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Sample records for diminish bacterial clearance

  1. Autophagic clearance of bacterial pathogens: molecular recognition of intracellular microorganisms.

    Science.gov (United States)

    Pareja, Maria Eugenia Mansilla; Colombo, Maria I

    2013-01-01

    Autophagy is involved in several physiological and pathological processes. One of the key roles of the autophagic pathway is to participate in the first line of defense against the invasion of pathogens, as part of the innate immune response. Targeting of intracellular bacteria by the autophagic machinery, either in the cytoplasm or within vacuolar compartments, helps to control bacterial proliferation in the host cell, controlling also the spreading of the infection. In this review we will describe the means used by diverse bacterial pathogens to survive intracellularly and how they are recognized by the autophagic molecular machinery, as well as the mechanisms used to avoid autophagic clearance.

  2. DJ-1/PARK7 Impairs Bacterial Clearance in Sepsis.

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    Amatullah, Hajera; Shan, Yuexin; Beauchamp, Brittany L; Gali, Patricia L; Gupta, Sahil; Maron-Gutierrez, Tatiana; Speck, Edwin R; Fox-Robichaud, Alison E; Tsang, Jennifer L Y; Mei, Shirley H J; Mak, Tak W; Rocco, Patricia R M; Semple, John W; Zhang, Haibo; Hu, Pingzhao; Marshall, John C; Stewart, Duncan J; Harper, Mary-Ellen; Liaw, Patricia C; Liles, W Conrad; Dos Santos, Claudia C

    2017-04-01

    Effective and rapid bacterial clearance is a fundamental determinant of outcomes in sepsis. DJ-1 is a well-established reactive oxygen species (ROS) scavenger. Because cellular ROS status is pivotal to inflammation and bacterial killing, we determined the role of DJ-1 in bacterial sepsis. We used cell and murine models with gain- and loss-of-function experiments, plasma, and cells from patients with sepsis. Stimulation of bone marrow-derived macrophages (BMMs) with endotoxin resulted in increased DJ-1 mRNA and protein expression. Cellular and mitochondrial ROS was increased in DJ-1-deficient ( -/- ) BMMs compared with wild-type. In a clinically relevant model of polymicrobial sepsis (cecal ligation and puncture), DJ-1 -/- mice had improved survival and bacterial clearance. DJ-1 -/- macrophages exhibited enhanced phagocytosis and bactericidal activity in vitro, and adoptive transfer of DJ-1 -/- bone marrow-derived mononuclear cells rescued wild-type mice from cecal ligation and puncture-induced mortality. In stimulated BMMs, DJ-1 inhibited ROS production by binding to p47 phox , a critical component of the NADPH oxidase complex, disrupting the complex and facilitating Nox2 (gp91 phox ) ubiquitination and degradation. Knocking down DJ-1 (siRNA) in THP-1 (human monocytic cell line) and polymorphonuclear cells from patients with sepsis enhanced bacterial killing and respiratory burst. DJ-1 protein levels were elevated in plasma from patients with sepsis. Higher levels of circulating DJ-1 were associated with increased organ failure and death. These novel findings reveal DJ-1 impairs optimal ROS production for bacterial killing with important implications for host survival in sepsis.

  3. Bacterial clearance after total splenectomy and splenic autotransplantation in rats

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    Marques, R.G. E-mail: rmarques@uerj.br; Petroianu, Andy; Oliveira, M.B.N. de; Bernardo-Filho, M.; Boasquevisque, E.M.; Portela, M.C

    2002-12-01

    Wistar rats submitted to isolated total splenectomy or total splenectomy combined with splenic autotransplantation were inoculated with {sup 99m}technetium-labeled Escherichia coli. Measurement of isotope uptake in the organs of the mononuclear phagocytic system showed a greater bacterial bloodstream clearance in rats with splenic autotransplantation. Although uptake of bacteria in the spleen was higher in the control group, the number of bacteria remaining in the bloodstream did not differ between groups. These results indicate that splenic autotransplantation preserves the phagocytic function of the spleen.

  4. Diminished ICAM-1 Expression and Impaired Pulmonary Clearance of Nontypeable Haemophilus influenzae in a Mouse Model of Chronic Obstructive Pulmonary Disease/Emphysema▿

    OpenAIRE

    Pang, Bing; Hong, Wenzhou; West-Barnette, Shayla L.; Kock, Nancy D.; Swords, W. Edward

    2008-01-01

    The airways of patients with chronic obstructive pulmonary disease (COPD) are continually colonized with bacterial opportunists like nontypeable Haemophilus influenzae (NTHi), and a wealth of evidence indicates that changes in bacterial populations within the lung can influence the severity of COPD. In this study, we used a murine model for COPD/emphysema to test the hypothesis that COPD affects pulmonary clearance. Mice were treated with a pulmonary bolus of elastase, and as reported previou...

  5. Chronic Liver Disease Impairs Bacterial Clearance in a Human Model of Induced Bacteremia

    OpenAIRE

    Ashare, Alix; Stanford, Clark; Hancock, Patricia; Stark, Donna; Lilli, Kathleen; Birrer, Emily; Nymon, Amanda; Doerschug, Kevin C.; Hunninghake, Gary W

    2009-01-01

    Sepsis often causes impaired hepatic function. Patients with liver disease have an increased risk of bacteremia. This is thought to be secondary to impaired reticuloendothelial system function. However, this has not been demonstrated clinically. Since transient bacteremia occurs following toothbrushing, we hypothesized that subjects with cirrhosis would have impaired bacterial clearance following toothbrushing compared with subjects with pulmonary disease and healthy controls. After baseline ...

  6. Bacterial clearance of biologic grafts used in hernia repair: an experimental study.

    Science.gov (United States)

    Harth, K C; Broome, A-M; Jacobs, M R; Blatnik, J A; Zeinali, F; Bajaksouzian, S; Rosen, M J

    2011-07-01

    Biologic grafts used in ventral hernia repair are derived from various sources and undergo different post-tissue-harvesting processing, handling, and sterilization techniques. It is unclear how these various characteristics impact graft response in the setting of contamination. We evaluated four materials in an infected hernia repair animal model using fluorescence imaging and quantitative culture studies. One hundred seven rats underwent creation of a chronic hernia. They were then repaired with one synthetic polyester control material (n = 12) and four different biologic grafts (n = 24 per material). Biologic grafts evaluated included Surgisis (porcine small intestinal submucosa), Permacol (crosslinked porcine dermis), Xenmatrix (noncrosslinked porcine dermis), and Strattice (noncrosslinked porcine dermis). Half of the repairs in each group were inoculated with Staphylococcus aureus at 10(4) CFU/ml and survived for 30 days without systemic antibiotics. Animals then underwent fluorescence imaging and quantitative bacterial studies. All clean repairs remained sterile. Rates of bacterial clearance were as follows: polyester synthetic 0%, Surgisis 58%, Permacol 67%, Xenmatrix 75%, and Strattice 92% (P=0.003). Quantitative bacterial counts had a similar trend in bacterial clearance: polyester synthetic 1×10(6) CFU/g, Surgisis 4.3×10(5) CFU/g, Permacol 1.7×10(3) CFU/g, Xenmatrix 46 CFU/g, and Strattice 31 CFU/g (P=0.001). Fluorescence imaging was unable to detect low bacterial fluorescence counts observed on bacterial studies. Biologic grafts, in comparison to synthetic material, are able to clear a Staphylococcus aureus contamination; however, they are able to do so at different rates. Bacterial clearance correlated to the level of residual bacterial burden observed in our study. Post-tissue-harvesting processing, handling, and sterilization techniques may contribute to this observed difference in ability to clear bacteria.

  7. Bacterial clearance of biologic grafts used in hernia repair: an experimental study

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    Harth, K. C.; Broome, A.-M.; Jacobs, M. R.; Blatnik, J. A.; Zeinali, F.; Bajaksouzian, S.

    2011-01-01

    Background Biologic grafts used in ventral hernia repair are derived from various sources and undergo different post-tissue-harvesting processing, handling, and sterilization techniques. It is unclear how these various characteristics impact graft response in the setting of contamination. We evaluated four materials in an infected hernia repair animal model using fluorescence imaging and quantitative culture studies. Methods One hundred seven rats underwent creation of a chronic hernia. They were then repaired with one synthetic polyester control material (n = 12) and four different biologic grafts (n = 24 per material). Biologic grafts evaluated included Surgisis (porcine small intestinal submucosa), Permacol (crosslinked porcine dermis), Xenmatrix (noncrosslinked porcine dermis), and Strattice (noncrosslinked porcine dermis). Half of the repairs in each group were inoculated with Staphylococcus aureus at 104 CFU/ml and survived for 30 days without systemic antibiotics. Animals then underwent fluorescence imaging and quantitative bacterial studies. Results All clean repairs remained sterile. Rates of bacterial clearance were as follows: polyester synthetic 0%, Surgisis 58%, Permacol 67%, Xenmatrix 75%, and Strattice 92% (P = 0.003). Quantitative bacterial counts had a similar trend in bacterial clearance: polyester synthetic 1 × 106 CFU/g, Surgisis 4.3 × 105 CFU/g, Permacol 1.7 × 103 CFU/g, Xenmatrix 46 CFU/g, and Strattice 31 CFU/g (P = 0.001). Fluorescence imaging was unable to detect low bacterial fluorescence counts observed on bacterial studies. Conclusion Biologic grafts, in comparison to synthetic material, are able to clear a Staphylococcus aureus contamination; however, they are able to do so at different rates. Bacterial clearance correlated to the level of residual bacterial burden observed in our study. Post-tissue-harvesting processing, handling, and sterilization techniques may contribute to this observed difference in ability to clear bacteria

  8. Importance of bacterial replication and alveolar macrophage-independent clearance mechanisms during early lung infection with Streptococcus pneumoniae.

    Science.gov (United States)

    Camberlein, Emilie; Cohen, Jonathan M; José, Ricardo; Hyams, Catherine J; Callard, Robin; Chimalapati, Suneeta; Yuste, Jose; Edwards, Lindsey A; Marshall, Helina; van Rooijen, Nico; Noursadeghi, Mahdad; Brown, Jeremy S

    2015-03-01

    Although the importance of alveolar macrophages for host immunity during early Streptococcus pneumoniae lung infection is well established, the contribution and relative importance of other innate immunity mechanisms and of bacterial factors are less clear. We have used a murine model of S. pneumoniae early lung infection with wild-type, unencapsulated, and para-amino benzoic acid auxotroph mutant TIGR4 strains to assess the effects of inoculum size, bacterial replication, capsule, and alveolar macrophage-dependent and -independent clearance mechanisms on bacterial persistence within the lungs. Alveolar macrophage-dependent and -independent (calculated indirectly) clearance half-lives and bacterial replication doubling times were estimated using a mathematical model. In this model, after infection with a high-dose inoculum of encapsulated S. pneumoniae, alveolar macrophage-independent clearance mechanisms were dominant, with a clearance half-life of 24 min compared to 135 min for alveolar macrophage-dependent clearance. In addition, after a high-dose inoculum, successful lung infection required rapid bacterial replication, with an estimated S. pneumoniae doubling time of 16 min. The capsule had wide effects on early lung clearance mechanisms, with reduced half-lives of 14 min for alveolar macrophage-independent and 31 min for alveolar macrophage-dependent clearance of unencapsulated bacteria. In contrast, with a lower-dose inoculum, the bacterial doubling time increased to 56 min and the S. pneumoniae alveolar macrophage-dependent clearance half-life improved to 42 min and was largely unaffected by the capsule. These data demonstrate the large effects of bacterial factors (inoculum size, the capsule, and rapid replication) and alveolar macrophage-independent clearance mechanisms during early lung infection with S. pneumoniae. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  9. Diminished ICAM-1 expression and impaired pulmonary clearance of nontypeable Haemophilus influenzae in a mouse model of chronic obstructive pulmonary disease/emphysema.

    Science.gov (United States)

    Pang, Bing; Hong, Wenzhou; West-Barnette, Shayla L; Kock, Nancy D; Swords, W Edward

    2008-11-01

    The airways of patients with chronic obstructive pulmonary disease (COPD) are continually colonized with bacterial opportunists like nontypeable Haemophilus influenzae (NTHi), and a wealth of evidence indicates that changes in bacterial populations within the lung can influence the severity of COPD. In this study, we used a murine model for COPD/emphysema to test the hypothesis that COPD affects pulmonary clearance. Mice were treated with a pulmonary bolus of elastase, and as reported previously, the lungs of these mice were pathologically similar to those with COPD/emphysema at approximately 1 month posttreatment. Pulmonary clearance of NTHi was significantly impaired in elastase-treated versus mock-treated mice. While histopathologic analysis revealed minimal differences in localized lung inflammation between the two groups, lower levels of intercellular adhesion molecule 1 (ICAM-1) were observed for the airway epithelial surface of elastase-treated mice than for those of control mice. Following infection, elastase-treated mice had lung pathology consistent with pneumonia for as long as 72 h postinfection, whereas at the same time point, mock-treated mice had cleared NTHi and showed little apparent pathology. Large aggregates of bacteria were observed within damaged lung tissue of the elastase-treated mice, whereas sparse individual bacteria were observed in lungs of mock-treated mice at the same time point postinfection. Additional infection studies showed that NTHi mutants with biofilm defects were less persistent in the elastase-treated mice than the parent strain. These findings establish a model for COPD-related infections and support the hypotheses that ICAM-1 promotes clearance of NTHi. Furthermore, the data indicate that NTHi may form biofilms within the context of COPD-related infections.

  10. Hyperglycemia Impairs Neutrophil-Mediated Bacterial Clearance in Mice Infected with the Lyme Disease Pathogen.

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    Ashkan Javid

    Full Text Available Insulin-insufficient type 1 diabetes is associated with attenuated bactericidal function of neutrophils, which are key mediators of innate immune responses to microbes as well as pathological inflammatory processes. Neutrophils are central to immune responses to the Lyme pathogen Borrelia burgdorferi. The effect of hyperglycemia on host susceptibility to and outcomes of B. burgdorferi infection has not been examined. The present study investigated the impact of sustained obesity-independent hyperglycemia in mice on bacterial clearance, inflammatory pathology and neutrophil responses to B. burgdorferi. Hyperglycemia was associated with reduced arthritis incidence but more widespread tissue colonization and reduced clearance of bacterial DNA in multiple tissues including brain, heart, liver, lung and knee joint. B. burgdorferi uptake and killing were impaired in neutrophils isolated from hyperglycemic mice. Thus, attenuated neutrophil function in insulin-insufficient hyperglycemia was associated with reduced B. burgdorferi clearance in target organs. These data suggest that investigating the effects of comorbid conditions such as diabetes on outcomes of B. burgdorferi infections in humans may be warranted.

  11. The effects of pneumoperitoneum and controlled ventilation on peritoneal lymphatic bacterial clearance: experimental results in rats

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    Armando Angelo Casaroli

    2011-01-01

    Full Text Available OBJECTIVE: To evaluate the effect of pneumoperitoneum, both alone and in combination with controlled ventilation, on peritoneal lymphatic bacterial clearance using a rat bacterial peritonitis model. METHOD: A total of 69 male Wistar rats were intraperitoneally inoculated with an Escherichia coli solution (109 colony-forming units (cfu/mL and divided into three groups of 23 animals each: A (control group, B (pneumoperitoneum under 5 mmHg of constant pressure, and C (endotracheal intubation, controlled ventilation, and pneumoperitoneum as in Group B. The animals were sacrificed after 30 min under these conditions, and blood, mediastinal ganglia, lungs, peritoneum, liver, and spleen cultures were performed. RESULTS: Statistical analyses comparing the number of cfu/sample in each of the cultures showed that no differences existed between the three groups. CONCLUSION: Based on our results, we concluded that pneumoperitoneum, either alone or in association with mechanical ventilation, did not modify the bacterial clearance through the diaphragmatic lymphatic system of the peritoneal cavity.

  12. Porphyromonas gingivalis manipulates complement and TLR signaling to uncouple bacterial clearance from inflammation and promote dysbiosis

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    Maekawa, Tomoki; Krauss, Jennifer L.; Abe, Toshiharu; Jotwani, Ravi; Triantafilou, Martha; Triantafilou, Kathy; Hashim, Ahmed; Hoch, Shifra; Curtis, Michael A.; Nussbaum, Gabriel; Lambris, John D.; Hajishengallis, George

    2014-01-01

    SUMMARY Certain low-abundance bacterial species, such as the periodontitis-associated oral bacterium Porphyromonas gingivalis can subvert host immunity to remodel a normally symbiotic microbiota into a dysbiotic, disease-provoking state. However, such pathogens also exploit inflammation to thrive in dysbiotic conditions. How these bacteria evade immunity while maintaining inflammation is unclear. As previously reported, P. gingivalis remodels the oral microbiota into a dysbiotic state by exploiting complement. Now we show that in neutrophils P. gingivalis disarms a host-protective TLR2-MyD88 pathway via proteasomal degradation of MyD88, whereas it activates an alternate TLR2-Mal-PI3K pathway. This alternate TLR2-Mal-PI3K pathway blocks phagocytosis, provides ‘bystander’ protection to otherwise susceptible bacteria, and promotes dysbiotic inflammation in vivo. This mechanism to disengage bacterial clearance from inflammation required an intimate crosstalk between TLR2 and the complement receptor C5aR, and can contribute to the persistence of microbial communities that drive dysbiotic diseases. PMID:24922578

  13. Survival, bacterial clearance and thrombocytopenia are improved in polymicrobial sepsis by targeting nuclear transport shuttles.

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    Ruth Ann Veach

    Full Text Available The rising tide of sepsis, a leading cause of death in the US and globally, is not adequately controlled by current antimicrobial therapies and supportive measures, thereby requiring new adjunctive treatments. Severe microvascular injury and multiple organ failure in sepsis are attributed to a "genomic storm" resulting from changes in microbial and host genomes encoding virulence factors and endogenous inflammatory mediators, respectively. This storm is mediated by stress-responsive transcription factors that are ferried to the nucleus by nuclear transport shuttles importins/karyopherins. We studied the impact of simultaneously targeting two of these shuttles, importin alpha 5 (Imp α5 and importin beta 1 (Imp β1, with a cell-penetrating Nuclear Transport Modifier (NTM in a mouse model of polymicrobial sepsis. NTM reduced nuclear import of stress-responsive transcription factors nuclear factor kappa B, signal transducer and activator of transcription 1 alpha, and activator protein 1 in liver, which was also protected from sepsis-associated metabolic changes. Strikingly, NTM without antimicrobial therapy improved bacterial clearance in blood, spleen, and lungs, wherein a 700-fold reduction in bacterial burden was achieved while production of proinflammatory cytokines and chemokines in blood plasma was suppressed. Furthermore, NTM significantly improved thrombocytopenia, a prominent sign of microvascular injury in sepsis, inhibited neutrophil infiltration in the liver, decreased L-selectin, and normalized plasma levels of E-selectin and P-selectin, indicating reduced microvascular injury. Importantly, NTM combined with antimicrobial therapy extended the median time to death from 42 to 83 hours and increased survival from 30% to 55% (p = 0.022 as compared to antimicrobial therapy alone. This study documents the fundamental role of nuclear signaling mediated by Imp α5 and Imp β1 in the mechanism of polymicrobial sepsis and highlights the

  14. Modulation of immune signaling, bacterial clearance, and corneal integrity by toll-like receptors during streptococcus pneumoniae keratitis.

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    Tullos, Nathan A; Thompson, Hilary W; Taylor, Sidney D; Sanders, Melissa; Norcross, Erin W; Tolo, Isaiah; Moore, Quincy; Marquart, Mary E

    2013-10-01

    Bacterial keratitis, without effective antimicrobial treatment, leads to poor patient prognosis. Even after bacterial clearance, the host inflammatory response can contribute to corneal damage. Though Streptococcus pneumoniae (pneumococcus) is a common cause of bacterial keratitis, the role of host innate immunity during pneumococcal keratitis is not well characterized. This study investigated the role of Toll-like receptors (TLRs) during pneumococcal keratitis. C57BL/6, as well as TLR2(-/-) and TLR4(-/-) mice, were infected with S. pneumoniae, and infected corneas were examined for 21 days. Quantitative real-time reverse-transcriptase polymerase chain reaction was performed using primers for genes involved in the inflammatory response and TLR signaling. Bacterial survival and leukocyte invasion were examined over a 72-h period. The corneal expression of TLR2, TLR4, and other inflammatory genes was increased at 72 h post-infection (p.i.) compared to uninfected C57BL/6 scratch controls. TLR2(-/-) mice showed a significant increase in bacterial survival at 24 h p.i. likely due to decreased neutrophil infiltration; however, after Day 5 p.i. observed clinical scores of TLR2(-/-) and C57BL/6 mice were not significantly different. In contrast, permanent corneal damage was observed for TLR4(-/-) mice over 21 days. Initially, both TLR(-/-) mouse strains exhibited lower expression levels in many immune genes, but returned to similar or elevated levels compared to C57BL/6 mice by 72 h p.i. TLR2 and TLR4 are involved in the response to pneumococcal keratitis and TLR2 may aid in bacterial clearance by recruitment of neutrophils to the cornea, whereas TLR4 may be necessary to modulate the immune response to limit cellular damage.

  15. Bacterial clearance is improved in septic mice by platelet-activating factor-acetylhydrolase (PAF-AH administration.

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    Mariana G A Teixeira-da-Cunha

    Full Text Available Current evidence indicates that dysregulation of the host inflammatory response to infectious agents is central to the mortality of patients with sepsis. Strategies to block inflammatory mediators such as PAF have been investigated as adjuvant therapies for sepsis. PAF-AH, the enzyme responsible for PAF degradation, showed positive results in pre-clinical studies and phase II clinical trials, but the results of a phase III study were disappointing. In this study, we investigated the potential protective mechanism of PAF-AH in sepsis using the murine model of cecal ligation and puncture (CLP. Treatment with rPAF-AH increased peritoneal fluid levels of the anti-inflammatory mediators MCP-1/CCL2 after CLP. The numbers of bacteria (CFU in the peritoneal cavity were decreased in the rPAF-AH-treated group, indicating more efficient bacterial clearance after rPAF-AH treatment. Interestingly, we observed increased levels of nitric oxide (NO after PAF-AH administration, and rPAF-AH treatment did not decrease CFU numbers either in iNOS-deficient mice or in CCR2-deficient mice. We concluded that administration of exogenous rPAF-AH reduced inflammatory injury, altered cytokine levels and favored bacterial clearance with a clear impact on mortality through modulation of MCP-1/CCL2 and NO levels in a clinically relevant sepsis model.

  16. Bacterial clearance is improved in septic mice by platelet-activating factor-acetylhydrolase (PAF-AH) administration.

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    Teixeira-da-Cunha, Mariana G A; Gomes, Rachel N; Roehrs, Nathassia; Bozza, Fernando A; Prescott, Stephen M; Stafforini, Diana; Zimmerman, Guy A; Bozza, Patricia T; Castro-Faria-Neto, Hugo C

    2013-01-01

    Current evidence indicates that dysregulation of the host inflammatory response to infectious agents is central to the mortality of patients with sepsis. Strategies to block inflammatory mediators such as PAF have been investigated as adjuvant therapies for sepsis. PAF-AH, the enzyme responsible for PAF degradation, showed positive results in pre-clinical studies and phase II clinical trials, but the results of a phase III study were disappointing. In this study, we investigated the potential protective mechanism of PAF-AH in sepsis using the murine model of cecal ligation and puncture (CLP). Treatment with rPAF-AH increased peritoneal fluid levels of the anti-inflammatory mediators MCP-1/CCL2 after CLP. The numbers of bacteria (CFU) in the peritoneal cavity were decreased in the rPAF-AH-treated group, indicating more efficient bacterial clearance after rPAF-AH treatment. Interestingly, we observed increased levels of nitric oxide (NO) after PAF-AH administration, and rPAF-AH treatment did not decrease CFU numbers either in iNOS-deficient mice or in CCR2-deficient mice. We concluded that administration of exogenous rPAF-AH reduced inflammatory injury, altered cytokine levels and favored bacterial clearance with a clear impact on mortality through modulation of MCP-1/CCL2 and NO levels in a clinically relevant sepsis model.

  17. Atg7 deficiency impairs host defense against Klebsiella pneumoniae by impacting bacterial clearance, survival and inflammatory responses in mice.

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    Ye, Yan; Li, Xuefeng; Wang, Wenxue; Ouedraogo, Kiswendsida Claude; Li, Yi; Gan, Changpei; Tan, Shirui; Zhou, Xikun; Wu, Min

    2014-09-01

    Klebsiella pneumoniae (Kp) is a Gram-negative bacterium that can cause serious infections in humans. Autophagy-related gene 7 (Atg7) has been implicated in certain bacterial infections; however, the role of Atg7 in macrophage-mediated immunity against Kp infection has not been elucidated. Here we showed that Atg7 expression was significantly increased in murine alveolar macrophages (MH-S) upon Kp infection, indicating that Atg7 participated in host defense. Knocking down Atg7 with small-interfering RNA increased bacterial burdens in MH-S cells. Using cell biology assays and whole animal imaging analysis, we found that compared with wild-type mice atg7 knockout (KO) mice exhibited increased susceptibility to Kp infection, with decreased survival rates, decreased bacterial clearance, and intensified lung injury. Moreover, Kp infection induced excessive proinflammatory cytokines and superoxide in the lung of atg7 KO mice. Similarly, silencing Atg7 in MH-S cells markedly increased expression levels of proinflammatory cytokines. Collectively, these findings reveal that Atg7 offers critical resistance to Kp infection by modulating both systemic and local production of proinflammatory cytokines. Copyright © 2014 the American Physiological Society.

  18. Oral application of bacterial lysate in infancy diminishes the prevalence of atopic dermatitis in children at risk for atopy.

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    Lau, S

    2014-06-01

    Numerous interventions such as avoidance of food allergens, prolonged breast feeding and supplementation of pro-and/or prebiotics have been tried as primary prevention of atopic dermatitis. Recent data suggest that prevention of infantile eczema is possible in a subgroup of children by feeding bacterial lysates early in life. Bacterial lysates of Escherichia coli and Enterococcus faecalis were found to impair allergic immune responses in rats. An interventional trial in 606 infants at risk for atopy showed a reduction of atopic dermatitis at the end of the treatment phase (month 2 until month 7) of 50% in a subgroup of children with single heredity for atopy. This was even more pronounced in the group of children with paternal heredity for atopy. This effect was still seen at age 1 year. There was no effect on food sensitisation. In conclusion, an immune modulation in terms of prevention of atopic dermatitis in infancy if single atopic family history is present seems to be possible by feeding bacterial lysates early in life.

  19. Hindlimb suspension and SPE-like radiation impairs clearance of bacterial infections.

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    Minghong Li

    Full Text Available A major risk of extended space travel is the combined effects of weightlessness and radiation exposure on the immune system. In this study, we used the hindlimb suspension model of microgravity that includes the other space stressors, situational and confinement stress and alterations in food intake, and solar particle event (SPE-like radiation to measure the combined effects on the ability to control bacterial infections. A massive increase in morbidity and decrease in the ability to control bacterial growth was observed using 2 different types of bacteria delivered by systemic and pulmonary routes in 3 different strains of mice. These data suggest that an astronaut exposed to a strong SPE during extended space travel is at increased risk for the development of infections that could potentially be severe and interfere with mission success and astronaut health.

  20. A streptococcal protease that degrades CXC chemokines and impairs bacterial clearance from infected tissues

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    Hidalgo-Grass, Carlos; Mishalian, Inbal; Dan-Goor, Mary; Belotserkovsky, Ilia; Eran, Yoni; Nizet, Victor; Peled, Amnon; Hanski, Emanuel

    2006-01-01

    Group A Streptococcus (GAS) causes the life-threatening infection in humans known as necrotizing fasciitis (NF). Infected subcutaneous tissues from an NF patient and mice challenged with the same GAS strain possessed high bacterial loads but a striking paucity of infiltrating polymorphonuclear leukocytes (PMNs). Impaired PMN recruitment was attributed to degradation of the chemokine IL-8 by a GAS serine peptidase. Here, we use bioinformatics approach coupled with target mutagenesis to identif...

  1. Intermittent fasting promotes bacterial clearance and intestinal IgA production in Salmonella typhimurium-infected mice.

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    Godínez-Victoria, M; Campos-Rodriguez, R; Rivera-Aguilar, V; Lara-Padilla, E; Pacheco-Yepez, J; Jarillo-Luna, R A; Drago-Serrano, M E

    2014-05-01

    The impact of intermittent fasting versus ad libitum feeding during Salmonella typhimurium infection was evaluated in terms of duodenum IgA levels, bacterial clearance and intestinal and extra-intestinal infection susceptibility. Mice that were intermittently fasted for 12 weeks or fed ad libitum were infected with S. typhimurium and assessed at 7 and 14 days post-infection. Next, we evaluated bacterial load in the faeces, Peyer's patches, spleen and liver by plate counting, as well as total and specific intestinal IgA and plasmatic corticosterone levels (by immunoenzymatic assay) and lamina propria IgA levels in plasma cells (by cytofluorometry). Polymeric immunoglobulin receptor, α- and J-chains, Pax-5 factor, pro-inflammatory cytokine (tumour necrosis factor-α and interferon-γ) and anti-inflammatory cytokine (transforming growth factor-β) mRNA levels were assessed in mucosal and liver samples (by real-time PCR). Compared with the infected ad libitum mice, the intermittently fasted infected animals had (1) lower intestinal and systemic bacterial loads; (2) higher SIgA and IgA plasma cell levels; (3) higher mRNA expression of most intestinal parameters; and (4) increased or decreased corticosterone levels on day 7 and 14 post-infection, respectively. No contribution of liver IgA was observed at the intestinal level. Apparently, the changes following metabolic stress induced by intermittent fasting during food deprivation days increased the resistance to S. typhimurium infection by triggering intestinal IgA production and presumably, pathogen elimination by phagocytic inflammatory cells. © 2014 John Wiley & Sons Ltd.

  2. Low-Dose Oxygen Enhances Macrophage-Derived Bacterial Clearance following Cigarette Smoke Exposure

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    William G. Bain

    2016-01-01

    Full Text Available Background. Chronic obstructive pulmonary disease (COPD is a common, smoking-related lung disease. Patients with COPD frequently suffer disease exacerbations induced by bacterial respiratory infections, suggestive of impaired innate immunity. Low-dose oxygen is a mainstay of therapy during COPD exacerbations; yet we understand little about whether oxygen can modulate the effects of cigarette smoke on lung immunity. Methods. Wild-type mice were exposed to cigarette smoke for 5 weeks, followed by intratracheal instillation of Pseudomonas aeruginosa (PAO1 and 21% or 35–40% oxygen. After two days, lungs were harvested for PAO1 CFUs, and bronchoalveolar fluid was sampled for inflammatory markers. In culture, macrophages were exposed to cigarette smoke and oxygen (40% for 24 hours and then incubated with PAO1, followed by quantification of bacterial phagocytosis and inflammatory markers. Results. Mice exposed to 35–40% oxygen after cigarette smoke and PAO1 had improved survival and reduced lung CFUs and inflammation. Macrophages from these mice expressed less TNF-α and more scavenger receptors. In culture, macrophages exposed to cigarette smoke and oxygen also demonstrated decreased TNF-α secretion and enhanced phagocytosis of PAO1 bacteria. Conclusions. Our findings demonstrate a novel, protective role for low-dose oxygen following cigarette smoke and bacteria exposure that may be mediated by enhanced macrophage phagocytosis.

  3. An epoxide hydrolase secreted by Pseudomonas aeruginosa decreases mucociliary transport and hinders bacterial clearance from the lung.

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    Hvorecny, Kelli L; Dolben, Emily; Moreau-Marquis, Sophie; Hampton, Thomas H; Shabaneh, Tamer B; Flitter, Becca A; Bahl, Christopher D; Bomberger, Jennifer M; Levy, Bruce D; Stanton, Bruce A; Hogan, Deborah A; Madden, Dean R

    2018-01-01

    The opportunistic pathogen Pseudomonas aeruginosa colonizes the lungs of susceptible individuals by deploying virulence factors targeting host defenses. The secreted factor Cif (cystic fibrosis transmembrane conductance regulator inhibitory factor) dysregulates the endocytic recycling of CFTR and thus reduces CFTR abundance in host epithelial membranes. We have postulated that the decrease in ion secretion mediated by Cif would slow mucociliary transport and decrease bacterial clearance from the lungs. To test this hypothesis, we explored the effects of Cif in cultured epithelia and in the lungs of mice. We developed a strategy to interpret the "hurricane-like" motions observed in reconstituted cultures and identified a Cif-mediated decrease in the velocity of mucus transport in vitro. Presence of Cif also increased the number of bacteria recovered at two time points in an acute mouse model of pneumonia caused by P. aeruginosa. Furthermore, recent work has demonstrated an inverse correlation between the airway concentrations of Cif and 15-epi-lipoxin A4, a proresolving lipid mediator important in host defense and the resolution of pathogen-initiated inflammation. Here, we observe elevated levels of 15-epi-lipoxin A4 in the lungs of mice infected with a strain of P. aeruginosa that expresses only an inactive form of cif compared with those mice infected with wild-type P. aeruginosa. Together these data support the inclusion of Cif on the list of virulence factors that assist P. aeruginosa in colonizing and damaging the airways of compromised patients. Furthermore, this study establishes techniques that enable our groups to explore the underlying mechanisms of Cif effects during respiratory infection.

  4. [Diminished culpability].

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    Ohman, Luis; Fantini, Adrián P

    2016-05-01

    One of the central matters in forensic psychiatry is its culpability. Day after day we, the mental health professionals, are subpoenaed in different courts of our country to assess the mental state of a given individual in order to endorse a judge so that he can issue their view pertaining the culpability and the responsibility of accused subjects. Our current National Criminal Code, dating from 1921, in Art. 34 sub 1 holds for culpability a dichotomous model in which an individual is responsible and must be accountable for his behavior or not responsible and in such case must no be held accountable in criminal courts. This dichotomous model often does not permit the correct analysis of the psychopathology making sometimes the psychiatrist to force a conclusion according to this paradigm imposed by Justice. As we all know reality does not reflect itself under discrete categories and notwithstanding this is the written norm, people, thoughts, emotions and behaviors manifest in dimensions where boundaries are not always clear. Hence, we are considering it necessary to give effect to the impulses for the reform of the existing Criminal Code to lead to diminish culpability.

  5. Synthetic furanones inhibit quorum-sensing and enhance bacterial clearance in Pseudomonas aeruginosa lung infection in mice

    DEFF Research Database (Denmark)

    Wu, H; Song, Z; Hentzer, M

    2004-01-01

    INTRODUCTION: Antibiotics are used to treat bacterial infections by killing the bacteria or inhibiting their growth, but resistance to antibiotics can develop readily. The discovery that bacterial quorum-sensing regulates bacterial virulence as well as the formation of biofilms opens up new ways...

  6. Synthetic furanones inhibit quorum-sensing and enhance bacterial clearance in Pseudomonas aeruginosa lung infection in mice

    DEFF Research Database (Denmark)

    Wu, H.; Song, Z.; Hentzer, Morten

    2004-01-01

    Introduction: Antibiotics are used to treat bacterial infections by killing the bacteria or inhibiting their growth, but resistance to antibiotics can develop readily. The discovery that bacterial quorum-sensing regulates bacterial virulence as well as the formation of biofilms opens up new ways...

  7. Using the rate of bacterial clearance determined by real-time polymerase chain reaction as a timely surrogate marker to evaluate the appropriateness of antibiotic usage in critical patients with Acinetobacter baumannii bacteremia.

    Science.gov (United States)

    Chuang, Yu-Chung; Chang, Shan-Chwen; Wang, Wei-Kung

    2012-08-01

    Bacteremia caused by Acinetobacter baumannii is becoming more frequent among critically ill patients, and has been associated with high mortality and prolonged hospital stay. Multidrug resistance and delay in blood culture have been shown to be significant barriers to appropriate antibiotic treatment. Quantitative polymerase chain reaction assays were recently used to monitor bacterial loads; we hypothesized that the rate of bacterial clearance determined by quantitative polymerase chain reaction can be used as a timely surrogate marker to evaluate the appropriateness of antibiotic usage. Prospective observational study. University hospital and research laboratory. Patients with culture-proven A. baumannii bacteremia in the intensive care units were prospectively enrolled from April 2008 to February 2009. Plasmid Oxa-51/pCRII-TOPO, which contained a 431-bp fragment of the A. baumannii-specific Oxa-51 gene in a pCRII-TOPO vector, was used as the standard. Sequential bacterial DNA loads in the blood were measured by a quantitative polymerase chain reaction assay. We enrolled 51 patients with A. baumannii bacteremia, and examined 318 sequential whole blood samples. The initial mean bacterial load was 2.15 log copies/mL, and the rate of bacterial clearance was 0.088 log copies/mL/day. Multivariate linear regression using the generalized estimation equation approach revealed that the use of immunosuppressants was an independent predictor for slower bacterial clearance (coefficient, 1.116; prate of bacterial clearance experienced higher in-hospital mortality (odds ratio, 2.323; p=.04) Immunosuppression and appropriate antibiotic usage were independent factors affecting the rate of clearance of A. baumannii bacteremia in critical patients. These findings highlight the importance of appropriate antibiotic usage and development of effective antibiotics against A. baumannii in an era of emerging antibiotic resistance. The rate of bacterial clearance could serve as a timely

  8. Cytotoxic T-lymphocyte antigen 4 blockade augments the T-cell response primed by attenuated Listeria monocytogenes resulting in more rapid clearance of virulent bacterial challenge.

    Science.gov (United States)

    Rowe, Jared H; Johanns, Tanner M; Ertelt, James M; Lai, Joseph C; Way, Sing Sing

    2009-09-01

    Cytotoxic T-lymphocyte antigen 4 (CTLA-4) uniformly suppresses antigen-specific T cells during chronic infection with bacterial, parasitic or viral pathogens. However, the importance of CTLA-4 in controlling the T-cell response during acute infection or after priming with live attenuated vaccine vectors has not been well characterized. Since strategies aimed at blocking CTLA-4 are being actively developed to therapeutically augment T-cell-mediated immunity, the effects of CTLA-4 blockade on T-cell activation during these conditions need to be more clearly defined. We have examined the role of CTLA-4 in a prime-challenge model of acute bacterial infection using both attenuated and virulent strains of the intracellular bacterium Listeria monocytogenes. Although Foxp3(+) CD4(+) T cells are the predominant CTLA-4-expressing cell type in naïve mice, antigen-specific Foxp3(-) CD4(+) cells upregulate CTLA-4 expression after primary L. monocytogenes infection. Blockade of CTLA-4 results in increased numbers of L. monocytogenes-specific CD4 and CD8 T cells after primary infection with attenuated L. monocytogenes, and confers more rapid bacterial clearance after secondary challenge with virulent L. monocytogenes. Accordingly, CTLA-4 plays an important suppressive role in T-cell priming and protective immunity in a prime-challenge model of acute bacterial infection.

  9. Regulatory T cell suppressive potency dictates the balance between bacterial proliferation and clearance during persistent Salmonella infection.

    Directory of Open Access Journals (Sweden)

    Tanner M Johanns

    2010-08-01

    Full Text Available The pathogenesis of persistent infection is dictated by the balance between opposing immune activation and suppression signals. Herein, virulent Salmonella was used to explore the role and potential importance of Foxp3-expressing regulatory T cells in dictating the natural progression of persistent bacterial infection. Two distinct phases of persistent Salmonella infection are identified. In the first 3-4 weeks after infection, progressively increasing bacterial burden was associated with delayed effector T cell activation. Reciprocally, at later time points after infection, reductions in bacterial burden were associated with robust effector T cell activation. Using Foxp3(GFP reporter mice for ex vivo isolation of regulatory T cells, we demonstrate that the dichotomy in infection tempo between early and late time points is directly paralleled by drastic changes in Foxp3(+ Treg suppressive potency. In complementary experiments using Foxp3(DTR mice, the significance of these shifts in Treg suppressive potency on infection outcome was verified by enumerating the relative impacts of regulatory T cell ablation on bacterial burden and effector T cell activation at early and late time points during persistent Salmonella infection. Moreover, Treg expression of CTLA-4 directly paralleled changes in suppressive potency, and the relative effects of Treg ablation could be largely recapitulated by CTLA-4 in vivo blockade. Together, these results demonstrate that dynamic regulation of Treg suppressive potency dictates the course of persistent bacterial infection.

  10. Distinguishing aggregate formation and aggregate clearance using cell based assays

    NARCIS (Netherlands)

    E. Eenjes, E.; J.M. Dragich; H. Kampinga (Harm); A. Yamamoto, A.

    2016-01-01

    textabstractThe accumulation of ubiquitinated proteinaceous inclusions represents a complex process, reflecting the disequilibrium between aggregate formation and aggregate clearance. Although decreasing aggregate formation or augmenting aggregate clearance will ultimately lead to diminished

  11. A galectin from the kuruma shrimp (Marsupenaeus japonicus) functions as an opsonin and promotes bacterial clearance from hemolymph.

    Science.gov (United States)

    Shi, Xiu-Zhen; Wang, Lei; Xu, Sen; Zhang, Xiao-Wen; Zhao, Xiao-Fan; Vasta, Gerardo Raul; Wang, Jin-Xing

    2014-01-01

    Galectins are a lectin family characterized by a conserved sequence motif in the carbohydrate recognition domain, which preferential binds to galactosyl moieties. However, few studies about the biological roles of galectins in invertebrates have been reported except for the galectin (CvGal1) from the eastern oyster Crassostrea virginica. Furthermore, galectins have been described in only a few crustacean species, and no functional studies have been reported so far. In this study, we identified and functionally characterized a galectin from the kuruma shrimp Marsupenaeus japonicus, which we designated MjGal. Upon Vibrio anguillarum challenge, expression of MjGal was up-regulated mostly in hemocytes and hepatopancreas, and the protein bound to both Gram-positive and Gram-negative bacteria through the recognition of lipoteichoic acid (LTA) or lipopolysaccharide (LPS), respectively. By also binding to the shrimp hemocyte surface, MjGal functions as an opsonin for microbial pathogens, promoting their phagocytosis. Further, as shown by RNA interference, MjGal participates in clearance of bacteria from circulation, and thereby contributes to the shrimp's immune defense against infectious challenge. Elucidation of functional and mechanistic aspects of shrimp immunity will enable the development of novel strategies for intervention in infectious diseases currently affecting the shrimp farming industry worldwide.

  12. Adjunctive Corticosteroid Treatment Against Yersinia pestis Improves Bacterial Clearance, Immunopathology, and Survival in the Mouse Model of Bubonic Plague.

    Science.gov (United States)

    Levy, Yinon; Vagima, Yaron; Tidhar, Avital; Zauberman, Ayelet; Aftalion, Moshe; Gur, David; Fogel, Itay; Chitlaru, Theodor; Flashner, Yehuda; Mamroud, Emanuelle

    2016-09-15

    Plague is initiated by Yersinia pestis, a highly virulent bacterial pathogen. In late stages of the infection, bacteria proliferate extensively in the internal organs despite the massive infiltration of neutrophils. The ineffective inflammatory response associated with tissue damage may contribute to the low efficacy of antiplague therapies during late stages of the infection. In the present study, we address the possibility of improving therapeutic efficacy by combining corticosteroid administration with antibody therapy in the mouse model of bubonic plague. Mice were subcutaneously infected with a fully virulent Y. pestis strain and treated at progressive stages of the disease with anti-Y. pestis antibodies alone or in combination with the corticosteroid methylprednisolone. The addition of methylprednisolone to antibody therapy correlated with improved mouse survival, a significant decrease in the amount of neutrophils and matrix metalloproteinase 9 in the tissues, and the mitigation of tissue damage. Interestingly, the combined treatment led to a decrease in the bacterial loads in infected organs. Corticosteroids induce an unexpectedly effective antibacterial response apart from their antiinflammatory properties, thereby improving treatment efficacy. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  13. Mucociliary clearance

    DEFF Research Database (Denmark)

    Munkholm, Mathias; Mortensen, Jann

    2014-01-01

    Mucociliary clearance has long been known to be a significant innate defence mechanism against inhaled microbes and irritants. Important knowledge has been gathered regarding the anatomy and physiology of this system, and in recent years, extensive studies of the pathophysiology related to lung...... pharmacological interventions on clearance rate, to study the importance of defective mucus clearance in different lung diseases or as a diagnostic tool in the work-up of patients with recurrent airway diseases. The aim of this review is to provide an overview of the anatomy, physiology, pathophysiology...... diseases characterized by defective mucus clearance have resulted in a variety of therapies, which might be able to enhance clearance from the lungs. In addition, ways to study in vivo mucociliary clearance in humans have been developed. This can be used as a means to assess the effect of different...

  14. Human Neutrophil Clearance of Bacterial Pathogens Triggers Anti-Microbial γδ T Cell Responses in Early Infection

    Science.gov (United States)

    Roberts, Gareth W.; Heuston, Sinéad; Brown, Amanda C.; Chess, James A.; Toleman, Mark A.; Gahan, Cormac G. M.; Hill, Colin; Parish, Tanya; Williams, John D.; Davies, Simon J.; Johnson, David W.; Topley, Nicholas; Moser, Bernhard; Eberl, Matthias

    2011-01-01

    Human blood Vγ9/Vδ2 T cells, monocytes and neutrophils share a responsiveness toward inflammatory chemokines and are rapidly recruited to sites of infection. Studying their interaction in vitro and relating these findings to in vivo observations in patients may therefore provide crucial insight into inflammatory events. Our present data demonstrate that Vγ9/Vδ2 T cells provide potent survival signals resulting in neutrophil activation and the release of the neutrophil chemoattractant CXCL8 (IL-8). In turn, Vγ9/Vδ2 T cells readily respond to neutrophils harboring phagocytosed bacteria, as evidenced by expression of CD69, interferon (IFN)-γ and tumor necrosis factor (TNF)-α. This response is dependent on the ability of these bacteria to produce the microbial metabolite (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP), requires cell-cell contact of Vγ9/Vδ2 T cells with accessory monocytes through lymphocyte function-associated antigen-1 (LFA-1), and results in a TNF-α dependent proliferation of Vγ9/Vδ2 T cells. The antibiotic fosmidomycin, which targets the HMB-PP biosynthesis pathway, not only has a direct antibacterial effect on most HMB-PP producing bacteria but also possesses rapid anti-inflammatory properties by inhibiting γδ T cell responses in vitro. Patients with acute peritoneal-dialysis (PD)-associated bacterial peritonitis – characterized by an excessive influx of neutrophils and monocytes into the peritoneal cavity – show a selective activation of local Vγ9/Vδ2 T cells by HMB-PP producing but not by HMB-PP deficient bacterial pathogens. The γδ T cell-driven perpetuation of inflammatory responses during acute peritonitis is associated with elevated peritoneal levels of γδ T cells and TNF-α and detrimental clinical outcomes in infections caused by HMB-PP positive microorganisms. Taken together, our findings indicate a direct link between invading pathogens, neutrophils, monocytes and microbe-responsive γδ T cells in early

  15. Dietary pectin-derived acidic oligosaccharides improve the pulmonary bacterial clearance of Pseudomonas aeruginosa lung infection in mice by modulating intestinal microbiota and immunity.

    Science.gov (United States)

    Bernard, Henry; Desseyn, Jean-Luc; Bartke, Nana; Kleinjans, Lennart; Stahl, Bernd; Belzer, Clara; Knol, Jan; Gottrand, Frédéric; Husson, Marie-Odile

    2015-01-01

    A predominantly T-helper type 2 (Th2) immune response is critical in the prognosis of pulmonary Pseudomonas aeruginosa infection. But the mucosal and systemic immune responses can be influenced by the intestinal microbiota. We assessed the effect of microbiota compositional changes induced by a diet enriched in 5% acidic oligosaccharides derived from pectin (pAOS) on the immune response and outcome of chronic pulmonary P. aeruginosa infection in mice. pAOS promoted Th1 polarization by increasing interferon γ release, upregulating t-bet gene expression, decreasing interleukin 4 secretion, and downregulating gata3 gene expression. pAOS also sustained the release of keratinocyte chemoattractant, recruited polynuclear leukocytes and macrophages, stimulated M1 macrophage activation and interleukin 10 release, and decreased tumor necrosis factor α release in the lung. These effects led to increased bacterial clearance after the first and second P. aeruginosa infections. pAOS modified the intestinal microbiota by stimulating the growth of species involved in immunity development, such as Bifidobacterium species, Sutturella wadsworthia, and Clostridium cluster XIVa organisms, and at the same time increased the production of butyrate and propionate. These results suggest that pAOS may have beneficial effects by limiting the number and severity of pulmonary exacerbations in patients chronically infected with P. aeruginosa, such as individuals with cystic fibrosis. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  16. Distinguishing aggregate formation and aggregate clearance using cell-based assays

    NARCIS (Netherlands)

    Eenjes, Evelien; Dragich, Joanna M.; Kampinga, Harm H.; Yamamoto, Ai

    2016-01-01

    The accumulation of ubiquitylated proteinaceous inclusions represents a complex process, reflecting the disequilibrium between aggregate formation and aggregate clearance. Although decreasing aggregate formation or augmenting aggregate clearance will ultimately lead to a diminished aggregate burden,

  17. Distinguishing aggregate formation and aggregate clearance using cell-based assays

    NARCIS (Netherlands)

    Eenjes, E. (Evelien); Dragich, J.M. (Joanna M.); H. Kampinga (Harm); Yamamoto, A. (Ai)

    2016-01-01

    textabstractThe accumulation of ubiquitylated proteinaceous inclusions represents a complex process, reflecting the disequilibrium between aggregate formation and aggregate clearance. Although decreasing aggregate formation or augmenting aggregate clearance will ultimately lead to a diminished

  18. Pre-adapting parasitic phages to a pathogen leads to increased pathogen clearance and lowered resistance evolution with Pseudomonas aeruginosacystic fibrosis bacterial isolates

    DEFF Research Database (Denmark)

    Friman, Ville-Petri; Soanes-Brown, Daniel; Sierocinski, Pawel

    2016-01-01

    determined if in vitro experimental coevolution can increase the efficiency of phage therapy by limiting the resistance evolution of intermittent and chronic cystic fibrosis Pseudomonas aeruginosa lung isolates to four different phages. We first pre-adapted all phage strains against all bacterial strains...... and then compared the efficacy of pre-adapted and non-adapted phages against ancestral bacterial strains. We found that evolved phages were more efficient in reducing bacterial densities than ancestral phages. This was primarily because only 50% of bacterial strains were able to evolve resistance to evolved phages......Recent years have seen renewed interest in phage therapy - the use of viruses to specifically kill disease-causing bacteria – because of the alarming rise in antibiotic resistance. However, a major limitation of phage therapy is the ease at with bacteria can evolve resistance to phages. Here we...

  19. IL-22 production is regulated by IL-23 during Listeria monocytogenes infection but is not required for bacterial clearance or tissue protection.

    Directory of Open Access Journals (Sweden)

    Amy C Graham

    Full Text Available Listeria monocytogenes (LM is a gram-positive bacterium that is a common contaminant of processed meats and dairy products. In humans, ingestion of LM can result in intracellular infection of the spleen and liver, which can ultimately lead to septicemia, meningitis, and spontaneous abortion. Interleukin (IL-23 is a cytokine that regulates innate and adaptive immune responses by inducing the production of IL-17A, IL-17F, and IL-22. We have recently demonstrated that the IL-23/IL-17 axis is required for optimal recruitment of neutrophils to the liver, but not the spleen, during LM infection. Furthermore, these cytokines are required for the clearance of LM during systemic infection. In other infectious models, IL-22 induces the secretion of anti-microbial peptides and protects tissues from damage by preventing apoptosis. However, the role of IL-22 has not been thoroughly investigated during LM infection. In the present study, we show that LM induces the production of IL-22 in vivo. Interestingly, IL-23 is required for the production of IL-22 during primary, but not secondary, LM infection. Our findings suggest that IL-22 is not required for clearance of LM during primary or secondary infection, using both systemic and mucosal models of infection. IL-22 is also not required for the protection of LM infected spleens and livers from organ damage. Collectively, these data indicate that IL-22 produced during LM infection must play a role other than clearance of LM or protection of tissues from pathogen- or immune-mediated damage.

  20. Mucosal immunization with the Moraxella catarrhalis porin m35 induces enhanced bacterial clearance from the lung: a possible role for opsonophagocytosis

    Directory of Open Access Journals (Sweden)

    Donna eEaston

    2011-05-01

    Full Text Available Moraxella catarrhalis is a significant cause of respiratory tract infection against which a vaccine is sought. Several outer membrane proteins are currently under investigation as potential vaccine antigens, including the porin M35. We have previously shown that the third external loop of M35 was immunodominant over the remainder of the protein for antibody produced in mice against the refolded recombinant protein. However, as this loop is predicted to fold inside the porin channel we also predicted that it would not be accessible to these antibodies when M35 is expressed on the surface of the bacteria in its native conformation. This study investigated the functional activity of antibodies against M35 and those specific for the loop 3 region of M35 in vitro and in vivo. Antisera from mice immunized with M35 or the loop 3-deletion, M35loop3–, recombinant proteins were not bactericidal but did have enhanced opsonic activity, whereas antibodies raised against the loop 3 peptide were not opsonising indicating that the immunodominant loop 3 of M35 was not accessible to antibody as we had previously predicted. Mucosal immunization with M35, M35 that had an antigenically altered loop 3 (M35(ID78 and M35loop3– enhanced the clearance of M. catarrhalis from the lungs of mice challenged with live M. catarrhalis. The in vivo clearance of bacteria in the mice with the M35-derived protein constructs correlated significantly (p<0.001 with the opsonic activity assessed an in vitro opsonophagocytosis assay. This study has demonstrated that the immunodominat B-cell epitope to loop 3 of the M. catarrhalis outer membrane protein M35 is not associated with immune protection and that M35-specific antibodies are not bactericidal but are opsonising. The opsonising activity correlated with in vivo clearance of the bacteria suggesting that opsonising antibody may be a good correlate of immune protection.

  1. Airway Clearance Techniques (ACTs)

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    Full Text Available ... CF Treatments and Therapies Airway Clearance Airway Clearance Techniques (ACTs) There are different ways to clear your ... for fitting ACTs into daily life Airway Clearance Techniques | Webcast To learn more about how you can ...

  2. Airway Clearance Techniques (ACTs)

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    Full Text Available ... Airway Clearance Airway Clearance Techniques (ACTs) There are different ways to clear your airways. Most are easy ... to loosen mucus from airway walls. See how different airway clearance techniques work to help you clear ...

  3. MyD88 deficiency markedly worsens tissue inflammation and bacterial clearance in mice infected with Treponema pallidum, the agent of syphilis.

    Directory of Open Access Journals (Sweden)

    Adam C Silver

    Full Text Available Research on syphilis, a sexually transmitted infection caused by the non-cultivatable spirochete Treponema pallidum, has been hampered by the lack of an inbred animal model. We hypothesized that Toll-like receptor (TLR-dependent responses are essential for clearance of T. pallidum and, consequently, compared infection in wild-type (WT mice and animals lacking MyD88, the adaptor molecule required for signaling by most TLRs. MyD88-deficient mice had significantly higher pathogen burdens and more extensive inflammation than control animals. Whereas tissue infiltrates in WT mice consisted of mixed mononuclear and plasma cells, infiltrates in MyD88-deficient animals were predominantly neutrophilic. Although both WT and MyD88-deficient mice produced antibodies that promoted uptake of treponemes by WT macrophages, MyD88-deficient macrophages were deficient in opsonophagocytosis of treponemes. Our results demonstrate that TLR-mediated responses are major contributors to the resistance of mice to syphilitic disease and that MyD88 signaling and FcR-mediated opsonophagocytosis are linked to the macrophage-mediated clearance of treponemes.

  4. MyD88 Deficiency Markedly Worsens Tissue Inflammation and Bacterial Clearance in Mice Infected with Treponema pallidum, the Agent of Syphilis

    Science.gov (United States)

    Silver, Adam C.; Dunne, Dana W.; Zeiss, Caroline J.; Bockenstedt, Linda K.; Radolf, Justin D.; Salazar, Juan C.; Fikrig, Erol

    2013-01-01

    Research on syphilis, a sexually transmitted infection caused by the non-cultivatable spirochete Treponema pallidum, has been hampered by the lack of an inbred animal model. We hypothesized that Toll-like receptor (TLR)-dependent responses are essential for clearance of T. pallidum and, consequently, compared infection in wild-type (WT) mice and animals lacking MyD88, the adaptor molecule required for signaling by most TLRs. MyD88-deficient mice had significantly higher pathogen burdens and more extensive inflammation than control animals. Whereas tissue infiltrates in WT mice consisted of mixed mononuclear and plasma cells, infiltrates in MyD88-deficient animals were predominantly neutrophilic. Although both WT and MyD88-deficient mice produced antibodies that promoted uptake of treponemes by WT macrophages, MyD88-deficient macrophages were deficient in opsonophagocytosis of treponemes. Our results demonstrate that TLR-mediated responses are major contributors to the resistance of mice to syphilitic disease and that MyD88 signaling and FcR-mediated opsonophagocytosis are linked to the macrophage-mediated clearance of treponemes. PMID:23940747

  5. Reprogramming diminishes retention of Mycobacterium leprae in Schwann cells and elevates bacterial transfer property to fibroblasts [v2; ref status: indexed, http://f1000r.es/280

    Directory of Open Access Journals (Sweden)

    Toshihiro Masaki

    2013-11-01

    Full Text Available Background: Bacterial pathogens can manipulate or subvert host tissue cells to their advantage at different stages during infection, from initial colonization in primary host niches to dissemination. Recently, we have shown that Mycobacterium leprae (ML, the causative agent of human leprosy, reprogrammed its preferred host niche de-differentiated adult Schwann cells to progenitor/stem cell-like cells (pSLC which appear to facilitate bacterial spread. Here, we studied how this cell fate change influences bacterial retention and transfer properties of Schwann cells before and after reprogramming. Results: Using primary fibroblasts as bacterial recipient cells, we showed that non-reprogrammed Schwann cells, which preserve all Schwann cell lineage and differentiation markers, possess high bacterial retention capacity when co-cultured with skin fibroblasts; Schwann cells failed to transfer bacteria to fibroblasts at higher numbers even after co-culture for 5 days. In contrast, pSLCs, which are derived from the same Schwann cells but have lost Schwann cell lineage markers due to reprogramming, efficiently transferred bacteria to fibroblasts within 24 hours. Conclusions: ML-induced reprogramming converts lineage-committed Schwann cells with high bacterial retention capacity to a cell type with pSLC stage with effective bacterial transfer properties. We propose that such changes in cellular properties may be associated with the initial intracellular colonization, which requires long-term bacterial retention within Schwann cells, in order to spread the infection to other tissues, which entails efficient bacterial transfer capacity to cells like fibroblasts which are abundant in many tissues, thereby potentially maximizing bacterial dissemination. These data also suggest how pathogens could take advantage of multiple facets of host cell reprogramming according to their needs during infection.

  6. Reprogramming diminishes retention of Mycobacterium leprae in Schwann cells and elevates bacterial transfer property to fibroblasts [v3; ref status: indexed, http://f1000r.es/2ae

    Directory of Open Access Journals (Sweden)

    Toshihiro Masaki

    2013-11-01

    Full Text Available Background: Bacterial pathogens can manipulate or subvert host tissue cells to their advantage at different stages during infection, from initial colonization in primary host niches to dissemination. Recently, we have shown that Mycobacterium leprae (ML, the causative agent of human leprosy, reprogrammed its preferred host niche de-differentiated adult Schwann cells to progenitor/stem cell-like cells (pSLC which appear to facilitate bacterial spread. Here, we studied how this cell fate change influences bacterial retention and transfer properties of Schwann cells before and after reprogramming. Results: Using primary fibroblasts as bacterial recipient cells, we showed that non-reprogrammed Schwann cells, which preserve all Schwann cell lineage and differentiation markers, possess high bacterial retention capacity when co-cultured with skin fibroblasts; Schwann cells failed to transfer bacteria to fibroblasts at higher numbers even after co-culture for 5 days. In contrast, pSLCs, which are derived from the same Schwann cells but have lost Schwann cell lineage markers due to reprogramming, efficiently transferred bacteria to fibroblasts within 24 hours. Conclusions: ML-induced reprogramming converts lineage-committed Schwann cells with high bacterial retention capacity to a cell type with pSLC stage with effective bacterial transfer properties. We propose that such changes in cellular properties may be associated with the initial intracellular colonization, which requires long-term bacterial retention within Schwann cells, in order to spread the infection to other tissues, which entails efficient bacterial transfer capacity to cells like fibroblasts which are abundant in many tissues, thereby potentially maximizing bacterial dissemination. These data also suggest how pathogens could take advantage of multiple facets of host cell reprogramming according to their needs during infection.

  7. Evaluation of cell-mediated immune responses and bacterial clearance in 6-10 months old water buffalo (Bubalus bubalis) experimentally vaccinated with four dosages of commercial Brucella abortus strain RB51 vaccine.

    Science.gov (United States)

    Diptee, M D; Adesiyun, A A; Asgarali, Z; Campbell, M; Fosgate, G T

    2005-07-15

    Thirty water buffalo, obtained from a brucellosis-free farm, were used to evaluate cell-mediated immune responses and bacterial clearance in response to vaccination with Brucella abortus strain RB51 (RB51) in a dose-response study. The animals were randomly divided into five treatment groups. Groups I--V received the recommended dose (RD) of RB51 vaccine once, RD twice 4 weeks apart, double RD once, double RD twice 4 weeks apart and saline once, respectively. Cell-mediated immune response to RB51 was assessed by the histological examination of haematoxylin and eosin (H&E) stained sections of lymph nodes draining the sites of inoculation and by comparison of stimulation indices (SI) derived from gamma interferon (IFN-gamma) assay. A mixture of cytoplasmic proteins from B. melitensis B115 (brucellergene) was used as a specific antigenic stimulus to peripheral blood mononuclear cells (PBMC) and lymph node mononuclear cells (LNMC) up to 22 post-initial-inoculation week (PIW). Supernatants harvested at 18-24h after the in vitro antigenic stimulus were assayed for their IFN-gamma content by using a commercial sandwich enzyme-linked immunosorbent assay (ELISA) kit. Clearance of RB51 was assessed by the sequential immunohistochemical examination of sections of draining lymph nodes post-inoculation. There was no observable expansion of the deep cortex of lymph nodes on H&E sections indicating poor T-cell stimulation. All group V (control) water buffalo PBMC ELISA values were negative (SIRB51 occurred between 4 and 6 PIW in treatment groups I and III and between 6 and 12 PIW in groups II and IV. RB51 was not detected in any of the control animals at sampling intervals post-inoculation.

  8. Airway Clearance Techniques (ACTs)

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    Full Text Available ... of treatment options. Airway Clearance Active Cycle of Breathing Technique Airway Clearance Techniques Autogenic Drainage Basics of ... Pulmonary Exacerbations Clinical Care Guidelines SCREENING & TREATING DEPRESSION & ANXIETY GUIDELINES Clinician Resources As a clinician, you’re ...

  9. Airway Clearance Techniques (ACTs)

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    Full Text Available ... Team Your cystic fibrosis care team includes a group of CF health care professionals who partner with ... Airway Clearance Airway Clearance Techniques (ACTs) There are different ways to clear your airways. Most are easy ...

  10. Airway Clearance Techniques (ACTs)

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    Full Text Available ... Treatments and Therapies Airway Clearance Airway Clearance Techniques (ACTs) There are different ways to clear your airways. ... or caregiver. Older kids and adults can choose ACTs that they can do on their own. Share ...

  11. Airway Clearance Techniques (ACTs)

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    Full Text Available ... Twitter YouTube Instagram Email DONATE Breadcrumb Navigation Home Life With CF Treatments and Therapies Airway Clearance Airway Clearance Techniques (ACTs) There are different ways to clear your airways. Most are easy to ...

  12. Airway Clearance Techniques (ACTs)

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    Full Text Available ... many challenges, including medical, social, and financial. By learning more about how you can manage your disease every day, you can ... Clearance Active Cycle of Breathing Technique (ACBT) Airway Clearance Techniques ( ...

  13. Distinct roles of TNF-related apoptosis-inducing ligand (TRAIL) in viral and bacterial infections: from pathogenesis to pathogen clearance.

    Science.gov (United States)

    Gyurkovska, Valeriya; Ivanovska, Nina

    2016-06-01

    Apoptotic death of different cells observed during infection is thought to limit overwhelming inflammation in response to microbial challenge. However, the underlying apoptotic death mechanisms have not been well defined. Tumor necrosis factor (TNF) related apoptosis-inducing ligand (TRAIL) is a type II transmembrane protein belonging to the TNF superfamily, which is involved not only in tumor growth suppression but in infection control and also in the regulation of both innate and adaptive immune responses. In this review, we have summarized data of recent studies on the influence of the TRAIL/TRAIL receptor (TRAIL-R) system on the development of viral and bacterial infections. TRAIL may have a dual function in the immune system being able to kill infected cells and also to participate in the pathogenesis of multiple infections. Moreover, many pathogens have evolved mechanisms to manipulate TRAIL signaling thus increasing pathogen replication. Present data highlight an essential role for the TRAIL/TRAIL-R system in the regulation and modulation of apoptosis and show that TRAIL has distinct roles in pathogenesis and pathogen elimination. Knowledge of the factors that determine whether TRAIL is helpful or harmful supposes its potential therapeutic implications that are only beginning to be explored.

  14. Security Clearance Tracking System

    Data.gov (United States)

    National Archives and Records Administration — SCTS supports the adjudication process of private background investigations and clearances for potential employees, contractors, interns and student workers.

  15. Airway Clearance Techniques (ACTs)

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    Full Text Available ... Folding Consortium Mucociliary Clearance Consortium SUCCESS WITH THERAPIES RESEARCH CONSORTIUM Therapeutics Development Network TDN Coordinating Center Study Services Working With the TDN Tools and Resources ...

  16. Lactate production and clearance in exercise. Effects of training. A mini-review

    DEFF Research Database (Denmark)

    Stallknecht, B; Vissing, J; Galbo, H

    1998-01-01

    conditions. Due to influence on hormonal response, mitochondrial oxidative capacity and fiber recruitment, training diminishes glycogenolysis and lactate production. Training also increases lactate clearance. This reflects increased hepatic capacity for gluconeogenesis as well as increased lactate transport...

  17. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... decisions about your health care. CF Genetics: The Basics CF Mutations Video Series CFTR2 Personalized Medicine Types ... of Breathing Technique Airway Clearance Techniques Autogenic Drainage Basics of Lung Care Chest Physical Therapy Coughing and ...

  18. Airway Clearance Techniques (ACTs)

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    Full Text Available ... Care Guidelines Pancreatic Enzymes Clinical Care Guidelines Vitamin D Deficiency Clinical Care Guidelines Other CF-related Conditions ... Reports Research Consortia CF Biomarker Consortium CFTR 3-D Structure Consortium CFTR Folding Consortium Mucociliary Clearance Consortium ...

  19. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... Clinical Care Guidelines Liver Disease Clinical Care Guidelines Respiratory Care Guidelines CF Airway Clearance Therapies Clinical Care ... attack bacteria. Choose What's Best for You Your respiratory therapist or another member of your CF care ...

  20. Airway Clearance Techniques (ACTs)

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    Full Text Available ... Medications Antibiotics Bronchodilators Mucus Thinners Nebulizer Care at Home Vascular Access Devices: PICCs and Ports Partnerships for ... Facebook Twitter YouTube Instagram Email DONATE Breadcrumb Navigation Home Life With CF Treatments and Therapies Airway Clearance ...

  1. Airway Clearance Techniques (ACTs)

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    Full Text Available ... CYSTIC FIBROSIS Learn about cystic fibrosis, a genetic lung disorder that affects the pancreas and other organs, ... Clearance Techniques (ACTs) Autogenic Drainage (AD) Basics of Lung Care Chest Physical Therapy Coughing and Huffing High- ...

  2. Airway Clearance Techniques (ACTs)

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    Full Text Available ... a Family Parenting as an Adult With CF Treatments & Therapies People with cystic fibrosis are living longer ... to specialized CF care and a range of treatment options. Airway Clearance Active Cycle of Breathing Technique ...

  3. Airway Clearance Techniques (ACTs)

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    Full Text Available ... MEDICATIONS The Partnerships for Sustaining Daily Care Initiative Success With Therapies Research Consortium Your CF Care Team ... Structure Consortium CFTR Folding Consortium Mucociliary Clearance Consortium SUCCESS WITH THERAPIES RESEARCH CONSORTIUM Therapeutics Development Network TDN ...

  4. Airway Clearance Techniques (ACTs)

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    Full Text Available ... Clinician Career Development Awards Clinician Training Awards Mutation Analysis Program Network News Network News: NACFC 2017 Network ... for airway clearance. Facebook Twitter Email More Related Content Medications Autogenic Drainage Positive Expiratory Pressure High-Frequency ...

  5. Airway Clearance Techniques (ACTs)

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    Full Text Available ... Advocacy Achievements Advocacy News Briefings, Testimonies, and Regulatory Comments Congressional Cystic Fibrosis Caucus Our Policy Agenda Policy ... for airway clearance. Facebook Twitter Email More Related Content Medications Autogenic Drainage Positive Expiratory Pressure High-Frequency ...

  6. Airway Clearance Techniques (ACTs)

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    Full Text Available ... people with cystic fibrosis so that they make smart decisions about CF-related research, treatment, and access ... Facebook Twitter YouTube Instagram Email DONATE Breadcrumb Navigation Home Life With CF Treatments and Therapies Airway Clearance ...

  7. Airway Clearance Techniques (ACTs)

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    Full Text Available ... Consider Regarding a Lung Transplant Medications Antibiotics Bronchodilators Mucus Thinners Nebulizer Care at Home Vascular Access Devices ... them use percussion (clapping) or vibration to loosen mucus from airway walls. See how different airway clearance ...

  8. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... Medications Antibiotics Bronchodilators Mucus Thinners Nebulizer Care at Home Vascular Access Devices PICCs and Ports Partnerships for ... Facebook Twitter YouTube Instagram Email DONATE Breadcrumb Navigation Home Life With CF Treatments and Therapies Airway Clearance ...

  9. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... in CF Clinical Care Guidelines Cystic Fibrosis-Related Diabetes Clinical Care Guidelines Liver Disease Clinical Care Guidelines Respiratory Care Guidelines CF Airway Clearance Therapies Clinical Care Guidelines Chronic Medications to Maintain Lung Health Clinical Care Guidelines ...

  10. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... a Family Parenting as an Adult With CF Treatments & Therapies People with cystic fibrosis are living longer and ... to specialized CF care and a range of treatment options. Airway Clearance Active Cycle of Breathing Technique ( ...

  11. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... in CF Clinical Care Guidelines Cystic Fibrosis-Related Diabetes Clinical Care Guidelines Liver Disease Clinical Care Guidelines Respiratory Care Guidelines CF Airway Clearance Therapies Clinical Care Guidelines Chronic Medications to Maintain Lung ...

  12. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... Make a Charitable Gift Our Corporate Supporters Workplace Engagement DONATE YOUR PROPERTY eCards for a Cure About ... airway walls. See how different airway clearance techniques work to help you clear the thick, sticky mucus ...

  13. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... Beall Therapeutics Development Award Patient Registry Care Center Data CF Patient Registry Reports Research Consortia CF Biomarker Consortium CFTR 3-D Structure Consortium CFTR Folding Consortium Mucociliary Clearance Consortium SUCCESS ...

  14. Lithium clearance method and the renal response to low-dose dopamine in man

    DEFF Research Database (Denmark)

    Olsen, Niels Vidiendal; Olsen, M H; Fogh-Andersen, N

    1993-01-01

    .00 hours on three different occasions. After an overnight fast, the subjects were water-loaded and clearance studies were started at 09.00 hours with a 1h baseline period and three 1h periods during dopamine infusion. 2. Baseline sodium clearance with placebo was 0.65 +/- 0.35 ml/min, but with lithium.......05) and 10% (P sodium clearance were significantly diminished after 450mg (P ... values of sodium clearance and effective renal plasma flow.(ABSTRACT TRUNCATED AT 250 WORDS)...

  15. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... toddlers will need help from a parent or caregiver. Older kids and adults can choose ACTs that they can do on their ... (clapping) or vibration to loosen mucus from airway walls. See how different airway clearance techniques work to help you clear the thick, sticky mucus ...

  16. Cilia and Mucociliary Clearance.

    Science.gov (United States)

    Bustamante-Marin, Ximena M; Ostrowski, Lawrence E

    2017-04-03

    Mucociliary clearance (MCC) is the primary innate defense mechanism of the lung. The functional components are the protective mucous layer, the airway surface liquid layer, and the cilia on the surface of ciliated cells. The cilia are specialized organelles that beat in metachronal waves to propel pathogens and inhaled particles trapped in the mucous layer out of the airways. In health this clearance mechanism is effective, but in patients with primary cilia dyskinesia (PCD) the cilia are abnormal, resulting in deficient MCC and chronic lung disease. This demonstrates the critical importance of the cilia for human health. In this review, we summarize the current knowledge of the components of the MCC apparatus, focusing on the role of cilia in MCC. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

  17. Site clearance working group

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-03-01

    The Gulf of Mexico and Louisiana continue to be areas with a high level of facility removal, and the pace of removal is projected to increase. Regulations were promulgated for the Gulf of Mexico and Louisiana requiring that abandoned sites be cleared of debris that could interfere with fishing and shrimping activities. The site clearance regulations also required verification that the sites were clear. Additionally, government programs were established to compensate fishermen for losses associated with snagging their equipment on oil and gas related objects that remained on the water bottoms in areas other than active producing sites and sites that had been verified as clear of obstructions and snags. The oil and gas industry funds the compensation programs. This paper reviews the regulations and evolving operating practices in the Gulf of Mexico and Louisiana where site clearance and fisherman`s gear compensation regulations have been in place for a number of years. Although regulations and guidelines may be in place elsewhere in the world, this paper focuses on the Gulf of Mexico and Louisiana. Workshop participants are encouraged to bring up international issues during the course of the workshop. Additionally, this paper raises questions and focuses on issues that are of concern to the various Gulf of Mexico and Louisiana water surface and water bottom stakeholders. This paper does not have answers to the questions or issues. During the workshop participants will debate the questions and issues in an attempt to develop consensus opinions and/or make suggestions that can be provided to the appropriate organizations, both private and government, for possible future research or policy adjustments. Site clearance and facility removal are different activities. Facility removal deals with removal of the structures used to produce oil and gas including platforms, wells, casing, piles, pipelines, well protection structures, etc.

  18. Diminished neutrophil extracellular trap (NET) formation is a novel innate immune deficiency induced by acute ethanol exposure in polymicrobial sepsis, which can be rescued by CXCL1.

    Science.gov (United States)

    Jin, Liliang; Batra, Sanjay; Jeyaseelan, Samithamby

    2017-09-01

    Polymicrobial sepsis is the result of an exaggerated host immune response to bacterial pathogens. Animal models and human studies demonstrate that alcohol intoxication is a key risk factor for sepsis-induced mortality. Multiple chemokines, such as CXCL1, CXCL2 and CXCL5 are critical for neutrophil recruitment and proper function of neutrophils. However, it is not quite clear the mechanisms by which acute alcohol suppresses immune responses and whether alcohol-induced immunosuppression can be rescued by chemokines. Thus, we assessed whether acute ethanol challenge via gavage diminishes antibacterial host defense in a sepsis model using cecal ligation and puncture (CLP) and whether this immunosuppression can be rescued by exogenous CXCL1. We found acute alcohol intoxication augments mortality and enhances bacterial growth in mice following CLP. Ethanol exposure impairs critical antibacterial functions of mouse and human neutrophils including reactive oxygen species production, neutrophil extracellular trap (NET) formation, and NET-mediated killing in response to both Gram-negative (E. coli) and Gram-positive (Staphylococcus aureus) pathogens. As compared with WT (C57Bl/6) mice, CXCL1 knockout mice display early mortality following acute alcohol exposure followed by CLP. Recombinant CXCL1 (rCXCL1) in acute alcohol challenged CLP mice increases survival, enhances bacterial clearance, improves neutrophil recruitment, and enhances NET formation (NETosis). Recombinant CXCL1 (rCXCL1) administration also augments bacterial killing by alcohol-treated and E. coli- and S. aureus-infected neutrophils. Taken together, our data unveils novel mechanisms underlying acute alcohol-induced dysregulation of the immune responses in polymicrobial sepsis, and CXCL1 is a critical mediator to rescue alcohol-induced immune dysregulation in polymicrobial sepsis.

  19. Diminished neutrophil extracellular trap (NET formation is a novel innate immune deficiency induced by acute ethanol exposure in polymicrobial sepsis, which can be rescued by CXCL1.

    Directory of Open Access Journals (Sweden)

    Liliang Jin

    2017-09-01

    Full Text Available Polymicrobial sepsis is the result of an exaggerated host immune response to bacterial pathogens. Animal models and human studies demonstrate that alcohol intoxication is a key risk factor for sepsis-induced mortality. Multiple chemokines, such as CXCL1, CXCL2 and CXCL5 are critical for neutrophil recruitment and proper function of neutrophils. However, it is not quite clear the mechanisms by which acute alcohol suppresses immune responses and whether alcohol-induced immunosuppression can be rescued by chemokines. Thus, we assessed whether acute ethanol challenge via gavage diminishes antibacterial host defense in a sepsis model using cecal ligation and puncture (CLP and whether this immunosuppression can be rescued by exogenous CXCL1. We found acute alcohol intoxication augments mortality and enhances bacterial growth in mice following CLP. Ethanol exposure impairs critical antibacterial functions of mouse and human neutrophils including reactive oxygen species production, neutrophil extracellular trap (NET formation, and NET-mediated killing in response to both Gram-negative (E. coli and Gram-positive (Staphylococcus aureus pathogens. As compared with WT (C57Bl/6 mice, CXCL1 knockout mice display early mortality following acute alcohol exposure followed by CLP. Recombinant CXCL1 (rCXCL1 in acute alcohol challenged CLP mice increases survival, enhances bacterial clearance, improves neutrophil recruitment, and enhances NET formation (NETosis. Recombinant CXCL1 (rCXCL1 administration also augments bacterial killing by alcohol-treated and E. coli- and S. aureus-infected neutrophils. Taken together, our data unveils novel mechanisms underlying acute alcohol-induced dysregulation of the immune responses in polymicrobial sepsis, and CXCL1 is a critical mediator to rescue alcohol-induced immune dysregulation in polymicrobial sepsis.

  20. Clearance of mutant huntingtin.

    Science.gov (United States)

    Li, Xiao-Jiang; Li, He; Li, Shihua

    2010-07-01

    Mutant huntingtin (htt) carries an expanded polyglutamine (polyQ) repeat (> 36 glutamines) in its N-terminal region, which leads htt to become misfolded and kill neuronal cells in Huntington disease (HD). The cytotoxicity of N-terminal mutant htt fragments is evident by severe neurological phenotypes of transgenic mice that express these htt fragments. Clearance of mutant htt is primarily mediated by the ubiquitin-proteasomal sysmtem (UPS) and autophagy. However, the relative efficiency of these two systems to remove toxic forms of mutant htt has not been rigorously compared. Using cellular and mouse models of HD, we found that inhibiting the UPS leads to a greater accumulation of mutant htt than inhibiting autophagy. Moreover, N-terminal mutant htt fragments, but not full-length mutant htt, accumulate in the HD mouse brains after inhibiting the UPS. These findings suggest that the UPS is more efficient than autophagy to remove N-terminal mutant htt.

  1. Aerial Refueling Clearance Process Guide

    Science.gov (United States)

    2014-08-21

    R. 4.9.3 Ball Valve/Leakage R. dhkARSAG DOC dtd. 6dec. 13; rev.21jan.14 Aerial Refueling Tanker/Receiver Clearance Compatibility Assessment Checklist...Clearance 9.6 Receiver Canopy/Boom Clearance 9.7 Lightning /Static Discharge Impact 10. Standards Compliance 10.1 STANAG 7191 Boom/ Recp. 10.2 AR...Type R. 4.9.1 Gate/Leakage R. 4.9.2 Poppet/Leakage R. 4.9.3 Ball Valve/Leakage R. 4.9.4 Other Leakage Source R. 4.10 Fuel Ingestion Hazard……... R. 5.0

  2. Lithium clearance in chronic nephropathy

    DEFF Research Database (Denmark)

    Kamper, A L; Holstein-Rathlou, N H; Leyssac, P P

    1989-01-01

    1. Lithium clearance measurements were made in 72 patients with chronic nephropathy of different aetiology and moderate to severely reduced renal function. 2. Lithium clearance was strictly correlated with glomerular filtration rate, and there was no suggestion of distal tubular reabsorption...... of lithium or influence of osmotic diuresis. 3. Fractional reabsorption of lithium was reduced in most patients with glomerular filtration rates below 25 ml/min. 4. Calculated fractional distal reabsorption of sodium was reduced in most patients with glomerular filtration rates below 50 ml/min. 5. Lithium...... that lithium clearance may be a measure of the delivery of sodium and water from the renal proximal tubule. With this assumption it was found that adjustment of the sodium excretion in chronic nephropathy initially takes place in the distal parts of the nephron (loop of Henle, distal tubule and collecting duct...

  3. Lactate clearance in cardiorespiratory emergency

    Directory of Open Access Journals (Sweden)

    Serena Greco

    2007-08-01

    Full Text Available Early goal directed therapy has been found to improve prognosis in septic patients, if the therapeutic goal is achieved within the first six hours. The aim of our study is to demonstrate that in patients with acute cardiorespiratory failure, rapid (within 2 hours lactate clearance can help define patients’ prognosis. 67 consecutive patients, admitted to our 16-bed Emergency Medicine ward for acute cardiorespiratory failure (age 75,9 ± 9,8 (APACHE II score 19,0 ± 4,1, were included in the study. Blood lactate concentration was read at admission and after 2, 6 and 24 hours. We evaluated mortality at seven days and the use of orotracheal intubation (patients with negative outcome vs. discharge or transfer to a non-emergency ward with subsequent discharge (patients with negative outcome. Lactate concentration at admission was 4,6 ± 2,5 mmol/l; lactate clearance (% at 2 hours was 40,4 ± 32,1 in patients with a positive outcome and –8,3 ± 5,0 in patients with a negative outcome (p < 0,05. Lactate clearance at 2 hours < 25% is correlated to a negative outcome with an 84,2% sensitivity and a 79,2% specificity. The positive predictive value was 61,5% and the negative predictive value was 92,2%. Systematic lactate clearance monitoring can be used in cases of acute cardiorespiratory insufficiency to identify patients with a high risk of negative outcome. In our study, low clearance at two hours was associated with an increase in mortality and/or the need for orotracheal intubation. Conversely, a clearance at two hours of > 25% in most cases confirms the therapeutic strategy undertaken. Serial evaluation of blood lactate concentration may therefore be useful in guiding treatment strategies.

  4. Rumination is associated with diminished performance monitoring.

    Science.gov (United States)

    Tanovic, Ema; Hajcak, Greg; Sanislow, Charles A

    2017-09-01

    Rumination is a construct that cuts across a variety of disorders, including anxiety and depression. It has been associated with deficits in cognitive control thought to confer risk for psychopathology. One aspect of cognitive control that is especially relevant to the content of ruminative thoughts is error processing. We examined the relation of rumination and 2 electrophysiological indices of error processing, error-related negativity (ERN), an early index of error detection, and error positivity (Pe), a later index of error awareness. Consistent with prior work, ERN was negatively correlated with anxiety (i.e., more anxious individuals were characterized by larger ERNs). After controlling for anxiety, rumination-but not worry-predicted ERN attenuation. No significant relation between rumination and Pe emerged. Findings suggest that rumination may diminish resources early in the processes of performance monitoring and the recruitment of cognitive control. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  5. Mechanisms of phagocytosis and host clearance of Pseudomonas aeruginosa

    Science.gov (United States)

    Lovewell, Rustin R.; Patankar, Yash R.

    2014-01-01

    Pseudomonas aeruginosa is an opportunistic bacterial pathogen responsible for a high incidence of acute and chronic pulmonary infection. These infections are particularly prevalent in patients with chronic obstructive pulmonary disease and cystic fibrosis: much of the morbidity and pathophysiology associated with these diseases is due to a hypersusceptibility to bacterial infection. Innate immunity, primarily through inflammatory cytokine production, cellular recruitment, and phagocytic clearance by neutrophils and macrophages, is the key to endogenous control of P. aeruginosa infection. In this review, we highlight recent advances toward understanding the innate immune response to P. aeruginosa, with a focus on the role of phagocytes in control of P. aeruginosa infection. Specifically, we summarize the cellular and molecular mechanisms of phagocytic recognition and uptake of P. aeruginosa, and how current animal models of P. aeruginosa infection reflect clinical observations in the context of phagocytic clearance of the bacteria. Several notable phenotypic changes to the bacteria are consistently observed during chronic pulmonary infections, including changes to mucoidy and flagellar motility, that likely enable or reflect their ability to persist. These traits are likewise examined in the context of how the bacteria avoid phagocytic clearance, inflammation, and sterilizing immunity. PMID:24464809

  6. Autophagy enhances bacterial clearance during P. aeruginosa lung infection

    National Research Council Canada - National Science Library

    Junkins, Robert D; Shen, Ann; Rosen, Kirill; McCormick, Craig; Lin, Tong-Jun

    2013-01-01

    .... aeruginosa is primarily considered an extacellular pathogen, recent reports have demonstrated that throughout the course of infection the bacterium acquires the ability to enter and reside within host cells...

  7. Diminishing musyarakah investment model based on equity

    Science.gov (United States)

    Jaffar, Maheran Mohd; Zain, Shaharir Mohamad; Jemain, Abdul Aziz

    2017-11-01

    Most of the mudharabah and musyarakah contract funds are involved in debt financing. This does not support the theory that profit sharing contract is better than that of debt financing due to the sharing of risks and ownership of equity. Indeed, it is believed that Islamic banking is a financial model based on equity or musyarakah which emphasis on the sharing of risks, profit and loss in the investment between the investor and entrepreneur. The focus of this paper is to introduce the mathematical model that internalizes diminishing musyarakah, the sharing of profit and equity between entrepreneur and investor. The entrepreneur pays monthly-differed payment to buy out the equity that belongs to the investor (bank) where at the end of the specified period, the entrepreneur owns the business and the investor (bank) exits the joint venture. The model is able to calculate the amount of equity at any time for both parties and hence would be a guide in helping to estimate the value of investment should the entrepreneur or investor exit before the end of the specified period. The model is closer to the Islamic principles for justice and fairness.

  8. Diminished choice effect on anticipating improbable rewards.

    Science.gov (United States)

    Chen, Weiran; Li, Qi; Mei, Shuting; Yi, Wei; Yang, Guochun; Zhou, Shiyu; Liu, Xun; Zheng, Ya

    2018-02-01

    Previous research found that the neural substrates underlying perceived control highly overlap those of reward system, especially during reward anticipation stage. The current event-related potential study examined whether the experience of choice by which individuals exercise control is modulated by reward probability during reward anticipation stage as indexed by the stimulus-preceding negativity (SPN). Thirty participants performed a cued gambling task during which choices could be made either by themselves (a choice condition) or by a computer (a no-choice condition) with three levels of reward probability (low, medium, and high) while their EEG was recording. As expected, the participants perceived higher control during the choice compared to no-choice condition. Correspondingly, the SPN was enhanced in the choice condition than the no-choice condition. Critically, the SPN choice effect was present when reward probability was high and medium, but was diminished when reward probability was low. These findings suggest that the perceived control as exercised by choice is associated with reward anticipation, which may be sensitive to the fundamental properties of reward. Copyright © 2018 Elsevier Ltd. All rights reserved.

  9. Diminished aversive classical conditioning in pathological gamblers.

    Science.gov (United States)

    Brunborg, Geir Scott; Johnsen, Bjørn Helge; Mentzoni, Rune Aune; Myrseth, Helga; Molde, Helge; Lorvik, Ingjerd Meen; Bu, Eli Torild Hellandsjø; Pallesen, Ståle

    2012-09-01

    Impaired ability to form associations between negative events in gambling and aversive somatic reactions may be a predisposing factor for pathological gambling. The current study investigated whether a group of pathological gamblers and a control group differed in aversive classical conditioning. A differential aversive classical conditioning paradigm, which consisted of three phases. In the habituation phase, one 850-Hz tone stimulus and one 1500-Hz tone stimulus were presented three times each in random order. In the acquisition phase, the two tones were presented 10 times each in random order, and one was always followed by a 100-dB burst of white noise. In the extinction phase the two tones were presented three times each without the white noise. University laboratory testing facilities and out-patient treatment facilities. Twenty pathological gamblers and 20 control participants. Duration of seven cardiac interbeat-intervals (IBIs) following tone offset, gambling severity, tobacco and alcohol use, anxiety and depression. No group differences were found in the habituation and acquisition phases. However, a significant group × stimuli × trials × IBIs interaction effect was found in the extinction phase (P classical conditioning, but that the control group did. Pathological gamblers have a diminished capacity to form associations between aversive events and stimuli that predict aversive events. Aversion learning is likely to be an ineffective treatment for pathological gamblers. © 2012 The Authors, Addiction © 2012 Society for the Study of Addiction.

  10. A Decade of Diminishing Sunspot Vigor

    Science.gov (United States)

    Livingston, W. C.; Penn, M.; Svalgard, L.

    2011-05-01

    1A Decade of Diminishing Sunspot Vigor William Livingston1 Matt Penn1 Leif Svalgard2 Sunspots are small dark areas on the solar disk where internal magnetism, 1500 to 3500 Gauss, has been buoyed to the surface. (Spot life times are the order of one day to a couple of weeks or more. They are thought to be dark because convection inhibits the outward transport of energy there). Their "vigor” can be described by spot area, spot brightness intensity, and magnetic field. From 2001 to 2011 we have measured field strength and brightness at the darkest position in umbrae of 1750 spots using the Zeeman splitting of the Fe 1564.8 nm line. Only one observation per spot per day is carried out during our monthly telescope time of 3-4 days average. Over this interval the temporal mean magnetic field has declined about 500 Gauss and mean spot intensity has risen about 20%. We do not understand the physical mechanism behind these changes or the effect, if any, it will have on the Earth environment. 1. wcl@noao.edu mpenn@noao.edu 2. leif@leif.org

  11. Household Clearances in Victorian Fiction

    Directory of Open Access Journals (Sweden)

    David Trotter

    2008-04-01

    Full Text Available The deathbed apart, there are few scenes more profoundly disturbing in nineteenth-century fiction than the household clearance, or the process of 'selling up': the identification of domestic material goods for sale at auction, either in situ, or elsewhere. Of course, we shouldn't be surprised at this, if the Victorians took the idea of home anything like as seriously as they made out. How could such a violation or wilful sacrifice of domesticity not be profoundly disturbing? This essay argues that scenes of household clearance in nineteenth-century fiction possess a density and an edge which exceed any shock they might have administered to the sensibilities of the house-proud. Such scenes expose to critical view an aspect of existence otherwise generally understood, then as now, not to require or to benefit from illumination. The aims of the essay are twofold: 1 to demonstrate the pervasiveness of scenes of household clearance in Victorian fiction, with reference to Dickens, Thackeray, Eliot, Hardy, and others; 2 to put forward an explanation for the imaginative charge they carry, which runs counter to a strong emphasis in the current understanding of nineteenth-century fiction's perspective on a newly abundant material culture.

  12. Bacterial Keratitis

    Science.gov (United States)

    ... Español Eye Health / Eye Health A-Z Bacterial Keratitis Sections What Is Bacterial Keratitis? Bacterial Keratitis Symptoms ... Lens Care Bacterial Keratitis Treatment What Is Bacterial Keratitis? Leer en Español: ¿Qué Es la Queratitis Bacteriana? ...

  13. Necroptosis Promotes Staphylococcus aureus Clearance by Inhibiting Excessive Inflammatory Signaling

    Directory of Open Access Journals (Sweden)

    Kipyegon Kitur

    2016-08-01

    Full Text Available Staphylococcus aureus triggers inflammation through inflammasome activation and recruitment of neutrophils, responses that are critical for pathogen clearance but are associated with substantial tissue damage. We postulated that necroptosis, cell death mediated by the RIPK1/RIPK3/MLKL pathway, would function to limit pathological inflammation. In models of skin infection or sepsis, Mlkl−/− mice had high bacterial loads, an inability to limit interleukin-1b (IL-1b production, and excessive inflammation. Similarly, mice treated with RIPK1 or RIPK3 inhibitors had increased bacterial loads in a model of sepsis. Ripk3−/− mice exhibited increased staphylococcal clearance and decreased inflammation in skin and systemic infection, due to direct effects of RIPK3 on IL-1b activation and apoptosis. In contrast to Casp1/4−/− mice with defective S. aureus killing, the poor outcomes of Mlkl−/− mice could not be attributed to impaired phagocytic function. We conclude that necroptotic cell death limits the pathological inflammation induced by S. aureus.

  14. Lithium clearance in chronic nephropathy

    DEFF Research Database (Denmark)

    Kamper, A L; Holstein-Rathlou, N H; Leyssac, P P

    1989-01-01

    of lithium or influence of osmotic diuresis. 3. Fractional reabsorption of lithium was reduced in most patients with glomerular filtration rates below 25 ml/min. 4. Calculated fractional distal reabsorption of sodium was reduced in most patients with glomerular filtration rates below 50 ml/min. 5. Lithium...... that lithium clearance may be a measure of the delivery of sodium and water from the renal proximal tubule. With this assumption it was found that adjustment of the sodium excretion in chronic nephropathy initially takes place in the distal parts of the nephron (loop of Henle, distal tubule and collecting duct......). With more severe impairment the proximal tubule also becomes involved in the adjustment....

  15. Green technology; only Forest Clearance is needed

    Indian Academy of Sciences (India)

    First page Back Continue Last page Graphics. How was Forest Clearance granted before the procedures for constitution of ESZ was completed? How was Forest Clearance granted before the procedures for constitution of ESZ was completed? How was land in Murmurwadi still under litigation made available? How was ...

  16. Intelligent Engine Systems: HPT Clearance Control

    Science.gov (United States)

    2008-01-01

    The Advanced Thermally Actuated Clearance Control System underwent several studies. Improved flow path isolation quantified what can be gained by making the HPT case nearly adiabatic. The best method of heat transfer was established, and finally two different borrowed air cooling circuits were evaluated to be used for the HPT Active Clearance Control System.

  17. Clearance of materials from accelerator facilities

    Directory of Open Access Journals (Sweden)

    Rokni Sayed H.

    2017-01-01

    Full Text Available A new Technical Standard that supports the clearance of materials and equipment (personal property from U.S. Department of Energy (DOE accelerator facilities has been developed. The Standard focuses on personal property that has the potential to be radiologically impacted by accelerator operations. It addresses material clearance programs and protocols for off-site releases without restriction on use. Common metals with potential volumetric activation are of main interest with technical bases provided in Appendices of the Standard. The clearance protocols in the Standard include three elements: 1 clearance criteria, 2 process knowledge, and 3 measurement methods. This paper presents the technical aspects of the new Standard, discusses operational experience gained in clearance of materials and equipment from several accelerator facilities at SLAC and examples as to how this Standard can be applied to benefit the entirety of the DOE Accelerator Complex.

  18. 77 FR 21989 - Critical Infrastructure Private Sector Clearance Program Request

    Science.gov (United States)

    2012-04-12

    ... SECURITY Critical Infrastructure Private Sector Clearance Program Request AGENCY: National Protection and... information provided. SUPPLEMENTARY INFORMATION: The Critical Infrastructure Private Sector Clearance Program (PSCP) sponsors clearances for private sector partners who are responsible for critical infrastructure...

  19. Bacterial meningitis

    NARCIS (Netherlands)

    Roos, Karen L.; van de Beek, Diederik

    2010-01-01

    Bacterial meningitis is a neurological emergency. Empiric antimicrobial and adjunctive therapy should be initiated as soon as a single set of blood cultures has been obtained. Clinical signs suggestive of bacterial meningitis include fever, headache, meningismus, vomiting, photophobia, and an

  20. Global smoothness preservation and the variation-diminishing property

    Directory of Open Access Journals (Sweden)

    Gavrea Ioan

    1999-01-01

    Full Text Available In the center of our paper are two counterexamples showing the independence of the concepts of global smoothness preservation and variation diminution for sequences of approximation operators. Under certain additional assumptions it is shown that the variation-diminishing property is the stronger one. It is also demonstrated, however, that there are positive linear operators giving an optimal pointwise degree of approximation, and which preserve global smoothness, monotonicity and convexity, but are not variation-diminishing.

  1. Compressor airfoil tip clearance optimization system

    Science.gov (United States)

    Little, David A.; Pu, Zhengxiang

    2015-08-18

    A compressor airfoil tip clearance optimization system for reducing a gap between a tip of a compressor airfoil and a radially adjacent component of a turbine engine is disclosed. The turbine engine may include ID and OD flowpath boundaries configured to minimize compressor airfoil tip clearances during turbine engine operation in cooperation with one or more clearance reduction systems that are configured to move the rotor assembly axially to reduce tip clearance. The configurations of the ID and OD flowpath boundaries enhance the effectiveness of the axial movement of the rotor assembly, which includes movement of the ID flowpath boundary. During operation of the turbine engine, the rotor assembly may be moved axially to increase the efficiency of the turbine engine.

  2. 32 CFR 154.16 - Security clearance.

    Science.gov (United States)

    2010-07-01

    ... U.S. Senate and House of Representatives do not require personnel security clearances. They may be... part. The Director, Washington Headquarters Services (WHS) will initiate the required investigation...

  3. Keratoconus fittings: apical clearance or apical support?

    Science.gov (United States)

    McMonnies, Charles W

    2004-07-01

    To examine the relative merits of apical support and apical clearance fitting of rigid gas-permeable contact lenses for keratoconus. After an historic review of fitting approaches for keratoconus, a case report is described in which an adventitious apical clearance fitting for early keratoconus might have been associated with accelerated progress of the ectasia. The hypothesis that apical clearance fittings increase the risk of accelerating ectasia progression in early keratoconus is examined in counterpoint to the hypothesis that apical support fittings increase the risk of apical scarring. Reference is made to the responses of normal corneas to apical clearance fitting and to apical contact fittings used in orthokeratology fittings. The tendency for corneas to mold to contact lens curvature is reviewed. The possibility that reduced corneal thickness or tissue softening and associated changes to the biomechanical properties of the cornea in keratoconus may facilitate molding with apical clearance fitting is examined. Known and putative risk factors for fitting complications that are associated with apical clearance and apical touch contact lens fitting are given as a basis for the reader to draw conclusions about the management of contact lens fitting for keratoconus. The possibility of symptomless adverse responses is a strong indication for frequent routine aftercare reviews.

  4. Bacterial conjunctivitis

    OpenAIRE

    Epling, John

    2012-01-01

    Conjunctivitis causes irritation, itching, foreign body sensation, and watering or discharge of the eye. Most cases in adults are probably due to viral infection, but children are more likely to develop bacterial conjunctivitis than viral forms. The main bacterial pathogens are Staphylococcus species in adults, and Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis in children.A bacterial cause is more likely if there is gluing of the eyelids and no itch.Contact le...

  5. Bacterial conjunctivitis

    OpenAIRE

    Epling, John

    2010-01-01

    Conjunctivitis causes irritation, itching, foreign body sensation, and watering or discharge of the eye. Most cases in adults are probably due to viral infection, but children are more likely to develop bacterial conjunctivitis than viral forms. The main bacterial pathogens are Staphylococcus species in adults, and Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis in children.A bacterial cause is more likely if there is glueing of the eyelids and no itch.Contact l...

  6. Lower metabolic clearance of tizanidine in Japanese subjects.

    Science.gov (United States)

    Momo, Kenji; Homma, Masato; Kohda, Yukinao

    2013-12-01

    Our aim was to determine whether metabolic clearance, renal clearance, or both elimination pathways contribute to ethnic differences in tizanidine clearance, which is ~ 2-fold higher in Caucasians than in Asians. The pharmacokinetic parameters of tizanidine in 9 healthy male Japanese subjects were compared with those of Caucasians in previous studies. Metabolic clearance of tizanidine was lower in Japanese than in Caucasian subjects (5.9 vs. 8.1 - 10.9 l/h/kg), although renal clearances were similar (0.040 vs. 0.047 - 0.055 l/h/kg). The results suggest that ethnic differences in tizanidine clearance are due to differences in metabolic clearance.

  7. Bacterial Meningitis

    Science.gov (United States)

    ... Vaccine Schedules Preteen & Teen Vaccines Meningococcal Disease Sepsis Bacterial Meningitis Language: English (US) Español (Spanish) Recommend on ... Symptoms Diagnosis Treatment Prevention Reference Español: Meningitis bacteriana Bacterial meningitis is very serious and can be deadly. Death ...

  8. Bacterial adhesion

    NARCIS (Netherlands)

    Loosdrecht, van M.C.M.

    1988-01-01

    As mentioned in the introduction of this thesis bacterial adhesion has been studied from a variety of (mostly practice oriented) starting points. This has resulted in a range of widely divergent approaches. In order to elucidate general principles in bacterial adhesion phenomena, we felt it

  9. Bacterial Leaching

    Indian Academy of Sciences (India)

    Worldwide reserves of high-grade ores are diminishing at an alarming rate due to the rapid increase in the demand for metals. However there exist large stockpiles of low and lean grade ores yet to be mined. The problem is that the recovery of metals from low and lean grade ores using conventional techniques is very.

  10. Incidental finding of hypertension and diminished femoral pulses ...

    African Journals Online (AJOL)

    Incidental finding of hypertension and diminished femoral pulses: short-segment stenosis of the aorta just distal to the origin of the left subclavian artery. ... Young patients may present within the first few weeks of life with poor feeding, tachypnea and lethargy. They usually progress to overt congestive heart failure and shock.

  11. Is proprioception diminished in patients with patellar tendinopathy?

    NARCIS (Netherlands)

    Groot, H.E.; van der Worp, H.; Nijenbanning, L.; Diercks, R.L.; Zwerver, J.; van den Akker-Scheek, I.

    2016-01-01

    PURPOSE: Patellar tendinopathy is a highly prevalent overuse injury, and most treatments are only effective to some extent. This persistence of complaints could be linked to changed proprioception. One study showed diminished proprioception in athletes with lateral epicondylitis. Aim of this study

  12. Standardizing the measurement of parasite clearance in falciparum malaria: the parasite clearance estimator

    Directory of Open Access Journals (Sweden)

    Flegg Jennifer A

    2011-11-01

    Full Text Available Abstract Background A significant reduction in parasite clearance rates following artesunate treatment of falciparum malaria, and increased failure rates following artemisinin combination treatments (ACT, signaled emergent artemisinin resistance in Western Cambodia. Accurate measurement of parasite clearance is therefore essential to assess the spread of artemisinin resistance in Plasmodium falciparum. The slope of the log-parasitaemia versus time relationship is considered to be the most robust measure of anti-malarial effect. However, an initial lag phase of numerical instability often precedes a steady exponential decline in the parasite count after the start of anti-malarial treatment. This lag complicates the clearance estimation, introduces observer subjectivity, and may influence the accuracy and consistency of reported results. Methods To address this problem, a new approach to modelling clearance of malaria parasites from parasitaemia-time profiles has been explored and validated. The methodology detects when a lag phase is present, selects the most appropriate model (linear, quadratic or cubic to fit log-transformed parasite data, and calculates estimates of parasite clearance adjusted for this lag phase. Departing from previous approaches, parasite counts below the level of detection are accounted for and not excluded from the calculation. Results Data from large clinical studies with frequent parasite counts were examined. The effect of a lag phase on parasite clearance rate estimates is discussed, using individual patient data examples. As part of the World Wide Antimalarial Resistance Network's (WWARN efforts to make innovative approaches available to the malaria community, an automated informatics tool: the parasite clearance estimator has been developed. Conclusions The parasite clearance estimator provides a consistent, reliable and accurate method to estimate the lag phase and malaria parasite clearance rate. It could be used

  13. Diminished primary and secondary influenza virus-specific CD8(+) T-cell responses in CD4-depleted Ig(-/-) mice

    DEFF Research Database (Denmark)

    Riberdy, J M; Christensen, Jan Pravsgaard; Branum, K

    2000-01-01

    Optimal expansion of influenza virus nucleoprotein (D(b)NP(366))-specific CD8(+) T cells following respiratory challenge of naive Ig(-/-) microMT mice was found to require CD4(+) T-cell help, and this effect was also observed in primed animals. Absence of the CD4(+) population was consistently...... correlated with diminished recruitment of virus-specific CD8(+) T cells to the infected lung, delayed virus clearance, and increased morbidity. The splenic CD8(+) set generated during the recall response in Ig(-/-) mice primed at least 6 months previously showed a normal profile of gamma interferon...... production subsequent to short-term, in vitro stimulation with viral peptide, irrespective of a concurrent CD4(+) T-cell response. Both the magnitude and the localization profiles of virus-specific CD8(+) T cells, though perhaps not their functional characteristics, are thus modified in mice lacking CD4(+) T...

  14. Pharmacologic agents for mucus clearance in bronchiectasis.

    Science.gov (United States)

    Nair, Girish B; Ilowite, Jonathan S

    2012-06-01

    There are no approved pharmacologic agents to enhance mucus clearance in non-cystic fibrosis (CF) bronchiectasis. Evidence supports the use of hyperosmolar agents in CF, and studies with inhaled mannitol and hypertonic saline are ongoing in bronchiectasis. N-acetylcysteine may act more as an antioxidant than a mucolytic in other lung diseases. Dornase α is beneficial to patients with CF, but is not useful in patients with non-CF bronchiectasis. Mucokinetic agents such as β-agonists have the potential to improve mucociliary clearance in normals and many disease states, but have not been adequately studied in patients with bronchiectasis. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Airway clearance techniques for bronchiectasis.

    Science.gov (United States)

    Lee, Annemarie L; Burge, Angela T; Holland, Anne E

    2015-11-23

    People with non-cystic fibrosis bronchiectasis commonly experience chronic cough and sputum production, features that may be associated with progressive decline in clinical and functional status. Airway clearance techniques (ACTs) are often prescribed to facilitate expectoration of sputum from the lungs, but the efficacy of these techniques in a stable clinical state or during an acute exacerbation of bronchiectasis is unclear. Primary: to determine effects of ACTs on rates of acute exacerbation, incidence of hospitalisation and health-related quality of life (HRQoL) in individuals with acute and stable bronchiectasis. Secondary: to determine whether:• ACTs are safe for individuals with acute and stable bronchiectasis; and• ACTs have beneficial effects on physiology and symptoms in individuals with acute and stable bronchiectasis. We searched the Cochrane Airways Group Specialised Register of trials from inception to November 2015 and PEDro in March 2015, and we handsearched relevant journals. Randomised controlled parallel and cross-over trials that compared an ACT versus no treatment, sham ACT or directed coughing in participants with bronchiectasis. We used standard methodological procedures as expected by The Cochrane Collaboration. Seven studies involving 105 participants met the inclusion criteria of this review, six of which were cross-over in design. Six studies included adults with stable bronchiectasis; the other study examined clinically stable children with bronchiectasis. Three studies provided single treatment sessions, two lasted 15 to 21 days and two were longer-term studies. Interventions varied; some control groups received a sham intervention and others were inactive. The methodological quality of these studies was variable, with most studies failing to use concealed allocation for group assignment and with absence of blinding of participants and personnel for outcome measure assessment. Heterogeneity between studies precluded inclusion of

  16. Prediction of hepatic microsomal intrinsic clearance and human clearance values for drugs.

    Science.gov (United States)

    Nikolic, Katarina; Agababa, Danica

    2009-10-01

    Twenty-nine drugs of different structures were used in theoretical QSAR analysis of human hepatic microsomal intrinsic clearance (in vitro T(1/2) and in vitro CL'(int)) and whole body clearance (CL(blood)). The examined compounds demonstrated a wide range of scaled intrinsic clearance values. Constitutional, geometrical, physico-chemical and electronic descriptors were computed for the examined structures by use of the Marvin Sketch 5.1.3_2, the Chem3D Ultra 7.0.0 and the Dragon 5.4 program. Partial least squares regression (PLSR), has been applied for selection of the most relevant molecular descriptors and development of quantitative structure-activity relationship (QSAR) model for human hepatic microsomal intrinsic clearance (in vitro T(1/2)). Optimal QSAR models with nine and ten variables, R(2)>0.808 and cross-validation parameter q(pre)(2)>0.623, were selected and compared. Since the microsomal in vitro T(1/2) data can be used for calculation of in vitro CL'(int) and in vivo CL(blood), the developed QSAR model will enable one to analyze the kinetics of cytochrome P450-mediated reactions in term of intrinsic clearance and whole body clearance. A comparison is made between predictions produced from the QSAR analysis and experimental data, and there appears to be generally satisfactory correlations with the literature values for intrinsic clearance data.

  17. Bacterial Vaginosis

    Science.gov (United States)

    ... Pediatrician Health Issues Conditions Abdominal ADHD Allergies & Asthma Autism Cancer Chest & Lungs Chronic Conditions Cleft & Craniofacial Developmental ... most common vaginal infection in sexually active teenaged girls . It appears to be caused by a bacterial ...

  18. Bacterial Vaginosis

    Science.gov (United States)

    ... Archive STDs Home Page Bacterial Vaginosis (BV) Chlamydia Gonorrhea Genital Herpes Hepatitis HIV/AIDS & STDs Human Papillomavirus ( ... of getting other STDs, such as chlamydia and gonorrhea . These bacteria can sometimes cause pelvic inflammatory disease ( ...

  19. MINDFULNESS – MAY DIMINISH STRESS AND INCREASE ENERGY

    Directory of Open Access Journals (Sweden)

    Andronicus TORP

    2015-06-01

    Full Text Available Mindfulness is increasingly being applied in companies as a means to increase, among others, employee wellbeing and energy, and in the same time to diminish stress. This paper argues that there seems to be scientific evidence showing that certain mindfulness techniques may diminish stress and increase energy, yet it seems that there is a period in the beginning of the mindfulness practice where the techniques have the opposite effects. These findings seem to be contradictory to past findings, which indicated that only two thirds of people practicing mindfulness techniques have positive effects from that practice. It may be that everybody can have positive effects from the practice of the mentioned techniques, just that some need to practice for a longer period before obtaining these positive effects. Further scientific studies seem to be needed in order to clarify the full spectrum of effects and consequences of practicing different mindfulness techniques, and just as important, if these effects are valid for everybody.

  20. Metabolic reprogramming induced by ketone bodies diminishes pancreatic cancer cachexia.

    Science.gov (United States)

    Shukla, Surendra K; Gebregiworgis, Teklab; Purohit, Vinee; Chaika, Nina V; Gunda, Venugopal; Radhakrishnan, Prakash; Mehla, Kamiya; Pipinos, Iraklis I; Powers, Robert; Yu, Fang; Singh, Pankaj K

    2014-01-01

    Aberrant energy metabolism is a hallmark of cancer. To fulfill the increased energy requirements, tumor cells secrete cytokines/factors inducing muscle and fat degradation in cancer patients, a condition known as cancer cachexia. It accounts for nearly 20% of all cancer-related deaths. However, the mechanistic basis of cancer cachexia and therapies targeting cancer cachexia thus far remain elusive. A ketogenic diet, a high-fat and low-carbohydrate diet that elevates circulating levels of ketone bodies (i.e., acetoacetate, β-hydroxybutyrate, and acetone), serves as an alternative energy source. It has also been proposed that a ketogenic diet leads to systemic metabolic changes. Keeping in view the significant role of metabolic alterations in cancer, we hypothesized that a ketogenic diet may diminish glycolytic flux in tumor cells to alleviate cachexia syndrome and, hence, may provide an efficient therapeutic strategy. We observed reduced glycolytic flux in tumor cells upon treatment with ketone bodies. Ketone bodies also diminished glutamine uptake, overall ATP content, and survival in multiple pancreatic cancer cell lines, while inducing apoptosis. A decrease in levels of c-Myc, a metabolic master regulator, and its recruitment on glycolytic gene promoters, was in part responsible for the metabolic phenotype in tumor cells. Ketone body-induced intracellular metabolomic reprogramming in pancreatic cancer cells also leads to a significantly diminished cachexia in cell line models. Our mouse orthotopic xenograft models further confirmed the effect of a ketogenic diet in diminishing tumor growth and cachexia. Thus, our studies demonstrate that the cachectic phenotype is in part due to metabolic alterations in tumor cells, which can be reverted by a ketogenic diet, causing reduced tumor growth and inhibition of muscle and body weight loss.

  1. Diminished Reality Based on Image Inpainting Considering Background Geometry.

    Science.gov (United States)

    Kawai, Norihiko; Sato, Tomokazu; Yokoya, Naokazu

    2016-03-01

    Diminished reality aims to remove real objects from video images and fill in the missing regions with plausible background textures in real time. Most conventional methods based on image inpainting achieve diminished reality by assuming that the background around a target object is almost planar. This paper proposes a new diminished reality method that considers background geometries with less constraints than the conventional ones. In this study, we approximate the background geometry by combining local planes, and improve the quality of image inpainting by correcting the perspective distortion of texture and limiting the search area for finding similar textures as exemplars. The temporal coherence of texture is preserved using the geometries and camera pose estimated by visual-simultaneous localization and mapping (SLAM). The mask region that includes a target object is robustly set in each frame by projecting a 3D region, rather than tracking the object in 2D image space. The effectiveness of the proposed method is successfully demonstrated using several experimental environments.

  2. Clearance of seborrhoeic keratoses with topical dobesilate

    OpenAIRE

    Cuevas, Pedro; Angulo, Javier; Salgüero, Irene; Giménez-Gallego, Guillermo

    2012-01-01

    A patient with two seborrhoeic keratoses in the face received a single daily application of dobesilate cream during 6 months. Dobesilate achieved complete clearance of the seborrhoeic keratosis lesions with good cosmoses, suggesting that this compound is a safe and efficient candidate in the treatment of seborrhoeic keratoses.

  3. Clearance of seborrhoeic keratoses with topical dobesilate.

    Science.gov (United States)

    Cuevas, Pedro; Angulo, Javier; Salgüero, Irene; Giménez-Gallego, Guillermo

    2012-06-21

    A patient with two seborrhoeic keratoses in the face received a single daily application of dobesilate cream during 6 months. Dobesilate achieved complete clearance of the seborrhoeic keratosis lesions with good cosmoses, suggesting that this compound is a safe and efficient candidate in the treatment of seborrhoeic keratoses.

  4. Apoptotic Cell Clearance in Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Qian Zheng

    2017-12-01

    Full Text Available The swift clearance of apoptotic cells (ACs (efferocytosis by phagocytes is a critical event during development of all multicellular organisms. It is achieved through phagocytosis by professional or amateur phagocytes. Failure in this process can lead to the development of inflammatory autoimmune or neurodegenerative diseases. AC clearance has been conserved throughout evolution, although many details in its mechanisms remain to be explored. It has been studied in the context of mammalian macrophages, and in the nematode Caenorhabditis elegans, which lacks “professional” phagocytes such as macrophages, but in which other cell types can engulf apoptotic corpses. In Drosophila melanogaster, ACs are engulfed by macrophages, glial, and epithelial cells. Drosophila macrophages perform similar functions to those of mammalian macrophages. They are professional phagocytes that participate in phagocytosis of ACs and pathogens. Study of AC clearance in Drosophila has identified some key elements, like the receptors Croquemort and Draper, promoting Drosophila as a suitable model to genetically dissect this process. In this review, we survey recent works of AC clearance pathways in Drosophila, and discuss the physiological outcomes and consequences of this process.

  5. Bromsulphalein (BSP) clearance in ageing rats

    NARCIS (Netherlands)

    Hollander, C.F.; Leeuw-Israel, F.R. de; Arp-Neefjes, J.M.

    1968-01-01

    Liver function in ageing rats was studied, using the bromsulphalein (BSP) clearance test. The test was done on ultramicro scale. This made it possible to repeat the test several times in the same animal and to start a longitudinal study. In 3-month-old rats the BSP retentions, measured 15, 30 and 45

  6. Frequency of stone clearance after extracorporeal shockwave ...

    African Journals Online (AJOL)

    A. Khalique

    2017-02-24

    Feb 24, 2017 ... Abstract. Objective: To determine the rate of stone clearance after extracorporeal shockwave lithotripsy (ESWL) for renal stones in adult patients with renal insufficiency. Subjects and methods: This is a cross-sectional descriptive study of 117 adult patients who underwent. ESWL. The indications for ESWL ...

  7. Augmenting solute clearance in peritoneal dialysis

    NARCIS (Netherlands)

    Krediet, R. T.; Douma, C. E.; van Olden, R. W.; Ho-Dac-Pannekeet, M. M.; Struijk, D. G.

    1998-01-01

    BACKGROUND: The removal of low molecular weight solutes by peritoneal dialysis is less than by hemodialysis. The targets for Kt/Vurea and creatinine clearance formulated in the Dialysis Outcome Quality Initiative are unlikely to be achieved in a substantial portion of peritoneal dialysis patients.

  8. 19 CFR 122.26 - Entry and clearance.

    Science.gov (United States)

    2010-04-01

    ... AIR COMMERCE REGULATIONS Private Aircraft § 122.26 Entry and clearance. Private aircraft, as defined... information as set forth in § 122.22(c), and grants electronic clearance via electronic mail or telephone. ...

  9. The influence of body posture on lithium clearance

    DEFF Research Database (Denmark)

    Kamper, A L; Strandgaard, S; Holstein-Rathlou, N H

    1988-01-01

    To establish appropriate standard circumstances for lithium clearance measurements, a study was undertaken in 12 healthy volunteers. In each subject, the glomerular filtration rate (GFR), as estimated by [51Cr]EDTA plasma clearance, and the renal clearances of lithium, sodium and potassium were m...... during moderate physical activity. Hence, when renal tubular function is studied with the lithium clearance method, standardization of posture and physical activity is important. In such studies physical activity such as walking should particularly be avoided....

  10. Bacterial conjunctivitis.

    Science.gov (United States)

    Epling, John

    2012-02-20

    Most cases of conjunctivitis in adults are probably due to viral infection, but children are more likely to develop bacterial conjunctivitis than they are viral forms. The main bacterial pathogens are Haemophilus influenzae and Streptococcus pneumoniae in adults and children, and Moraxella catarrhalis in children. Contact lens wearers may be more likely to develop gram-negative infections. Bacterial keratitis occurs in up to 30 per 100,000 contact lens wearers. We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of empirical treatment in adults and children with suspected bacterial conjunctivitis? What are the effects of treatment in adults and children with bacteriologically confirmed bacterial conjunctivitis? What are the effects of treatment in adults and children with clinically confirmed gonococcal conjunctivitis? We searched: Medline, Embase, The Cochrane Library, and other important databases up to July 2011 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). We found 44 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. In this systematic review we present information relating to the effectiveness and safety of the following interventions: ocular decongestants, oral antibiotics, parenteral antibiotics, saline, topical antibiotics, and warm compresses.

  11. Evaluation of an Active Clearance Control System Concept

    Science.gov (United States)

    Steinetz, Bruce M.; Lattime, Scott B.; Taylor, Shawn; DeCastro, Jonathan A.; Oswald, Jay; Melcher, Kevin J.

    2005-01-01

    Reducing blade tip clearances through active tip clearance control in the high pressure turbine can lead to significant reductions in emissions and specific fuel consumption as well as dramatic improvements in operating efficiency and increased service life. Current engines employ scheduled cooling of the outer case flanges to reduce high pressure turbine tip clearances during cruise conditions. These systems have relatively slow response and do not use clearance measurement, thereby forcing cold build clearances to set the minimum clearances at extreme operating conditions (e.g., takeoff, reburst) and not allowing cruise clearances to be minimized due to the possibility of throttle transients (e.g., step change in altitude). In an effort to improve upon current thermal methods, a first generation mechanically-actuated active clearance control (ACC) system has been designed and fabricated. The system utilizes independent actuators, a segmented shroud structure, and clearance measurement feedback to provide fast and precise active clearance control throughout engine operation. Ambient temperature performance tests of this first generation ACC system assessed individual seal component leakage rates and both static and dynamic overall system leakage rates. The ability of the nine electric stepper motors to control the position of the seal carriers in both open- and closed-loop control modes for single and multiple cycles was investigated. The ability of the system to follow simulated engine clearance transients in closed-loop mode showed the system was able to track clearances to within a tight tolerance ( 0.001 in. error).

  12. 14 CFR 1260.63 - Customs clearance and visas.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Customs clearance and visas. 1260.63 Section 1260.63 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION GRANTS AND COOPERATIVE AGREEMENTS General Special Conditions § 1260.63 Customs clearance and visas. Customs Clearance and Visas (For...

  13. BACTERIAL CONSORTIUM

    Directory of Open Access Journals (Sweden)

    Payel Sarkar

    2013-01-01

    Full Text Available Petroleum aromatic hydrocarbons like benzen e, toluene, ethyl benzene and xylene, together known as BTEX, has almost the same chemical structure. These aromatic hydrocarbons are released as pollutants in th e environment. This work was taken up to develop a solvent tolerant bacterial cons ortium that could degrade BTEX compounds as they all share a common chemical structure. We have isolated almost 60 different types of bacterial strains from different petroleum contaminated sites. Of these 60 bacterial strains almost 20 microorganisms were screene d on the basis of capability to tolerate high concentration of BTEX. Ten differe nt consortia were prepared and the compatibility of the bacterial strains within the consortia was checked by gram staining and BTEX tolerance level. Four successful mi crobial consortia were selected in which all the bacterial strains concomitantly grew in presence of high concentration of BTEX (10% of toluene, 10% of benzene 5% ethyl benzene and 1% xylene. Consortium #2 showed the highest growth rate in pr esence of BTEX. Degradation of BTEX by consortium #2 was monitored for 5 days by gradual decrease in the volume of the solvents. The maximum reduction observed wa s 85% in 5 days. Gas chromatography results also reveal that could completely degrade benzene and ethyl benzene within 48 hours. Almost 90% degradation of toluene and xylene in 48 hours was exhibited by consortium #2. It could also tolerate and degrade many industrial solvents such as chloroform, DMSO, acetonitrile having a wide range of log P values (0.03–3.1. Degradation of aromatic hydrocarbon like BTEX by a solvent tolerant bacterial consortium is greatly significant as it could degrade high concentration of pollutants compared to a bacterium and also reduces the time span of degradation.

  14. Elements to diminish radioactive accidents; Elementos para disminuir accidentes radiactivos

    Energy Technology Data Exchange (ETDEWEB)

    Cortes I, M.E.; Ramirez G, F.P. [Instituto Mexicano del Petroleo, Eje Central Lazaro Cardenas 152, C.P. 07730 Mexico D.F. (Mexico)

    1998-12-31

    In this work it is presented an application of the cause-effect diagram method or Ichikawa method identifying the elements that allow to diminish accidents when the radioactive materials are transported. It is considered the transport of hazardous materials which include radioactive materials in the period: December 1996 until March 1997. Among the identified elements by this method it is possible to mention: the road type, the radioactive source protection, the grade driver responsibility and the preparation that the OEP has in the radioactive material management. It is showed the differences found between the country inner roads and the Mexico City area. (Author)

  15. Inflammasome Activation by ATP Enhances Citrobacter rodentium Clearance through ROS Generation

    Directory of Open Access Journals (Sweden)

    Michael Bording-Jorgensen

    2017-01-01

    Full Text Available Background: Nod-like receptor family, pyrin domain containing 3 (NLRP3 is an important cytosolic sensor of cellular stress and infection. Once activated, NLRP3 forms a multiprotein complex (inflammasome that triggers the maturation and secretion of interleukin (IL-1β and IL-18. We aimed to define the consequences of NLRP3 induction, utilizing exogenous adenosine triphosphate (ATP as an inflammasome activator, to determine if inflammasome activation increases macrophage killing of Citrobacter rodentium and define mechanisms. Methods: Bacterial survival was measured using a gentamicin protection assay. Inflammasome activation or inhibition in mouse J774A.1 macrophages were assessed by measuring IL-1β; cytokines and reactive oxygen species (ROS were measured by ELISA and DCFDA, respectively. Results: Activation of the inflammasome increased bacterial killing by macrophages and its inhibition attenuated this effect with no impact on phagocytosis or cell death. Furthermore, inflammasome activation suppressed pro-inflammatory cytokines during infection, possibly due to more effective bacterial killing. While the infection increased ROS production, this effect was reduced by inflammasome inhibitors, indicating that ROS is inflammasome-dependent. ROS inhibitors increased bacterial survival in the presence of ATP, suggesting that inflammasome-induced bacterial killing is mediated, at least in part, by ROS activity. Conclusion: Improving inflammasome activity during infection may increase bacterial clearance by macrophages and reduce subsequent microbe-induced inflammation.

  16. Simulation and experiment of the effect of clearance of impeller wear-rings on the performance of centrifugal pump

    Science.gov (United States)

    Chen, S. X.; Pan, Z. Y.; Wu, Y. L.; Zhang, D. Q.

    2012-11-01

    The effect of clearance of impeller wear-rings on the performance of a centrifugal pump was investigated numerically and experimentally. The whole flow field model including front and back shrouds of pump was designed so as to accurately calculate the head and efficiency of the centrifugal pump. Based on RNG k-ε turbulence model, three wear-rings schemes were established, and the effects of clearance of impeller wear-rings on the hydraulic efficiency and mechanical efficiency of the centrifugal pump was analyzed, chiefly from the turbulent kinetic energy, vorticity and radial force angles. According to the results, it can be drawn that the head and total efficiency of the centrifugal pump increase as the clearance value of wear-rings narrows. The following reasons may account for it: firstly, as the clearance value of wear-rings declines, the turbulent kinetic energy and energy dissipation decrease within the impeller, and the impact of secondary flow at the inlet of impeller on the mainstream weakens slowly, which leads to a lower hydraulic loss, thus a higher hydraulic efficiency; secondly, radial force decreases with the clearance value of wear-rings, so the eccentric whirl of centrifugal pump is dampened, which results in a lower mechanical loss and a higher mechanical efficiency; thirdly, the front shroud leakage diminishes with the clearance value of wear-rings, therefore, the volume loss is reduced and volume efficiency improved. Finally, the first wear-ring scheme of impeller is adopted after comprehensive comparison of these three wear-ring schemes, because its efficiency is highest and it satisfies the requirements of the engineering application.

  17. CO2 clearance by membrane lungs.

    Science.gov (United States)

    Sun, Liqun; Kaesler, Andreas; Fernando, Piyumindri; Thompson, Alex J; Toomasian, John M; Bartlett, Robert H

    2017-10-01

    Commercial membrane lungs are designed to transfer a specific amount of oxygen per unit of venous blood flow. Membrane lungs are much more efficient at removing CO2 than adding oxygen, but the range of CO2 transfer is rarely reported. Commercial membrane lungs were studied with the goal of evaluating CO2 removal capacity. CO2 removal was measured in 4 commercial membrane lungs under standardized conditions. CO2 clearance can be greater than 4 times that of oxygen at a given blood flow when the gas to blood flow ratio is elevated to 4:1 or 8:1. The CO2 clearance was less dependent on surface area and configuration than oxygen transfer. Any ECMO system can be used for selective CO2 removal.

  18. Gas turbine engine active clearance control

    Science.gov (United States)

    Deveau, Paul J. (Inventor); Greenberg, Paul B. (Inventor); Paolillo, Roger E. (Inventor)

    1985-01-01

    Method for controlling the clearance between rotating and stationary components of a gas turbine engine are disclosed. Techniques for achieving close correspondence between the radial position of rotor blade tips and the circumscribing outer air seals are disclosed. In one embodiment turbine case temperature modifying air is provided in flow rate, pressure and temperature varied as a function of engine operating condition. The modifying air is scheduled from a modulating and mixing valve supplied with dual source compressor air. One source supplies relatively low pressure, low temperature air and the other source supplies relatively high pressure, high temperature air. After the air has been used for the active clearance control (cooling the high pressure turbine case) it is then used for cooling the structure that supports the outer air seal and other high pressure turbine component parts.

  19. Bomb strike experiment for mine clearance operations

    OpenAIRE

    Ray, Gregory P.

    2006-01-01

    The Bomb Strike Experiment for Mine Countermeasure Operations, currently sponsored through the Office of Naval Research mine impact burial prediction project, is part of a multi-year, comprehensive effort aimed at enhancing the Navyâ s fleet naval mine clearance capability and success. The investigation discussed in this paper examines the experimental and theoretical characteristics of a rigid body falling through the air, water, and sediment column at high speed. Several experiments were ...

  20. Bacterial stress

    Indian Academy of Sciences (India)

    First page Back Continue Last page Graphics. Bacterial stress. Physicochemical and chemical parameters: temperature, pressure, pH, salt concentration, oxygen, irradiation. Nutritional depravation: nutrient starvation, water shortage. Toxic compounds: Antibiotics, heavy metals, toxins, mutagens. Interactions with other cells: ...

  1. Bacterial lipases

    NARCIS (Netherlands)

    Jaeger, Karl-Erich; Ransac, Stéphane; Dijkstra, Bauke W.; Colson, Charles; Heuvel, Margreet van; Misset, Onno

    Many different bacterial species produce lipases which hydrolyze esters of glycerol with preferably long-chain fatty acids. They act at the interface generated by a hydrophobic lipid substrate in a hydrophilic aqueous medium. A characteristic property of lipases is called interfacial activation,

  2. Bacterial meningitis

    NARCIS (Netherlands)

    Heckenberg, Sebastiaan G. B.; Brouwer, Matthijs C.; van de Beek, Diederik

    2014-01-01

    Bacterial meningitis is a neurologic emergency. Vaccination against common pathogens has decreased the burden of disease. Early diagnosis and rapid initiation of empiric antimicrobial and adjunctive therapy are vital. Therapy should be initiated as soon as blood cultures have been obtained,

  3. Bacterial Cryoprotectants

    Indian Academy of Sciences (India)

    culture plate, whereas no growth was detected under similar conditions without betaine. They also observed that uptake of betaine into the bacterial cell was .... lar content of bound water, and (4) modifying the growth of ice crystals in the extracellular environment. Conclusion. At the present time, betaine serves as a model ...

  4. Bacterial mitosis

    DEFF Research Database (Denmark)

    Møller-Jensen, Jakob; Borch, Jonas; Dam, Mette

    2003-01-01

    Bacterial DNA segregation takes place in an active and ordered fashion. In the case of Escherichia coli plasmid R1, the partitioning system (par) separates paired plasmid copies and moves them to opposite cell poles. Here we address the mechanism by which the three components of the R1 par system...

  5. Bacterial Cryoprotectants

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 7; Issue 11. Bacterial Cryoprotectants. M K Chattopadhyay. General Article Volume 7 Issue 11 November 2002 pp 59-63. Fulltext. Click here to view fulltext PDF. Permanent link: http://www.ias.ac.in/article/fulltext/reso/007/11/0059-0063. Keywords.

  6. Group Interaction Sustains Positive Moods and Diminishes Negative Moods.

    Science.gov (United States)

    Park, Ernest S; Hinsz, Verlin B

    2015-12-01

    The social interactions of task groups were investigated for their influences on member moods. Initially, participants' received an induction of positive, negative, or neutral moods via listening to music that continued throughout the experimental session. Moods were measured after the induction. Students then made decisions on four choice dilemmas alone or as members of a four-person group. Subsequently, positive and negative moods were again measured. Positive moods of participants who worked with other group members on the task were sustained, but diminished for those working alone. Negative moods of participants working in groups diminished over time, but were sustained for those working individually. These results were interpreted in the context of motivational systems theory of group involvement (Park & Hinsz, 2006). Additionally, although there was a tendency for member moods to homogenize over assessments, this did not reach significance. Results document the affective benefits that often accompany task group interaction suggesting that group interaction has features of positive mood induction. This report highlights the need to consider social influences on affect in task settings so that group dynamics, processes, and behaviors can be better understood.

  7. Metabolic Requirements of Escherichia coli in Intracellular Bacterial Communities during Urinary Tract Infection Pathogenesis.

    Science.gov (United States)

    Conover, Matt S; Hadjifrangiskou, Maria; Palermo, Joseph J; Hibbing, Michael E; Dodson, Karen W; Hultgren, Scott J

    2016-04-12

    Uropathogenic Escherichia coli (UPEC) is the primary etiological agent of over 85% of community-acquired urinary tract infections (UTIs). Mouse models of infection have shown that UPEC can invade bladder epithelial cells in a type 1 pilus-dependent mechanism, avoid a TLR4-mediated exocytic process, and escape into the host cell cytoplasm. The internalized UPEC can clonally replicate into biofilm-like intracellular bacterial communities (IBCs) of thousands of bacteria while avoiding many host clearance mechanisms. Importantly, IBCs have been documented in urine from women and children suffering acute UTI. To understand this protected bacterial niche, we elucidated the transcriptional profile of bacteria within IBCs using microarrays. We delineated the upregulation within the IBC of genes involved in iron acquisition, metabolism, and transport. Interestingly, lacZ was highly upregulated, suggesting that bacteria were sensing and/or utilizing a galactoside for metabolism in the IBC. A ΔlacZ strain displayed significantly smaller IBCs than the wild-type strain and was attenuated during competitive infection with a wild-type strain. Similarly, a galK mutant resulted in smaller IBCs and attenuated infection. Further, analysis of the highly upregulated gene yeaR revealed that this gene contributes to oxidative stress resistance and type 1 pilus production. These results suggest that bacteria within the IBC are under oxidative stress and, consistent with previous reports, utilize nonglucose carbon metabolites. Better understanding of the bacterial mechanisms used for IBC development and establishment of infection may give insights into development of novel anti-virulence strategies. Urinary tract infections (UTIs) are one of the most common bacterial infections, impacting mostly women. Every year, millions of UTIs occur in the U.S. with most being caused by uropathogenic E. coli(UPEC). During a UTI, UPEC invade bladder cells and form an intracellular bacterial community

  8. mTORC1-independent TFEB activation via Akt inhibition promotes cellular clearance in neurodegenerative storage diseases

    Science.gov (United States)

    Palmieri, Michela; Pal, Rituraj; Nelvagal, Hemanth R.; Lotfi, Parisa; Stinnett, Gary R.; Seymour, Michelle L.; Chaudhury, Arindam; Bajaj, Lakshya; Bondar, Vitaliy V.; Bremner, Laura; Saleem, Usama; Tse, Dennis Y.; Sanagasetti, Deepthi; Wu, Samuel M.; Neilson, Joel R.; Pereira, Fred A.; Pautler, Robia G.; Rodney, George G.; Cooper, Jonathan D.; Sardiello, Marco

    2017-01-01

    Neurodegenerative diseases characterized by aberrant accumulation of undigested cellular components represent unmet medical conditions for which the identification of actionable targets is urgently needed. Here we identify a pharmacologically actionable pathway that controls cellular clearance via Akt modulation of transcription factor EB (TFEB), a master regulator of lysosomal pathways. We show that Akt phosphorylates TFEB at Ser467 and represses TFEB nuclear translocation independently of mechanistic target of rapamycin complex 1 (mTORC1), a known TFEB inhibitor. The autophagy enhancer trehalose activates TFEB by diminishing Akt activity. Administration of trehalose to a mouse model of Batten disease, a prototypical neurodegenerative disease presenting with intralysosomal storage, enhances clearance of proteolipid aggregates, reduces neuropathology and prolongs survival of diseased mice. Pharmacological inhibition of Akt promotes cellular clearance in cells from patients with a variety of lysosomal diseases, thus suggesting broad applicability of this approach. These findings open new perspectives for the clinical translation of TFEB-mediated enhancement of cellular clearance in neurodegenerative storage diseases. PMID:28165011

  9. Carbon Nanotubes in the Human Respiratory Tract-Clearance Modeling.

    Science.gov (United States)

    Sturm, Robert

    2017-03-01

    Clearance of single-wall carbon nanotubes (SWCNT, diameter: 5 nm) and multi-wall carbon nanotubes (MWCNT, diameter: 50 nm) in the respiratory tract was predicted for various age groups (infants, children, adolescents, and adults). The model was founded on the assumption that lung clearance takes place in three distinct phases: (i) fast mucociliary clearance, (ii) slow bronchial clearance, and (iii) alveolar clearance. To each of these phases a specific fraction of deposited particles was attributed, the amount of which depended on particles' geometry and particles' deposition sites in the respiratory system. Clearance velocities were expressed by respective clearance half-times ranging from several hours in the case of fast clearance to tens of days in the case of slow clearance. Results of the simulations clearly demonstrate that for the specific deposition scenario (sitting, nasal breathing) considered here fast clearance fraction exhibits a slight decrease with increasing age, but total clearance times (i.e. time spans, within which 100% of the deposited particulate mass are removed) are rather constant among the age groups. Nanotubes deposited in the respiratory bronchioles and alveoli are usually subject to a long-term storage in these structures and, thus, may trigger malignant transformations in adjacent cells and tissues. © The Author 2017. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.

  10. Effect of salivary agglutination on oral streptococcal clearance by human polymorphonuclear neutrophil granulocytes.

    Science.gov (United States)

    Itzek, A; Chen, Z; Merritt, J; Kreth, J

    2017-06-01

    Salivary agglutination is an important host defense mechanism to aggregate oral commensal bacteria as well as invading pathogens. Saliva flow and subsequent swallowing more easily clear aggregated bacteria compared with single cells. Phagocytic clearance of bacteria through polymorphonuclear neutrophil granulocytes also seems to increase to a certain extent with the size of bacterial aggregates. To determine a connection between salivary agglutination and the host innate immune response by phagocytosis, an in vitro agglutination assay was developed reproducing the average size of salivary bacterial aggregates. Using the oral commensal Streptococcus gordonii as a model organism, the effect of salivary agglutination on phagocytic clearance through polymorphonuclear neutrophil granulocytes was investigated. Here we describe how salivary aggregates of S. gordonii are readily cleared through phagocytosis, whereas single bacterial cells showed a significant delay in being phagocytosed and killed. Furthermore, before phagocytosis the polymorphonuclear neutrophil granulocytes were able to induce a specific de-aggregation, which was dependent on serine protease activity. The data presented suggest that salivary agglutination of bacterial cells leads to an ideal size for recognition by polymorphonuclear neutrophil granulocytes. As a first line of defense, these phagocytic cells are able to recognize the aggregates and de-aggregate them via serine proteases to a more manageable size for efficient phagocytosis and subsequent killing in the phagolysosome. This observed mechanism not only prevents the rapid spreading of oral bacterial cells while entering the bloodstream but would also avoid degranulation of involved polymorphonuclear neutrophil granulocytes, so preventing collateral damage to nearby tissue. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Bacterial Adhesion & Blocking Bacterial Adhesion

    DEFF Research Database (Denmark)

    Vejborg, Rebecca Munk

    2008-01-01

    components. These substances may both mediate and stabilize the bacterial biofilm. Finally, several adhesive structures were examined, and a novel physiological biofilm phenotype in E.coli biofilms was characterized, namely cell chain formation. The autotransporter protein, antigen 43, was implicated...

  12. Bacterial lipases

    OpenAIRE

    Jaeger, Karl-Erich; Ransac, Stéphane; Dijkstra, Bauke W.; Colson, Charles; Heuvel, Margreet van; Misset, Onno

    1994-01-01

    Many different bacterial species produce lipases which hydrolyze esters of glycerol with preferably long-chain fatty acids. They act at the interface generated by a hydrophobic lipid substrate in a hydrophilic aqueous medium. A characteristic property of lipases is called interfacial activation, meaning a sharp increase in lipase activity observed when the substrate starts to form an emulsion, thereby presenting to the enzyme an interfacial area. As a consequence, the kinetics of a lipase rea...

  13. [Caesarean section: History, epidemiology, and ethics to diminish its incidence].

    Science.gov (United States)

    Martínez-Salazar, Gerardo Jesús; Grimaldo-Valenzuela, Pedro Mario; Vázquez-Peña, Gloria Gabriela; Reyes-Segovia, Carlos; Torres-Luna, Gabriela; Escudero-Lourdes, Gabriela Virginia

    2015-01-01

    Cesarean section has become the most performed surgery and it has been enhanced with the use of antibiotics and improvement in surgical techniques. The aim of this systematic review is to describe and clarify some historical and ethical characteristics of this surgery, pointing out some aspects about its epidemiological behavior, becoming a topic that should be treated globally, giving priority to the prevention and identification of factors that may increase the incidence rates. Today, this "epidemic" reported rates higher than fifty percent, so it is considered a worldwide public health problem. Consequently, in Mexico strategies aimed at its reduction have been implemented. However, sociocultural, economic, medicolegal and biomedical factors are aspects that may difficult this goal. As we decrease the percentage of cesarean section in nulliparous patients, we diminish the number of iterative cesarean and its associated complications. This aim must be achieved through the adherence to the guidelines which promote interest in monitoring and delivery care in health institutions of our country.

  14. Acrylamide diminishing in potato chips by using commercial Asparaginase

    DEFF Research Database (Denmark)

    Pedreschi, Franco; Mariotti, Salomé; Granby, Kit

    2011-01-01

    In April 2002, Swedish researchers shocked the food safety world when they presented preliminary findings of acrylamide in some fried and baked foods, most notably potato chips and French fries. Asparagine is an aminoacid precursor of acrylamide formation through Maillard reaction. Asparaginase...... enzyme converts free asparagine into aspartic acid; another amino acid that does not form acrylamide and also maintains intact the food sensorial properties. The objective of this research was to compare the effect of different temperature-time asparaginase treatments over the acrylamide content....... Soaking blanched potato chips in a 10000 ASNU/l asparaginase solution for 20 min at 50°C was the most effective time-temperature combination asparaginase treatment in order to diminish the acrylamide content in potato chips in -90 %....

  15. Glucose clearance is higher in arm than leg muscle in type 2 diabetes

    DEFF Research Database (Denmark)

    Olsen, David B; Sacchetti, Massimo; Dela, Flemming

    2005-01-01

    Insulin-mediated glucose clearance (GC) is diminished in type 2 diabetes. Skeletal muscle has been estimated to account for essentially all of the impairment. Such estimations were based on leg muscle and extrapolated to whole body muscle mass. However, skeletal muscle is not a uniform tissue...... and insulin resistance may not be evenly distributed. We measured basal and insulin-mediated (1 pmol min-1 kg-1) GC simultaneously in the arm and leg in type 2 diabetes patients (TYPE 2) and controls (CON) (n=6 for both). During the clamp arterio-venous glucose extraction was higher in CON versus TYPE 2......, regardless of insulin resistance, which may indicate better preserved insulin sensitivity in arm than leg muscle in type 2 diabetes....

  16. Robotic Range Clearance Competition (R2C2)

    Science.gov (United States)

    2011-10-01

    clearance times by two thirds and costs by one third if automated clearing equipment is used (Skibba, 2003 - Honey Lake Robotic Range Clearance Operations...September 2012. 9. REFERENCES Skibba K. Brian, Honey Lake Robotic Range Clearance Operations, AFRL-RX-TY-TR- 2010-0003, Tyndall AFB: AFRL Materials...Location Date Kick Off Event Crystal City 22 October 2009 Industry Day Tyndall AFB 10 Dec 2009 Signed Letters of Intent Online 3 May 2010 Category

  17. Surfactant secretion and clearance in the newborn

    Energy Technology Data Exchange (ETDEWEB)

    Stevens, P.A.; Wright, J.R.; Clements, J.A. (Univ. of California, San Francisco (USA))

    1989-10-01

    Pregnant rabbits (30 days) were injected intravenously with (3H)choline 8 h before delivery. The fetuses were delivered, and lung lavage and lamellar body phospholipids (PL) were analyzed. Some newborns also received radioactively labeled surfactant intratracheally on delivery and were permitted to breathe. With time, intratracheal label decreased in lavage and appeared in the lamellar body fraction, and intravenous label accumulated in both pools. Using a tracer analysis for non-steady state, we calculated surfactant secretion and clearance rates for the newborn period. Before birth, both rates rose slightly from 1.8 micrograms PL.g body wt-1.h-1 at 6 h before birth to 7.3 at birth. Immediately after birth, secretion rate rose to 37.7 micrograms PL.g body wt-1.h-1. Between 1.5 and 2 h after birth it fell to a minimum of 1.8 micrograms PL.g body wt-1.h-1 and then rose slowly to 6.0 at 12 h. After birth, clearance rate increased less than secretion rate (maximum 24.7 micrograms PL.g body wt-1.h-1 shortly after birth) then followed the same pattern but did not balance secretion rate in the 1st day.

  18. Is proprioception diminished in patients with patellar tendinopathy?

    Science.gov (United States)

    Groot, H E; van der Worp, H; Nijenbanning, L; Diercks, R L; Zwerver, J; van den Akker-Scheek, I

    2016-03-01

    Patellar tendinopathy is a highly prevalent overuse injury, and most treatments are only effective to some extent. This persistence of complaints could be linked to changed proprioception. One study showed diminished proprioception in athletes with lateral epicondylitis. Aim of this study was to determine differences in proprioception, by measuring threshold to detect passive motion (TTDPM) between recreational athletes diagnosed with patellar tendinopathy and healthy controls. The TTDPM as measure of proprioception was determined in 22 recreational athletes with patellar tendinopathy and 22 healthy recreational athletes using a validated instrument. Amount of knee flexion and extension before the movement was noticed by the subject was determined. 80 measurements per athlete (left and right leg, towards extension and flexion and with two starting angles of 20° and 40° flexion) were performed. Mean TTDPM was compared between groups and among the injured recreational athletes between the affected and unaffected knee. No significant difference in TTDPM was found between recreational athletes with patellar tendinopathy and healthy controls. We did find a significant difference between the injured and non-injured knee in recreational athletes with patellar tendinopathy; mean TTDPM was 0.02° higher in the injured knee (p=0.044). No difference was found in proprioception between recreational athletes with patellar tendinopathy and healthy recreational athletes. It is unclear whether such a small difference in TTDPM between affected and unaffected knee is important in clinical setting. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Image-Based Models for Specularity Propagation in Diminished Reality.

    Science.gov (United States)

    Hadj Said, Souheil; Tamaazousti, Mohamed; Bartoli, Adrien

    2017-05-18

    The aim of Diminished Reality (DR) is to remove a target object in a live video stream seamlessly. In our approach, the area of the target object is replaced with new texture that blends with the rest of the image. The result is then propagated to the next frames of the video. One of the important stages of this technique is to update the target region with respect to the illumination change. This is a complex and recurrent problem when the viewpoint changes. We show that the state-of-the-art in DR fails in solving this problem, even under simple scenarios. We then use local illumination models to address this problem. According to these models, the variation in illumination only affects the specular component of the image. In the context of DR, the problem is therefore solved by propagating the specularities in the target area. We list a set of structural properties of specularities which we incorporate in two new models for specularity propagation. Our first model includes the same property as the previous approaches, which is the smoothness of illumination variation, but has a different estimation method based on the Thin-Plate Spline. Our second model incorporates more properties of the specularity's shape on planar surfaces. Experimental results on synthetic and real data show that our strategy substantially improves the rendering quality compared to the state-of-the-art in DR.

  20. Dehydroepiandrosterone (DHEA) supplementation in diminished ovarian reserve (DOR).

    Science.gov (United States)

    Gleicher, Norbert; Barad, David H

    2011-05-17

    With infertility populations in the developed world rapidly aging, treatment of diminished ovarian reserve (DOR) assumes increasing clinical importance. Dehydroepiandrosterone (DHEA) has been reported to improve pregnancy chances with DOR, and is now utilized by approximately one third of all IVF centers world-wide. Increasing DHEA utilization and publication of a first prospectively randomized trial now warrants a systematic review. PubMed, Cochrane and Ovid Medline were searched between 1995 and 2010 under the following strategy: [DHEA or androgens or testosterone > and ]. Bibliographies of relevant publications were further explored for additional relevant citations. Since only one randomized study has been published, publications, independent of evidence levels and quality assessment, were reviewed. Current best available evidence suggests that DHEA improves ovarian function, increases pregnancy chances and, by reducing aneuploidy, lowers miscarriage rates. DHEA over time also appears to objectively improve ovarian reserve. Recent animal data support androgens in promoting preantral follicle growth and reduction in follicle atresia. Improvement of oocyte/embryo quality with DHEA supplementation potentially suggests a new concept of ovarian aging, where ovarian environments, but not oocytes themselves, age. DHEA may, thus, represent a first agent beneficially affecting aging ovarian environments. Others can be expected to follow.

  1. Overeducation and depressive symptoms: diminishing mental health returns to education.

    Science.gov (United States)

    Bracke, Piet; Pattyn, Elise; von dem Knesebeck, Olaf

    2013-11-01

    In general, well-educated people enjoy better mental health than those with less education. As a result, some wonder whether there are limits to the mental health benefits of education. Inspired by the literature on the expansion of tertiary education, this article explores marginal mental health returns to education and studies the mental health status of overeducated people. To enhance the validity of the findings we use two indicators of educational attainment - years of education and ISCED97 categories - and two objective indicators of overeducation (the realised matches method and the job analyst method) in a sample of the working population of 25 European countries (unweighted sample N = 19,089). Depression is measured using an eight-item version of the CES-D scale. We find diminishing mental health returns to education. In addition, overeducated people report more depression symptoms. Both findings hold irrespective of the indicators used. The results must be interpreted in the light of the enduring expansion of education, as our findings show that the discussion of the relevance of the human capital perspective, and the diploma disease view on the relationship between education and modern society, is not obsolete. © 2013 The Authors. Sociology of Health & Illness © 2013 Foundation for the Sociology of Health & Illness/John Wiley & Sons Ltd.

  2. Normal aging selectively diminishes alpha lateralization in visual spatial attention.

    Science.gov (United States)

    Hong, Xiangfei; Sun, Junfeng; Bengson, Jesse J; Mangun, George R; Tong, Shanbao

    2015-02-01

    EEG studies of cue-induced visual alpha power (8-13 Hz) lateralization have been conducted on young adults without examining differences that may develop as a consequence of normal aging. Here, we examined age-related differences in spatial attention by comparing healthy older and younger adults. Our key finding is that cue-induced alpha power lateralization was observed in younger, but not older adults, even though both groups exhibited classic event-related potential signatures of spatial orienting. Specifically, both younger and older adults showed significant early directing-attention negativity (EDAN), anterior directing-attention negativity (ADAN), late directing-attention positivity (LDAP) and contingent negative variation (CNV). Furthermore, target-evoked sensory components were enhanced for attended relative to unattended targets in both younger and older groups. This pattern of results suggests that although older adults can successfully allocate spatial attention, they do so without the lateralization of alpha power that is commonly observed in younger adults. Taken together, our findings demonstrate that younger and older adults might engage different neural mechanisms for attentional orienting, and that alpha power lateralization during visual spatial attention is a phenomenon that diminishes during normal aging. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Adaptive training diminishes distractibility in aging across species.

    Science.gov (United States)

    Mishra, Jyoti; de Villers-Sidani, Etienne; Merzenich, Michael; Gazzaley, Adam

    2014-12-03

    Aging is associated with deficits in the ability to ignore distractions, which has not yet been remediated by any neurotherapeutic approach. Here, in parallel auditory experiments with older rats and humans, we evaluated a targeted cognitive training approach that adaptively manipulated distractor challenge. Training resulted in enhanced discrimination abilities in the setting of irrelevant information in both species that was driven by selectively diminished distraction-related errors. Neural responses to distractors in auditory cortex were selectively reduced in both species, mimicking the behavioral effects. Sensory receptive fields in trained rats exhibited improved spectral and spatial selectivity. Frontal theta measures of top-down engagement with distractors were selectively restrained in trained humans. Finally, training gains generalized to group and individual level benefits in aspects of working memory and sustained attention. Thus, we demonstrate converging cross-species evidence for training-induced selective plasticity of distractor processing at multiple neural scales, benefitting distractor suppression and cognitive control. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Deletion of murine choline dehydrogenase results in diminished sperm motility.

    Science.gov (United States)

    Johnson, Amy R; Craciunescu, Corneliu N; Guo, Zhong; Teng, Ya-Wen; Thresher, Randy J; Blusztajn, Jan K; Zeisel, Steven H

    2010-08-01

    Choline dehydrogenase (CHDH) catalyzes the conversion of choline to betaine, an important methyl donor and organic osmolyte. We have previously identified single nucleotide polymorphisms (SNPs) in the human CHDH gene that, when present, seem to alter the activity of the CHDH enzyme. These SNPs occur frequently in humans. We created a Chdh(-/-) mouse to determine the functional effects of mutations that result in decreased CHDH activity. Chdh deletion did not affect fetal viability or alter growth or survival of these mice. Only one of eleven Chdh(-/-) males was able to reproduce. Loss of CHDH activity resulted in decreased testicular betaine and increased choline and PCho concentrations. Chdh(+/+) and Chdh(-/-) mice produced comparable amounts of sperm; the impaired fertility was due to diminished sperm motility in the Chdh(-/-) males. Transmission electron microscopy revealed abnormal mitochondrial morphology in Chdh(-/-) sperm. ATP content, total mitochondrial dehydrogenase activity and inner mitochondrial membrane polarization were all significantly reduced in sperm from Chdh(-/-) animals. Mitochondrial changes were also detected in liver, kidney, heart, and testis tissues. We suggest that men who have SNPs in CHDH that decrease the activity of the CHDH enzyme could have decreased sperm motility and fertility.

  5. Overexpression of Catalase Diminishes Oxidative Cysteine Modifications of Cardiac Proteins.

    Directory of Open Access Journals (Sweden)

    Chunxiang Yao

    Full Text Available Reactive protein cysteine thiolates are instrumental in redox regulation. Oxidants, such as hydrogen peroxide (H2O2, react with thiolates to form oxidative post-translational modifications, enabling physiological redox signaling. Cardiac disease and aging are associated with oxidative stress which can impair redox signaling by altering essential cysteine thiolates. We previously found that cardiac-specific overexpression of catalase (Cat, an enzyme that detoxifies excess H2O2, protected from oxidative stress and delayed cardiac aging in mice. Using redox proteomics and systems biology, we sought to identify the cysteines that could play a key role in cardiac disease and aging. With a 'Tandem Mass Tag' (TMT labeling strategy and mass spectrometry, we investigated differential reversible cysteine oxidation in the cardiac proteome of wild type and Cat transgenic (Tg mice. Reversible cysteine oxidation was measured as thiol occupancy, the ratio of total available versus reversibly oxidized cysteine thiols. Catalase overexpression globally decreased thiol occupancy by ≥1.3 fold in 82 proteins, including numerous mitochondrial and contractile proteins. Systems biology analysis assigned the majority of proteins with differentially modified thiols in Cat Tg mice to pathways of aging and cardiac disease, including cellular stress response, proteostasis, and apoptosis. In addition, Cat Tg mice exhibited diminished protein glutathione adducts and decreased H2O2 production from mitochondrial complex I and II, suggesting improved function of cardiac mitochondria. In conclusion, our data suggest that catalase may alleviate cardiac disease and aging by moderating global protein cysteine thiol oxidation.

  6. Measuring mental illness stigma with diminished social desirability effects.

    Science.gov (United States)

    Michaels, Patrick J; Corrigan, Patrick W

    2013-06-01

    For persons with mental illness, stigma diminishes employment and independent living opportunities as well as participation in psychiatric care. Public stigma interventions have sought to ameliorate these consequences. Evaluation of anti-stigma programs' impact is typically accomplished with self-report questionnaires. However, cultural mores encourage endorsement of answers that are socially preferred rather than one's true belief. This problem, social desirability, has been circumvented through development of faux knowledge tests (KTs) (i.e., Error-Choice Tests); written to assess prejudice. Our KT uses error-choice test methodology to assess stigmatizing attitudes. Test content was derived from review of typical KTs for façade reinforcement. Answer endorsement suggests bias or stigma; such determinations were based on the empirical literature. KT psychometrics were examined in samples of college students, community members and mental health providers and consumers. Test-retest reliability ranged from fair (0.50) to good (0.70). Construct validity analyses of public stigma indicated a positive relationship with the Attribution Questionnaire and inverse relationships with Self-Determination and Empowerment Scales. No significant relationships were observed with self-stigma measures (recovery, empowerment). This psychometric evaluation study suggests that a self-administered questionnaire may circumvent social desirability and have merit as a stigma measurement tool.

  7. Major surgery diminishes systemic arginine availability and suppresses nitric oxide response to feeding in patients with early stage breast cancer.

    Science.gov (United States)

    Engelen, Mariëlle P K J; Klimberg, V Suzanne; Allasia, Arianna; Deutz, Nicolaas E P

    2017-08-05

    Plasma arginine (ARG) levels are reduced in breast cancer, suggesting diminished systemic ARG availability. ARG and its product nitric oxide (NO) are important in early postoperative recovery due to its roles in immune function and wound healing. It remains unclear whether major surgery further diminishes systemic ARG availability due to enhanced ARG catabolism and/or insufficient endogenous ARG synthesis negatively affecting NO synthesis in patients with early stage breast cancer. In 9 women with early stage breast malignancy and 9 healthy women with genetic predisposition to breast cancer, whole body ARG and citrulline (CIT) rates of appearances were measured to determine their production rates prior to and within 24 h after major breast surgery by stable isotope methodology in the postabsorptive and postprandial state. The conversions of CIT > ARG, ARG > CIT, and ARG > Urea (markers of de novo ARG and NO synthesis, arginase activity, respectively), and ARG clearance (reflecting ARG disposal capacity) were calculated. Prior to surgery, plasma ARG, CIT and glutamine concentrations were lower in cancer (P  ARG (P  CIT conversion (P  CIT conversion, plasma CIT (P early stage breast cancer further reduces systemic ARG availability in the early phase of recovery due to a combined process of increased ARG catabolism and impaired endogenous ARG synthesis. The suppressed postprandial NO increase in early stage cancer suggests that specific nutritional approaches are advised to increase ARG availability after major surgery although the effects on postoperative recovery remain unclear. This trial was registered at clinicaltrials.gov as NCT00497380. Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  8. Protracted bacterial bronchitis: reinventing an old disease.

    Science.gov (United States)

    Craven, Vanessa; Everard, Mark L

    2013-01-01

    Chronic cough is common in the paediatric population, yet the true prevalence of this condition remains difficult to define. Protracted bacterial bronchitis (PBB) is a disease caused by the chronic infection of the conducting airways. In many children the condition appears to be secondary to impaired mucociliary clearance that creates a niche for bacteria to become established, probably in the form of biofilms. In others, immunodeficiencies, which may be subtle, appear to be a factor. PBB causes persistent coughing and disturbed sleep, and affects exercise tolerance, causing significant levels of morbidity. PBB has remained largely unrecognised and is often misdiagnosed as asthma.

  9. Cerebrospinal Fluid Clearance in Alzheimer Disease Measured with Dynamic PET.

    Science.gov (United States)

    de Leon, Mony J; Li, Yi; Okamura, Nobuyuki; Tsui, Wai H; Saint-Louis, Les A; Glodzik, Lidia; Osorio, Ricardo S; Fortea, Juan; Butler, Tracy; Pirraglia, Elizabeth; Fossati, Silvia; Kim, Hee-Jin; Carare, Roxana O; Nedergaard, Maiken; Benveniste, Helene; Rusinek, Henry

    2017-09-01

    Evidence supporting the hypothesis that reduced cerebrospinal fluid (CSF) clearance is involved in the pathophysiology of Alzheimer disease (AD) comes primarily from rodent models. However, unlike rodents, in which predominant extracranial CSF egress is via olfactory nerves traversing the cribriform plate, human CSF clearance pathways are not well characterized. Dynamic PET with 18 F-THK5117, a tracer for tau pathology, was used to estimate the ventricular CSF time-activity as a biomarker for CSF clearance. We tested 3 hypotheses: extracranial CSF is detected at the superior turbinates; CSF clearance is reduced in AD; and CSF clearance is inversely associated with amyloid deposition. Methods: Fifteen subjects, 8 with AD and 7 normal control volunteers, were examined with 18 F-THK5117. Ten subjects additionally underwent 11 C-Pittsburgh compound B ( 11 C-PiB) PET scanning, and 8 were 11 C-PiB-positive. Ventricular time-activity curves of 18 F-THK5117 were used to identify highly correlated time-activity curves from extracranial voxels. Results: For all subjects, the greatest density of CSF-positive extracranial voxels was in the nasal turbinates. Tracer concentration analyses validated the superior nasal turbinate CSF signal intensity. AD patients showed ventricular tracer clearance reduced by 23% and 66% fewer superior turbinate CSF egress sites. Ventricular CSF clearance was inversely associated with amyloid deposition. Conclusion: The human nasal turbinate is part of the CSF clearance system. Lateral ventricle and superior nasal turbinate CSF clearance abnormalities are found in AD. Ventricular CSF clearance reductions are associated with increased brain amyloid depositions. These data suggest that PET-measured CSF clearance is a biomarker of potential interest in AD and other neurodegenerative diseases. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

  10. Loneliness in older adults is associated with diminished cortisol output.

    Science.gov (United States)

    Schutter, N; Holwerda, T J; Stek, M L; Dekker, J J M; Rhebergen, D; Comijs, H C

    2017-04-01

    Loneliness in older adults has been associated with increased mortality and health problems. One of the assumed underlying mechanisms is dysregulation of the hypothalamic-pituitary-adrenocortical axis (HPA-axis). The purpose of this study was to investigate whether loneliness in older adults is associated with HPA-axis dysregulation and whether this association differs between depressed and non-depressed persons. Cross-sectional data of 426 lonely and non-lonely older adults in the Netherlands Study of Depression in Older Persons (NESDO) were used. Linear regression analyses and multinominal logistic regression analyses were performed to examine the association between loneliness and morning cortisol, cortisol awakening response, diurnal slope and dexamethasone suppression ratio. In all analyses, confounders were introduced. In order to examine whether the association between loneliness and cortisol measures is different in depressed versus non-depressed persons, an interaction term for loneliness x depression diagnosis was tested. Cortisol output in the first hour after awakening and dexamethasone suppression ratio was lower in lonely participants. There were no significant interactions between loneliness and depression diagnosis in the association with the cortisol measures. This study is the first to investigate the association between the HPA-axis and loneliness in a large group of older adults aged 60-93years. We found lower cortisol output in the first hour after awakening and lower dexamethasone suppression ratio in lonely older depressed and non-depressed adults. Whether diminished cortisol output is the underlying mechanism that leads to health problems in lonely older adults is an interesting object for further study. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Cysteamine-mediated clearance of antibiotic-resistant pathogens in human cystic fibrosis macrophages.

    Directory of Open Access Journals (Sweden)

    Chandra L Shrestha

    Full Text Available Members of the Burkholderia cepacia complex are virulent, multi-drug resistant pathogens that survive and replicate intracellularly in patients with cystic fibrosis (CF. We have discovered that B. cenocepacia cannot be cleared from CF macrophages due to defective autophagy, causing continued systemic inflammation and infection. Defective autophagy in CF is mediated through constitutive reactive oxygen species (ROS activation of transglutaminase-2 (TG2, which causes the sequestration (accumulation of essential autophagy initiating proteins. Cysteamine is a TG2 inhibitor and proteostasis regulator with the potential to restore autophagy. Therefore, we sought to examine the impact of cysteamine on CF macrophage autophagy and bacterial killing. Human peripheral blood monocyte-derived macrophages (MDMs and alveolar macrophages were isolated from CF and non-CF donors. Macrophages were infected with clinical isolates of relevant CF pathogens. Cysteamine caused direct bacterial growth killing of live B. cenocepacia, B. multivorans, P. aeruginosa and MRSA in the absence of cells. Additionally, B. cenocepacia, B. multivorans, and P. aeruginosa invasion were significantly decreased in CF MDMs treated with cysteamine. Finally, cysteamine decreased TG2, p62, and beclin-1 accumulation in CF, leading to increased Burkholderia uptake into autophagosomes, increased macrophage CFTR expression, and decreased ROS and IL-1β production. Cysteamine has direct anti-bacterial growth killing and improves human CF macrophage autophagy resulting in increased macrophage-mediated bacterial clearance, decreased inflammation, and reduced constitutive ROS production. Thus, cysteamine may be an effective adjunct to antibiotic regimens in CF.

  12. Blood flow and clearance in tendons. Studies with dogs.

    Science.gov (United States)

    Hooper, G; Davies, R; Tothill, P

    1984-05-01

    Blood flow in intact tendons in dogs was measured using 57Co-labelled microspheres and compared with the simultaneous clearance of a diffusible radionuclide, 85Sr, by the same tendons. Clearance was significantly greater than flow in all tendons, indicating that diffusion from surrounding tissues may be important in the nutrition of normal tendons.

  13. Estimation of hepatic blood flow by hydrogen gas clearance

    NARCIS (Netherlands)

    Gouma, D. J.; Coelho, J. C.; Schlegel, J.; Fisher, J. D.; Li, Y. F.; Moody, F. G.

    1986-01-01

    The hydrogen gas clearance technique was evaluated to estimate regional hepatic blood flow. Initially, the H2 gas method was compared to the indocyanine green clearance in mini pigs. The blood flow measured by the H2 gas method (0.49 +/- 0.03 ml/min/gm) was only 39% of the calculated blood flow by

  14. 32 CFR 644.516 - Clearance of Air Force lands.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 4 2010-07-01 2010-07-01 true Clearance of Air Force lands. 644.516 Section 644... Excess Land and Improvements § 644.516 Clearance of Air Force lands. The Chief of Engineers has no responsibility for inspecting or clearing excess Air Force land of explosives or chemical/biological contaminants...

  15. 19 CFR 4.61 - Requirements for clearance.

    Science.gov (United States)

    2010-04-01

    ... TREASURY VESSELS IN FOREIGN AND DOMESTIC TRADES Foreign Clearances § 4.61 Requirements for clearance. (a... either on the Customs Form 1300 or by approved electronic means. Customs port directors may permit the... (see § 4.71). (16) Inspection of meat, meat-food products, and inedible fats (see § 4.72). (17...

  16. 77 FR 44641 - Critical Infrastructure Private Sector Clearance Program Request

    Science.gov (United States)

    2012-07-30

    ...: Once. Affected Public: Designated private sector employees of critical infrastructure entities or... SECURITY Critical Infrastructure Private Sector Clearance Program Request AGENCY: National Protection and... Collection Request (ICR) to the Office of Management and Budget (OMB) for review and clearance in accordance...

  17. 48 CFR 32.502-2 - Contract finance office clearance.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Contract finance office clearance. 32.502-2 Section 32.502-2 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION... finance office clearance. The contracting officer shall obtain the approval of the contract finance office...

  18. 48 CFR 832.502-2 - Contract finance office clearance.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Contract finance office clearance. 832.502-2 Section 832.502-2 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS... finance office clearance. Contracting officers must obtain approval from the DSPE before taking the...

  19. 48 CFR 1432.502-2 - Contract finance office clearance.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Contract finance office clearance. 1432.502-2 Section 1432.502-2 Federal Acquisition Regulations System DEPARTMENT OF THE INTERIOR... finance office clearance. The CO shall obtain approval of the bureau finance office prior to taking...

  20. 32 CFR 644.522 - Clearance of military scrap.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 4 2010-07-01 2010-07-01 true Clearance of military scrap. 644.522 Section 644... Excess Land and Improvements § 644.522 Clearance of military scrap. Military scrap can contain or be... destruction, by using command, of all military scrap and scrap metal from lands suitable for cultivation or...

  1. Discrepancy between circadian rhythms of inulin and creatinine clearance

    NARCIS (Netherlands)

    van Acker, B. A.; Koomen, G. C.; Koopman, M. G.; Krediet, R. T.; Arisz, L.

    1992-01-01

    To elucidate the disparity between circadian rhythmicity of inulin and creatinine clearance, we simultaneously measured inulin and creatinine clearances every 3 hours during 1 day in 14 normal subjects and in 8 patients with nephrotic syndrome. All patients and normal subjects had a circadian rhythm

  2. Allometric scaling for predicting human clearance of bisphenol A

    Energy Technology Data Exchange (ETDEWEB)

    Collet, Séverine H., E-mail: s.collet@envt.fr; Picard-Hagen, Nicole, E-mail: n.hagen-picard@envt.fr; Lacroix, Marlène Z., E-mail: m.lacroix@envt.fr; Puel, Sylvie, E-mail: s.puel@envt.fr; Viguié, Catherine, E-mail: c.viguie@envt.fr; Bousquet-Melou, Alain, E-mail: a.bousquet-Melou@envt.fr; Toutain, Pierre-Louis, E-mail: pltoutain@wanadoo.fr; Gayrard, Véronique, E-mail: v.gayrard@envt.fr

    2015-05-01

    The investigation of interspecies differences in bisphenol A (BPA) pharmacokinetics (PK) may be useful for translating findings from animal studies to humans, identifying major processes involved in BPA clearance mechanisms, and predicting BPA PK parameters in man. For the first time, a large range of species in terms of body weight, from 0.02 kg (mice) to 495 kg (horses) was used to predict BPA clearance in man by an allometric approach. BPA PK was evaluated after intravenous administration of BPA in horses, sheep, pigs, dogs, rats and mice. A non-compartmental analysis was used to estimate plasma clearance and steady state volume of distribution and predict BPA PK parameters in humans from allometric scaling. In all the species investigated, BPA plasma clearance was high and of the same order of magnitude as their respective hepatic blood flow. By an allometric scaling, the human clearance was estimated to be 1.79 L/min (equivalent to 25.6 mL/kg.min) with a 95% prediction interval of 0.36 to 8.83 L/min. Our results support the hypothesis that there are highly efficient and hepatic mechanisms of BPA clearance in man. - Highlights: • Allometric scaling was used to predict BPA pharmacokinetic parameters in humans. • In all species, BPA plasma clearance approached hepatic blood flow. • Human BPA clearance was estimated to be 1.79 L/min.

  3. 75 FR 52798 - State-07, Cryptographic Clearance Records

    Science.gov (United States)

    2010-08-27

    ..., the user account is disabled. RETENTION AND DISPOSAL: Records are retired in accordance with published..., Cryptographic Clearance Records Summary: Notice is hereby given that the Department of State proposes to amend an existing system of records, Cryptographic Clearance Records, State-07, pursuant to the provisions...

  4. How to diminish calcium loss and muscle atrophy in space

    Science.gov (United States)

    Gorgolewski, S.

    perfect relaxation when asleep or awake. We have to check in space if we can thus diminish the use of medicaments or even eliminate them. Slow Yoga exercises decrease also the amount on food required because life is not so energy demanding in space as it is here under the earth's gravitation. We can stay lean and healthy with such static yet most effective physical exercises. In addition it gives us for free a vegetarian life style, just another benefit so useful in space travel.

  5. Diminished Mercury Emission From Water Surfaces by Duckweed (Lemna minor)

    Science.gov (United States)

    Wollenberg, J. L.; Peters, S. C.

    2007-12-01

    Aquatic plants of the family Lemnaceae (generally referred to as duckweeds) are a widely distributed type of floating vegetation in freshwater systems. Under suitable conditions, duckweeds form a dense vegetative mat on the water surface, which reduces light penetration into the water column and decreases the amount of exposed water surface. These two factors would be expected to reduce mercury emission by limiting a) direct photoreduction of Hg(II), b) indirect reduction via coupled DOC photooxidation-Hg(II) reduction, and c) gas diffusion across the water-air interface. Conversely, previous studies have demonstrated transpiration of Hg(0) by plants, so it is therefore possible that the floating vegetative mat would enhance emission via transpiration of mercury vapor. The purpose of this experiment was to determine whether duckweed limits mercury flux to the atmosphere by shading and the formation of a physical barrier to diffusion, or whether it enhances emission from aquatic systems via transpiration of Hg(0). Deionized water was amended with mercury to achieve a final concentration of approximately 35 ng/L and allowed to equilibrate prior to the experiment. Experiments were conducted in rectangular polystyrene flux chambers with measured UV-B transmittance greater than 60% (spectral cutoff approximately 290 nm). Light was able to penetrate the flux chamber from the sides as well as the top throughout the experiment, limiting the effect of shading by duckweed on the water surface. Flux chambers contained 8L of water with varying percent duckweed cover, and perforated plastic sheeting was used as an abiotic control. Exposures were conducted outside on days with little to no cloud cover. Real time mercury flux was measured using atomic absorption (Mercury Instruments UT-3000). Total solar and ultraviolet radiation, as well as a suite of meteorological parameters, were also measured. Results indicate that duckweed diminishes mercury emission from the water surface

  6. BACTERIAL PLASMIDS

    Directory of Open Access Journals (Sweden)

    Marina Dinic

    2007-12-01

    Full Text Available Plasmids, extrachromosomal DNA, were identified in bacteria pertaining to family of Enterobacteriacae for the very first time. After that, they were discovered in almost every single observed strain. The structure of plasmids is made of circular double chain DNA molecules which are replicated autonomously in a host cell. Their length may vary from few up to several hundred kilobase (kb. Among the bacteria, plasmids are mostly transferred horizontally by conjugation process. Plasmid replication process can be divided into three stages: initiation, elongation, and termination. The process involves DNA helicase I, DNA gyrase, DNA polymerase III, endonuclease, and ligase.Plasmids contain genes essential for plasmid function and their preservation in a host cell (the beginning and the control of replication. Some of them possess genes whichcontrol plasmid stability. There is a common opinion that plasmids are unnecessary fora growth of bacterial population and their vital functions; thus, in many cases they can be taken up or kicked out with no lethal effects to a plasmid host cell. However,there are numerous biological functions of bacteria related to plasmids. Plasmids identification and classification are based upon their genetic features which are presented permanently in all of them, and these are: abilities to preserve themselves in a host cell and to control a replication process. In this way, plasmids classification among incompatibility groups is performed. The method of replicon typing, which is based on genotype and not on phenotype characteristics, has the same results as in compatibility grouping.

  7. When the most potent combination of antibiotics selects for the greatest bacterial load: the smile-frown transition.

    Directory of Open Access Journals (Sweden)

    Rafael Pena-Miller

    Full Text Available Conventional wisdom holds that the best way to treat infection with antibiotics is to 'hit early and hit hard'. A favoured strategy is to deploy two antibiotics that produce a stronger effect in combination than if either drug were used alone. But are such synergistic combinations necessarily optimal? We combine mathematical modelling, evolution experiments, whole genome sequencing and genetic manipulation of a resistance mechanism to demonstrate that deploying synergistic antibiotics can, in practice, be the worst strategy if bacterial clearance is not achieved after the first treatment phase. As treatment proceeds, it is only to be expected that the strength of antibiotic synergy will diminish as the frequency of drug-resistant bacteria increases. Indeed, antibiotic efficacy decays exponentially in our five-day evolution experiments. However, as the theory of competitive release predicts, drug-resistant bacteria replicate fastest when their drug-susceptible competitors are eliminated by overly-aggressive treatment. Here, synergy exerts such strong selection for resistance that an antagonism consistently emerges by day 1 and the initially most aggressive treatment produces the greatest bacterial load, a fortiori greater than if just one drug were given. Whole genome sequencing reveals that such rapid evolution is the result of the amplification of a genomic region containing four drug-resistance mechanisms, including the acrAB efflux operon. When this operon is deleted in genetically manipulated mutants and the evolution experiment repeated, antagonism fails to emerge in five days and antibiotic synergy is maintained for longer. We therefore conclude that unless super-inhibitory doses are achieved and maintained until the pathogen is successfully cleared, synergistic antibiotics can have the opposite effect to that intended by helping to increase pathogen load where, and when, the drugs are found at sub-inhibitory concentrations.

  8. Analysis of viral clearance unit operations for monoclonal antibodies.

    Science.gov (United States)

    Miesegaes, George; Lute, Scott; Brorson, Kurt

    2010-06-01

    Demonstration of viral clearance is a critical step in assuring the safety of biotechnology products. We generated a viral clearance database that contains product information, unit operation process parameters, and viral clearance data from monoclonal antibody and antibody-related regulatory submissions to FDA. Here we present a broad overview of the database and resulting analyses. We report that the diversity of model viruses tested expands as products transition to late-phase. We also present averages and ranges of viral clearance results by Protein A and ion exchange chromatography steps, low pH chemical inactivation, and virus filtration, focusing on retro- and parvoviruses. For most unit operations, an average log reduction value (LRV, a measure of clearance power) for retrovirus of >4 log(10) were measured. Cases where clearance data fell outside of the anticipated range (i.e., outliers) were rationally explained. Lastly, a historical analysis did not find evidence of any improvement trend in viral clearance over time. The data collectively suggest that many unit operations in general can reliably clear viruses.

  9. Numerical simulation of tip clearance impact on a pumpjet propulsor

    Directory of Open Access Journals (Sweden)

    Lin Lu

    2016-05-01

    Full Text Available Numerical simulation based on the Reynolds Averaged Navier–Stokes (RANS Computational Fluid Dynamics (CFD method had been carried out with the commercial code ANSYS CFX. The structured grid and SST k–ω turbulence model had been adopted. The impact of non-condensable gas (NCG on cavitation performance had been introduced into the Schnerr and Sauer cavitation model. The numerical investigation of cavitating flow of marine propeller E779A was carried out with different advance ratios and cavitation numbers to verify the numerical simulation method. Tip clearance effects on the performance of pumpjet propulsor had been investigated. Results showed that the structure and characteristics of the tip leakage vortex and the efficiency of the propulsor dropped more sharply with the increase of the tip clearance size. Furthermore, the numerical simulation of tip clearance cavitation of pumpjet propulsor had been presented with different rotational speed and tip clearance size. The mechanism of tip clearance cavitation causing a further loss of the efficiency had been studied. The influence of rotational speed and tip clearance size on tip clearance cavitation had been investigated.

  10. Integrated Turbine Tip Clearance and Gas Turbine Engine Simulation

    Science.gov (United States)

    Chapman, Jeffryes W.; Kratz, Jonathan; Guo, Ten-Huei; Litt, Jonathan

    2016-01-01

    Gas turbine compressor and turbine blade tip clearance (i.e., the radial distance between the blade tip of an axial compressor or turbine and the containment structure) is a major contributing factor to gas path sealing, and can significantly affect engine efficiency and operational temperature. This paper details the creation of a generic but realistic high pressure turbine tip clearance model that may be used to facilitate active tip clearance control system research. This model uses a first principles approach to approximate thermal and mechanical deformations of the turbine system, taking into account the rotor, shroud, and blade tip components. Validation of the tip clearance model shows that the results are realistic and reflect values found in literature. In addition, this model has been integrated with a gas turbine engine simulation, creating a platform to explore engine performance as tip clearance is adjusted. Results from the integrated model explore the effects of tip clearance on engine operation and highlight advantages of tip clearance management.

  11. Aerosol Medications for Treatment of Mucus Clearance Disorders.

    Science.gov (United States)

    Rubin, Bruce K

    2015-06-01

    Airway mucus hypersecretion and secretion retention can result from inflammation, irritation, stimulation, or mucus-producing tumors. Secretion clearance can be furthered hampered by ciliary dysfunction and by weakness or restrictive lung disease, leading to an ineffective cough. There are a number of different mucoactive medications that have been used to reduce hypersecretion, make secretions easier to transport, or increase the efficiency of cough or mucus clearance. In this paper, I review the pathophysiology of secretory hyper-responsiveness and mucus hypersecretion and discuss the different aerosol medications that can be used to augment secretion clearance. Copyright © 2015 by Daedalus Enterprises.

  12. Vancomycin prophylaxis of experimental Streptococcus sanguis. Inhibition of bacterial adherence rather than bacterial killing.

    Science.gov (United States)

    Bernard, J P; Francioli, P; Glauser, M P

    1981-01-01

    Using a strain of Streptococcus sanguis tolerant to vancomycin to infect aortic vegetations in rats, we found that prophylactic intravenous vancomycin given 30 min before bacterial challenge decreased the incidence of endocarditis from 88 to 8% (P less than 10(-5)). Because peak vancomycin serum levels were below the minimal bactericidal concentration, mechanisms of protection other than bacterial killing were investigated. S. sanguis were incubated with inhibitory concentration of vancomycin (50 microgram/ml) for 10 h and washed. 85% of rats (73/86) inoculated with control bacteria developed endocarditis, whereas only 42% (33/78) of those inoculated with vancomycin-exposed bacteria did so (P less than 10(-5)). When rats were killed 30 min after bacterial challenge, S. sanguis were detected by culture of the vegetations in 44% of rats injected with control bacteria, but in only 13% of those challenged with vancomycin-exposed bacteria (P less than 0.03). Enhanced clearance of vancomycin-exposed streptococci was not responsible for this protection because blood cultures showed no difference in the level and duration of bacteremia after injection of control or vancomycin-exposed S. sanguis. Moreover, this protection was not abolished in neutropenic rats injected with vancomycin-exposed bacteria, despite more prolonged bacteremia. These results suggest that vancomycin exerted its protection by lowering adherence of tolerant S. sanguis to vegetations rather than through bactericidal activity or enhanced clearance of bacteria by phagocytic cells. In the choice of antibiotics for prophylaxis of endocarditis, reduction of bacterial adhesion may be a criterion as important as bacterial killing. PMID:7287904

  13. Rapid Treponema pallidum clearance from blood and ulcer samples following single dose benzathine penicillin treatment of early syphilis.

    Science.gov (United States)

    Tipple, Craig; Jones, Rachael; McClure, Myra; Taylor, Graham

    2015-02-01

    Currently, the efficacy of syphilis treatment is measured with anti-lipid antibody tests. These can take months to indicate cure and, as a result, syphilis treatment trials require long periods of follow-up. The causative organism, Treponema pallidum (T. pallidum), is detectable in the infectious lesions of early syphilis using DNA amplification. Bacteraemia can likewise be identified, typically in more active disease. We hypothesise that bacterial clearance from blood and ulcers will predict early the standard serology-measured treatment response and have developed a qPCR assay that could monitor this clearance directly in patients with infectious syphilis. Patients with early syphilis were given an intramuscular dose of benzathine penicillin. To investigate the appropriate sampling timeframe samples of blood and ulcer exudate were collected intensively for T. pallidum DNA (tpp047 gene) and RNA (16S rRNA) quantification. Sampling ended when two consecutive PCRs were negative. Four males were recruited. The mean peak level of T. pallidum DNA was 1626 copies/ml whole blood and the mean clearance half-life was 5.7 hours (std. dev. 0.53). The mean peak of 16S rRNA was 8879 copies/ml whole blood with a clearance half-life of 3.9 hours (std. dev. 0.84). From an ulcer, pre-treatment, 67,400 T. pallidum DNA copies and 7.08 x 107 16S rRNA copies were detected per absorbance strip and the clearance half-lives were 3.2 and 4.1 hours, respectively. Overall, T. pallidum nucleic acids were not detected in any sample collected more than 56 hours (range 20-56) after treatment. All patients achieved serologic cure. In patients with active early syphilis, measuring T. pallidum levels in blood and ulcer exudate may be a useful measure of treatment success in therapeutic trials. These laboratory findings need confirmation on a larger scale and in patients receiving different therapies.

  14. Traffic incident management in hazardous materials spills in incident clearance.

    Science.gov (United States)

    2009-01-01

    Hazardous materials spills provide unique challenges to traffic incident clearance. When hazardous materials are present, not only do response personnel have to deal with typical traffic incident issues, they also must deal with potential chemical ha...

  15. IFNL4 affects clearance of hepatitis C virus

    Science.gov (United States)

    Scientists have discovered a new human interferon gene, Interferon Lambda 4 (IFNL4), that affects clearance of the hepatitis C virus. They also identified an inherited genetic variant within IFNL4 that predicts how people respond to treatment for hepatit

  16. 49 CFR 229.71 - Clearance above top of rail.

    Science.gov (United States)

    2010-10-01

    ....71 Clearance above top of rail. No part or appliance of a locomotive except the wheels, flexible nonmetallic sand pipe extension tips, and trip cock arms may be less than 21/2 inches above the top of rail. ...

  17. Clearance capacity of rat liver Kupffer, endothelial, and parenchymal cells

    NARCIS (Netherlands)

    Praaning-van Dalen, D.P.; Brouwer, A.; Knook, D.L.

    1981-01-01

    The clearance of five radioactively labeled test substances - polyvinylpyrrolidone, colloidal albumin, antimony sulfur colloid, endotoxin, and heparin - by the reticuloendothelial system was studied after i.v. injection of these substances into rats. The participation of parenchymal, Kupffer, and

  18. JAVAMIX: A Tactical Decision Aid to Evaluate Minefield Clearance Plans

    National Research Council Canada - National Science Library

    Filho, Jose

    2001-01-01

    A Tactical Decision Aid (TDA) for mixed minefield clearance, JAVAMIX, was designed, developed and tested, The TDA uses a Monte Carlo Simulation and it is based on the Monte Carlo option of the TDA MIXER (Washburn, 1995...

  19. Prevention of bacterial adhesion

    DEFF Research Database (Denmark)

    Klemm, Per; Vejborg, Rebecca Munk; Hancock, Viktoria

    2010-01-01

    Management of bacterial infections is becoming increasingly difficult due to the emergence and increasing prevalence of bacterial pathogens that are resistant to available antibiotics. Conventional antibiotics generally kill bacteria by interfering with vital cellular functions, an approach...... that imposes selection pressure for resistant bacteria. New approaches are urgently needed. Targeting bacterial virulence functions directly is an attractive alternative. An obvious target is bacterial adhesion. Bacterial adhesion to surfaces is the first step in colonization, invasion, and biofilm formation...

  20. Intradialytic clearance of opioids: methadone versus hydromorphone.

    Science.gov (United States)

    Perlman, Ryan; Giladi, Hili; Brecht, Krista; Ware, Mark A; Hebert, Terence E; Joseph, Lawrence; Shir, Yoram

    2013-12-01

    Opioids are commonly prescribed to patients with chronic pain associated with end-stage renal disease requiring hemodialysis. The stability of opioid analgesia during dialysis may vary among different opioids. No studies to date have corroborated this clinical observation by directly comparing plasma concentrations of different opioids during dialysis. We compared changes in peridialysis plasma concentrations of 2 pharmacokinetically distinct opioids, methadone and hydromorphone (HM). Fourteen dialysis patients with chronic pain received either methadone or HM for at least 2 weeks before beginning the study. Blood samples were obtained immediately before, during, and after hemodialysis in 2 separate dialysis sessions, 1 week apart, and were analyzed for opioid concentrations. Methadone plasma concentrations were more stable during hemodialysis compared to HM: the mean percent change of methadone plasma levels was 14.9% ± 8.2% (± SD) compared with 55.1% ± 8.1% in the HM treatment group, a difference of 40.2% (95% confidence interval 17.14 to 63.14). The mean plasma clearance of methadone was 19.9 ± 8.5 mL/min (± SD) compared with 105.7 ± 8.3 mL/min for HM, a difference of 85.7 mL/min (95% confidence interval 61.9 to 109.1). There were no differences between the 2 opioid groups in pain scores, side effect profile, and quality of life. Methadone therapy was not associated with an increased rate of adverse events. If confirmed by larger clinical studies, methadone could be considered as one of the opioids of choice in dialysis patients. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  1. Mechanistic evaluation of virus clearance by depth filtration.

    Science.gov (United States)

    Venkiteshwaran, Adith; Fogle, Jace; Patnaik, Purbasa; Kowle, Ron; Chen, Dayue

    2015-01-01

    Virus clearance by depth filtration has not been well-understood mechanistically due to lack of quantitative data on filter charge characteristics and absence of systematic studies. It is generally believed that both electrostatic interactions and sized based mechanical entrapment contribute to virus clearance by depth filtration. In order to establish whether the effectiveness of virus clearance correlates with the charge characteristics of a given depth filter, a counter-ion displacement technique was employed to determine the ionic capacity for several depth filters. Two depth filters (Millipore B1HC and X0HC) with significant differences in ionic capacities were selected and evaluated for their ability to eliminate viruses. The high ionic capacity X0HC filter showed complete porcine parvovirus (PPV) clearance (eliminating the spiked viruses to below the limit of detection) under low conductivity conditions (≤2.5 mS/cm), achieving a log10 reduction factor (LRF) of > 4.8. On the other hand, the low ionic capacity B1HC filter achieved only ∼2.1-3.0 LRF of PPV clearance under the same conditions. These results indicate that parvovirus clearance by these two depth filters are mainly achieved via electrostatic interactions between the filters and PPV. When much larger xenotropic murine leukemia virus (XMuLV) was used as the model virus, complete retrovirus clearance was obtained under all conditions evaluated for both depth filters, suggesting the involvement of mechanisms other than just electrostatic interactions in XMuLV clearance. © 2014 American Institute of Chemical Engineers.

  2. Cerebrospinal fluid clearance in Alzheimer disease measured with dynamic PET

    DEFF Research Database (Denmark)

    De Leon, Mony J.; Li, Yi; Okamura, Nobuyuki

    2017-01-01

    Evidence supporting the hypothesis that reduced cerebrospinal fluid (CSF) clearance is involved in the pathophysiology of Alzheimer disease (AD) comes primarily from rodent models. However, unlike rodents, in which predominant extracranial CSF egress is via olfactory nerves traversing the cribrif......Evidence supporting the hypothesis that reduced cerebrospinal fluid (CSF) clearance is involved in the pathophysiology of Alzheimer disease (AD) comes primarily from rodent models. However, unlike rodents, in which predominant extracranial CSF egress is via olfactory nerves traversing...

  3. A simplified experimental model for clearance of some pathogenic bacteria using common bacterivorous ciliated spp. in Tigris river

    Science.gov (United States)

    Ali, Talib Hassan; Saleh, Dhuha Saad

    2014-03-01

    Bacteria-specific uptake rates of three different protozoan taxa on a pure and mixed bacterial community was studied by means of a simplified and functionally reproducible experimental model. The bacterial species Shigella flexneri, Escherichia coli and Salmonella typhi were isolated and classified from stool samples of patients suffering from diarrhea. Paramecium caudatum, Tetrahymena pyriformis and Halteria grandinella, free living ciliate Protozoans, were isolated and identified from Tigris river water. Pure and mixed ( E. coli + S. typhi), ( E. coli + Sh. flexneri) bacterial cultures were used with each ciliate genera to evaluate the following: predator duplication rate, prey reduction rate, clearance rate and net grazing rate. We used selective lactose fermentation phenomena of enteric bacteria on MacConkey medium for the quantification of bacteria cultural characteristics. The final bacteria concentration was reduced by growing protozoa of 98-99.9 % compared to protozoa-free controls. It showed that Tetrahymena pyriformis had the highest duplication rate (4.13 time/day) in both types of cultures (pure and mixed), followed by Paramecium caudatum and Halteria grandinella, respectively. Paramecium caudatum had the highest rate of ingestion in both types of cultures (26 × 103 bacteria/organism/hr) and yielded the longest time required for 90 % bacterial reduction in a pure suspension of S. typhi (166 h). Clearance rates of pathogenic bacteria by ciliates ranged between 106 nanoliter/organism/h by P. caudatum to S. typhi and 1.92 nanoliter/organism/h seen in T. pyriformis in ( E. coli + S. typhi) mixed culture. We used aquatic experimental microcosms under controlled conditions to explore bacteria-dependent ciliate growth and examined whether these ciliates could discriminate between equally sized bacterial preys in a mixture.

  4. Synthetic Decapeptide Enhances Bacterial Clearance and Accelerates Healing in the Wounds of Restraint-Stressed Mice

    Science.gov (United States)

    2012-02-06

    showed that KSL, at concen trations up to 1 mg/ml, did not induce cell death or compromise the membrane integrity of human gingival fibroblasts... membranes , required for perme abilization (Choi et al., 2004). KSLW (MW 1308), is an analog of the parent KSL molecule, in which the Lys6 residue is...capacity for self assembly into micelles above a low critical micellar concentration ( CMC ) (Kabanov et al., 2002). They are high molecular weight, non ionic

  5. Hyaluronic acid conjugation facilitates clearance of intracellular bacterial infections by streptomycin with neglectable nephrotoxicity.

    Science.gov (United States)

    Qiu, Yuanhao; Hou, Yilin; Sun, Feifei; Chen, Peng; Wang, Dongdong; Mu, Haibo; Zhang, Xiaoli; Ding, Kan; Duan, Jinyou

    2017-09-01

    Antibiotics such as β-lactams and aminoglycosides are often subtherapeutic to intracellular infections due to their high hydrophilicity, resulting in low effectiveness against intracellular pathogens and the emergence of antibiotic resistance. Here we reported that an endogenous aminoglycan, hyaluronic acid could be an effective carbohydrate carrier of the aminoglycoside antibiotic, streptomycin against intracellular pathogens. This conjugation could enhance phagocytic activity, and facilitated the entry of streptomycin into host cells via a CD44-mediated pathway. It appeared that this conjugate could clear intracellular bacteria in phagocytic or nonphagocytic cells in a short-term therapy (4 h) at a lower effective dose. In addition, this conjugate was more efficient in reducing bacteria burden in an in vivo acute infection model than streptomycin did. Interestingly, subcutaneous injection of this conjugate at an excess amount had undetectable side effects such as nephrotoxicity. These results suggested that hyaluronic acid might be an efficient Trojan horse for the delivery of hydrophilic antibiotics to deal with intracellular infections. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  6. Pregnancy Complications: Bacterial Vaginosis

    Science.gov (United States)

    ... baby Common illnesses Family health & safety Complications & Loss Pregnancy complications Preterm labor & premature birth The newborn intensive care ... Point, NY 10980 Close X Home > Complications & Loss > Pregnancy complications > Bacterial vaginosis and pregnancy Bacterial vaginosis and pregnancy ...

  7. Diminished adrenal sensitivity to endogenous and exogenous adrenocorticotropic hormone in critical illness: A prospective cohort study

    NARCIS (Netherlands)

    M.F.C. de Jong (Margriet F.C.); N. Molenaar (Nienke); A. Beishuizen (Albertus); A.J. Groeneveld

    2015-01-01

    textabstractIntroduction: Adrenal dysfunction may represent critical illness-related corticosteroid insufficiency (CIRCI), as evidenced by a diminished cortisol response to exogenous adrenocorticotropic hormone (ACTH), but this concept and its clinical significance remain highly controversial. We

  8. Beef heifers with diminished numbers of antral follicles have decreased uterine protein concentrations

    Science.gov (United States)

    Previous research demonstrated a favorable relationship between the number of follicles detectable in the bovine ovary by ultrasonography and fertility, and bovine females with diminished numbers of antral follicles had smaller reproductive tracts. Therefore, we hypothesized that uterine function w...

  9. TREM2 deficiency reduces the efficacy of immunotherapeutic amyloid clearance.

    Science.gov (United States)

    Xiang, Xianyuan; Werner, Georg; Bohrmann, Bernd; Liesz, Arthur; Mazaheri, Fargol; Capell, Anja; Feederle, Regina; Knuesel, Irene; Kleinberger, Gernot; Haass, Christian

    2016-09-01

    Immunotherapeutic approaches are currently the most advanced treatments for Alzheimer's disease (AD). Antibodies against amyloid β-peptide (Aβ) bind to amyloid plaques and induce their clearance by microglia via Fc receptor-mediated phagocytosis. Dysfunctions of microglia may play a pivotal role in AD pathogenesis and could result in reduced efficacy of antibody-mediated Aβ clearance. Recently, heterozygous mutations in the triggering receptor expressed on myeloid cells 2 (TREM2), a microglial gene involved in phagocytosis, were genetically linked to late onset AD Loss of TREM2 reduces the ability of microglia to engulf Aβ. We have now investigated whether loss of TREM2 affects the efficacy of immunotherapeutic approaches. We show that anti-Aβ antibodies stimulate Aβ uptake and amyloid plaque clearance in a dose-dependent manner in the presence or absence of TREM2. However, TREM2-deficient N9 microglial cell lines, macrophages as well as primary microglia showed significantly reduced uptake of antibody-bound Aβ and as a consequence reduced clearance of amyloid plaques. Titration experiments revealed that reduced efficacy of amyloid plaque clearance by Trem2 knockout cells can be compensated by elevating the concentration of therapeutic antibodies. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.

  10. Pulmonary function and clearance after prolonged sulfuric acid aerosol exposure

    Energy Technology Data Exchange (ETDEWEB)

    Ives, P.J. (ABB Environmental, Chapel Hill, NC (United States)); Gerrity, T.R.; DeWitt, P.; Folinsbee, L.J. (Environmental Protection Agency, Chapel Hill, NC (United States))

    1991-03-15

    The authors studied pulmonary function and clearance responses after a 4 H exposure to 75-100 {mu}g/m{sup 3} sulfuric acid aerosol (SAA). Healthy subjects, who exercised for 30 min/H at ventilation of about 25 L/min, were exposed once to clean air and once to SAA. Oral hygiene and acidic juice gargle were used to minimize oral ammonia. Lung function tests, including spirometry, plethysmography, and partial flow-volume (PEFV) curves were performed before and after exposure. Clearance of 99m-Technetium labeled iron oxide was assessed after each exposure. The first moment of fractional tracheobronchial retention (M1TBR), after correcting for 24 H retention and normalizing to time zero, was used as an index of clearance. There were no significant changes in lung volumes, airways resistance, or maximum expiratory flows after SAA exposure. Flow at 40% of total lung capacity on PEFV curves decreased 17% (NS) after SAA exposure. Tracheobronchial clearance was accelerated after a single exposure to SAA; M1TBR decreased from 73 {plus minus} 5 min (air) to 69 {plus minus} 5 min (SAA). These results suggest that acute prolonged exposure to low levels of SAA has minimal effects on lung mechanics in healthy subjects but does produce a modest acceleration of particle clearance.

  11. Dps promotes survival of nontypeable Haemophilus influenzae in biofilm communities in vitro and resistance to clearance in vivo

    Directory of Open Access Journals (Sweden)

    Bing ePang

    2012-05-01

    Full Text Available Nontypeable Haemophilus influenzae (NTHi is a common airway commensal and opportunistic pathogen that persists within surface-attached biofilm communities. In this study, we tested the hypothesis that bacterial stress-responses are activated within biofilms. Transcripts for several factors associated with bacterial resistance to environmental stress were increased in biofilm cultures as compared to planktonic cultures. Among these, a homolog of the DNA-binding protein from starved cells (dps was chosen for further study. An isogenic NTHi 86-028NP dps mutant was generated and tested for resistance to environmental stress, revealing a significant survival defects in high-iron conditions, which was mediated by oxidative stress and was restored by genetic complementation. As expected, NTHi 86-028NP dps had a general stress-response defect, exhibiting decreased resistance to many types of environmental stress. While no differences were observed in density and structure of NTHi 86-028NP and NTHi 86-028NP dps biofilms, bacterial survival was decreased in NTHi 86-028NP dps biofilms as compared to the parental strain. The role of dps persistence in vivo was tested in animal infection studies. NTHi 86-028NP dps had decreased resistance to clearance after pulmonary infection of elastase-treated mice as compared to NTHi 86-028NP, whereas minimal differences were observed in clearance from mock-treated mice. Similarly, lower numbers of NTHi 86-028NP dps were recovered from middle-ear effusions and bullar homogenates in the chinchilla model for otitis media. Therefore, we conclude that Dps promotes bacterial survival within NTHi biofilm communities both in vitro and in chronic infections in vivo.

  12. Antipyrine clearance during experimental and occupational exposure to toluene

    DEFF Research Database (Denmark)

    Døssing, M; Bælum, Jesper; Lundqvist, G R

    1983-01-01

    Exposure to toluene vapour enhances hepatic microsomal enzyme function in animals as assessed by the metabolism of the test drug antipyrine. Thirty six printing trade workers with long term occupational exposure to a mixture of organic solvents and 39 matched controls were randomly allocated...... into four groups. Eighteen printers and 21 controls were exposed to 100 ppm of toluene during 6.5 hours in an exposure chamber. The remaining 18 printers and 18 controls were exposed to 0 ppm of toluene under similar conditions. The salivary clearance of antipyrine was measured immediately after the stay...... clearance 12 printing trade workers with 17 years (median) of occupational exposure to toluene vapour at concentrations of about 100 ppm were investigated before and four weeks after cessation of exposure. No difference in antipyrine clearance was found either within the groups or between the groups at any...

  13. APPLICATION OF DSM IN OBSTACLE CLEARANCE SURVEYING OF AERODROME

    Directory of Open Access Journals (Sweden)

    X. Qiao

    2016-06-01

    Full Text Available Compared to the wide use of digital elevation model (DEM, digital surface model (DSM receives less attention because that it is composed by not only terrain surface, but also vegetations and man-made objects which are usually regarded as useless information. Nevertheless, these objects are useful for the identification of obstacles around an aerodrome. The primary objective of the study was to determine the applicability of DSM in obstacle clearance surveying of aerodrome. According to the requirements of obstacle clearance surveying at QT airport, aerial and satellite imagery were used to generate DSM, by means of photogrammetry, which was spatially analyzed with the hypothetical 3D obstacle limitation surfaces (OLS to identify the potential obstacles. Field surveying was then carried out to retrieve the accurate horizontal position and height of the obstacles. The results proved that the application of DSM could make considerable improvement in the efficiency of obstacle clearance surveying of aerodrome.

  14. Using wearable UWB radios to measure foot clearance during walking.

    Science.gov (United States)

    Qi, Yongbin; Soh, Cheong Boon; Gunawan, Erry; Low, Kay-Soon; Maskooki, Arash

    2013-01-01

    Foot clearance above ground is a key factor for a better understanding of the complicated relationship between falls and gait. This paper proposes a wearable system using UWB transceivers to monitor the vertical heel/toe clearance during walking. First, a pair of very small and light antennas is placed on a point approximating to the heel/toe of the foot, acting as a transmitter and receiver. Then, the reflected signal from ground is captured and propagation delay is detected using noise suppressed Modified-Phase-Only-Correlator (MPOC). The performance of the UWB-based system was compared with an ultrasound system for stationary movements. The experimental results show that an overall mean difference between these two systems is about 0.634mm with correlation coefficient value of 0.9604. The UWB-based system is then used to measure foot clearance during walking which shows promising results for gait events detection.

  15. Coal fly ash impairs airway antimicrobial peptides and increases bacterial growth.

    Directory of Open Access Journals (Sweden)

    Jennifer A Borcherding

    Full Text Available Air pollution is a risk factor for respiratory infections, and one of its main components is particulate matter (PM, which is comprised of a number of particles that contain iron, such as coal fly ash (CFA. Since free iron concentrations are extremely low in airway surface liquid (ASL, we hypothesize that CFA impairs antimicrobial peptides (AMP function and can be a source of iron to bacteria. We tested this hypothesis in vivo by instilling mice with Pseudomonas aeruginosa (PA01 and CFA and determine the percentage of bacterial clearance. In addition, we tested bacterial clearance in cell culture by exposing primary human airway epithelial cells to PA01 and CFA and determining the AMP activity and bacterial growth in vitro. We report that CFA is a bioavailable source of iron for bacteria. We show that CFA interferes with bacterial clearance in vivo and in primary human airway epithelial cultures. Also, we demonstrate that CFA inhibits AMP activity in vitro, which we propose as a mechanism of our cell culture and in vivo results. Furthermore, PA01 uses CFA as an iron source with a direct correlation between CFA iron dissolution and bacterial growth. CFA concentrations used are very relevant to human daily exposures, thus posing a potential public health risk for susceptible subjects. Although CFA provides a source of bioavailable iron for bacteria, not all CFA particles have the same biological effects, and their propensity for iron dissolution is an important factor. CFA impairs lung innate immune mechanisms of bacterial clearance, specifically AMP activity. We expect that identifying the PM mechanisms of respiratory infections will translate into public health policies aimed at controlling, not only concentration of PM exposure, but physicochemical characteristics that will potentially cause respiratory infections in susceptible individuals and populations.

  16. Influence of Chronic Amphetamine Treatment and Acute Withdrawal on Serotonin Synthesis and Clearance Mechanisms in the Rat Ventral Hippocampus

    Science.gov (United States)

    Barr, Jeffrey L.; Scholl, Jamie L.; Solanki, Rajeshwari R.; Watt, Michael J.; Lowry, Christopher A.; Renner, Kenneth J.; Forster, Gina L.

    2012-01-01

    Amphetamine withdrawal in both humans and rats is associated with increased anxiety states, which are thought to contribute to drug relapse. Serotonin in the ventral hippocampus mediates affective behaviors, and reduced serotonin levels in this region are observed in rat models of high anxiety, including during withdrawal from chronic amphetamine. This goal of this study was to understand the mechanisms by which reduced ventral hippocampus serotonergic neurotransmission occurs during amphetamine withdrawal. Serotonin synthesis (assessed by accumulation of serotonin precursor as a measure of the capacity of in vivo tryptophan hydroxylase activity), expression of serotonergic transporters, and in vivo serotonergic clearance using in vivo microdialysis, were assessed in the ventral hippocampus in adult male Sprague Dawley rats at 24 hours withdrawal from chronic amphetamine. Overall, results showed that diminished extracellular serotonin at 24 hours withdrawal from chronic amphetamine was not accompanied by a change in capacity for serotonin synthesis (in vivo tryptophan hydroxylase activity), nor serotonin transporter expression or function in the ventral hippocampus, but instead was associated with increased expression and function of organic cation transporters (low affinity, high capacity serotonin transporters). These findings suggest that 24 hours withdrawal from chronic amphetamine reduces the availability of extracellular serotonin in the ventral hippocampus by increasing organic cation transporter-mediated serotonin clearance, which may represent at future pharmacological target for reversing anxiety states during drug withdrawal. PMID:23157166

  17. Cathelicidin host defence peptide augments clearance of pulmonary Pseudomonas aeruginosa infection by its influence on neutrophil function in vivo.

    Directory of Open Access Journals (Sweden)

    Paula E Beaumont

    Full Text Available Cathelicidins are multifunctional cationic host-defence peptides (CHDP; also known as antimicrobial peptides and an important component of innate host defence against infection. In addition to microbicidal potential, these peptides have properties with the capacity to modulate inflammation and immunity. However, the extent to which such properties play a significant role during infection in vivo has remained unclear. A murine model of acute P. aeruginosa lung infection was utilised, demonstrating cathelicidin-mediated enhancement of bacterial clearance in vivo. The delivery of exogenous synthetic human cathelicidin LL-37 was found to enhance a protective pro-inflammatory response to infection, effectively promoting bacterial clearance from the lung in the absence of direct microbicidal activity, with an enhanced early neutrophil response that required both infection and peptide exposure and was independent of native cathelicidin production. Furthermore, although cathelicidin-deficient mice had an intact early cellular inflammatory response, later phase neutrophil response to infection was absent in these animals, with significantly impaired clearance of P. aeruginosa. These findings demonstrate the importance of the modulatory properties of cathelicidins in pulmonary infection in vivo and highlight a key role for cathelicidins in the induction of protective pulmonary neutrophil responses, specific to the infectious milieu. In additional to their physiological roles, CHDP have been proposed as future antimicrobial therapeutics. Elucidating and utilising the modulatory properties of cathelicidins has the potential to inform the development of synthetic peptide analogues and novel therapeutic approaches based on enhancing innate host defence against infection with or without direct microbicidal targeting of pathogens.

  18. Mucociliary clearance, airway inflammation and nasal symptoms in urban motorcyclists

    Directory of Open Access Journals (Sweden)

    Tereza C.S. Brant

    2014-01-01

    Full Text Available OBJECTIVES: There is evidence that outdoor workers exposed to high levels of air pollution exhibit airway inflammation and increased airway symptoms. We hypothesized that these workers would experience increased airway symptoms and decreased nasal mucociliary clearance associated with their exposure to air pollution. METHODS: In total, 25 non-smoking commercial motorcyclists, aged 18-44 years, were included in this study. These drivers work 8-12 hours per day, 5 days per week, driving on urban streets. Nasal mucociliary clearance was measured by the saccharine transit test; airway acidification was measured by assessing the pH of exhaled breath condensate; and airway symptoms were measured by the Sino-nasal Outcome Test-20 questionnaire. To assess personal air pollution exposure, the subjects used a passive-diffusion nitrogen dioxide (NO2 concentration-monitoring system during the 14 days before each assessment. The associations between NO2 and the airway outcomes were analyzed using the Mann-Whitney test and the Chi-Square test. Clinicaltrials.gov: NCT01976039. RESULTS: Compared with clearance in healthy adult males, mucociliary clearance was decreased in 32% of the motorcyclists. Additionally, 64% of the motorcyclists had airway acidification and 92% experienced airway symptoms. The median personal NO2 exposure level was 75 mg/m3 for these subjects and a significant association was observed between NO2 and impaired mucociliary clearance (p = 0.036. CONCLUSION: Non-smoking commercial motorcyclists exhibit increased airway symptoms and airway acidification as well as decreased nasal mucociliary clearance, all of which are significantly associated with the amount of exposure to air pollution.

  19. Effect of Internal Clearance on Load Distribution and Life of Radially Loaded Ball and Roller Bearings

    Science.gov (United States)

    Oswald, Fred B.; Zaretsky, Erwin V.; Poplawski, Joseph V.

    2012-01-01

    The effect of internal clearance on radially loaded deepgroove ball and cylindrical roller bearing load distribution and fatigue life was determined for four clearance groups defined in the bearing standards. The analysis was extended to negative clearance (interference) conditions to produce a curve of life factor versus internal clearance. Rolling-element loads can be optimized and bearing life maximized for a small negative operating clearance. Life declines gradually with positive clearance and rapidly with increasing negative clearance. Relationships were found between bearing life and internal clearance as a function of ball or roller diameter, adjusted for load. Results are presented as life factors for radially loaded bearings independent of bearing size or applied load. In addition, a modified Stribeck Equation is presented that relates the maximum rolling-element load to internal bearing clearance.

  20. IRF8 directs stress induced autophagy in macrophages and promotes clearance of Listeria monocytogenes

    Science.gov (United States)

    Gupta, Monica; Shin, Dong-Mi; Ramakrishna, Lakshmi; Goussetis, Dennis J.; Platanias, Leonidas C.; Xiong, Huabao; Morse, Herbert C.; Ozato, Keiko

    2015-01-01

    Autophagy, activated by many stresses, plays a critical role in innate immune responses. Here we show that Interferon Regulatory Factor 8 (IRF8) is required for expression of autophagy-related genes in dendritic cells. Furthermore in macrophages, IRF8 is induced by multiple autophagy-inducing stresses, including IFNγ and toll like receptor stimulation, bacterial infection, starvation and by macrophage colony-stimulating factor. IRF8 directly activates many genes involved in various steps of autophagy, promoting autophagosome formation and lysosomal fusion. Consequently, Irf8-/- macrophages are deficient in autophagic activity, and excessively accumulate SQSTM1 and ubiquitin-bound proteins. We show that clearance of Listeria monocytogenes in macrophages requires IRF8-dependent activation of autophagy genes and subsequent autophagic capturing and degradation of Listeria antigens. These processes are defective in Irf8-/- macrophages where uninhibited bacterial growth ensues. Together, these data suggest that IRF8 is a major autophagy regulator in macrophages, essential for macrophage maturation, survival and innate immune responses. PMID:25775030

  1. Histamine 1 Receptor Blockade Enhances Eosinophil-Mediated Clearance of Adult Filarial Worms

    Science.gov (United States)

    Fox, Ellen Mueller; Morris, Christopher P.; Hübner, Marc P.; Mitre, Edward

    2015-01-01

    Filariae are tissue-invasive nematodes that cause diseases such as elephantiasis and river blindness. The goal of this study was to characterize the role of histamine during Litomosoides sigmodontis infection of BALB/c mice, a murine model of filariasis. Time course studies demonstrated that while expression of histidine decarboxylase mRNA increases throughout 12 weeks of infection, serum levels of histamine exhibit two peaks—one 30 minutes after primary infection and one 8 weeks later. Interestingly, mice treated with fexofenadine, a histamine receptor 1 inhibitor, demonstrated significantly reduced worm burden in infected mice compared to untreated infected controls. Although fexofenadine-treated mice had decreased antigen-specific IgE levels as well as lower splenocyte IL-5 and IFNγ production, they exhibited a greater than fourfold rise in eosinophil numbers at the tissue site where adult L. sigmodontis worms reside. Fexofenadine-mediated clearance of L. sigmodontis worms was dependent on host eosinophils, as fexofenadine did not decrease worm burdens in eosinophil-deficient dblGATA mice. These findings suggest that histamine release induced by tissue invasive helminths may aid parasite survival by diminishing eosinophilic responses. Further, these results raise the possibility that combining H1 receptor inhibitors with current anthelmintics may improve treatment efficacy for filariae and other tissue-invasive helminths. PMID:26204515

  2. Prevention of bacterial adhesion

    DEFF Research Database (Denmark)

    Klemm, Per; Vejborg, Rebecca Munk; Hancock, Viktoria

    2010-01-01

    Management of bacterial infections is becoming increasingly difficult due to the emergence and increasing prevalence of bacterial pathogens that are resistant to available antibiotics. Conventional antibiotics generally kill bacteria by interfering with vital cellular functions, an approach...... that imposes selection pressure for resistant bacteria. New approaches are urgently needed. Targeting bacterial virulence functions directly is an attractive alternative. An obvious target is bacterial adhesion. Bacterial adhesion to surfaces is the first step in colonization, invasion, and biofilm formation....... As such, adhesion represents the Achilles heel of crucial pathogenic functions. It follows that interference with adhesion can reduce bacterial virulence. Here, we illustrate this important topic with examples of techniques being developed that can inhibit bacterial adhesion. Some of these will become...

  3. Mucociliary and cough clearance as a biomarker for therapeutic development

    DEFF Research Database (Denmark)

    Bennett, William D; Daviskas, Evangelia; Hasani, Amir

    2010-01-01

    A workshop/symposium on “Mucociliary and Cough Clearance (MCC/CC) as a Biomarker for Therapeutic Development” was held on October 21–22, 2008, in Research Triangle Park, NC, to discuss the methods for measurement of MCC/CC and how they may be optimized for assessing new therapies designed...... to improve clearance of airway secretions from the lungs. The utility of MCC/CC as a biomarker for disease progression and therapeutic intervention is gaining increased recognition as a valuable tool in the clinical research community. A number of investigators currently active in using MCC/CC for diagnostic...

  4. Diabetic nephropathy: glomerular filtration rate and estimated creatinine clearance

    OpenAIRE

    Guimarães, J; Bastos, M.; Melo, M.; Carvalheiro, M.

    2007-01-01

    OBJECTIVE: To assess in diabetic nephropathy, the accuracy of estimated creatinine clearance (calculated with the Cockroft Gault formula) and the clearance of the Tc99m-DTPA, to measure the glomerular filtration rate (GFR). PATIENTS AND METHODS: We analysed the GFR measure by Tc99m-DTPA method and the estimated by the Cockroft Gault formula, in 21 subjects with type 1 or type 2 diabetes. RESULTS: There was a strong positive correlation between the two methods but the Cockroft Gault formula un...

  5. Effect of oral N-acetylcysteine on mucus clearance.

    Science.gov (United States)

    Millar, A B; Pavia, D; Agnew, J E; Lopez-Vidriero, M T; Lauque, D; Clarke, S W

    1985-07-01

    Oral N-acetylcysteine has been advocated as a mucolytic agent for use in chronic bronchitis. We have investigated the effects of regular use of this drug at a dose of 200 mg thrice daily for 4 weeks in nine patients with chronic bronchitis on lung function, lung mucociliary clearance and sputum viscosity in a controlled, double-blind, crossover study. No significant differences were found in lung function, mucociliary clearance curves or sputum viscosity following treatment with N-acetylcysteine compared to control or placebo measurements.

  6. The influence of body posture on lithium clearance

    DEFF Research Database (Denmark)

    Kamper, A L; Strandgaard, S; Holstein-Rathlou, N H

    1988-01-01

    measured four times at 1-week intervals: two in the supine and one in the sitting position, and one when the subject was walking around. Glomerular filtration rate was not influenced by posture changes. On the contrary, lithium clearance, which in the supine position was 30 +/- 9 ml/min (1 SD), tended...... during moderate physical activity. Hence, when renal tubular function is studied with the lithium clearance method, standardization of posture and physical activity is important. In such studies physical activity such as walking should particularly be avoided....

  7. Which subgroups of fire fighters are more prone to work-related diminished health requirements?

    Science.gov (United States)

    Plat, Marie-Christine J; Frings-Dresen, Monique H W; Sluiter, Judith K

    2012-10-01

    To determine whether certain subgroups of fire fighters are prone to work-related diminished health requirements. The health requirements for fire-fighting were tested in a workers' health surveillance (WHS) setting. These health requirements included psychological, physical and sense-related components as well as cardiovascular risk factors. The odds ratio (OR) and 95% confidence interval (95% CI) for the presence of the diminished health requirements were calculated for the subgroups of gender, professionalism and age. The prevalence of diminished psychological requirements was equivalent among the subgroups, and no significant high-risk group was identified. As compared to men fire fighters, women fire fighters were more likely to have diminished physical requirements (OR 28.5; 95% CI 12.1-66.9) and less likely to have cardiovascular risk factors (OR 0.3; 0.1-0.5). As compared to volunteer fire fighters, professionals were less likely to have diminished physical requirements (OR 0.5; 0.3-0.9), but professionals had a higher prevalence of cardiovascular risk factors with an odds ratio of 1.9 (1.1-3.2). As compared to the youngest fire fighters, the oldest fire fighters were more likely to have diminished sense-related requirements (OR 7.1; 3.4-15.2); a similar comparison could be made between oldest and middle-aged fire fighters (OR 5.1; 2.5-10.5). In addition, the oldest fire fighters were more likely to have cardiovascular risk factors when compared to the youngest (OR 4.4; 1.7-11.1) and to the middle-aged fire fighters (OR 3.1; 1.2-7.9). Subgroups (gender, professionalism and age) of fire fighters are prone to at least one specific work-related diminished health requirement. Therefore, parts of the WHS could be applied with more attention to these high-risk groups.

  8. Control of influenza infection is impaired by diminished interferon-γ secretion by CD4 T cells in the lungs of toddler mice.

    Science.gov (United States)

    Verhoeven, David; Perry, Sheldon; Pryharski, Karin

    2016-07-01

    Respiratory viral infections, such as influenza, can lead to delayed viral clearance in toddlers, possibly exacerbating disease morbidity. We hypothesized that defective CD4 T cells in toddlers may contribute to a failure to clear virus at a similar rate to adults. Thus, we developed a young mouse model to examine potential divergent responses between toddlers and adults. We determined that young mice (toddler mice, 21 d old) were actively generating and recruiting effector/memory T cells, whereas memory populations were firmly established in older, adult mice (8-10 wk old). We infected toddler and adult mice with influenza A/PR8/34 (H1N1) and found young mice had elevated morbidity, as measured by enhanced weight loss and lower partial pressure of oxygen levels, throughout the infection, thus, modeling the higher morbidity observed in children (infection. Early viral loads were comparable to adult mice, but toddler mice failed to clear virus by 10 d postinfection. This delayed clearance corresponded to poor lung recruitment of CD4 T cells, lower antiviral T cell responses, and lower B cell/antibodies in the lungs. Mechanistically, diminished interferon-γ was detected in the lungs of toddler mice throughout the infection and corresponded to intrinsic, rather than extrinsic, CD4 T cell limitations in interferon-γ transcription. Moreover, defects in interferon-γ production appeared downstream from signal transducer and activator of transcription 4 in the interleukin-12 signaling pathway, suggesting maturational delays different from neonates. Importantly, recombinant interferon-γ supplementation rescued CD4 T cell numbers in the lungs and influenza-specific antibody formation. This study highlights the intrinsic limitations in CD4 T cell effector functions that may arise in toddlers and contribute to disease pathology. © Society for Leukocyte Biology.

  9. Working strategy for bacterial contamination control on sugarcane micropropagation

    Directory of Open Access Journals (Sweden)

    Yelenys Alvarado-Capó

    2003-04-01

    Full Text Available The most important losses in labs are caused by microbial contamination. Though several methods have been assayed and put into practice to eliminate or to diminish bacterial contamination of in vitro culture in cells and plant tissues, none has been completely effective. In the present research the aim was to find effective methods to prevent and to control the bacterial contamination of in vitro culture of sugarcane. The culture media for the in vitro plant multiplication was modified by adding nutritive substances in order to evaluate its effect on bacterial contamination percent and its phytotoxicity on in vitro plants. It was also evaluated the effect of modification of the initial pH of the in vitro plant culture medium and bacterial contaminants. It was proved that it is possible, without damaging the in vitro plant, to increase the growing of bacterial contaminants by adding coconut water (100.0 ml.l-1 or yeast extract (250.0 mg.l-1 to the culture medium of multiplication of the sugarcane. The use of the initial pH 6.5 favors the early appearance of bacterial contaminants detecting them since the first 24 hours without a negative effect to the in vitro plant. Evaluating these results a working strategy was set for the prevention and control of bacterial contamination in sugarcane micropropagation by applying early detection methods. Key words: bacteria, coconut water, Saccharum spp. hybrid, yeast extract

  10. Diminished criminal responsibility ofalcohol intoxicated homicide offenders according ofdemographic factors, family rate and alcohol dependence

    Directory of Open Access Journals (Sweden)

    Anna Sieradzka

    2013-03-01

    Full Text Available Ethanol intoxication is commonly considered as a risk factor of a criminal offence. This study is an attempt to assess selected demographic data, family situation, and alcohol dependence in homicide offenders or a severe body injury in relation to a judgment of diminished criminal responsibility. The examined group consisted of 90 suspects in the pub‑ lic prosecutor’s investigation. The subjects underwent a six-week forensic psychiatry observation during 2004–2008 at the Forensic Psychiatry Unit in High Security Prison No in Łódź. Analysed retrospectively was the medical documentation collected during the forensic psychiatry observation, including available medical documentation and categorical forensic psychiatry observation opinions issued by two expert psychiatrists. According to the collected materials, it was established that in the performed study none of the offenders who during ethanol intoxication committed a homicide or a severe body injury was acknowledged to be criminally responsible. A greatly diminished criminal responsibility was significantly more frequently evaluated in the case of divorced subjects who were not witnesses to aggression in their families and were not punished with a court verdict. Among the subjects with a greatly diminished criminal responsibility the alcohol dependence was diagnosed much less frequently. Besides, the offenders with a great‑ ly diminished criminal responsibility were older than those with a slightly diminished responsibility and evaluated as criminally responsible.

  11. Bacterial Vaginosis and the Natural History of Human Papillomavirus

    Directory of Open Access Journals (Sweden)

    Caroline C. King

    2011-01-01

    Full Text Available Objective. To evaluate associations between common vaginal infections and human papillomavirus (HPV. Study Design. Data from up to 15 visits on 756 HIV-infected women and 380 high-risk HIV-uninfected women enrolled in the HIV Epidemiology Research Study (HERS were evaluated for associations of bacterial vaginosis, trichomoniasis, and vaginal Candida colonization with prevalent HPV, incident HPV, and clearance of HPV in multivariate analysis. Results. Bacterial vaginosis (BV was associated with increased odds for prevalent (aOR = 1.14, 95% CI: 1.04, 1.26 and incident (aOR = 1.24, 95% CI: 1.04, 1.47 HPV and with delayed clearance of infection (aHR = 0.84, 95% CI: 0.72, 0.97. Whereas BV at the preceding or current visit was associated with incident HPV, in an alternate model for the outcome of incident BV, HPV at the current, but not preceding, visit was associated with incident BV. Conclusion. These findings underscore the importance of prevention and successful treatment of bacterial vaginosis.

  12. Anatomical factors predicting lower calyceal stone clearance after ...

    African Journals Online (AJOL)

    M. Khan

    2016-02-17

    Feb 17, 2016 ... 1992;147:322–4. [6] Elbahanasy AM, Shalhav AL, Hoenig DM, Elashry OM, Smith DS,. McDougall EM, et al. Lower caliceal stone clearance after shock wave lithotripsy or ureteroscopy: the impact of lower pole radiographic anatomy. J Urol 1998;159:676–82. [7] Kiely EA, Madigan D, Ryan PC, Butler MR.

  13. Celllular Uptake and Clearance of TIO2 Nanoparticles

    Science.gov (United States)

    Differential rates of cellular uptake and clearance of engineered nanomaterials may influence the propensity for tissue accumulation under chronic exposure conditions. A retinal pigment epithelial cell line (ARPE-19) was used to investigate 1) if Ti02 (Degussa, P25) nanoparticles...

  14. Hyperinsulinism and polycystic ovary syndrome (PCOS): role of insulin clearance.

    Science.gov (United States)

    Amato, M C; Vesco, R; Vigneri, E; Ciresi, A; Giordano, C

    2015-12-01

    Insulin resistance and compensatory hyperinsulinism are the predominant metabolic defects in polycystic ovary syndrome (PCOS). However, hyperinsulinism, as well as being compensatory, can also express a condition of reduced insulin clearance. Our aim was to evaluate the differences in insulin action and metabolism between women with PCOS (with normal glucose tolerance) and age- and BMI-matched women with prediabetes (without hyperandrogenism and ovulatory disorders). 22 women with PCOS and 21 age/BMI-matched women with prediabetes were subjected to a Hyperinsulinemic-euglycemic clamp and an Oral Glucose tolerance Test (OGTT). Insulin sensitivity was assessed by the glucose infusion rate during clamp (M value); insulin secretion by Insulinogenic index, Oral Disposition Index (DIo) and AUC(2h-insulin) during OGTT; and insulin clearance by the metabolic clearance rate of insulin (MCRI) during clamp. Women with PCOS showed significantly higher levels of AUC(2h-insulin) (p PCOS [420 (IQR 227-588) vs. 743 (IQR 597-888) ml m(-2) min(-1): p PCOS group, a strong independent inverse correlation was only observed between MCRI and AUC(2h-insulin) (PCOS: β:-0.878; p PCOS there is peripheral insulin sensitivity similar to that of women with prediabetes. What sets PCOS apart is the hyperinsulinism, today still simplistically defined "compensatory"; actually this is mainly related to decreased insulin clearance whose specific causes and dynamics have yet to be clarified.

  15. 19 CFR 148.23 - Examination and clearance of baggage.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Examination and clearance of baggage. 148.23 Section 148.23 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY... § 148.32. (2) Works of art classifiable under subheadings 9701.10.00 or 9701.90.00, HTSUS. (3) Works of...

  16. Mucociliary Clearance Time in Patients with and without Rhinitis ...

    African Journals Online (AJOL)

    While rhinitis is not a life-threatening condition, complications may occur and the condition can significantly impair quality of life. In order to measure the mucociliary clearance time in patients with and without rhinitis a study was conducted in the ENT, H&N, and orthopedic departments at KNH. Methods: 130 cases between ...

  17. 50 CFR 14.52 - Clearance of imported wildlife.

    Science.gov (United States)

    2010-10-01

    ... 50 Wildlife and Fisheries 1 2010-10-01 2010-10-01 false Clearance of imported wildlife. 14.52 Section 14.52 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR TAKING, POSSESSION, TRANSPORTATION, SALE, PURCHASE, BARTER, EXPORTATION, AND IMPORTATION OF WILDLIFE AND...

  18. In Vivo Renal Clearance, Biodistribution, Toxicity of Gold nanoclusters

    CERN Document Server

    Zhang, Xiao-Dong; Shen, Xiu; Liu, Pei-Xun; Fan, Fei-Yue; Fan, Sai-Jun; 10.1016/j.biomaterials.2012.03.020

    2012-01-01

    Gold nanoparticles have shown great prospective in cancer diagnosis and therapy, but they can not be metabolized and prefer to accumulate in liver and spleen due to their large size. The gold nanoclusters with small size can penetrate kidney tissue and have promise to decrease in vivo toxicity by renal clearance. In this work, we explore the in vivo renal clearance, biodistribution, and toxicity responses of the BSA- and GSH-protected gold nanoclusters for 24 hours and 28 days. The BSA-protected gold nanoclusters have low-efficient renal clearance and only 1% of gold can be cleared, but the GSH-protected gold nanoclusters have high-efficient renal clearance and 36 % of gold can be cleared after 24 hours. The biodistribution further reveals that 94% of gold can be metabolized for the GSH-protected nanoclusters, but only less than 5% of gold can be metabolized for the BSA-protected nanoclusters after 28 days. Both of the GSH- and BSA-protected gold nanoclusters cause acute infection, inflammation, and kidney fu...

  19. 20 CFR 655.150 - Interstate clearance of job order.

    Science.gov (United States)

    2010-04-01

    ... elapsed, and must refer each qualified U.S. worker who applies (or on whose behalf an application is made... EMPLOYMENT OF FOREIGN WORKERS IN THE UNITED STATES Labor Certification Process for Temporary Agricultural Employment in the United States (H-2A Workers) Post-Acceptance Requirements § 655.150 Interstate clearance of...

  20. Mucociliary and cough clearance as a biomarker for therapeutic development

    DEFF Research Database (Denmark)

    Bennett, William D; Daviskas, Evangelia; Hasani, Amir

    2010-01-01

    A workshop/symposium on “Mucociliary and Cough Clearance (MCC/CC) as a Biomarker for Therapeutic Development” was held on October 21–22, 2008, in Research Triangle Park, NC, to discuss the methods for measurement of MCC/CC and how they may be optimized for assessing new therapies designed...

  1. Factors affecting lower calyceal stone clearance after Extracorporeal ...

    African Journals Online (AJOL)

    shanker

    Abstract. Objective: Extracorporeal shock wave lithotripsy (ESWL) is one of the most commonly used procedures to remove renal calculi from the lower calyces. The aim of this work is to study the impact of radiological, anatomical and demographic factors on stone clearance after ESWL of lower calyceal calculi. Patients and ...

  2. Factors affecting lower calyceal stone clearance after Extracorporeal ...

    African Journals Online (AJOL)

    Objective: Extracorporeal shock wave lithotripsy (ESWL) is one of the most commonly used procedures to remove renal calculi from the lower calyces. The aim of this work is to study the impact of radiological, anatomical and demographic factors on stone clearance after ESWL of lower calyceal calculi. Patients and ...

  3. Spontaneous Clearance of Hepatitis C after Liver and Renal Transplantation

    Directory of Open Access Journals (Sweden)

    CH Dale

    2009-01-01

    Full Text Available Spontaneous clearance of hepatitis C virus (HCV is rare in immunocompromised patients, such as those who have undergone organ transplantation. It has been recognized that patients receiving liver transplantation for HCV-related disease have decreased graft and patient survival compared with those transplanted for other etiologies. There is a growing trend toward treating HCV recurrence aggressively after liver transplantation. For other organ transplant recipients with concurrent HCV, treatment is not often an option, given the high rates of graft rejection and loss secondary to interferon and its immunomodulatory effects. Although spontaneous clearance of HCV has been reported in recipients of solitary liver and renal transplants, a common factor arising in these cases has been previous exposure to interferon. To date, no reports of spontaneous clearance of HCV RNA have been reported in a multiorgan transplant recipient. A case of spontaneous clearance of HCV RNA in an immunocompromised patient, within five months of simultaneous liver and kidney retransplantation is described. Importantly, this patient had no previous exposure to interferon.

  4. The influence of body posture on lithium clearance

    DEFF Research Database (Denmark)

    Kamper, A L; Strandgaard, S; Holstein-Rathlou, N H

    1988-01-01

    measured four times at 1-week intervals: two in the supine and one in the sitting position, and one when the subject was walking around. Glomerular filtration rate was not influenced by posture changes. On the contrary, lithium clearance, which in the supine position was 30 +/- 9 ml/min (1 SD), tended...

  5. Tidal volume and alveolar clearance of insoluble particles.

    Science.gov (United States)

    John, J; Wollmer, P; Dahlbäck, M; Luts, A; Jonson, B

    1994-02-01

    We studied the effect of 3 h of large tidal volume ventilation on alveolar clearance of 0.63-micron fluorescent latex particles in rabbits during pentobarbital anesthesia. After particle deposition, six animals were killed as controls, six were subjected to large tidal volume ventilation with a peak pressure of 27 cmH2O, and six were subjected to conventional ventilation with a peak pressure of 11 cmH2O. Mean tidal volumes were 30.2 +/- 6.1 and 8.4 +/- 1.6 ml/kg in the large tidal volume and conventional groups, respectively. End-expiratory pressure was 2 cmH2O in all groups. Compliance decreased only after large tidal ventilation (P = 0.0036). Compared with controls the conventional ventilation group showed no alveolar clearance, but more particles were clustered within macrophages (P = 0.01). Compared with other groups the large tidal volume group had fewer alveolar particles (P = 0.0005), most of which were single particles. Accordingly, large tidal volumes enhance alveolar particle clearance, which is possibly related to distension-related evacuation of surfactant to proximal airways. Clearance may be due to accelerated motion of the particle-loaded macrophage in response to the fast film motion. Alternatively, single particles embedded in the surfactant film may be dragged by the fast-moving film toward the airways.

  6. Cell-phone use diminishes self-awareness of impaired driving.

    Science.gov (United States)

    Sanbonmatsu, David M; Strayer, David L; Biondi, Francesco; Behrends, Arwen A; Moore, Shannon M

    2016-04-01

    Multitasking diminishes the self-awareness of performance that is often essential for self-regulation and self-knowledge. Participants drove in a simulator while either talking or not talking on a hands-free cell phone. Following previous research, participants who talked on a cell phone made more serious driving errors than control participants who did not use a phone while driving. Control participants' assessments of the safeness of their driving and general ability to drive safely while distracted were negatively correlated with the actual number of errors made when they were driving. By contrast, cell-phone participants' assessments of the safeness of their driving and confidence in their driving abilities were uncorrelated with their actual errors. Thus, talking on a cell phone not only diminished the safeness of participants' driving, it diminished their awareness of the safeness of their driving.

  7. Solute clearance in CRRT: prescribed dose versus actual delivered dose.

    Science.gov (United States)

    Lyndon, William D; Wille, Keith M; Tolwani, Ashita J

    2012-03-01

    Substantial efforts have been made toward defining the dose threshold of continuous renal replacement therapy (CRRT) associated with improved survival in critically ill patients with acute kidney injury. Published studies have used prescribed effluent rates, expressed as total effluent volume (TEV) per weight and unit time (mL/kg/h), as a surrogate for dose. The purpose of this study was to compare differences in CRRT dose based on prescribed effluent rate, measured TEV and direct measurement of urea and creatinine clearance. We analyzed data that had been prospectively collected on 200 patients enrolled in a randomized trial comparing survival with a prescribed effluent rate of 20 mL/kg/h (standard dose) to 35 mL/kg/h (high dose) using pre-dilution continuous venovenous hemodiafiltration (CVVHDF). Filters were changed every 72 h. Blood urea nitrogen (BUN), serum creatinine (SCr), effluent urea nitrogen (EUN) and effluent creatinine (ECr) were collected daily. Actual delivered dose was calculated as: (EUN/BUN)*TEV for urea and (ECr/SCr)*TEV for creatinine. Data were available for 165 patients. In both groups, prescribed dose differed significantly from the measured TEV dose (P < 0.001). In the standard dose group, there was no difference between the measured TEV dose and actual delivered urea and creatinine clearances. However, in the high-dose group, measured TEV dose differed significantly from delivered urea clearance by 7.1% (P < 0.001) and creatinine clearance by 13.9% (P < 0.001). Dose based on prescribed effluent rate or measured TEV is a poor substitute for actual CVVHDF creatinine and urea clearance.

  8. Association of serum cytokines with oral HPV clearance.

    Science.gov (United States)

    Lam, Jennifer O; Bream, Jay H; Sugar, Elizabeth A; Coles, Christian L; Weber, Kathleen M; Burk, Robert D; Wiley, Dorothy J; Cranston, Ross D; Reddy, Susheel; Margolick, Joseph B; Strickler, Howard D; Wentz, Alicia; Jacobson, Lisa; Guo, Yingshi; Xiao, Weihong; Gillison, Maura L; D'Souza, Gypsyamber

    2016-07-01

    Initial studies suggest higher serum levels of some pro-inflammatory cytokines may be associated with decreased cervical human papillomavirus (HPV) clearance. However, the relationship of cytokines with oral HPV clearance has not been explored. From 2010 to 2014, oral rinse and serum samples were collected semi-annually from 1601 adults. Oral rinse samples were tested for HPV DNA using PCR. Based on oral HPV results, 931 serum samples were selected for cytokine evaluation to include a roughly equal number of prevalent (n=307), incident (n=313), and no oral HPV infections (n=311). Electrochemiluminescence multiplex assays were used to determine the concentrations of IL-6, IL-8, TNF-α, IFN-γ, IL-1β, IL-2, IL-4, IL-10, IL-12 and IL-13. The relationship between serum cytokine concentrations (categorized into quartiles) and oral HPV clearance was evaluated with Wei-Lin-Weissfeld regression models, adjusting for HPV infection type (prevalent vs. incident), age, HIV status, and CD4 T cell count. Higher TNF-α concentration was associated with decreased clearance in men (highest vs. lowest quartile, adjusted hazard ratio [aHR]=0.52, 95% CI=0.34-0.79) and women (aHR=0.76, 95% confidence interval [CI]=0.55-1.04), with stronger associations in men than women (p-interaction=0.049). Higher IL-2 concentration was associated with reduced clearance in men (aHR=0.69, 95% CI=0.50-0.95), but not women (p-interaction=0.058). Results were similar within CD4 T cell strata (CD4⩾500 or CD4HPV infection. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Ammonia clearance with haemofiltration in adults with liver disease.

    Science.gov (United States)

    Slack, Andrew J; Auzinger, Georg; Willars, Chris; Dew, Tracy; Musto, Rebecca; Corsilli, Daniel; Sherwood, Roy; Wendon, Julia A; Bernal, William

    2014-01-01

    Ammonia is recognized as a toxin central to complications of liver failure. Hyperammonaemia has important clinical consequences, but optimal means to reduce circulating levels are uncertain. In patients with liver disease, continuous renal replacement therapy (CRRT) with haemofiltration (HF) is often required to treat concurrent kidney injury, but its effects upon ammonia levels are poorly characterized. To evaluate the effect of HF at different treatment intensities on ammonia clearance (AC) and arterial ammonia concentration. Prospective study of adult patients with liver failure and arterial ammonia >100 μmol/L requiring CRRT using veno-venous HF. Arterial ammonia concentration and AC measured at 1 and 24 h after initiation of low (35 ml/kg/h) or high (90 ml/kg/h) filtration volume. Twenty-four patients (10 acute liver failure, 10 chronic liver disease and 4 following liver resection) were studied. Clearance of urea and ammonia solutes correlated closely (r = 0.819, P = 0.007). Ammonia clearance correlated closely with ultrafiltration rate (r = 0.86, P < 0.001). At 1 h, AC was 39 (34-54) ml/min (low volume) vs 85 (62-105) ml/min (high volume) CRRT, (P < 0.001) and at 24 h 44 (34-63) vs 105 (82-109) ml/min, (P = 0.01). Overall, a 22% reduction in median arterial ammonia concentration was observed over 24 h of HF from 156 (137-176) to 122 (85-133) μmol/L, (P ≤ 0.0001). Clinically significant ammonia clearance can be achieved in adult patients with hyperammonaemia utilizing continuous VVHF. Ammonia clearance is closely correlated with ultrafiltration rate. HF was associated with a fall in arterial ammonia concentration. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Airway epithelial NF-κB activation promotes Mycoplasma pneumoniae clearance in mice.

    Directory of Open Access Journals (Sweden)

    Di Jiang

    Full Text Available Respiratory infections including atypical bacteria Mycoplasma pneumoniae (Mp contribute to the pathobiology of asthma and chronic obstructive pulmonary disease (COPD. Mp infection mainly targets airway epithelium and activates various signaling pathways such as nuclear factor κB (NF-κB. We have shown that short palate, lung, and nasal epithelium clone 1 (SPLUNC1 serves as a novel host defense protein and is up-regulated upon Mp infection through NF-κB activation in cultured human and mouse primary airway epithelial cells. However, the in vivo role of airway epithelial NF-κB activation in host defense against Mp infection has not been investigated. In the current study, we investigated the effects of in vivo airway epithelial NF-κB activation on lung Mp clearance and its association with airway epithelial SPLUNC1 expression.Non-antimicrobial tetracycline analog 9-t-butyl doxycycline (9-TB was initially optimized in mouse primary tracheal epithelial cell culture, and then utilized to induce in vivo airway epithelial specific NF-κB activation in conditional NF-κB transgenic mice (CC10-(CAIKKβ with or without Mp infection. Lung Mp load and inflammation were evaluated, and airway epithelial SPLUNC1 protein was examined by immunohistochemistry. We found that 9-TB treatment in NF-κB transgene positive (Tg+, but not transgene negative (Tg- mice significantly reduced lung Mp load. Moreover, 9-TB increased airway epithelial SPLUNC1 protein expression in NF-κB Tg+ mice.By using the non-antimicrobial 9-TB, our study demonstrates that in vivo airway epithelial NF-κB activation promotes lung bacterial clearance, which is accompanied by increased epithelial SPLUNC1 expression.

  11. In vivo Distribution and Clearance of Purified Capsular Polysaccharide from Burkholderia pseudomallei in a Murine Model.

    Directory of Open Access Journals (Sweden)

    Teerapat Nualnoi

    2016-12-01

    Full Text Available Burkholderia pseudomallei is the causative agent of melioidosis, a severe infection prominent in northern Australia and Southeast Asia. The "gold standard" for melioidosis diagnosis is bacterial isolation, which takes several days to complete. The resulting delay in diagnosis leads to delayed treatments, which could result in death. In an attempt to develop better methods for early diagnosis of melioidosis, B. pseudomallei capsular polysaccharide (CPS was identified as an important diagnostic biomarker. A rapid lateral flow immunoassay utilizing CPS-specific monoclonal antibody was developed and tested in endemic regions worldwide. However, the in vivo fate and clearance of CPS has never been thoroughly investigated. Here, we injected mice with purified CPS intravenously and determined CPS concentrations in serum, urine, and major organs at various intervals. The results indicate that CPS is predominantly eliminated through urine and no CPS accumulation occurs in the major organs. Immunoblot analysis demonstrated that intact CPS was excreted through urine. To understand how a large molecule like CPS was eliminated without degradation, a 3-dimenational structure of CPS was modeled. The predicted CPS structure has a rod-like shape with a small diameter that could allow it to flow through the glomerulus of the kidney. CPS clearance was determined using exponential decay models and the corrected Akaike Information Criterion. The results show that CPS has a relatively short serum half-life of 2.9 to 4.4 hours. Therefore, the presence of CPS in the serum and/or urine suggests active melioidosis infection and provides a marker to monitor treatment of melioidosis.

  12. IFN-γ stimulates autophagy-mediated clearance of Burkholderia cenocepacia in human cystic fibrosis macrophages.

    Directory of Open Access Journals (Sweden)

    Kaivon Assani

    Full Text Available Burkholderia cenocepacia is a virulent pathogen that causes significant morbidity and mortality in patients with cystic fibrosis (CF, survives intracellularly in macrophages, and uniquely causes systemic infections in CF. Autophagy is a physiologic process that involves engulfing non-functional organelles and proteins and delivering them for lysosomal degradation, but also plays a role in eliminating intracellular pathogens, including B. cenocepacia. Autophagy is defective in CF but can be stimulated in murine CF models leading to increased clearance of B. cenocepacia, but little is known about autophagy stimulation in human CF macrophages. IFN-γ activates macrophages and increases antigen presentation while also inducing autophagy in macrophages. We therefore, hypothesized that treatment with IFN-γ would increase autophagy and macrophage activation in patients with CF. Peripheral blood monocyte derived macrophages (MDMs were obtained from CF and non-CF donors and subsequently infected with B. cenocepacia. Basal serum levels of IFN-γ were similar between CF and non-CF patients, however after B. cenocepacia infection there is deficient IFN-γ production in CF MDMs. IFN-γ treated CF MDMs demonstrate increased co-localization with the autophagy molecule p62, increased autophagosome formation, and increased trafficking to lysosomes compared to untreated CF MDMs. Electron microscopy confirmed IFN-γ promotes double membrane vacuole formation around bacteria in CF MDMs, while only single membrane vacuoles form in untreated CF cells. Bacterial burden is significantly reduced in autophagy stimulated CF MDMs, comparable to non-CF levels. IL-1β production is decreased in CF MDMs after IFN-γ treatment. Together, these results demonstrate that IFN-γ promotes autophagy-mediated clearance of B. cenocepacia in human CF macrophages.

  13. Peritonitis - spontaneous bacterial

    Science.gov (United States)

    Spontaneous bacterial peritonitis (SBP); Ascites - peritonitis; Cirrhosis - peritonitis ... who are on peritoneal dialysis for kidney failure. Peritonitis may have other causes . These include infection from ...

  14. The roles of haemocytes and the lymphoid organ in the clearance of injected Vibrio bacteria in Penaeus monodon shrimp.

    Science.gov (United States)

    van de Braak, C B T; Botterblom, M H A; Taverne, N; van Muiswinkel, W B; Rombout, J H W M; van der Knaap, W P W

    2002-10-01

    In order to study the reaction of Penaeus monodon haemocytes, live Vibrio anguillarum bacteria were injected and the shrimp were periodically sampled. Immuno-double staining analysis with specific antisera against the haemocyte granules and bacteria showed that large numbers of haemocytes encapsulated the bacteria at the site of injection. A rapid decrease of live circulating bacteria was detected in the haemolymph. Bacterial clearance in the haemolymph was induced by humoral factors, as observed by agglutinated bacteria, and followed by uptake in different places in the body. Bacteria mainly accumulated in the lymphoid organ (LO), where they, or their degradation products, could be detected for at least 7 days after injection. The LO consists of folded tubules with a central haemal lumen and a wall, layered with cells. The haemolymph, including the antigens, seemed to migrate from the central tubular lumen through the wall, where the bacteria are arrested and their degradation is started. Electron microscopy of the LO revealed the presence of many phagocytic cells that morphologically resemble small-granular haemocytes. It is proposed that haemocytes settle in the tubule walls before they phagocytose. Immunostaining suggests that many of the haemocytes degranulate in the LO, producing a layer of fibrous material in the outer tubule wall. These findings might contribute to the reduced haemocyte concentration in the haemolymph of diseased animals or following injection of foreign material. It is proposed that the LO is a filter for virtually all foreign material encountered in the haemolymph. Observations from the present study are similar to clearance mechanisms in the hepatic haemolymph vessel in most decapod crustaceans that do not possess a LO. The experimental shrimp appeared to contain many LO spheroids, where bacterial antigens were finally observed as well. It is proposed that the spheroids have a degradation function for both bacterial and viral material

  15. A comparison of analytic procedures for measurement of fractional dextran clearances

    NARCIS (Netherlands)

    Hemmelder, MH; de Jong, PE; de Zeeuw, D

    1998-01-01

    Fractional dextran clearances have been extensively used to study glomerular size selectivity. We report on an analysis of different laboratory procedures involved in measuring fractional dextran clearances. The deproteinization of plasma samples by 20% trichloroacetic acid (TCA) revealed a protein

  16. Rapid Treponema pallidum clearance from blood and ulcer samples following single dose benzathine penicillin treatment of early syphilis.

    Directory of Open Access Journals (Sweden)

    Craig Tipple

    2015-02-01

    Full Text Available Currently, the efficacy of syphilis treatment is measured with anti-lipid antibody tests. These can take months to indicate cure and, as a result, syphilis treatment trials require long periods of follow-up. The causative organism, Treponema pallidum (T. pallidum, is detectable in the infectious lesions of early syphilis using DNA amplification. Bacteraemia can likewise be identified, typically in more active disease. We hypothesise that bacterial clearance from blood and ulcers will predict early the standard serology-measured treatment response and have developed a qPCR assay that could monitor this clearance directly in patients with infectious syphilis. Patients with early syphilis were given an intramuscular dose of benzathine penicillin. To investigate the appropriate sampling timeframe samples of blood and ulcer exudate were collected intensively for T. pallidum DNA (tpp047 gene and RNA (16S rRNA quantification. Sampling ended when two consecutive PCRs were negative. Four males were recruited. The mean peak level of T. pallidum DNA was 1626 copies/ml whole blood and the mean clearance half-life was 5.7 hours (std. dev. 0.53. The mean peak of 16S rRNA was 8879 copies/ml whole blood with a clearance half-life of 3.9 hours (std. dev. 0.84. From an ulcer, pre-treatment, 67,400 T. pallidum DNA copies and 7.08 x 107 16S rRNA copies were detected per absorbance strip and the clearance half-lives were 3.2 and 4.1 hours, respectively. Overall, T. pallidum nucleic acids were not detected in any sample collected more than 56 hours (range 20-56 after treatment. All patients achieved serologic cure. In patients with active early syphilis, measuring T. pallidum levels in blood and ulcer exudate may be a useful measure of treatment success in therapeutic trials. These laboratory findings need confirmation on a larger scale and in patients receiving different therapies.

  17. 48 CFR 245.7101-4 - DD Form 1640, Request for Plant Clearance.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false DD Form 1640, Request for Plant Clearance. 245.7101-4 Section 245.7101-4 Federal Acquisition Regulations System DEFENSE... Forms 245.7101-4 DD Form 1640, Request for Plant Clearance. Use to request plant clearance assistance or...

  18. Bacterie remt phytophthora

    NARCIS (Netherlands)

    Knuivers, M.; Overbeek, van L.S.

    2009-01-01

    Bacteriën kunnen aardappelplanten weerbaarder maken tegen phytophthora. Uit kas-experimenten van Plant Research International (PRI) blijkt dat de aanwezigheid van de bacteriePseudomonas putida(isolaat P9) in twee late aardappelrassen leidt tot een vertraging met 45 procent van het ziekteverloop na

  19. common bacterial pathogens seen.

    African Journals Online (AJOL)

    Background: Bacterial infections are important causes of morbidity in the neonatal period. Therefore identification of infecting organisms and the risk factors for possible bacterial infection in the newborn is of great importance. Institution early appropriate therapy is an important step in combating morbidity and mortality in this ...

  20. Can Using Human Examples Diminish the Number of Misconceptions Held Concerning Mendelian Genetics Concepts?

    Science.gov (United States)

    Moore, John M.

    2000-01-01

    Explores high school biology and the teaching of genetics. The question is asked, Can the use of relevant, meaningful human genetics concepts diminish the number of misconceptions formed between new and existing concepts? Can the application of the Ausubelian learning theory also decrease the acquisition of misconceptions? (SAH)

  1. Dietary long-chain omega-3 fatty acids do not diminish eosinophilic pulmonary inflammation in mice

    Science.gov (United States)

    The effects of fish oil supplements on diminishing airway inflammation in asthma have been studied in mouse models and human intervention trials with varying results. However, the independent effects of the main omega-3 PUFAs found in fish oil, eicosapentaenoic acid (EPA) and docosahexaenoic acid (D...

  2. An Empirical Study of Education Divide Diminishment through Online Learning Courses

    Science.gov (United States)

    Hsieh, Ming-Yuan

    2017-01-01

    According to the swift development of education system, Taiwanese government is always devoting diminishing the educational divide between rural and urban regions. This research focuses on this educational divide by cross-employing the Grey Relational Analysis (GRA) of quantitative analysis and the Fuzzy Set Qualitative Comparative Analysis…

  3. [Physical activity diminishes aging-related decline of physical and cognitive performance].

    Science.gov (United States)

    Apor, Péter; Babai, László

    2014-05-25

    Aging-related decline of muscle force, walking speed, locomotor coordination, aerobic capacity and endurance exert prognostic impact on life expectancy. Proper use of training may diminish the aging process and it may improve the quality of life of elderly persons. This paper provides a brief summary on the impact of training on aging-related decline of physical and cognitive functions.

  4. Respiratory and hemodynamic effects of diminished expiratory flow during artificial ventilation

    NARCIS (Netherlands)

    W. van Rooyen (Willem)

    1986-01-01

    textabstractThe supposition, that a diminished expiratory flow (DEF) during artificial ventilation will improve blood-gas exchange. especially in obstructive pulmonary disease and that DEF improves blood-gas exchange better than a comparable positive end-expiratory pressure (PEEP. producing the same

  5. Less Guilty by Reason of Adolescence: Developmental Immaturity, Diminished Responsibility, and the Juvenile Death Penalty

    Science.gov (United States)

    Steinberg, Laurence; Scott, Elizabeth S.

    2003-01-01

    The authors use a developmental perspective to examine questions about the criminal culpability of juveniles and the juvenile death penalty. Under principles of criminal law, culpability is mitigated when the actor's decision-making capacity is diminished, when the criminal act was coerced, or when the act was out of character. The authors argue…

  6. Diminishing Marginal Returns From Genomic Selection As More Selection Candidates Are Phenotyped

    DEFF Research Database (Denmark)

    Okeno, Tobias O; Henryon, Mark; Sørensen, Anders Christian

    We used stochastic simulation to test hypotheses that, (i) phenotyping proportion of high ranking selection candidates based on estimated breeding values (EBV) before genotyping could realize as much genetic gains as phenotyping all candidates, and (ii) there is diminishing return to selection...

  7. Diminishing Footprints: Exploring the Local and Global Challenges to Place-Based Environmental Education

    Science.gov (United States)

    Chang, David

    2017-01-01

    An efficacious response to the ecological crisis requires a thorough examination of our material entitlements and a willingness to reduce our ecological impact by diminishing current levels of consumption. Drawing on the example of air pollution in China, I present a case for the reduction of consumption and impact as a worthy outcome of…

  8. Nonsuicidal self-injury and diminished pain perception: the role of emotion dysregulation

    NARCIS (Netherlands)

    Franklin, J.C.; Aaron, R.V.; Arthur, M.S.; Shorkey, S.P.; Prinstein, M.J.

    2012-01-01

    Nonsuicidal self-injury (NSSI) is the deliberate destruction of one's own body tissue in the absence of suicidal intent (e.g., cutting or burning the skin). Previous studies have found that people with a history of NSSI display diminished pain perception. However, it remains unclear why this effect

  9. Epstein-Barr virus reactivation associated with diminished cell-mediated immunity in antarctic expeditioners

    Science.gov (United States)

    Mehta, S. K.; Pierson, D. L.; Cooley, H.; Dubow, R.; Lugg, D.

    2000-01-01

    Epstein-Barr virus (EBV) reactivation and cell-mediated immune (CMI) responses were followed in 16 Antarctic expeditioners during winter-over isolation at 2 Australian National Antarctic Research Expedition stations. Delayed-type hypersensitivity (DTH) skin testing was used as an indicator of the CMI response, that was evaluated 2 times before winter isolation and 3 times during isolation. At all 5 evaluation times, 8 or more of the 16 subjects had a diminished CMI response. Diminished DTH was observed on every test occasion in 4/16 subjects; only 2/16 subjects exhibited normal DTH responses for all 5 tests. A polymerase chain reaction (PCR) assay was used to detect EBV DNA in saliva specimens collected before, during, and after the winter isolation. EBV DNA was present in 17% (111/642) of the saliva specimens; all 16 subjects shed EBV in their saliva on at least 1 occasion. The probability of EBV shedding increased (P = 0.013) from 6% before or after winter isolation to 13% during the winter period. EBV appeared in saliva during the winter isolation more frequently (P < 0.0005) when DTH response was diminished than when DTH was normal. The findings indicate that the psychosocial, physical, and other stresses associated with working and living in physical isolation during the Antarctic winter result in diminished CMI and an accompanying increased reactivation and shedding of latent viruses.

  10. Vimentin in Bacterial Infections

    DEFF Research Database (Denmark)

    Mak, Tim N; Brüggemann, Holger

    2016-01-01

    Despite well-studied bacterial strategies to target actin to subvert the host cell cytoskeleton, thus promoting bacterial survival, replication, and dissemination, relatively little is known about the bacterial interaction with other components of the host cell cytoskeleton, including intermediate...... filaments (IFs). IFs have not only roles in maintaining the structural integrity of the cell, but they are also involved in many cellular processes including cell adhesion, immune signaling, and autophagy, processes that are important in the context of bacterial infections. Here, we summarize the knowledge...... about the role of IFs in bacterial infections, focusing on the type III IF protein vimentin. Recent studies have revealed the involvement of vimentin in host cell defenses, acting as ligand for several pattern recognition receptors of the innate immune system. Two main aspects of bacteria...

  11. Microwave Sensor for Blade Tip Clearance and Structural Health Measurements

    Science.gov (United States)

    Woike, Mark R.; Bencic, Timothy J.

    2008-01-01

    The use of microwave based sensors for the health monitoring of rotating machinery is being explored at the NASA Glenn Research Center. The microwave sensor works on the principle of sending a continuous signal towards a rotating component and measuring the reflected signal. The phase shift of the reflected signal is proportional to the distance between the sensor and the component that is being measured. This type of sensor is beneficial in that it has the ability to operate at extremely high temperatures and is unaffected by contaminants that may be present in the rotating machinery. It is intended to use these probes in the hot sections of turbine engines for closed loop turbine clearance control and structural health measurements. Background on the sensors, an overview of their calibration and preliminary results from using them to make blade tip clearance and health measurements on a large axial vane fan will be presented.

  12. Gas film lubrication equations for very small clearances

    Energy Technology Data Exchange (ETDEWEB)

    Sobehart, J.R. [Los Alamos National Lab., NM (United States); Reyna, L.G. [International Business Machines Corp., Yorktown Heights, NY (United States). Thomas J. Watson Research Center

    1994-05-01

    In the hard disk magnetic recording technology, the slider carrying the magnetic elements is supported above the magnetic disk by a self-acting air bearing, which produces the load support. A lubricating film must support a required load with suitably small frictional energy losses and without introducing undesirable instabilities. Under submicron clearance conditions, gas film flow can not be described with continuum models since the molecular mean free path is not negligible compared with the clearance. Accurate results for the load-carrying capacity of gas films for arbitrary Knudsen number are very important since they strongly influence the design of the flying head slider and, consequently, the performance of the magnetic disk storage unit. Here we generalize the previous lubrication equations for arbitrary Knudsen number, accommodation coefficient and a small inclination of the slider relative to the magnetic disk surface.

  13. Respiratory Protection Program medical clearance for respirator use

    Science.gov (United States)

    1993-01-01

    Background on occupational exposure to various inhalents is discussed including on-site hazard control measures, procedures, physiological effects, and interpretation of results for the medical clearance of employee for use of personal respiratory protection devices. The purpose of the Respiratory Protection Program at LeRC is outlined, and the specifics of the Medical Surveillance Program for Respiratory Protection at LeRC are discussed.

  14. Harnessing Apoptotic Cell Clearance to Treat Autoimmune Arthritis

    OpenAIRE

    Philippe Saas; Francis Bonnefoy; Eric Toussirot; Sylvain Perruche

    2017-01-01

    Early-stage apoptotic cells possess immunomodulatory properties. Proper apoptotic cell clearance during homeostasis has been shown to limit subsequent immune responses. Based on these observations, early-stage apoptotic cell infusion has been used to prevent unwanted inflammatory responses in different experimental models of autoimmune diseases or transplantation. Moreover, this approach has been shown to be feasible without any toxicity in patients undergoing allogeneic hematopoietic cell tr...

  15. Ship manoeuvring at very small and negative under keel clearance

    OpenAIRE

    Vantorre, M.; Delefortrie, G.; Laforce, E.; De Vlieger, H.; Claeys, S.

    2004-01-01

    A selection of results of systematic captive manoeuvring test series with a container carrier model above a solid bottom as well as above and in simulated mud layers is presented. The effect of under keel clearance - with emphasis on very small and even negative values referred to the water-mud interface - on linear manoeuvring coefficients and dynamic stability parameters is discussed. Controllability and manoeuvrability appear to be affected particularly by the influence of water depth on t...

  16. The kidneys play a central role in the clearance of rhGH in rats

    DEFF Research Database (Denmark)

    Vestergaard, Bill; Thygesen, Peter; Kreilgaard, Mads

    2016-01-01

    The kidneys are thought to play an important role in the clearance of recombinant human growth hormone (rhGH), but the relative importance is not clear. Obtaining knowledge of clearance pathway is an important prerequisite for the development of new long acting growth hormone analogues targeted...... at treatment of patients with growth hormone disorders. The purpose of this study was to investigate the relative importance of the kidneys in the clearance of rhGH. The study employed a newly validated nephrectomy rat model and a population based pharmacokinetic approach to assess renal clearance of rh...... that renal clearance plays a pivotal role in the elimination of rhGH in rats....

  17. Reducing prescribing errors through creatinine clearance alert redesign.

    Science.gov (United States)

    Melton, Brittany L; Zillich, Alan J; Russell, Scott A; Weiner, Michael; McManus, M Sue; Spina, Jeffrey R; Russ, Alissa L

    2015-10-01

    Literature has shown that computerized creatinine clearance alerts reduce errors during prescribing, and applying human factors principles may further reduce errors. Our objective was to apply human factors principles to creatinine clearance alert design and assess whether the redesigned alerts increase usability and reduce prescribing errors compared with the original alerts. Twenty Veterans Affairs (VA) outpatient providers (14 physicians, 2 nurse practitioners, and 4 clinical pharmacists) completed 2 usability sessions in a counterbalanced study to evaluate original and redesigned alerts. Each session consisted of fictional patient scenarios with 3 medications that warranted prescribing changes because of renal impairment, each associated with creatinine clearance alerts. Quantitative and qualitative data were collected to assess alert usability and the occurrence of prescribing errors. There were 43% fewer prescribing errors with the redesigned alerts compared with the original alerts (P = .001). Compared with the original alerts, redesigned alerts significantly reduced prescribing errors for allopurinol and ibuprofen (85% vs 40% and 65% vs 25%, P = .012 and P = .008, respectively), but not for spironolactone (85% vs 65%). Nine providers (45%) voiced confusion about why the alert was appearing when they encountered the original alert design. When laboratory links were presented on the redesigned alert, laboratory information was accessed 3.5 times more frequently. Although prescribing errors were high with both alert designs, the redesigned alerts significantly improved prescribing outcomes. This investigation provides some of the first evidence on how alerts may be designed to support safer prescribing for patients with renal impairment. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. The use of manual hyperinflation in airway clearance.

    Science.gov (United States)

    Denehy, L

    1999-10-01

    Manual lung hyperinflation (MH) is one of a number of techniques which are employed by the physiotherapist in the critical care setting. The technique was first described with physiotherapy 30 yrs ago and commonly involves a slow, deep inspiration, inspiratory pause and fast unobstructed expiration. The use of MH varies between and within countries. It is commonly employed by physiotherapists to assist in the removal of secretions and re-expand areas of atelectasis. Despite the popularity of the technique, research examining its efficacy is conflicting, especially the effect of MH on cardiovascular parameters. Recent studies examining mucociliary transport in intubated and ventilated patients have shown impaired clearance of secretions, but research evaluating the role of MH specifically in airway clearance is scant. The use of the additional physiotherapy techniques, gravity assisted drainage and chest wall vibrations, may enhance the efficacy of MH in promoting airway clearance, but further research is necessary. Controversy exists regarding the safety and effectiveness of application of manual lung hyperinflation in intubated patients. Clearly, more randomized controlled studies are necessary in order to provide a sound scientific rationale for the application of manual lung hyperinflation in the treatment of critically ill patients.

  19. Effects of rapid maxillary expansion on nasal mucociliary clearance.

    Science.gov (United States)

    Babacan, Hasan; Doruk, Cenk; Uysal, Ismail Onder; Yuce, Salim

    2016-03-01

    To evaluate the changes in nasal mucociliary clearance in orthodontic patients after rapid maxillary expansion (RME) therapy. Forty-two children (25 boys and 17 girls) participated in this study. The RME group consisted of 21 patients (mean age, 13.8 years), who had undergone RME at the initiation of orthodontic treatment. The control group consisted of 21 subjects (mean age, 13.6 years), who were attending the department of orthodontics for active orthodontic treatment. The nasal mucociliary clearance was assessed by the saccharin test. Saccharin transit times (STTs) were measured for each treated subject before expansion (T1), after RME (T2), and after a 3-month retention period (T3). Records were obtained at the same time intervals for each group. The STT decreased significantly in the RME group after expansion and retention (P expansion and retention (P maxillary narrowness and without any history of nasal or systemic disease were within normal limits. However, RME increased the mucociliary clearance in patients who had maxillary narrowness, having positive effects on nasal physiology and increasing nasal cavity volume.

  20. Nonpharmacologic airway clearance techniques in hospitalized patients: a systematic review.

    Science.gov (United States)

    Andrews, Jeff; Sathe, Nila A; Krishnaswami, Shanthi; McPheeters, Melissa L

    2013-12-01

    Nonpharmacologic airway clearance techniques are used to reduce the sequelae of obstructive secretions. We systematically reviewed comparative studies of nonpharmacologic interventions that health professionals can employ to achieve mucus clearance in hospitalized or postoperative patients without cystic fibrosis, over the age of 12 months. We searched MEDLINE and other databases from 1990 to 2012 to identify relevant literature. Two reviewers independently assessed each study against predetermined inclusion/exclusion criteria. Two reviewers also independently extracted data regarding subject and intervention characteristics and outcomes, and assigned overall quality ratings. The 32 studies meeting the review criteria included 24 randomized controlled trials, 7 crossover randomized controlled trials, and one prospective cohort study. Studies were typically small and together included a total of 2,453 subjects (mean 76/study). Studies generally examined chest physical therapy/physiotherapy modalities in postoperative or critically ill subjects or those with COPD. Interventions, comparators, and populations varied considerably across studies, hampering our ability to draw firm conclusions. Interventions, including conventional chest physical therapy/physiotherapy, intrapulmonary percussive ventilation, and positive expiratory pressure, typically provided small benefits in pulmonary function, gas exchange, oxygenation, and need for/duration of ventilation, among other outcomes, but differences between groups were generally small and not significant. Harms of the techniques were not consistently reported, though airway clearance techniques were generally considered safe in studies that did comment on adverse effects. Further research with clearly characterized populations and interventions is needed to understand the potential benefits and harms of these techniques.

  1. Dysregulation of Nutrient Sensing and CLEARance in Presenilin Deficiency

    Directory of Open Access Journals (Sweden)

    Kavya Reddy

    2016-03-01

    Full Text Available Attenuated auto-lysosomal system has been associated with Alzheimer disease (AD, yet all underlying molecular mechanisms leading to this impairment are unknown. We show that the amino acid sensing of mechanistic target of rapamycin complex 1 (mTORC1 is dysregulated in cells deficient in presenilin, a protein associated with AD. In these cells, mTORC1 is constitutively tethered to lysosomal membranes, unresponsive to starvation, and inhibitory to TFEB-mediated clearance due to a reduction in Sestrin2 expression. Normalization of Sestrin2 levels through overexpression or elevation of nuclear calcium rescued mTORC1 tethering and initiated clearance. While CLEAR network attenuation in vivo results in buildup of amyloid, phospho-Tau, and neurodegeneration, presenilin-knockout fibroblasts and iPSC-derived AD human neurons fail to effectively initiate autophagy. These results propose an altered mechanism for nutrient sensing in presenilin deficiency and underline an importance of clearance pathways in the onset of AD.

  2. RENAL CLEARANCE AND URINARY EXCRETION OF CIPROFLOXACIN IN GOATS

    Directory of Open Access Journals (Sweden)

    Z. IQBAL, I. JAVED, B. ASLAM, F. MUHAMMAD AND I. U. JAN

    2007-10-01

    Full Text Available The renal clearance and urinary excretion of ciprofloxacin were investigated in eight healthy female goats. In each animal, ciprofloxacin was administered intramuscularly at the rate of 5 mg/kg body weight. Following drug administration, blood and urine samples were collected at different time intervals and analyzed for ciprofloxacin and creatinine. High performance liquid chromatography (HPLC was used to determine the drug concentration in the plasma and urine. The value of diuresis after single administration of ciprofloxacin was 0.073 ± 0.014 ml/min/kg. Mean (± SE values for renal clearance of creatinine and ciprofloxacin were 1.870 ± 0.385 and 0.982 ± 0.166 ml/min/kg, respectively. The ratio between the renal clearance of ciprofloxacin and that of creatinine remained less than one, which was indicative of back diffusion. The mean (± SE value for the cumulative percent of ciprofloxacin dose excreted at 10 hours following its intramuscular administration was 13.03 ± 2.07. Based on these results, it was evident that besides glomerular filtration, renal handling of drug involved back diffusion also. It was concluded that in local goats glomerular filtration rate (GFR was lower than that reported for their foreign counterparts.

  3. In silico prediction of total human plasma clearance.

    Science.gov (United States)

    Berellini, Giuliano; Waters, Nigel J; Lombardo, Franco

    2012-08-27

    The prediction of the total human plasma clearance of novel chemical entities continues to be of paramount importance in drug design and optimization, because it impacts both dose size and dose regimen. Although many in vivo and in vitro methods have been proposed, a well-constructed, well-validated, and less resource-intensive computational tool would still be very useful in an iterative compound design cycle. A new completely in silico linear PLS (partial least-squares) model to predict the human plasma clearance was built on the basis of a large data set of 754 compounds using physicochemical descriptors and structural fragments, the latter able to better represent biotransformation processes. The model has been validated using the "ELASTICO" approach (Enhanced Leave Analog-Structural, Therapeutic, Ionization Class Out) based on ten therapeutic/structural analog classes. The model yields a geometric mean fold error (GMFE) of 2.1 and a percentage of compounds predicted within 2- and 3-fold error of 59% and 80%, respectively, showing an improved performance when compared with previous published works in predicting clearance of neutral compounds, and a very good performance with ionized molecules at pH 7.5, able to compare favorably with fairly accurate in vivo methods.

  4. Capreomycin kinetics in renal impairment and clearance by hemodialysis.

    Science.gov (United States)

    Lehmann, C R; Garrett, L E; Winn, R E; Springberg, P D; Vicks, S; Porter, D K; Pierson, W P; Wolny, J D; Brier, G L; Black, H R

    1988-11-01

    The single-dose kinetics of capreomycin are described for 12 renal patients and seven healthy control subjects. Creatinine clearances (CrCl) ranged from zero to 121 ml/min. After single-dose intravenous infusions, mean +/- SD capreomycin clearance values (L/kg/h x 10(-2)) were 0.558 +/- 0.160 for the dialysis group (n = 4, CrCl = 1.4 +/- 1.9), 1.77 +/- 0.45 for the moderate renal group (n = 3, CrCl = 25 +/- 5), 2.82 +/- 1.52 for the mild renal group (n = 4, CrCl = 46 +/- 5), and 5.73 +/- 1.54 for the normal renal group (n = 7, CrCl = 109 +/- 11); p less than 0.01, using analysis of variance. The correlation between capreomycin clearance and CrCl was r = 0.90. Hemodialysis cleared clinically significant amounts of capreomycin. These data imply that capreomycin maintenance doses need to be reduced for renal patients.

  5. Modeling the Potential for Vaccination to Diminish the Burden of Invasive Non-typhoidal Salmonella Disease in Young Children in Mali, West Africa.

    Directory of Open Access Journals (Sweden)

    Kristin Bornstein

    2017-02-01

    Full Text Available In sub-Saharan Africa, systematic surveillance of young children with suspected invasive bacterial disease (e.g., septicemia, meningitis has revealed non-typhoidal Salmonella (NTS to be a major pathogen exhibiting high case fatality (~20%. Where infant vaccination against Haemophilus influenzae type b (Hib and Streptococcus pneumoniae has been introduced to prevent invasive disease caused by these pathogens, as in Bamako, Mali, their burden has decreased markedly. In parallel, NTS has become the predominant invasive bacterial pathogen in children aged <5 years. While NTS is believed to be acquired orally via contaminated food/water, epidemiologic studies have failed to identify the reservoir of infection or vehicles of transmission. This has precluded targeting food chain interventions to diminish disease transmission but conversely has fostered the development of vaccines to prevent invasive NTS (iNTS disease. We developed a mathematical model to estimate the potential impact of NTS vaccination programs in Bamako.A Markov chain transmission model was developed utilizing age-specific Bamako demographic data and hospital surveillance data for iNTS disease in children aged <5 years and assuming vaccine coverage and efficacy similar to the existing, successfully implemented, Hib vaccine. Annual iNTS hospitalizations and deaths in children <5 years, with and without a Salmonella Enteritidis/Salmonella Typhimurium vaccine, were the model's outcomes of interest. Per the model, high coverage/high efficacy iNTS vaccination programs would drastically diminish iNTS disease except among infants age <8 weeks.The public health impact of NTS vaccination shifts as disease burden, vaccine coverage, and serovar distribution vary. Our model shows that implementing an iNTS vaccine through an analogous strategy to the Hib vaccination program in Bamako would markedly reduce cases and deaths due to iNTS among the pediatric population. The model can be adjusted for

  6. Bacterial hemorrhagic enterocolitis.

    Science.gov (United States)

    Ina, Kenji; Kusugami, Kazuo; Ohta, Michio

    2003-01-01

    Bacterial diarrhea can be classified into two clinical entities, noninflammatory diarrhea and inflammatory diarrhea syndromes. The latter type of diarrhea is characterized by bloody and puruloid mucus stool, and is often accompanied by fever, tenesmus, and severe abdominal pain. Pathogenic bacteria causing the inflammatory diarrhea syndrome include Salmonella, Vibrio, Shigella, enteroinvasive and enterohemorrhagic Escherichia coli, Campylobacter, Yersinia, Chlamydia, and Clostridium difficile. The pathologic changes in the inflammatory diarrhea syndrome range from a superficial exudative enterocolitis to a transmural enterocolitis with overt ulceration. This syndrome is also designated as bacterial hemorrhagic enterocolitis because of its usual manifestation by bloody diarrhea. The diagnostic approach needs information on the patient's age, travel history, epidemiological associations, sexual practice, and medical history, including usage of antibiotics. Bacterial information can be obtained by microscopic study, culture, and the identification of specific bacterial toxins. Flexible colonoscopy with biopsy is useful for the differentiation of bacterial hemorrhagic enterocolitis from idiopathic ulcerative colitis and ischemic colitis. Physicians should be familiar with the diagnostic modalities used to detect the specific pathogens causing hemorrhagic bacterial enterocolitis; namely, bacterial culture, serology, histology, and nucleic acid technologies.

  7. Numerical investigation of tip clearance effects on the performance of ducted propeller

    Directory of Open Access Journals (Sweden)

    Ding Yongle

    2015-09-01

    Full Text Available Tip clearance loss is a limitation of the improvement of turbomachine performance. Previous studies show the Tip clearance loss is generated by the leakage flow through the tip clearance, and is roughly linearly proportional to the gap size. This study investigates the tip clearance effects on the performance of ducted propeller. The investigation was carried out by solving the Navier-Stokes equations with the commercial Computational Fluid Dynamic (CFD code CFX14.5. These simulations were carried out to determine the underlying mechanisms of the tip clearance effects. The calculations were performed at three different chosen advance ratios. Simulation results showed that the tip loss slope was not linearly at high advance due to the reversed pressure at the leading edge. Three type of vortical structures were observed in the tip clearance at different clearance size.

  8. Chronic filarial infection provides protection against bacterial sepsis by functionally reprogramming macrophages.

    Directory of Open Access Journals (Sweden)

    Fabian Gondorf

    2015-01-01

    Full Text Available Helminths immunomodulate their hosts and induce a regulatory, anti-inflammatory milieu that prevents allergies and autoimmune diseases. Helminth immunomodulation may benefit sepsis outcome by preventing exacerbated inflammation and severe pathology, but the influence on bacterial clearance remains unclear. To address this, mice were chronically infected with the filarial nematode Litomosoides sigmodontis (L.s. and the outcome of acute systemic inflammation caused by i.p. Escherichia coli injection was determined. L.s. infection significantly improved E. coli-induced hypothermia, bacterial clearance and sepsis survival and correlated with reduced concentrations of associated pro-inflammatory cytokines/chemokines and a less pronounced pro-inflammatory macrophage gene expression profile. Improved sepsis outcome in L.s.-infected animals was mediated by macrophages, but independent of the alternatively activated macrophage subset. Endosymbiotic Wolbachia bacteria that are present in most human pathogenic filariae, as well as L.s., signal via TLR2 and modulate macrophage function. Here, gene expression profiles of peritoneal macrophages from L.s.-infected mice revealed a downregulation of genes involved in TLR signaling, and pulsing of macrophages in vitro with L.s. extract reduced LPS-triggered activation. Subsequent transfer improved sepsis outcome in naïve mice in a Wolbachia- and TLR2-dependent manner. In vivo, phagocytosis was increased in macrophages from L.s.-infected wild type, but not TLR2-deficient animals. In association, L.s. infection neither improved bacterial clearance in TLR2-deficient animals nor ameliorated E. coli-induced hypothermia and sepsis survival. These results indicate that chronic L.s. infection has a dual beneficial effect on bacterial sepsis, reducing pro-inflammatory immune responses and improving bacterial control. Thus, helminths and their antigens may not only improve the outcome of autoimmune and allergic diseases

  9. Interfering with bacterial gossip

    DEFF Research Database (Denmark)

    Bjarnsholt, Thomas; Tolker-Nielsen, Tim; Givskov, Michael

    2011-01-01

    defense. Antibiotics exhibit a rather limited effect on biofilms. Furthermore, antibiotics have an ‘inherent obsolescence’ because they select for development of resistance. Bacterial infections with origin in bacterial biofilms have become a serious threat in developed countries. Pseudomonas aeruginosa...... that appropriately target bacteria in their relevant habitat with the aim of mitigating their destructive impact on patients. In this review we describe molecular mechanisms involved in “bacterial gossip” (more scientifically referred to as quorum sensing (QS) and c-di-GMP signaling), virulence, biofilm formation......, resistance and QS inhibition as future antimicrobial targets, in particular those that would work to minimize selection pressures for the development of resistant bacteria....

  10. Aortic bacterial endarteritis.

    Science.gov (United States)

    Ma Maroto, M J; Gorodezky, M; Contreras, R; C'ardenas, M

    1975-01-01

    Micotic aneurisms are very rare. They are produced as a consequence of a bacterial infection of the endartery. They are divided into "primary", or those of an unknown septic focus, and "secondary" to bacterial endocarditis, to intravascular in infection or to infection located in a neighboring region. Two cases of the National Institute of Cardiology of Mexico are presented, with "primary" micotic aneurysm, which is the least frequent. One of them was because of bacterial endarteritis located in the thoracic aorta, an extremely rate entity. Due to the frequent rupture of these aneurysm with a very high mortality, emphasis is placed on the convenience of rapid surgical treatment of patients diagnosed.

  11. Harnessing Bacterial Signals for Suppression of Biofilm Formation in the Nosocomial Fungal Pathogen Aspergillus fumigatus

    OpenAIRE

    Reen, F. Jerry; Phelan, John P.; Woods, David F.; Shanahan, Rachel; Cano, Rafael; Clarke, Sarah; McGlacken, Gerard P.; O’Gara, Fergal

    2016-01-01

    Faced with the continued emergence of antibiotic resistance to all known classes of antibiotics, a paradigm shift in approaches toward antifungal therapeutics is required. Well characterized in a broad spectrum of bacterial and fungal pathogens, biofilms are a key factor in limiting the effectiveness of conventional antibiotics. Therefore, therapeutics such as small molecules that prevent or disrupt biofilm formation would render pathogens susceptible to clearance by existing drugs. This is t...

  12. Diminished brain resilience syndrome: A modern day neurological pathology of increased susceptibility to mild brain trauma, concussion, and downstream neurodegeneration

    National Research Council Canada - National Science Library

    Wendy Morley; Stephanie Seneff

    2014-01-01

    .... Diminished brain resilience syndrome is a term coined by the lead author to describe a particular physiological state of nutrient functional deficiency and disrupted homeostatic mechanisms leading...

  13. Bacterial intermediate filaments

    DEFF Research Database (Denmark)

    Charbon, Godefroid; Cabeen, M.; Jacobs-Wagner, C.

    2009-01-01

    Crescentin, which is the founding member of a rapidly growing family of bacterial cytoskeletal proteins, was previously proposed to resemble eukaryotic intermediate filament (IF) proteins based on structural prediction and in vitro polymerization properties. Here, we demonstrate that crescentin...

  14. Bacterial Skin Infections

    Science.gov (United States)

    ... Summer Camp Tips for Kids With Asthma, Allergies Antioxidants: The Good Health Helpers As Stroke 'Liquefies' Brain ... Cancer Additional Content Medical News Overview of Bacterial Skin Infections By A. Damian Dhar, MD, JD, Private ...

  15. When bacterial tracheitis complicates

    Directory of Open Access Journals (Sweden)

    Joana Teixeira

    2015-12-01

    Full Text Available Introduction: Viral croup is the most common cause of stridor in children seen at emergency room. In the absence of response to treatment with corticosteroids and nebulized adrenaline, bacterial tracheitis should be considered. Case Report: A six year-old child, was admitted in emergency room with stridor, respiratory distress and fever, with partial response to therapy with nebulized epinephrine. Ceftriaxone was prescribed for suspected bacterial laryngotracheobronchitis. Despite therapy, developed cervical cellulitis with progression to retropharyngeal abscess and mediastinitis. Good outcome after therapy with ceftriaxone, clindamycin and vancomycin. Discussion/Conclusion: The authors describe an original case of a bacterial tracheitis complicated with retropharyngeal abcess and mediastinitis, emphasizing that bacterial tracheitis is potentially life threatening, requiring a high index of suspicion for early diagnosis.

  16. Bacterial Wound Culture

    Science.gov (United States)

    ... and services. Advertising & Sponsorship: Policy | Opportunities Bacterial Wound Culture Share this page: Was this page helpful? Also known as: Aerobic Wound Culture; Anaerobic Wound Culture Formal name: Culture, wound Related ...

  17. Diminishing returns in social evolution: the not-so-tragic commons.

    Science.gov (United States)

    Foster, K R

    2004-09-01

    A challenge for evolutionary theory is to understand how cooperation can occur in the presence of competition and cheating, a problem known as the tragedy of commons. Here I examine how varying the fitness returns from reproductive competition or cooperation affects the negative impact of competition on a social group. Varying linear returns does not affect the impact of competition. However, diminishing returns, where additional investments in either competition or cooperation give smaller and smaller rewards, reduce the effects of competition on the group. I show that diminishing returns are common in many systems, including social vertebrates, microbes, social insects and mutualisms among species. This suggests that the tragedy of the commons is not so tragic and that the disruptive effects of competition upon social life will often be minor.

  18. Diminishing returns and tradeoffs constrain the laboratory optimization of an enzyme.

    Science.gov (United States)

    Tokuriki, Nobuhiko; Jackson, Colin J; Afriat-Jurnou, Livnat; Wyganowski, Kirsten T; Tang, Renmei; Tawfik, Dan S

    2012-01-01

    Optimization processes, such as evolution, are constrained by diminishing returns-the closer the optimum, the smaller the benefit per mutation, and by tradeoffs-improvement of one property at the cost of others. However, the magnitude and molecular basis of these parameters, and their effect on evolutionary transitions, remain unknown. Here we pursue a complete functional transition of an enzyme with a >10(9)-fold change in the enzyme's selectivity using laboratory evolution. We observed strong diminishing returns, with the initial mutations conferring >25-fold higher improvements than later ones, and asymmetric tradeoffs whereby the gain/loss ratio of the new/old activity decreased 400-fold from the beginning of the trajectory to its end. We describe the molecular basis for these phenomena and suggest they have an important role in shaping natural proteins. These findings also suggest that the catalytic efficiency and specificity of many natural enzymes may be far from their optimum.

  19. Repeated exposure to media violence is associated with diminished response in an inhibitory frontolimbic network.

    Science.gov (United States)

    Kelly, Christopher R; Grinband, Jack; Hirsch, Joy

    2007-12-05

    Media depictions of violence, although often claimed to induce viewer aggression, have not been shown to affect the cortical networks that regulate behavior. Using functional magnetic resonance imaging (fMRI), we found that repeated exposure to violent media, but not to other equally arousing media, led to both diminished response in right lateral orbitofrontal cortex (right ltOFC) and a decrease in right ltOFC-amygdala interaction. Reduced function in this network has been previously associated with decreased control over a variety of behaviors, including reactive aggression. Indeed, we found reduced right ltOFC responses to be characteristic of those subjects that reported greater tendencies toward reactive aggression. Furthermore, the violence-induced reduction in right ltOFC response coincided with increased throughput to behavior planning regions. These novel findings establish that even short-term exposure to violent media can result in diminished responsiveness of a network associated with behaviors such as reactive aggression.

  20. Bacterial proteases and virulence

    DEFF Research Database (Denmark)

    Frees, Dorte; Brøndsted, Lone; Ingmer, Hanne

    2013-01-01

    Bacterial pathogens rely on proteolysis for variety of purposes during the infection process. In the cytosol, the main proteolytic players are the conserved Clp and Lon proteases that directly contribute to virulence through the timely degradation of virulence regulators and indirectly by providing....... These extracellular proteases are activated in complex cascades involving auto-processing and proteolytic maturation. Thus, proteolysis has been adopted by bacterial pathogens at multiple levels to ensure the success of the pathogen in contact with the human host....

  1. Diminished adrenal sensitivity to endogenous and exogenous adrenocorticotropic hormone in critical illness: a prospective cohort study

    OpenAIRE

    de Jong, Margriet FC; Molenaar, Nienke; Beishuizen, Albertus; Groeneveld, AB Johan

    2015-01-01

    textabstractIntroduction: Adrenal dysfunction may represent critical illness-related corticosteroid insufficiency (CIRCI), as evidenced by a diminished cortisol response to exogenous adrenocorticotropic hormone (ACTH), but this concept and its clinical significance remain highly controversial. We studied the adrenal response to exogenous ACTH as a function of the endogenous cortisol-to-ACTH ratio, a measure of adrenal sensitivity, and of clinical variables, during critical illness and recover...

  2. Repeated Exposure to Media Violence Is Associated with Diminished Response in an Inhibitory Frontolimbic Network

    OpenAIRE

    Kelly, Christopher R.; Jack Grinband; Joy Hirsch

    2007-01-01

    BACKGROUND: Media depictions of violence, although often claimed to induce viewer aggression, have not been shown to affect the cortical networks that regulate behavior. METHODOLOGY/PRINCIPAL FINDINGS: Using functional magnetic resonance imaging (fMRI), we found that repeated exposure to violent media, but not to other equally arousing media, led to both diminished response in right lateral orbitofrontal cortex (right ltOFC) and a decrease in right ltOFC-amygdala interaction. Reduced function...

  3. Diminished temporal coding with sensorineural hearing loss emerges in background noise.

    Science.gov (United States)

    Henry, Kenneth S; Heinz, Michael G

    2012-10-01

    Behavioral studies in humans suggest that sensorineural hearing loss (SNHL) decreases sensitivity to the temporal structure of sound, but neurophysiological studies in mammals provide little evidence for diminished temporal coding. We found that SNHL in chinchillas degraded peripheral temporal coding in background noise substantially more than in quiet. These results resolve discrepancies between previous studies and help to explain why perceptual difficulties in hearing-impaired listeners often emerge in noisy situations.

  4. Diminishing seasonality of self-harm: Temporal trends in Hong Kong SAR.

    Science.gov (United States)

    Kwok, Chi-Leung; Yip, Paul S F

    2017-01-01

    The study of temporal variation in self-harm is important to understanding the underlying mechanisms of its occurrence. There are fewer studies on temporal variation in self-harm than in suicide. The aim of this study was to examine the seasonality of self-harm in Hong Kong and to test the hypothesis of diminishing seasonality. We used secondary data from medical records of self-harm obtained from all the public hospitals in Hong Kong under the management of the Hospital Authority. We identified 59,473 distinct episodes involving 36,411 patients. From these, monthly statistics of self-harm from January 2002 to December 2011 were calculated. Harmonic analysis was conducted to examine the presence and magnitude of seasonality. A bi-seasonal pattern alongside a stronger one-cycle pattern from 2002 to 2006 was identified. During the period 1997-2001, this contracted to a one-cycle pattern with a peak in summer (May to July) and a nadir in winter (December). The magnitude of seasonality diminished greatly, as shown by harmonic analysis. The extent of diminishing seasonality was larger among women and people under 55 years old. The study covered only self-harm patients who had visited a hospital. Cases which required no medical attention and those where the patient consulted private doctors could not be included, indicating bias towards more severe cases of injury and poisoning. This study provides some evidence of diminishing and even vanishing seasonality of self-harm in Hong Kong, a phenomenon mainly found in younger individuals. It could be related to the increasing use of social media to connect people, especially the younger generation. The impact of seasonal events and activities, as in the past, has become less significant in the social media era. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. [Diagnosis of bacterial vaginosis].

    Science.gov (United States)

    Djukić, Slobodanka; Ćirković, Ivana; Arsić, Biljana; Garalejić, Eliana

    2013-01-01

    Bacterial vaginosis is a common, complex clinical syndrome characterized by alterations in the normal vaginal flora. When symptomatic, it is associated with a malodorous vaginal discharge and on occasion vaginal burning or itching. Under normal conditions, lactobacilli constitute 95% of the bacteria in the vagina. Bacterial vaginosis is associated with severe reduction or absence of the normal H2O2-producing lactobacilli and overgrowth of anaerobic bacteria and Gardnerella vaginalis, Atopobium vaginae, Mycoplasma hominis and Mobiluncus species. Most types of infectious disease are diagnosed by culture, by isolating an antigen or RNA/DNA from the microbe, or by serodiagnosis to determine the presence of antibodies to the microbe. Therefore, demonstration of the presence of an infectious agent is often a necessary criterion for the diagnosis of the disease. This is not the case for bacterial vaginosis, since the ultimate cause of the disease is not yet known. There are a variety of methods for the diagnosis of bacterial vaginosis but no method can at present be regarded as the best. Diagnosing bacterial vaginosis has long been based on the clinical criteria of Amsel, whereby three of four defined criteria must be satisfied. Nugent's scoring system has been further developed and includes validation of the categories of observable bacteria structures. Up-to-date molecular tests are introduced, and better understanding of vaginal microbiome, a clear definition for bacterial vaginosis, and short-term and long-term fluctuations in vaginal microflora will help to better define molecular tests within the broader clinical context.

  6. Modeling the Potential for Vaccination to Diminish the Burden of Invasive Non-typhoidal Salmonella Disease in Young Children in Mali, West Africa.

    Science.gov (United States)

    Bornstein, Kristin; Hungerford, Laura; Hartley, David; Sorkin, John D; Tapia, Milagritos D; Sow, Samba O; Onwuchekwa, Uma; Simon, Raphael; Tennant, Sharon M; Levine, Myron M

    2017-02-01

    In sub-Saharan Africa, systematic surveillance of young children with suspected invasive bacterial disease (e.g., septicemia, meningitis) has revealed non-typhoidal Salmonella (NTS) to be a major pathogen exhibiting high case fatality (~20%). Where infant vaccination against Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae has been introduced to prevent invasive disease caused by these pathogens, as in Bamako, Mali, their burden has decreased markedly. In parallel, NTS has become the predominant invasive bacterial pathogen in children aged vaccines to prevent invasive NTS (iNTS) disease. We developed a mathematical model to estimate the potential impact of NTS vaccination programs in Bamako. A Markov chain transmission model was developed utilizing age-specific Bamako demographic data and hospital surveillance data for iNTS disease in children aged vaccine coverage and efficacy similar to the existing, successfully implemented, Hib vaccine. Annual iNTS hospitalizations and deaths in children vaccine, were the model's outcomes of interest. Per the model, high coverage/high efficacy iNTS vaccination programs would drastically diminish iNTS disease except among infants age vaccination shifts as disease burden, vaccine coverage, and serovar distribution vary. Our model shows that implementing an iNTS vaccine through an analogous strategy to the Hib vaccination program in Bamako would markedly reduce cases and deaths due to iNTS among the pediatric population. The model can be adjusted for use elsewhere in Africa where NTS epidemiologic patterns, serovar prevalence, and immunization schedules differ from Bamako.

  7. Apical clearance rigid contact lenses induce corneal steepening.

    Science.gov (United States)

    Swarbrick, Helen A; Hiew, Ross; Kee, Ai Vy; Peterson, Sophia; Tahhan, Nina

    2004-06-01

    Anecdotal reports suggest that steeply fitted rigid contact lenses can induce corneal steepening and myopic shifts in refraction. This study investigated changes in corneal topography, corneal thickness, and refraction after short-term wear of apical clearance lenses. : Ten young adults participated in the study in which apical clearance lenses (Conoid, Hydron Pty. Ltd., Frenchs Forest, NSW, Australia), fitted approximately 0.3 mm steeper than the flattest keratometric reading, were worn for 4 h. A polymethyl methacrylate (PMMA) lens was worn in one eye, and a Boston XO lens (Bausch & Lomb, Rochester, NY) was worn in the other. Lenses were nonfenestrated in the first trial, and a single midperipheral fenestration was incorporated for a second trial. Corneal topography was monitored using the EyeSys topographic analysis system (EyeSys Vision, Inc., Houston, TX); central corneal thickness was quantified using ultrasonic pachometry; and refraction and anterior ocular response were also monitored. Significant central corneal edema (8.2 +/- 2.2%) was demonstrated in the PMMA lens-wearing eye only. Fenestration did not reduce the edema response. We found significant corneal steepening over a 5- to 6-mm central zone, which was more pronounced in the PMMA lens-wearing eye and was modified by lens fenestration. The curvature changes altered central corneal shape from prolate (Q = -0.06 +/- 0.10) to oblate (Q = -0.26 +/- 0.31). A slight myopic shift in refraction (-0.38 +/- 0.60 D) was found with the PMMA lenses only. : Apical clearance lenses induce corneal steepening after short-term wear. Although corneal molding is implicated as the primary factor driving the shape change, corneal edema and postlens tear film pressures can modify this response.

  8. Hyaluronate effect on bacterial biofilm in ENT district infections: a review.

    Science.gov (United States)

    Marcuzzo, Alberto Vito; Tofanelli, Margherita; Boscolo Nata, Francesca; Gatto, Annalisa; Tirelli, Giancarlo

    2017-09-01

    Bacterial resistance is a growing phenomenon which led the scientific community to search for new therapeutic targets, such as biofilm. A bacterial biofilm is a surface-associated agglomerate of microorganisms embedded in a self-produced extracellular polymeric matrix made of polysaccharides, nucleic acids, and proteins. Scientific literature offers several reports on a biofilm's role in infections regarding various body districts. The presence of a bacterial biofilm is responsible for poor efficacy of antibiotic therapies along with bacterial infections in ear, nose, and throat (ENT) districts such as the oral cavity, ear, nasal cavities, and nasal sinuses. In particular, bacterial biofilms are associated with recalcitrant and symptomatically more severe forms of chronic rhinosinusitis. As of today, there are no therapeutic options for the eradication of bacterial biofilm in ENT districts. Hyaluronic acid is a glycosaminoglycan composed of glucuronic acid and N-acetylglucosamine disaccharide units. Its efficacy in treating rhinosinusitis, whether or not associated with polyposis, is well documented, as well as results from its effects on mucociliary clearance, free radical production and mucosal repair. This review's aim is to evaluate the role of bacterial biofilms and the action exerted on it by hyaluronic acid in ENT pathology, with particular attention to the rhinosinusal district. In conclusion, this paper underlines how the efficacy of hyaluronate as an anti-bacterial biofilm agent is well demonstrated by in vitro studies; it is, however, only preliminarily demonstrated by clinical studies. © 2017 APMIS. Published by John Wiley & Sons Ltd.

  9. Antioxidant supplementation enhances bacterial peritonitis in mice by inhibiting phagocytosis.

    Science.gov (United States)

    Goswami, Manish; Sharma, Deepak; Khan, Nazir M; Checker, Rahul; Sandur, Santosh Kumar; Jawali, Narendra

    2014-03-01

    Antioxidants are known to exhibit numerous health benefits including anti-ageing, anti-apoptotic and immuno-stimulatory effects. However, we present the data showing counterproductive effects of therapeutically relevant antioxidants on bacterial clearance by the immune system in a murine peritonitic model. The antioxidants ascorbic acid, glutathione and N-acetylcysteine augmented morbidity and mortality in mice carrying Eshcerichia coli-induced acute bacterial peritonitis. Treatment of peritonitic mice with antioxidants significantly increased their bacterial load in the range of 0.3-2 logs. Antioxidant administration to peritonitic mice resulted in decreased numbers of macrophages, B-cells and dendritic cells at the primary site of infection and increased neutrophil infiltration. Serum TNF-α levels were also decreased in antioxidant-treated peritonitic mice. In vitro experiments showed that antioxidants reduced the phagocytic efficacy of peritoneal macrophages by ~60-75% and also decreased E. coli-induced oxidative burst in macrophages cells. Taken together, our data indicate that the antioxidants increased the severity of peritonitis by decreasing the phagocytic efficiency, oxidative burst, and TNF-α production, and increasing neutrophil infiltration. Based on these results, we propose that antioxidant supplementation during the course of bacterial infection is not recommended as it could be detrimental for the host. In addition, the present study underlines the importance of timing and context of antioxidant administration rather than indiscriminate usage to gain the best possible therapeutic advantage of these redox compounds.

  10. Dual clearance squeeze film damper for high load conditions

    Science.gov (United States)

    Fleming, D. P.

    1985-01-01

    Squeeze film dampers are widely used to control vibrations in aircraft turbine engines and other rotating machinery. However, if shaft unbalance rises appreciably above the design value (e.g., due to a turbine blade loss), a conventional squeeze film becomes overloaded, and is no longer effective in controlling vibration amplitudes and bearing forces. A damper concept characterized by two oil films is described. Under normal conditions, only one low-clearance film is active, allowing precise location of the shaft centerline. Under high unbalance conditions, both films are active, controlling shaft vibration in a near-optimum manner, and allowing continued operation until a safe shutdown can be made.

  11. A modification of the saccharine test for nasal mucociliary clearance.

    Science.gov (United States)

    Deitmer, T

    1986-12-01

    The saccharine test for assessing mucociliary clearance in the nose is the most practicable method. As the used sodium salt of saccharine is well water soluble, there is suspicion of interference with the very delicate two-layer-system of mucus or transport merely in the periciliary fluid, thus bringing about methodical errors. This is avoided by using inert tracers such as radioactively tagged ion exchange resin particles, which on the other hand must be observed with expensive equipment. A synthesis of both methods is demonstrated by using saccharine loaden ion exchange resin particles. The validity of the test is proven in vitro and in vivo.

  12. Exercise training and metformin, but not exercise training alone, decreases insulin production and increases insulin clearance in adults with prediabetes.

    Science.gov (United States)

    Viskochil, Richard; Malin, Steven K; Blankenship, Jennifer M; Braun, Barry

    2017-07-01

    medication, may diminish the benefits of exercise when used in combination. In this study, however, metformin combined with exercise training, but not exercise alone, lowered proinsulin concentrations and increased insulin clearance in adults with prediabetes. This may directly influence personalized prescriptions of lifestyle and/or pharmacology to reduce diabetes risk. Copyright © 2017 the American Physiological Society.

  13. Urticaria and bacterial infections.

    Science.gov (United States)

    Minciullo, Paola L; Cascio, Antonio; Barberi, Giuseppina; Gangemi, Sebastiano

    2014-01-01

    The association between urticaria and infectious diseases has been discussed for >100 years. However, a causal relationship with underlying or precipitating infection is difficult to establish. The purpose of this work was to perform a systematic analysis of the published cases of urticaria associated with bacterial infections. We give an umbrella breakdown of up-to-date systematic reviews and other important publications on the complex association of urticaria and bacterial infections. We did a Medline search, for English language articles published until January 2014, using the key words "urticaria" and "bacteria/bacterial disease"; a second analysis was performed in groups of bacteria and using each germ name as a key word. Many bacterial infections have been associated with urticaria manifestation, such as Helicobacter pylori, Streptococcus, Staphylococcus, Mycoplasma pneumonia, Salmonella, Brucella, Mycobacterium leprae, Borrelia, Chlamydia pneumonia, and Yersinia enterocolitica. In some cases the skin manifestations, described as urticaria, could be caused by the presence of the microorganism in the skin, or for the action of their toxins, or to the complement activation mediated by circulating immune complexes. Although only a weak association with urticaria of unclear pathogenesis exists, clinicians should consider these bacterial agents in the workup of the patients with urticaria. The eradication of the infection could, in fact, lead to the resolution of urticaria. Prospective studies and well-structured research are obviously needed to better clarify the real role of bacteria in the pathogenesis of urticaria and their relative prevalence.

  14. Bacterial Cell Mechanics.

    Science.gov (United States)

    Auer, George K; Weibel, Douglas B

    2017-07-25

    Cellular mechanical properties play an integral role in bacterial survival and adaptation. Historically, the bacterial cell wall and, in particular, the layer of polymeric material called the peptidoglycan were the elements to which cell mechanics could be primarily attributed. Disrupting the biochemical machinery that assembles the peptidoglycan (e.g., using the β-lactam family of antibiotics) alters the structure of this material, leads to mechanical defects, and results in cell lysis. Decades after the discovery of peptidoglycan-synthesizing enzymes, the mechanisms that underlie their positioning and regulation are still not entirely understood. In addition, recent evidence suggests a diverse group of other biochemical elements influence bacterial cell mechanics, may be regulated by new cellular mechanisms, and may be triggered in different environmental contexts to enable cell adaptation and survival. This review summarizes the contributions that different biomolecular components of the cell wall (e.g., lipopolysaccharides, wall and lipoteichoic acids, lipid bilayers, peptidoglycan, and proteins) make to Gram-negative and Gram-positive bacterial cell mechanics. We discuss the contribution of individual proteins and macromolecular complexes in cell mechanics and the tools that make it possible to quantitatively decipher the biochemical machinery that contributes to bacterial cell mechanics. Advances in this area may provide insight into new biology and influence the development of antibacterial chemotherapies.

  15. Antagonism of miR-328 increases the antimicrobial function of macrophages and neutrophils and rapid clearance of non-typeable Haemophilus influenzae (NTHi from infected lung.

    Directory of Open Access Journals (Sweden)

    Hock L Tay

    2015-04-01

    Full Text Available Pathogenic bacterial infections of the lung are life threatening and underpin chronic lung diseases. Current treatments are often ineffective potentially due to increasing antibiotic resistance and impairment of innate immunity by disease processes and steroid therapy. Manipulation miRNA directly regulating anti-microbial machinery of the innate immune system may boost host defence responses. Here we demonstrate that miR-328 is a key element of the host response to pulmonary infection with non-typeable haemophilus influenzae and pharmacological inhibition in mouse and human macrophages augments phagocytosis, the production of reactive oxygen species, and microbicidal activity. Moreover, inhibition of miR-328 in respiratory models of infection, steroid-induced immunosuppression, and smoke-induced emphysema enhances bacterial clearance. Thus, miRNA pathways can be targeted in the lung to enhance host defence against a clinically relevant microbial infection and offer a potential new anti-microbial approach for the treatment of respiratory diseases.

  16. Antagonism of miR-328 increases the antimicrobial function of macrophages and neutrophils and rapid clearance of non-typeable Haemophilus influenzae (NTHi) from infected lung.

    Science.gov (United States)

    Tay, Hock L; Kaiko, Gerard E; Plank, Maximilian; Li, JingJing; Maltby, Steven; Essilfie, Ama-Tawiah; Jarnicki, Andrew; Yang, Ming; Mattes, Joerg; Hansbro, Philip M; Foster, Paul S

    2015-04-01

    Pathogenic bacterial infections of the lung are life threatening and underpin chronic lung diseases. Current treatments are often ineffective potentially due to increasing antibiotic resistance and impairment of innate immunity by disease processes and steroid therapy. Manipulation miRNA directly regulating anti-microbial machinery of the innate immune system may boost host defence responses. Here we demonstrate that miR-328 is a key element of the host response to pulmonary infection with non-typeable haemophilus influenzae and pharmacological inhibition in mouse and human macrophages augments phagocytosis, the production of reactive oxygen species, and microbicidal activity. Moreover, inhibition of miR-328 in respiratory models of infection, steroid-induced immunosuppression, and smoke-induced emphysema enhances bacterial clearance. Thus, miRNA pathways can be targeted in the lung to enhance host defence against a clinically relevant microbial infection and offer a potential new anti-microbial approach for the treatment of respiratory diseases.

  17. Highly Heterogeneous Soil Bacterial Communities around Terra Nova Bay of Northern Victoria Land, Antarctica

    Science.gov (United States)

    Lim, Hyoun Soo; Hong, Soon Gyu; Kim, Ji Hee; Lee, Joohan; Choi, Taejin; Ahn, Tae Seok; Kim, Ok-Sun

    2015-01-01

    Given the diminished role of biotic interactions in soils of continental Antarctica, abiotic factors are believed to play a dominant role in structuring of microbial communities. However, many ice-free regions remain unexplored, and it is unclear which environmental gradients are primarily responsible for the variations among bacterial communities. In this study, we investigated the soil bacterial community around Terra Nova Bay of Victoria Land by pyrosequencing and determined which environmental variables govern the bacterial community structure at the local scale. Six bacterial phyla, Actinobacteria, Proteobacteria, Acidobacteria, Chloroflexi, Cyanobacteria, and Bacteroidetes, were dominant, but their relative abundance varied greatly across locations. Bacterial community structures were affected little by spatial distance, but structured more strongly by site, which was in accordance with the soil physicochemical compositions. At both the phylum and species levels, bacterial community structure was explained primarily by pH and water content, while certain earth elements and trace metals also played important roles in shaping community variation. The higher heterogeneity of the bacterial community structure found at this site indicates how soil bacterial communities have adapted to different compositions of edaphic variables under extreme environmental conditions. Taken together, these findings greatly advance our understanding of the adaption of soil bacterial populations to this harsh environment. PMID:25799273

  18. Understanding of the Interaction between Clearance Leakage Flow and Main Passage Flow in a VGT Turbine

    Directory of Open Access Journals (Sweden)

    Ben Zhao

    2015-02-01

    Full Text Available The clearance flow between the nozzle and endwall in a variable geometry turbine (VGT has been numerically investigated to understand the clearance effect on the VGT performance and internal flow. It was found that the flow rate through turbine increases but the turbine efficiency decreases with height of clearance. Detailed flow field analyses indicated that most of the efficiency loss resulting from the leakage flow occurs at the upstream of the rotor area, that is, in the nozzle endwall clearance and between the nozzle vanes. There are two main mechanisms associated with this efficiency loss. One is due to the formation of the local vortex flow structure between the clearance flow and the main flow. The other is due to the impact of the clearance flow on the main flow after the nozzle throat. This impact reduces the span of shockwave with increased shockwave magnitude by changing the trajectory of the main flow.

  19. Blood clearance of Howell-Jolly bodies in an experimental autogenic splenic implant model.

    Science.gov (United States)

    Marques, R G; Lucena, S B S G; Caetano, C E R; de Sousa, V Oliveira; Portela, M C; Petroianu, A

    2014-06-01

    various bacteria, have demonstrated that ASIs can increase the rate of bacterial clearance and decrease mortality from sepsis. Clinical studies have shown their ability to remove colloidal substances and altered erythrocyte corpuscular inclusions, such as Howell-Jolly, Heinz and Pappenheimer bodies, from the bloodstream. In this experimental study the functional and morphological regeneration of ASIs was studied over time in rats. © 2014 BJS Society Ltd. Published by John Wiley & Sons Ltd.

  20. Enhanced clearance of Escherichia coli and Staphylococcus aureus in mice treated with cyclophosphamide and lactoferrin.

    Science.gov (United States)

    Artym, Jolanta; Zimecki, Michal; Kruzel, Marian L

    2004-09-01

    Previous studies on cyclophosphamide (CP)-immunocompromised mice showed accelerated reconstitution of immune system function following oral treatment with lactoferrin (LF). The aim of this investigation was to evaluate the ability of mice, treated with a sublethal dose of CP and given LF, to combat bacterial infections. Mice were injected with a single, intraperitoneal dose of CP (350 mg/kg body weight). One group of CP-treated mice was also given LF in drinking water (0.5% solution) for 14 days. Untreated and LF-treated mice served as controls. On day 15 following CP administration, mice were infected intravenously with 10(8) Escherichia coli or 5 x 10(7) Staphylococcus aureus. Twenty-four hours later, the number of colony-forming units (CFU) in spleens and livers were determined. Phenotypic analysis of blood leukocytes was determined, as well as the ability of splenic and peritoneal cells to produce IL-6 spontaneously and in the presence of lipopolysaccharide (LPS). Treatment with CP, or with CP and LF, led to profound reduction of E. coli CFU in the liver and the spleen; treatment with LF alone had significant inhibitory effects on organ enumerated CFU. S. aureus CFUs were also significantly reduced in spleens of mice treated with CP or CP/LF and, to a lesser degree, after LF alone. These effects were also significantly reduced in the livers. Analysis of blood cellular phenotype revealed total number of peripheral leukocytes was lower in the CP-treated group (52.6%) but not significantly different from control values in CP/LF and LF-treated groups (90.7% and 104.6%, respectively). Conversely, percentage of blood neutrophils was markedly elevated in CP and CP/LF groups--62% and 42.5% vs. 18.4% in controls. These findings were accompanied by production of IL-6 by splenic and peritoneal cells which was significantly increased in CP- and CP/LF-treated groups. It was concluded that the increased clearance of bacteria in the organs of mice treated with CP and CP

  1. Brain-wide pathway for waste clearance captured by contrast-enhanced MRI

    OpenAIRE

    Iliff, Jeffrey J; Lee, Hedok; Yu, Mei; Feng, Tian; Logan, Jean; Nedergaard, Maiken; Benveniste, Helene

    2013-01-01

    The glymphatic system is a recently defined brain-wide paravascular pathway for cerebrospinal fluid (CSF) and interstitial fluid (ISF) exchange that facilitates efficient clearance of solutes and waste from the brain. CSF enters the brain along para-arterial channels to exchange with ISF, which is in turn cleared from the brain along para-venous pathways. Because soluble amyloid β clearance depends on glymphatic pathway function, we proposed that failure of this clearance system contributes t...

  2. Population differences in ganciclovir clearance as determined by nonlinear mixed-effects modelling.

    OpenAIRE

    Yuen, G J; Drusano, G. L.; Fletcher, C.; Capparelli, E; Connor, J D; Lalezari, J P; Drew, L.; Follansbee, S; Busch, D.; Jacobson, M.

    1995-01-01

    We examined the pharmacokinetics of ganciclovir in different populations of cytomegalovirus (CMV)-infected patients through the use of nonlinear mixed-effects modelling. As expected, patient weight and estimated creatinine clearance were shown to be important covariates in the serum ganciclovir clearance. Unexpectedly, major differences in ganciclovir clearance between different populations of patients were found. Human immunodeficiency virus (HIV)-infected patients with CMV retinitis cleared...

  3. Lipoproteins of Bacterial Pathogens▿

    Science.gov (United States)

    Kovacs-Simon, A.; Titball, R. W.; Michell, S. L.

    2011-01-01

    Bacterial lipoproteins are a set of membrane proteins with many different functions. Due to this broad-ranging functionality, these proteins have a considerable significance in many phenomena, from cellular physiology through cell division and virulence. Here we give a general overview of lipoprotein biogenesis and highlight examples of the roles of lipoproteins in bacterial disease caused by a selection of medically relevant Gram-negative and Gram-positive pathogens: Mycobacterium tuberculosis, Streptococcus pneumoniae, Borrelia burgdorferi, and Neisseria meningitidis. Lipoproteins have been shown to play key roles in adhesion to host cells, modulation of inflammatory processes, and translocation of virulence factors into host cells. As such, a number of lipoproteins have been shown to be potential vaccines. This review provides a summary of some of the reported roles of lipoproteins and of how this knowledge has been exploited in some cases for the generation of novel countermeasures to bacterial diseases. PMID:20974828

  4. Considerations on bacterial nucleoids.

    Science.gov (United States)

    Feijoo-Siota, Lucía; Rama, José Luis R; Sánchez-Pérez, Angeles; Villa, Tomás G

    2017-07-01

    The classic genome organization of the bacterial chromosome is normally envisaged with all its genetic markers linked, thus forming a closed genetic circle of duplex stranded DNA (dsDNA) and several proteins in what it is called as "the bacterial nucleoid." This structure may be more or less corrugated depending on the physiological state of the bacterium (i.e., resting state or active growth) and is not surrounded by a double membrane as in eukayotic cells. The universality of the closed circle model in bacteria is however slowly changing, as new data emerge in different bacterial groups such as in Planctomycetes and related microorganisms, species of Borrelia, Streptomyces, Agrobacterium, or Phytoplasma. In these and possibly other microorganisms, the existence of complex formations of intracellular membranes or linear chromosomes is typical; all of these situations contributing to weakening the current cellular organization paradigm, i.e., prokaryotic vs eukaryotic cells.

  5. Studying bacterial multispecies biofilms

    DEFF Research Database (Denmark)

    Røder, Henriette Lyng; Sørensen, Søren Johannes; Burmølle, Mette

    2016-01-01

    the approaches used to study these complex communities. This review focuses on the establishment of multispecies biofilms in vitro, interspecies interactions in microhabitats, and how to select communities for evaluation. Studies have used different experimental approaches; here we evaluate the benefits......, but the identity and significance of interspecies bacterial interactions is neglected in these analyses. There is therefore an urgent need for bridging the gap between metagenomic analysis and in vitro models suitable for studies of bacterial interactions.Bacterial interactions and coadaptation are important...... at the microscale of complex communities, including biofilms.Studies of multispecies biofilms and the interactions shaping these are conducted in traditional approaches used for single-species biofilms with some adjustments; but a crucial point for consideration is which strains to combine and where these should...

  6. Histamine Clearance Through Polyspecific Transporters in the Brain.

    Science.gov (United States)

    Yoshikawa, Takeo; Yanai, Kazuhiko

    2017-01-01

    Histamine plays an important role as a neurotransmitter in diverse brain functions, and clearance of histamine is essential to avoid excessive histaminergic neuronal activity. Histamine N-methyltransferase, which is an enzyme in the central nervous system that metabolizes histamine, is localized to the cytosol. This suggests that a histamine transport process is essential to inactivate histamine. Previous reports have shown the importance of astrocytes for histamine transport, although neuronal histamine transport could not be ruled out. High-affinity and selective histamine transporters have not yet been discovered, although it has been reported that the following three polyspecific transporters transport histamine: organic cation transporter (OCT) 2, OCT3, and plasma membrane monoamine transporter (PMAT). The K m values of human OCT2, OCT3, and PMAT are 0.54, 0.64, and 4.4 mM, respectively. The three transporters are expressed in the brain, and their regional distribution is different. Recent studies revealed the contribution of OCT3 and PMAT to histamine transport by primary human astrocytes. Several investigations using mice supported the importance of OCT3 for histamine clearance in the brain. However, further studies are required to elucidate the detailed mechanism of histamine transport in the brain.

  7. Ketamine Inhibits Lung Fluid Clearance through Reducing Alveolar Sodium Transport

    Directory of Open Access Journals (Sweden)

    Yong Cui

    2011-01-01

    Full Text Available Ketamine is a broadly used anaesthetic for analgosedation. Accumulating clinical evidence shows that ketamine causes pulmonary edema with unknown mechanisms. We measured the effects of ketamine on alveolar fluid clearance in human lung lobes ex vivo. Our results showed that intratracheal instillation of ketamine markedly decreased the reabsorption of 5% bovine serum albumin instillate. In the presence of amiloride (a specific ENaC blocker, fluid resolution was not further decreased, suggesting that ketamine could decrease amiloride-sensitive fraction of AFC associated with ENaC. Moreover, we measured the regulation of amiloride-sensitive currents by ketamine in A549 cells using whole-cell patch clamp mode. Our results suggested that ketamine decreased amiloride-sensitive Na+ currents (ENaC activity in a dose-dependent fashion. These data demonstrate that reduction in lung ENaC activity and lung fluid clearance following administration of ketamine may be the crucial step of the pathogenesis of resultant pulmonary edema.

  8. A porphyrin-PEG polymer with rapid renal clearance.

    Science.gov (United States)

    Huang, Haoyuan; Hernandez, Reinier; Geng, Jumin; Sun, Haotian; Song, Wentao; Chen, Feng; Graves, Stephen A; Nickles, Robert J; Cheng, Chong; Cai, Weibo; Lovell, Jonathan F

    2016-01-01

    Tetracarboxylic porphyrins and polyethylene glycol (PEG) diamines were crosslinked in conditions that gave rise to a water-soluble porphyrin polyamide. Using PEG linkers 2 kDa or larger prevented fluorescence self-quenching. This networked porphyrin mesh was retained during dialysis with membranes with a 100 kDa pore size, yet passed through the membrane when centrifugal filtration was applied. Following intravenous administration, the porphyrin mesh, but not the free porphyrin, was rapidly cleared via renal excretion. The process could be monitored by fluorescence analysis of collected urine, with minimal background due to the large Stokes shift of the porphyrin (230 nm separating excitation and emission peaks). In a rhabdomyolysis mouse model of renal failure, porphyrin mesh urinary clearance was significantly impaired. This led to slower accumulation in the bladder, which could be visualized non-invasively via fluorescence imaging. Without further modification, the porphyrin mesh was chelated with (64)Cu for dynamic whole body positron emission tomography imaging of renal clearance. Together, these data show that small porphyrin-PEG polymers can serve as effective multimodal markers of renal function. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Activity-Dependent Plasticity of Astroglial Potassium and Glutamate Clearance

    Directory of Open Access Journals (Sweden)

    Giselle Cheung

    2015-01-01

    Full Text Available Recent evidence has shown that astrocytes play essential roles in synaptic transmission and plasticity. Nevertheless, how neuronal activity alters astroglial functional properties and whether such properties also display specific forms of plasticity still remain elusive. Here, we review research findings supporting this aspect of astrocytes, focusing on their roles in the clearance of extracellular potassium and glutamate, two neuroactive substances promptly released during excitatory synaptic transmission. Their subsequent removal, which is primarily carried out by glial potassium channels and glutamate transporters, is essential for proper functioning of the brain. Similar to neurons, different forms of short- and long-term plasticity in astroglial uptake have been reported. In addition, we also present novel findings showing robust potentiation of astrocytic inward currents in response to repetitive stimulations at mild frequencies, as low as 0.75 Hz, in acute hippocampal slices. Interestingly, neurotransmission was hardly affected at this frequency range, suggesting that astrocytes may be more sensitive to low frequency stimulation and may exhibit stronger plasticity than neurons to prevent hyperexcitability. Taken together, these important findings strongly indicate that astrocytes display both short- and long-term plasticity in their clearance of excess neuroactive substances from the extracellular space, thereby regulating neuronal activity and brain homeostasis.

  10. Role of Erythrocyte CD47 in Intracerebral Hematoma Clearance.

    Science.gov (United States)

    Ni, Wei; Mao, Shanshan; Xi, Guohua; Keep, Richard F; Hua, Ya

    2016-02-01

    Enhancing hematoma clearance through phagocytosis may reduce brain injury after intracerebral hemorrhage. In the current study, we investigated the role of cluster of differentiation 47 (CD47) in regulating erythrophagocytosis and brain injury after intracerebral hemorrhage in nude mice. This study was in 2 parts. First, male adult nude mice had an intracaudate injection of 30 μL saline, blood from male adult wild-type (WT) mice, or blood from CD47 knockout mice. Second, mice had an intracaudate injection of 30 μL CD47 knockout blood with clodronate or control liposomes. Clodronate liposomes were also tested in saline-injected mice. All mice then had magnetic resonance imaging to measure hematoma size and brain swelling. Brains were used for immunohistochemistry and Western blot. Erythrophagocytosis occurred in and around the hematoma. Injection of CD47 knockout blood resulted in quicker clot resolution, less brain swelling, and less neurological deficits compared with wild-type blood. Higher brain heme oxygenase-1 levels and more microglial activation (mostly M2 polarized microglia) at day 3 were found after CD47 knockout blood injection. Co-injection of clodronate liposomes, to deplete phagocytes, caused more severe brain swelling and less clot resolution. These results indicated that CD47 has a key role in hematoma clearance after intracerebral hemorrhage. © 2016 American Heart Association, Inc.

  11. Diagnosis of bacterial vaginosis

    Directory of Open Access Journals (Sweden)

    Đukić Slobodanka

    2013-01-01

    Full Text Available Bacterial vaginosis is a common, complex clinical syndrome characterized by alterations in the normal vaginal flora. When symptomatic, it is associated with a malodorous vaginal discharge and on occasion vaginal burning or itching. Under normal conditions, lactobacilli constitute 95% of the bacteria in the vagina. Bacterial vaginosis is associated with severe reduction or absence of the normal H2O2­producing lactobacilli and overgrowth of anaerobic bacteria and Gardnerella vaginalis, Atopobium vaginae, Mycoplasma hominis and Mobiluncus species. Most types of infectious disease are diagnosed by culture, by isolating an antigen or RNA/DNA from the microbe, or by serodiagnosis to determine the presence of antibodies to the microbe. Therefore, demonstration of the presence of an infectious agent is often a necessary criterion for the diagnosis of the disease. This is not the case for bacterial vaginosis, since the ultimate cause of the disease is not yet known. There are a variety of methods for the diagnosis of bacterial vaginosis but no method can at present be regarded as the best. Diagnosing bacterial vaginosis has long been based on the clinical criteria of Amsel, whereby three of four defined criteria must be satisfied. Nugent’s scoring system has been further developed and includes validation of the categories of observable bacteria structures. Up­to­date molecular tests are introduced, and better understanding of vaginal microbiome, a clear definition for bacterial vaginosis, and short­term and long­term fluctuations in vaginal microflora will help to better define molecular tests within the broader clinical context.

  12. Effectiveness of small barriers as means to reduce clearance distances

    Energy Technology Data Exchange (ETDEWEB)

    Tchouvelev, Andrei V.; Cheng, Zhong [A.V.Tchouvelev and Associates, 6591 Spinnaker Circle, Mississauga, Ont. (Canada); Agranat, Vladimir M. [Hydrogenics Corp., 5985 McLaughlin Road, Mississauga, Ont. (Canada); Zhubrin, Serguei V. [Flowsolve Limited, 130 Arthur Road, London SW19 8AA (United Kingdom)

    2007-07-15

    Hydrogen clearance or safety distance can be defined as the minimum distance between a hydrogen leak source and surrounding equipment, property or personnel beyond which the risk to the said recipients associated with existing hydrogen hazards is deemed acceptable. The same principal is applied to determine clearances to ignition sources and air intakes only the criteria in this case are the risk of ignition or the risk of intaking a flammable mixture. The study of effects of small barriers as means to reduce clearance distances for compressed hydrogen releases is important for the development of installation codes and risk mitigation requirements. In this paper, computational fluid dynamics (CFD) modeling techniques were applied to the numerical simulation of the effects of a protective wall of 1 m by 1 m on reducing the size of hydrogen cloud. The protective wall was 1 m away from a 70 MPa (700 bar) 60 L tank, from which an incidental hydrogen release impinged horizontally onto the wall, causing a complicated 3D dispersion of hydrogen cloud. In-house CFD codes first accurately estimated the non-linear hydrogen mass release rate decreasing with time. Then the effects of the wall on the propagation speed of the hydrogen cloud moving behind the wall were investigated using the PHOENICS software package, provided with both the ideal gas law and the real gas law expressed by the Abel-Nobel equation of state (AN-EOS). The distributions of lower flammability limit (LFL) and 50% of LFL hydrogen clouds were described in detail based on the numerical results. It was found that the 50% of LFL hydrogen clouds (2% vol) could propagate behind the wall in less than 0.2 s after the onset of the release. The horizontal extents corresponding to 50% of LFL hydrogen cloud on the central vertical plane are 9.6 m at 5 s when they are predicted using the ideal gas law. When using the real gas law, the predicted extents decrease to 6.3 m at 5 s. The ideal gas law significantly

  13. Self-focused cognitive emotion regulation style as associated with widespread diminished EEG fractal dimension.

    Science.gov (United States)

    Bornas, Xavier; Tortella-Feliu, Miquel; Balle, Maria; Llabrés, Jordi

    2013-01-01

    The cognitive regulation of emotions is important for human adaptation. Self-focused emotion regulation (ER) strategies have been linked to the development and persistence of anxiety and depression. A vast array of research has provided valuable knowledge about the neural correlates of the use of specific self-focused ER strategies; however, the resting neural correlates of cognitive ER styles, which reflect an individual's disposition to engage in different forms of ER in order to manage distress, are largely unknown. In this study, associations between theoretically negative ER style (self-focused or not) and the complexity (fractal dimension, FD) of the resting EEG at frontal, central, parietal, and occipital regions were investigated in 58 healthy volunteers. The Cognitive Emotion Regulation Questionnaire was used as the self-report measure of ER style. Results showed that a diminished FD over the scalp significantly correlated with self-focused ER style scores, even after controlling for negative affect, which has been also considered to influence the use of ER strategies. The lower the EEG FD, the higher were the self-focused ER style scores. Correlational analyses of specific self-focused ER strategies showed that self-blaming and rumination were negatively associated with diminished FD of the EEG, but catastrophizing and blaming others were not. No significant correlations were found for ER strategies more focused on situation or others. Results are discussed within the self-organized criticality theory of brain dynamics: The diminished FD of the EEG may reflect a disposition to engage in self-focused ER strategies as people prone to ruminate and self-blame show a less complex resting EEG activity, which may make it more difficult for them to exit their negative emotional state.

  14. Artery to Vein Differences in Nitric Oxide Metabolites Are Diminished in Sepsis

    Science.gov (United States)

    Morgan, Mary Anne M.; Frasier, Lauren M.; Stewart, Judith C.; Mack, Cynthia M.; Gough, Michael S.; Graves, Brian T.; Apostolakos, Michael J.; Doolin, Kathleen P.; Darling, Denise C.; Frampton, Mark W.; Pietropaoli, Anthony P.

    2012-01-01

    Objective Nitric oxide (NO) deficiency may contribute to microvascular dysfunction in sepsis. Current physiologic paradigms contend that nitrite and/ or S-nitrosohemoglobin (SNOHb) mediate intravascular delivery of NO. These NO metabolites are purportedly consumed during hemoglobin deoxygenation producing NO and coupling intravascular NO delivery with metabolic demand. Systemic nitrite and SNOHb consumption can be assessed by comparing their concentrations in arterial vs. venous blood. We hypothesized that arterial vs. venous (A-V) differences in nitrite and SNOHb are diminished in sepsis and associated with mortality. Design Case-control and prospective cohort study Setting Adult intensive care units of an academic medical center Patients and subjects 87 critically ill septic patients and 52 control subjects Interventions None Measurements and Main Results Nitrite and SNOHb were measured using tri-iodide-based reductive chemiluminescence. In control subjects, arterial plasma, whole blood and red blood cell nitrite levels were higher than the corresponding venous levels. In contrast, SNOHb was higher in venous compared to arterial blood. In septic patients, A-V RBC nitrite and SNOHb differences were absent. Moreover, the plasma nitrite A-V difference was absent in non-survivors. Conclusions In health, nitrite levels are higher in arterial vs. venous blood (suggesting systemic nitrite consumption) whereas SNOHb levels are higher in venous vs. arterial blood (suggesting systemic SNOHb production). These A-V differences are diminished in sepsis, and diminished A-V plasma nitrite differences are associated with mortality. These data suggest pathologic disruption of systemic nitrite utilization in sepsis. PMID:20081526

  15. Chemosensory impairment does not diminish eating pleasure and appetite in independently living older adults.

    Science.gov (United States)

    Arganini, Claudia; Sinesio, Fiorella

    2015-10-01

    This study aims to evaluate the impact of chemosensory impairment on diminished eating pleasure and appetite in independently living Italian older adults. 239 individuals (65 to 101 years old, 157 women), with no severe medical conditions and good cognitive performance were recruited. Olfactory and gustatory functions were measured using a short version of Sniffin' Sticks and Taste Strips tests (Burghart). Information about socio-demographic characteristics, health, perceived smell and taste impairment, diminished eating pleasure and appetite were obtained with a specially designed questionnaire. Prevalence of chemosensory impairment detected in this sample is high, being 41% for taste and 33% for olfaction. However, the frequency of self-reported impairment is consistently lower than the measured one, especially in men and in older subjects. Measured chemosensory impairment is not significantly related with eating pleasure and appetite. On the other hand, factors significantly influencing decline of eating pleasure are: living alone, dietary restriction and perceived taste impairment. Meanwhile, a significant influence of dietary restriction, dentures and subjective health status on appetite decline is observed. The results of this study show that chemosensory impairment may not be related with diminished eating pleasure and appetite, while other non-physiological factors such as loneliness, dietary restrictions and subjective health should be taken more into account in order to develop effective strategies to counteract malnutrition in the elderly. In addition, low awareness of chemosensory impairment among this sample highlights the importance of measuring sensory acuity rather than asking by questionnaire or interview, in order to obtain reliable data. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  16. The TP73 gene polymorphism (rs4648551, A>G is associated with diminished ovarian reserve.

    Directory of Open Access Journals (Sweden)

    Laura Diniz Vagnini

    Full Text Available It's known that the members of the TP53 family are involved in the regulation of female reproduction. Studies in mice showed that the TP73 gene (member of this family plays a role in the size of follicular pool, ovulation rate and maintenance of genomic stability. In the present study we analyzed data from 605 patients with ≤ 37 years attending their first intracytoplasmic sperm injection (ICSI. The association between the TP73 polymorphism (rs4648551, A>G and the following parameters related to ovarian reserve, like age, antral follicular count (AFC, anti-Mullerian hormone levels (AMH and ovarian response prediction index (ORPI was evaluated. Our results showed an association of the AA genotype with diminished ovarian reserve (AMH <1, AFC ≤9. Women presenting the AA genotype had a 2.0-fold increased risk for having AMH <1 and AFC ≤9 (OR 2.0, 95% CI 1.23-3.31, P = 0.005. Patients presenting AA genotype had the lowest levels of AMH (P = 0.02, the lowest number of antral follicles (P = 0.01 and the lowest ORPI (P = 0.007. Analyzing the alleles, we can see an enrichment of the A allele in the group of diminished ovarian reserve (OR 1.4, 95%CI 1.02-1.83, P = 0.04. To the best of our knowledge, the present study is the first to analyze this polymorphism in humans for assessing the numbers of ovarian follicles and AMH levels and, therefore, the ovarian reserve. Our findings can contribute to the use of this polymorphism as a potential marker of diminished ovarian reserve.

  17. Bacterial blight of cotton

    Directory of Open Access Journals (Sweden)

    Aïda JALLOUL

    2015-04-01

    Full Text Available Bacterial blight of cotton (Gossypium ssp., caused by Xanthomonas citri pathovar malvacearum, is a severe disease occurring in all cotton-growing areas. The interactions between host plants and the bacteria are based on the gene-for-gene concept, representing a complex resistance gene/avr gene system. In light of the recent data, this review focuses on the understanding of these interactions with emphasis on (1 the genetic basis for plant resistance and bacterial virulence, (2 physiological mechanisms involved in the hypersensitive response to the pathogen, including hormonal signaling, the oxylipin pathway, synthesis of antimicrobial molecules and alteration of host cell structures, and (3 control of the disease.

  18. Bacterial meningitis in infants.

    Science.gov (United States)

    Ku, Lawrence C; Boggess, Kim A; Cohen-Wolkowiez, Michael

    2015-03-01

    Neonatal bacterial meningitis is uncommon but devastating. Morbidity among survivors remains high. The types and distribution of pathogens are related to gestational age, postnatal age, and geographic region. Confirming the diagnosis is difficult. Clinical signs are often subtle, lumbar punctures are frequently deferred, and cerebrospinal fluid (CSF) cultures can be compromised by prior antibiotic exposure. Infants with bacterial meningitis can have negative blood cultures and normal CSF parameters. Promising tests such as the polymerase chain reaction require further study. Prompt treatment with antibiotics is essential. Clinical trials investigating a vaccine for preventing neonatal Group B Streptococcus infections are ongoing. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Not All Children with Cystic Fibrosis Have Abnormal Esophageal Neutralization during Chemical Clearance of Acid Reflux.

    Science.gov (United States)

    Woodley, Frederick W; Moore-Clingenpeel, Melissa; Machado, Rodrigo Strehl; Nemastil, Christopher J; Jadcherla, Sudarshan R; Hayes, Don; Kopp, Benjamin T; Kaul, Ajay; Di Lorenzo, Carlo; Mousa, Hayat

    2017-09-01

    Acid neutralization during chemical clearance is significantly prolonged in children with cystic fibrosis, compared to symptomatic children without cystic fibrosis. The absence of available reference values impeded identification of abnormal findings within individual patients with and without cystic fibrosis. The present study aimed to test the hypothesis that significantly more children with cystic fibrosis have acid neutralization durations during chemical clearance that fall outside the physiological range. Published reference value for acid neutralization duration during chemical clearance (determined using combined impedance/pH monitoring) was used to assess esophageal acid neutralization efficiency during chemical clearance in 16 children with cystic fibrosis (3 to cystic fibrosis. Duration of acid neutralization during chemical clearance exceeded the upper end of the physiological range in 9 of 16 (56.3%) children with and in 3 of 16 (18.8%) children without cystic fibrosis (p=0.0412). The likelihood ratio for duration indicated that children with cystic fibrosis are 2.1-times more likely to have abnormal acid neutralization during chemical clearance, and children with abnormal acid neutralization during chemical clearance are 1.5-times more likely to have cystic fibrosis. Significantly more (but not all) children with cystic fibrosis have abnormally prolonged esophageal clearance of acid. Children with cystic fibrosis are more likely to have abnormal acid neutralization during chemical clearance. Additional studies involving larger sample sizes are needed to address the importance of genotype, esophageal motility, composition and volume of saliva, and gastric acidity on acid neutralization efficiency in cystic fibrosis children.

  20. Clearance rate of Mytilus edulis (L.) as a function of current velocity and mussel aggregation

    DEFF Research Database (Denmark)

    Nielsen, Pernille; Vismann, Bent

    2014-01-01

    The aim of the current study was to investigate the effect of water current velocities on the clearance rate of Mytilus edulis when different numbers of mussels were used in the experiments. An automatic setup, which controlled and monitored the algal concentration continually, was used to measure...... the effect of increasing current velocity (0.05-1.4 m/sec) on the M. edulis clearance rate. Clearance rate measurements were performed under constant food concentrations of 3,000 cells/mL of Rhodomonas salina on either 3 mussels or 20 mussels. We found that the clearance rate of 20 mussels was unaffected...

  1. The Role of Radial Clearance on the Performance of Foil Air Bearings

    Science.gov (United States)

    Radil, Kevin; Howard, Samuel; Dykas, Brian

    2002-01-01

    Load capacity tests were conducted to determine how radial clearance variations affect the load capacity coefficient of foil air bearings. Two Generation III foil air bearings with the same design but possessing different initial radial clearances were tested at room temperature against an as-ground PS304 coated journal operating at 30,000 rpm. Increases in radial clearance were accomplished by reducing the journal's outside diameter via an in-place grinding system. From each load capacity test the bearing load capacity coefficient was calculated from the rule-of-thumb (ROT) model developed for foil air bearings. The test results indicate that, in terms of the load capacity coefficient, radial clearance has a direct impact on the performance of the foil air bearing. Each test bearing exhibited an optimum radial clearance that resulted in a maximum load capacity coefficient. Relative to this optimum value are two separate operating regimes that are governed by different modes of failure. Bearings operating with radial clearances less than the optimum exhibit load capacity coefficients that are a strong function of radial clearance and are prone to a thermal runaway failure mechanism and bearing seizure. Conversely, a bearing operating with a radial clearance twice the optimum suffered only a 20 percent decline in its maximum load capacity coefficient and did not experience any thermal management problems. However, it is unknown to what degree these changes in radial clearance had on other performance parameters, such as the stiffness and damping properties of the bearings.

  2. 77 FR 28853 - Proposed Information Collection; Comment Request; Generic Clearance for Usability Data Collections

    Science.gov (United States)

    2012-05-16

    ... Clearance for Usability Data Collections AGENCY: National Institute of Standards and Technology (NIST... data collections will be designed to determine requirement and evaluate the usability and utility of...

  3. Analysis of foot clearance in firefighters during ascent and descent of stairs.

    Science.gov (United States)

    Kesler, Richard M; Horn, Gavin P; Rosengren, Karl S; Hsiao-Wecksler, Elizabeth T

    2016-01-01

    Slips, trips, and falls are a leading cause of injury to firefighters with many injuries occurring while traversing stairs, possibly exaggerated by acute fatigue from firefighting activities and/or asymmetric load carriage. This study examined the effects that fatigue, induced by simulated firefighting activities, and hose load carriage have on foot clearance while traversing stairs. Landing and passing foot clearances for each stair during ascent and descent of a short staircase were investigated. Clearances decreased significantly (p stair clearance or an increased risk of over-stepping during descent. Copyright © 2015 Elsevier Ltd and The Ergonomics Society. All rights reserved.

  4. 76 FR 59379 - Proposed Information Collection; Comment Request; Generic Clearance for Research in Development...

    Science.gov (United States)

    2011-09-26

    ... Treasury Department Clearance Officer, Department of the Treasury, Room 11010, 1750 Pennsylvania Avenue, NW... during the shopping, application, and origination process. In addition, the CFPB may perform qualitative...

  5. A total variation diminishing finite difference algorithm for sonic boom propagation models

    Science.gov (United States)

    Sparrow, Victor W.

    1993-01-01

    It is difficult to accurately model the rise phases of sonic boom waveforms with traditional finite difference algorithms because of finite difference phase dispersion. This paper introduces the concept of a total variation diminishing (TVD) finite difference method as a tool for accurately modeling the rise phases of sonic booms. A standard second order finite difference algorithm and its TVD modified counterpart are both applied to the one-way propagation of a square pulse. The TVD method clearly outperforms the non-TVD method, showing great potential as a new computational tool in the analysis of sonic boom propagation.

  6. Symptoms of Diminished Autonomy over Cigarettes with Non-Daily Use

    Directory of Open Access Journals (Sweden)

    Judith A. Savageau

    2008-12-01

    Full Text Available Data from a nationally representative sample of smokers (ages 12-22 years, n=2,091 was examined to investigate the prevalence of symptoms of diminished autonomy over cigarettes. Six symptoms were assessed: failed cessation, smoking despite a desire to quit, and a need or urge to smoke, irritability, restlessness, or disrupted concentration attributed to nicotine withdrawal. One or more of the six symptoms were present in 18.9% of subjects who smoked less often than once per week. Among subjects who had not smoked 20 cigarettes in their lifetime, 12.6% had symptoms of nicotine withdrawal, and 25% had made an unsuccessful quit attempt.

  7. Costs of water treatment due to diminished water quality: A case study in Texas

    Science.gov (United States)

    Dearmont, David; McCarl, Bruce A.; Tolman, Deborah A.

    1998-04-01

    The cost of municipal water treatment due to diminished water quality represents an important component of the societal costs of water pollution. Here the chemical costs of municipal water treatment are expressed as a function of raw surface water quality. Data are used for a 3-year period for 12 water treatment plants in Texas. Results show that when regional raw water contamination is present, the chemical cost of water treatment is increased by 95 per million gallons (per 3785 m3) from a base of 75. A 1% increase in turbidity is shown to increase chemical costs by 0.25%.

  8. Safety and efficacy of levofloxacin versus ciprofloxacin for the treatment of chronic bacterial prostatitis in Chinese patients

    Science.gov (United States)

    Zhang, Zhi-Chao; Jin, Feng-Shuo; Liu, Dong-Ming; Shen, Zhou-Jun; Sun, Ying-Hao; Guo, Ying-Lu

    2012-01-01

    Levofloxacin is a synthetic fluoroquinolone that is usually used to treat chronic bacterial prostatitis. We investigated the safety and efficacy of levofloxacin compared with ciprofloxacin for the treatment of chronic bacterial prostatitis in Chinese patients. This was a multicenter, open-label, randomized controlled non-inferiority trial. Four hundred and seventy-one patients with clinical symptoms/signs were enrolled into the study, and 408 patients were microbiologically confirmed chronic bacterial prostatitis, who were randomized to either oral levofloxacin (500 mg q.d.) or ciprofloxacin (500 mg b.i.d.) for 4 weeks. Bacterial clearance rate, clinical symptoms/signs, adverse reactions and disease recurrence were assessed. The clinical symptoms and signs (including dysuria, perineal discomfort or pain) and bacteria cultures in 209 patients treated with levofloxacin and 199 patients treated with ciprofloxacin were similar. The most common bacteria were Escherichia coli and Staphylococcus aureus. One to four weeks after the end of 4 weeks treatment, the bacterial clearance rate (86.06% vs. 60.03% Plevofloxacin-treated group than in the ciprofloxacin-treated group. The microbiological recurrence rate was significantly lower in the levofloxacin-treated group than in the ciprofloxacin-treated group (4.00% vs. 19.25% Plevofloxacin-treated group than in ciprofloxacin-treated group. Levofloxacin showed some advantages over ciprofloxacin in terms of clinical efficacy and disease recurrence, with a low rate of adverse events, for the treatment of chronic bacterial prostatitis in Chinese patients. PMID:22864282

  9. Bronchoscintigraphy and pulmonary clearance of {sup 99{sup m}}Tc-albumin colloid in study of mucociliary clearance

    Energy Technology Data Exchange (ETDEWEB)

    Mortensen, Jann

    1998-12-31

    A radioaerosol based method for measuring MC was introduced. It included an inhalation protocol that resulted in a predominant deposition of radioaerosol in the central bronchi and two simple procedures of evaluation: 1) a visual semi-quantitative bronchoscintigraphic analysis, and 2) a quantitative analysis of the retention of the radioactivity at different points after the inhalation. The results showed that bronchoscintigraphy was a simple technique that may be used to visualize a stimulation of mucociliary transport in the central airways of individuals that do not suffer from too much mucus hypersecretion. Comparison of the MC between individuals, however, should preferably be performed by the method of quantitative analysis of the radioactivity disappearance. A change of MC was found to be one of the first detectable effects on lung function of tobacco smoking. It could be effectively detected by measurement of radioaerosol clearance both by bronchoscintigraphy and simple quantification of the MC. The MC may be either acutely enhanced, reduced or not changed by smoking. Long-term smoking impairs MC. The enhancement of MC by {beta}{sub 2}-agonists was very limited in most patients with CF. In the hope of increasing mucus transport in patients with CF, these are treated with various chest physiotherapy techniques. The radioaerosol based method of measurement of MC could assess mucus clearance by chest physiotherapy and cough. (au) 141 refs.

  10. Osmotic diuresis-induced hypernatremia: better explained by solute-free water clearance or electrolyte-free water clearance?

    Science.gov (United States)

    Popli, Subhash; Tzamaloukas, Antonios H; Ing, Todd S

    2014-01-01

    Hypernatremia may result from inadequate water intake, excessive water loss or a combination of the two. Osmotic diuresis leads to losses of both solute and water. The relationship between solute and water losses determines the resulting changes in serum osmolality and sodium concentration. Total solute loss is routinely higher than loss of water in osmotic diuresis. Theoretically, then, decreases in serum osmolality (and serum sodium concentration) should follow. In clinical situations of osmotic diuresis, however, reduction in osmolality can take place, but not reduction in serum sodium concentration. It is of note that serum sodium concentration changes are related to urinary losses of sodium and potassium but not to the loss of total solute. In osmotic diuresis, the combined loss of sodium and potassium per liter of urine is lower than the concurrent serum sodium level. Consequently, hypernatremia can ensue. A patient who presented with osmotic diuresis and hypernatremia is described here. In this patient, we have shown that electrolyte-free water clearance is a better index of the effect of osmotic diuresis on serum sodium concentration than the classic solute-free water clearance.

  11. BACTERIAL WATERBORNE PATHOGENS

    Science.gov (United States)

    Bacterial pathogens are examples of classical etiological agents of waterborne disease. While these agents no longer serve as major threats to U.S. water supplies, they are still important pathogens in areas with substandard sanitation and poor water treatment facilities. In th...

  12. Bacterial Infections - Multiple Languages

    Science.gov (United States)

    ... Know - Af-Soomaali (Somali) PDF Centers for Disease Control and Prevention Spanish (español) Expand Section Bacterial Infections: MedlinePlus Health Topic - English Infecciones bacterianas: Tema de salud de MedlinePlus - español (Spanish) ...

  13. [Spontaneous bacterial peritonitis].

    Science.gov (United States)

    Velkey, Bálint; Vitális, Eszter; Vitális, Zsuzsanna

    2017-01-01

    Spontaneous bacterial peritonitis occurs most commonly in cirrhotic patients with ascites. Pathogens get into the circulation by intestinal translocation and colonize in peritoneal fluid. Diagnosis of spontaneous bacterial peritonitis is based on elevated polymorphonuclear leukocyte count in the ascites (>0,25 G/L). Ascites culture is often negative but aids to get information about antibiotic sensitivity in positive cases. Treatment in stable patient can be intravenous then orally administrated ciprofloxacin or amoxicillin/clavulanic acid, while in severe cases intravenous III. generation cephalosporin. Nosocomial spontaneous bacterial peritonitis often caused by Gram-positive bacteria and multi-resistant pathogens can also be expected thus carbapenem should be the choice of the empiric treatment. Antibiotic prophylaxis should be considered. Norfloxacin is used most commonly, but changes are expected due to increase in quinolone resistance. As a primary prophylaxis, a short-term antibiotic treatment is recommended after gastrointestinal bleeding for 5 days, while long-term prophylaxis is for patients with low ascites protein, and advanced disease (400 mg/day). Secondary prophylaxis is recommended for all patients recovered from spontaneous bacterial peritonitis. Due to increasing antibiotic use of antibiotics prophylaxis is debated to some degree. Orv. Hetil., 2017, 158(2), 50-57.

  14. Elucidating Sources and Roles of Granzymes A and B during Bacterial Infection and Sepsis

    Directory of Open Access Journals (Sweden)

    Maykel A. Arias

    2014-07-01

    Full Text Available During bacterial sepsis, proinflammatory cytokines contribute to multiorgan failure and death in a process regulated in part by cytolytic cell granzymes. When challenged with a sublethal dose of the identified mouse pathogen Brucella microti, wild-type (WT and granzyme A (gzmA−/− mice eliminate the organism from liver and spleen in 2 or 3 weeks, whereas the bacteria persist in mice lacking perforin or granzyme B as well as in mice depleted of Tc cells. In comparison, after a fatal challenge, only gzmA−/− mice exhibit increased survival, which correlated with reduced proinflammatory cytokines. Depletion of natural killer (NK cells protects WT mice from sepsis without influencing bacterial clearance and the transfer of WT, but not gzmA−/− NK, cells into gzmA−/− recipients restores the susceptibility to sepsis. Therefore, infection-related pathology, but not bacterial clearance, appears to require gzmA, suggesting the protease may be a therapeutic target for the prevention of bacterial sepsis without affecting immune control of the pathogen.

  15. Diminished Auditory Responses during NREM Sleep Correlate with the Hierarchy of Language Processing.

    Directory of Open Access Journals (Sweden)

    Meytal Wilf

    Full Text Available Natural sleep provides a powerful model system for studying the neuronal correlates of awareness and state changes in the human brain. To quantitatively map the nature of sleep-induced modulations in sensory responses we presented participants with auditory stimuli possessing different levels of linguistic complexity. Ten participants were scanned using functional magnetic resonance imaging (fMRI during the waking state and after falling asleep. Sleep staging was based on heart rate measures validated independently on 20 participants using concurrent EEG and heart rate measurements and the results were confirmed using permutation analysis. Participants were exposed to three types of auditory stimuli: scrambled sounds, meaningless word sentences and comprehensible sentences. During non-rapid eye movement (NREM sleep, we found diminishing brain activation along the hierarchy of language processing, more pronounced in higher processing regions. Specifically, the auditory thalamus showed similar activation levels during sleep and waking states, primary auditory cortex remained activated but showed a significant reduction in auditory responses during sleep, and the high order language-related representation in inferior frontal gyrus (IFG cortex showed a complete abolishment of responses during NREM sleep. In addition to an overall activation decrease in language processing regions in superior temporal gyrus and IFG, those areas manifested a loss of semantic selectivity during NREM sleep. Our results suggest that the decreased awareness to linguistic auditory stimuli during NREM sleep is linked to diminished activity in high order processing stations.

  16. Ski diminishes TGF-β1-induced myofibroblast phenotype via up-regulating Meox2 expression.

    Science.gov (United States)

    Chen, Zhaowei; Li, Wenjing; Ning, Yan; Liu, Tong; Shao, Jingxiang; Wang, Yaojun

    2014-12-01

    The aim of the present work was to investigate the mechanism of transforming growth factor (TGF)-β1 and Sloan-Kettering Institute (Ski) in the pathogenesis of hypertrophic scars (HS). Wound healing is an inherent process, but the aberrant wound healing of skin injury may lead to HS. There has been growing evidence suggesting a role for TGF-β1 and Ski in the pathogenesis of fibrosis. The MTT assay was used to detect the cell proliferation induced by TGF-β1. The Ski gene was transduced into cells with an adenovirus, and then the function of Ski in cell proliferation and differentiation was observed. Ski mRNA levels were measured by RT-PCR. Western blotting was used to detect the protein expression of α-SMA, E-cadherin, Meox1, Meox2, Zeb1 and Zeb2. TGF-β1 can promote human skin fibroblast (HSF) cell proliferation in a time-dependent manner, but the promoting effect could be suppressed by Ski. TGF-β1 also induces the formation of the myofibroblast phenotype and the effect of TGF-β1 could be diminished by Ski. Also, Ski modulates the cardiac myofibroblast phenotype and function through suppression of Zeb2 by up-regulating the expression of Meox2. Ski diminishes the myofibroblast phenotype induced by TGF-β1 through the suppression of Zeb2 by up-regulating the expression of Meox2. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Repeated exposure to media violence is associated with diminished response in an inhibitory frontolimbic network.

    Directory of Open Access Journals (Sweden)

    Christopher R Kelly

    Full Text Available BACKGROUND: Media depictions of violence, although often claimed to induce viewer aggression, have not been shown to affect the cortical networks that regulate behavior. METHODOLOGY/PRINCIPAL FINDINGS: Using functional magnetic resonance imaging (fMRI, we found that repeated exposure to violent media, but not to other equally arousing media, led to both diminished response in right lateral orbitofrontal cortex (right ltOFC and a decrease in right ltOFC-amygdala interaction. Reduced function in this network has been previously associated with decreased control over a variety of behaviors, including reactive aggression. Indeed, we found reduced right ltOFC responses to be characteristic of those subjects that reported greater tendencies toward reactive aggression. Furthermore, the violence-induced reduction in right ltOFC response coincided with increased throughput to behavior planning regions. CONCLUSIONS: These novel findings establish that even short-term exposure to violent media can result in diminished responsiveness of a network associated with behaviors such as reactive aggression.

  18. Diminished ovarian reserve, premature ovarian failure, poor ovarian responder--a plea for universal definitions.

    Science.gov (United States)

    Cohen, J; Chabbert-Buffet, N; Darai, E

    2015-12-01

    Diminished ovarian reserve (DOR) is characterized by poor fertility outcomes, and it represents a major challenge in reproductive medicine. Although consensus exists on the concept of DOR, its definition remains blurry. DOR has to be distinguished from premature ovarian failure (POF) and poor ovarian responders (POR), who are clearly defined. We performed a PubMed search with the terms "diminished ovarian reserve" and "in vitro fertilization (IVF)" to assess the homogeneity of the definition of DOR. Out of 121 articles, 14 gave a definition for DOR. Only one definition was used by two different teams (basal follicle-stimulating hormone (FSH) value >10 IU/l) and eight teams used 11 different definitions. Among those, four definitions did not include antral follicular count (AFC) and seven studies did. Two definitions included the results from a previous cycle. The heterogeneity in the definition of DOR used in these studies contributes to confusing results. Hence, there is a need for a clear definition of DOR. It appears that AFC and anti-Müllerian hormone (AMH) serum levels are the most relevant criteria. One option could be the use of the following definition: (i) woman with any of the risk factors for POR and/or (ii) an abnormal ovarian reserve test (i.e., antral follicular count (AFC) hypothesis requires validation.

  19. Epstein-Barr virus reactivation associated with diminished cell-mediated immunity in antarctic expeditioners

    Science.gov (United States)

    Mehta, S. K.; Pierson, D. L.; Cooley, H.; Dubow, R.; Lugg, D.

    2000-01-01

    Epstein-Barr virus (EBV) reactivation and cell-mediated immune (CMI) responses were followed in 16 Antarctic expeditioners during winter-over isolation at 2 Australian National Antarctic Research Expedition stations. Delayed-type hypersensitivity (DTH) skin testing was used as an indicator of the CMI response, that was evaluated 2 times before winter isolation and 3 times during isolation. At all 5 evaluation times, 8 or more of the 16 subjects had a diminished CMI response. Diminished DTH was observed on every test occasion in 4/16 subjects; only 2/16 subjects exhibited normal DTH responses for all 5 tests. A polymerase chain reaction (PCR) assay was used to detect EBV DNA in saliva specimens collected before, during, and after the winter isolation. EBV DNA was present in 17% (111/642) of the saliva specimens; all 16 subjects shed EBV in their saliva on at least 1 occasion. The probability of EBV shedding increased (P = 0.013) from 6% before or after winter isolation to 13% during the winter period. EBV appeared in saliva during the winter isolation more frequently (P viruses.

  20. When is diminishment a form of enhancement? Rethinking the enhancement debate in biomedical ethics

    Directory of Open Access Journals (Sweden)

    Brian D. Earp

    2014-02-01

    Full Text Available The enhancement debate in neuroscience and biomedical ethics tends to focus on the augmentation of certain capacities or functions: memory, learning, attention, and the like. Typically, the point of contention is whether these augmentative enhancements are permissible for individuals with no particular ‘medical’ disadvantage along any of the dimensions of interest. Less frequently addressed in the literature, however, is the fact that sometimes the diminishment of a capacity or function, under the right set of circumstances, could plausibly contribute to an individual’s overall well-being: more is not always better, and sometimes less is more. Such cases may be especially likely, we suggest, when trade-offs in our modern environment have shifted since the environment of evolutionary adaptation. In this article, we introduce the notion of diminishment as enhancement and go on to defend a welfarist conception of enhancement. We show how this conception resolves a number of definitional ambiguities in the enhancement literature, and we suggest that it can provide a useful framework for thinking about the use of emerging neurotechnologies to promote human flourishing.

  1. Lactate Clearance Predicts Survival Among Patients in the Emergency Department with Severe Sepsis

    Directory of Open Access Journals (Sweden)

    Sundeep R. Bhat

    2015-12-01

    Full Text Available Introduction: Lactate clearance has been implicated as a predictor of mortality among emergency department (ED patients with severe sepsis or septic shock. We aimed to validate prior studies showing that lactate clearance during the ED stay is associated with decreased mortality. Methods: Retrospective dual-centered cross-sectional study using patients identified in the YaleNew Haven Hospital Emergency Medicine sepsis registry with severe sepsis or septic shock who had initial lactate levels measured in the ED and upon arrival (<24 hours to the hospital floor. Lactate clearance was calculated as percent of serum lactate change from ED to floor measurement. We compared mortality and hospital interventions between patients who cleared lactate and those who did not. Results: 207 patients (110 male; 63.17±17.9 years were included. Two reviewers extracted data with 95% agreement. One hundred thirty-six patients (65.7% had severe sepsis and 71 patients (34.3% had septic shock. There were 171 patients in the clearance group and 36 patients in the non-clearance group. The 28-day mortality rates were 15.2% in the lactate clearance group and 36.1% in the non-clearance group (p<0.01. Vasopressor support was initiated more often in the nonclearance group (61.1% than in the clearance group (36.8%, p<0.01 and mechanical ventilation was used in 66.7% of the non-clearance group and 36.3% of the clearance group (p=0.001. Conclusion: Patients who do not clear their lactate in the ED have significantly higher mortality than those with decreasing lactate levels. Our results are confirmatory of other literature supporting that lactate clearance may be used to stratify mortality-risk among patients with severe sepsis or septic shock.

  2. Esophageal clearance scintigraphy in, diabetic patients; A preliminary study

    Energy Technology Data Exchange (ETDEWEB)

    Karayalcin, B.; Karayalcin, U.; Aburano, Tamio; Nakajima, Kenichi; Hisada, Kinichi; Morise, Toshio; Okada, Toshihide; Takeda, Ryoyu (Kanazawa Univ. (Japan). School of Medicine)

    1992-05-01

    The aim of this preliminary study was to evaluate the predictive value of esophageal clearance scintigraphy (ECS) in the diagnosis of esophageal autonomic neuropathy in diabetic patients without any esophageal symptoms. A single swallon ECS was performed in 12 diabetic patients and 15 normal volunteers, and esophageal transit time (ETT) and esophageal (Es) T 1/2 values were calculated. ETT and Es 1/2 were found to be significantly prolonged in the diabetic group (p<0.01 and p<0.05, respectively). In this preliminary study, our results strongly suggest that ECS may be an important noninvasive diagnostic tool in the evaluation of diabetic patients with asymptomatic esophageal autonomic neuropathy. (author).

  3. Container scanning to reduce time of customs clearance process

    Directory of Open Access Journals (Sweden)

    Yuri da Cunha Ferreira,

    2015-12-01

    Full Text Available One way to increase customs clearance efficiency and to assure supply chain security is the use of non-intrusive inspection equipment, such as scanners. In Brazil, scanners are new, but their use at port terminals is growing rapidly. Considering the possibility of Brazilian Customs requesting 100% scanning of loads, this study aims to assess the operational impacts of this possible request at a specific port terminal. This is the originality of this research. To do so, this study uses applied simulation methods in a case study. Results show that for the current scenario, scanners do not appear to be an operational bottleneck at this port, but the scanning capacity will be exceeded with the planned port expansion. Hence, scheduling rules for single machines were applied to optimize scanning performance. These heuristics provided good performance, suggesting that scanners can provide benefits to priority cargo handling, and could eventually increase the performance of port terminals throughout the country.

  4. Macrophage Clearance of Apoptotic Cells: A Critical Assessment

    Directory of Open Access Journals (Sweden)

    Siamon Gordon

    2018-01-01

    Full Text Available As the body continues to grow and age, it becomes essential to maintain a balance between living and dying cells. Macrophages and dendritic cells play a central role in discriminating among viable, apoptotic, and necrotic cells, as selective and efficient phagocytes, without inducing inappropriate inflammation or immune responses. A great deal has been learnt concerning clearance receptors for modified and non-self-ligands on potential targets, mediating their eventual uptake, disposal, and replacement. In this essay, we assess current understanding of the phagocytic recognition of apoptotic cells within their tissue environment; we conclude that efferocytosis constitutes a more complex process than simply removal of corpses, with regulatory interactions between the target and effector cells, which determine the outcome of this homeostatic process.

  5. Type 1 interferons contribute to the clearance of senescent cell.

    Science.gov (United States)

    Katlinskaya, Yuliya V; Carbone, Christopher J; Yu, Qiujing; Fuchs, Serge Y

    2015-01-01

    The major known function of cytokines that belong to type I interferons (IFN, including IFNα and IFNβ) is to mount the defense against viruses. This function also protects the genetic information of host cells from alterations in the genome elicited by some of these viruses. Furthermore, recent studies demonstrated that IFN also restrict proliferation of damaged cells by inducing cell senescence. Here we investigated the subsequent role of IFN in elimination of the senescent cells. Our studies demonstrate that endogenous IFN produced by already senescent cells contribute to increased expression of the natural killer (NK) receptor ligands, including MIC-A and ULBP2. Furthermore, neutralization of endogenous IFN or genetic ablation of its receptor chain IFNAR1 compromises the recognition of senescent cells and their clearance in vitro and in vivo. We discuss the role of IFN in protecting the multi-cellular host from accumulation of damaged senescent cells and potential significance of this mechanism in human cancers.

  6. Control of intestinal bacterial proliferation in regulation of lifespan in Caenorhabditis elegans

    Directory of Open Access Journals (Sweden)

    Portal-Celhay Cynthia

    2012-03-01

    Full Text Available Abstract Background A powerful approach to understanding complex processes such as aging is to use model organisms amenable to genetic manipulation, and to seek relevant phenotypes to measure. Caenorhabditis elegans is particularly suited to studies of aging, since numerous single-gene mutations have been identified that affect its lifespan; it possesses an innate immune system employing evolutionarily conserved signaling pathways affecting longevity. As worms age, bacteria accumulate in the intestinal tract. However, quantitative relationships between worm genotype, lifespan, and intestinal lumen bacterial load have not been examined. We hypothesized that gut immunity is less efficient in older animals, leading to enhanced bacterial accumulation, reducing longevity. To address this question, we evaluated the ability of worms to control bacterial accumulation as a functional marker of intestinal immunity. Results We show that as adult worms age, several C. elegans genotypes show diminished capacity to control intestinal bacterial accumulation. We provide evidence that intestinal bacterial load, regulated by gut immunity, is an important causative factor of lifespan determination; the effects are specified by bacterial strain, worm genotype, and biologic age, all acting in concert. Conclusions In total, these studies focus attention on the worm intestine as a locus that influences longevity in the presence of an accumulating bacterial population. Further studies defining the interplay between bacterial species and host immunity in C. elegans may provide insights into the general mechanisms of aging and age-related diseases.

  7. Selective labelling and eradication of antibiotic-tolerant bacterial populations in Pseudomonas aeruginosa biofilms

    DEFF Research Database (Denmark)

    Chua, Song Lin; Yam, Joey Kuok Hoong; Hao, Piliang

    2016-01-01

    Drug resistance and tolerance greatly diminish the therapeutic potential of antibiotics against pathogens. Antibiotic tolerance by bacterial biofilms often leads to persistent infections, but its mechanisms are unclear. Here we use a proteomics approach, pulsed stable isotope labelling with amino...... research avenues for designing more efficient treatments against biofilm-associated infections....... development. The macrolide erythromycin, which has been previously shown to inhibit the motility and QS of P. aeruginosa, boosts biofilm eradication by colistin. Our work provides insights on the mechanisms underlying the formation of antibiotic-tolerant populations in bacterial biofilms and indicates...

  8. Exploring anti-bacterial compounds against intracellular Legionella.

    Directory of Open Access Journals (Sweden)

    Christopher F Harrison

    Full Text Available Legionella pneumophila is a ubiquitous fresh-water bacterium which reproduces within its erstwhile predators, environmental amoeba, by subverting the normal pathway of phagocytosis and degradation. The molecular mechanisms which confer resistance to amoeba are apparently conserved and also allow replication within macrophages. Thus, L. pneumophila can act as an 'accidental' human pathogen and cause a severe pneumonia known as Legionnaires' disease. The intracellular localisation of L. pneumophila protects it from some antibiotics, and this fact must be taken into account to develop new anti-bacterial compounds. In addition, the intracellular lifestyle of L. pneumophila may render the bacteria susceptible to compounds diminishing bacterial virulence and decreasing intracellular survival and replication of this pathogen. The development of a single infection cycle intracellular replication assay using GFP-producing L. pneumophila and Acanthamoebacastellanii amoeba is reported here. This fluorescence-based assay allows for continuous monitoring of intracellular replication rates, revealing the effect of bacterial gene deletions or drug treatment. To examine how perturbations of the host cell affect L. pneumophila replication, several known host-targeting compounds were tested, including modulators of cytoskeletal dynamics, vesicle scission and Ras GTPase localisation. Our results reveal a hitherto unrealized potential antibiotic property of the β-lactone-based Ras depalmitoylation inhibitor palmostatin M, but not the closely related inhibitor palmostatin B. Further characterisation indicated that this compound caused specific growth inhibition of Legionella and Mycobacterium species, suggesting that it may act on a common bacterial target.

  9. Diminished insulin-mediated forearm blood flow and muscle glucose uptake in young men with low birth weight

    DEFF Research Database (Denmark)

    Sonne, M P; Højbjerre, L; Alibegovic, A C

    2009-01-01

    with venous occlusion plethysmography and intra-arterial infusions of adenosine and acetylcholine, before and during a hyperinsulinemic isoglycemic clamp. RESULTS: Forearm blood flow response to systemic hyperinsulinemia was diminished in LBW compared to controls (p

  10. Thoracolumbar spine clearance: Clinical examination for patients with distracting injuries.

    Science.gov (United States)

    Cason, Ben; Rostas, Jack; Simmons, Jon; Frotan, Mohammed A; Brevard, Sidney B; Gonzalez, Richard P

    2016-01-01

    The purpose of this study was to prospectively assess the sensitivity of clinical examination to screen for thoracolumbar spine (TLS) injury in awake and alert blunt trauma patients with distracting injuries. From December 2012 to June 2014, all blunt trauma patients older than 13 years were prospectively evaluated as per standard TLS examination protocol at a Level 1 trauma center. Awake and alert patients with Glasgow Coma Scale (GCS) score of 14 or greater underwent clinical examination of the TLS. Clinical examination was performed regardless of distracting injuries. Patients with no complaints of pain or tenderness on examination of the TLS were considered clinically cleared of injury. Patients with distracting injuries, including those clinically cleared and those with complaints of TLS pain or tenderness, underwent computed tomographic scan of the entire TLS. Patients with minor distracting injuries were not considered to have a distracting injury. A total of 950 blunt trauma patients were entered, 530 (56%) of whom had at least one distracting injury. Two hundred nine patients (40%) with distracting injuries had a positive TLS clinical examination result, of whom 50 (25%) were diagnosed with TLS injury. Three hundred twenty-one patients (60%) with distracting injuries were initially clinically cleared, in whom 17 (5%) TLS injuries were diagnosed. There were no missed injuries that required surgical intervention, with only four injuries receiving TLS orthotic bracing. This yielded an overall clinical clearance sensitivity for injury of 75% and sensitivity for clinically significant injury of 89%. In awake and alert blunt trauma patients with distracting injuries, clinical examination is a sensitive screening method for significant TLS injury. Radiologic assessment may be unnecessary for safe clearance of the asymptomatic TLS in patients with distracting injuries. These findings suggest significant potential reduction of both health care cost and patient

  11. Atorvastatin delays the glucose clearance rate in hypercholesterolemic rabbits.

    Science.gov (United States)

    Cheng, Daxin; Wang, Yanli; Gao, Shoucui; Wang, Xiaojing; Sun, Wentao; Bai, Liang; Cheng, Gong; Chu, Yonglie; Zhao, Sihai; Liu, Enqi

    2015-05-01

    The administration of statin might increase the risk of new-onset diabetes in hypercholesterolemic patients based on the recent clinical evidence. However, the causal relationship must be clarified and confirmed in animal experiments. Therefore, we mimicked hypercholesterolemia by feeding rabbits a high-cholesterol diet (HCD) and performed 16 weeks of atorvastatin administration to investigate the effect of statin on glucose metabolism. The intravenous glucose tolerance test showed that plasma glucose levels in the statin-treated rabbits were consistently higher and that there was a slower rate of glucose clearance from the blood than in HCD rabbits. The incremental area under the curve for glucose in the statin-treated rabbits was also significantly larger than in the HCD rabbits. However, there was no significant difference between the two groups in the intravenous insulin tolerance test. The glucose-lowering ability of exogenous insulin was not impaired by statin treatment in hypercholesterolemic rabbits. The administration of a single dose of statin did not affect glucose metabolism in normal rabbits. The statin also significantly increased the levels of high-density lipoprotein cholesterol, alanine aminotransferase and aspartate transaminase and decreased plasma levels of total cholesterol, triglycerides and low-density lipoprotein cholesterol in the hypercholesterolemic rabbits, whereas it did not affect plasma levels of glucose and insulin. The current results showed that atorvastatin treatment resulted in a significant delay of glucose clearance in hypercholesterolemic rabbits, and this rabbit model could be suitable for studying the effects of statin on glucose metabolism. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  12. Glycoprotein Ibalpha signalling in platelet apoptosis and clearance

    NARCIS (Netherlands)

    van der Wal, E.

    2010-01-01

    Storage of platelets at low temperature reduces bacterial growth and might better preserve the haemostatic function of platelets than current procedures. Incubation at 0C is known to expose ?-N-acetyl-D-glucosamine-residues on glycoprotein (GP)Ibalpha inducing receptor-clustering and platelet

  13. Plasma clearance of noradrenaline does not change with age in normal subjects

    DEFF Research Database (Denmark)

    Hilsted, J; Christensen, N J; Larsen, S

    1985-01-01

    Noradrenaline kinetics (plasma concentrations, plasma clearance and appearance rates) were investigated in seven elderly healthy subjects and in six young healthy subjects. Forearm venous plasma noradrenaline concentrations were higher in the elderly subjects compared with the young subjects....... Plasma clearance of noradrenaline was identical in the two groups. The increase in plasma noradrenaline concentration, with age, probably reflects an increased sympathetic nervous activity....

  14. 76 FR 35069 - Agency Information Collection Activities; Proposed Collection; Comment Request; Generic Clearance...

    Science.gov (United States)

    2011-06-15

    ..., in accordance with the Administration's commitment to improving service delivery. By qualitative... Request; Generic Clearance for the Collection of Qualitative Feedback on Agency Service Delivery AGENCY...): ``Generic Clearance for the Collection of Qualitative Feedback on Agency Service Delivery '' to OMB for...

  15. 77 FR 6128 - Agency Information Collection Activities: Proposed Collection; Comment Request; Generic Clearance...

    Science.gov (United States)

    2012-02-07

    ... Administration's commitment to improving service delivery. By qualitative feedback we mean information that... Collection; Comment Request; Generic Clearance for the Collection of Qualitative Feedback on Agency Service... Collection Request (Generic ICR): ``Generic Clearance for the Collection of Qualitative Feedback on Agency...

  16. 76 FR 25693 - Agency Information Collection Activities: Proposed Collection; Comment Request; Generic Clearance...

    Science.gov (United States)

    2011-05-05

    ... Administration's commitment to improving service delivery. By qualitative feedback we mean information that... Clearance for the Collection of Qualitative Feedback on Agency Service Delivery AGENCY: U.S. Department of...): ``Generic Clearance for the Collection of Qualitative Feedback on Agency Service Delivery'' to OMB for...

  17. 77 FR 15139 - Agency Information Collection Activities: Comment Request; Generic Survey Clearance for the...

    Science.gov (United States)

    2012-03-14

    ..., contracts, and cooperative agreements to colleges, universities, and other eligible institutions, and... Clearance (TOC), NSF primarily uses the data from the EHR Generic Clearance for program planning, management... attainment of NSF's program, project, and strategic goals, and as identified by the President's...

  18. Renal Clearance: Using an Interactive Activity to Visualize a Tricky Concept

    Science.gov (United States)

    Hull, Kerry

    2016-01-01

    Renal clearance, the volume of blood cleared of a substance in a particular time period, is commonly recognized as one of the most difficult concepts in physiology. This difficulty may in part reflect the quantitative nature of renal clearance since many life sciences majors perceive that mathematics is irrelevant to their discipline. Students may…

  19. 32 CFR 644.535 - Support in clearance of Air Force lands.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 4 2010-07-01 2010-07-01 true Support in clearance of Air Force lands. 644.535 Section 644.535 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) REAL... Excess Land and Improvements § 644.535 Support in clearance of Air Force lands. Where Air Force range...

  20. 78 FR 69643 - Proposed Information Collection; Comment Request; Generic Clearance for Customer Satisfaction...

    Science.gov (United States)

    2013-11-20

    ... extension of the generic clearance to conduct customer satisfaction research which may be in the form of... customer satisfaction research efforts. Each research design is reviewed for content, utility, and user... Census Bureau Proposed Information Collection; Comment Request; Generic Clearance for Customer...

  1. 75 FR 38775 - Proposed Information Collection; Comment Request; Generic Clearance for Customer Satisfaction...

    Science.gov (United States)

    2010-07-06

    ...; Generic Clearance for Customer Satisfaction Research AGENCY: U.S. Census Bureau. ACTION: Notice. SUMMARY... Bureau is requesting an extension of the generic clearance to conduct customer satisfaction research... on feedback from its various customer satisfaction research efforts. Each research design is reviewed...

  2. Delayed clearance of serum HBsAg in compensated cirrhosis B

    DEFF Research Database (Denmark)

    Fattovich, G; Giustina, G; Sanchez-Tapias, J

    1998-01-01

    The aim of this study was to evaluate the incidence, prognostic factors and clinical significance of delayed clearance of serum HBsAg in compensated cirrhosis B.......The aim of this study was to evaluate the incidence, prognostic factors and clinical significance of delayed clearance of serum HBsAg in compensated cirrhosis B....

  3. Factors Associated with Spontaneous Clearance of Hepatitis C Virus in Chinese Population

    Directory of Open Access Journals (Sweden)

    Fei Kong

    2014-01-01

    Full Text Available Hepatitis C virus (HCV infections spontaneously clear in approximately 15–45% of infected individuals. Factors which influence spontaneous HCV clearance remain to be identified. The purpose of the present study was to identify variables associated with spontaneous HCV clearance in a referred population of Chinese patients. The prevalence of host, viral, and environmental factors known to influence the outcome of HCV infections was compared in 92 HCV spontaneous clearance subjects and 318 HCV persistent infection subjects. Univariate and multivariate analyses were performed to identify those factors associated with spontaneous HCV clearance. In univariate analysis, female gender, a history of icteric hepatitis, serologic evidence of concurrent HBV infection, and rs12979860 CC genotype were positively associated with spontaneous HCV clearance, while alcohol consumption was negatively associated with clearance. In multivariate analysis, female gender, a history of icteric hepatitis, concurrent HBV infection, and rs12979860 CC genotype remained independent variables associated with spontaneous HCV clearance. Spontaneous HCV clearance is more likely to occur in females, subjects with a history of icteric hepatitis, HBV coinfections, and those with the rs12979860 CC genotype.

  4. Factors affecting lower calyceal stone clearance after Extracorporeal shock wave lithotripsy

    Directory of Open Access Journals (Sweden)

    S. Azab

    2013-03-01

    Conclusions: There is no statistically significant effect of stone size, anatomy of the lower calyx and BMI on stone clearance after ESWL of lower calyceal stones. However, small stone size (≤2 cm, a shorter and wider infundibulum and a larger lower-pole infundibulopelvic angle seem to promote a more rapid and more complete stone clearance.

  5. 78 FR 48076 - Facility Security Clearance and Safeguarding of National Security Information and Restricted Data

    Science.gov (United States)

    2013-08-07

    ... [NRC-2011-0268] RIN 3150-AJ07 Facility Security Clearance and Safeguarding of National Security..., Classified National Security Information. The rule would allow licensees flexibility in determining the means... to 10 CFR part 95. PART 95--FACILITY SECURITY CLEARANCE AND SAFEGUARDING OF NATIONAL SECURITY...

  6. 78 FR 69286 - Facility Security Clearance and Safeguarding of National Security Information and Restricted Data

    Science.gov (United States)

    2013-11-19

    ... COMMISSION 10 CFR Part 95 RIN 3150-AJ07 Facility Security Clearance and Safeguarding of National Security..., Classified National Security Information. In addition, this direct final rule allowed licensees flexibility... required security education training for employees of NRC licensees possessing security clearances so that...

  7. 32 CFR 644.68 - Title Clearance-Certificate of Title and Title Insurance.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 4 2010-07-01 2010-07-01 true Title Clearance-Certificate of Title and Title... (CONTINUED) REAL PROPERTY REAL ESTATE HANDBOOK Acquisition Procurement of Title Evidence, Title Clearance, and Closings § 644.68 Title Clearance—Certificate of Title and Title Insurance. (a) Curative action...

  8. Lithium clearance method and the renal response to low-dose dopamine in man

    DEFF Research Database (Denmark)

    Olsen, N V; Olsen, M H; Fogh-Andersen, N

    1993-01-01

    -induced changes in effective renal plasma flow, glomerular filtration rate or osmolal clearance. Neither lithium nor dopamine influenced plasma concentrations of renin, aldosterone or atrial natriuretic peptide. 4. In conclusion, single test doses of lithium, as normally used in lithium clearance studies...

  9. Measurement of glomerular filtration rate in adults: accuracy of five single-sample plasma clearance methods

    DEFF Research Database (Denmark)

    Rehling, M; Rabøl, A

    1989-01-01

    investigation the total plasma clearance of 51Cr-EDTA (ethylenediaminetetra-acetate) was assessed from 13 blood samples taken 5-300 min post-injection in 44 adult patients with GFR greater than 15 ml min-1. In 34 of these patients the plasma clearance of 99Tcm-DTPA (diethylenetriaminepenta...

  10. 30 CFR 27.36 - Test for adequacy of electrical insulation and clearances.

    Science.gov (United States)

    2010-07-01

    ... Test for adequacy of electrical insulation and clearances. MSHA shall examine, and test in a manner it deems suitable, electrical insulation and clearances between electrical conductors to determine adequacy... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Test for adequacy of electrical insulation and...

  11. 76 FR 61132 - Privacy Act; System of Records: State-77, Country Clearance Records

    Science.gov (United States)

    2011-10-03

    ... disabled. ] RETENTION AND DISPOSAL: Records are disposed of in accordance with published Department of... Act; System of Records: State-77, Country Clearance Records SUMMARY: Notice is hereby given that the Department of State proposes to create a system of records, Country Clearance Records, State-77, pursuant to...

  12. 49 CFR 236.73 - Open-wire transmission line; clearance to other circuits.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Open-wire transmission line; clearance to other... line; clearance to other circuits. Open-wire transmission line operating at voltage of 750 volts or... THE INSTALLATION, INSPECTION, MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES...

  13. 30 CFR 77.807-1 - High-voltage powerlines; clearances above ground.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false High-voltage powerlines; clearances above... OF UNDERGROUND COAL MINES Surface High-Voltage Distribution § 77.807-1 High-voltage powerlines; clearances above ground. High-voltage powerlines located above driveways, haulageways, and railroad tracks...

  14. Combating chronic bacterial infections by manipulating cyclic nucleotide-regulated biofilm formation.

    Science.gov (United States)

    An, Shi-Qi; Ryan, Robert P

    2016-06-01

    Many pathogenic bacteria can form biofilms in clinical settings with major consequences for the progression of infections. Bacterial biofilm communities are typically much more resistant to both antibiotic treatment and clearance by the immune system in comparison to free-living cells. Therefore, drugs that specifically target the formation or maintenance of biofilms would be very valuable additions to current clinical options. Cyclic nucleotide second messengers, in particular cyclic-diguanosine-GMP (c-di-GMP), are now known to play a major role in biofilm formation, and maintenance, in many bacterial species. In this special report, we will review recent progress toward the development of drugs that interfere with c-di-GMP signaling as a route to control biofilm infections. We will focus on the chronic infections associated with the notorious opportunistic pathogen Pseudomonas aeruginosa, although the principles outlined here are also relevant to most bacterial pathogens.

  15. Effect of prior immobilization on muscular glucose clearance in resting and running rats

    DEFF Research Database (Denmark)

    Vissing, J; Ohkuwa, T; Ploug, Thorkil

    1988-01-01

    -induced increase in glucose clearance of red muscles is affected by prior immobilization. The 2-[3H]deoxy-D-glucose (2DG) bolus injection method was used to determine glucose clearance of individual muscles. At rest, glucose clearance was markedly impaired in rats with previously immobilized red muscles compared...... affects steps involved in insulin-mediated action that are not part of contraction-induced glucose uptake and metabolism. Presence of intracellular 2DG shows that separate determination of phosphorylated 2DG is necessary for accurate estimates of glucose metabolism and that accumulation of phosphorylated......In vitro studies have shown that prior disuse impairs the glucose clearance of red skeletal muscle because of a developed insensitivity to insulin. We studied whether an impaired glucose clearance is present in vivo in 42-h immobilized muscles of resting rats and, furthermore, whether the exercise...

  16. Clearance properties of nano-sized particles and molecules as imaging agents: considerations and caveats.

    Science.gov (United States)

    Longmire, Michelle; Choyke, Peter L; Kobayashi, Hisataka

    2008-10-01

    Nanoparticles possess enormous potential as diagnostic imaging agents and hold promise for the development of multimodality agents with both imaging and therapeutic capabilities. Yet, some of the most promising nanoparticles demonstrate prolonged tissue retention and contain heavy metals. This presents serious concerns for toxicity. The creation of nanoparticles with optimal clearance characteristics will minimize toxicity risks by reducing the duration of exposure to these agents. Given that many nanoparticles possess easily modifiable surface and interior chemistry, if nanoparticle characteristics associated with optimal clearance from the body were well established, it would be feasible to design and create agents with more favorable clearance properties. This article presents a thorough discussion of the physiologic aspects of nanoparticle clearance, focusing on renal mechanisms, and provides an overview of current research investigating clearance of specific types of nanoparticles and nano-sized macromolecules, including dendrimers, quantum dots, liposomes and carbon, gold and silica-based nanoparticles.

  17. Physiological stability and renal clearance of ultrasmall zwitterionic gold nanoparticles: Ligand length matters

    Science.gov (United States)

    Ning, Xuhui; Peng, Chuanqi; Li, Eric S.; Xu, Jing; Vinluan, Rodrigo D.; Yu, Mengxiao; Zheng, Jie

    2017-05-01

    Efficient renal clearance has been observed from ultrasmall zwitterionic glutathione-coated gold nanoparticles (GS-AuNPs), which have broad preclinical applications in cancer diagnosis and kidney functional imaging. However, origin of such efficient renal clearance is still not clear. Herein, we conducted head-to-head comparison on physiological stability and renal clearance of two zwitterionic luminescent AuNPs coated with cysteine and glycine-cysteine (Cys-AuNPs and Gly-Cys-AuNPs), respectively. While both of them exhibited similar surface charges and the same core sizes, additional glycine slightly increased the hydrodynamic diameter of the AuNPs by 0.4 nm but significantly enhanced physiological stability of the AuNPs as well as altered their clearance pathways. These studies indicate that the ligand length, in addition to surface charges and size, also plays a key role in the physiological stability and renal clearance of ultrasmall zwitterionic inorganic NPs.

  18. Vest Chest Physiotherapy Airway Clearance is Associated with Nitric Oxide Metabolism

    Directory of Open Access Journals (Sweden)

    Joseph H. Sisson

    2013-01-01

    Full Text Available Background. Vest chest physiotherapy (VCPT enhances airway clearance in cystic fibrosis (CF by an unknown mechanism. Because cilia are sensitive to nitric oxide (NO, we hypothesized that VCPT enhances clearance by changing NO metabolism. Methods. Both normal subjects and stable CF subjects had pre- and post-VCPT airway clearance assessed using nasal saccharin transit time (NSTT followed by a collection of exhaled breath condensate (EBC analyzed for NO metabolites (. Results. VCPT shorted NSTT by 35% in normal and stable CF subjects with no difference observed between the groups. EBC concentrations decreased 68% in control subjects after VCPT (before = 115 ± 32 μM versus after = 37 ± 17 μM; . CF subjects had a trend toward lower EBC . Conclusion. We found an association between VCPT-stimulated clearance and exhaled levels in human subjects. We speculate that VCPT stimulates clearance via increased NO metabolism.

  19. Practical permeability-based hepatic clearance classification system (HepCCS) in drug discovery.

    Science.gov (United States)

    Fan, Peter W; Song, Yang; Berezhkovskiy, Leonid M; Cheong, Jonathan; Plise, Emile G; Khojasteh, S Cyrus

    2014-01-01

    The use of liver microsomes and hepatocytes to predict total in vivo clearance is standard practice in the pharmaceutical industry; however, metabolic stability data alone cannot always predict in vivo clearance accurately. Apparent permeability generated from Mardin-Darby canine kidney cells and rat hepatocyte uptake for 33 discovery compounds were obtained. When there is underprediction of in vivo clearance, compounds with low apparent permeability (less than 3 × 10(-6) cm/s) all exhibited hepatic uptake. A systematic approach in the form of a classification system (hepatic clearance classification system) and decision tree that will help drug discovery scientists understand in vitro-in vivo clearance prediction disconnect early is proposed.

  20. Bacterial Genome Instability

    Science.gov (United States)

    Darmon, Elise

    2014-01-01

    SUMMARY Bacterial genomes are remarkably stable from one generation to the next but are plastic on an evolutionary time scale, substantially shaped by horizontal gene transfer, genome rearrangement, and the activities of mobile DNA elements. This implies the existence of a delicate balance between the maintenance of genome stability and the tolerance of genome instability. In this review, we describe the specialized genetic elements and the endogenous processes that contribute to genome instability. We then discuss the consequences of genome instability at the physiological level, where cells have harnessed instability to mediate phase and antigenic variation, and at the evolutionary level, where horizontal gene transfer has played an important role. Indeed, this ability to share DNA sequences has played a major part in the evolution of life on Earth. The evolutionary plasticity of bacterial genomes, coupled with the vast numbers of bacteria on the planet, substantially limits our ability to control disease. PMID:24600039

  1. Carbohydrate mediated bacterial adhesion.

    Science.gov (United States)

    Pieters, Roland J

    2011-01-01

    In the process of adhesion, bacteria often carry proteins on their surface, adhesins, that bind to specific components of tissue cells or the extracellular matrix. In many cases these components are carbohydrate structures. The carbohydrate binding specificities of many bacteria have been uncovered over the years. The design and synthesis of inhibitors of bacterial adhesion has the potential to create new therapeutics for the prevention and possibly treatment of bacterial infections. Unfortunately, the carbohydrate structures often bind only weakly to the adhesion proteins, although drug design approaches can improve the situation. Furthermore, in some cases linking carbohydrates covalently together, to create so-called multivalent systems, can also significantly enhance the inhibitory potency. Besides adhesion inhibition as a potential therapeutic strategy, the adhesion proteins can also be used for detection. Novel methods to do this are being developed. These include the use of microarrays and glyconanoparticles. New developments in these areas are discussed.

  2. Adult bacterial meningitis

    DEFF Research Database (Denmark)

    Meyer, C N; Samuelsson, I S; Galle, M

    2004-01-01

    Episodes of adult bacterial meningitis (ABM) at a Danish hospital in 1991-2000 were identified from the databases of the Department of Clinical Microbiology, and compared with data from the Danish National Patient Register and the Danish National Notification System. Reduced penicillin susceptibi......Episodes of adult bacterial meningitis (ABM) at a Danish hospital in 1991-2000 were identified from the databases of the Department of Clinical Microbiology, and compared with data from the Danish National Patient Register and the Danish National Notification System. Reduced penicillin...... susceptibility occurred in 21 (23%) of 92 cases of known aetiology, compared to an estimated 6% in nationally notified cases (p treatment was appropriate in 97% of ABM cases in the study population, and in 99.6% of nationally notified cases. The notification rate...... treatment for ABM should not be based exclusively on clinical notification systems with possible unbalanced under-reporting....

  3. Cooperative Bacterial Foraging Optimization

    Directory of Open Access Journals (Sweden)

    Hanning Chen

    2009-01-01

    Full Text Available Bacterial Foraging Optimization (BFO is a novel optimization algorithm based on the social foraging behavior of E. coli bacteria. This paper presents a variation on the original BFO algorithm, namely, the Cooperative Bacterial Foraging Optimization (CBFO, which significantly improve the original BFO in solving complex optimization problems. This significant improvement is achieved by applying two cooperative approaches to the original BFO, namely, the serial heterogeneous cooperation on the implicit space decomposition level and the serial heterogeneous cooperation on the hybrid space decomposition level. The experiments compare the performance of two CBFO variants with the original BFO, the standard PSO and a real-coded GA on four widely used benchmark functions. The new method shows a marked improvement in performance over the original BFO and appears to be comparable with the PSO and GA.

  4. Adaptive Bacterial Foraging Optimization

    OpenAIRE

    Hanning Chen; Yunlong Zhu; Kunyuan Hu

    2011-01-01

    Bacterial Foraging Optimization (BFO) is a recently developed nature-inspired optimization algorithm, which is based on the foraging behavior of E. coli bacteria. Up to now, BFO has been applied successfully to some engineering problems due to its simplicity and ease of implementation. However, BFO possesses a poor convergence behavior over complex optimization problems as compared to other nature-inspired optimization techniques. This paper first analyzes how ...

  5. Bacterial transformation of terpenoids

    Science.gov (United States)

    Grishko, V. V.; Nogovitsina, Y. M.; Ivshina, I. B.

    2014-04-01

    Data on the bacterial transformation of terpenoids published in the literature in the past decade are analyzed. Possible pathways for chemo-, regio- and stereoselective modifications of terpenoids are discussed. Considerable attention is given to new technological approaches to the synthesis of terpenoid derivatives suitable for the use in the perfume and food industry and promising as drugs and chiral intermediates for fine organic synthesis. The bibliography includes 246 references.

  6. Bacterial terpene cyclases.

    Science.gov (United States)

    Dickschat, Jeroen S

    2016-01-01

    Covering: up to 2015. This review summarises the accumulated knowledge about characterised bacterial terpene cyclases. The structures of identified products and of crystallised enzymes are included, and the obtained insights into enzyme mechanisms are discussed. After a summary of mono-, sesqui- and diterpene cyclases the special cases of the geosmin and 2-methylisoborneol synthases that are both particularly widespread in bacteria will be presented. A total number of 63 enzymes that have been characterised so far is presented, with 132 cited references.

  7. [Potentiative effects of noradrenaline on the neurogenic vasoreactivity diminished by cooling].

    Science.gov (United States)

    Iartsev, V N; Karachentseva, O V; Dvoretskiĭ, D P

    2013-08-01

    The effect of 0.03--1.0 μM noradrenaline on the response to electrical field stimulation of the juvenile rat tail artery segment at 36 degrees C and after cooling to 25 degrees C was studied. At 25 degrees C, the neurogenic vasoconstriction was inhibited, but low dose noradrenaline potentiate the constriction. This potentiation was greater at 25 degrees C than at 36 degrees C, following spontaneous decline in the constriction counteracted by noradrenaline. At low temperature, the potentiative effects of noradrenaline were greater at high frequency of electrical field stimulation. The phenomenon of increase in the noradrenaline-evoked potentiation of neurogenic vasoconstriction inhibited by cold may be of importance for thermoregulation. It could provide restoration of diminished effectiveness of the neurogenic contractile signal thus leading to low heat emission at low temperature.

  8. [NORADRENALINE-EVOKED RESTORATION OF THE NEUROGENIC VASOREACTIVITY DIMINISHED BY ACIDOSIS].

    Science.gov (United States)

    Yartsev, V N; Karachentseva, O V

    2015-09-01

    The effect of 0.03-1.0 μM noradrenaline on the neurogenic contractile response to electrical field stimulation of the juvenile rat tail artery segment in control conditions and after the solution pH decrease from 7.4 to 6.6 was studied. Acidosis were shown to inhibit this response significantly at all frequencies of stimulation used (3, 5, 10, and 40 Hz). Noradrenaline potentiated neurogenic vasoconstriction diminished spontaneously or by low pH. The potentiative effect of noradrenaline in acidic solution was more pronounced at higher frequencies of stimulation and noradrenaline concentrations. This phenomenon can, at least in part, account for blood flow redistribution from less important organs to vital ones during exercise which is characterized by acidosis, augmented sympathetic nerve activity and increased levels of noradrenaline.

  9. [Comparative analysis of the potentiative effect of noradrenaline on the neurogenic vasoconstriction diminished by various factors].

    Science.gov (United States)

    Iartsev, V N; Karachentsev, O V; Dvoretskiĭ, D P

    2015-01-01

    The effect of 0.03-1.0 μM noradrenaline on the neurogenic response to electrical field stimulation of the juvenile rat tail artery segment in control conditions, after cooling from 36 to 25 degrees C, and after solution pH decrease from 7.4 to 6.6 was studied. Noradrenaline was shown to potentiate neurogenic vasoconstriction diminished by low temperature or low pH. Decrease in neurogenic vasoconstriction being equal, low dose noradrenaline was most effective at low temperature and high dose noradrenaline was most effective at low pH. 1.0 μM noradrenaline was equally effective in both cases. Increase in the neurogenic tone of the rat tail artery evoked by noradrenaline at low temperature and acidosis may contribute to decrease in heat emission at low ambient temperature in vivo.

  10. Cp/Heph mutant mice have iron-induced neurodegeneration diminished by deferiprone

    Science.gov (United States)

    Zhao, Liangliang; Hadziahmetovic, Majda; Wang, Chenguang; Xu, Xueying; Song, Ying; Jinnah, H.A.; Wodzinska, Jolanta; Iacovelli, Jared; Wolkow, Natalie; Krajacic, Predrag; Weissberger, Alyssa Cwanger; Connelly, John; Spino, Michael; Lee, Michael K.; Connor, James; Giasson, Benoit; Harris, Z. Leah; Dunaief, Joshua L.

    2016-01-01

    Brain iron accumulates in several neurodegenerative diseases and can cause oxidative damage, but mechanisms of brain iron homeostasis are incompletely understood. Patients with mutations in the cellular iron-exporting ferroxidase ceruloplasmin (Cp) have brain iron accumulation causing neurodegeneration. Here, we assessed the brains of mice with combined mutation of Cp and its homolog hephaestin. Compared to single mutants, brain iron accumulation was accelerated in double mutants in the cerebellum, substantia nigra, and hippocampus. Iron accumulated within glia, while neurons were iron deficient. There was loss of both neurons and glia. Mice developed ataxia and tremor, and most died by 9 months. Treatment with the oral iron chelator deferiprone diminished brain iron levels, protected against neuron loss, and extended lifespan. Ferroxidases play important, partially overlapping roles in brain iron homeostasis by facilitating iron export from glia, making iron available to neurons. PMID:26303407

  11. Diminished exercise capacity and mitochondrial bc1 complex deficiency in tafazzin-knockdown mice.

    Directory of Open Access Journals (Sweden)

    Corey ePowers

    2013-04-01

    Full Text Available The phospholipid, cardiolipin, is essential for maintaining mitochondrial structure and optimal function. Cardiolipin-deficiency in humans, Barth syndrome, is characterized by exercise intolerance, dilated cardiomyopathy, neutropenia and 3-methyl-glutaconic aciduria. The causative gene is the mitochondrial acyl-transferase, tafazzin that is essential for remodeling acyl chains of cardiolipin. We sought to determine metabolic rates in tafazzin-deficient mice during resting and exercise, and investigate the impact of cardiolipin deficiency on mitochondrial respiratory chain activities. Tafazzin knockdown in mice markedly impaired oxygen consumption rates during an exercise, without any significant effect on resting metabolic rates. CL-deficiency resulted in significant reduction of mitochondrial respiratory reserve capacity in neonatal cardiomyocytes that is likely to be caused by diminished activity of complex-III, which requires CL for its assembly and optimal activity. Our results may provide mechanistic insights of Barth syndrome pathogenesis.

  12. Diminished electron cloud broadening in a silicon drift detector by sawtooth p{sup +} strips

    Energy Technology Data Exchange (ETDEWEB)

    Sonsky, J.; Valk, H.; Allier, C.P.; Hollander, R.W.; Eijk, C.W.E. van; Sarro, P.M. [Delft Univ. of Technology (Netherlands)

    1999-02-01

    Already in 1993, sawtooth-shaped p{sup +} strips were proposed to diminish lateral diffusion in linear multi-anode silicon drift detectors. The sawtooth structure generates small electric fields directed parallel to the detector surface and perpendicular to the drift direction. These fields confine the drifting electrons within a sawtooth period. In this paper the authors present for the first time experimental proof of the applicability of the concept. For a sawtooth period of 500 {micro}m, the authors have tested the confinement of electron clouds as a function of injected charge up to 5 {times} 10{sup 6} electrons. The maximum number of electrons for which full confinement is achieved has been measured as a function of the potential gutter depth generated by different sawtooth angles.

  13. SAT predicts GPA better for high ability subjects: Implications for Spearman's Law of Diminishing Returns.

    Science.gov (United States)

    Coyle, Thomas; Snyder, Anissa; Pillow, David; Kochunov, Peter

    2011-04-01

    This research examined the predictive validity of the SAT (formerly, the Scholastic Aptitude Test) for high and low ability groups. SAT scores and college GPAs were obtained from the 1997 National Longitudinal Survey of Youth. Subjects were classified as high or low ability by g factor scores from the Armed Services Vocational Aptitude Battery. SAT correlations with GPA were higher for high than low ability subjects. SAT g loadings (i.e., SAT correlations with g) were equivalent for both groups. This is the first study to show that the predictive validity of the SAT varies for ability groups that differ in g. The results contradict a presumption, based on Spearman's Law of Diminishing Returns, that a test's predictive validity should be lower for high ability subjects. Further research is needed to identify factors that contribute to the predictive validity of the SAT for groups that differ in g.

  14. Online Interaction in Higher Education: Is There Evidence of Diminishing Returns?

    Directory of Open Access Journals (Sweden)

    Jonatan Castaño-Muñoz

    2013-12-01

    Full Text Available Online interaction is considered to be a key aspect of effective e-learning and improved academic achievement. However, few studies have examined how effectiveness varies with the degree of interaction intensity. Using data for 17,090 students from three Catalan universities, in this paper we study the productivity associated with five different levels of interaction intensity in learning. We also compare the results obtained for fully online education with those for face-to-face learning. The analyses show that interaction in online education has diminishing returns, while in face-to-face learning it does not do so in a pure way. These results have implications for determining the optimum level of interaction that should be sought when designing courses and educational policies.

  15. A short educational intervention diminishes causal illusions and specific paranormal beliefs in undergraduates.

    Science.gov (United States)

    Barberia, Itxaso; Tubau, Elisabet; Matute, Helena; Rodríguez-Ferreiro, Javier

    2018-01-01

    Cognitive biases such as causal illusions have been related to paranormal and pseudoscientific beliefs and, thus, pose a real threat to the development of adequate critical thinking abilities. We aimed to reduce causal illusions in undergraduates by means of an educational intervention combining training-in-bias and training-in-rules techniques. First, participants directly experienced situations that tend to induce the Barnum effect and the confirmation bias. Thereafter, these effects were explained and examples of their influence over everyday life were provided. Compared to a control group, participants who received the intervention showed diminished causal illusions in a contingency learning task and a decrease in the precognition dimension of a paranormal belief scale. Overall, results suggest that evidence-based educational interventions like the one presented here could be used to significantly improve critical thinking skills in our students.

  16. Diminishing Risk for Age-Related Macular Degeneration with Nutrition: A Current View

    Directory of Open Access Journals (Sweden)

    Allen Taylor

    2013-07-01

    Full Text Available Age-related macular degeneration (AMD is the leading cause of blindness in the elderly. Clinical hallmarks of AMD are observed in one third of the elderly in industrialized countries. Preventative interventions through dietary modification are attractive strategies, because they are more affordable than clinical therapies, do not require specialists for administration and many studies suggest a benefit of micro- and macro-nutrients with respect to AMD with few, if any, adverse effects. The goal of this review is to provide information from recent literature on the value of various nutrients, particularly omega-3 fatty acids, lower glycemic index diets and, perhaps, some carotenoids, with regard to diminishing risk for onset or progression of AMD. Results from the upcoming Age-Related Eye Disease Study (AREDS II intervention trial should be particularly informative.

  17. Factors effective on peritoneal phosphorus transport and clearance in peritoneal dialysis patients
.

    Science.gov (United States)

    Cebeci, Egemen; Gursu, Meltem; Uzun, Sami; Karadag, Serhat; Kazancioglu, Rumeyza; Ozturk, Savas

    2017-02-01

    Transport characteristics of phosphorus are different from other small solutes that are evaluated in routine peritoneal equilibration test (PET) in peritoneal dialysis (PD) patients. We aimed to evaluate peritoneal phosphorus clearance and permeability, and their relationship with peritoneal membrane transport type and creatinine clearance as well as factors affecting peritoneal phosphorus clearance. 70 adult patients on a PD program were included in our study. Phosphorus transport status was classified according to dialysate/plasma (D/P) phosphorus at the 4th hour of PET as slow transporter ( 0.67). We evaluated the relationship of peritoneal phosphorus clearance and transport type with PD regime, phosphorus level, and presence of residual renal function in addition to investigating factors that are effective on peritoneal phosphorus clearance. D/P phosphorus and peritoneal phosphorus clearance were positively correlated with D/P creatinine and peritoneal creatinine clearance, respectively. Automated PD and continuous ambulatory PD patients were similar regarding phosphorus and creatinine clearances and transport status based on D/P phosphorus. The major determinant of peritoneal phosphorus clearance was anuria status. Anuric patients had higher dialysate volume (11.6 ± 3.0 L vs. 8.4 ± 2.1 L, p 2 vs. 48.4 ± 14.0 L/week/1.73 m2, p = 0.001). Hyperphosphatemia was present in 40% and 11% of anuric patients and those with residual renal function, respectively (p = 0.005). Peritoneal phosphorus transport characteristics are similar to that of creatinine. Although increased dialysis dose may increase peritoneal phosphorus clearance, it may be insufficient to prevent hyperphosphatemia in anuric patients.
.

  18. Factors contributing to delay in parasite clearance in uncomplicated falciparum malaria in children

    Directory of Open Access Journals (Sweden)

    Sijuade Abayomi

    2010-02-01

    Full Text Available Abstract Background Drug resistance in Plasmodium falciparum is common in many endemic and other settings but there is no clear recommendation on when to change therapy when there is delay in parasite clearance after initiation of therapy in African children. Methods The factors contributing to delay in parasite clearance, defined as a clearance time > 2 d, in falciparum malaria were characterized in 2,752 prospectively studied children treated with anti-malarial drugs between 1996 and 2008. Results 1,237 of 2,752 children (45% had delay in parasite clearance. Overall 211 children (17% with delay in clearance subsequently failed therapy and they constituted 72% of those who had drug failure, i.e., 211 of 291 children. The following were independent risk factors for delay in parasite clearance at enrolment: age less than or equal to 2 years (Adjusted odds ratio [AOR] = 2.13, 95% confidence interval [CI]1.44-3.15, P 50,000/ul (AOR = 2.21, 95% CI = 1.77-2.75, P 20000/μl a day after treatment began, were independent risk factors for delay in clearance. Non-artemisinin monotherapies were associated with delay in clearance and treatment failures, and in those treated with chloroquine or amodiaquine, with pfmdr 1/pfcrt mutants. Delay in clearance significantly increased gametocyte carriage (P Conclusion Delay in parasite clearance is multifactorial, is related to drug resistance and treatment failure in uncomplicated malaria and has implications for malaria control efforts in sub-Saharan Africa.

  19. Effect of posture on creatinine clearance in late pregnancy and after pregnancy.

    Science.gov (United States)

    Lohsiriwat, Supatra; Imrittha, Nathi

    2008-06-01

    To assess creatinine clearance that indicates glomerular filtration rate (GFR) and to demonstrate the effect of posture on creatinine clearance in late pregnancy compared to the non-pregnant state. Twenty-six healthy pregnant women aged 19-30 years were studied for two sessions, first in their third trimester of pregnancy and then in a non-pregnant state at 6-12 weeks after delivery. In both sessions, creatinine clearance was assessed at three periods: the 24-h baseline, and at the end of 2-h sitting and 2-h lying (in left lateral decubitus position) periods. Urine and blood samples were collected for creatinine clearance measurement. The results showed that the 24-h creatinine clearance in late pregnancy was 28.3% higher than that in the non-pregnant state (122.6 +/- 26.2 vs 95.3 +/- 15.1 mL/min per 1.73 m2, P < 0.001). In late pregnancy, after 2-h sitting, creatinine clearance decreased significantly (10%) compared to the 24-h baseline (122.6 +/- 26.2 vs 110.4 +/- 28.6 mL/min per 1.73 m2, P < 0.001). Creatinine clearance rose back to the high baseline level after the pregnant woman laid in left lateral decubitus for 2 h. The decrease in creatinine clearance during prolonged sitting was not seen in the non-pregnant state. At any posture, the creatinine clearance was always higher in the pregnant state than in the non-pregnant. This study showed that creatinine clearance in late pregnancy was much higher than in the non-pregnant state, and was affected by sitting for up to 2 h. It might be wise for women to lay down in the left lateral decubitus position for a while after many hours of sitting when pregnancy is approaching its term.

  20. Lung Clearance Index and Structural Lung Disease on Computed Tomography in Early Cystic Fibrosis.

    Science.gov (United States)

    Ramsey, Kathryn A; Rosenow, Tim; Turkovic, Lidija; Skoric, Billy; Banton, Georgia; Adams, Anne-Marie; Simpson, Shannon J; Murray, Conor; Ranganathan, Sarath C; Stick, Stephen M; Hall, Graham L

    2016-01-01

    The lung clearance index is a measure of ventilation distribution derived from the multiple-breath washout technique. It has been suggested as a surrogate for chest computed tomography to detect structural lung abnormalities in individuals with cystic fibrosis (CF); however, the associations between lung clearance index and early structural lung disease are unclear. We assessed the ability of the lung clearance index to reflect structural lung disease on the basis of chest computed tomography across the entire pediatric age range. Lung clearance index was assessed in 42 infants (ages 0-2 yr), 39 preschool children (ages 3-6 yr), and 38 school-age children (7-16 yr) with CF before chest computed tomography and in 72 healthy control subjects. Scans were evaluated for CF-related structural lung disease using the Perth-Rotterdam Annotated Grid Morphometric Analysis for Cystic Fibrosis quantitative outcome measure. In infants with CF, lung clearance index is insensitive to structural disease (κ = -0.03 [95% confidence interval, -0.05 to 0.16]). In preschool children with CF, lung clearance index correlates with total disease extent. In school-age children, lung clearance index correlates with extent of total disease, bronchiectasis, and air trapping. In preschool and school-age children, lung clearance index has a good positive predictive value (83-86%) but a poor negative predictive value (50-55%) to detect the presence of bronchiectasis. These data suggest that lung clearance index may be a useful surveillance tool to monitor structural lung disease in preschool and school-age children with CF. However, lung clearance index cannot replace chest computed tomography to screen for bronchiectasis in this population.

  1. Combing bacterial turbulence.

    Science.gov (United States)

    Sokolov, Andrey; Nishiguchi, Daiki; Aronson, Igor

    Living systems represented by ensembles of motile organisms demonstrate a transition from a chaotic motion to a highly ordered state. Examples of such living systems include suspensions of bacteria, schools of fish, flocks of birds and even crowds of people. In spite of significant differences in interacting mechanisms and motion scales, ordered living systems have many similarities: short-range alignment of organism, turbulent-like motion, emergence of large-scale flows and dynamic vortices. In this work, we rectify a turbulent dynamics in suspensions of swimming bacteria Bacillus subtilis by imposing periodical constraints on bacterial motion. Bacteria, swimming between periodically placed microscopic vertical pillars, may self-organize in a stable lattice of vortices. We demonstrate the emergence of a strong anti-ferromagnetic order of bacterial vortices in a rectangular lattice of pillars. Hydrodynamic interaction between vortices increases the stability of an emerged pattern. The highest stability of vortices in the anti-ferromagnetic lattice and the fastest vortices speed were observed in structures with the periods comparable with a correlation length of bacterial unconstrained motion. A.S and I.A were supported by the US DOE, Office of Basic Energy Sciences, Division of Materials Science And Engineering, under contract No. DE AC02-06CH11357 and D.N was supported by ALPS and JSPS Grant No. 26-9915.

  2. Adaptive Bacterial Foraging Optimization

    Directory of Open Access Journals (Sweden)

    Hanning Chen

    2011-01-01

    Full Text Available Bacterial Foraging Optimization (BFO is a recently developed nature-inspired optimization algorithm, which is based on the foraging behavior of E. coli bacteria. Up to now, BFO has been applied successfully to some engineering problems due to its simplicity and ease of implementation. However, BFO possesses a poor convergence behavior over complex optimization problems as compared to other nature-inspired optimization techniques. This paper first analyzes how the run-length unit parameter of BFO controls the exploration of the whole search space and the exploitation of the promising areas. Then it presents a variation on the original BFO, called the adaptive bacterial foraging optimization (ABFO, employing the adaptive foraging strategies to improve the performance of the original BFO. This improvement is achieved by enabling the bacterial foraging algorithm to adjust the run-length unit parameter dynamically during algorithm execution in order to balance the exploration/exploitation tradeoff. The experiments compare the performance of two versions of ABFO with the original BFO, the standard particle swarm optimization (PSO and a real-coded genetic algorithm (GA on four widely-used benchmark functions. The proposed ABFO shows a marked improvement in performance over the original BFO and appears to be comparable with the PSO and GA.

  3. Vision-guided ocular growth in a mutant chicken model with diminished visual acuity.

    Science.gov (United States)

    Ritchey, Eric R; Zelinka, Christopher; Tang, Junhua; Liu, Jun; Code, Kimberly A; Petersen-Jones, Simon; Fischer, Andy J

    2012-09-01

    Visual experience is known to guide ocular growth. We tested the hypothesis that vision-guided ocular growth is disrupted in a model system with diminished visual acuity. We examine whether ocular elongation is influenced by form-deprivation (FD) and lens-imposed defocus in the Retinopathy, Globe Enlarged (RGE) chicken. Young RGE chicks have poor visual acuity, without significant retinal pathology, resulting from a mutation in guanine nucleotide-binding protein β3 (GNB3), also known as transducin β3 or Gβ3. The mutation in GNB3 destabilizes the protein and causes a loss of Gβ3 from photoreceptors and ON-bipolar cells (Ritchey et al., 2010). FD increased ocular elongation in RGE eyes in a manner similar to that seen in wild-type (WT) eyes. By comparison, the excessive ocular elongation that results from hyperopic defocus was increased, whereas myopic defocus failed to significantly decrease ocular elongation in RGE eyes. Brief daily periods of unrestricted vision interrupting FD prevented ocular elongation in RGE chicks in a manner similar to that seen in WT chicks. Glucagonergic amacrine cells differentially expressed the immediate early gene Egr1 in response to growth-guiding stimuli in RGE retinas, but the defocus-dependent up-regulation of Egr1 was lesser in RGE retinas compared to that of WT retinas. We conclude that high visual acuity, and the retinal signaling mediated by Gβ3, is not required for emmetropization and the excessive ocular elongation caused by FD and hyperopic defocus. However, the loss of acuity and Gβ3 from RGE retinas causes enhanced responses to hyperopic defocus and diminished responses to myopic defocus. Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. Lumbar Radiculopathy Confounded: Total Knee Arthroplasty Diminishes the Patellar Tendon Reflex.

    Science.gov (United States)

    McNabb, David Clinton; Olcott, Christopher W; Del Gaizo, Daniel J; Vaughn, Bradley K; Lim, Moe R

    2015-12-01

    Patellar tendon reflexes were elicited among patients who had had a unilateral total knee replacement, those planned for unilateral total knee replacement, and a cohort of controlled patients. Patellar tendon reflex (PTR) response was measured with surface electromyography. The aim of this study was to determine if total knee arthroplasty significantly alters the PTR. As part of the clinical evaluation of the spine, extremity reflexes are provoked. Reflex variation between right and left extremities can be a pathological finding in disease of the spine. It has been noted that in patients who have undergone total knee arthroplasty (TKA), the PTR is diminished on the operative side compared with the contralateral nonoperative side. PTR is part of the clinical exam when evaluating a patient for lumbar radiculopathy. The right and left patellar tendon reflex intensities were measured by quadriceps surface electromyography in 3 groups of patients. Group 1 consisted of 21 patients with unilateral TKA who were at least 6 months postoperative. Group 2 consisted of 18 patients with unilateral severe knee arthritis indicated for TKA. Group 3, serving as the control group, included 20 patients with no evidence of knee arthritis in either knee. The average reflex response for each group was recorded and comparisons were then made between each group. Patients who have undergone unilateral TKA have a PTR on average of 55.1% of their contralateral uninvolved side. This is statistically significant when compared with reflexes in patients who are planned for unilateral total knee arthroplasty, 96.03% (P = 0.001) and when compared with patients without evidence for knee arthritis, 102.2% (P < 0.001). The results of this case control study show that TKAs do significantly diminish PTRs when compared with a contralateral uninvolved knee in the same patient. 3.

  5. Diminished adrenal sensitivity to endogenous and exogenous adrenocorticotropic hormone in critical illness: a prospective cohort study.

    Science.gov (United States)

    de Jong, Margriet F C; Molenaar, Nienke; Beishuizen, Albertus; Groeneveld, A B Johan

    2015-01-06

    Adrenal dysfunction may represent critical illness-related corticosteroid insufficiency (CIRCI), as evidenced by a diminished cortisol response to exogenous adrenocorticotropic hormone (ACTH), but this concept and its clinical significance remain highly controversial. We studied the adrenal response to exogenous ACTH as a function of the endogenous cortisol-to-ACTH ratio, a measure of adrenal sensitivity, and of clinical variables, during critical illness and recovery from the acute phase. We prospectively included 59 consecutive septic and nonseptic patients in the intensive care unit with treatment-insensitive hypotension in whom CIRCI was suspected; patients having received etomidate and prolonged corticosteroids were excluded. An ACTH test (250 μg) was performed, followed by a second test after ≥7 days in acute-phase survivors. Serum total and free cortisol, ACTH, and clinical variables were assessed. Patients were divided according to responses (delta, Δ) of cortisol to ACTH at the first and second tests. Patients with low (cortisol (n = 14 to 17) had higher baseline cortisol and ACTH but lower cortisol/ACTH ratios than patients with a normal Δ cortisol (≥250 nM) in the course of time. A low Δ cortisol in time was associated with more-severe disease, culture-positive sepsis, and prolonged activated prothrombin time. Results for free cortisol were similar. Even though the pituitary-adrenal axis is activated after stress during critical illness, diminished adrenal sensitivity to endogenous ACTH predicts a low increase of cortisol to exogenous ACTH, suggesting adrenal dysfunction, irrespective of the stage of disease. The data further suggest a role of disease severity and culture-positive sepsis.

  6. Diminished pulmonary function in pectus excavatum: from denying the problem to finding the mechanism.

    Science.gov (United States)

    Kelly, Robert E; Obermeyer, Robert J; Nuss, Donald

    2016-09-01

    Recently, technical improvement in the ability to measure lung function and the severity of chest deformity have enabled progress in understanding the mechanism of limitations of lung function in pectus excavatum. After establishing that most patients with pectus excavatum do have symptoms of exercise intolerance, easy fatigability, and shortness of breath with exertion, lung function has been evaluated by a variety of methods in different centers. Spirometry, plethysmography, exercise testing, oculo electronic plethysmography, and imaging methods have been used to assess lung function in pectus excavatum and its response to surgery. Not all patients with pectus excavatum have subnormal static pulmonary function testing; some have above-average values. However, in more than 1500 adult and pediatric surgical patients with anatomically severe pectus excavatum at a single center, the bell curve of FVC, FEV1, and FEF 25-75 is shifted to significantly lower values in pectus excavatum. The curve is shifted to higher values after operation by approximately one standard deviation. Previous work has demonstrated that patients with more anatomically severe pectus excavatum are more likely to have diminished PFT's. A mechanism for this effect is seen by oculo electronic plethysmography, which demonstrates that the depressed portion of the chest does not move on respiration. After Nuss procedure, the chest wall motion used to create suction to draw air into the lungs is indistinguishable from that of persons with a normal chest, and the intrathoracic volume is markedly increased. Pectus excavatum is accompanied in most patients by diminished static pulmonary function. Correction by Nuss procedure results in improvement in chest wall motion; this improvement in the thoracic bellows action is accompanied by improvement in pulmonary function testing.

  7. Selfishness and altruism can coexist when help is subject to diminishing returns.

    Science.gov (United States)

    Sibly, R M; Curnow, R N

    2011-08-01

    Altruism and selfishness are 30-50% heritable in man in both Western and non-Western populations. This genetically based variation in altruism and selfishness requires explanation. In non-human animals, altruism is generally directed towards relatives, and satisfies the condition known as Hamilton's rule. This nepotistic altruism evolves under natural selection only if the ratio of the benefit of receiving help to the cost of giving it exceeds a value that depends on the relatedness of the individuals involved. Standard analyses assume that the benefit provided by each individual is the same but it is plausible in some cases that as more individuals contribute, help is subject to diminishing returns. We analyse this situation using a single-locus two-allele model of selection in a diploid population with the altruistic allele dominant to the selfish allele. The analysis requires calculation of the relationship between the fitnesses of the genotypes and the frequencies of the genes. The fitnesses vary not only with the genotype of the individual but also with the distribution of phenotypes amongst the sibs of the individual and this depends on the genotypes of his parents. These calculations are not possible by direct fitness or ESS methods but are possible using population genetics. Our analysis shows that diminishing returns change the operation of natural selection and the outcome can now be a stable equilibrium between altruistic and selfish alleles rather than the elimination of one allele or the other. We thus provide a plausible genetic model of kin selection that leads to the stable coexistence in the same population of both altruistic and selfish individuals. This may explain reported genetic variation in altruism in man.

  8. Acute pancreatitis in mice impairs bacterial clearance from the lungs, whereas concurrent pneumonia prolongs the course of pancreatitis

    NARCIS (Netherlands)

    van Westerloo, David J.; Schultz, Marcus J.; Bruno, Marco J.; de Vos, Alex F.; Florquin, Sandrine; van der Poll, Tom

    2004-01-01

    Objective: Nosocomial pneumonia is a feared complication in the critically ill patient. Serious acute pancreatitis is frequently complicated by infections. The objectives of this study were to determine the influence of acute pancreatitis on host defense against Pseudomonas pneumonia and to

  9. Anti-Pseudomonas aeruginosa IgY antibodies augment bacterial clearance in a murine pneumonia model

    DEFF Research Database (Denmark)

    Thomsen, K.; Christophersen, L.; Bjarnsholt, T.

    2016-01-01

    Background: Oral prophylactic therapy by gargling with pathogen-specific egg yolk immunoglobulins (IgY) may reduce the initial airway colonization with Pseudomonas aeruginosa in cystic fibrosis (CF) patients. IgY antibodies impart passive immunization and we investigated the effects of anti...

  10. IL-10-deficient mice demonstrate multiple organ failure and increased mortality during Escherichia coli peritonitis despite an accelerated bacterial clearance

    NARCIS (Netherlands)

    Sewnath, M. E.; Olszyna, D. P.; Birjmohun, R.; ten Kate, F. J.; Gouma, D. J.; van der Poll, T.

    2001-01-01

    To determine the role of endogenous IL-10 in local antibacterial host defense and in the development of a systemic inflammatory response syndrome during abdominal sepsis, IL-10 gene-deficient (IL-10(-/-)) and wild-type (IL-10(+/+)) mice received an i.p. injection with Escherichia coli. Peritonitis

  11. Oscillating devices for airway clearance in people with cystic fibrosis.

    Science.gov (United States)

    Morrison, Lisa; Innes, Stephanie

    2017-05-04

    Chest physiotherapy is widely prescribed to assist the clearance of airway secretions in people with cystic fibrosis. Oscillating devices generate intra- or extra-thoracic oscillations orally or external to the chest wall. Internally they create variable resistances within the airways, generating controlled oscillating positive pressure which mobilises mucus. Extra-thoracic oscillations are generated by forces outside the respiratory system, e.g. high frequency chest wall oscillation. This is an update of a previously published review. To identify whether oscillatory devices, oral or chest wall, are effective for mucociliary clearance and whether they are equivalent or superior to other forms of airway clearance in the successful management of secretions in people with cystic fibrosis. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and hand searches of relevant journals and abstract books of conference proceedings. Latest search of the Cystic Fibrosis Trials Register: 27 April 2017.In addition we searched the trials databases ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform. Latest search of trials databases: 26 April 2017. Randomised controlled studies and controlled clinical studies of oscillating devices compared with any other form of physiotherapy in people with cystic fibrosis. Single-treatment interventions (therapy technique used only once in the comparison) were excluded. Two authors independently applied the inclusion criteria to publications and assessed the quality of the included studies. The searches identified 76 studies (302 references); 35 studies (total of 1138 participants) met the inclusion criteria. Studies varied in duration from up to one week to one year; 20 of the studies were cross-over in design. The studies also varied in type of intervention and the outcomes measured, data were not

  12. Rapid and Profound Shifts in the Vaginal Microbiota Following Antibiotic Treatment for Bacterial Vaginosis.

    Science.gov (United States)

    Mayer, Bryan T; Srinivasan, Sujatha; Fiedler, Tina L; Marrazzo, Jeanne M; Fredricks, David N; Schiffer, Joshua T

    2015-09-01

    Bacterial vaginosis (BV) is a common polymicrobial disease associated with numerous negative reproductive health outcomes, including an increased risk of human immunodeficiency virus acquisition. BV is treatable with antibiotics, but relapse is common. A more detailed understanding of bacterial dynamics during antibiotic therapy for BV could identify conditions that favor establishment, maintenance, and eradication of BV-associated bacterial species, thereby improving treatment outcomes. We used mathematical models to analyze daily quantitative measurements of 11 key bacterial species during metronidazole treatment for 15 cases of BV. We identified complete reorganization of vaginal bacterial composition within a day of initiating therapy. Although baseline bacterial levels predicted a longer time to clearance, all anaerobic species were eliminated rapidly within a median of 3 days. However, reemergence of BV-associated species was common following treatment cessation. Gardnerella vaginalis, a facultative anaerobe, was cleared more slowly than anaerobic BV-associated species, and levels of G. vaginalis often rebounded during treatment. We observed gradual Lactobacillus species growth, indicating that untargeted microbes fill the transient vacuum formed during treatment. Under antibiotic pressure, the human microbiome can undergo rapid shifts on a scale of hours. When treatment is stopped, BV-associated bacteria quickly reemerge, suggesting a possible role for intermittent prophylactic treatment. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  13. Numerical Investigation of Pressure Fluctuation Characteristics in a Centrifugal Pump with Variable Axial Clearance

    Directory of Open Access Journals (Sweden)

    Lei Cao

    2016-01-01

    Full Text Available Clearance flows in the sidewall gaps of centrifugal pumps are unsteady as well as main flows in the volute casing and impeller, which may cause vibration and noise, and the corresponding pressure fluctuations are related to the axial clearance size. In this paper, unsteady numerical simulations were conducted to predict the unsteady flows within the entire flow passage of a centrifugal pump operating in the design condition. Pressure fluctuation characteristics in the volute casing, impeller, and sidewall gaps were investigated with three axial clearance sizes. Results show that an axial clearance variation affects the pressure fluctuation characteristics in each flow domain by different degree. The greatest pressure fluctuation occurs at the blade pressure surface and is almost not influenced by the axial clearance variation which has a certainly effect on the pressure fluctuation characteristics around the tongue. The maximum pressure fluctuation amplitude in the sidewall gaps is larger than that in the volute casing, and different spectrum characteristics show up in the three models due to the interaction between the clearance flow and the main flow as well as the rotor-stator interaction. Therefore, clearance flow should be taken into consideration in the hydraulic design of centrifugal pumps.

  14. Airway clearance techniques used by people with cystic fibrosis in the UK.

    Science.gov (United States)

    Hoo, Z H; Daniels, T; Wildman, M J; Teare, M D; Bradley, J M

    2015-12-01

    To describe the current use of airway clearance techniques among people with cystic fibrosis (CF) in the UK, and the baseline characteristics for users of different airway clearance techniques. Analysis of the UK CF Registry 2011 data. All people with CF in the UK aged ≥11 years (n=6372). Of the 6372 people on the UK CF registry in 2011, 89% used airway clearance techniques. The most commonly used primary techniques were forced expiratory techniques (28%) and oscillating positive expiratory pressure (PEP) (23%). Postural drainage and high-frequency chest wall oscillation were used by 4% and 1% of people with CF, respectively. The male:female ratio of individuals who used exercise as their primary airway clearance technique was 2:1, compared with 1:1 for other techniques. Individuals with more severe lung disease tended to use devices such as non-invasive ventilation or high-frequency chest wall oscillation. Forced expiratory techniques and oscillating PEP are the most common airway clearance techniques used by people with CF in the UK, and postural drainage and high-frequency chest wall oscillation are the least common techniques. This is significant in terms of planning airway clearance technique trials, where postural drainage has been used traditionally as the comparator. The use of airway clearance techniques varies between countries, but the reasons for these differences are unknown. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

  15. A bodyweight-dependent allometric exponent for scaling clearance across the human life-span.

    Science.gov (United States)

    Wang, Chenguang; Peeters, Mariska Y M; Allegaert, Karel; Blussé van Oud-Alblas, Heleen J; Krekels, Elke H J; Tibboel, Dick; Danhof, Meindert; Knibbe, Catherijne A J

    2012-06-01

    To explore different allometric equations for scaling clearance across the human life-span using propofol as a model drug. Data from seven previously published propofol studies ((pre)term neonates, infants, toddlers, children, adolescents and adults) were analysed using NONMEM VI. To scale clearance, a bodyweight-based exponential equation with four different structures for the exponent was used: (I) 3/4 allometric scaling model; (II) mixture model; (III) bodyweight-cut-point separated model; (IV) bodyweight-dependent exponent model. Model I adequately described clearance in adults and older children, but overestimated clearance of neonates and underestimated clearance of infants. Use of two different exponents in Model II and Model III showed significantly improved performance, but yielded ambiguities on the boundaries of the two subpopulations. This discontinuity was overcome in Model IV, in which the exponent changed sigmoidally from 1.35 at a hypothetical bodyweight of 0 kg to a value of 0.56 from 10 kg onwards, thereby describing clearance of all individuals best. A model was developed for scaling clearance over the entire human life-span with a single continuous equation, in which the exponent of the bodyweight-based exponential equation varied with bodyweight.

  16. Modelling of Outer and Inner Film Oil Pressure for Floating Ring Bearing Clearance in Turbochargers

    Science.gov (United States)

    Zhang, Hao; Shi, Zhanqun; Gu, Fengshou; Ball, Andrew

    2011-07-01

    Floating ring bearing is widely used in turbochargers to undertake the extreme condition of high rotating speed and high operating temperature. It is also the most concerned by the designers and users alike due to its high failure rate and high maintenance cost. Any little clearance change may result in oil leakage, which in turn cause blue smoke or black smoke according to leakage types. However, there is no condition monitoring of this bearing because it is almost impossible to measure the clearance especially the inner clearance, in which the inner oil film directly bears the high speed rotation. In stead of measuring clearance directly, this paper has proposed a method that uses film pressure as a measure to monitor the bearing clearance and its variation. A non-linear mathematical model is developed by using Reynolds equations with non-linear oil film pressure. A full description of the outer and inner film is provided along both axial and radial directions. A numerical simulation is immediately carried out. Variable clearance changes are investigated using the mathematical model. Results show the relationship between clearance and film pressure.

  17. Predictive value of the efficacy of tolvaptan in liver cirrhosis patients using free water clearance.

    Science.gov (United States)

    Miyaaki, Hisamitsu; Nakamura, Yutaka; Ichikawa, Tatsuki; Taura, Naota; Miuma, Satoshi; Shibata, Hidetaka; Honda, Takuya; Nakao, Kazuhiko

    2015-11-01

    Tolvaptan, an arginine vasopressin V2 antagonist, is available for patients with refractory ascites. Free water clearance was evaluated as a predictor of tolvaptan efficacy. Twenty-one patients with refractory ascites were enrolled in the present study. Liver function test, renal function test, urine volume, free water clearance and osmotic pressure were measured at baseline (day 0) and for each dose of tolvaptan (1.875, 3.75 and 7.5 mg), and compared for efficacy. Tolvaptan increased urine volume and free water clearance decreased osmotic pressure at each dose of tolvaptan, compared to pretreatment levels. Compared to baseline, an increased volume of free water clearance at 1.875 mg of tolvaptan showed a significant correlation with body weight reduction (r=0.480 and P=0.028). Any factors (age, liver function test and renal function test) at pretreatment showed no significant correlation with body weight reduction. An increased volume of urine and osmotic pressure at each dose was not significantly correlated with the tolvaptan effect. Compared to baseline, an increased volume of free water clearance at 1.875 mg of tolvaptan in responders was significantly increased, compared to non-responders (270±241 ml/day: 27±257 ml/day; P=0.042). In conclusion, an increased volume of free water clearance on day 1 was significantly associated with body weight reduction. Free water clearance could be a simple and useful marker for the prediction of tolvaptan efficacy.

  18. Effect of clearance on cartilage tribology in hip hemi-arthroplasty.

    Science.gov (United States)

    Lizhang, Jia; Taylor, Simon D; Jin, Zhongmin; Fisher, John; Williams, Sophie

    2013-12-01

    Hemi-arthroplasty of the hip (an artificial femoral head articulating against the natural acetabulum) is used to treat fractured necks of femur; however, there is evidence that articulation causes erosion of the cartilage, resulting in pain for the patient. Parameters that may influence this cartilage erosion include head material and roughness, clearance between the head and acetabulum and activity levels of the patient. This study has assessed the effect of clearance of hemi-arthroplasty articulations on the contact stress, friction and cartilage deformation in an in vitro tribological simulation of the hemi-arthroplasty joint that applied dynamic loads and motion. It has been demonstrated that peak contact stress increased from 5.6 to 10.6 MPa as radial clearance increased from small (1.8 mm). In all samples, friction factor increased with time and was significantly less with extra-large clearances compared to small (<0.6 mm), medium (0.6-1.2 mm) and large (1.2-1.8 mm) clearances. The cartilage deformation observed was significantly greater in acetabulum samples paired to give small or extra-large clearances compared to those with medium or large clearances.

  19. Radiology of bacterial pneumonia

    Energy Technology Data Exchange (ETDEWEB)

    Vilar, Jose E-mail: vilar_jlu@gva.es; Domingo, Maria Luisa; Soto, Cristina; Cogollos, Jonathan

    2004-08-01

    Bacterial pneumonia is commonly encountered in clinical practice. Radiology plays a prominent role in the evaluation of pneumonia. Chest radiography is the most commonly used imaging tool in pneumonias due to its availability and excellent cost benefit ratio. CT should be used in unresolved cases or when complications of pneumonia are suspected. The main applications of radiology in pneumonia are oriented to detection, characterisation and follow-up, especially regarding complications. The classical classification of pneumonias into lobar and bronchial pneumonia has been abandoned for a more clinical classification. Thus, bacterial pneumonias are typified into three main groups: Community acquired pneumonia (CAD), Aspiration pneumonia and Nosocomial pneumonia (NP).The usual pattern of CAD is that of the previously called lobar pneumonia; an air-space consolidation limited to one lobe or segment. Nevertheless, the radiographic patterns of CAD may be variable and are often related to the causative agent. Aspiration pneumonia generally involves the lower lobes with bilateral multicentric opacities. Nosocomial Pneumonia (NP) occurs in hospitalised patients. The importance of NP is related to its high mortality and, thus, the need to obtain a prompt diagnosis. The role of imaging in NP is limited but decisive. The most valuable information is when the chest radiographs are negative and rule out pneumonia. The radiographic patterns of NP are very variable, most commonly showing diffuse multifocal involvement and pleural effusion. Imaging plays also an important role in the detection and evaluation of complications of bacterial pneumonias. In many of these cases, especially in hospitalised patients, chest CT must be obtained in order to better depict these associate findings.

  20. Bacterial mitotic machineries

    DEFF Research Database (Denmark)

    Gerdes, Kenn; Møller-Jensen, Jakob; Ebersbach, Gitte

    2004-01-01

    Here, we review recent progress that yields fundamental new insight into the molecular mechanisms behind plasmid and chromosome segregation in prokaryotic cells. In particular, we describe how prokaryotic actin homologs form mitotic machineries that segregate DNA before cell division. Thus, the Par......M protein of plasmid R1 forms F actin-like filaments that separate and move plasmid DNA from mid-cell to the cell poles. Evidence from three different laboratories indicate that the morphogenetic MreB protein may be involved in segregation of the bacterial chromosome....

  1. Can calcium ionophore "use" in patients with diminished ovarian reserve increase fertilization and pregnancy rates? A randomized, controlled study.

    Science.gov (United States)

    Caglar Aytac, Pinar; Kilicdag, Esra Bulgan; Haydardedeoglu, Bulent; Simsek, Erhan; Cok, Tayfun; Parlakgumus, Huriye Ayse

    2015-11-01

    To determine whether calcium ionophore solution can improve the fertilization rate in patients with diminished ovarian reserve whose partners have normal sperm parameters. Between January 2014 and August 2014, patients with diminished ovarian reserve were randomized to make artificial oocyte activation with calcium ionophore solution. University hospital. A total of 296 patients who had diminished ovarian reserve and partners with normal sperm parameters were included in the study. Metaphase 2 oocytes were treated with calcium ionophore solution (GM508 Cult-Active) for 15 minutes just after intracytoplasmic sperm injection. Fertilization rate, implantation rate, clinical pregnancy rate, ongoing pregnancy rate. Fertilization, implantation, pregnancy, and ongoing pregnancy rates for the calcium ionophore and control groups were 60.7% and 55.4%, 12.8% and 10.7%, 21% and 12.8%, and 10.9% and 6.1%, respectively. This is the first prospective, randomized, controlled study to analyze the effect of calcium ionophore solution on fertilization rate in patients with diminished ovarian reserve. We did not observe any differences in fertilization, clinical pregnancy, or ongoing pregnancy rates between the groups. We propose that fertilization ratios could not be increased by artificial oocyte activation via application of calcium ionophore solution in patients with diminished ovarian reserve. NCT02045914. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  2. Application of numerical method in calculating the internal rate of return of joint venture investment using diminishing musyarakah model

    Science.gov (United States)

    Ruslan, Siti Zaharah Mohd; Jaffar, Maheran Mohd

    2017-05-01

    Islamic banking in Malaysia offers variety of products based on Islamic principles. One of the concepts is a diminishing musyarakah. The concept of diminishing musyarakah helps Muslims to avoid transaction which are based on riba. The diminishing musyarakah can be defined as an agreement between capital provider and entrepreneurs that enable entrepreneurs to buy equity in instalments where profits and losses are shared based on agreed ratio. The objective of this paper is to determine the internal rate of return (IRR) for a diminishing musyarakah model by applying a numerical method. There are several numerical methods in calculating the IRR such as by using an interpolation method and a trial and error method by using Microsoft Office Excel. In this paper we use a bisection method and secant method as an alternative way in calculating the IRR. It was found that the diminishing musyarakah model can be adapted in managing the performance of joint venture investments. Therefore, this paper will encourage more companies to use the concept of joint venture in managing their investments performance.

  3. Vitamin D Levels in Patients with Autoimmune Thyroiditis with Diminished Thyroid Function

    Directory of Open Access Journals (Sweden)

    V.V. Povoroznyuk

    2014-08-01

    Full Text Available The study examined vitamin D levels in 75 patients with autoimmune thyroiditis (AIT with diminished thyroid function. The objective of the study — to determine the content of 25(OHD in patients with overt and subclinical hypothyroidism on the background of AIT. Materials and Methods. 75 patients (59 women and 16 men and 25 apparently healthy subjects (matched for age and sex were followed. The levels of thyroid stimulating hormone (TSH, free thyroxine (fT4, free triiodothyronine (fT3, antibodies to thyroid peroxidase (TPO, and the content of 25(OHD in the blood serum were determined. Results. Patients with AІT were divided according to the levels of TSH and thyroid hormones into the group with subclinical (n = 21 and overt (n = 54 hypothyroidism. TSH level was significantly higher in the group with subclinical (6.80 ± 1.84 mcU/ml and overt hypothyroidism (11.38 ± 2.16 mcU/ml compared with the control group (2.11 ± 0.37 mcU/ml (p < 0.05. The level of antibodies to TPO was 312.83 ± 7.19 U/ml in subclinical hypothyroidism and 546.29 ± 9.81 U/ml — in overt hypothyroidism. 25(OHD level in blood serum was significantly lower in subclinical (18.8 ± 1.2 nmol/l and overt hypothyroidism (21.7 ± 1.3 nmol/l compared with the control group (27.3 ± 1.4 nmol/l (p < 0.05. Highly reliable negative correlation was established between the level of TSH, antibodies to TPO and vitamin D (p < 0.001. Also highly reliable positive correlation was established between the levels of serum 25(OHD and fT4 content (p < 0.001, between TSH and TPO antibody levels (p < 0.05. Conclusions. Vitamin D deficiency is combined with the presence of AIT with diminished thyroid function (in subclinical and overt hypothyroidism. Further studies are needed to determine vitamin D deficiency as a causal factor of AIT.

  4. Evaluation of terrain geomorphometric characteristics for ground clearance charts production

    Directory of Open Access Journals (Sweden)

    Mirko A. Borisov

    2011-01-01

    Full Text Available Geomorphometric exploration applied in the military terrain analysis is based on the GIS methodology of spatial analyses and is related primarily to military terrain analyses. It includes relief assessment aiming at producing ground clearance charts for the analysis of terrain maneuverability and its deployment, cover and concealment possibilities. An evaluation analysis of geomorphological parameters was performed for the Avala test area using a few terrain parameters (visibility, terrain aspect and slope as well as some terrain qualitative categories (e.g. vegetation density. Terrain slope Slope and aspect are morphometric terrain parameters that can be derived directly from the DTM using some GIS operations. Slope is the first derivative of a surface and has both magnitude and direction. Slope is perhaps the most important aspect of the surface form, since surfaces are formed completely of slopes, and slope angles control the gravitational force available for geomorphic work. Mathematically, the tangent of the slope angle is the first derivative of altitude, and it is a tangent or percent slope as this surface parameter is generally referred to. Slope is defined at each point as the slope of a plane tangent to the surface at that point. In practice, however, slope is generally measured over a finite distance, especially when data are obtained from a contour map. Terrain aspect Aspect is also the first derivative of a surface and has both magnitude and direction. The term aspect is defined as the direction of the biggest slope vector on the tangent plane projected onto the horizontal plane. Aspect is the bearing (or azimuth of the slope direction, and its angle ranges from 0 to 360°. Analyses of terrain slope and ground clearance for military forces The analysis of land assessment of the Avala test area included the definition of relief categories in relation to cover and concealment purposes with the aim to include the geomorphological basis

  5. Mechanism of hard nanomaterial clearance by the liver

    Science.gov (United States)

    Tsoi, Kim M.; MacParland, Sonya A.; Ma, Xue-Zhong; Spetzler, Vinzent N.; Echeverri, Juan; Ouyang, Ben; Fadel, Saleh M.; Sykes, Edward A.; Goldaracena, Nicolas; Kaths, Johann M.; Conneely, John B.; Alman, Benjamin A.; Selzner, Markus; Ostrowski, Mario A.; Adeyi, Oyedele A.; Zilman, Anton; McGilvray, Ian D.; Chan, Warren C.W.

    2016-01-01

    The liver and spleen are major biological barriers to translating nanomedicines because they sequester the majority of administered nanomaterials and prevent delivery to diseased tissue. Here we examined the blood clearance mechanism of administered hard nanomaterials in relation to blood flow dynamics, organ microarchitecture, and cellular phenotype. We found that nanomaterial velocity reduces 1000-fold as they enter and traverse the liver, leading to 7.5 times more nanomaterial interaction with hepatic cells relative to peripheral cells. In the liver, Kupffer cells (84.8%±6.4%), hepatic B cells (81.5±9.3%), and liver sinusoidal endothelial cells (64.6±13.7%) interacted with administered PEGylated quantum dots but splenic macrophages took up less (25.4±10.1%) due to differences in phenotype. The uptake patterns were similar for two other nanomaterial types and five different surface chemistries. Potential new strategies to overcome off-target nanomaterial accumulation may involve manipulating intra-organ flow dynamics and modulating cellular phenotype to alter hepatic cell interaction. PMID:27525571

  6. Clearance of inhaled particles from the human nose

    Energy Technology Data Exchange (ETDEWEB)

    Proctor, D.F.; Andersen, I.; Lundqvist, G.

    1973-01-01

    Nasal mucus flow transports particles at a rate of 5 mm/min (albeit much slower rates have been recorded). Transport is not affected by humidity. Anatomy of the nose shows air passage decreases to approx. 0.3 cm/sup 2/ in the anterior nares. This point has the highest air velocity (highest impaction) of entire respiratory tract. Immediately posterior (main nasal passage), the stream cross-section widens while the stream remains narrow. Opportunity for adsorption of gases is greatest in this low-velocity, high surface air passage (mucus passes through here). Subsequent bending and narrowing of airway toward nasopharnyx offers a second impaction area. Resistance could not predict gas absorption, as this absorption occurs mostly in low-resistance passages. The nasal mucus stream ends on the posterior aspect of the soft palate where wiping action of swallowing clears it. The anterior spot with highest air velocity is not ciliated. Clearance is possibly by anterior motion (e.g., sneezing) rather than by swallowing which would take longer.

  7. Protein Kinase C-Regulated Aβ Production and Clearance

    Directory of Open Access Journals (Sweden)

    Taehyun Kim

    2011-01-01

    Full Text Available Alzheimer’s disease (AD is the most common form of dementia among the elderly population. AD, which is characterized as a disease of cognitive deficits, is mainly associated with an increase of amyloid β-peptide (Aβ in the brain. A growing body of recent studies suggests that protein kinase C (PKC promotes the production of the secretory form of amyloid precursor protein (sAPPα via the activation of α-secretase activity, which reduces the accumulation of pathogenic Aβ levels in the brain. Moreover, activation of PKCα and mitogen-activated protein kinase (MAPK is known to increase sAPPα. A novel type of PKC, PKCε, activates the Aβ degrading activity of endothelin converting enzyme type 1 (ECE-1, which might be mediated via the MAPK pathway as well. Furthermore, dysregulation of PKC-MAPK signaling is known to increase Aβ levels in the brain, which results in AD phenotypes. Here, we discuss roles of PKC in Aβ production and clearance and its implication in AD.

  8. Highly Catalytic Nanodots with Renal Clearance for Radiation Protection

    CERN Document Server

    Zhang, Xiao-Dong; Wang, Junying; Yang, Jiang; Chen, Jie; Shen, Xiu; Deng, Jiao; Deng, Dehui; Long, Wei; Sun, Yuan-Ming; Liu, Changlong; Li, Meixian

    2016-01-01

    Ionizing radiation (gamma and x-ray) is widely used in industry and medicine, but it can also pose a significant hazardous effect on health and induce cancer, physical deformity and even death, due to DNA damages and invasion of free radicals. There is therefore an urgent unmet demand in designing highly efficient radioprotectants with synergetic integration of effective renal clearance and low toxicity. In this study, we designed ultrasmall (sub-5 nm) highly catalytically active and cysteine-protected MoS2 dots as radioprotectants and investigated their application in protection against ionizing radiation. In vivo preclinical studies showed that the surviving fraction of MoS2-treated mice can appreciably increase to up to 79 % when they were exposed to high-energy ionizing radiation. Furthermore, MoS2 dots can contribute in cleaning up the accumulated free radicals within the body, repairing DNA damages and recovering all vital chemical and biochemical indicators, suggesting their unique role as free radical...

  9. A Microwave Blade Tip Clearance Sensor for Propulsion Health Monitoring

    Science.gov (United States)

    Woike, Mark R.; Abdul-Aziz, Ali; Bencic, Timothy J.

    2010-01-01

    Microwave sensor technology is being investigated by the NASA Glenn Research Center as a means of making non-contact structural health measurements in the hot sections of gas turbine engines. This type of sensor technology is beneficial in that it is accurate, it has the ability to operate at extremely high temperatures, and is unaffected by contaminants that are present in turbine engines. It is specifically being targeted for use in the High Pressure Turbine (HPT) and High Pressure Compressor (HPC) sections to monitor the structural health of the rotating components. It is intended to use blade tip clearance to monitor blade growth and wear and blade tip timing to monitor blade vibration and deflection. The use of microwave sensors for this application is an emerging concept. Techniques on their use and calibration needed to be developed. As a means of better understanding the issues associated with the microwave sensors, a series of experiments have been conducted to evaluate their performance for aero engine applications. This paper presents the results of these experiments.

  10. Effect of Cilia Beat Frequency on Mucociliary Clearance

    Directory of Open Access Journals (Sweden)

    Sedaghat M. H.

    2016-12-01

    Full Text Available Background: The airway surface liquid (ASL, which is a fluid layer coating the interior epithelial surface of the bronchi and bronchiolesis, plays an important defensive role against foreign particles and chemicals entering lungs. Objective: Numerical investigation has been employed to solve two-layer model consisting of mucus layer as a viscoelastic fluid and periciliary liquid layer as a Newtonian fluid to study the effects of cilia beat frequency (CBF at various amounts of mucus properties on muco-ciliary transport problem. Methods: Hybrid finite difference-lattice Boltzmann-method (FB-LBM has been used to solve the momentum equations and to simulate cilia forces, and also the PCLmucus interface more accurately, immersed boundary method (IBM has been employed. The main contribution of the current study is to use an Oldroyd-B model as the constitutive equation of mucus. Results: Our results show that increasing CBF and decreasing mucus viscosity ratio have great effects on mucus flow, but the effect of viscosity ratio is more significant. The results also illustrate that the relation between cilia beat frequency and mean mucus velocity is almost linear and it has similar behavior at different values of viscosity ratio. Conclusion: Numerical investigation based on hybrid IB-FD-LBM has been used to study the effect of CBF at various mounts of mucus viscosity ratio on the muco-ciliary clearance. The results showed that the effect of viscosity ratio on the muco-ciliary transport process is more significant compared with CBF.

  11. Nonlinear Dynamics Response of a Planar Mechanism with Two Driving Links and Prismatic Pair Clearance

    Directory of Open Access Journals (Sweden)

    Lijuan Wu

    2017-01-01

    Full Text Available The influence of the joint clearance on the dynamic response of a planar mechanism with two driving links and prismatic pair clearance is investigated under variable input speeds of the system. The simulation model was built with a nonlinear impact model. The normal contact force is characterized by Hertz contact theory and an energy dissipation term. A tangential friction force is involved in the simulation model based on Coulomb’s friction law. The simulation results indicate that the largest Lyapunov exponents are dependent on the clearance size and the input speed.

  12. The extended clearance model and its use for the interpretation of hepatobiliary elimination data

    Directory of Open Access Journals (Sweden)

    Gian Camenisch

    2015-03-01

    Full Text Available Hepatic elimination is a function of the interplay between different processes such as sinusoidal uptake, intracellular metabolism, canalicular (biliary secretion, and sinusoidal efflux. In this review, we outline how drugs can be classified according to their in vitro determined clearance mechanisms using the extended clearance model as a reference. The approach enables the determination of the rate-determining hepatic clearance step. Some successful applications will be highlighted, together with a discussion on the major consequences for the pharmacokinetics and the drug-drug interaction potential of drugs. Special emphasize is put on the role of passive permeability and active transport processes in hepatic elimination.

  13. Whole body and regional clearances of noradrenaline and adrenaline in man

    DEFF Research Database (Denmark)

    Christensen, N J; Galbo, H; Gjerris, Anne Cathrine Roslev

    1984-01-01

    we found no correlation between clearance values based on venous and arterial sampling. In other experiments we measured the influence of physical exercise in young healthy subjects on the clearance rate of plasma adrenaline (A). The clearance of A, which at rest averaged 1.9 l/min tended to increase...... at low work loads and to decrease below resting levels at high exercise intensity. The changes were, however, small (+/- 20% of resting values). The regional extraction ratio of NA was 0.5 to 0.6 in the forearm, the liver and the kidney.(ABSTRACT TRUNCATED AT 250 WORDS)...

  14. A Reduced Model for Prediction of Thermal and Rotational Effects on Turbine Tip Clearance

    Science.gov (United States)

    Kypuros, Javier A.; Melcher, Kevin J.

    2003-01-01

    This paper describes a dynamic model that was developed to predict changes in turbine tip clearance the radial distance between the end of a turbine blade and the abradable tip seal. The clearance is estimated by using a first principles approach to model the thermal and mechanical effects of engine operating conditions on the turbine sub-components. These effects are summed to determine the resulting clearance. The model is demonstrated via a ground idle to maximum power transient and a lapse-rate takeoff transient. Results show the model demonstrates the expected pinch point behavior. The paper concludes by identifying knowledge gaps and suggesting additional research to improve the model.

  15. The effects of vaccination and immunity on bacterial infection dynamics in vivo.

    Directory of Open Access Journals (Sweden)

    Chris Coward

    2014-09-01

    Full Text Available Salmonella enterica infections are a significant global health issue, and development of vaccines against these bacteria requires an improved understanding of how vaccination affects the growth and spread of the bacteria within the host. We have combined in vivo tracking of molecularly tagged bacterial subpopulations with mathematical modelling to gain a novel insight into how different classes of vaccines and branches of the immune response protect against secondary Salmonella enterica infections of the mouse. We have found that a live Salmonella vaccine significantly reduced bacteraemia during a secondary challenge and restrained inter-organ spread of the bacteria in the systemic organs. Further, fitting mechanistic models to the data indicated that live vaccine immunisation enhanced both the bacterial killing in the very early stages of the infection and bacteriostatic control over the first day post-challenge. T-cell immunity induced by this vaccine is not necessary for the enhanced bacteriostasis but is required for subsequent bactericidal clearance of Salmonella in the blood and tissues. Conversely, a non-living vaccine while able to enhance initial blood clearance and killing of virulent secondary challenge bacteria, was unable to alter the subsequent bacterial growth rate in the systemic organs, did not prevent the resurgence of extensive bacteraemia and failed to control the spread of the bacteria in the body.

  16. “Queasy does it”: False alcohol beliefs and memories may lead to diminished alcohol preferences

    Science.gov (United States)

    Clifasefi, Seema L.; Bernstein, Daniel M.; Mantonakis, Antonia; Loftus, Elizabeth F.

    2013-01-01

    Studies have shown that false memories can be implanted via innocuous suggestions, and that these memories can play a role in shaping people’s subsequent attitudes and preferences. The current study explored whether participants (N=147) who received a false suggestion that they had become ill drinking a particular type of alcohol would increase their confidence that the event had occurred, and whether their new-found belief would subsequently affect their alcohol preferences. Results indicated that participants who received a suggestion that they had gotten sick drinking rum or vodka before the age of 16 reported increased confidence that the suggested experience had occurred. Moreover, participants who received a false alcohol suggestion also showed a strong trend to report diminished preference for the specified type of alcohol after the false suggestion. Implantation of a false memory related to one’s past drinking experiences may influence current drink preferences and could be an important avenue for further exploration in the development of alcohol interventions. PMID:23500110

  17. Confronting diminished epistemic privilege and epistemic injustice in pregnancy by challenging a "panoptics of the womb".

    Science.gov (United States)

    Freeman, Lauren

    2015-02-01

    This paper demonstrates how the problematic kinds of epistemic power that physicians have can diminish the epistemic privilege that pregnant women have over their bodies and can put them in a state of epistemic powerlessness. This result, I argue, constitutes an epistemic injustice for many pregnant women. A reconsideration of how we understand and care for pregnant women and of the physician-patient relationship can provide us with a valuable context and starting point for helping to alleviate the knowledge/power problems that are symptomatic of the current system and structure of medicine. I suggest that we can begin to confront this kind of injustice if medicine adopts a more phenomenological understanding of bodies and if physicians and patients--in this case, pregnant women--become what I call "epistemic peers." © The Author 2014. Published by Oxford University Press, on behalf of the Journal of Medicine and Philosophy Inc. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  18. Diminished neural responses predict enhanced intrinsic motivation and sensitivity to external incentive.

    Science.gov (United States)

    Marsden, Karen E; Ma, Wei Ji; Deci, Edward L; Ryan, Richard M; Chiu, Pearl H

    2015-06-01

    The duration and quality of human performance depend on both intrinsic motivation and external incentives. However, little is known about the neuroscientific basis of this interplay between internal and external motivators. Here, we used functional magnetic resonance imaging to examine the neural substrates of intrinsic motivation, operationalized as the free-choice time spent on a task when this was not required, and tested the neural and behavioral effects of external reward on intrinsic motivation. We found that increased duration of free-choice time was predicted by generally diminished neural responses in regions associated with cognitive and affective regulation. By comparison, the possibility of additional reward improved task accuracy, and specifically increased neural and behavioral responses following errors. Those individuals with the smallest neural responses associated with intrinsic motivation exhibited the greatest error-related neural enhancement under the external contingency of possible reward. Together, these data suggest that human performance is guided by a "tonic" and "phasic" relationship between the neural substrates of intrinsic motivation (tonic) and the impact of external incentives (phasic).

  19. Application of the Diminishing Returns Concept in the Hydroecologic Restoration of Riverscapes

    Energy Technology Data Exchange (ETDEWEB)

    Diefenderfer, Heida L.; Johnson, Gary E.; Skalski, John R.; Breithaupt, Stephen A.; Coleman, Andre M.

    2012-03-17

    Principles for optimizing the number and placement of ecological restoration actions on rivers and coasts would be useful in project engineering design and program planning. This study demonstrated that the yield of inundated floodplain habitat area from dike breaching conforms to a diminishing returns model. The aggregate effects of establishing hydrologic connections between a tidally influenced main stem river and the floodplain were experimentally examined using a hydrodynamic model. Restoration clusters of size 1, 4, 8, and more, replicated and randomized within the landscape, yielded average wetted floodplain area conforming with an exponential rise to maximum curve2(0.99)r=. Analysis of the average incremental change in floodplain inundation produced per breach showed that opening 25 % of the channels crossing the dike provided the maximum return on investment as measured by wetted area. Midstream breaches yielded 60 % and upstream breaches 2 % of the wetted area produced by downstream breaches. Dike-breach restoration programs therefore can be optimized by strategic determination of the spatial configuration and number of demolitions, though biological factors such as the accessibility of floodplain habitat and total length of channels connected also need to be considered. These findings have implications for cost-benefit analyses in restoration program planning.

  20. Failure to Demonstrate That Playing Violent Video Games Diminishes Prosocial Behavior

    Science.gov (United States)

    Tear, Morgan J.; Nielsen, Mark

    2013-01-01

    Background Past research has found that playing a classic prosocial video game resulted in heightened prosocial behavior when compared to a control group, whereas playing a classic violent video game had no effect. Given purported links between violent video games and poor social behavior, this result is surprising. Here our aim was to assess whether this finding may be due to the specific games used. That is, modern games are experienced differently from classic games (more immersion in virtual environments, more connection with characters, etc.) and it may be that playing violent video games impacts prosocial behavior only when contemporary versions are used. Methods and Findings Experiments 1 and 2 explored the effects of playing contemporary violent, non-violent, and prosocial video games on prosocial behavior, as measured by the pen-drop task. We found that slight contextual changes in the delivery of the pen-drop task led to different rates of helping but that the type of game played had little effect. Experiment 3 explored this further by using classic games. Again, we found no effect. Conclusions We failed to find evidence that playing video games affects prosocial behavior. Research on the effects of video game play is of significant public interest. It is therefore important that speculation be rigorously tested and findings replicated. Here we fail to substantiate conjecture that playing contemporary violent video games will lead to diminished prosocial behavior. PMID:23844191

  1. Diminishing willingness to pay per quality-adjusted life year: valuing acute foodborne illness.

    Science.gov (United States)

    Haninger, Kevin; Hammitt, James K

    2011-09-01

    We design and conduct a stated-preference survey to estimate willingness to pay (WTP) to reduce foodborne risk of acute illness and to test whether WTP is proportional to the corresponding gain in expected quality-adjusted life years (QALYs). If QALYs measure utility for health, then economic theory requires WTP to be nearly proportional to changes in both health quality and duration of illness and WTP could be estimated by multiplying the expected change in QALYs by an appropriate monetary value. WTP is elicited using double-bounded, dichotomous-choice questions in which respondents (randomly selected from the U.S. general adult population, n = 2,858) decide whether to purchase a more expensive food to reduce the risk of foodborne illness. Health risks vary by baseline probability of illness, reduction in probability, duration and severity of illness, and conditional probability of mortality. The expected gain in QALYs is calculated using respondent-assessed decrements in health-related quality of life if ill combined with the duration of illness and reduction in probability specified in the survey. We find sharply diminishing marginal WTP for severity and duration of illness prevented. Our results suggest that individuals do not have a constant rate of WTP per QALY, which implies that WTP cannot be accurately estimated by multiplying the change in QALYs by an appropriate monetary value. © 2011 Society for Risk Analysis.

  2. Diminished N1 auditory evoked potentials to oddball stimuli in misophonia patients

    Directory of Open Access Journals (Sweden)

    Arjan eSchröder

    2014-04-01

    Full Text Available Misophonia (hatred of sound is a newly defined psychiatric condition in which ordinary human sounds, such as breathing and eating, trigger impulsive aggression. In the current study we investigated if a dysfunction in the brain’s early auditory processing system could be present in misophonia. We screened 20 patients with misophonia with the diagnostic criteria for misophonia, and 14 matched healthy controls without misophonia, and investigated any potential deficits in auditory processing of misophonia patients using auditory event-related potentials (ERPs during an oddball task.Subjects watched a neutral silent movie while being presented a regular frequency of beep sounds in which oddball tones of 250 Hz and 4000 Hz were randomly embedded in a stream of repeated 1000 Hz standard tones. We examined the P1, N1 and P2 components locked to the onset of the tones.For misophonia patients, the N1 peak evoked by the oddball tones had a smaller mean peak amplitude than the control group. However, no significant differences were found in P1 and P2 components evoked by the oddball tones. There were no significant differences between the misophonia patients and their controls in any of the ERP components to the standard tones.The diminished N1 component to oddball tones in misophonia patients suggests an underlying neurobiological deficit in misophonia patients. This reduction might reflect a basic impairment in auditory processing in misophonia patients.

  3. Diminished facial emotion expression and associated clinical characteristics in Anorexia Nervosa.

    Science.gov (United States)

    Lang, Katie; Larsson, Emma E C; Mavromara, Liza; Simic, Mima; Treasure, Janet; Tchanturia, Kate

    2016-02-28

    This study aimed to investigate emotion expression in a large group of children, adolescents and adults with Anorexia Nervosa (AN), and investigate the associated clinical correlates. One hundred and forty-one participants (AN=66, HC= 75) were recruited and positive and negative film clips were used to elicit emotion expressions. The Facial Activation Coding system (FACES) was used to code emotion expression. Subjective ratings of emotion were collected. Individuals with AN displayed less positive emotions during the positive film clip compared to healthy controls (HC). There was no significant difference between the groups on the Positive and Negative Affect Scale (PANAS). The AN group displayed emotional incongruence (reporting a different emotion to what would be expected given the stimuli, with limited facial affect to signal the emotion experienced), whereby they reported feeling significantly higher rates of negative emotion during the positive clip. There were no differences in emotion expression between the groups during the negative film clip. Despite this individuals with AN reported feeling significantly higher levels of negative emotions during the negative clip. Diminished positive emotion expression was associated with more severe clinical symptoms, which could suggest that these individuals represent a group with serious social difficulties, which may require specific attention in treatment. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  4. Thalidomide results in diminished ovarian reserve in reproductive age female IBD patients.

    Science.gov (United States)

    Peng, Xiang; Zhi, Min; Wei, Ming; Li, Ting-Ting; Zhang, Min; Zhang, Yuan-Qi; He, Huan; Su, Mingli; Wang, Wei; Chen, Jun-Rong; Tang, Jian; Gao, Xiang; Hu, Pin-Jin; Liang, Xiao-Yan

    2017-05-01

    The effectiveness of thalidomide in treating inflammatory bowel disease (IBD) has been widely recognized. Meanwhile, many serious adverse drug reactions have been observed, but no know reports on ovarian reserve function.Female patients, ranging in age between 18 and 40, were referred to our institution to undergo sex hormone detection and ultrasonic scanning for ovarian function assessment, between February 1, 2016 and September 31, 2016.Thirty-three patients treated with thalidomide (group A), 73 patients without thalidomide (group B), and 78 healthy women as control were studied. Menstrual disorder was higher in group A than group B (78.8% vs 57.2%, P thalidomide were the independent risk factors in diminished ovarian reserve (DOR), and when dose reached 75 mg/day, 5 g total, or when treatment time reached 10 months respectively. These influence may increasing (P Thalidomide was an independent risk factor leading to DOR in female IBD patients, the influence may increasing when daily dose and accumulated dose reached 75 mg/day and 5 g total dose, but may be reversed by stopping.

  5. Amygdalin blocks bladder cancer cell growth in vitro by diminishing cyclin A and cdk2.

    Science.gov (United States)

    Makarević, Jasmina; Rutz, Jochen; Juengel, Eva; Kaulfuss, Silke; Reiter, Michael; Tsaur, Igor; Bartsch, Georg; Haferkamp, Axel; Blaheta, Roman A

    2014-01-01

    Amygdalin, a natural compound, has been used by many cancer patients as an alternative approach to treat their illness. However, whether or not this substance truly exerts an anti-tumor effect has never been settled. An in vitro study was initiated to investigate the influence of amygdalin (1.25-10 mg/ml) on the growth of a panel of bladder cancer cell lines (UMUC-3, RT112 and TCCSUP). Tumor growth, proliferation, clonal growth and cell cycle progression were investigated. The cell cycle regulating proteins cdk1, cdk2, cdk4, cyclin A, cyclin B, cyclin D1, p19, p27 as well as the mammalian target of rapamycin (mTOR) related signals phosphoAkt, phosphoRaptor and phosphoRictor were examined. Amygdalin dose-dependently reduced growth and proliferation in all three bladder cancer cell lines, reflected in a significant delay in cell cycle progression and G0/G1 arrest. Molecular evaluation revealed diminished phosphoAkt, phosphoRictor and loss of Cdk and cyclin components. Since the most outstanding effects of amygdalin were observed on the cdk2-cyclin A axis, siRNA knock down studies were carried out, revealing a positive correlation between cdk2/cyclin A expression level and tumor growth. Amygdalin, therefore, may block tumor growth by down-modulating cdk2 and cyclin A. In vivo investigation must follow to assess amygdalin's practical value as an anti-tumor drug.

  6. Amygdalin blocks bladder cancer cell growth in vitro by diminishing cyclin A and cdk2.

    Directory of Open Access Journals (Sweden)

    Jasmina Makarević

    Full Text Available Amygdalin, a natural compound, has been used by many cancer patients as an alternative approach to treat their illness. However, whether or not this substance truly exerts an anti-tumor effect has never been settled. An in vitro study was initiated to investigate the influence of amygdalin (1.25-10 mg/ml on the growth of a panel of bladder cancer cell lines (UMUC-3, RT112 and TCCSUP. Tumor growth, proliferation, clonal growth and cell cycle progression were investigated. The cell cycle regulating proteins cdk1, cdk2, cdk4, cyclin A, cyclin B, cyclin D1, p19, p27 as well as the mammalian target of rapamycin (mTOR related signals phosphoAkt, phosphoRaptor and phosphoRictor were examined. Amygdalin dose-dependently reduced growth and proliferation in all three bladder cancer cell lines, reflected in a significant delay in cell cycle progression and G0/G1 arrest. Molecular evaluation revealed diminished phosphoAkt, phosphoRictor and loss of Cdk and cyclin components. Since the most outstanding effects of amygdalin were observed on the cdk2-cyclin A axis, siRNA knock down studies were carried out, revealing a positive correlation between cdk2/cyclin A expression level and tumor growth. Amygdalin, therefore, may block tumor growth by down-modulating cdk2 and cyclin A. In vivo investigation must follow to assess amygdalin's practical value as an anti-tumor drug.

  7. Metabolic Evidence of Diminished Lipid Oxidation in Women With Polycystic Ovary Syndrome

    Science.gov (United States)

    Whigham, Leah D.; Butz, Daniel E.; Dashti, Hesam; Tonelli, Marco; Johnson, LuAnn K.; Cook, Mark E.; Porter, Warren P.; Eghbalnia, Hamid R.; Markley, John L.; Lindheim, Steven R.; Schoeller, Dale A.; Abbott, David H.; Assadi-Porter, Fariba M.

    2014-01-01

    Polycystic ovary syndrome (PCOS), a common female endocrinopathy, is a complex metabolic syndrome of enhanced weight gain. The goal of this pilot study was to evaluate metabolic differences between normal (n=10) and PCOS (n=10) women via breath carbon isotope ratio, urinary nitrogen and nuclear magnetic resonance (NMR)-determined serum metabolites. Breath carbon stable isotopes measured by cavity ring down spectroscopy (CRDS) indicated diminished (p<0.030) lipid use as a metabolic substrate during overnight fasting in PCOS compared to normal women. Accompanying urinary analyses showed a trending correlation (p<0.057) between overnight total nitrogen and circulating testosterone in PCOS women, alone. Serum analyzed by NMR spectroscopy following overnight, fast and at 2 h following an oral glucose tolerance test showed that a transient elevation in blood glucose levels decreased circulating levels of lipid, glucose and amino acid metabolic intermediates (acetone, 2-oxocaporate, 2-aminobutyrate, pyruvate, formate, and sarcosine) in PCOS women, whereas the 2 h glucose challenge led to increases in the same intermediates in normal women. These pilot data suggest that PCOS-related inflexibility in fasting-related switching between lipid and carbohydrate/protein utilization for carbon metabolism may contribute to enhanced weight gain. PMID:24765590

  8. Diminishing proportional risk of sudden death with advancing age: implications for prevention of sudden death.

    Science.gov (United States)

    Krahn, Andrew D; Connolly, Stuart J; Roberts, Robin S; Gent, Michael

    2004-05-01

    Advances in primary and secondary prevention of sudden death have led to a wide array of potentially beneficial therapies. Identification of patients most likely to benefit would be of use when considering costly interventions such as an implantable defibrillator. We sought to determine the effect of advancing age on the mode of death in the Amiodarone Trialists Metanalysis. Patients (n = 6252; age, 61.2+/-10.5 years; 83% men) were included in an analysis of predictors of sudden death (SD) and all-cause death (ACD), based on baseline variables at enrollment. Patients were divided into 5 age groups: 80 years. During a mean of 16.8+/-10.3 months of follow-up, there were 1023 deaths, with an annual overall mortality rate of 11.7%. Both sudden death and nonsudden death rates increased with age, although the increase of nonsudden death with age was more dramatic. The overall proportion of death that was sudden (SD/ACD ratio) was 0.41, falling from 0.51 before age 50 years to 0.26 after age 80 years (P =.002 for trend). The SD/ACD ratio was not affected by sex, New York Heart Association Class, or left ventricular ejection fraction. Although the incidence of sudden death increases with age, the proportion of death that is sudden diminishes markedly. This finding may influence the yield of interventions targeted at prevention of sudden death.

  9. Differences in chunking behavior between young and older adults diminish with extended practice.

    Science.gov (United States)

    Barnhoorn, J S; Van Asseldonk, E H F; Verwey, W B

    2017-12-21

    Previous research found reduced motor chunking behavior in older adults compared to young adults. However, it remains unclear whether older adults are unable to use a chunking strategy or whether they are just slower in developing them. Our goal was to investigate the effect of extended practice on the development of chunking behavior in healthy older adults. A group of young and a group of healthy older adults between 74 and 85 years of age visited the lab on 2 days. A sequence of 3 and a sequence of 6 elements were both practiced 432 times in a discrete sequence production task. We found that age differences in chunking behavior, as measured by the difference between initiation and execution of the sequence, diminish with extended practice. Furthermore, in older, but not in young adults, slow responses that are often interpreted as the first response of a next motor chunk were associated with a finger that was also slow during performance of the random sequences. This finding calls for more attention to biomechanical factors in future theory about aging and sequence learning.

  10. Failure to demonstrate that playing violent video games diminishes prosocial behavior.

    Science.gov (United States)

    Tear, Morgan J; Nielsen, Mark

    2013-01-01

    Past research has found that playing a classic prosocial video game resulted in heightened prosocial behavior when compared to a control group, whereas playing a classic violent video game had no effect. Given purported links between violent video games and poor social behavior, this result is surprising. Here our aim was to assess whether this finding may be due to the specific games used. That is, modern games are experienced differently from classic games (more immersion in virtual environments, more connection with characters, etc.) and it may be that playing violent video games impacts prosocial behavior only when contemporary versions are used. Experiments 1 and 2 explored the effects of playing contemporary violent, non-violent, and prosocial video games on prosocial behavior, as measured by the pen-drop task. We found that slight contextual changes in the delivery of the pen-drop task led to different rates of helping but that the type of game played had little effect. Experiment 3 explored this further by using classic games. Again, we found no effect. We failed to find evidence that playing video games affects prosocial behavior. Research on the effects of video game play is of significant public interest. It is therefore important that speculation be rigorously tested and findings replicated. Here we fail to substantiate conjecture that playing contemporary violent video games will lead to diminished prosocial behavior.

  11. Failure to demonstrate that playing violent video games diminishes prosocial behavior.

    Directory of Open Access Journals (Sweden)

    Morgan J Tear

    Full Text Available BACKGROUND: Past research has found that playing a classic prosocial video game resulted in heightened prosocial behavior when compared to a control group, whereas playing a classic violent video game had no effect. Given purported links between violent video games and poor social behavior, this result is surprising. Here our aim was to assess whether this finding may be due to the specific games used. That is, modern games are experienced differently from classic games (more immersion in virtual environments, more connection with characters, etc. and it may be that playing violent video games impacts prosocial behavior only when contemporary versions are used. METHODS AND FINDINGS: Experiments 1 and 2 explored the effects of playing contemporary violent, non-violent, and prosocial video games on prosocial behavior, as measured by the pen-drop task. We found that slight contextual changes in the delivery of the pen-drop task led to different rates of helping but that the type of game played had little effect. Experiment 3 explored this further by using classic games. Again, we found no effect. CONCLUSIONS: We failed to find evidence that playing video games affects prosocial behavior. Research on the effects of video game play is of significant public interest. It is therefore important that speculation be rigorously tested and findings replicated. Here we fail to substantiate conjecture that playing contemporary violent video games will lead to diminished prosocial behavior.

  12. A change will do us good: threats diminish typical preferences for male leaders.

    Science.gov (United States)

    Brown, Elizabeth R; Diekman, Amanda B; Schneider, Monica C

    2011-07-01

    The current research explores role congruity processes from a new vantage point by investigating how the need for change might shift gender-based leadership preferences. According to role congruity theory, favorability toward leaders results from alignment between what is desired in a leadership role and the characteristics stereotypically ascribed to the leader. Generally speaking, these processes lead to baseline preferences for male over female leaders. In this research, the authors propose that a shift in gender-based leadership preferences will emerge under conditions of threat. Because the psychological experience of threat signals a need for change, individuals will favor candidates who represent new directions in leadership rather than consistency with past directions in leadership. Specifically, they find that threat evokes an implicit preference for change over stability (Experiment 1) and gender stereotypes align women with change but men with stability (Experiments 2a and 2b). Consequently, the typical preference for male leaders is diminished, or even reversed, under threat (Experiments 3 and 4). Moreover, the shift away from typical gender-based leadership preferences occurs especially among individuals who highly legitimize the sociopolitical system (Experiment 4), suggesting that these preference shifts might serve to protect the underlying system. © 2011 by the Society for Personality and Social Psychology, Inc

  13. No Spearman’s Law of Diminishing Returns for the working memory and intelligence relationship

    Directory of Open Access Journals (Sweden)

    Kroczek Bartłomiej

    2016-04-01

    Full Text Available Spearman’s Law of Diminishing Returns (SLODR holds that correlation between general (g/fluid (Gf intelligence factor and other cognitive abilities weakens with increasing ability level. Thus, cognitive processing in low ability people is most strongly saturated by g/Gf, whereas processing in high ability people depends less on g/Gf. Numerous studies demonstrated that low g is more strongly correlated with crystallized intelligence/creativity/processing speed than is high g, however no study tested an analogous effect in the case of working memory (WM. Our aim was to investigate SLODR for the relationship between Gf and WM capacity, using a large data set from our own previous studies. We tested alternative regression models separately for three types of WM tasks that tapped short-term memory storage, attention control, and relational integration, respectively. No significant SLODR effect was found for any of these tasks. Each task shared with Gf virtually the same amount of variance in the case of low- and high-ability people. This result suggests that Gf and WM rely on one and the same (neurocognitive mechanism.

  14. Partial enterectomy in the rat does not diminish muscle glutamine production.

    Science.gov (United States)

    Deutz, N E; Dejong, C H; Athanasas, G; Soeters, P B

    1992-12-01

    The hypothesis was posed that consumption of the amino acid glutamine by the splanchnic tissues is an important regulating mechanism for its production in muscle. Therefore, glutamine consumption or production in portal-drained viscera (PDV), liver, and hindquarter was measured by determining fluxes and intracellular concentrations after 80% enterectomy or SHAM operation in rats. Moreover, fluxes and intracellular concentrations of several other amino acids, ammonia, and liver urea production were determined concomitantly. After enterectomy, arterial glutamine concentration was increased, PDV glutamine consumption was decreased by 77%, and liver glutamine consumption was unchanged compared with values in SHAM-operated rats. Although hindquarter glutamine production remained unchanged after enterectomy, intracellular glutamate concentration (glutamine precursor) was lower, suggesting that enterectomy induces changes in muscle metabolism without changing the flux of glutamine. For the remaining gut, it was calculated that after enterectomy glutamine consumption per gram remaining gut tissue increased. These results cast doubt on the hypothesis that diminished splanchnic glutamine uptake can reduce muscle glutamine production.

  15. Marriage of scintillator and semiconductor for synchronous radiotherapy and deep photodynamic therapy with diminished oxygen dependence.

    Science.gov (United States)

    Zhang, Chen; Zhao, Kuaile; Bu, Wenbo; Ni, Dalong; Liu, Yanyan; Feng, Jingwei; Shi, Jianlin

    2015-02-02

    Strong oxygen dependence and limited penetration depth are the two major challenges facing the clinical application of photodynamic therapy (PDT). In contrast, ionizing radiation is too penetrative and often leads to inefficient radiotherapy (RT) in the clinic because of the lack of effective energy accumulation in the tumor region. Inspired by the complementary advantages of PDT and RT, we present herein the integration of a scintillator and a semiconductor as an ionizing-radiation-induced PDT agent, achieving synchronous radiotherapy and depth-insensitive PDT with diminished oxygen dependence. In the core-shell Ce(III)-doped LiYF4@SiO2@ZnO structure, the downconverted ultraviolet fluorescence from the Ce(III)-doped LiYF4 nanoscintillator under ionizing irradiation enables the generation of electron-hole (e(-)-h(+)) pairs in ZnO nanoparticles, giving rise to the formation of biotoxic hydroxyl radicals. This process is analogous to a type I PDT process for enhanced antitumor therapeutic efficacy. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Two Days' Sleep Debt Causes Mood Decline During Resting State Via Diminished Amygdala-Prefrontal Connectivity.

    Science.gov (United States)

    Motomura, Yuki; Katsunuma, Ruri; Yoshimura, Michitaka; Mishima, Kazuo

    2017-10-01

    Sleep debt (SD) has been suggested to evoke emotional instability by diminishing the suppression of the amygdala by the medial prefrontal cortex (MPFC). Here, we investigated how short-term SD affects resting-state functional connectivity between the amygdala and MPFC, self-reported mood, and sleep parameters. Eighteen healthy adult men aged 29 ± 8.24 years participated in a 2-day sleep control session (SC; time in bed [TIB], 9 hours) and 2-day SD session (TIB, 3 hours). On day 2 of each session, resting-state functional magnetic resonance imaging was performed, followed immediately by measuring self-reported mood on the State-Trait Anxiety Inventory-State subscale (STAI-S). STAI-S score was significantly increased, and functional connectivity between the amygdala and MPFC was significantly decreased in SD compared with SC. Significant correlations were observed between reduced rapid eye movement (REM) sleep and reduced left amygdala-MPFC functional connectivity (FCL_amg-MPFC) and between reduced FCL_amg-MPFC and increased STAI-S score in SD compared with SC. These findings suggest that reduced MPFC functional connectivity of amygdala activity is involved in mood deterioration under SD, and that REM sleep reduction is involved in functional changes in the corresponding brain regions. Having adequate REM sleep may be important for mental health maintenance.

  17. Ambient groundwater flow diminishes nitrate processing in the hyporheic zone of streams

    Science.gov (United States)

    Azizian, Morvarid; Boano, Fulvio; Cook, Perran L. M.; Detwiler, Russell L.; Rippy, Megan A.; Grant, Stanley B.

    2017-05-01

    Modeling and experimental studies demonstrate that ambient groundwater reduces hyporheic exchange, but the implications of this observation for stream N-cycling is not yet clear. Here we utilize a simple process-based model (the Pumping and Streamline Segregation or PASS model) to evaluate N-cycling over two scales of hyporheic exchange (fluvial ripples and riffle-pool sequences), ten ambient groundwater and stream flow scenarios (five gaining and losing conditions and two stream discharges), and three biogeochemical settings (identified based on a principal component analysis of previously published measurements in streams throughout the United States). Model-data comparisons indicate that our model provides realistic estimates for direct denitrification of stream nitrate, but overpredicts nitrification and coupled nitrification-denitrification. Riffle-pool sequences are responsible for most of the N-processing, despite the fact that fluvial ripples generate 3-11 times more hyporheic exchange flux. Across all scenarios, hyporheic exchange flux and the Damköhler Number emerge as primary controls on stream N-cycling; the former regulates trafficking of nutrients and oxygen across the sediment-water interface, while the latter quantifies the relative rates of organic carbon mineralization and advective transport in streambed sediments. Vertical groundwater flux modulates both of these master variables in ways that tend to diminish stream N-cycling. Thus, anthropogenic perturbations of ambient groundwater flows (e.g., by urbanization, agricultural activities, groundwater mining, and/or climate change) may compromise some of the key ecosystem services provided by streams.

  18. Reducing the Polluting Emissions. A Source for Diminishing the Climate Changes

    Directory of Open Access Journals (Sweden)

    Emilian M. DOBRESCU

    2009-06-01

    Full Text Available The USA and the Western Europe are responsible for 2/3 of the CO2 emissions accumulated until today. On the other hand, Africa has produced only 3% of polluting emission since 1900 until today, by burning mineral fuels. Since 1992, the most industrialized countries have promised to help ôthe most vulnerable nations face the adverse consequences of climate changesö by supporting the costs of adaptation. The commitment was included in the convention frame that gave birth to the Kyoto Treaty, which was rejected by the George W. Bush Administration, even though the initial document, issued in 1992, had been signed by George Bush. The industrialized countries that signed the Kyoto Treaty have decided to create a special fund for ôclimate adaptationö. Hundreds of millions of dollars had to be used in order to diminish the impact of the global warming in the most exposed areas.Lately, maybe because the CO2 emissions increase due to human activities, the planet climate has changed for worse. 2007 was a key year in evaluating the reply the planet would give to the global overheating, mainly caused by the green-house effect and worsen by El Nino oceanic stream. This superposition of climate factors made 2007 to be one of the warmest years ever registered.

  19. The central role of diminishing sea ice in recent Arctic temperature amplification.

    Science.gov (United States)

    Screen, James A; Simmonds, Ian

    2010-04-29

    The rise in Arctic near-surface air temperatures has been almost twice as large as the global average in recent decades-a feature known as 'Arctic amplification'. Increased concentrations of atmospheric greenhouse gases have driven Arctic and global average warming; however, the underlying causes of Arctic amplification remain uncertain. The roles of reductions in snow and sea ice cover and changes in atmospheric and oceanic circulation, cloud cover and water vapour are still matters of debate. A better understanding of the processes responsible for the recent amplified warming is essential for assessing the likelihood, and impacts, of future rapid Arctic warming and sea ice loss. Here we show that the Arctic warming is strongest at the surface during most of the year and is primarily consistent with reductions in sea ice cover. Changes in cloud cover, in contrast, have not contributed strongly to recent warming. Increases in atmospheric water vapour content, partly in response to reduced sea ice cover, may have enhanced warming in the lower part of the atmosphere during summer and early autumn. We conclude that diminishing sea ice has had a leading role in recent Arctic temperature amplification. The findings reinforce suggestions that strong positive ice-temperature feedbacks have emerged in the Arctic, increasing the chances of further rapid warming and sea ice loss, and will probably affect polar ecosystems, ice-sheet mass balance and human activities in the Arctic.

  20. Diminished autophagy limits cardiac injury in mouse models of type 1 diabetes.

    Science.gov (United States)

    Xu, Xianmin; Kobayashi, Satoru; Chen, Kai; Timm, Derek; Volden, Paul; Huang, Yuan; Gulick, James; Yue, Zhenyu; Robbins, Jeffrey; Epstein, Paul N; Liang, Qiangrong

    2013-06-21

    Cardiac autophagy is inhibited in type 1 diabetes. However, it remains unknown if the reduced autophagy contributes to the pathogenesis of diabetic cardiomyopathy. We addressed this question using mouse models with gain- and loss-of-autophagy. Autophagic flux was inhibited in diabetic hearts when measured at multiple time points after diabetes induction by streptozotocin as assessed by protein levels of microtubule-associated protein light chain 3 form 2 (LC3-II) or GFP-LC3 puncta in the absence and presence of the lysosome inhibitor bafilomycin A1. Autophagy in diabetic hearts was further reduced in beclin 1- or Atg16-deficient mice but was restored partially or completely by overexpression of beclin 1 to different levels. Surprisingly, diabetes-induced cardiac damage was substantially attenuated in beclin 1- and Atg16-deficient mice as shown by improved cardiac function as well as reduced levels of oxidative stress, interstitial fibrosis, and myocyte apoptosis. In contrast, diabetic cardiac damage was dose-dependently exacerbated by beclin 1 overexpression. The cardioprotective effects of autophagy deficiency were reproduced in OVE26 diabetic mice. These effects were associated with partially restored mitophagy and increased expression and mitochondrial localization of Rab9, an essential regulator of a non-canonical alternative autophagic pathway. Together, these findings demonstrate that the diminished autophagy is an adaptive response that limits cardiac dysfunction in type 1 diabetes, presumably through up-regulation of alternative autophagy and mitophagy.

  1. Diminished Autophagy Limits Cardiac Injury in Mouse Models of Type 1 Diabetes*

    Science.gov (United States)

    Xu, Xianmin; Kobayashi, Satoru; Chen, Kai; Timm, Derek; Volden, Paul; Huang, Yuan; Gulick, James; Yue, Zhenyu; Robbins, Jeffrey; Epstein, Paul N.; Liang, Qiangrong

    2013-01-01

    Cardiac autophagy is inhibited in type 1 diabetes. However, it remains unknown if the reduced autophagy contributes to the pathogenesis of diabetic cardiomyopathy. We addressed this question using mouse models with gain- and loss-of-autophagy. Autophagic flux was inhibited in diabetic hearts when measured at multiple time points after diabetes induction by streptozotocin as assessed by protein levels of microtubule-associated protein light chain 3 form 2 (LC3-II) or GFP-LC3 puncta in the absence and presence of the lysosome inhibitor bafilomycin A1. Autophagy in diabetic hearts was further reduced in beclin 1- or Atg16-deficient mice but was restored partially or completely by overexpression of beclin 1 to different levels. Surprisingly, diabetes-induced cardiac damage was substantially attenuated in beclin 1- and Atg16-deficient mice as shown by improved cardiac function as well as reduced levels of oxidative stress, interstitial fibrosis, and myocyte apoptosis. In contrast, diabetic cardiac damage was dose-dependently exacerbated by beclin 1 overexpression. The cardioprotective effects of autophagy deficiency were reproduced in OVE26 diabetic mice. These effects were associated with partially restored mitophagy and increased expression and mitochondrial localization of Rab9, an essential regulator of a non-canonical alternative autophagic pathway. Together, these findings demonstrate that the diminished autophagy is an adaptive response that limits cardiac dysfunction in type 1 diabetes, presumably through up-regulation of alternative autophagy and mitophagy. PMID:23658055

  2. Diminished whole-brain but enhanced peri-sylvian connectivity in absolute pitch musicians.

    Science.gov (United States)

    Jäncke, Lutz; Langer, Nicolas; Hänggi, Jürgen

    2012-06-01

    Several anatomical studies have identified specific anatomical features within the peri-sylvian brain system of absolute pitch (AP) musicians. In this study we used graph theoretical analysis of cortical thickness covariations (as indirect indicator of connectivity) to examine whether AP musicians differ from relative pitch musicians and nonmusicians in small-world network characteristics. We measured "local connectedness" (local clustering = γ), "global efficiency of information transfer" (path length = λ), "small-worldness" (σ = γ/λ), and "degree" centrality as measures of connectivity. Although all groups demonstrated typical small-world features, AP musicians showed significant small-world alterations. "Degree" as a measure of interconnectedness was globally significantly decreased in AP musicians. These differences let us suggest that AP musicians demonstrate diminished neural integration (less connections) among distant brain regions. In addition, AP musicians demonstrated significantly increased local connectivity in peri-sylvian language areas of which the planum temporale, planum polare, Heschl's gyrus, lateral aspect of the superior temporal gyrus, STS, pars triangularis, and pars opercularis were hub regions. All of these brain areas are known to be involved in higher-order auditory processing, working or semantic memory processes. Taken together, whereas AP musicians demonstrate decreased global interconnectedness, the local connectedness in peri-sylvian brain areas is significantly higher than for relative pitch musicians and nonmusicians.

  3. Do online reviews diminish physician authority? The case of cosmetic surgery in the U.S.

    Science.gov (United States)

    Menon, Alka V

    2017-05-01

    This article analyzes the substance and perception of online physician reviews, which are qualitative and quantitative assessments of physicians written and shared by patients, in the case of U.S. cosmetic surgery. Like other cash-pay medical specialties, cosmetic surgery is elective and paid for largely out of pocket, with patients having latitude in their choice of surgeon. Drawing on qualitative data from interviews, observations of an American Society of Aesthetic Plastic Surgery professional meeting, and online reviews from the platforms RealSelf and Yelp, I identify two interdependent contributors to physician authority: reputation and expertise. I argue that surgeons see reviews overwhelmingly as a threat to their reputation, even as actual review content often positively reinforces physician expertise and enhances physician reputation. I show that most online reviews linked to interview participants are positive, according considerable deference to surgeons. Reviews add patients' embodied and consumer expertise as a circumscribed supplement to surgeons' technical expertise. Moreover, reviews change the doctor-patient relationship by putting it on display for a larger audience of prospective patients, enabling patients and review platforms to affect physician reputation. Surgeons report changing how they practice to establish and maintain their reputations. This research demonstrates how physician authority in medical consumerist contexts is a product of reputation as well as expertise. Consumerism changes the doctor-patient relationship and makes surgeons feel diminished authority by dint of their reputational vulnerability to online reviews. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Diminished Effort on a Progressive Ratio Task in Both Unipolar and Bipolar Depression

    Science.gov (United States)

    Hershenberg, Rachel; Satterthwaite, Theodore D.; Daldal, Aylin; Katchmar, Natalie; Moore, Tyler M.; Kable, Joseph W.; Wolf, Daniel H.

    2016-01-01

    Background Amotivation, or decisional anhedonia, is a prominent and disabling feature of depression. However, this aspect of depression remains understudied, and no prior work has applied objective laboratory tests of motivation in both unipolar and bipolar depression. Methods We assessed motivation deficits using a Progressive Ratio Task (PRT) that indexes willingness to exert effort for monetary reward. The PRT was administered to 96 adults ages 18–60 including 25 participants with a current episode of unipolar depression, 28 with bipolar disorder (current episode depressed), and 43 controls without any lifetime history of Axis I psychiatric disorders. Results Depressed participants exhibited significantly lower motivation than control participants as objectively defined by progressive ratio breakpoints. Both the unipolar and bipolar groups were lower than controls but did not differ from each other. Limitations Medication use differed across groups, and we did not have a separate control task to measure psychomotor activity; however neither medication effects or psychomotor slowing are likely to explain our findings. Conclusions Our study fills an important gap in the literature by providing evidence that diminished effort on the PRT is present across depressed patients who experience either unipolar or bipolar depression. This adds to growing evidence for shared mechanisms of reward and motivation dysfunction, and highlights the importance of improving the assessment and treatment of motivation deficits across the mood disorders spectrum. PMID:26919058

  5. Increased conformity offers diminishing returns for reducing total knee replacement wear.

    Science.gov (United States)

    Fregly, Benjamin J; Marquez-Barrientos, Carlos; Banks, Scott A; DesJardins, John D

    2010-02-01

    Wear remains a significant problem limiting the lifespan of total knee replacements (TKRs). Though increased conformity between TKR components has the potential to decrease wear, the optimal amount and planes of conformity have not been investigated. Furthermore, differing conformities in the medial and lateral compartments may provide designers the opportunity to address both wear and kinematic design goals simultaneously. This study used a computational model of a Stanmore knee simulator machine and a previously validated wear model to investigate this issue for simulated gait. TKR geometries with different amounts and planes of conformity on the medial and lateral sides were created and tested in two phases. The first phase utilized a wide range of sagittal and coronal conformity combinations to blanket a physically realistic design space. The second phase performed a focused investigation of the conformity conditions from the first phase to which predicted wear volume was sensitive. For the first phase, sagittal but not coronal conformity was found to have a significant effect on predicted wear volume. For the second phase, increased sagittal conformity was found to decrease predicted wear volume in a nonlinear fashion, with reductions gradually diminishing as conformity increased. These results suggest that TKR geometric design efforts aimed at minimizing wear should focus on sagittal rather than coronal conformity and that at least moderate sagittal conformity is desirable in both compartments.

  6. Swimming Behaviour and Otolith Characteristics of wildtype and mutant Zebrafish (AIE) under diminished Gravity Conditions

    Science.gov (United States)

    Weigele, J.; Anken, R.; Hilbig, R.

    During microgravity humans often suffer from sensorimotor disorders e g motion sickness a kinetosis Using fish as vertebrate model systems we could previously provide ample evidence that the individually different susceptibility to such disorders is based on an individually differently pronounced asymmetric mineralisation calcification of inner ear stones otoliths In the course of a preliminary study we subjected mutant zebrafish Danio rerio due to malformation of the inner ear - see below - this mutant was termed Asymmetric Inner Ear AIE to diminished gravity conditions during parabolic aircraft flight PF As compared to wildtype WT animals the mutants showed a pronounced kinetotic behaviour The gross-morphology of the inner ears of AIE and WT animals strikingly differed In WT specimens the saccular otoliths were located at the periphery of the inner ear whereas the utricular stones were positioned mediad as it is usually the case in teleosts in most AIE animals dissected however the respective otoliths were positioned in an opposite arrangement Moreover the mutants sported transparent otoliths whereas the otoliths of WT specimens had an opaque appearance This finding clearly indicates that mutant otoliths differed from wildtype ones in their lattice structure i e the calcium carbonate polymorph and thus the compostion of the proteinacious matrix which is a template for calcium carbonate deposition In the course of the present study the PF experiment is scheduled to be carried out in March 2006 we intend to statistically verify

  7. Gamma-variate plasma clearance versus urinary plasma clearance of 51Cr-EDTA in patients with cirrhosis with and without fluid retention

    DEFF Research Database (Denmark)

    Fuglsang, Stefan; Henriksen, Ulrik L; Hansen, Hanne Boskov

    2017-01-01

    In patients with fluid retention, the plasma clearance of (51) Cr-EDTA (Clexp obtained by multiexponential fit) may overestimate the glomerular filtration rate (GFR). The present study was undertaken to compare a gamma-variate plasma clearance (Clgv) with the urinary plasma clearance of (51) Cr......-EDTA (Clu ) in patients with cirrhosis with and without fluid retention. A total of 81 patients with cirrhosis (22 without fluid retention, 59 with ascites) received a quantitative intravenous injection of (51) Cr-EDTA followed by plasma and quantitative urinary samples for 5 h. Clgv was determined from...... the injected dose relative to the plasma concentration-time area, obtained by a gamma-variate iterative fit. Clexp and Clu were determined by standard technique. In patients without fluid retention, Clgv , Clexp and Clu were closely similar. The difference between Clgv and Clu (Clgv - Clu = ΔCl) was mean -0...

  8. Emotional reactivity in depression: diminished responsiveness to anticipated reward but not to anticipated punishment or to nonreward or avoidance.

    Science.gov (United States)

    McFarland, Brian R; Klein, Daniel N

    2009-01-01

    This study compared depressed and nondepressed participants' emotional reactivity to anticipated reward, anticipated punishment, failure to obtain a reward, and successful avoidance of punishment. This study compared residualized change scores on target emotions for currently depressed (n=19), previously depressed (n=19), and never-depressed (n=43) participants during four experimental conditions: anticipated reward (cash), anticipated punishment (cold pressor), nonreward (failure to earn cash), and avoidance (successful avoidance of a cold pressor). Currently depressed participants' reactivity in response to anticipated reward was significantly diminished compared with never depressed participants', and marginally diminished compared with previously depressed participants'. Currently depressed, previously depressed, and never-depressed participants did not differ significantly in their emotional reactivity to anticipated punishment or to nonreward or avoidance. These results suggest that depressed individuals' diminished emotional reactivity may be mainly a state effect and may be limited to anticipated reward. (c) 2008 Wiley-Liss, Inc.

  9. Animal Models of Bacterial Keratitis

    Science.gov (United States)

    Marquart, Mary E.

    2011-01-01

    Bacterial keratitis is a disease of the cornea characterized by pain, redness, inflammation, and opacity. Common causes of this disease are Pseudomonas aeruginosa and Staphylococcus aureus. Animal models of keratitis have been used to elucidate both the bacterial factors and the host inflammatory response involved in the disease. Reviewed herein are animal models of bacterial keratitis and some of the key findings in the last several decades. PMID:21274270

  10. Animal Models of Bacterial Keratitis

    Directory of Open Access Journals (Sweden)

    Mary E. Marquart

    2011-01-01

    Full Text Available Bacterial keratitis is a disease of the cornea characterized by pain, redness, inflammation, and opacity. Common causes of this disease are Pseudomonas aeruginosa and Staphylococcus aureus. Animal models of keratitis have been used to elucidate both the bacterial factors and the host inflammatory response involved in the disease. Reviewed herein are animal models of bacterial keratitis and some of the key findings in the last several decades.

  11. Long-term follow-up of patients with spontaneous clearance of hepatitis C: does viral clearance mean cure?

    LENUS (Irish Health Repository)

    Iqbal, M

    2017-06-01

    Up to 40% of patients with hepatitis C virus (HCV) antibodies are negative for HCV RNA at initial evaluation. If there is a risk of viral re-activation, long term follow-up is required with attendant financial, psychological and medical implications. We investigated the risk of re-activation in the Irish anti-D cohort. Information was obtained from the national hepatitis C database which includes data on patients infected by anti-D immunoglobulin in two large outbreaks, 1977-9 and 1991-94. As part of a screening programme, starting in 1994, 64,907 females exposed to anti-D immunoglobulin were evaluated. Three hundred and forty-seven were found to be antibody positive but HCV RNA negative at initial assessment. 93% had subsequent RNA tests. There was no evidence of HCV recurrence in patients whose infection resolved spontaneously. It appears that two initial sequential negative results for HCV RNA are sufficient to confirm spontaneous viral clearance and probable cure of hepatitis C virus infection.

  12. Changes in glomerular filtration rate, lithium clearance and plasma protein clearances in the early phase after unilateral nephrectomy in living healthy renal transplant donors

    DEFF Research Database (Denmark)

    Strandgaard, S; Kamper, A; Skaarup, P

    1988-01-01

    1. Glomerular and tubular function was studied before and 2 months after unilateral nephrectomy in 14 healthy kidney donors by measurement of the clearances of 51Cr-labelled ethylenediaminetetra-acetate, lithium, beta 2-microglobulin, albumin and immunoglobulin G. 2. The glomerular filtration rate...... (GFR) of the kidney that remained in the donor rose from 45 +/- 10 (mean +/- SD) to 59 +/- 10 ml/min (P less than 0.01) 5 days after contralateral nephrectomy and remained at this level through the observation period. 3. The lithium clearance (CLi) of the remaining kidney rose from 11.6 +/- 3.7 to 20...

  13. Association between augmented renal clearance and clinical failure of antibiotic treatment in brain-injured patients with ventilator-acquired pneumonia: A preliminary study.

    Science.gov (United States)

    Carrie, Cédric; Bentejac, Merry; Cottenceau, Vincent; Masson, Françoise; Petit, Laurent; Cochard, Jean-François; Sztark, François

    2018-02-01

    This preliminary study aimed to determine whether augmented renal clearance (ARC) impacts negatively on the clinical outcome in traumatic brain-injured patients (TBI) treated for a first episode of ventilator-acquired pneumonia (VAP). During a 5-year period, all TBI patients who had developed VAP were retrospectively reviewed to assess variables associated with clinical failure in multivariate analysis. Clinical failure was defined as an impaired clinical response with a need for escalating antibiotics during treatment and/or within 15 days after the end-of-treatment. Recurrence was considered if at least one of the initial causative bacterial strains was growing at a significant concentration from a second sample. Augmented renal clearance (ARC) was defined by an enhanced creatinine clearance exceeding 130mL/min/1.73m2 calculated from a urinary sample during the first three days of antimicrobial therapy. During the study period, 223 TBI patients with VAP were included and 59 (26%) presented a clinical failure. Factors statistically associated with clinical failure were GSC≤7 (OR=2.2 [1.1-4.4], P=0.03), early VAP (OR=3.9 [1.9-7.8], P=0.0001), bacteraemia (OR=11 [2.2-54], P=0.003) and antimicrobial therapy≤7 days (OR=3.7 [1.8-7.4], P=0.0003). ARC was statistically associated with recurrent infections with an OR of 4.4 [1.2-16], P=0.03. ARC was associated with recurrent infection after a first episode of VAP in TBI patients. The optimal administration and dosing of the antimicrobial agents in this context remain to be determined. Copyright © 2017 Société française d'anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.

  14. Increased Hepatic Insulin Clearance After Roux-en-Y Gastric Bypass

    DEFF Research Database (Denmark)

    Bojsen-Møller, Kirstine N; Dirksen, Carsten; Jørgensen, Nils B

    2013-01-01

    Context:Roux-en-Y gastric bypass (RYGB) improves glucose tolerance and ameliorates fasting hyperinsulinemia within days after surgery. Improvements in hepatic insulin sensitivity and insulin clearance could contribute importantly to these effects.Objective:The objective of the investigation...

  15. Intra-operative colloid administration increases the clearance of a post-operative fluid load

    DEFF Research Database (Denmark)

    Borup, Tine; Hahn, Robert; Holte, K

    2009-01-01

    BACKGROUND: It is unknown whether an intra-operative colloid infusion alters the dynamics of a crystalloid load administered post-operatively. METHODS: Ten patients received 12.5 ml/kg of Ringer's lactate over 30 min 1-3 days before and 4 h after laparoscopic cholecystectomy, during which 10 ml....../kg of a colloid solution, hydroxyethylstarch (HES 130/0.4), was infused. The total body clearance of the pre- and post-operative test infusions was taken as the ratio between the urinary excretion and the Hb-derived dilution of venous plasma over 150 min. The plasma clearance of the infused fluid was calculated...... using volume kinetics based on the plasma dilution alone. The pre-operative plasma clearance was compared with the post-operative plasma clearance and patients served as their own control. RESULTS: The urinary excretion averaged 350 ml for the pre-operative infusion and 612 ml post-operatively, which...

  16. Effect of needle puncture and electro-acupuncture on mucociliary clearance in anesthetized quails

    National Research Council Canada - National Science Library

    Tai, Shusheng; Wang, Jiulin; Sun, Feng; Xutian, Stevenson; Wang, Tianshan; King, Malcolm

    2006-01-01

    ... to treat patients with the diseases. Since the impaired mucociliary clearance is among the most important features of airway inflammation in most obstructive respiratory diseases, the effect of needle puncture and electro-acupuncture...

  17. 76 FR 44938 - Agency Information Collection Activities: Proposed Collection; Comment Request; Generic Clearance...

    Science.gov (United States)

    2011-07-27

    ... Administration's commitment to improving service delivery. By qualitative feedback we mean information that... of Qualitative Feedback on Agency Service Delivery: National Cancer Center (NCI) ACTION: 30-Day... Information Collection Request (Generic ICR): ``Generic Clearance for the Collection of Qualitative Feedback...

  18. Using radioaerosols to monitor physiotherapy-enhanced mucus clearance at different levels of the bronchial tree

    Energy Technology Data Exchange (ETDEWEB)

    Hasani, A.; Pavia, D.; Clarke, S.W.; Agnew, J.E. (Royal Free Hospital, London (United Kingdom))

    1993-01-01

    Patients with airways obstruction often find it difficult to clear excess lung secretions. Frequent coughing can clear the larger airways but may itself further damage the airways ciliated epithelium. Various physiotherapy regimes have been proposed yet objective evidence of their efficacy is sparse. Deposited aerosol particles - with an appropriate label for gamma imaging - can track clearance from different lung regions. Published reports have however tended to be equivocal in respect of clearance from the more distal conducting airways. Questions also arise as to coordination of transport rates at different levels of the bronchial tree. We therefore sought to re-assess requirements for effective analysis of physiotherapy-enhanced clearance to yield data on both peripheral and central airways clearance. (author).

  19. CYP1A2 polymorphism and theophylline clearance in Korean non-smoking asthmatics

    National Research Council Canada - National Science Library

    Yim, Eun-Young; Kang, Hye-Ryun; Jung, Jae-Woo; Sohn, Seong-Wook; Cho, Sang-Heon

    2013-01-01

    .... However, the underlying mechanism remains unknown in humans. We investigated the relationship between differences in theophylline clearance and genetic polymorphisms in the CYP1A2 and CYP2E1 gene in 89 Korean asthmatic patients...

  20. Tramadol and o-desmethyl tramadol clearance maturation and disposition in humans

    DEFF Research Database (Denmark)

    Allegaert, Karel; Holford, Nick; Anderson, Brian J

    2015-01-01

    BACKGROUND AND OBJECTIVES: We aimed to study the impact of size, maturation and cytochrome P450 2D6 (CYP2D6) genotype activity score as predictors of intravenous tramadol disposition. METHODS: Tramadol and O-desmethyl tramadol (M1) observations in 295 human subjects (postmenstrual age 25 weeks...... to 84.8 years, weight 0.5-186 kg) were pooled. A population pharmacokinetic analysis was performed using a two-compartment model for tramadol and two additional M1 compartments. Covariate analysis included weight, age, sex, disease characteristics (healthy subject or patient) and CYP2D6 genotype...... activity. A sigmoid maturation model was used to describe age-related changes in tramadol clearance (CLPO), M1 formation clearance (CLPM) and M1 elimination clearance (CLMO). A phenotype-based mixture model was used to identify CLPM polymorphism. RESULTS: Differences in clearances were largely accounted...