, we compared power output during the Wingate anaerobic test between preconditioning by exposure to temperature 10 degrees C and 25 degrees C. Eight healthy males carried out the Wingate test for 30 seconds, after pre-conditioning for 60 minutes using a perfusion suit with water at a temperature of 10 degrees C or 25 degrees C. We evaluated the peak power (PP) and peak power slope (PS) of the power output. Mean skin temperature (T(sk)) at 60 minutes of pre-conditioning in the 10 degrees C trial was significantly lower than in the 25 degrees C trial (p < 0.05). PP and also PS were significantly lower in the 10 degrees C trial than in the 25 degrees C trial. Changes (Δ) in PP between the 10 degrees C trial and the 25 degrees C trial were strongly correlated with ΔT(sk) and Δ in thigh and leg skin temperature (ΔT(thigh) and ΔT(leg), respectively), whereas ΔPS was strongly correlated with ΔT(sk), but not with ΔT(thigh) and ΔT(leg). Whole body skin surface cooling prior to exercise restricts anaerobic capacity, especially in the initial phase of exercise.

  16. Increasing Resistance to Extended-Spectrum Cephalosporins, Fluoroquinolone, and Carbapenem in Gram-Negative Bacilli and the Emergence of Carbapenem Non-Susceptibility in Klebsiella pneumoniae: Analysis of Korean Antimicrobial Resistance Monitoring System (KARMS) Data From 2013 to 2015.

    Science.gov (United States)

    Kim, Dokyun; Ahn, Ji Young; Lee, Chae Hoon; Jang, Sook Jin; Lee, Hyukmin; Yong, Dongeun; Jeong, Seok Hoon; Lee, Kyungwon

    2017-05-01

    National surveillance of antimicrobial resistance becomes more important for the control of antimicrobial resistance and determination of treatment guidelines. We analyzed Korean Antimicrobial Resistance Monitoring System (KARMS) data collected from 2013 to 2015. Of the KARMS participants, 16 secondary or tertiary hospitals consecutively reported antimicrobial resistance rates from 2013 to 2015. Data from duplicate isolates and institutions with fewer than 20 isolates were excluded. To determine the long-term trends, previous KARMS data from 2004 to 2012 were also considered. The prevalence of methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium from 2013 to 2015 was 66-72% and 29-31%, respectively. The resistance rates of Escherichia coli to cefotaxime and cefepime gradually increased to 35% and 31%, respectively, and fluoroquinolone resistance reached 48% in 2015. The resistance rates of Klebsiella pneumoniae to cefotaxime, cefepime, and carbapenem were 38-41%, 33-41%, and carbapenem susceptibility rates of E. coli and K. pneumoniae decreased from 100% and 99.3% in 2011 to 99.0% and 97.0% in 2015, respectively. The resistance rate of Pseudomonas aeruginosa to carbapenem increased to 35% and the prevalence of carbapenem-resistant Acinetobacter baumannii increased from 77% in 2013 to 85% in 2015. Between 2013 and 2015, the resistance rates of E. coli to third- and fourth-generation cephalosporins increased continuously, while carbapenem-susceptibility gradually decreased, particularly in K. pneumoniae. The prevalence of carbapenem-resistant P. aeruginosa and A. baumannii increased significantly; therefore, few treatment options remain for these resistant strains. © The Korean Society for Laboratory Medicine

  17. The wind resistance of asphalt roofing shingles

    Science.gov (United States)

    Dixon, Craig Robert

    Asphalt shingle roofing is the leading cause of hurricane wind-related insured losses in residential buildings. Damage statistics generated from recent hurricanes indicate shingle roofs sustain damage in wind velocities below design-level with damage frequency increasing with shingle roof age. The objective of this dissertation is the identification of primary mechanisms triggering the failure of shingle roof systems in wind. The research goal is to reduce future shingle roof wind damage and improve our ability to predict asphalt shingle wind resistance. Five studies comprising this dissertation addressed the adhesive consistency and strength of aged asphalt shingles, system-level wind resistance, and the load model underpinning the ASTM D7158 wind test standard. The most significant and unexpected finding was partially unsealed shingles on field, hip, and ridge locations on Florida and Texas homes. Location on the shingle's sealant strip where unsealed and failure mode were consistent at each location. Total quantity of partially unsealed shingles in the field of the roof significantly increased with age, aligning with damage statistics. Full-scale wind tunnel tests demonstrate partially unsealed shingles are more vulnerable than fully sealed due to increased distributed force on sealant strip and concentrated force at the adhered and non-adhered interface. Uplift resistance was measured in artificially and naturally aged shingles. For artificially aged shingles, one of three products evaluated had statistically significant decreases in mean uplift resistance as exposure time increased. However, resistance was above design-level at all exposure test intervals. Naturally aged shingles also had resistance above design-level. Combined results demonstrate that reduced uplift capacity can occur, but high initial bond strength promotes long-term uplift resistance. Wind loads exerted on the shingles sealant strip load path were directly measured on fully sealed and

  18. Cytokine-Induced Killer Cells Modulates Resistance to Cisplatin in the A549/DDP Cell Line.

    Science.gov (United States)

    Yang, Lili; Du, Chunjuan; Wu, Lei; Yu, Jinpu; An, Xiumei; Yu, Wenwen; Cao, Shui; Li, Hui; Ren, Xiubao

    2017-01-01

    Background Cytokine-induced killer (CIK) cells can potentially enhance the tumor-killing activity of chemotherapy. Objective This study aimed to evaluate the effects of CIK cells on cisplatin (DDP) resistance in the human lung adenocarcinoma cell line A549/DDP. Methods The detect resistance index, drug resistance related-genes and cytokine secretion of A549/DDP co-cultured with CIK cells were assayed in vitro . Results After A549/DDP co-culture with CIK cells, the DDP resistance of A549/DDP significantly decreased in a time-dependent manner. The DDP resistance of A549/DDP co-cultured with CIK cells for 20 h decreased 4.93-fold compared with that of A549/DDP cells cultured alone ( P A549/DDP significantly decreased after co-culture with CIK cells ( P A549/DDP with CIK cells. The expression of GST-π was restored by adding the neutralizing IFN-γ. Conclusion CIK cells can reverse the drug resistance of A549/DDP in a time-dependent manner by reducing GST-π expression to increase the accumulation of DDP. The effect of CIK cells on re-sensitizing lung cancer cells to the chemotherapy drug was partially dependent on the secretion of IFN-γ.

  19. Antimicrobial Resistance

    Science.gov (United States)

    ... life-threatening infections – to a last resort treatment (carbapenem antibiotics) has spread to all regions of the ... unit patients. In some countries, because of resistance, carbapenem antibiotics do not work in more than half ...

  20. Reduction in mRNA and protein expression of a nicotinic acetylcholine receptor α8 subunit is associated with resistance to imidacloprid in the brown planthopper, Nilaparvata lugens.

    Science.gov (United States)

    Zhang, Yixi; Wang, Xin; Yang, Baojun; Hu, Yuanyuan; Huang, Lixin; Bass, Chris; Liu, Zewen

    2015-11-01

    Target-site resistance is commonly caused by qualitative changes in insecticide target-receptors and few studies have implicated quantitative changes in insecticide targets in resistance. Here we show that resistance to imidacloprid in a selected strain of Nilaparvata lugens is associated with a reduction in expression levels of the nicotinic acetylcholine receptor (nAChR) subunit Nlα8. Synergism bioassays of the selected strain suggested resistance was conferred, in part, by a target-site mechanism. Sequencing of N. lugens nAChR subunit genes identified no mutations associated with resistance, however, a decrease in mRNA and protein levels of Nlα8 was observed during selection. RNA interference knockdown of Nlα8 decreased the sensitivity of N. lugens to imidacloprid, demonstrating that a decrease in Nlα8 expression is sufficient to confer resistance in vivo. Radioligand binding assays revealed that the affinity of the high-affinity imidacloprid-binding site of native nAChRs was reduced by selection, and reducing the amount of Nlα8 cRNA injected into Xenopus oocytes significantly decreased imidacloprid potency on recombinant receptors. Taken together, these results provide strong evidence that a decrease in Nlα8 levels confers resistance to imidacloprid in N. lugens, and thus provides a rare example of target-site resistance associated with a quantitative rather than qualitative change. In insects, target-site mutations often cause high resistance to insecticides, such as neonicotinoids acting on nicotinic acetylcholine receptors (nAChRs). Here we found that a quantitative change in target-protein level, decrease in mRNA and protein levels of Nlα8, contributed importantly to imidacloprid resistance in Nilaparvata lugens. This finding provides a new target-site mechanism of insecticide resistance. © 2015 International Society for Neurochemistry.

  1. Aerobic exercise reduces blood pressure in resistant hypertension.

    Science.gov (United States)

    Dimeo, Fernando; Pagonas, Nikolaos; Seibert, Felix; Arndt, Robert; Zidek, Walter; Westhoff, Timm H

    2012-09-01

    Regular physical exercise is broadly recommended by current European and American hypertension guidelines. It remains elusive, however, whether exercise leads to a reduction of blood pressure in resistant hypertension as well. The present randomized controlled trial examines the cardiovascular effects of aerobic exercise on resistant hypertension. Resistant hypertension was defined as a blood pressure ≥140/90 mm Hg in spite of 3 antihypertensive agents or a blood pressure controlled by ≥4 antihypertensive agents. Fifty subjects with resistant hypertension were randomly assigned to participate or not to participate in an 8- to 12-week treadmill exercise program (target lactate, 2.0±0.5 mmol/L). Blood pressure was assessed by 24-hour monitoring. Arterial compliance and cardiac index were measured by pulse wave analysis. The training program was well tolerated by all of the patients. Exercise significantly decreased systolic and diastolic daytime ambulatory blood pressure by 6±12 and 3±7 mm Hg, respectively (P=0.03 each). Regular exercise reduced blood pressure on exertion and increased physical performance as assessed by maximal oxygen uptake and lactate curves. Arterial compliance and cardiac index remained unchanged. Physical exercise is able to decrease blood pressure even in subjects with low responsiveness to medical treatment. It should be included in the therapeutic approach to resistant hypertension.

  2. Increased beta1 integrin is associated with decreased survival in invasive breast cancer.

    Science.gov (United States)

    Yao, Evelyn S; Zhang, Hui; Chen, Yunn-Yi; Lee, Brian; Chew, Karen; Moore, Dan; Park, Catherine

    2007-01-15

    Aberrant microenvironments and loss of balance in cell-extracellular matrix signaling are associated with breast cancer invasion, metastasis, and resistance to therapy. We have recently shown that increased beta1 integrin signaling is involved in malignant progression and that inhibitory antibody to beta1 integrin leads to selective apoptosis and decreased proliferation in three-dimensional cultures and in xenograft models of breast cancer in vivo. To investigate the clinical importance of these findings, in the present study we examined the expression of beta1 integrin and extracellular beta1 integrin ligands fibronectin and laminin-1 in a cohort of 249 breast cancer patients who had a median follow-up of 8.4 years. Among the 149 scorable cases, the highest beta1 integrin intensity score (3+ versus 0-2+) was associated with significantly decreased 10-year overall survival of 48% versus 71% (Pintegrin intensity score was significantly correlated with fibronectin expression (Kendall's tau-b=0.19; P=0.03). In a multivariate Cox proportional hazards model, beta1 integrin intensity score remained a significant independent predictor of overall survival [hazard ratio (HR), 1.69; 95% confidence interval (95% CI), 1.19-2.38; Pintegrin expression has potential prognostic value in invasive breast cancer and that coexpression of fibronectin may help identify patients with more aggressive tumors who may benefit from targeted therapy.

  3. Persistent amenorrhea and decreased DHEAS to cortisol ratio after recovery from anorexia nervosa.

    Science.gov (United States)

    Andrisani, Alessandra; Sabbadin, Chiara; Minardi, Silvia; Favaro, Angela; Donà, Gabriella; Bordin, Luciana; Ambrosini, Guido; Armanini, Decio

    2017-04-01

    Persistent amenorrhea is a frequent condition affecting anorexic patients after stable weight recovery. It has been proposed that it could be due to alterations of the hypothalamic-pituitary-gonadal axis linked with persistent hormonal impairments, such as relative hypercortisolemia and hypoleptinemia, and psychological symptoms related to anorexia nervosa (AN). The aim of our study was to evaluate the metabolic and hormonal pattern involved in the persistence of amenorrhea after recovery from AN. Eight weight-recovered anorexic patients with amenorrhea were investigated and matched with 10 healthy eumenorrhoic women, comparable for age and BMI. Data showed basal FSH and LH values similar in both groups and a normal pituitaric response to LHRH administration. Morning serum cortisol was normal but significantly higher in patients, while dehydroepiandrosterone sulfate (DHEAS) to cortisol ratio, leptin and vitamin D were significantly lower in patients than controls. Women with previous AN presented insulin resistance and two patients showed an overall picture consistent with polycystic ovary syndrome (PCOS). In conclusion, long-lasting amenorrhea after recovery from AN is linked with a persistent hypothalamic dysfunction, although other concomitant causes like PCOS and insulin resistance should be considered. Decreased DHEAS to cortisol ratio is a new finding which could be correlated to the persistent hypogonadism.

  4. Antibiotic Resistance in Staphylococcus aureus Strains Isolated from Clinical Specimens

    Directory of Open Access Journals (Sweden)

    M. Sirin

    2016-04-01

    Full Text Available Aim: The aim of this study was to determine the antibiotic susceptibilities of S.aureus strains isolated from various clinical specimens between the years 2011-2014 and to investigate the changes of these susceptibilities over the years. Material and Method: Identification and antibiotic susceptibility testing of the strains were performed by Vitek 2 compact automated system (bioMérieux, France. The strains found to be intermediate susceptible to vancomycin and teicoplanin were also tested by E-test method. Results: S.aureus strains (n=1442 were most commonly isolated from wound, urine and blood samples. The isolation rates of methicillin-resistant S.aureus (MRSA in hospitalized patients were significantly higher than the isolation rates of MRSA in outpatients. All strains were susceptible to vancomycin, teicoplanin, linezolid and tigecycline. The total of four years resistance rates of MRSA strains to erythromycin, clindamycin, ciprofloxacin, moxifloxacin, gentamicin, co-trimoxazole, fusidic acid were significantly higher than the resistance rates of methicillin-sensitive S.aureus (MSSA. The changes in the rates of antibiotic resistance were not statistically significant in MSSA strains over the years, and statistically significant decrease was found in erythromycin, clindamycin, ciprofloxacin, moxifloxacin and gentamicin resistance in MRSA strains. Discussion: Glycopeptides, linezolid and tigecycline were the most effective antibiotics against S.aureus strains. It was considered as necessary to detect antimicrobial resistance profiles by effective surveillance studies and monitor the changes occurred over the years in order to prevent the development of resistance and control of infections.

  5. Physiological changes with periodized resistance training in women tennis players.

    Science.gov (United States)

    Kraemer, William J; Hakkinen, Keijo; Triplett-Mcbride, N Travis; Fry, Andrew C; Koziris, L Perry; Ratamess, Nicholas A; Bauer, Jeffrey E; Volek, Jeff S; McConnell, Tim; Newton, Robert U; Gordon, Scott E; Cummings, Don; Hauth, John; Pullo, Frank; Lynch, J Michael; Fleck, Steven J; Mazzetti, Scott A; Knuttgen, Howard G

    2003-01-01

    To compare the physiological and performance adaptations between periodized and nonperiodized resistance training in women collegiate tennis athletes. Thirty women (19 +/- 1 yr) were assigned to either a periodized resistance training group (P), nonperiodized training group (NV), or a control group (C). Assessments for body composition, anaerobic power, VO2(max), speed, agility, maximal strength, jump height, tennis-service velocity, and resting serum hormonal concentrations were performed before and after 4, 6, and 9 months of resistance training performed 2-3 d.wk (-1). Nine months of resistance training resulted in significant increases in fat-free mass; anaerobic power; grip strength; jump height; one-repetition maximum (1-RM) leg press, bench press, and shoulder press; serve, forehand, and backhand ball velocities; and resting serum insulin-like growth factor-1, testosterone, and cortisol concentrations. Percent body fat and VO2(max) decreased significantly in the P and NV groups after training. During the first 6 months, periodized resistance training elicited significantly greater increases in 1-RM leg press (9 +/- 2 vs 4.5 +/- 2%), bench press (22 +/- 5 vs 11 +/- 8%), and shoulder press (24 +/- 7 vs 18 +/- 6%) than the NV group. The absolute 1-RM leg press and shoulder press values in the P group were greater than the NV group after 9 months. Periodized resistance training also resulted in significantly greater improvements in jump height (50 +/- 9 vs 37 +/- 7%) and serve (29 +/- 5 vs 16 +/- 4%), forehand (22 +/- 3 vs 17 +/- 3%), and backhand ball velocities (36 +/- 4 vs 14 +/- 4%) as compared with nonperiodized training after 9 months. These data demonstrated that periodization of resistance training over 9 months was superior for enhancing strength and motor performance in collegiate women tennis players.

  6. Type 2 Diabetes, Diabetes Genetic Score and Risk of Decreased Renal Function and Albuminuria: A Mendelian Randomization Study.

    Science.gov (United States)

    Xu, Min; Bi, Yufang; Huang, Ya; Xie, Lan; Hao, Mingli; Zhao, Zhiyun; Xu, Yu; Lu, Jieli; Chen, Yuhong; Sun, Yimin; Qi, Lu; Wang, Weiqing; Ning, Guang

    2016-04-01

    Type 2 diabetes (T2D) is a risk factor for dysregulation of glomerular filtration rate (GFR) and albuminuria. However, whether the association is causal remains unestablished. We performed a Mendelian Randomization (MR) analysis in 11,502 participants aged 40 and above, from a well-defined community in Shanghai during 2011-2013, to explore the causal association between T2D and decreased estimated GFR (eGFR) and increased urinary albumin-to-creatinine ratio (uACR). We genotyped 34 established T2D common variants in East Asians, and created a T2D-genetic risk score (GRS). We defined decreased eGFR as eGFRgenetically determined T2D and decreased eGFR (OR=1.47, 95% CI: 1.15, 1.88, P=0.0003). When grouping the genetic loci according to their relations with either insulin secretion (IS) or insulin resistance (IR), we found both IS_GRS and IR_GRS were significantly related to decreased eGFR (both P<0.02). In addition, T2D_GRS and IS_GRS were significantly associated with Log-uACR (both P=0.04). Our results provide novel evidence for a causal association between T2D and decreased eGFR by using MR approach in a Chinese population. Copyright © 2016. Published by Elsevier B.V.

  7. Physiological and biochemical characteristics of laboratory induced mutants of Botrytis cinerea with resistance to fluazinam.

    Science.gov (United States)

    Shao, Wenyong; Zhang, Yu; Ren, Weichao; Chen, Changjun

    2015-01-01

    Botrytis cinerea is a necrotrophic and filamentous fungus with a high risk of developing resistance to fungicides. The pyridinamine fungicide fluazinam has been reported to have excellent activity against B. cinerea and better effect on controlling gray mold. In this study, the physiological and biochemical characteristics of laboratory-induced mutants of B. cinerea with resistance to fluazinam has been investigated. Compared to the wild-type strains, the fluazinam-resistant mutants had a significant decrease in respiratory rate, glycerol, oxalate, and ATP contents, and an increase in ATPase activity and sensitivity to osmotic pressure, but did not differ in cell membrane permeability. Sequencing indicated that two parental strains and four resistant mutants were identical in the nucleotide sequence of F-ATPase gene. These results will enrich our understanding of the resistance mechanism of B. cinerea to fluazinam. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Trends in Decline of Antiretroviral Resistance among ARV-Experienced Patients in the HIV Outpatient Study: 1999–2008

    Directory of Open Access Journals (Sweden)

    Kate Buchacz

    2012-01-01

    Full Text Available Background. Little is known about temporal trends in frequencies of clinically relevant ARV resistance mutations in HIV strains from U.S. patients undergoing genotypic testing (GT in routine HIV care. Methods. We analyzed cumulative frequency of HIV resistance among patients in the HIV Outpatient Study (HOPS who, during 1999–2008 and while prescribed antiretrovirals, underwent GT with plasma HIV RNA >1,000 copies/mL. Exposure ≥4 months to each of three major antiretroviral classes (NRTI, NNRTI and PI was defined as triple-class exposure (TCE. Results. 906 patients contributed 1,570 GT results. The annual frequency of any major resistance mutations decreased during 1999–2008 (88% to 79%, P=0.05. Resistance to PIs decreased among PI-exposed patients (71% to 46%, P=0.010 as exposure to ritonavir-boosted PIs increased (6% to 81%, P<0.001. Non-significant declines were observed in resistance to NRTIs among NRTI-exposed (82% to 67%, and triple-class-resistance among TCE patients (66% to 41%, but not to NNRTIs among NNRTI-exposed. Conclusions. HIV resistance was common but declined in HIV isolates from subgroups of ARV-experienced HOPS patients during 1999–2008. Resistance to PIs among PI-exposed patients decreased, possibly due to increased representation of patients whose only PI exposures were to boosted PIs.

  9. Adriamycin resistance, heat resistance and radiation response in Chinese hamster fibroblasts

    International Nuclear Information System (INIS)

    Wallner, K.; Li, G.

    1985-01-01

    Previous investigators have demonstrated synergistic interaction between hyperthermia and radiation or Adriamycin (ADR), using cell lines that are sensitive to heat or ADR alone. The authors investigated the effect of heat, radiation or ADR on Chinese hamster fibroblasts (HA-1), their heat resistant variants and their ADR resistant variants. Heat for ADR resistance did not confer cross resistance to radiation. Cells resistant to heat did show cross resistance to ADR. While cells selected for ADR resistance were not cross resistant to heat, they did not exhibit drug potentiation by hyperthermia, characteristic of ADR sensitive cells. Cytofluorometric measurement showed decreased ADR uptake in both heat and ADR resistant cells. The possibility of cross resistance between heat and ADR should be considered when designing combined modality trials

  10. Early experience with tedizolid: clinical efficacy, pharmacodynamics, and resistance.

    Science.gov (United States)

    Rybak, Jeffrey M; Marx, Kayleigh; Martin, Craig A

    2014-11-01

    Antimicrobial resistance among gram-positive organisms such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) continues to limit therapeutic options. The oxazolidinones are a synthetic class of agents now commonly relied on for the treatment of serious MRSA and VRE infections. With increasing utilization of linezolid, resistant pathogens have once again begun to emerge. Tedizolid, a next-generation oxazolidinone, possesses a spectrum of activity including MRSA and VRE, with significantly enhanced potency also against linezolid-resistant strains. Preclinical and early clinical studies have reported positive results, demonstrating a favorable pharmacokinetic profile in combination with key potential safety advantages. In two phase III clinical trials, tedizolid was found noninferior to linezolid in the treatment of acute bacterial skin and skin structure infections. Investigations for treatment of ventilator-acquired and health care-associated pneumonia are currently underway. Tedizolid has been subjected to pharmacodynamics studies throughout its development that have highlighted properties unique to this agent. Considerable accumulations in epithelial lining fluid and antimicrobial activity greatly augmented by the presence of granulocytes suggest that slow but bactericidal activity may be possible in some clinical scenarios. Structural distinctions between tedizolid and linezolid suggest that tedizolid has decreased vulnerability to oxazolidinone resistance mechanisms. Tedizolid minimum inhibitory concentrations are essentially unchanged in organisms possessing the chloramphenicol-florfenicol resistance gene, a horizontally transferable linezolid resistance mechanism. Although the clinical experience with tedizolid remains limited, early data suggest a potential role in the treatment of serious infections due to multidrug-resistant gram-positive pathogens. © 2014 Pharmacotherapy Publications, Inc.

  11. Sand resistance of sunscreens.

    Science.gov (United States)

    Caswell, Michael; Wood, Caryl; Martinez, Alexa

    2012-01-01

    Like water resistance in sunscreens, sand resistance in sunscreens is the ability of the sunscreen to retain its effectiveness while undergoing sand treatment. The influence of the type of sand on the sand resistance of sunscreens has not been described. The sand resistance of a control standard sunscreen, P2, and data on three grades of Quickrete commercial grade sand, #1961, #1962, and #1152, are described. These sands represent a fine sand, a medium sand, and an all-purpose sand. Using the methodology described in the 2007 proposed amendment of the Final Monograph (1) with one exception, we obtained an SPF of 16.5 (1.6) for the control standard, compared to the expected SPF of 16.3 (3.4). After a five-minute treatment of sand #1961, #1962, or #1151, the SPF of the control standard was 18.3 (1.6), 18.4 (2.0), and 17.5 (2.2), respectively. Thus, all three sands exhibited a similar sand-resistance response. Thus, there was no significant difference in the average SPF with and without sand. The medium grade sand, Quickrete commercial grade #1962, was preferred for sand-resistance testing because the fine sand was difficult to remove from the subject's backs and the coarse sand was unpleasant to the subjects.

  12. On statistical significance of signal

    International Nuclear Information System (INIS)

    Zhu Yongsheng

    2006-01-01

    A definition for the statistical significance of a signal in an experiment is proposed by establishing a correlation between the observed p-value and the normal distribution integral probability, which is suitable for both counting experiment and continuous test statistics. The explicit expressions to calculate the statistical significance for both cases are given. (author)

  13. Adriamycin resistance and radiation response

    International Nuclear Information System (INIS)

    Belli, J.A.; Harris, J.R.

    1979-01-01

    Mammalian cells (V79) in culture developed resistance to Adriamycin during continuous exposure to low levels of drug. This resistance was accompanied by change in x-ray survival properties which, in turn, depended upon the isolation of subpopulations from resistant sub lines. These changes in x-ray survival properties were characterized by reduced D/sub Q/ values and a decrease in the D/sub O/. However, these changes were not observed together in the same cell sub line. Adriamycin-resistant cells did not appear to be radiation damage repair deficient. Other phenotypic changes (cell morphology, DNA content and chromosome number) suggested mutational events coincident with the development of Adriamycin resistance

  14. Antimicrobial resistance trends among Escherichia coli isolates obtained from dairy cattle in the northeastern United States, 2004-2011.

    Science.gov (United States)

    Cummings, Kevin J; Aprea, Victor A; Altier, Craig

    2014-01-01

    Monitoring antimicrobial resistance trends among bacteria isolated from food animals and people is necessary to inform risk analyses and guide public policy regarding antimicrobial use. Our objectives were to describe the antimicrobial resistance status of Escherichia coli isolates from dairy cattle in the northeastern United States and to identify trends in resistance to selected antimicrobial agents over time. We collected data retrospectively for all bovine E. coli isolates that were obtained from samples submitted to Cornell University's Animal Health Diagnostic Center between January 1, 2004 and December 31, 2011. We investigated temporal trends in the prevalence of resistant E. coli for each antimicrobial agent using the Cochran-Armitage trend test. Antimicrobial susceptibility testing was performed on 3373 bovine E. coli isolates from clinical samples submitted during the study period. Overall resistance to each antimicrobial agent ranged from 2.7% (enrofloxacin) to 91.3% (oxytetracycline). There was evidence of a significantly decreasing trend in prevalence of resistance to several agents: chlortetracycline, florfenicol, neomycin, oxytetracycline, spectinomycin, and trimethoprim/sulfamethoxazole. However, a significantly increasing trend in prevalence of resistance to enrofloxacin was also evident. These results do not support the idea that current antimicrobial use practices on dairy operations are driving a general increase in the emergence and dissemination of drug-resistant E. coli in the region served by the laboratory. However, resistance to some drugs remained consistently high during the study period, and increasing resistance to enrofloxacin is a key area of concern.

  15. OBESITY-RELATED CARDIOVASCULAR RISK FACTORS AFTER LONG- TERM RESISTANCE TRAINING AND GINGER SUPPLEMENTATION

    Directory of Open Access Journals (Sweden)

    Sirvan Atashak

    2011-12-01

    Full Text Available Obesity and its metabolic consequences are major risk factors for cardiovascular morbidity and mortality. However, lifestyle interventions, including exercise training and dietary components may decrease cardiovascular risk. Hence, this study was conducted to assess the effects of ginger supplementation and progressive resistance training on some cardiovascular risk factors in obese men. In a randomized double-blind design, 32 obese Iranian men (BMI > 30 were assigned in to one of four groups: Placebo (PL, n = 8; ginger group (GI, n = 8 that consumed 1 gr ginger/d for 10 wk; resistance training plus placebo (RTPL, n = 8; and 1gr ginger plus resistance exercise (RTGI, n = 8. Progressive resistance training was performed three days per week for 10 weeks and included eight exercises. At baseline and after 10 weeks, body composition and anthropometric indices were measured. To identify other risk factors, venous blood samples were obtained before and 48-72 hours after the last training session for measurement of blood lipids (LDL-C, HDL-C, TG, systemic inflammation (CRP, and insulin resistance (HOMA-IR. After 10 weeks both RTGI and RTPL groups showed significant decreases in waist circumference (WC, waist-to-hip ratio (WHR, body fat percent, body fat mass, total cholesterol, and insulin resistance (p < 0.05 and a significant increase in fat free mass (FFM (p < 0.05, while it remained unchanged in PL and GI. Further, significant decreases in the mean values of CRP were observed in all groups except PL (p < 0.05. Our results reveal that resistance training is an effective therapeutic strategy to reduce cardiovascular risk in obese Iranian men. Further, ginger supplementation alone or in combination with resistance training, also reduces chronic inflammation. However more research on the efficacy of this supplement to reduce cardiovascular risk in humans is required.

  16. Predator decline leads to decreased stability in a coastal fish community.

    Science.gov (United States)

    Britten, Gregory L; Dowd, Michael; Minto, Cóilín; Ferretti, Francesco; Boero, Ferdinando; Lotze, Heike K

    2014-12-01

    Fisheries exploitation has caused widespread declines in marine predators. Theory predicts that predator depletion will destabilise lower trophic levels, making natural communities more vulnerable to environmental perturbations. However, empirical evidence has been limited. Using a community matrix model, we empirically assessed trends in the stability of a multispecies coastal fish community over the course of predator depletion. Three indices of community stability (resistance, resilience and reactivity) revealed significantly decreasing stability concurrent with declining predator abundance. The trophically downgraded community exhibited weaker top-down control, leading to predator-release processes in lower trophic levels and increased susceptibility to perturbation. At the community level, our results suggest that high predator abundance acts as a stabilising force to the naturally stochastic and highly autocorrelated dynamics in low trophic species. These findings have important implications for the conservation and management of predators in marine ecosystems and provide empirical support for the theory of predatory control. © 2014 John Wiley & Sons Ltd/CNRS.

  17. Efflux system overexpression and decreased OprD contribute to the carbapenem heterogeneity in Pseudomonas aeruginosa.

    Science.gov (United States)

    Ikonomidis, Alexandros; Tsakris, Athanassios; Kantzanou, Maria; Spanakis, Nicholas; Maniatis, Antonios N; Pournaras, Spyros

    2008-02-01

    Pseudomonas aeruginosa strains exhibiting a heterogeneous mode of growth against carbapenems have been described recently. This study investigated the underlying molecular mechanisms in four genetically unrelated P. aeruginosa clinical isolates that were previously characterized by population analyses as heterogeneously resistant against carbapenems. Mutant subpopulations of all four isolates had at least fourfold higher minimum inhibitory concentrations than those of native cells for imipenem and meropenem. The heterogeneous subpopulations, when compared with the respective native ones, had significantly increased transcription levels of the mexB and mexY genes (Pefflux systems, in part, and the decrease of OprD contribute to the heterogeneous growth against carbapenems in our P. aeruginosa clinical isolates.

  18. Role of sialic acid in insulin action and the insulin resistance of diabetes mellitus

    International Nuclear Information System (INIS)

    Salhanick, A.I.; Amatruda, J.M.

    1988-01-01

    Adipocytes treated with neuraminidase show markedly reduced responsiveness to insulin without any alteration in insulin binding. In addition, several studies have separately demonstrated both insulin resistance and decreases in membrane sialic acid content and associated biosynthetic enzymes in diabetes mellitus. In the present study, the authors investigated the role that sialic acid residues may play in insulin action and in the hepatic insulin resistance associated with nonketotic diabetes. Primary cultures of hepatocytes from normal rats treated with neuraminidase demonstrated a dose-dependent decrease in insulin-stimulated lipogenesis. At a concentration of neuraminidase that decreases insulin action by 50%, 23% of total cellular sialic acid content was released. Neuraminidase-releasable sialic acid was significantly decreased in hepatocytes from diabetic rats and this was associated with significant insulin resistance. Treatment of hepatocytes from diabetic rats with cytidine 5'-monophospho-N-acetylneuraminic acid (CMP-NANA) enhanced insulin responsiveness 39%. The enhanced insulin responsiveness induced by CMP-NANA was blocked by cytidine 5'-monophosphate (CMP) suggesting that the CMP-NANA effect was catalyzed by a cell surface sialyl-transferase. CMP reduced neuraminidase-releasable [ 14 C]sialic acid incorporation into hepatocytes by 43%. The data demonstrate a role for cell surface sialic acid residues in hepatic insulin action and support a role for decreased cell surface sialic acid residues in the insulin resistance of diabetes mellitus

  19. Fluoxetine treatment for major depression decreases the plasma ...

    African Journals Online (AJOL)

    The levels of all five cytokine of patients with MDD were significantly decreased after treatment. However, the levels remained significantly higher than those of the healthy controls (p<0.001). In the seven depressed subjects whose HDRS score fell to below seven after antidepressant therapy comparing with those subjects ...

  20. Thyroidectomy decreases snoring and sleep apnea symptoms.

    Science.gov (United States)

    Reiher, Alexandra E; Mazeh, Haggi; Schaefer, Sarah; Chen, Herbert; Sippel, Rebecca S

    2012-11-01

    Patients with goiter often complain of compressive symptoms, which may contribute to symptoms of obstructive sleep apnea (OSA). However, the impact of thyroid enlargement on these symptoms is not clear. Therefore, we sought to evaluate whether symptoms of sleep apnea resolved after thyroidectomy by using a validated questionnaire. The Berlin Questionnaire, a validated sleep apnea assessment tool, was provided to patients at a single academic institution before and after thyroidectomy. Patients who admitted to symptoms of snoring were asked to complete the questionnaire before and 8 weeks after surgery to assess for improvement in symptoms. The questionnaire uses 3 categories of questions to determine risk of sleep apnea. Two symptom categories must be positive for a patient to be considered high risk for sleep apnea. Forty-five patients completed both pre- and postoperative questionnaires. The average age of patients completing the questionnaire was 53±2 years, and 78% of patients were female. Average body mass index was 33.3±1.4 kg/m(2). Based on their preoperative questionnaire score, 71% of patients were considered to be high risk for OSA, and this decreased to 51% after surgery (p=0.002). Overall scores significantly improved after surgery (mean 2.0 vs. 1.6, psymptoms, gland weight at resection, presence of thyroiditis, or the largest dimension of the gland at resection. Thyroid surgery appears to significantly improve symptoms of OSA in patients who screened positive for symptoms before surgery. Evaluation of patients with OSA should include evaluation of thyroid disease, as symptoms of sleep apnea may improve with thyroidectomy.

  1. Effects of cosmic ray decreases on cloud microphysics

    DEFF Research Database (Denmark)

    Svensmark, J.; Enghoff, M. B.; Svensmark, H.

    2012-01-01

    the minimum in atmospheric ionization and less significant responses for effective radius and cloud condensation nuclei (equations for atmospheric parameters. Furthermore principal components analysis gives a total significance......Using cloud data from MODIS we investigate the response of cloud microphysics to sudden decreases in galactic cosmic radiation – Forbush decreases – and find responses in effective emissivity, cloud fraction, liquid water content, and optical thickness above the 2–3 sigma level 6–9 days after...... ionization. These results support the suggestion that ions play a significant role in the life-cycle of clouds....

  2. Hyper-arousal decreases human visual thresholds.

    Directory of Open Access Journals (Sweden)

    Adam J Woods

    Full Text Available Arousal has long been known to influence behavior and serves as an underlying component of cognition and consciousness. However, the consequences of hyper-arousal for visual perception remain unclear. The present study evaluates the impact of hyper-arousal on two aspects of visual sensitivity: visual stereoacuity and contrast thresholds. Sixty-eight participants participated in two experiments. Thirty-four participants were randomly divided into two groups in each experiment: Arousal Stimulation or Sham Control. The Arousal Stimulation group underwent a 50-second cold pressor stimulation (immersing the foot in 0-2° C water, a technique known to increase arousal. In contrast, the Sham Control group immersed their foot in room temperature water. Stereoacuity thresholds (Experiment 1 and contrast thresholds (Experiment 2 were measured before and after stimulation. The Arousal Stimulation groups demonstrated significantly lower stereoacuity and contrast thresholds following cold pressor stimulation, whereas the Sham Control groups showed no difference in thresholds. These results provide the first evidence that hyper-arousal from sensory stimulation can lower visual thresholds. Hyper-arousal's ability to decrease visual thresholds has important implications for survival, sports, and everyday life.

  3. Resident resistance.

    Science.gov (United States)

    Price, J L; Cleary, B

    1999-01-01

    Clearly, faculty must work hard with residents to explore the nature of their resistance to a program's learning and growth opportunities. Initial steps to a deeper, more effective, and longer-lasting change process must be pursued. If resident resistance is mishandled or misunderstood, then learning and professional growth may be sidetracked and the purposes of residency training defeated. Listening to the whole person of the resident and avoiding the trap of getting caught up in merely responding to select resident behaviors that irritate us is critical. Every faculty member in the family practice residency program must recognize resistance as a form of defense that cannot immediately be torn down or taken away. Resident defenses have important purposes to play in stress reduction even if they are not always healthy. Residents, especially interns, use resistance to avoid a deeper and more truthful look at themselves as physicians. A family practice residency program that sees whole persons in their residents and that respects resident defenses will effectively manage the stress and disharmony inherent to the resistant resident.

  4. Resistance Mechanisms in an In Vitro-Selected Amoxicillin-Resistant Strain of Helicobacter pylori▿

    OpenAIRE

    Co, Edgie-Mark A.; Schiller, Neal L.

    2006-01-01

    We investigated the β-lactam resistance mechanism(s) of an in vitro-selected amoxicillin-resistant Helicobacter pylori strain (AmoxR). Our results demonstrated that resistance is due to a combination of amino acid substitutions in penicillin binding protein 1 (PBP1), HopB, and HopC identified in AmoxR, resulting in decreased affinity of PBP1 for amoxicillin and decreased accumulation of penicillin.

  5. Markov Networks of Collateral Resistance: National Antimicrobial Resistance Monitoring System Surveillance Results from Escherichia coli Isolates, 2004-2012.

    Directory of Open Access Journals (Sweden)

    William J Love

    2016-11-01

    Full Text Available Surveillance of antimicrobial resistance (AMR is an important component of public health. Antimicrobial drug use generates selective pressure that may lead to resistance against to the administered drug, and may also select for collateral resistances to other drugs. Analysis of AMR surveillance data has focused on resistance to individual drugs but joint distributions of resistance in bacterial populations are infrequently analyzed and reported. New methods are needed to characterize and communicate joint resistance distributions. Markov networks are a class of graphical models that define connections, or edges, between pairs of variables with non-zero partial correlations and are used here to describe AMR resistance relationships. The graphical least absolute shrinkage and selection operator is used to estimate sparse Markov networks from AMR surveillance data. The method is demonstrated using a subset of Escherichia coli isolates collected by the National Antimicrobial Resistance Monitoring System between 2004 and 2012 which included AMR results for 16 drugs from 14418 isolates. Of the 119 possible unique edges, 33 unique edges were identified at least once during the study period and graphical density ranged from 16.2% to 24.8%. Two frequent dense subgraphs were noted, one containing the five β-lactam drugs and the other containing both sulfonamides, three aminoglycosides, and tetracycline. Density did not appear to change over time (p = 0.71. Unweighted modularity did not appear to change over time (p = 0.18, but a significant decreasing trend was noted in the modularity of the weighted networks (p < 0.005 indicating relationships between drugs of different classes tended to increase in strength and frequency over time compared to relationships between drugs of the same class. The current method provides a novel method to study the joint resistance distribution, but additional work is required to unite the underlying biological and genetic

  6. Chemotherapy decreases epiphyseal strength and increases bone fracture risk.

    Science.gov (United States)

    Van Leeuwen, Barbara L; Verkerke, Gerard J; Hartel, Rene M; Sluiter, Willem J; Kamps, Willem A; Jansen, Henk W B; Hoekstra, Harald J

    2003-08-01

    To establish the effect of three frequently used chemotherapeutic agents in childhood cancer on the skeleton, growing male Wistar rats were studied. Treatment with doxorubicin, methotrexate, and cisplatin reduces the proximal tibial growth plate shear strength because of a decreased surface area and maximum shear stress. After treatment the bone fracture risk of the tibia and femur is increased because of decreased bending resistance. Doxorubicin and cisplatin reduce the maximum shear stress of the proximal tibial growth plate, none of the chemotherapeutic agents inhibit bone mineralization. These effects are caused by treatment-induced malnutrition and the accompanying weight reduction and a direct effect of the chemotherapeutic agents on the skeleton. The current study confirmed the importance of preventing malnutrition during chemotherapeutic treatment in view of possible skeletal complications. During followup of children treated with chemotherapy, attention should be given to signs and symptoms suggestive of such complications.

  7. Arterial wave reflection decreases gradually from supine to upright

    DEFF Research Database (Denmark)

    van den Bogaard, Bas; Westerhof, Berend E; Best, Hendrik

    2011-01-01

    BACKGROUND. An increase in total peripheral resistance (TPR) usually increases arterial wave reflection. During passive head-up tilt (HUT), however, arterial wave reflection decreases with increasing TPR. This study addressed whether arterial wave reflection gradually decreases during HUT. METHODS....... In 10 healthy volunteers (22-39 years, nine males), we recorded finger arterial pressures in supine position (0°), and 30°and 70°degrees HUT and active standing (90°). Aortic pressure was constructed from the finger pressure signal and hemodynamics were calculated. Arterial wave reflection...... from 0.9 dyn s/cm(5) at 0? to 1.2, 1.4 and 1.4 dyn s/cm(5) at 30°, 70° and 90° (p wave reflection...

  8. MULTI-DRUG RESISTANCE PATTERNS OF ENTERIC BACTERIA IN TWO POPULATIONS OF FREE-RANGING EASTERN BOX TURTLES (TERRAPENE CAROLINA CAROLINA).

    Science.gov (United States)

    Rasmussen, Cari; Allender, Matthew C; Phillips, Christopher A; Byrd, John; Lloyd, Terrell; Maddox, Carol

    2017-09-01

    Gram-negative isolates (n = 84) from 71% of free-ranging Eastern box turtles (Terrapene carolina carolina) in Illinois and Tennessee, United States, demonstrated resistance to at least one antibiotic while 30% of isolates demonstrated resistance to two or more antibiotics. Resistance was observed against cefoxitin, amoxicillin-clavulanic acid, cefazolin, ampicillin, ticarcillin, cefovecin, and ceftiofur. Gram-positive bacteria were isolated from 49 turtles, and all were observed to be resistant to two or more antibiotics. Gram-positive isolate resistance was observed to penicillin, cefoxitin, oxacillin, clindamycin, amikacin, enrofloxacin, cefovecin, ceftiofur, cefazolin, marbofloxacin, gentamicin, erythromycin, trimethoprim-sulfamethoxazole, and chloramphenicol. Health parameters including packed cell volume, total white blood cell count (WBC), total solids (TS), and weight were not significantly different based on antibiotic resistance patterns; however, decreasing WBC and TS were observed when the number of antibiotic-resistant detections in Gram-positive bacteria increased.

  9. Antibiotics resistance of Helicobacter pylori in children with upper gastrointestinal symptoms in Hangzhou, China.

    Science.gov (United States)

    Shu, Xiaoli; Yin, Guofeng; Liu, Mingnan; Peng, Kerong; Zhao, Hong; Jiang, Mizu

    2018-03-12

    The decreasing eradication rate of Helicobacter pylori is mainly because of the progressive increase in its resistance to antibiotics. Studies on antimicrobial susceptibility of H. pylori in children are limited. This study aimed to investigate the resistance rates and patterns of H. pylori strains isolated from children. Gastric mucosa biopsy samples obtained from children who had undergone upper gastrointestinal endoscopy were cultured for H. pylori, and susceptibility to six antibiotics (clarithromycin, amoxicillin, gentamicin, furazolidone, metronidazole, and levofloxacin) was tested from 2012-2014. A total of 545 H. pylori strains were isolated from 1390 children recruited. The total resistance rates of H. pylori to clarithromycin, metronidazole, and levofloxacin were 20.6%, 68.8%, and 9.0%, respectively. No resistance to amoxicillin, gentamicin, and furazolidone was detected. 56.1% strains were single resistance, 19.6% were resistant to more than one antibiotic, 16.7% for double resistance, and 2.9% for triple resistance in 413 strains against any antibiotic. And the H. pylori resistance rate increased significantly from 2012-2014. There was no significant difference in the resistance rates to clarithromycin, metronidazole, and levofloxacin between different gender, age groups, and patients with peptic ulcer diseases or nonulcer diseases. Antibiotic resistance was indicated in H. pylori strains isolated from children in Hangzhou, and it increased significantly during the 3 years. Our data strongly support current guidelines, which recommend antibiotic susceptibility tests prior to eradication therapy. © 2018 John Wiley & Sons Ltd.

  10. The RESET Mindset Model applied on decreasing antibiotic usage in dairy cattle in the Netherlands.

    Science.gov (United States)

    Lam, T J G M; Jansen, J; Wessels, R J

    2017-01-01

    Prudent use of antibiotics is important to prevent antibiotic resistance in humans and in animals. For this reason politicians demanded a decrease of total antibiotic use and of use of critically important antibiotics in animal husbandry in the Netherlands. In the dairy sector the use of antibiotics almost halved in the years 2009-2015, with a decrease of the use of critically important antibiotics to very low levels. To realize a sustainable decrease in antibiotic usage, the mindset towards the subject was considered crucial. Based on several models from social psychology, the RESET Mindset Model was used. This model contains the most important cues to change human behaviour, being Rules and regulations, Education and information, Social pressure, Economics, and Tools. To change behaviour of groups in order to reach a tipping point, it is of utmost importance to not choose among the different cues, but to use them all. In order to decrease antibiotic usage in dairy cattle in the Netherlands several actions, obliged as well as voluntary, were undertaken. An independent veterinary medicine authority was founded that became active for all animal sectors. In the dairy sector a national database on antibiotic usage called MediRund was developed, which made transparency and benchmarking on antibiotic usage at the national and the herd level possible. Several other activities are described, such as herd health and treatment plans, selective dry cow therapy, and the strong limitation on the use of critically important antibiotics. Antibiotic usage at the herd level, referred to as the 'antibiotic number', became an important and socially accepted herd level parameter. The actions undertaken worked through different cues, all part of the RESET Mindset Model. As such, different types of dairy farmers sensitive to different types of cues were motivated to change their behaviour. Antibiotic usage in dairy cattle in the Netherlands decreased significantly by intense

  11. The RESET Mindset Model applied on decreasing antibiotic usage in dairy cattle in the Netherlands

    OpenAIRE

    Lam, T. J. G. M.; Wessels, R. J.; Jansen, Jolanda

    2017-01-01

    BACKGROUND: Prudent use of antibiotics is important to prevent antibiotic resistance in humans and in animals. For this reason politicians demanded a decrease of total antibiotic use and of use of critically important antibiotics in animal husbandry in the Netherlands. In the dairy sector the use of antibiotics almost halved in the years 2009-2015, with a decrease of the use of critically important antibiotics to very low levels. THEORY OF BEHAVIOUR CHANGE: To realize a sustainable decrease i...

  12. Historical Significant Volcanic Eruption Locations

    Data.gov (United States)

    Department of Homeland Security — A significant eruption is classified as one that meets at least one of the following criteriacaused fatalities, caused moderate damage (approximately $1 million or...

  13. Anticoagulant Resistance

    DEFF Research Database (Denmark)

    Heiberg, Ann-Charlotte

    Although sewer rat control is carried out in more than 80 % of all Danish municipalities, with usage of large amounts of anticoagulant rodenticides, knowledge on anticoagulant resistance among rats living in the sewers is limited. As rat problems in urban areas are believed to be related to sewer...... problems (70-90 % in UK and DK) unawareness of resistance amongst these populations of Brown rats may constitute a future control problem and knowledge on this issue has become crucial. Rats were captured in sewers from seven different locations in the suburban area of Copenhagen. Locations was chosen...... to represent different sewer rat management strategies i) no anticoagulants for approx. 20 years ii) no anticoagulants for the last 5 years and iii) continuous control for many years. Animals were tested for resistance to bromadiolone by Blood-Clotting Response test, as bromadiolone is the most frequently used...

  14. Reducing Resistance

    DEFF Research Database (Denmark)

    Lindell, Johanna

    care may influence decisions on antibiotic use. Based on video-and audio recordings of physician-patient consultations it is investigated how treatment recommendations are presented, can be changed, are forecast and explained, and finally, how they seemingly meet resistance and how this resistance......Antibiotic resistance is a growing public health problem both nationally and internationally, and efficient strategies are needed to reduce unnecessary use. This dissertation presents four research studies, which examine how communication between general practitioners and patients in Danish primary...... is responded to.The first study in the dissertation suggests that treatment recommendations on antibiotics are often done in a way that encourages patient acceptance. In extension of this, the second study of the dissertation examines a case, where acceptance of such a recommendation is changed into a shared...

  15. Antibiotic misuse in the community--a contributor to resistance?

    LENUS (Irish Health Repository)

    Carey, B

    2012-02-03

    The problem of antibiotic resistance is associated with the indiscriminate usage of antibiotics. Efforts have been directed at encouraging the rational use of these drugs to reduce the volume of antibiotic consumption and decrease resistance rates. There is evidence to suggest that the misuse of antibiotics by patients may also contribute to the problem. We describe a survey of a random selection of patients attending a General Practitioners\\' surgery over a six week period in an effort to estimate the level of non-compliance to antibiotic therapy in the community. The results suggest that there may be a significant level of antibiotic misuse prevalent in the local community. We discuss these results and present evidence in the literature suggesting how antibiotic misuse may affect resistance in the community. The factors affecting patient compliance to therapy are outlined along with suggested measures to improve compliance among patients.

  16. Increasing incidence of resistance to antimicrobials in Sidamo.

    Science.gov (United States)

    Belihu, A; Lindtjorn, B

    1999-07-01

    This study compares the prevailing sensitivity of bacterial isolates to common antimicrobials during the two-year 1985-87, 1990-92 and 1996-97 periods at Yirga Alem Hospital in southern Ethiopia. All specimens were from patients attending the hospital. We studied 1371 specimens, 337,671 and 363 specimens from the periods 1985-87, 1990-92 and 1996-97, respectively. The study confirms earlier observations of widespread resistance to commonly used antibiotics. Significant increases in the rate of resistance during this thirteen-year period were observed for Neisseria gonorrhoea against erythromycin, trimethoprim-sulphamethoxazole and tetracyclines, for Escherichia coli against ampicillin and trimethoprim-sulphamethoxazole and for Proteus species against ampicillin. We observed a decrease in the prevalence of resistance for Klebsiella and Proteus species against chloramphenicol.

  17. Analysis of IRS-1-mediated phosphatidylinositol 3-kinase activation in the adipose tissue of polycystic ovary syndrome patients complicated with insulin resistance

    International Nuclear Information System (INIS)

    Chu Yongli; Qiu Hongyu; Sun Yongyu; Li Min; Li Hongfa

    2004-01-01

    Objective: To investigate the insulin receptor substance-1 (IRS-1)-mediated phosphatidylinositol-3 (PI-3) kinase activity in adipose tissue of polycystic ovary syndrome (PCOS) patients, and to explore molecular mechanisms of insulin resistance of PCOS. Methods: Blood and adipose tissue samples from patients with PCOS with insulin resistance (n=19), PCOS without insulin resistance (n=10) and controls (n=15) were collected. Serum luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone (T) were measured by chemiluminescence assay. Fasting insulin (FIN) was measured by radioimmunoassay. Fasting plasma glucose (FPG) was measured by oxidase assay. Insulin resistance index (IR) was calculated using homeostasis model assessment (HOMA) to analyze the relationship between these markers and insulin resistance. The tyrosine phosphorylation of IRS-1 was measured by immunoprecipitation and enhanced chemiluminescent immunoblotting technique. PI-3 kinase activity was detected by immunoprecipitation, thin-layer chromatography and gamma scintillation counting. The results were analyzed by statistical methods. Results: 1) The levels of serum LH, LH/FSH, T, FIN and HOMA-IR in PCOS without insulin resistance were significantly higher than those of control group (all P<0.05); the levels of serum LH, LH/FSH, T, FIN and HOMA-IR in PCOS with insulin resistance were significantly higher than those of PCOS without insulin resistance (all P<0.05). 2) The tyrosine phosphorylation analysis of IRS-1 showed that IRS-1 tyrosine phosphorylation was significantly decreased in PCOS with insulin resistance compared to that of PCOS without insulin resistance and control groups (P<0.01). 3) PI-3 kinase activity was significantly decreased (P<0.01) and negatively correlated with HOMA-IR. Conclusion: In consequence of the weaker signal caused by the change of upper stream signal molecule IRS-1 tyrosine phosphorylation, PI-3 kinase activity decreased, it affects the insulin signal

  18. Monoamine oxidase A (MAO A) inhibitors decrease glioma progression

    Science.gov (United States)

    Vaikari, Vijaya Pooja; Kota, Rajesh; Chen, Kevin; Yeh, Tzu-Shao; Jhaveri, Niyati; Groshen, Susan L.; Olenyuk, Bogdan Z.; Chen, Thomas C.; Hofman, Florence M.; Shih, Jean C.

    2016-01-01

    Glioblastoma (GBM) is an aggressive brain tumor which is currently treated with temozolomide (TMZ). Tumors usually become resistant to TMZ and recur; no effective therapy is then available. Monoamine Oxidase A (MAO A) oxidizes monoamine neurotransmitters resulting in reactive oxygen species which cause cancer. This study shows that MAO A expression is increased in human glioma tissues and cell lines. MAO A inhibitors, clorgyline or the near-infrared-dye MHI-148 conjugated to clorgyline (NMI), were cytotoxic for glioma and decreased invasion in vitro. Using the intracranial TMZ-resistant glioma model, clorgyline or NMI alone or in combination with low-dose TMZ reduced tumor growth and increased animal survival. NMI was localized specifically to the tumor. Immunocytochemistry studies showed that the MAO A inhibitor reduced proliferation, microvessel density and invasion, and increased macrophage infiltration. In conclusion, we have identified MAO A inhibitors as potential novel stand-alone drugs or as combination therapy with low dose TMZ for drug-resistant gliomas. NMI can also be used as a non-invasive imaging tool. Thus has a dual function for both therapy and diagnosis. PMID:26871599

  19. Stability and fitness of anilinopyrimidine-resistant strains of Botrytis cinerea.

    Science.gov (United States)

    Bardas, G A; Myresiotis, C K; Karaoglanidis, G S

    2008-04-01

    frequency decreased significantly after five culture or disease cycles, while in the remaining two pairs resistance frequency increased significantly after five disease cycles or remained stable for one pair after five culture cycles on artificial nutrient media.

  20. Effects of meson mass decrease on superfluiding in nuclear matter

    Energy Technology Data Exchange (ETDEWEB)

    Tanigawa, T. [Kyushu Univ., Faculty of Science, Fukuoka (Japan); Matsuzaki, M.

    1999-08-01

    {sup 1}S{sub 0} pairing in nuclear matter is investigated by taking the hadron mass decrease into account via the 'In-Medium Bonn potential' which was recently proposed by Rapp et al. The resulting gap is significantly reduced in comparison with the one obtained with the original Bonn-B potential and we ascertain that the meson mass decrease is mainly responsible for this reduction. (author)

  1. Decreasing mislabeled laboratory specimens using barcode technology and bedside printers.

    Science.gov (United States)

    Brown, Judy E; Smith, Nancy; Sherfy, Beth R

    2011-01-01

    Mislabeling of laboratory samples has been found to be a high-risk issue in acute care hospitals. The goal of this study was to decrease mislabeled blood specimens. In the first year after the implementation of a positive patient identification system using barcoding and computer technology, the number of labeling errors decreased from 103 to 8 per year. The outcome was clinically and statistically significant (P < .001).

  2. The effects of tertiary wastewater treatment on the prevalence of antimicrobial resistant bacteria

    DEFF Research Database (Denmark)

    Guardabassi, L.; Wong, Danilo Lo Fo; Dalsgaard, A.

    2002-01-01

    and anaerobically digested sludge by bacteriological counts on media selective for coliforms (MacConkey agar) and Acinetobacter spp. (Baumann agar). In addition, the level of antimicrobial susceptibility was determined by the disc-diffusion method in 442 Acinetobacter isolates identified by colony hybridisation......-resistant presumptive coliforms and Acinetobacter spp. in treated sewage and digested sludge were not significantly higher compared with raw sewage. On the contrary at one plant, statistically significant decreases were observed in the prevalence of ampicillin-resistant presumptive Acinetobacter spp. (p = 0.......0188) following sewage treatment, and in the prevalence of either ampicillin-resistant presumptive Acinetobacter spp. (p = 0.0013) or ampicillin- and gentamicin-resistant presumptive coliforms (p = 0.0273 and p = 0.0186) following sludge treatment. The results obtained by bacteriological counts were confirmed...

  3. Antimicrobial resistance programs in canada 1995-2010: a critical evaluation

    Directory of Open Access Journals (Sweden)

    Conly John M

    2012-02-01

    Full Text Available Abstract Background In Canada, systematic efforts for controlling antibiotic resistance began in 1997 following a national Consensus Conference. The Canadian strategy produced 27 recommendations, one of which was the formation of the Canadian Committee on Antibiotic Resistance (CCAR. In addition several other organizations began working on a national or provincial basis over the ensuing years on one or more of the 3 identified core areas of the strategy. Critical evaluation of the major programs within Canada which focused on antimicrobial resistance and the identified core components has not been previously conducted. Findings Data was collected from multiple sources to determine the components of four major AMR programs that were considered national based on their scope or in the delivery of their mandates. Assessment of program components was adapted from the report from the International Forum on Antibiotic Resistance colloquium. Most of the programs used similar tools but only the Do Bugs Need Drugs Program (DBND had components directed towards day cares and schools. Surveillance programs for antimicrobial resistant pathogens have limitations and/or significant sources of bias. Overall, there has been a 25.3% decrease in oral antimicrobial prescriptions in Canada since 1995, mainly due to decreases in β lactams, sulphonamides and tetracyclines in temporal association with multiple programs with the most comprehensive and sustained national programs being CCAR and DBND. Conclusions Although there has been a substantial decrease in oral antimicrobial prescriptions in Canada since 1995, there remains a lack of leadership and co-ordination of antimicrobial resistance activities.

  4. Whole-body vibration augments resistance training effects on body composition in postmenopausal women.

    Science.gov (United States)

    Fjeldstad, Cecilie; Palmer, Ian J; Bemben, Michael G; Bemben, Debra A

    2009-05-20

    Age-related changes in body composition are well-documented with a decrease in lean body mass and a redistribution of body fat generally observed. Resistance training alone has been shown to have positive effects on body composition, however, these benefits may be enhanced by the addition of a vibration stimulus. The purpose of this study was to determine the effects of 8 months of resistance training with and without whole-body vibration (WBV) on body composition in sedentary postmenopausal women. Fifty-five women were assigned to resistance only (RG, n=22), vibration plus resistance (VR, n=21) or non-exercising control (CG, n=12) groups. Resistance training (3 sets 10 repetitions 80% strength) was performed using isotonic weight training equipment and whole-body vibration was done with the use of the power plate (Northbrooke, IL) vibration platform for three times per week for 8 months. Total and regional body composition was assessed from the total body DXA scans at baseline (pre) and after 8 months (post) of training. In the VR group, total % body fat decreased from pre- to post-time points (pbody fat (ptraining groups exhibited significant increases in bone free lean tissue mass for the total body, arm and trunk regions from pre to post (ptraining alone and with whole-body vibration resulted in positive body composition changes by increasing lean tissue. However, only the combination of resistance training and whole-body vibration was effective for decreasing percent body fat.

  5. Mastery Learning and the Decreasing Variability Hypothesis.

    Science.gov (United States)

    Livingston, Jennifer A.; Gentile, J. Ronald

    1996-01-01

    This report results from studies that tested two variations of Bloom's decreasing variability hypothesis using performance on successive units of achievement in four graduate classrooms that used mastery learning procedures. Data do not support the decreasing variability hypothesis; rather, they show no change over time. (SM)

  6. Significance evaluation in factor graphs

    DEFF Research Database (Denmark)

    Madsen, Tobias; Hobolth, Asger; Jensen, Jens Ledet

    2017-01-01

    in genomics and the multiple-testing issues accompanying them, accurate significance evaluation is of great importance. We here address the problem of evaluating statistical significance of observations from factor graph models. Results Two novel numerical approximations for evaluation of statistical...... significance are presented. First a method using importance sampling. Second a saddlepoint approximation based method. We develop algorithms to efficiently compute the approximations and compare them to naive sampling and the normal approximation. The individual merits of the methods are analysed both from....... Conclusions The applicability of saddlepoint approximation and importance sampling is demonstrated on known models in the factor graph framework. Using the two methods we can substantially improve computational cost without compromising accuracy. This contribution allows analyses of large datasets...

  7. Whey protein supplementation during resistance training augments lean body mass.

    Science.gov (United States)

    Volek, Jeff S; Volk, Brittanie M; Gómez, Ana L; Kunces, Laura J; Kupchak, Brian R; Freidenreich, Daniel J; Aristizabal, Juan C; Saenz, Catherine; Dunn-Lewis, Courtenay; Ballard, Kevin D; Quann, Erin E; Kawiecki, Diana L; Flanagan, Shawn D; Comstock, Brett A; Fragala, Maren S; Earp, Jacob E; Fernandez, Maria L; Bruno, Richard S; Ptolemy, Adam S; Kellogg, Mark D; Maresh, Carl M; Kraemer, William J

    2013-01-01

    Compared to soy, whey protein is higher in leucine, absorbed quicker and results in a more pronounced increase in muscle protein synthesis. To determine whether supplementation with whey promotes greater increases in muscle mass compared to soy or carbohydrate, we randomized non-resistance-trained men and women into groups who consumed daily isocaloric supplements containing carbohydrate (carb; n = 22), whey protein (whey; n = 19), or soy protein (soy; n = 22). All subjects completed a supervised, whole-body periodized resistance training program consisting of 96 workouts (~9 months). Body composition was determined at baseline and after 3, 6, and 9 months. Plasma amino acid responses to resistance exercise followed by supplement ingestion were determined at baseline and 9 months. Daily protein intake (including the supplement) for carb, whey, and soy was 1.1, 1.4, and 1.4 g·kg body mass⁻¹, respectively. Lean body mass gains were significantly (p mass decreased slightly but there were no differences between groups. Fasting concentrations of leucine were significantly elevated (20%) and postexercise plasma leucine increased more than 2-fold in whey. Fasting leucine concentrations were positively correlated with lean body mass responses. Despite consuming similar calories and protein during resistance training, daily supplementation with whey was more effective than soy protein or isocaloric carbohydrate control treatment conditions in promoting gains in lean body mass. These results highlight the importance of protein quality as an important determinant of lean body mass responses to resistance training.

  8. Relationship between insulin resistance and plasma endothelin in hypertension patients

    International Nuclear Information System (INIS)

    Duan Yongqiang; Wang Zuobing; Yu Hui; Cao Wei; Wang Jing; Li Xiaoqin

    2011-01-01

    To explore the relationship between plasma endothelin and hypertension insulin resistance, and the improvement of insulin resistance in hypertension patients treated with captopril and l-amlodipine, 25 patients with primary hypertension and impaired glucose tolerance were selected and treated by captopril and l-amlodipine. Systolic pressure, diastolic pressure, fasting blood glucose, insulin and insulin antibody were measured before and after treatment and compared with healthy controls. The results showed that the plasma ET-1 level in hypertension group was significantly higher than that of healthy controls (P<0.01), and he plasma ET-1 level was positively correlated with FPG, FINS, Anti-INS, HOMA-IR. The systolic pressure, diastolic pressure, fasting blood glucose, insulin, insulin antibody and insulin resistance index in hypertension patients were decreased significantly after treatment (P<0.05). There is a good correlation between endothelin and insulin resistance index in hypertension patients. Captopril and l-amlodipine had obvious improvement effect on insulin resistance in hypertension patients. (authors)

  9. Abundances of tetracycline, sulphonamide and beta-lactam antibiotic resistance genes in conventional wastewater treatment plants (WWTPs) with different waste load

    DEFF Research Database (Denmark)

    Laht, Mailis; Karkman, Antti; Voolaid, Veiko

    2014-01-01

    abundances with 16S rRNA gene abundances while assessing if the respective genes increased or decreased during treatment. ARGs were detected in most samples; sul1, sul2, and tetM were detected in all samples. Statistically significant differences (adjusted peffluent were......Antibiotics and antibiotic resistant bacteria enter wastewater treatment plants (WWTPs), an environment where resistance genes can potentially spread and exchange between microbes. Several antibiotic resistance genes (ARGs) were quantified using qPCR in three WWTPs of decreasing capacity located...... detected in only four cases. Effluent values for blaoxa-58 and tetC decreased in the two larger plants while tetM decreased in the medium-sized plant. Only blashv-34 increased in the effluent from the medium-sized plant. In all other cases the purification process caused no significant change...

  10. Resistance welding

    DEFF Research Database (Denmark)

    Bay, Niels; Zhang, Wenqi; Rasmussen, Mogens H.

    2003-01-01

    Resistance welding comprises not only the well known spot welding process but also more complex projection welding operations, where excessive plastic deformation of the weld point may occur. This enables the production of complex geometries and material combinations, which are often not possible...

  11. Drug resistance

    NARCIS (Netherlands)

    Gorter, J.A.; Potschka, H.; Noebels, J.L.; Avoli, M.; Rogawski, M.A.; Olsen, R.W.; Delgado-Escueta, A.V.

    2012-01-01

    Drug resistance remains to be one of the major challenges in epilepsy therapy. Identification of factors that contribute to therapeutic failure is crucial for future development of novel therapeutic strategies for difficult-to-treat epilepsies. Several clinical studies have shown that high seizure

  12. Anesthesia with propofol induces insulin resistance systemically in skeletal and cardiac muscles and liver of rats

    Energy Technology Data Exchange (ETDEWEB)

    Yasuda, Yoshikazu; Fukushima, Yuji; Kaneki, Masao [Department of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Shriners Hospitals for Children, Harvard Medical School, Boston, MA 02114 (United States); Martyn, J.A. Jeevendra, E-mail: jmartyn@partners.org [Department of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Shriners Hospitals for Children, Harvard Medical School, Boston, MA 02114 (United States)

    2013-02-01

    Highlights: ► Propofol, as a model anesthetic drug, induced whole body insulin resistance. ► Propofol anesthesia decreased glucose infusion rate to maintain euglycemia. ► Propofol decreased insulin-mediated glucose uptake in skeletal and cardiac muscles. ► Propofol increased hepatic glucose output confirming hepatic insulin resistance. -- Abstract: Hyperglycemia together with hepatic and muscle insulin resistance are common features in critically ill patients, and these changes are associated with enhanced inflammatory response, increased susceptibility to infection, muscle wasting, and worsened prognosis. Tight blood glucose control by intensive insulin treatment may reduce the morbidity and mortality in intensive care units. Although some anesthetics have been shown to cause insulin resistance, it remains unknown how and in which tissues insulin resistance is induced by anesthetics. Moreover, the effects of propofol, a clinically relevant intravenous anesthetic, also used in the intensive care unit for sedation, on insulin sensitivity have not yet been investigated. Euglycemic hyperinsulinemic clamp study was performed in rats anesthetized with propofol and conscious unrestrained rats. To evaluate glucose uptake in tissues and hepatic glucose output [{sup 3}H]glucose and 2-deoxy[{sup 14}C]glucose were infused during the clamp study. Anesthesia with propofol induced a marked whole-body insulin resistance compared with conscious rats, as reflected by significantly decreased glucose infusion rate to maintain euglycemia. Insulin-stimulated tissue glucose uptake was decreased in skeletal muscle and heart, and hepatic glucose output was increased in propofol anesthetized rats. Anesthesia with propofol induces systemic insulin resistance along with decreases in insulin-stimulated glucose uptake in skeletal and heart muscle and attenuation of the insulin-mediated suppression of hepatic glucose output in rats.

  13. Anesthesia with propofol induces insulin resistance systemically in skeletal and cardiac muscles and liver of rats

    International Nuclear Information System (INIS)

    Yasuda, Yoshikazu; Fukushima, Yuji; Kaneki, Masao; Martyn, J.A. Jeevendra

    2013-01-01

    Highlights: ► Propofol, as a model anesthetic drug, induced whole body insulin