Activated protein C ameliorates Bacillus anthracis lethal toxin-induced lethal pathogenesis in rats

PubMed Central

2012-01-01

Background Lethal toxin (LT) is a major virulence factor of Bacillus anthracis. Sprague Dawley rats manifest pronounced lung edema and shock after LT treatments, resulting in high mortality. The heart failure that is induced by LT has been suggested to be a principal mechanism of lung edema and mortality in rodents. Since LT-induced death occurs more rapidly in rats than in mice, suggesting that other mechanisms in addition to the heart dysfunction may be contributed to the fast progression of LT-induced pathogenesis in rats. Coagulopathy may contribute to circulatory failure and lung injury. However, the effect of LT on coagulation-induced lung dysfunction is unclear. Methods To investigate the involvement of coagulopathy in LT-mediated pathogenesis, the mortality, lung histology and coagulant levels of LT-treated rats were examined. The effects of activated protein C (aPC) on LT-mediated pathogenesis were also evaluated. Results Fibrin depositions were detected in the lungs of LT-treated rats, indicating that coagulation was activated. Increased levels of plasma D-dimer and thrombomodulin, and the ameliorative effect of aPC further suggested that the activation of coagulation-fibrinolysis pathways plays a role in LT-mediated pathogenesis in rats. Reduced mortality was associated with decreased plasma levels of D-dimer and thrombomodulin following aPC treatments in rats with LT-mediated pathogenesis. Conclusions These findings suggest that the activation of coagulation in lung tissue contributes to mortality in LT-mediated pathogenesis in rats. In addition, anticoagulant aPC may help to develop a feasible therapeutic strategy. PMID:23170801

Bacillus anthracis Cell Wall Peptidoglycan but Not Lethal or Edema Toxins Produces Changes Consistent With Disseminated Intravascular Coagulation in a Rat Model

PubMed Central

Qiu, Ping; Li, Yan; Shiloach, Joseph; Cui, Xizhong; Sun, Junfeng; Trinh, Loc; Kubler-Kielb, Joanna; Vinogradov, Evgeny; Mani, Haresh; Al-Hamad, Mariam; Fitz, Yvonne; Eichacker, Peter Q.

2013-01-01

Background. Disseminated intravascular coagulation (DIC) appears to be important in the pathogenesis of Bacillus anthracis infection, but its causes are unclear. Although lethal toxin (LT) and edema toxin (ET) could contribute, B. anthracis cell wall peptidoglycan (PGN), not the toxins, stimulates inflammatory responses associated with DIC. Methods and Results. To better understand the pathogenesis of DIC during anthrax, we compared the effects of 24-hour infusions of PGN, LT, ET, or diluent (control) on coagulation measures 6, 24, or 48 hours after infusion initiation in 135 rats. No control recipient died. Lethality rates (approximately 30%) did not differ among PGN, LT, and ET recipients (P = .78). Thirty-three of 35 deaths (94%) occurred between 6 and 24 hours after the start of challenge. Among challenge components, PGN most consistently altered coagulation measures. Compared with control at 6 hours, PGN decreased platelet and fibrinogen levels and increased prothrombin and activated partial thromboplastin times and tissue factor, tissue factor pathway inhibitor, protein C, plasminogen activator inhibitor (PAI), and thrombin-antithrombin complex levels, whereas LT and ET only decreased the fibrinogen level or increased the PAI level (P ≤ .05). Nearly all effects associated with PGN infusion significantly differed from changes associated with toxin infusion (P ≤ .05 for all comparisons except for PAI level). Conclusion. DIC during B. anthracis infection may be related more to components such as PGN than to LT or ET. PMID:23737601

Long-Term Cold Acclimation Extends Survival Time at 0°C and Modifies the Metabolomic Profiles of the Larvae of the Fruit Fly Drosophila melanogaster

PubMed Central

Koštál, Vladimír; Korbelová, Jaroslava; Rozsypal, Jan; Zahradníčková, Helena; Cimlová, Jana; Tomčala, Aleš; Šimek, Petr

2011-01-01

Background Drosophila melanogaster is a chill-susceptible insect. Previous studies on this fly focused on acute direct chilling injury during cold shock and showed that lower lethal temperature (LLT, approximately −5°C) exhibits relatively low plasticity and that acclimations, both rapid cold hardening (RCH) and long-term cold acclimation, shift the LLT by only a few degrees at the maximum. Principal Findings We found that long-term cold acclimation considerably improved cold tolerance in fully grown third-instar larvae of D. melanogaster. A comparison of the larvae acclimated at constant 25°C with those acclimated at constant 15°C followed by constant 6°C for 2 d (15°C→6°C) showed that long-term cold acclimation extended the lethal time for 50% of the population (Lt50) during exposure to constant 0°C as much as 630-fold (from 0.137 h to 86.658 h). Such marked physiological plasticity in Lt50 (in contrast to LLT) suggested that chronic indirect chilling injury at 0°C differs from that caused by cold shock. Long-term cold acclimation modified the metabolomic profiles of the larvae. Accumulations of proline (up to 17.7 mM) and trehalose (up to 36.5 mM) were the two most prominent responses. In addition, restructuring of the glycerophospholipid composition of biological membranes was observed. The relative proportion of glycerophosphoethanolamines (especially those with linoleic acid at the sn-2 position) increased at the expense of glycerophosphocholines. Conclusion Third-instar larvae of D. melanogaster improved their cold tolerance in response to long-term cold acclimation and showed metabolic potential for the accumulation of proline and trehalose and for membrane restructuring. PMID:21957472

Susceptibility to anthrax lethal toxin-induced rat death is controlled by a single chromosome 10 locus that includes rNlrp1.

PubMed

Newman, Zachary L; Printz, Morton P; Liu, Shihui; Crown, Devorah; Breen, Laura; Miller-Randolph, Sharmina; Flodman, Pamela; Leppla, Stephen H; Moayeri, Mahtab

2010-05-20

Anthrax lethal toxin (LT) is a bipartite protease-containing toxin and a key virulence determinant of Bacillus anthracis. In mice, LT causes the rapid lysis of macrophages isolated from certain inbred strains, but the correlation between murine macrophage sensitivity and mouse strain susceptibility to toxin challenge is poor. In rats, LT induces a rapid death in as little as 37 minutes through unknown mechanisms. We used a recombinant inbred (RI) rat panel of 19 strains generated from LT-sensitive and LT-resistant progenitors to map LT sensitivity in rats to a locus on chromosome 10 that includes the inflammasome NOD-like receptor (NLR) sensor, Nlrp1. This gene is the closest rat homolog of mouse Nlrp1b, which was previously shown to control murine macrophage sensitivity to LT. An absolute correlation between in vitro macrophage sensitivity to LT-induced lysis and animal susceptibility to the toxin was found for the 19 RI strains and 12 additional rat strains. Sequencing Nlrp1 from these strains identified five polymorphic alleles. Polymorphisms within the N-terminal 100 amino acids of the Nlrp1 protein were perfectly correlated with LT sensitivity. These data suggest that toxin-mediated lethality in rats as well as macrophage sensitivity in this animal model are controlled by a single locus on chromosome 10 that is likely to be the inflammasome NLR sensor, Nlrp1.

Acaricidal activity of extracts of neem (Azadirachta indica) oil against the larvae of the rabbit mite Sarcoptes scabiei var. cuniculi in vitro.

PubMed

Du, Yong-Hua; Jia, Ren-Yong; Yin, Zhong-Qiong; Pu, Zhong-Hui; Chen, Jiao; Yang, Fan; Zhang, Yu-Qun; Lu, Yang

2008-10-20

The acaricidal activity of the petroleum ether extract, the chloroform extract and the acetic ether extract of neem (Azadirachta indica) oil against Sarcoptes scabiei var. cuniculi larvae was tested in vitro. A complementary log-log (CLL) model was used to analyze the data of the toxicity tests. The results showed that at all test time points, the petroleum ether extract demonstrated the highest activity against the larvae of S. scabiei var. cuniculi, while the activities of the chloroform extract and the acetic ether extract were similar. The activities of both the petroleum ether extract and the chloroform extract against the larvae showed the relation of time and concentration dependent. The median lethal concentration (LC50) of the petroleum ether extract (1.3 microL/mL) was about three times that of the chloroform extract (4.1 microL/mL) at 24 h post-treatment. At the concentrations of 500.0 microL/mL, the median lethal time (LT50) of the petroleum ether extract and the chloroform extract was 8.4 and 9.6 h, respectively.

Divergent thermal specialisation of two South African entomopathogenic nematodes.

PubMed

Hill, Matthew P; Malan, Antoinette P; Terblanche, John S

2015-01-01

Thermal physiology of entomopathogenic nematodes (EPN) is a critical aspect of field performance and fitness. Thermal limits for survival and activity, and the ability of these limits to adjust (i.e., show phenotypic flexibility) depending on recent thermal history, are generally poorly established, especially for non-model nematode species. Here we report the acute thermal limits for survival, and the thermal acclimation-related plasticity thereof for two key endemic South African EPN species, Steinernema yirgalemense and Heterorhabditis zealandica. Results including LT50 indicate S. yirgalemense (LT50 = 40.8 ± 0.3 °C) has greater high temperature tolerance than H. zealandica (LT50 = 36.7 ± 0.2 °C), but S. yirgalemense (LT50 = -2.4 ± 0 °C) has poorer low temperature tolerance in comparison to H. zealandica (LT50 = -9.7 ± 0.3 °C), suggesting these two EPN species occupy divergent thermal niches to one another. Acclimation had both negative and positive effects on temperature stress survival of both species, although the overall variation meant that many of these effects were non-significant. There was no indication of a consistent loss of plasticity with improved basal thermal tolerance for either species at upper lethal temperatures. At lower temperatures measured for H. zealandica, the 5 °C acclimation lowered survival until below -12.5 °C, where after it increased survival. Such results indicate that the thermal niche breadth of EPN species can differ significantly depending on recent thermal conditions, and should be characterized across a broad range of species to understand the evolution of thermal limits to performance and survival in this group.

[Thermal tolerance of some marine copepods].

PubMed

Liao, Yi-Bo; Chen, Quan-Zhen; Zeng, Jiang-Ning; Xu, Xiao-Qun; Shou, Lu; Liu, Jing-Jing; Jiang, Zhi-Bing; Zheng, Ping

2008-02-01

By using experimental ecological methods, the 24 hours semi-lethal temperature (24 h LT50) of typical copepods living in the coastal area of East China Sea was determined to elucidate the effects of thermal discharge from power station on the coastal ecosystem. The results indicated that different copepods at same natural acclimated temperature and specific copepod at different initial acclimated temperature had different thermal tolerance capability. The 24h LT50 of Calanus sinicus and Sinocalanus tenellus at natural acclimated temperature 13.5 degrees C was 26.9 degrees C and 25.4 degrees C, of Acartiella sinensis and Corycaeus affinis at natural acclimated temperature 14.2 degrees C was 26.7 degrees C and 30.5 degrees C, and of Centropages dorsispinatus, Paracalanus crassirostris, Acartia spinicauda and Euterpina acutifrons at natural acclimated temperature 28.0 degrees C was 34.0 degrees C, 34.3 degrees C, 35.7 degrees C and 36.0 degrees C, respectively. The 24h LT50 of S. tenellus at natural acclimated temperature 13.5 degrees C and 23.5 degrees C was 25.4 degrees C and 33.0 degrees C, respectively.

The use of Aedes aegypti larvae attractants to enhance the effectiveness of larvicides.

PubMed

Gonzalez, Paula V; Harburguer, Laura; González-Audino, Paola A; Masuh, Héctor M

2016-06-01

Aedes aegypti (L.) is an important dengue, chikungunya, and yellow fever vector. Immature stages of this species inhabit human-made containers placed in residential landscapes, and the application of larvicides inside containers that cannot be eliminated is still considered a priority in control programs. Larvicidal efficacy is influenced by several factors, including the formulation used, the water quality, and the susceptibility of larvae, among others. If an attractant can be incorporated into a slow-release larvicide formulation, it will be feasible to direct the larvae into the source of insecticide and thereby improving its efficacy. We studied the influence of 1-octen-3ol and 3-methylphenol on the rate of Ae. aegypti larvae mortality using the larvicides Bacillus thuringiensis var. israelensis (Bti), temephos, and spinosad. These chemicals were combined with the larvicides mixed with agar during the bioassays. Mortality was registered every 10 min, and a lethal time 50 (LT50) was calculated. The inclusion of the Ae. aegypti larvae attractants with the larvicides into a solid agar matrix improved their efficiency obtaining a strong and marked reduction in the LT50 compared with the use of larvicides alone.

Alveolar Macrophages Prevent Lethal Influenza Pneumonia By Inhibiting Infection Of Type-1 Alveolar Epithelial Cells

PubMed Central

Cardani, Amber; Boulton, Adam; Kim, Taeg S.; Braciale, Thomas J.

2017-01-01

The Influenza A virus (IAV) is a major human pathogen that produces significant morbidity and mortality. To explore the contribution of alveolar macrophages (AlvMΦs) in regulating the severity of IAV infection we employed a murine model in which the Core Binding Factor Beta gene is conditionally disrupted in myeloid cells. These mice exhibit a selective deficiency in AlvMΦs. Following IAV infection these AlvMΦ deficient mice developed severe diffuse alveolar damage, lethal respiratory compromise, and consequent lethality. Lethal injury in these mice resulted from increased infection of their Type-1 Alveolar Epithelial Cells (T1AECs) and the subsequent elimination of the infected T1AECs by the adaptive immune T cell response. Further analysis indicated AlvMΦ-mediated suppression of the cysteinyl leukotriene (cysLT) pathway genes in T1AECs in vivo and in vitro. Inhibition of the cysLT pathway enzymes in a T1AECs cell line reduced the susceptibility of T1AECs to IAV infection, suggesting that AlvMΦ-mediated suppression of this pathway contributes to the resistance of T1AECs to IAV infection. Furthermore, inhibition of the cysLT pathway enzymes, as well as blockade of the cysteinyl leukotriene receptors in the AlvMΦ deficient mice reduced the susceptibility of their T1AECs to IAV infection and protected these mice from lethal infection. These results suggest that AlvMΦs may utilize a previously unappreciated mechanism to protect T1AECs against IAV infection, and thereby reduce the severity of infection. The findings further suggest that the cysLT pathway and the receptors for cysLT metabolites represent potential therapeutic targets in severe IAV infection. PMID:28085958

Role of the protective antigen octamer in the molecular mechanism of anthrax lethal toxin stabilization in plasma

PubMed Central

Kintzer, Alexander F.; Sterling, Harry J.; Tang, Iok I.; Abdul-Gader, Ali; Miles, Andrew J.; Wallace, B. A.; Williams, Evan R.; Krantz, Bryan A.

2010-01-01

Anthrax is caused by strains of Bacillus anthracis that produce two key virulence factors, anthrax toxin (Atx) and a poly-γ-D-glutamic acid capsule. Atx is comprised of three-proteins: protective antigen (PA) and two enzymes, lethal factor (LF) and edema factor (EF). To disrupt cell function, these components must assemble into holotoxin complexes, which contain either a ring-shaped homooctameric or homoheptameric PA oligomer bound to multiple copies of either LF and/or EF, producing lethal toxin (LT), edema toxin, or mixtures thereof. Once a host cell endocytoses these complexes, PA converts into a membrane-inserted channel that translocates LF and EF into the cytosol. LT may assemble on host cell surfaces or extracellularly in plasma. We show that under physiological conditions in bovine plasma that LT complexes containing heptameric PA aggregate and inactivate more readily than LT complexes containing octameric PA. LT complexes containing octameric PA possess enhanced stability, channel forming activity, and macrophage cytotoxicity relative to those containing heptameric PA. Under physiological conditions, multiple biophysical probes reveal that heptameric PA can prematurely adopt the channel conformation, but octameric PA complexes remain in their soluble prechannel configuration allowing them to resist aggregation and inactivation. We conclude that PA may form an octameric oligomeric state as a means to produce a more stable and active LT complex that may circulate freely in the blood. PMID:20433851

Acaricidal activity of petroleum ether extract of neem (Azadirachta indica) oil and its four fractions separated by column chromatography against Sarcoptes scabiei var. cuniculi larvae in vitro.

PubMed

Deng, Yunxia; Shi, Dongxia; Yin, Zhongqiong; Guo, Jianhong; Jia, Renyong; Xu, Jiao; Song, Xu; Lv, Cheng; Fan, Qiaojia; Liang, Xiaoxia; Shi, Fei; Ye, Gang; Zhang, Wei

2012-04-01

The petroleum ether extract of neem oil and its four fractions separated by column chromatography was diluted at different concentrations with liquid paraffin. The acaricidal bioassay was conducted using a dipping method. The results indicated that the median lethal concentration (LC50) of the petroleum ether extract (at the concentration of 500.0ml/l) was 70.9ml/l, 24h after treatment. At concentrations of 500.0, 250.0, 125.0, 62.5 and 31.2ml/l, the median lethal times (LT50) of the petroleum ether extract were 8.7, 8.8, 10.8, 11.5 and 13.1h, respectively. Thin-layer chromatography (TLC) showed that the petroleum ether extract of neem oil separated into four fractions (F1-F4). Acaricidal activity of 68.3% and 100.0% in the F2 and F4 was confirmed. These results suggest that petroleum ether extracts of neem oil and its four fractions possess useful acaricidal activity in vitro. Copyright © 2012 Elsevier Inc. All rights reserved.

Acaricidal activity of four fractions and octadecanoic acid-tetrahydrofuran-3,4-diyl ester isolated from chloroform extracts of neem (Azadirachta indica) oil against Sarcoptes scabiei var. cuniculi larvae in vitro.

PubMed

Du, Yong-Hua; Li, Jin-Liang; Jia, Ren-Yong; Yin, Zhong-Qiong; Li, Xu-Ting; Lv, Cheng; Ye, Gang; Zhang, Li; Zhang, Yu-Qun

2009-07-07

Four fractions obtained from chloroform extracts of neem (Azadirachta indica) oil by column chromatography were investigated for acaricidal activity against Sarcoptes scabiei var. cuniculi larvae in vitro. Octadecanoic acid-tetrahydrofuran-3,4-diyl ester was isolated from an active fraction of the chloroform extract and its toxicity against S. scabiei larvae was tested in vitro. A complementary log-log model was used to analyse the toxicity data. Activity was found in the third fraction, with 100% corrected mortality after 4.5 h of exposure at a concentration of 200 mg ml(-1). This fraction was repeatedly re-crystallised in acetone to yield a white amorphous powder, identified as octadecanoic acid-tetrahydrofuran-3,4-diyl ester, with a median lethal concentration (LC(50)) of 0.1 mg ml(-1) at 24 h post-treatment. The median lethal time (LT(50)) for this compound was 15.3 h at a concentration of 7.5 mg ml(-1).

Maternal Vaccination with a Fimbrial Tip Adhesin and Passive Protection of Neonatal Mice against Lethal Human Enterotoxigenic Escherichia coli Challenge

PubMed Central

Luiz, Wilson B.; Rodrigues, Juliana F.; Crabb, Joseph H.

2015-01-01

Globally, enterotoxigenic Escherichia coli (ETEC) is a leading cause of childhood and travelers' diarrhea, for which an effective vaccine is needed. Prevalent intestinal colonization factors (CFs) such as CFA/I fimbriae and heat-labile enterotoxin (LT) are important virulence factors and protective antigens. We tested the hypothesis that donor strand-complemented CfaE (dscCfaE), a stabilized form of the CFA/I fimbrial tip adhesin, is a protective antigen, using a lethal neonatal mouse ETEC challenge model and passive dam vaccination. For CFA/I-ETEC strain H10407, which has been extensively studied in volunteers, an inoculum of 2 × 107 bacteria resulted in 50% lethal doses (LD50) in neonatal DBA/2 mice. Vaccination of female DBA/2 mice with CFA/I fimbriae or dscCfaE, each given with a genetically attenuated LT adjuvant (LTK63) by intranasal or orogastric delivery, induced high antigen-specific serum IgG and fecal IgA titers and detectable milk IgA responses. Neonates born to and suckled by dams antenatally vaccinated with each of these four regimens showed 78 to 93% survival after a 20× LD50 challenge with H10407, compared to 100% mortality in pups from dams vaccinated with sham vaccine or LTK63 only. Crossover experiments showed that high pup survival rates after ETEC challenge were associated with suckling but not birthing from vaccinated dams, suggesting that vaccine-specific milk antibodies are protective. In corroboration, preincubation of the ETEC inoculum with antiadhesin and antifimbrial bovine colostral antibodies conferred a dose-dependent increase in pup survival after challenge. These findings indicate that the dscCfaE fimbrial tip adhesin serves as a protective passive vaccine antigen in this small animal model and merits further evaluation. PMID:26371126

The Xenon Test Chamber Q-SUN® for testing realistic tolerances of fungi exposed to simulated full spectrum solar radiation.

PubMed

Dias, Luciana P; Araújo, Claudinéia A S; Pupin, Breno; Ferreira, Paulo C; Braga, Gilberto Ú L; Rangel, Drauzio E N

2018-06-01

The low survival of insect-pathogenic fungi when used for insect control in agriculture is mainly due to the deleterious effects of ultraviolet radiation and heat from solar irradiation. In this study, conidia of 15 species of entomopathogenic fungi were exposed to simulated full-spectrum solar radiation emitted by a Xenon Test Chamber Q-SUN XE-3-HC 340S (Q-LAB ® Corporation, Westlake, OH, USA), which very closely simulates full-spectrum solar radiation. A dendrogram obtained from cluster analyses, based on lethal time 50 % and 90 % calculated by Probit analyses, separated the fungi into three clusters: cluster 3 contains species with highest tolerance to simulated full-spectrum solar radiation, included Metarhizium acridum, Cladosporium herbarum, and Trichothecium roseum with LT 50  > 200 min irradiation. Cluster 2 contains eight species with moderate UV tolerance: Aschersonia aleyrodis, Isaria fumosorosea, Mariannaea pruinosa, Metarhizium anisopliae, Metarhizium brunneum, Metarhizium robertsii, Simplicillium lanosoniveum, and Torrubiella homopterorum with LT 50 between 120 and 150 min irradiation. The four species in cluster 1 had the lowest UV tolerance: Lecanicillium aphanocladii, Beauveria bassiana, Tolypocladium cylindrosporum, and Tolypocladium inflatum with LT 50  < 120 min irradiation. The QSUN Xenon Test Chamber XE3 is often used by the pharmaceutical and automotive industry to test light stability and weathering, respectively, but it was never used to evaluate fungal tolerance to full-spectrum solar radiation before. We conclude that the equipment provided an excellent tool for testing realistic tolerances of fungi to full-spectrum solar radiation of microbial agents for insect biological control in agriculture. Copyright © 2018 British Mycological Society. Published by Elsevier Ltd. All rights reserved.

[The establishment of the immortalized mouse brain microvascular pericytes model and its preliminary application in screening of cerebrovascular toxicants].

PubMed

Zhao, H P; Gao, Y F; Xia, D; Zhao, Z Q; Wu, S; Wang, X H; Liu, H X; Xiao, C; Xing, X M; He, Y

2018-05-06

Objective: To establish the immortalized mouse brain microvascular pericytes model and to apply to the cerebrovascular toxicants screening study. Methods: Brain pericytes were isolated from 3 weeks of mice by tissue digestion. Immortalized pericyte cell line was constructed by infecting with LT retrovirus. Monoclone was selected to purify the immortalized pericyte cell line. The pericyte characteristics and purity were explored by immunocytochemistry. Cell proliferation was measured by using the Pomega MTS cell Proliferation Colorimetric Assay Kit. Pericytes were treated with 0, 160, 320, 640, 1 280, 2 560 μmol/L lead acetate, 0, 5, 10, 20, 40, 80 μmol/L cadmium chloride and 0, 5, 10, 20, 40, 80 μmol/L sodium arsenite in 24 hours. Cell toxicity of each group was determined by MTS assay, median lethal dose (LD(50)) was calculated in linear regression. Results: Mouse brain pericytes were successfully isolated by tissue separation and enzyme digestion method. After immortalized by LT retroviruses, monoclone was selected and expanded to establish pericyte cell line. The brain pericytes exhibited typical long spindle morphology and positive staining for α-SMA and Vimentin. The proliferation of brain pericytes cell lines was very slowly, and the doubling time was about 48 hours. The proliferation of immortalized brain pericytes cell lines was very quickly, and the doubling time was about 24 hours. After lead acetate, cadmium chloride and sodium arsenite treatment for 24 hours respectively, gradual declines in cell viability were observed. The LD(50) of lead acetate was 2 025.0 μmol/L, the LD(50) of cadmium chloride was 36.6 μmol/L, and the LD(50) of sodium arsenite was 33.2 μmol/L. Conclusion: The immortalized mouse brain microvascular pericyte model is established successfully by infecting with LT retrovirus, and can be applied to screen cerebrovascular toxicants. The toxicity of these toxicants to immortalized mouse brain microvascular pericyte is in sequence: sodium arsenite,cadmium chloride, lead acetate.

Survival of Primates in Lethal Septic Shock Following Delayed Treatment with Steroid.

DTIC Science & Technology

1981-02-26

TECHNICAL REPORT NO. 142 SURVIVAL OF PRIMATES IN LETHAL SEPTIC SHOCK FOLLOWING DELAYED TREAMENT WIn STEROID L. B. Hinshaw, L. T. Archer, B. K. Belier ...2. Schumer W: Steroids in the treatment of clinical septic shock. Ann Surg 184:333-341, 1976. 3. Hinshaw LB, Belier PK, Archer LT, Flournoy DJ, White...not preventable by antibiotic alone. Infect Immun ZS:538-5)7, 1979. 6. Hinshaw LB, Archer LT, Belier -Todd BK, Coalson .JJ, Flournoy DL, Passey R

The effect of deletion of the edema factor on Bacillus anthracis pathogenicity in guinea pigs and rabbits.

PubMed

Levy, Haim; Weiss, Shay; Altboum, Zeev; Schlomovitz, Josef; Rothschild, Nili; Glinert, Itai; Sittner, Assa; Kobiler, David

2012-01-01

Bacillus anthracis secretes three major components, which assemble into two bipartite toxins: lethal toxin (LT), composed of lethal factor (LF) and protective antigen (PA) and edema toxin (ET), composed of edema factor (EF) and PA. EF is a potent calmodulin-dependent adenylate cyclase, which is internalized into the target cell following PA binding. Once inside the cell, EF elevates cAMP levels, interrupting intracellular signaling. Effects of ET were demonstrated on monocytes, neutrophils and T-cells. In an earlier work we demonstrated that a deletion of LF in a fully virulent strain had no effect in guinea pigs and a significant, but not major, effect in the rabbit model. These results suggested that EF might play an important role in the development of infection and mortality following exposure to B. anthracis spores. To evaluate the role of EF in B. anthracis pathogenicity we deleted the cya gene, which encodes the EF protein, in the fully virulent Vollum strain. The Δcya mutant was fully virulent in the guinea pig model as determined by LD(50) experiments. In the rabbit model, when infected subcutaneously, the absence of EF had no effect on the virulence of the mutant. However an increase of two orders of magnitude in the LD(50) was demonstrated when the rabbits were infected by intranasal instillation accompanied with partial mortality and increased mean time to death. These results argue that in the guinea pig model the presence of one of the toxins, ET or LT is sufficient for the development of the infection. In the rabbit model ET plays a role in respiratory infection, most probably mediating the early steps of host colonization. Copyright © 2011 Elsevier Ltd. All rights reserved.

[Freezing resistance and injury indices for different cultivars of winter-spring wheat in Huang-Huai-Hai Plain. I . Comparison of freezing resistance for different cultivars of winter-spring wheat during mid-winter period].

PubMed

Mu, Cheng-ying; Yang, Xiao-guang; Yang, Jie; Li, Ke-nan; Zheng, Dong-xiao

2015-10-01

The relationships between mortality rate and low temperature for different cultivars of winter-spring wheat during mid-winter period were identified through two-year outdoor potting experiments and indoor manually controlled freezing experiments. We defined the lethally critical temperature and the density of antifreeze capability when the mortality rate reached 10%, 20% and 50% for different cultivars of winter-spring wheat during mid-winter period. The strong-winterness wheat (Yanda 1817 and Jing 411) showed the best freezing resistance and the 50%-lethal temperatures (LT50) of these two cultivars were -21.5 °C and -21.2 °C, respectively. The freezing resistance of winterness wheat and weak-winternes wheat were worse than that of strong-winterness wheat. The LT50 of winterness wheat cultivars Nongda 211 and Nongda 5363 were -21.1 °C and -20.3 °C, while that of weak-winterness wheat cultivars Zheng 366 and Ping' an 8 were -18.5 °C and -18.4 °C , respectively. Springness wheat (Zheng 9023 and Yanzhan 4110) showed the worst freezing resistance, and the LT50 were -15.4 °C and -14.7 °C, respectively. When temperature declined to freezing injury occurred, mortality rate increment for weak-winterness wheat was the highest for each 1 °C decrease. The mortality rates of weak-winterness wheat cultivars Zheng 366 and Ping' an 8 increased by 16.8% and 25.8%, and that of winterness wheat cultivars Nongda 211 and Nongda 5363 increased by 14.7% and 18.9%. The mortality rate of strong-winterness wheat cultivars Yanda 1817 and Jing 411 increased by 15.4% and 13.1%, and that of springiness wheat cultivas Zheng 9023 and Yanzhan 4110 increased by 13.8% and 15.1%. Comparatively, if temperature decreased continuously after the occurrence of freezing injury, the weak-winterness wheat would suffer greater risk.

Interactions between Entomopathogenic Fungus, Metarhizium anisopliae and Sublethal Doses of Spinosad for Control of House Fly, Musca domestica

PubMed Central

Sharififard, M; Mossadegh, MS; Vazirianzadeh, B; Zarei-Mahmoudabadi, A

2011-01-01

Background: Metarhizium anisopliae strain IRAN 437C is one of the most virulent fungal isolates against house fly, Musca domestica. The objective of this study was to determine the interaction of this isolate with sublethal doses of spinosad against housefly. Methods: In adult bioassay, conidia of entomopathogenic fungus were applied as inoculated bait at 105 and 107 spore per gram and spinosad at 0.5, 1 and 1.5 μg (A.I.) per gram bait. In larval bioassay, conidia were applied as combination of spore with larval bedding at 106 and 108 spore per gram and spinosad at sublethals of 0.002, 0.004 and 0.006 μg (AI) per gram medium. Results: Adult mortality was 48% and 72% for fungus alone but ranged from 66–87% and 89–95% in combination treatments of 105 and 107 spore/g with sublethal doses of spinosad respectively. The interaction between 105 spore/g with sublethals exhibited synergistic effect, but in combination of 107 spore in spite of higher mortality, the interaction was additive. There was significant difference in LT50 among various treatments. LT50 values in all combination treatments were smaller than LT50 values in alone ones. Larval mortality was 36% and 69% for fungus alone but ranged from 58%–78% and 81%–100% in combination treatments of 106 and 108 spore/g medium with sublethals of spinosad respectively. The interaction was synergistic in all combination treatments of larvae. Conclusion: The interaction between M. anispliae and spinosad indicated a synergetic effect that increased the house fly mortality as well as reduced the lethal time. PMID:22808408

Laboratory Evaluation of Isaria fumosorosea CCM 8367 and Steinernema feltiae Ustinov against Immature Stages of the Colorado Potato Beetle

PubMed Central

Hussein, Hany M.; Skoková Habuštová, Oxana; Půža, Vladimír; Zemek, Rostislav

2016-01-01

The Colorado potato beetle, Leptinotarsa decemlineata, has developed resistance to most registered pesticides and has become one of the most difficult insect pests to control. Development of new biopesticides targeting this pest might solve the resistance problem and contribute to sustainable crop production. Laboratory experiments were conducted to assess the efficacy of Isaria fumosorosea (syn. Paecilomyces fumosoroseus) strain CCM 8367 against L. decemlineata when applied alone or combined with the entomopathogenic nematode Steinernema feltiae. The last-instar larvae of the Colorado potato beetle showed the highest susceptibility to I. fumosorosea followed by pre-pupae and pupae. The median lethal concentration (LC50) was estimated to be 1.03×106 blastospores/ml. The strain CCM 8367 was more virulent, causing 92.6% mortality of larvae (LT50 = 5.0 days) compared to the reference strain Apopka 97, which caused 54.5% mortality (LT50 = 7.0 days). The combined application of the fungus with the nematodes increased the mortality up to 98.0%. The best results were obtained when S. feltiae was applied simultaneously with I. fumosorosea (LT50 = 2.0 days); later application negatively affected both the penetration rate and the development of the nematodes. We can conclude that the strain CCM 8367 of I. fumosorosea is a prospective biocontrol agent against immature stages of L. decemlineata. For higher efficacy, application together with an entomopathogenic nematode is recommended. PMID:27015633

Selection of entomopathogenic fungi for aphid control.

PubMed

Vu, Van Hanh; Hong, Suk Il; Kim, Keun

2007-12-01

Twelve strains of entomopathogenic fungi such as Lecanicillium lecanii, Paecilomyces farinosus, Beauveria bassiana, Metarhizium anisopliae, Cordyceps scarabaeicola, and Nomuraea rileyi were screened for aphid control. At 25 degrees C and 75% relative humidity (RH), among tested entomopathogenic fungi, L. lecanii 41185 showed the highest virulent pathogenicity for both Myzus persicae and Aphis gossypii, and their control values were both nearly 100% 5 and 2 d after treatment, respectively. Moreover, at an RH of 45% and in a wide temperature range (20-30 degrees C), L. lecanii 41185 also exhibited the highest virulence to M. persicae. The control value of M. persicae and the 50% lethal time (LT50) decreased significantly as the applied conidial concentration increased. The 50% lethal concentration (LC50) of the conidial suspension of this fungus was determined to be 6.55x10(5) conidia/ml. The control values of M. persicae resulting from the application of 1x10(7) and 1x10(8) conidia/ml were nearly the same and were significantly higher than that of 1x10(6) conidia/ml. The tested entomopathogenic fungi grew in a broad temperature range (15-30 degrees C). Lecanicillium strains showed optimum growth at 25 degrees C. The aerial conidia of Lecanicillium strains also could germinate in a broad temperature range (15-30 degrees C) and L. lecanii 41185 was the only strain with conidial germination at 35 degrees C.

Vaccination with plasmid DNA encoding a mutant toxic shock syndrome toxin-1 ameliorates toxin-induced lethal shock in mice.

PubMed

Feng, Mao-Hui; Cui, Jing-Chun; Nakane, Akio; Hu, Dong-Liang

2013-09-01

Staphylococcal toxic shock syndrome toxin-1 (TSST-1), a superantigenic toxin produced by Staphylococcus (S.) aureus, is a major cause of septic shock and toxic shock syndrome. To investigate whether vaccination with a plasmid DNA encoding a non-toxic mutant TSST-1 (mTSST-1) can protect mice against wild-type TSST-1-induced lethal shock, the mice were intranasally immunized with the plasmid DNA (named pcDNA-mTSST-1) plus a mucosal adjuvant, a non-toxic mutant labile toxin (mLT). After the immunization, the mice were challenged with TSST-1 and lipopolysaccharide (LPS). The survival rate of mice immunized with pcDNA-mTSST-1 plus mLT was higher than that of the control mice immunized with PBS alone, mLT alone, pcDNA-mTSST-1 alone, or a parent plasmid plus mLT. The titers of interferon-γ (IFN-γ) in the sera of mice immunized with pcDNA-mTSST-1 plus mLT were significantly lower than those of the mLT control mice. Immunization with pcDNA-mTSST-1 plus mLT increased the serum levels of TSST-1-specific antibodies, especially immunoglobulin G1 (IgG1) and IgG2a subclasses. Furthermore, the sera obtained from mice immunized with pcDNA-mTSST-1 plus mLT significantly inhibited the TSST-1-induced secretion of IFN-γ and tumor necrosis factor-α (TNF-α) in murine spleen cells in vitro. These results indicate that immunization with pcDNA-mTSST-1 plus mLT provides protection against the lethal toxic shock of mice induced by wild-type TSST-1. The protective effect could be due to TSST-1-specific neutralizing antibodies as well as the inhibition of IFN-γ and TNF-α secretions. Since TSST-1 is commonly released by invasive S. aureus, the pcDNA-mTSST-1 should be useful in preventing toxin-induced shock resulting from S. aureus infection.

Leukotriene B4 receptor type 2 protects against pneumolysin-dependent acute lung injury.

PubMed

Shigematsu, Misako; Koga, Tomoaki; Ishimori, Ayako; Saeki, Kazuko; Ishii, Yumiko; Taketomi, Yoshitaka; Ohba, Mai; Jo-Watanabe, Airi; Okuno, Toshiaki; Harada, Norihiro; Harayama, Takeshi; Shindou, Hideo; Li, Jian-Dong; Murakami, Makoto; Hoka, Sumio; Yokomizo, Takehiko

2016-10-05

Although pneumococcal infection is a serious problem worldwide and has a high mortality rate, the molecular mechanisms underlying the lethality caused by pneumococcus remain elusive. Here, we show that BLT2, a G protein-coupled receptor for leukotriene B 4 and 12(S)-hydroxyheptadecatrienoic acid (12-HHT), protects mice from lung injury caused by a pneumococcal toxin, pneumolysin (PLY). Intratracheal injection of PLY caused lethal acute lung injury (ALI) in BLT2-deficient mice, with evident vascular leakage and bronchoconstriction. Large amounts of cysteinyl leukotrienes (cysLTs), classically known as a slow reactive substance of anaphylaxis, were detected in PLY-treated lungs. PLY-dependent vascular leakage, bronchoconstriction, and death were markedly ameliorated by treatment with a CysLT1 receptor antagonist. Upon stimulation by PLY, mast cells produced cysLTs that activated CysLT1 expressed in vascular endothelial cells and bronchial smooth muscle cells, leading to lethal vascular leakage and bronchoconstriction. Treatment of mice with aspirin or loxoprofen inhibited the production of 12-HHT and increased the sensitivity toward PLY, which was also ameliorated by the CysLT1 antagonist. Thus, the present study identifies the molecular mechanism underlying PLY-dependent ALI and suggests the possible use of CysLT1 antagonists as a therapeutic tool to protect against ALI caused by pneumococcal infection.

Leukotriene B4 receptor type 2 protects against pneumolysin-dependent acute lung injury

PubMed Central

Shigematsu, Misako; Koga, Tomoaki; Ishimori, Ayako; Saeki, Kazuko; Ishii, Yumiko; Taketomi, Yoshitaka; Ohba, Mai; Jo-Watanabe, Airi; Okuno, Toshiaki; Harada, Norihiro; Harayama, Takeshi; Shindou, Hideo; Li, Jian-Dong; Murakami, Makoto; Hoka, Sumio; Yokomizo, Takehiko

2016-01-01

Although pneumococcal infection is a serious problem worldwide and has a high mortality rate, the molecular mechanisms underlying the lethality caused by pneumococcus remain elusive. Here, we show that BLT2, a G protein-coupled receptor for leukotriene B4 and 12(S)-hydroxyheptadecatrienoic acid (12-HHT), protects mice from lung injury caused by a pneumococcal toxin, pneumolysin (PLY). Intratracheal injection of PLY caused lethal acute lung injury (ALI) in BLT2-deficient mice, with evident vascular leakage and bronchoconstriction. Large amounts of cysteinyl leukotrienes (cysLTs), classically known as a slow reactive substance of anaphylaxis, were detected in PLY-treated lungs. PLY-dependent vascular leakage, bronchoconstriction, and death were markedly ameliorated by treatment with a CysLT1 receptor antagonist. Upon stimulation by PLY, mast cells produced cysLTs that activated CysLT1 expressed in vascular endothelial cells and bronchial smooth muscle cells, leading to lethal vascular leakage and bronchoconstriction. Treatment of mice with aspirin or loxoprofen inhibited the production of 12-HHT and increased the sensitivity toward PLY, which was also ameliorated by the CysLT1 antagonist. Thus, the present study identifies the molecular mechanism underlying PLY-dependent ALI and suggests the possible use of CysLT1 antagonists as a therapeutic tool to protect against ALI caused by pneumococcal infection. PMID:27703200

Maternal vaccination with a fimbrial tip adhesin and passive protection of neonatal mice against lethal human enterotoxigenic Escherichia coli challenge.

PubMed

Luiz, Wilson B; Rodrigues, Juliana F; Crabb, Joseph H; Savarino, Stephen J; Ferreira, Luis C S

2015-12-01

Globally, enterotoxigenic Escherichia coli (ETEC) is a leading cause of childhood and travelers' diarrhea, for which an effective vaccine is needed. Prevalent intestinal colonization factors (CFs) such as CFA/I fimbriae and heat-labile enterotoxin (LT) are important virulence factors and protective antigens. We tested the hypothesis that donor strand-complemented CfaE (dscCfaE), a stabilized form of the CFA/I fimbrial tip adhesin, is a protective antigen, using a lethal neonatal mouse ETEC challenge model and passive dam vaccination. For CFA/I-ETEC strain H10407, which has been extensively studied in volunteers, an inoculum of 2 × 10(7) bacteria resulted in 50% lethal doses (LD50) in neonatal DBA/2 mice. Vaccination of female DBA/2 mice with CFA/I fimbriae or dscCfaE, each given with a genetically attenuated LT adjuvant (LTK63) by intranasal or orogastric delivery, induced high antigen-specific serum IgG and fecal IgA titers and detectable milk IgA responses. Neonates born to and suckled by dams antenatally vaccinated with each of these four regimens showed 78 to 93% survival after a 20× LD50 challenge with H10407, compared to 100% mortality in pups from dams vaccinated with sham vaccine or LTK63 only. Crossover experiments showed that high pup survival rates after ETEC challenge were associated with suckling but not birthing from vaccinated dams, suggesting that vaccine-specific milk antibodies are protective. In corroboration, preincubation of the ETEC inoculum with antiadhesin and antifimbrial bovine colostral antibodies conferred a dose-dependent increase in pup survival after challenge. These findings indicate that the dscCfaE fimbrial tip adhesin serves as a protective passive vaccine antigen in this small animal model and merits further evaluation. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Construction of a Hypervirulent and Specific Mycoinsecticide for Locust Control

PubMed Central

Fang, Weiguo; Lu, Hsiao-Ling; King, Glenn F.; St. Leger, Raymond J.

2014-01-01

Locusts and grasshoppers (acridids) are among the worst pests of crops and grasslands worldwide. Metarhizium acridum, a fungal pathogen that specifically infects acridids, has been developed as a control agent but its utility is limited by slow kill time and greater expense than chemical insecticides. We found that expression of four insect specific neurotoxins improved the efficacy of M. acridum against acridids by reducing lethal dose, time to kill and food consumption. Coinoculating recombinant strains expressing AaIT1(a sodium channel blocker) and hybrid-toxin (a blocker of both potassium and calcium channels), produced synergistic effects, including an 11.5-fold reduction in LC50, 43% reduction in LT50 and a 78% reduction in food consumption. However, specificity was retained as the recombinant strains did not cause disease in non-acridids. Our results identify a repertoire of toxins with different modes of action that improve the utility of fungi as specific control agents of insects. PMID:25475694

Soluble P-selectin rescues mice from anthrax lethal toxin-induced mortality through PSGL-1 pathway-mediated correction of hemostasis.

PubMed

Sun, Der-Shan; Chang, Yao-Wen; Kau, Jyh-Hwa; Huang, Hsin-Hsien; Ho, Pei-Hsun; Tzeng, Yin-Jeh; Chang, Hsin-Hou

2017-10-03

As one of the virulence factors of Bacillus anthracis, lethal toxin (LT) induces various pathogenic responses including the suppression of the coagulation system. In this study, we observed that LT markedly increased the circulating soluble P-selectin (sP-sel) levels and microparticle (MP) count in wild-type but not P-selectin (P-sel, Selp -/- ) or P-sel ligand-1 (PSGL-1, Selplg -/- ) knockout mice. Because sP-sel induces a hypercoagulable state through PSGL-1 pathway to generate tissue factor-positive MPs, we hypothesized that the increase in plasma sP-sel levels can be a self-rescue response in hosts against the LT-mediated suppression of the coagulation system. In agreement with our hypothesis, our results indicated that compared with wild-type mice, Selp -/- and Selplg -/- mice were more sensitive to LT. In addition, the recombinant sP-sel treatment markedly ameliorated LT-mediated pathogenesis and reduced mortality. As a result, elicitation of circulating sP-sel is potentially a self-rescue response, which is beneficial to host recovery from an LT-induced hypocoagulation state. These results suggest that the administration of sP-sel is likely to be useful in the development of a new strategy to treat anthrax.

Metabolic Depression is Delayed and Mitochondrial Impairment Averted during Prolonged Anoxia in the ghost shrimp, Lepidophthalmus louisianensis (Schmitt, 1935)

PubMed Central

Holman, Jeremy D.; Hand, Steven C.

2009-01-01

Lepidophthalmus louisianensis burrows deeply into oxygen-limited estuarine sediments and is subjected to extended anoxia at low tides. Large specimens (>2 g) have a lethal time for 50% mortality (LT50) of 64 h under anoxia at 25º C. Small specimens (<1 g) have a significantly higher LT50 of 113 h, which is the longest ever reported for a crustacean. Whole body lactate levels rise dramatically under anoxia and exceed 120 µmol g.f.w.−1 by 72 h. ATP, ADP, and AMP do not change during 48 h of anoxia, but arginine phosphate declines by over 50%. Thus arginine phosphate may help stabilize the ATP pool. Surprisingly, when compared to the aerobic resting rate, ATP production under anoxia is unchanged during the first 12 h, and drops to only about 50% between 12 and 48 h. Finally, after 48 h of anoxia, a major metabolic depression to less than 5% occurs. Downregulation of metabolism is delayed in L. louisianensis compared to many invertebrates that exhibit facultative anaerobiosis. Bioenergetic constraints as a result of eventual metabolic depression led to ionic disturbances like calcium overload and compromised membrane potential of mitochondria. Because these phenomena trigger apoptosis in mammalian species, we evaluated the susceptibility of ghost shrimp mitochondria to opening of the mitochondrial permeability transition pore (MPTP) and associated damage. Energized mitochondria isolated from hepatopancreas possess a pronounced capacity for calcium uptake. Exogenous calcium does not stimulate opening of the MPTP, which potentially could reduce cell death during prolonged anoxia. PMID:20160865

Upper lethal temperatures in three cold-tolerant insects are higher in winter than in summer.

PubMed

Vu, Henry M; Duman, John G

2017-08-01

Upper lethal temperatures (ULTs) of cold-adapted insect species in winter have not been previously examined. We anticipated that as the lower lethal temperatures (LLTs) decreased (by 20-30°C) with the onset of winter, the ULTs would also decrease accordingly. Consequently, given the recent increases in winter freeze-thaw cycles and warmer winters due to climate change, it became of interest to determine whether ambient temperatures during thaws were approaching ULTs during the cold seasons. However, beetle Dendroides canadensis (Coleoptera: Pyrochroidae) larvae had higher 24 and 48 h ULT 50 (the temperature at which 50% mortality occurred) in winter than in summer. The 24 and 48 h ULT 50 for D. canadensis in winter were 40.9 and 38.7°C, respectively. For D. canadensis in summer, the 24 and 48 h ULT 50 were 36.7 and 36.4°C. During the transition periods of spring and autumn, the 24 h ULT 50 was 37.3 and 38.5°C, respectively. While D. canadensis in winter had a 24 h LT 50 range between LLT and ULT of 64°C, the summer range was only 41°C. Additionally, larvae of the beetle Cucujus clavipes clavipes (Coleoptera: Cucujidae) and the cranefly Tipula trivittata (Diptera: Tipulidae) also had higher ULTs in winter than in summer. This unexpected phenomenon of increased temperature survivorship at both lower and higher temperatures in the winter compared with that in the summer has not been previously documented. With the decreased high temperature tolerance as the season progresses from winter to summer, it was observed that environmental temperatures are closest to upper lethal temperatures in spring. © 2017. Published by The Company of Biologists Ltd.

Side-by-side comparison of gene-based smallpox vaccine with MVA in nonhuman primates.

PubMed

Golden, Joseph W; Josleyn, Matthew; Mucker, Eric M; Hung, Chien-Fu; Loudon, Peter T; Wu, T C; Hooper, Jay W

2012-01-01

Orthopoxviruses remain a threat as biological weapons and zoonoses. The licensed live-virus vaccine is associated with serious health risks, making its general usage unacceptable. Attenuated vaccines are being developed as alternatives, the most advanced of which is modified-vaccinia virus Ankara (MVA). We previously developed a gene-based vaccine, termed 4pox, which targets four orthopoxvirus antigens, A33, B5, A27 and L1. This vaccine protects mice and non-human primates from lethal orthopoxvirus disease. Here, we investigated the capacity of the molecular adjuvants GM-CSF and Escherichia coli heat-labile enterotoxin (LT) to enhance the efficacy of the 4pox gene-based vaccine. Both adjuvants significantly increased protective antibody responses in mice. We directly compared the 4pox plus LT vaccine against MVA in a monkeypox virus (MPXV) nonhuman primate (NHP) challenge model. NHPs were vaccinated twice with MVA by intramuscular injection or the 4pox/LT vaccine delivered using a disposable gene gun device. As a positive control, one NHP was vaccinated with ACAM2000. NHPs vaccinated with each vaccine developed anti-orthopoxvirus antibody responses, including those against the 4pox antigens. After MPXV intravenous challenge, all control NHPs developed severe disease, while the ACAM2000 vaccinated animal was well protected. All NHPs vaccinated with MVA were protected from lethality, but three of five developed severe disease and all animals shed virus. All five NHPs vaccinated with 4pox/LT survived and only one developed severe disease. None of the 4pox/LT-vaccinated animals shed virus. Our findings show, for the first time, that a subunit orthopoxvirus vaccine delivered by the same schedule can provide a degree of protection at least as high as that of MVA.

Side-by-Side Comparison of Gene-Based Smallpox Vaccine with MVA in Nonhuman Primates

PubMed Central

Golden, Joseph W.; Josleyn, Matthew; Mucker, Eric M.; Hung, Chien-Fu; Loudon, Peter T.; Wu, T. C.; Hooper, Jay W.

2012-01-01

Orthopoxviruses remain a threat as biological weapons and zoonoses. The licensed live-virus vaccine is associated with serious health risks, making its general usage unacceptable. Attenuated vaccines are being developed as alternatives, the most advanced of which is modified-vaccinia virus Ankara (MVA). We previously developed a gene-based vaccine, termed 4pox, which targets four orthopoxvirus antigens, A33, B5, A27 and L1. This vaccine protects mice and non-human primates from lethal orthopoxvirus disease. Here, we investigated the capacity of the molecular adjuvants GM-CSF and Escherichia coli heat-labile enterotoxin (LT) to enhance the efficacy of the 4pox gene-based vaccine. Both adjuvants significantly increased protective antibody responses in mice. We directly compared the 4pox plus LT vaccine against MVA in a monkeypox virus (MPXV) nonhuman primate (NHP) challenge model. NHPs were vaccinated twice with MVA by intramuscular injection or the 4pox/LT vaccine delivered using a disposable gene gun device. As a positive control, one NHP was vaccinated with ACAM2000. NHPs vaccinated with each vaccine developed anti-orthopoxvirus antibody responses, including those against the 4pox antigens. After MPXV intravenous challenge, all control NHPs developed severe disease, while the ACAM2000 vaccinated animal was well protected. All NHPs vaccinated with MVA were protected from lethality, but three of five developed severe disease and all animals shed virus. All five NHPs vaccinated with 4pox/LT survived and only one developed severe disease. None of the 4pox/LT-vaccinated animals shed virus. Our findings show, for the first time, that a subunit orthopoxvirus vaccine delivered by the same schedule can provide a degree of protection at least as high as that of MVA. PMID:22860117

Laboratory Evaluation of the Toxicity of Systemic Insecticides to Emerald Ash Borer Larvae.

PubMed

Poland, Therese M; Ciaramitaro, Tina M; McCullough, Deborah G

2016-04-01

Emerald ash borer (Agrilus planipennis Fairmaire) (Coleoptera: Buprestidae), an invasive phloem-feeding insect native to Asia, threatens at least 16 North American ash (Fraxinus) species and has killed hundreds of millions of ash trees in landscapes and forests. We conducted laboratory bioassays to assess the relative efficacy of systemic insecticides to control emerald ash borer larvae in winter 2009 and 2010. Second- and third-instar larvae were reared on artificial diet treated with varying doses of emamectin benzoate (TREE-äge, Arborjet, Inc., Woburn, MA), imidacloprid (Imicide, J. J Mauget Co., Arcadia, CA), dinotefuran (Safari, Valent Professional Products, Walnut Creek, CA), and azadirachtin (TreeAzin, BioForest Technologies, Inc., Sault Ste. Marie, Ontario, and Azasol, Arborjet, Inc., Woburn, MA). All of the insecticides were toxic to emerald ash borer larvae, but lethal concentrations needed to kill 50% of the larvae (LC50), standardized by larval weight, varied with insecticide and time. On the earliest date with a significant fit of the probit model, LC50 values were 0.024 ppm/g at day 29 for TREE-äge, 0.015 ppm/g at day 63 for Imicide, 0.030 ppm/g at day 46 for Safari, 0.025 ppm/g at day 24 for TreeAzin, and 0.027 ppm/g at day 27 for Azasol. The median lethal time to kill 50% (LT50) of the tested larvae also varied with insecticide product and dose, and was longer for Imicide and Safari than for TREE-äge or the azadirachtin products. Insecticide efficacy in the field will depend on adult and larval mortality as well as leaf and phloem insecticide residues.

Selection of Annonaceae Species for the Control of Spodoptera frugiperda (Lepidoptera: Noctuidae) and Metabolic Profiling of Duguetia lanceolata Using Nuclear Magnetic Resonance Spectroscopy.

PubMed

Alves, D S; Machado, A R T; Campos, V A C; Oliveira, D F; Carvalho, G A

2016-04-01

This study was performed to investigate the activity of 19 dichloromethane-soluble fractions obtained from the methanolic extracts of 10 Annonaceae species against the fall armyworm, Spodoptera frugiperda (J. E. Smith). The stem bark of Duguetia lanceolata A. St.-Hil. showed the highest insecticidal activity, with a median lethal time (LT50) of 61.4 h and a median lethal concentration (LC50) of 946.5 µg/ml of diet. The dichloromethane-soluble fractions from six D. lanceolata specimens were subjected to evaluation of their activities against S. frugiperda and metabolomic analysis using hydrogen (1H) nuclear magnetic resonance (NMR) spectroscopy. Although all of the samples affected S. frugiperda mortality, their insecticidal activities varied according to the sample used in the experiments. Using partial least squares regression of the results, the D. lanceolata specimens were grouped according to their metabolite profile and insecticidal activity. A detailed analysis via uni- and bidimensional NMR spectroscopy showed that the peaks in the 1H NMR spectra associated with increased insecticidal activity could be attributed to 2,4,5-trimethoxystyrene, which suggests that this substance is involved in the insecticidal activity of the stem bark fraction of D. lanceolata.

Contractile actin cables induced by Bacillus anthracis lethal toxin depend on the histone acetylation machinery.

PubMed

Rolando, Monica; Stefani, Caroline; Doye, Anne; Acosta, Maria I; Visvikis, Orane; Yevick, Hannah G; Buchrieser, Carmen; Mettouchi, Amel; Bassereau, Patricia; Lemichez, Emmanuel

2015-10-01

It remains a challenge to decode the molecular basis of the long-term actin cytoskeleton rearrangements that are governed by the reprogramming of gene expression. Bacillus anthracis lethal toxin (LT) inhibits mitogen-activated protein kinase (MAPK) signaling, thereby modulating gene expression, with major consequences for actin cytoskeleton organization and the loss of endothelial barrier function. Using a laser ablation approach, we characterized the contractile and tensile mechanical properties of LT-induced stress fibers. These actin cables resist pulling forces that are transmitted at cell-matrix interfaces and at cell-cell discontinuous adherens junctions. We report that treating the cells with trichostatin A (TSA), a broad range inhibitor of histone deacetylases (HDACs), or with MS-275, which targets HDAC1, 2 and 3, induces stress fibers. LT decreased the cellular levels of HDAC1, 2 and 3 and reduced the global HDAC activity in the nucleus. Both the LT and TSA treatments induced Rnd3 expression, which is required for the LT-mediated induction of actin stress fibers. Furthermore, we reveal that treating the LT-intoxicated cells with garcinol, an inhibitor of histone acetyl-transferases (HATs), disrupts the stress fibers and limits the monolayer barrier dysfunctions. These data demonstrate the importance of modulating the flux of protein acetylation in order to control actin cytoskeleton organization and the endothelial cell monolayer barrier. © 2015 Wiley Periodicals, Inc.

Changes in transverse relaxation time of quadriceps femoris muscles after active recovery exercises with different intensities.

PubMed

Mukaimoto, Takahiro; Semba, Syun; Inoue, Yosuke; Ohno, Makoto

2014-01-01

The purpose of this study was to examine the changes in the metabolic state of quadriceps femoris muscles using transverse relaxation time (T2), measured by muscle functional magnetic resonance (MR) imaging, after inactive or active recovery exercises with different intensities following high-intensity knee-extension exercise. Eight healthy men performed recovery sessions with four different conditions for 20 min after high-intensity knee-extension exercise on separate days. During the recovery session, the participants conducted a light cycle exercise for 20 min using a cycle (50%, 70% and 100% of the lactate threshold (LT), respectively: active recovery), and inactive recovery. The MR images of quadriceps femoris muscles were taken before the trial and after the recovery session every 30 min for 120 min. The percentage changes in T2 for the rectus femoris and vastus medialis muscles after the recovery session in 50% LT and 70% LT were significantly lower than those in either inactive recovery or 100% LT. There were no significant differences in those for vastus lateralis and vastus intermedius muscles among the four trials. The percentage changes in T2 of rectus femoris and vastus medialis muscles after the recovery session in 50% LT and 70% LT decreased to the values before the trial faster than those in either inactive recovery or 100% LT. Those of vastus lateralis and vastus intermedius muscles after the recovery session in 50% LT and 70% LT decreased to the values before the trial faster than those in 100% LT. Although the changes in T2 after active recovery exercises were not uniform in exercised muscles, the results of this study suggest that active recovery exercise with the intensities below LT are more effective to recover the metabolic state of quadriceps femoris muscles after intense exercise than with either intensity at LT or inactive recovery.

Growth and survival of Apache Trout under static and fluctuating temperature regimes

USGS Publications Warehouse

Recsetar, Matthew S.; Bonar, Scott A.; Feuerbacher, Olin

2014-01-01

Increasing stream temperatures have important implications for arid-region fishes. Little is known about effects of high water temperatures that fluctuate over extended periods on Apache Trout Oncorhynchus gilae apache, a federally threatened species of southwestern USA streams. We compared survival and growth of juvenile Apache Trout held for 30 d in static temperatures (16, 19, 22, 25, and 28°C) and fluctuating diel temperatures (±3°C from 16, 19, 22 and 25°C midpoints and ±6°C from 19°C and 22°C midpoints). Lethal temperature for 50% (LT50) of the Apache Trout under static temperatures (mean [SD] = 22.8 [0.6]°C) was similar to that of ±3°C diel temperature fluctuations (23.1 [0.1]°C). Mean LT50 for the midpoint of the ±6°C fluctuations could not be calculated because survival in the two treatments (19 ± 6°C and 22 ± 6°C) was not below 50%; however, it probably was also between 22°C and 25°C because the upper limb of a ±6°C fluctuation on a 25°C midpoint is above critical thermal maximum for Apache Trout (28.5–30.4°C). Growth decreased as temperatures approached the LT50. Apache Trout can survive short-term exposure to water temperatures with daily maxima that remain below 25°C and midpoint diel temperatures below 22°C. However, median summer stream temperatures must remain below 19°C for best growth and even lower if daily fluctuations are high (≥12°C).

Heart-rate variability and training-intensity distribution in elite rowers.

PubMed

Plews, Daniel J; Laursen, Paul B; Kilding, Andrew E; Buchheit, Martin

2014-11-01

Elite endurance athletes may train in a polarized fashion, such that their training-intensity distribution preserves autonomic balance. However, field data supporting this are limited. The authors examined the relationship between heart-rate variability and training-intensity distribution in 9 elite rowers during the 26-wk build-up to the 2012 Olympic Games (2 won gold and 2 won bronze medals). Weekly averaged log-transformed square root of the mean sum of the squared differences between R-R intervals (Ln rMSSD) was examined, with respect to changes in total training time (TTT) and training time below the first lactate threshold (LT(2). Correlations (± 90% confidence limits) for Ln rMSSD were small vs TTT (r = .37 ± .80), moderate vs time LT2 (r = -.22 ± .50). These data provide supportive rationale for the polarized model of training, showing that training phases with increased time spent at high intensity suppress parasympathetic activity, while low-intensity training preserves and increases it. As such, periodized low-intensity training may be beneficial for optimal training programming.

[Screening of full human anthrax lethal factor neutralizing antibody in transgenic mice].

PubMed

Wang, Xiaolin; Chi, Xiangyang; Liu, Ju; Liu, Weicen; Liu, Shuling; Qiu, Shunfang; Wen, Zhonghua; Fan, Pengfei; Liu, Kun; Song, Xiaohong; Fu, Ling; Zhang, Jun; Yu, Changming

2016-11-25

Anthrax is a highly lethal infectious disease caused by the spore-forming bacterium Bacillus anthracis. The major virulence factor of B. anthracis consists of protective antigen (PA), lethal factor (LF) and edema factor (EF). PA binds with LF to form lethal toxin (LT), and PA binds with EF to form edema toxin (ET). Antibiotics is hard to work in advanced anthrax infections, because injuries and deaths of the infected are mainly caused by lethal toxin (LT). Thus, the therapeutic neutralizing antibody is the most effective treatment of anthrax. Currently most of the anthrax toxin antibodies are monoclonal antibodies (MAbs) for PA and US FDA has approved ABTHRAX humanized PA monoclonal antibody for the treatment of inhalational anthrax. Once B. anthracis was artificially reconstructed or PA had mutations within recognized neutralization epitopes, anti-PA MAbs would no longer be effective. Therefore, anti-LF MAbs is an important supplement for anthrax treatment. Most of the anti-LF antibodies are murine or chimeric antibodies. By contrast, fully human MAbs can avoid the high immunogenicity of murine antibodies. First, we used LF to immunize the transgenic mice and used fluorescent cell sorting to get antigen-specific memory B cells from transgenic mice spleen lymphocytes. By single cell PCR method, we quickly found two strains of anti-LF MAbs with binding activity, 1D7 and 2B9. Transiently transfected Expi 293F cells to obtain MAbs protein after purification. Both 1D7 and 2B9 efficiently neutralized LT in vitro, and had good synergistic effect when mixed with anti-PA MAbs. In summary, combining the advantages of transgenic mice, fluorescent cell sorting and single-cell PCR methods, this study shows new ideas and methods for the rapid screening of fully human monoclonal antibodies.

Chemical Composition of the Essential Oil of Nigeria Grown Hoslundia opposita Vahl (Lamiaceae) Dried Leaves and Its Bioactivity against Cowpea Seed Bruchid.

PubMed

Babarinde, Samuel Adelani; Pitan, Olufemi Olutoyin Richard; Olatunde, Ganiyu Olatunji; Ajala, Michael Oluwole

2017-06-01

Due to several ecological and human hazards of synthetic pesticides in postharvest crop protection, there is the need to search for eco-friendly alternatives. In this study, chemical composition and insecticidal activities of essential oil (EO) obtained from Hoslundia opposita dried leaves were evaluated against cowpea seed bruchid. Eight constituents, predominated by oxygenated monoterpenes (78.86%), were identified using Gas Chromatography (GC)/MS. The constituents were 1,8-cineole (1; 61.15%), followed by α-terpineol (2; 16.81%), β-phellandrene (3; 13.24%), β-farnesene (4; 3.55%), α-pinene (5; 1.89%), Germacrene D (6; 1.83%), cis-sabinene hydrate (7; 0.90%) and caryophyllene (8; 0.63%). In fumigation bioassay, at 6 h after exposure (HAE), 0.78 ml EO/l air caused 35.33% mortality which was significantly lower than 60.90% and 63.6% observed at 3.15 and 6.25 ml/l air, respectively. Mortality reached 90.0% at 24 HAE regardless of the applied concentration. Lethal time for 50% of the bruchids (LT 50 ) at concentration of 0.78 ml/l air (6.89 h) was higher than the LT 50 at 3.15 and 6.25 ml/l air (4.72 and 4.44 h, respectively). H. opposita EO reduced Callosobruchus maculatus oviposition, while progeny emergence observed in EO-treated seeds (2.42 - 25.73) was significantly (P < 0.05) lower than 51.56 observed in control. The results confirm H. opposita EO's potentials for control of cowpea bruchids. © 2017 Wiley-VHCA AG, Zurich, Switzerland.

Anthrax Lethal Toxin Impairs Innate Immune Functions of Alveolar Macrophages and Facilitates Bacillus anthracis Survival

PubMed Central

Ribot, Wilson J.; Panchal, Rekha G.; Brittingham, Katherine C.; Ruthel, Gordon; Kenny, Tara A.; Lane, Douglas; Curry, Bob; Hoover, Timothy A.; Friedlander, Arthur M.; Bavari, Sina

2006-01-01

Alveolar macrophages (AM) are very important for pulmonary innate immune responses against invading inhaled pathogens because they directly kill the organisms and initiate a cascade of innate and adaptive immune responses. Although several factors contribute to inhalational anthrax, we hypothesized that unimpeded infection of Bacillus anthracis is directly linked to disabling the innate immune functions contributed by AM. Here, we investigated the effects of lethal toxin (LT), one of the binary complex virulence factors produced by B. anthracis, on freshly isolated nonhuman primate AM. Exposure of AM to doses of LT that killed susceptible macrophages had no effect on the viability of AM, despite complete MEK1 cleavage. Intoxicated AM remained fully capable of B. anthracis spore phagocytosis. However, pretreatment of AM with LT resulted in a significant decrease in the clearance of both the Sterne strain and the fully virulent Ames strain of B. anthracis, which may have been a result of impaired AM secretion of proinflammatory cytokines. Our data imply that cytolysis does not correlate with MEK1 cleavage, and this is the first report of LT-mediated impairment of nonhuman primate AM bactericidal activity against B. anthracis. PMID:16926394

Cadmium modulates hematopoietic stem and progenitor cells and skews toward myelopoiesis in mice

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

Zhang, Yandong; Yu, Xinchun

The heavy metal cadmium (Cd) is known to modulate immunity and cause osteoporosis. However, how Cd influences on hematopoiesis remain largely unknown. Herein, we show that wild-type C57BL/6 (B6) mice exposed to Cd for 3 months had expanded bone marrow (BM) populations of long-term hematopoietic stem cells (LT-HSCs), common myeloid progenitors (CMPs) and granulocyte-macrophage progenitors (GMPs), while having reduced populations of multipotent progenitors (MPPs) and common lymphoid progenitors (CLPs). A competitive mixed BM transplantation assay indicates that BM from Cd-treated mice had impaired LT-HSC ability to differentiate into mature cells. In accordance with increased myeloid progenitors and decreased lymphoid progenitors,more » the BM and spleens of Cd-treated mice had more monocytes and/or neutrophils and fewer B cells and T cells. Cd impaired the ability of the non-hematopoietic system to support LT-HSCs, in that lethally irradiated Cd-treated recipients transplanted with normal BM cells had reduced LT-HSCs after the hematopoietic system was fully reconstituted. This is consistent with reduced osteoblasts, a known critical component for HSC niche, observed in Cd-treated mice. Conversely, lethally irradiated control recipients transplanted with BM cells from Cd-treated mice had normal LT-HSC reconstitution. Furthermore, both control mice and Cd-treated mice that received Alendronate, a clinical drug used for treating osteoporosis, had BM increases of LT-HSCs. Thus, the results suggest Cd increase of LT-HSCs is due to effects on HSCs and not on osteoblasts, although, Cd causes osteoblast reduction and impaired niche function for maintaining HSCs. Furthermore, Cd skews HSCs toward myelopoiesis. - Highlights: • Cd increases the number of LT-HSCs but impairs their development. • Cd-treated hosts have compromised ability to support LT-HSCs. • Cd promotes myelopoiesis at the expense of lymphopoiesis at the MPP level.« less

The light gene of Drosophila melanogaster encodes a homologue of VPS41, a yeast gene involved in cellular-protein trafficking.

PubMed

Warner, T S; Sinclair, D A; Fitzpatrick, K A; Singh, M; Devlin, R H; Honda, B M

1998-04-01

Mutations in a number of genes affect eye colour in Drosophila melanogaster; some of these "eye-colour" genes have been shown to be involved in various aspects of cellular transport processes. In addition, combinations of viable mutant alleles of some of these genes, such as carnation (car) combined with either light (lt) or deep-orange (dor) mutants, show lethal interactions. Recently, dor was shown to be homologous to the yeast gene PEP3 (VPS18), which is known to be involved in intracellular trafficking. We have undertaken to extend our earlier work on the lt gene, in order to examine in more detail its expression pattern and to characterize its gene product via sequencing of a cloned cDNA. The gene appears to be expressed at relatively high levels in all stages and tissues examined, and shows strong homology to VPS41, a gene involved in cellular-protein trafficking in yeast and higher eukaryotes. Further genetic experiments also point to a role for lt in transport processes: we describe lethal interactions between viable alleles of lt and dor, as well as phenotypic interactions (reductions in eye pigment) between allels of lt and another eye-colour gene, garnet (g), whose gene product has close homology to a subunit of the human adaptor complex, AP-3.

Upper thermal tolerances of early life stages of freshwater mussels

USGS Publications Warehouse

Pandolfo, Tamara J.; Cope, W. Gregory; Arellano, Consuelo; Bringolf, Robert B.; Barnhart, M. Christopher; Hammer, E

2010-01-01

Freshwater mussels (order Unioniformes) fulfill an essential role in benthic aquatic communities, but also are among the most sensitive and rapidly declining faunal groups in North America. Rising water temperatures, caused by global climate change, industrial discharges, drought, or land development, could further challenge imperiled unionid communities. The aim of our study was to determine the upper thermal tolerances of the larval (glochidia) and juvenile life stages of freshwater mussels. Glochidia of 8 species of mussels were tested: Lampsilis siliquoidea, Potamilus alatus, Ligumia recta, Ellipsaria lineolata,Lasmigona complanata, Megalonaias nervosa, Alasmidonta varicosa, and Villosa delumbis. Seven of these species also were tested as juveniles. Survival trends were monitored while mussels held at 3 acclimation temperatures (17, 22, and 27°C) were exposed to a range of common and extreme water temperatures (20–42°C) in standard acute laboratory tests. The average median lethal temperature (LT50) among species in 24-h tests with glochidia was 31.6°C and ranged from 21.4 to 42.7°C. The mean LT50 in 96-h juvenile tests was 34.7°C and ranged from 32.5 to 38.8°C. Based on comparisons of LT50s, thermal tolerances differed among species for glochidia, but not for juveniles. Acclimation temperature did not affect thermal tolerance for either life stage. Our results indicate that freshwater mussels already might be living close to their upper thermal tolerances in some systems and, thus, might be at risk from rising environmental temperatures.

Insecticidal evaluation of essential oils of Citrus sinensis L. (Myrtales: Myrtaceae) against housefly, Musca domestica L. (Diptera: Muscidae).

PubMed

Kumar, Peeyush; Mishra, Sapna; Malik, Anushree; Satya, Santosh

2012-05-01

The housefly, Musca domestica L., is one of the most common insects, associated with vectoring of various etiological agents. In order to search for effective control agent, the essential oil of sweet orange [Citrus sinensis (L.) Osbeck] was evaluated for its insecticidal activity against the larvae and pupae of housefly using contact toxicity and fumigation bioassays. In the contact toxicity assay, lethal concentration, LC(50) of C. sinensis essential oil against housefly larvae, varied between 3.93 and 0.71 μl/cm(2) for different observation days, while lethal time, LT(50), varied between 5.8 to 2.3 days. Mortality of larvae were significant with different concentrations (F = 2.79, df = 4, P < 0.05) and time (F = 6.69, df = 3, P < 0.01). In fumigant assay for housefly larvae, LC(50) of 71.2 and 52.6 μl/l was obtained in 24 and 48 h, respectively. Scanning electron microscopy of oil treated larvae revealed extreme dehydration and surface distortion while control larvae were free from any of the above symptoms and presented smooth surface, conforming effect of essential oil on housefly larvae. Percentage inhibition rate of oil against housefly pupae was 27.3-72.7% for contact toxicity and 46.4-100% for fumigation assay. Compositional analysis of C. sinensis essential oil using gas chromatography/mass spectrometry (GC-MS) revealed D: -limonene (73.24%), α-pinene (5.86%) and myrcene (4.45%) as major components whereas its vapour profile (solid-phase micro extraction-GC/MS) was dominated by D: -limonene at 92.57%. Significant activity of C. sinensis essential oil against larvae and pupae of housefly, pave the way for its use as eco-friendly housefly control measure.

Influence of exposure time on toxicity-An overview.

PubMed

Connell, Des W; Yu, Qiming J; Verma, Vibha

2016-04-29

Data on toxicity of chemicals is usually reported as the LD50, or LC50, with the exposure time from experimental testing in the laboratory reported. But the exposure time is not considered to be a quantifiable variable which can be used to evaluate its importance in expressed toxicity, often described in general terms such as acute, chronic and so on. For the last hundred years Habers Rule has been successfully used to extrapolate from reported exposure times to other exposure times which may be needed for setting standards, health risk assessments and other applications. But it has limitations particularly in environmental applications where exposure levels are low and exposure times are relatively long. The Reduced Life Expectancy (RLE) model overcomes these problems and can be utilised under all exposure conditions. It can be expressed as ln(LT50)=-a (LC50)(ν)+b where the constants ν, a and b can be evaluated by fitting the model to experimental data on the LC50, and corresponding LT50, together with the Normal Life Expectancy (NLE) of the organism being considered as a data point when the LC50 is zero. The constant, ν, at a value of unity gives a linear relationship and where ν<1 the relationship has a concave shape. In our extensive evaluations of the RLE model for fish, invertebrates and mammals involving 115 data sets and with a wide range of organic and inorganic toxicants the RLE model gave correlation coefficients of >0.8 with 107 sets of data. The RLE model can be used to extrapolate from a limited data set on exposure times and corresponding LT50 values to any exposure time and corresponding LT50 value. The discrepancy between Haber's Rule and RLE model increases as the exposure time increases. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

The use of the cannibalistic habit and elevated relative humidity to improve the storage and shipment of the predatory mite Neoseiulus californicus (Acari: Phytoseiidae).

PubMed

Ghazy, Noureldin Abuelfadl; Amano, Hiroshi

2016-07-01

This study investigated the feasibility of using the cannibalistic habits of the mite Neoseiulus californicus (McGregor) and controlling the relative humidity (RH) to prolong the survival time during the storage or shipment of this predatory mite. Three-day-old mated and unmated females were individually kept at 25 ± 1 °C in polypropylene vials (1.5 mL), each containing one of the following items or combinations of items: a kidney bean leaf disk (L), N. californicus eggs (E), and both a leaf disk and the eggs (LE). Because the leaf disk increased the RH in the vials, the RH was 95 ± 2 % under the L and LE treatments and 56 ± 6 % under the E treatment. The median lethal time (LT50) exceeded 50 days for the mated and unmated females under the LE treatment. However, it did not exceed 11 or 3 days for all females under the L or E treatments, respectively. Under the LE treatment, the mated and unmated females showed cannibalistic behavior and consumed an average of 5.2 and 4.6 eggs/female/10 days. Some of the females that survived for LT50 under each treatment were transferred and fed normally with a constant supply of Tetranychus urticae Koch. Unmated females were provided with adult males for 24 h for mating. Only females previously kept at LE treatment produced numbers of eggs equivalent to the control females (no treatment is applied). The results suggested that a supply of predator eggs and leaf material might have furnished nutrition and water vapor, respectively, and that this combination prolonged the survival time of N. californicus during storage. Moreover, this approach poses no risk of pest contamination in commercial products.

Causes of Rapid Carrion Beetle (Coleoptera: Silphidae) Death in Flooded Pitfall Traps, Response to Soil Flooding, Immersion Tolerance, and Swimming Behavior.

PubMed

Cavallaro, Michael C; Barnhart, M Christopher; Hoback, W Wyatt

2017-04-01

Terrestrial insects in water can often delay or escape drowning by floating and swimming. However, we observed that flooding of pitfall traps baited with rotting carrion results in high overnight mortality of captured beetles and reasoned that this risk may be enhanced by microbial respiration. By assessing carrion beetle (Coleoptera: Silphidae) response to flooding, tolerance to immersion, and swimming behavior, we offer insights to this cause of death and beetle behavioral physiology. Response of buried Nicrophorus orbicollis Say to soil flooding resulted in beetles moving to the soil surface. The lethal time to 50% mortality (LT50 (immersion); mean ± 95% CI) for Nicrophorus investigator Zetterstedt, Nicrophorus marginatus F., Necrodes surinamensis F., and Thanatophilus lapponicus Herbst was 14.8 ± 2.3, 9.0 ± 3.3, 3.2 ± 1.1, and 12.1 ± 2.5 h, respectively. Swimming behavior and survival time of N. investigator was tested using yeast:sucrose (Y:S) solutions to create a eutrophic, severely hypoxic aqueous environment. LT50 (swimming) for N. investigator was 7.5 ± 1.4, 6.0 ± 1.7, and 4.2 ± 1.2 h for the low, medium, and high Y:S solutions, respectively, and >24.0 h in control treatments. Nicrophorus investigator survived nearly twice as long when completely immersed in deoxygenated water, as might occur in flooded burrows, than when swimming on the surface. We document for the first time, the rapid induction of hypoxic coma and death for a terrestrial insect from enhanced microbial activity and CO2 production of an aqueous environment, as well as suggestions on trapping protocols related to the federally endangered Nicrophorus americanus Olivier. © The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

In vitro control of the camel nasal botfly, Cephalopina titillator, with doramectin, lavender, camphor, and onion oils.

PubMed

Khater, Hanem F; Ramadan, Mohamed Y; Mageid, Abla D Abdel

2013-07-01

Camels are very important livestock particularly in arid and semiarid lands. The oestrid fly, Cephalopina titillator (Clark), causes nasopharyngeal myiasis in camels, and it is widely distributed in many camel breeding areas triggering health hazards and severe economic losses in camels. The prevalence of infestation of camels (slaughtered at Tokh's slaughterhouse, Qalyubia Governorate, Egypt, during the period from September 2011 to March 2012) was 41.67 % (100 out of 240). Most infested camels developed clinical signs of nasal discharge, restlessness, loss of appetite, difficulty in breathing, frequent sneezing, and snoring. Postmortem examination of infested camels explained that breathing of the animal is greatly impaired because of blockage of the nasopharynx by larvae and/or mucofibrinous secretions. The larval count per camel ranged from 1 to 250 (mean 28.45 ± 6.48). In vitro larval immersion tests were carried out to determine the efficacy of doramectin (0.003 %) as well as some essential oils (50 % each) such as lavender, camphor, and onion oils against the second and third larval stages (L2 and L3) of C. titillator. Another trial had been done for imitating what could happen if the area around camels were treated with an insecticide or an insect repellent. All treated L2 died 18 h posttreatment (PT) with both doramectin and lavender, and 100 % mortality was reached for L3 after 24 and 30 h PT with lavender and doramectin, respectively. Doramectin and lavender induced the highest response against C. titillator as their lethal time (LT50) values after treatment of L2 were 3.40 and 3.60 h, respectively, and those of L3 were 4.99 and 5.53 h, respectively. Against both L2 and L3 of C. titillator and based on LT50 values of onion oil and those of other applied materials, doramectin and lavender oil were four times more effective than onion oil, and camphor oil was two times more effective than onion oil. Based on LT50 values of essential oils and those of doramectin, as a reference substance, the relative speed of efficacy indicated that camphor and onion oils were, respectively, two and four times less effective than doramectin and lavender. With regard to fumigant technique, neither the insecticide, New Pyrosol, nor the insect repellent, Keto, was effective in controlling C. titillator larvae. Our results indicated that doramectin and lavender could be selected as drugs of choice for controlling C. titillator, but it is not permitted to use doramectin on dairy animals during lactation. Lavender (50 %) has a great potential to be developed as a novel larvicide and could be used as nasal drench against nasal botfly which will reflect on camel production and the national economy.

Individual and Combined Effects of Bacillus Thuringiensis and Azadirachtin on Plodia Interpunctella Hübner (Lepidoptera: Pyralidae)

PubMed Central

Nouri-Ganbalani, Gadir; Borzoui, Ehsan; Abdolmaleki, Arman; Abedi, Zahra; George Kamita, Shizuo

2016-01-01

The Indianmeal moth, Plodia interpunctella Hübner (Lepidoptera: Pyralidae), is a major stored product pest that is found throughout the world. In this study, the effect of oral exposure to Bacillus thuringiensis (Berliner) subsp. kurstaki (Bacillales: Bacillaceae) and azadirachtin was evaluated in third instar P. interpunctella under laboratory conditions. The median lethal concentration (LC50) of Bt and azadirachtin on third instars was 490 and 241 μg a.i./ml, respectively. The median lethal time (LT50) of these insecticides was the same (4.5 d following exposure to 750 or 400 μg a.i./ml of Bt or azadirachtin, respectively). When the larvae fed on diet containing LC30 concentrations of both Bt and azadirachtin an additive interaction in terms of mortality was found. A synergistic interaction was found when the larvae fed on diet containing LC50 concentrations of both insecticides. Larvae that fed on insecticide-containing diet (either Bt or azadirachtin at an LC30 concentration, or both insecticides at LC30 or LC50 concentrations) showed lower glycogen and lipid levels, and generally lower protein content in comparison to control larvae. Larvae that fed on diet containing both Bt and azadirachtin showed reduced weight gain and nutritional indices in comparison to control larvae or larvae fed on the diet containing only one of the insecticides. Finally, exposure to both insecticides, either individually or in combination, reduced the level of digestive enzymes found in the midgut. Our findings indicate that both Bt and azadirachtin, either individually or in combination have significant potential for use in controlling of P. interpunctella. PMID:27638953

Individual and Combined Effects of Bacillus Thuringiensis and Azadirachtin on Plodia Interpunctella Hübner (Lepidoptera: Pyralidae).

PubMed

Nouri-Ganbalani, Gadir; Borzoui, Ehsan; Abdolmaleki, Arman; Abedi, Zahra; George Kamita, Shizuo

2016-01-01

The Indianmeal moth, Plodia interpunctella Hübner (Lepidoptera: Pyralidae), is a major stored product pest that is found throughout the world. In this study, the effect of oral exposure to Bacillus thuringiensis (Berliner) subsp. kurstaki (Bacillales: Bacillaceae) and azadirachtin was evaluated in third instar P. interpunctella under laboratory conditions. The median lethal concentration (LC50) of Bt and azadirachtin on third instars was 490 and 241 μg a.i./ml, respectively. The median lethal time (LT50) of these insecticides was the same (4.5 d following exposure to 750 or 400 μg a.i./ml of Bt or azadirachtin, respectively). When the larvae fed on diet containing LC30 concentrations of both Bt and azadirachtin an additive interaction in terms of mortality was found. A synergistic interaction was found when the larvae fed on diet containing LC50 concentrations of both insecticides. Larvae that fed on insecticide-containing diet (either Bt or azadirachtin at an LC30 concentration, or both insecticides at LC30 or LC50 concentrations) showed lower glycogen and lipid levels, and generally lower protein content in comparison to control larvae. Larvae that fed on diet containing both Bt and azadirachtin showed reduced weight gain and nutritional indices in comparison to control larvae or larvae fed on the diet containing only one of the insecticides. Finally, exposure to both insecticides, either individually or in combination, reduced the level of digestive enzymes found in the midgut. Our findings indicate that both Bt and azadirachtin, either individually or in combination have significant potential for use in controlling of P. interpunctella. © The Author 2016. Published by Oxford University Press on behalf of the Entomological Society of America.

Needle metabolome, freezing tolerance and gas exchange in Norway spruce seedlings exposed to elevated temperature and ozone concentration.

PubMed

Riikonen, Johanna; Kontunen-Soppela, Sari; Ossipov, Vladimir; Tervahauta, Arja; Tuomainen, Marjo; Oksanen, Elina; Vapaavuori, Elina; Heinonen, Jaakko; Kivimäenpää, Minna

2012-09-01

Northern forests are currently experiencing increasing mean temperatures, especially during autumn and spring. Consequently, alterations in carbon sequestration, leaf biochemical quality and freezing tolerance (FT) are likely to occur. The interactive effects of elevated temperature and ozone (O(3)), the most harmful phytotoxic air pollutant, on Norway spruce (Picea abies (L.) Karst.) seedlings were studied by analysing phenology, metabolite concentrations in the needles, FT and gas exchange. Sampling was performed in September and May. The seedlings were exposed to a year-round elevated temperature (+1.3 °C), and to 1.4× ambient O(3) concentration during the growing season in the field. Elevated temperature increased the concentrations of amino acids, organic acids of the citric acid cycle and some carbohydrates, and reduced the concentrations of phenolic compounds, some organic acids of the shikimic acid pathway, sucrose, cyclitols and steroids, depending on the timing of the sampling. Although growth onset occurred earlier at elevated temperature, the temperature of 50% lethality (LT(50)) was similar in the treatments. Photosynthesis and the ratio of photosynthesis to dark respiration were reduced by elevated temperature. Elevated concentrations of O(3) reduced the total concentration of soluble sugars, and tended to reduce LT(50) of the needles in September. These results show that alterations in needle chemical quality can be expected at elevated temperatures, but the seedlings' sensitivity to autumn and spring frosts is not altered. Elevated O(3) has the potential to disturb cold hardening of Norway spruce seedlings in autumn, and to alter the water balance of the seedling through changes in stomatal conductance (g(s)), while elevated temperature is likely to reduce g(s) and consequently reduce the O(3)-flux inside the leaves.

Adenoviral Expression of a Bispecific VHH-Based Neutralizing Agent That Targets Protective Antigen Provides Prophylactic Protection from Anthrax in Mice.

PubMed

Moayeri, Mahtab; Tremblay, Jacqueline M; Debatis, Michelle; Dmitriev, Igor P; Kashentseva, Elena A; Yeh, Anthony J; Cheung, Gordon Y C; Curiel, David T; Leppla, Stephen; Shoemaker, Charles B

2016-01-06

Bacillus anthracis, the causative agent of anthrax, secretes three polypeptides, which form the bipartite lethal and edema toxins (LT and ET, respectively). The common component in these toxins, protective antigen (PA), is responsible for binding to cellular receptors and translocating the lethal factor (LF) and edema factor (EF) enzymatic moieties to the cytosol. Antibodies against PA protect against anthrax. We previously isolated toxin-neutralizing variable domains of camelid heavy-chain-only antibodies (VHHs) and demonstrated their in vivo efficacy. In this work, gene therapy with an adenoviral (Ad) vector (Ad/VNA2-PA) (VNA, VHH-based neutralizing agents) promoting the expression of a bispecific VHH-based neutralizing agent (VNA2-PA), consisting of two linked VHHs targeting different PA-neutralizing epitopes, was tested in two inbred mouse strains, BALB/cJ and C57BL/6J, and found to protect mice against anthrax toxin challenge and anthrax spore infection. Two weeks after a single treatment with Ad/VNA2-PA, serum VNA2-PA levels remained above 1 μg/ml, with some as high as 10 mg/ml. The levels were 10- to 100-fold higher and persisted longer in C57BL/6J than in BALB/cJ mice. Mice were challenged with a lethal dose of LT or spores at various times after Ad/VNA2-PA administration. The majority of BALB/cJ mice having serum VNA2-PA levels of >0.1 μg/ml survived LT challenge, and 9 of 10 C57BL/6J mice with serum levels of >1 μg/ml survived spore challenge. Our findings demonstrate the potential for genetic delivery of VNAs as an effective method for providing prophylactic protection from anthrax. We also extend prior findings of mouse strain-based differences in transgene expression and persistence by adenoviral vectors. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Lethal and sublethal effects of essential oils from Eucalyptus camaldulensis and Heracleum persicum against the adults of Callosobruchus maculatus.

PubMed

Izakmehri, Khadijeh; Saber, Moosa; Mehrvar, Ali; Hassanpouraghdam, Mohammad Bagher; Vojoudi, Samad

2013-01-01

The cowpea weevil, Callosobruchus maculatus F. (Coleoptera: Bruchidae), is an important pest of stored cowpea, Vigna ungiculata (L.) Walpers (Fabales: Fabaceae), with ample distribution in tropical and subtropical regions. Many plant essential oils have a broad-spectrum activity against pest insects, and these oils traditionally have been used in the protection of stored products. In this study, the lethal and sublethal effects of essential oils from Eucalyptus camaldulensis Dehnh. (Myrtales: Myrtaceae) and Heracleum persicum Desf. (Apiales: Apiaceae) were evaluated on the adults of C. maculatus at 26 ± 1° C, 70 ± 5% RH, and a photoperiod of 16:8 L:D. The LC50 values of E. camaldulensis and H. persicum were 56.7 and 219.4 µL/L air after 12 hr and 26.1 and 136.4 µL/L air after 24 hr of exposure, respectively. The LT50 values of E. camaldulensis and H.persicum were 6.3 and 10.9 hr, respectively. The results showed that low lethal concentration (LC20) of essential oils negatively affected the longevity, fecundity, and fertility of female adults. The sex ratio of C. maculatus offspring was not significantly affected by essential oils. Therefore, these essential oils can be suggested for controlling C. maculatus in storage systems. The introduction of essential oils into storage systems could potentially decrease seed losses.

Lethal and Sublethal Effects of Essential Oils from Eucalyptus camaldulensis and Heracleum persicum Against the Adults of Callosobruchus Maculatus

PubMed Central

Izakmehri, Khadijeh; Saber, Moosa; Mehrvar, Ali; Hassanpouraghdam, Mohammad Bagher; Vojoudi, Samad

2013-01-01

The cowpea weevil, Callosobruchus maculatus F. (Coleoptera: Bruchidae), is an important pest of stored cowpea, Vigna ungiculata (L.) Walpers (Fabales: Fabaceae), with ample distribution in tropical and subtropical regions. Many plant essential oils have a broad-spectrum activity against pest insects, and these oils traditionally have been used in the protection of stored products. In this study, the lethal and sublethal effects of essential oils from Eucalyptus camaldulensis Dehnh. (Myrtales: Myrtaceae) and Heracleum persicum Desf. (Apiales: Apiaceae) were evaluated on the adults of C. maculatus at 26 ± 1° C, 70 ± 5% RH, and a photoperiod of 16:8 L:D. The LC50 values of E. camaldulensis and H. persicum were 56.7 and 219.4 µL/L air after 12 hr and 26.1 and 136.4 µL/L air after 24 hr of exposure, respectively. The LT50 values of E. camaldulensis and H.persicum were 6.3 and 10.9 hr, respectively. The results showed that low lethal concentration (LC20) of essential oils negatively affected the longevity, fecundity, and fertility of female adults. The sex ratio of C. maculatus offspring was not significantly affected by essential oils. Therefore, these essential oils can be suggested for controlling C. maculatus in storage systems. The introduction of essential oils into storage systems could potentially decrease seed losses. PMID:24773362

The Saccharomyces boulardii CNCM I-745 strain shows protective effects against the B. anthracis LT toxin.

PubMed

Pontier-Bres, Rodolphe; Rampal, Patrick; Peyron, Jean-François; Munro, Patrick; Lemichez, Emmanuel; Czerucka, Dorota

2015-10-30

The probiotic yeast Saccharomyces boulardii (S. boulardii) has been prescribed for the prophylaxis and treatment of several infectious diarrheal diseases. Gastrointestinal anthrax causes fatal systemic disease. In the present study, we investigated the protective effects conferred by Saccharomyces boulardii CNCM I-745 strain on polarized T84 columnar epithelial cells intoxicated by the lethal toxin (LT) of Bacillus anthracis. Exposure of polarized T84 cells to LT affected cell monolayer integrity, modified the morphology of tight junctions and induced the formation of actin stress fibers. Overnight treatment of cells with S. boulardii before incubation with LT maintained the integrity of the monolayers, prevented morphological modification of tight junctions, restricted the effects of LT on actin remodeling and delayed LT-induced MEK-2 cleavage. Mechanistically, we demonstrated that in the presence of S. boulardii, the medium is depleted of both LF and PA sub-units of LT and the appearance of a cleaved form of PA. Our study highlights the potential of the S. boulardii CNCM I-745 strain as a prophylactic agent against the gastrointestinal form of anthrax.

The Saccharomyces boulardii CNCM I-745 Strain Shows Protective Effects against the B. anthracis LT Toxin

PubMed Central

Pontier-Bres, Rodolphe; Rampal, Patrick; Peyron, Jean-François; Munro, Patrick; Lemichez, Emmanuel; Czerucka, Dorota

2015-01-01

The probiotic yeast Saccharomyces boulardii (S. boulardii) has been prescribed for the prophylaxis and treatment of several infectious diarrheal diseases. Gastrointestinal anthrax causes fatal systemic disease. In the present study, we investigated the protective effects conferred by Saccharomyces boulardii CNCM I-745 strain on polarized T84 columnar epithelial cells intoxicated by the lethal toxin (LT) of Bacillus anthracis. Exposure of polarized T84 cells to LT affected cell monolayer integrity, modified the morphology of tight junctions and induced the formation of actin stress fibers. Overnight treatment of cells with S. boulardii before incubation with LT maintained the integrity of the monolayers, prevented morphological modification of tight junctions, restricted the effects of LT on actin remodeling and delayed LT-induced MEK-2 cleavage. Mechanistically, we demonstrated that in the presence of S. boulardii, the medium is depleted of both LF and PA sub-units of LT and the appearance of a cleaved form of PA. Our study highlights the potential of the S. boulardii CNCM I-745 strain as a prophylactic agent against the gastrointestinal form of anthrax. PMID:26529015

Development and application of a species sensitivity distribution for temperature-induced mortality in the aquatic environment.

PubMed

de Vries, Pepijn; Tamis, Jacqueline E; Murk, Albertinka J; Smit, Mathijs G D

2008-12-01

Current European legislation has static water quality objectives for temperature effects, based on the most sensitive species. In the present study a species sensitivity distribution (SSD) for elevated temperatures is developed on the basis of temperature sensitivity data (mortality) of 50 aquatic species. The SSD applies to risk assessment of heat discharges that are localized in space or time. As collected median lethal temperatures (LT50 values) for different species depend on the acclimation temperature, the SSD is also a function of the acclimation temperature. Data from a thermal discharge in The Netherlands are used to show the applicability of the developed SSD in environmental risk assessment. Although restrictions exist in the application of the developed SSD, it is concluded that the SSD approach can be applied to assess the effects of elevated temperature. Application of the concept of SSD to temperature changes allows harmonization of environmental risk assessment for stressors in the aquatic environment. When a synchronization of the assessment methods is achieved, the steps to integration of risks from toxic and nontoxic stressors can be made.

Asymmetric Waveforms Decrease Lethal Thresholds in High Frequency Irreversible Electroporation Therapies

PubMed Central

Sano, Michael B.; Fan, Richard E.; Xing, Lei

2017-01-01

Irreversible electroporation (IRE) is a promising non-thermal treatment for inoperable tumors which uses short (50–100 μs) high voltage monopolar pulses to disrupt the membranes of cells within a well-defined volume. Challenges with IRE include complex treatment planning and the induction of intense muscle contractions. High frequency IRE (H-FIRE) uses bursts of ultrashort (0.25–5 μs) alternating polarity pulses to produce more predictable ablations and alleviate muscle contractions associated with IRE. However, H-FIRE generally ablates smaller volumes of tissue than IRE. This study shows that asymmetric H-FIRE waveforms can be used to create ablation volumes equivalent to standard IRE treatments. Lethal thresholds (LT) of 505 V/cm and 1316 V/cm were found for brain cancer cells when 100 μs IRE and 2 μs symmetric H-FIRE waveforms were used. In contrast, LT as low as 536 V/cm were found for 2 μs asymmetric H-FIRE waveforms. Reversible electroporation thresholds were 54% lower than LTs for symmetric waveforms and 33% lower for asymmetric waveforms indicating that waveform symmetry can be used to tune the relative sizes of reversible and irreversible ablation zones. Numerical simulations predicted that asymmetric H-FIRE waveforms are capable of producing ablation volumes which were 5.8–6.3x larger than symmetric H-FIRE waveforms indicating that in vivo investigation of asymmetric waveforms is warranted. PMID:28106146

Asymmetric Waveforms Decrease Lethal Thresholds in High Frequency Irreversible Electroporation Therapies

NASA Astrophysics Data System (ADS)

Sano, Michael B.; Fan, Richard E.; Xing, Lei

2017-01-01

Irreversible electroporation (IRE) is a promising non-thermal treatment for inoperable tumors which uses short (50-100 μs) high voltage monopolar pulses to disrupt the membranes of cells within a well-defined volume. Challenges with IRE include complex treatment planning and the induction of intense muscle contractions. High frequency IRE (H-FIRE) uses bursts of ultrashort (0.25-5 μs) alternating polarity pulses to produce more predictable ablations and alleviate muscle contractions associated with IRE. However, H-FIRE generally ablates smaller volumes of tissue than IRE. This study shows that asymmetric H-FIRE waveforms can be used to create ablation volumes equivalent to standard IRE treatments. Lethal thresholds (LT) of 505 V/cm and 1316 V/cm were found for brain cancer cells when 100 μs IRE and 2 μs symmetric H-FIRE waveforms were used. In contrast, LT as low as 536 V/cm were found for 2 μs asymmetric H-FIRE waveforms. Reversible electroporation thresholds were 54% lower than LTs for symmetric waveforms and 33% lower for asymmetric waveforms indicating that waveform symmetry can be used to tune the relative sizes of reversible and irreversible ablation zones. Numerical simulations predicted that asymmetric H-FIRE waveforms are capable of producing ablation volumes which were 5.8-6.3x larger than symmetric H-FIRE waveforms indicating that in vivo investigation of asymmetric waveforms is warranted.

Noninvasive Imaging Technologies Reveal Edema Toxin as a Key Virulence Factor in Anthrax

PubMed Central

Dumetz, Fabien; Jouvion, Grégory; Khun, Huot; Glomski, Ian Justin; Corre, Jean-Philippe; Rougeaux, Clémence; Tang, Wei-Jen; Mock, Michèle; Huerre, Michel; Goossens, Pierre Louis

2011-01-01

Powerful noninvasive imaging technologies enable real-time tracking of pathogen-host interactions in vivo, giving access to previously elusive events. We visualized the interactions between wild-type Bacillus anthracis and its host during a spore infection through bioluminescence imaging coupled with histology. We show that edema toxin plays a central role in virulence in guinea pigs and during inhalational infection in mice. Edema toxin (ET), but not lethal toxin (LT), markedly modified the patterns of bacterial dissemination leading, to apparent direct dissemination to the spleen and provoking apoptosis of lymphoid cells. Each toxin alone provoked particular histological lesions in the spleen. When ET and LT are produced together during infection, a specific temporal pattern of lesion developed, with early lesions typical of LT, followed at a later stage by lesions typical of ET. Our study provides new insights into the complex spatial and temporal effects of B. anthracis toxins in the infected host, suggesting a greater role than previously suspected for ET in anthrax and suggesting that therapeutic targeting of ET contributes to protection. PMID:21641378

Scorpion neurotoxin AaIT-expressing Beauveria bassiana enhances the virulence against Aedes albopictus mosquitoes.

PubMed

Deng, Sheng-Qun; Cai, Qun-Di; Deng, Ming-Zhi; Huang, Qiang; Peng, Hong-Juan

2017-12-01

To improve the insecticidal efficacy of this entomopathogen Beauveria bassiana, the fungus was genetically modified to express an insect-specific scorpion neurotoxin AaIT. The virulence of the recombinant B. bassiana strain (Bb-AaIT) against Aedes albopictus adults (which occurs via penetration through the cuticle during spore germination or by conidia ingestion), and the larvae (by conidia ingestion) was measured with bioassays. The median lethal concentration (LC 50 ) of Bb-AaIT against A. albopictus larvae was 313.3-fold lower on day 4 and 11.3-fold lower on day 10 than that of the wild type (WT). Through conidia feeding or body contact, Bb-AaIT killed 50% of adult female mosquitoes at 3.9- or 1.9-fold reduced concentrations on day 4 and at 2.1- or 2.4-fold reduced concentrations on day 10. Compared with the results for the WT, the median lethal time (LT 50 ) of Bb-AaIT was reduced by 28.6% at 1 × 10 7 conidia ml -1 and 34.3% at 1 × 10 6 conidia ml -1 in the larvae bioassay by conidia ingestion, while it decreased 32.3% at 1 × 10 7 conidia ml -1 by conidia ingestion and 24.2% at 1 × 10 8 conidia ml -1 by penetrating through the cuticle in the adult bioassay. All the differences were significant. Our findings indicated that Bb-AaIT had higher virulence and faster action than the WT in killing the larval and adult mosquitoes, and therefore, it is valuable for development as a commercial mosquito pesticide.

Protective Effect of Immunization of Rats with Holotoxin or B Subunit of Escherichia coli Heat-Labile Enterotoxin

PubMed Central

Klipstein, Frederick A.; Engert, Richard F.

1981-01-01

The relative immunogenicities of three forms of the Escherichia coli heatlabile enterotoxin (LT), the holotoxin, its B subunit, and the polymyxin-release form (PM LT) were compared by immunizing rats with various dosages of each given exclusively by the parenteral (IP/IP) or peroral (PO/PO) routes or by a combination of the two (IP/PO). The degree of protection was evaluated by challenge in ligated ileal loops, and the serum antitoxin response was determined by an enzyme-linked immunosorbent assay with homologous antigens. When given by the PO/PO route, each LT antigen provided only weak protection against the toxin and virtually none against viable LT-producing strains; serum antitoxin titers were not significantly increased. When the toxins were given after a parental primary immunization by either the IP/IP or the IP/PO routes, each LT antigen provided a dose-related increase in serum antitoxin titers and in the degree of protection against the toxin as well as against viable strains which produce LT alone (LT+/ST−) or in combination with the heat-stable toxin (LT+/ST+). The degree of protection against viable bacteria, particularly the LT+/ST+ strain, was stronger in animals which received booster immunizations by the PO route. When expressed on the basis of molar equivalents, holotoxin provided significant protection (a protection index of >5 against toxin challenge and >50% reduced secretion with bacterial challenge) with 4 to 15 times fewer moles than PM LT and up to 50 times fewer moles than the B subunit. These observations indicate that, on the basis of molar equivalents, the holotoxin (which contains one A plus five or six B subunits) is a more potent immunogen than either PM LT (which contains one A and probably one B subunit) or the B subunit. PMID:7011990

High-Force Versus Low-Force Lumbar Traction in Acute Lumbar Sciatica Due to Disc Herniation: A Preliminary Randomized Trial.

PubMed

Isner-Horobeti, Marie-Eve; Dufour, Stéphane Pascal; Schaeffer, Michael; Sauleau, Erik; Vautravers, Philippe; Lecocq, Jehan; Dupeyron, Arnaud

This study compared the effects of high-force versus low-force lumbar traction in the treatment of acute lumbar sciatica secondary to disc herniation. A randomized double blind trial was performed, and 17 subjects with acute lumbar sciatica secondary to disc herniation were assigned to high-force traction at 50% body weight (BW; LT50, n = 8) or low force traction at 10% BW (LT10, n = 9) for 10 sessions in 2 weeks. Radicular pain (visual analogue scale [VAS]), lumbo-pelvic-hip complex motion (finger-to-toe test), lumbar-spine mobility (Schöber-Macrae test), nerve root compression (straight-leg-raising test), disability (EIFEL score), drug consumption, and overall evaluation of each patient were measured at days 0, 7, 1, 4, and 28. Significant (P < .05) improvements were observed in the LT50 and LT10 groups, respectively, between day 0 and day 14 (end of treatment) for VAS (-44% and -36%), EIFEL score (-43% and -28%) and overall patient evaluation (+3.1 and +2.0 points). At that time, LT50 specifically improved in the finger-to-toe test (-42%), the straight-leg-raising test (+58), and drug consumption (-50%). No significant interaction effect (group-by-time) was revealed, and the effect of traction treatment was independent of the level of medication. During the 2-week follow-up at day 28, only the LT10 group improved (P < .05) in VAS (-52%) and EIFEL scores (-46%). During this period, no interaction effect (group-by-time) was identified, and the observed responses were independent of the level of medication. For this preliminary study, patients with acute lumbar sciatica secondary to disc herniation who received 2 weeks of lumbar traction reported reduced radicular pain and functional impairment and improved well-being regardless of the traction force group to which they were assigned. The effects of the traction treatment were independent of the initial level of medication and appeared to be maintained at the 2-week follow-up. Copyright © 2016. Published by Elsevier Inc.

Lung Transplantation for Cystic Fibrosis: Results, Indications, Complications, and Controversies

PubMed Central

Lynch, Joseph P.; Sayah, David M.; Belperio, John A.; Weigt, S. Sam

2016-01-01

Survival in patients with cystic fibrosis (CF) has improved dramatically over the past 30 to 40 years, with mean survival now approximately 40 years. Nonetheless, progressive respiratory insufficiency remains the major cause of mortality in CF patients, and lung transplantation (LT) is eventually required. Timing of listing for LT is critical, because up to 25 to 41% of CF patients have died while awaiting LT. Globally, approximately 16.4% of lung transplants are performed in adults with CF. Survival rates for LT recipients with CF are superior to other indications, yet LT is associated with substantial morbidity and mortality (~50% at 5-year survival rates). Myriad complications of LT include allograft failure (acute or chronic), opportunistic infections, and complications of chronic immunosuppressive medications (including malignancy). Determining which patients are candidates for LT is difficult, and survival benefit remains uncertain. In this review, we discuss when LT should be considered, criteria for identifying candidates, contraindications to LT, results post-LT, and specific complications that may be associated with LT. Infectious complications that may complicate CF (particularly Burkholderia cepacia spp., opportunistic fungi, and nontuberculous mycobacteria) are discussed. PMID:25826595

Heat Tolerance of the Brown Recluse Spider (Araneae: Sicariidae): Potential for Pest Control.

PubMed

Cramer, Kenneth L; Zagar, Lindsey M

2016-02-01

The brown recluse spider, Loxosceles reclusa Gertsch & Mulaik, is a well-known venomous spider common in the south-central United States where infestations can reach thousands of individuals in a single structure. Bites from this spider pose a risk of dermonecrotic lesions (loxoscelism) or, rarely, more serious systemic effects. The heat tolerance of this spider is understudied but may offer an alternative pest control solution to pesticides or fumigation, both of which have their disadvantages. We subjected brown recluse spiders to increasing temperatures to establish the upper lethal temperature (LT). Using probit analysis to generate probability of mortality at increasing temperatures, we then exposed adult spiders to the observed LT50 to simulate whole-room heat treatment. Laboratory results predict exposure to 48°C for 130 min will achieve 100% mortality of adult spiders. Field tests need to be conducted to determine the efficacy of heat treatment in a variety of real-world situations. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

In vitro pediculicidal activity of herbal shampoo base on Thai local plants against head louse (Pediculus humanus capitis De Geer).

PubMed

Rassami, Watcharawit; Soonwera, Mayura

2013-04-01

Head lice infestation, a worldwide head infestation caused Pediculus humanus capitis De Geer, is an important public health problem in Thailand. Several chemical pediculicides have lost in efficacy due to increasing resistance of lice against insecticide. Therefore, non-toxic alternative products, such as natural products from plants, e.g. plant extract pediculicides, are needed for head lice control. The aims of this study were to evaluate the potential of pediculicidal activity of herbal shampoo base on three species of Thai local plants (Accacia concinna (Willd.) DC, Averrhoa bilimbi Linn. and Tamarindus indica Linn.) against head lice and to compare them with carbaryl shampoo (Hafif shampoo®; 0.6% w/v carbaryl) and non-treatment control in order to assess their in vitro. Doses of 0.12 and 0.25 ml/cm2 of each herbal shampoo were applied to filter paper, and ten head lice were place on the filter paper. The mortalities of head lice on the filter paper were recorded at 1, 5, 10, 30 and 60 min by sterio-microscope. All herbal shampoos at 0.25 ml/cm2 were more effective pediculicide than carbaryl shampoo with 100% mortality at 5 min. The median lethal time (LT50) of all herbal shampoos at 0.25 ml/cm2 showed no significant differences over at 0.12 ml/cm2 (P<0.01). The most effective pediculicide was T. indica extract shampoo, followed by Av. bilimbi extract shampoo and Ac. concinna extract shampoo, with LT50 values<1.0 min. Our data showed that all herbal shampoos have high potential of pediculicide to head lice treatments for schoolchildren.

Influence of sediment presence on freshwater mussel thermal tolerance

USGS Publications Warehouse

Archambault, Jennifer M.; Cope, W. Gregory; Kwak, Thomas J.

2014-01-01

Median lethal temperature (LT50) data from water-only exposures with the early life stages of freshwater mussels suggest that some species may be living near their upper thermal tolerances. However, evaluation of thermal sensitivity has never been conducted in sediment. Mussels live most of their lives burrowed in sediment, so understanding the effect of sediment on thermal sensitivity is a necessary step in evaluating the effectiveness of the water-only standard method, on which the regulatory framework for potential thermal criteria currently is based, as a test of thermal sensitivity. We developed a method for testing thermal sensitivity of juvenile mussels in sediment and used the method to assess thermal tolerance of 4 species across a range of temperatures common during summer. Stream beds may provide a thermal refuge in the wild, but we hypothesized that the presence of sediment alone does not alter thermal sensitivity. We also evaluated the effects of 2 temperature acclimation levels (22 and 27°C) and 2 water levels (watered and dewatered treatments). We then compared results from the sediment tests to those conducted using the water-only standard methods. We also conducted water-only LT tests with mussel larvae (glochidia) for comparison with the juvenile life stage. We found few consistent differences in thermal tolerance between sediment and water-only treatments, between acclimation temperatures, between waterlevel treatments, among species, or between juvenile and glochidial life stages (LT50 range = 33.3-37.2°C; mean = 35.6°C), supporting our hypothesis that the presence of sediment alone does not alter thermal sensitivity. The method we developed has potential for evaluating the role of other stressors (e.g., contaminants) in a more natural and complex environment.

Lung transplantation for cystic fibrosis: results, indications, complications, and controversies.

PubMed

Lynch, Joseph P; Sayah, David M; Belperio, John A; Weigt, S Sam

2015-04-01

Survival in patients with cystic fibrosis (CF) has improved dramatically over the past 30 to 40 years, with mean survival now approximately 40 years. Nonetheless, progressive respiratory insufficiency remains the major cause of mortality in CF patients, and lung transplantation (LT) is eventually required. Timing of listing for LT is critical, because up to 25 to 41% of CF patients have died while awaiting LT. Globally, approximately 16.4% of lung transplants are performed in adults with CF. Survival rates for LT recipients with CF are superior to other indications, yet LT is associated with substantial morbidity and mortality (∼50% at 5-year survival rates). Myriad complications of LT include allograft failure (acute or chronic), opportunistic infections, and complications of chronic immunosuppressive medications (including malignancy). Determining which patients are candidates for LT is difficult, and survival benefit remains uncertain. In this review, we discuss when LT should be considered, criteria for identifying candidates, contraindications to LT, results post-LT, and specific complications that may be associated with LT. Infectious complications that may complicate CF (particularly Burkholderia cepacia spp., opportunistic fungi, and nontuberculous mycobacteria) are discussed. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

The Rise of Robots: The Military’s Use of Autonomous Lethal Force

DTIC Science & Technology

2015-02-17

AIR WAR COLLEGE AIR UNIVERSITY THE RISE OF ROBOTS: THE MILITARY’S USE OF AUTONOMOUS LETHAL FORCE by Christopher J. Spinelli, Lt Col...ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Air War ...Christopher J. Spinelli is currently an Air War College student and was the former Commander of the 445th Flight Test Squadron at Edwards Air Force Base

Noninvasive imaging technologies reveal edema toxin as a key virulence factor in anthrax.

PubMed

Dumetz, Fabien; Jouvion, Grégory; Khun, Huot; Glomski, Ian Justin; Corre, Jean-Philippe; Rougeaux, Clémence; Tang, Wei-Jen; Mock, Michèle; Huerre, Michel; Goossens, Pierre Louis

2011-06-01

Powerful noninvasive imaging technologies enable real-time tracking of pathogen-host interactions in vivo, giving access to previously elusive events. We visualized the interactions between wild-type Bacillus anthracis and its host during a spore infection through bioluminescence imaging coupled with histology. We show that edema toxin plays a central role in virulence in guinea pigs and during inhalational infection in mice. Edema toxin (ET), but not lethal toxin (LT), markedly modified the patterns of bacterial dissemination leading, to apparent direct dissemination to the spleen and provoking apoptosis of lymphoid cells. Each toxin alone provoked particular histological lesions in the spleen. When ET and LT are produced together during infection, a specific temporal pattern of lesion developed, with early lesions typical of LT, followed at a later stage by lesions typical of ET. Our study provides new insights into the complex spatial and temporal effects of B. anthracis toxins in the infected host, suggesting a greater role than previously suspected for ET in anthrax and suggesting that therapeutic targeting of ET contributes to protection. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Chloroquine derivatives block the translocation pores and inhibit cellular entry of Clostridium botulinum C2 toxin and Bacillus anthracis lethal toxin.

PubMed

Kreidler, Anna-Maria; Benz, Roland; Barth, Holger

2017-03-01

The pathogenic bacteria Clostridium botulinum and Bacillus anthracis produce the binary protein toxins C2 and lethal toxin (LT), respectively. These toxins consist of a binding/transport (B 7 ) component that delivers the separate enzyme (A) component into the cytosol of target cells where it modifies its specific substrate and causes cell death. The B 7 components of C2 toxin and LT, C2IIa and PA 63 , respectively, are ring-shaped heptamers that bind to their cellular receptors and form complexes with their A components C2I and lethal factor (LF), respectively. After receptor-mediated endocytosis of the toxin complexes, C2IIa and PA 63 insert into the membranes of acidified endosomes and form trans-membrane pores through which C2I and LF translocate across endosomal membranes into the cytosol. C2IIa and PA 63 also form channels in planar bilayer membranes, and we used this approach earlier to identify chloroquine as a potent blocker of C2IIa and PA 63 pores. Here, a series of chloroquine derivatives was investigated to identify more efficient toxin inhibitors with less toxic side effects. Chloroquine, primaquine, quinacrine, and fluphenazine blocked C2IIa and PA 63 pores in planar lipid bilayers and in membranes of living epithelial cells and macrophages, thereby preventing the pH-dependent membrane transport of the A components into the cytosol and protecting cells from intoxication with C2 toxin and LT. These potent inhibitors of toxin entry underline the central role of the translocation pores for cellular uptake of binary bacterial toxins and as relevant drug targets, and might be lead compounds for novel pharmacological strategies against severe enteric diseases and anthrax.

A Seven-Year Longitudinal Claim Analysis to Assess the Factors Contributing to the Increased Severity of Work-Related Injuries.

PubMed

Kalia, Nimisha; Lavin, Robert A; Yuspeh, Larry; Bernacki, Edward J; Tao, Xuguang Grant

2016-09-01

In recent decades, the frequency of Medical Only (MO) and Lost Time (LT) workers' compensation claims has decreased, while average severity (medical and indemnity costs) has increased. The aim of this study was to compare claim frequency, mix, and severity (cost) over two periods using a claim cohort follow-up method. Sixty-two thousand five hundred thirty-three claims during two periods (1999 to 2002 and 2003 to 2006) were followed seven years postinjury. Descriptive analysis and significant testing methods were used to compare claim frequency and costs. The number of claims per $1 M of premium decreased 50.4% for MO claims and 35.6% for LT claims, consequently increasing the LT claim proportion. The average cost of LT claims did not increase. The severity increase is attributable to the proportional change in LT and MO claims. While the number of LT claims decreased, the inflation-adjusted average cost of LT claims did not increase.

Optimizing repeat liver transplant graft utility through strategic matching of donor and recipient characteristics.

PubMed

Hung, Kenneth; Gralla, Jane; Dodge, Jennifer L; Bambha, Kiran M; Dirchwolf, Melisa; Rosen, Hugo R; Biggins, Scott W

2015-11-01

Repeat liver transplantation (LT) is controversial because of inferior outcomes versus primary LT. A minimum 1-year expected post-re-LT survival of 50% has been proposed. We aimed to identify combinations of Model for End-Stage Liver Disease (MELD), donor risk index (DRI), and recipient characteristics achieving this graft survival threshold. We identified re-LT recipients listed in the United States from March 2002 to January 2010 with > 90 days between primary LT and listing for re-LT. Using Cox regression, we estimated the expected probability of 1-year graft survival and identified combinations of MELD, DRI, and recipient characteristics attaining >50% expected 1-year graft survival. Re-LT recipients (n = 1418) had a median MELD of 26 and median age of 52 years. Expected 1-year graft survival exceeded 50% regardless of MELD or DRI in Caucasian recipients who were not infected with hepatitis C virus (HCV) of all ages and Caucasian HCV-infected recipients <50 years old. As age increased in HCV-infected Caucasian and non-HCV-infected African American recipients, lower MELD scores or lower DRI grafts were needed to attain the graft survival threshold. As MELD scores increased in HCV-infected African American recipients, lower-DRI livers were required to achieve the graft survival threshold. Use of high-DRI livers (>1.44) in HCV-infected recipients with a MELD score > 26 at re-LT failed to achieve the graft survival threshold with recipient age ≥ 60 years (any race), as well as at age ≥ 50 years for Caucasians and at age < 50 years for African Americans. Strategic donor selection can achieve >50% expected 1-year graft survival even in high-risk re-LT recipients (HCV infected, older age, African American race, high MELD scores). Low-risk transplant recipients (age < 50 years, non-HCV-infected) can achieve the survival threshold with varying DRI and MELD scores. © 2015 American Association for the Study of Liver Diseases.

Contact and fumigant toxicity of hexane flower bud extract of Syzygium aromaticum and its compounds against Pediculus humanus capitis (Phthiraptera: Pediculidae).

PubMed

Bagavan, Asokan; Rahuman, Abdul Abdul; Kamaraj, Chinnaperumal; Elango, Gandhi; Zahir, Abdul Abduz; Jayaseelan, Chidambaram; Santhoshkumar, Thirunavukkarasu; Marimuthu, Sampath

2011-11-01

The head lice, Pediculus humanus capitis De Geer is an obligate ectoparasite of humans that causes pediculosis capitis, a nuisance for millions of people worldwide, with high prevalence in children. P. humanus capitis has been treated by methods that include the physical remotion of lice, various domestic treatments, and conventional insecticides. None of these methods render complete protection, and there is clear evidence for the evolution of resistance and cross-resistance to conventional insecticides. Non-toxic alternative options are hence needed for head lice treatment and/or prevention, and natural products from plants are good candidates for safer control agents that may provide good anti-lice activity. The plant extracts are good and safe alternatives due to their low toxicity to mammals and easy biodegradability. The present study carried out the pediculocidal activity using the hexane flower bud extract of Syzygium aromaticum (Myrtaceae) against P. humanus capitis examined by direct contact and fumigant toxicity (closed- and open-container methods) bioassay. The chemical composition of S. aromaticum flower bud hexane extract was analyzed by gas chromatography-mass spectrometry. The major chemical constituent (58.79%) of flower bud hexane extract S. aromaticum was identified as chavibetol (5-allyl-2-methoxyphenol) by comparison of mass spectral data and retention times. The hexane extract of S. aromaticum was subjected to gas chromatography analysis, and totally 47 compounds were detected, of which chavibetol was predominantly present. The other major constituents present in the hexane extract were eugenol acetate (phenol,2-methoxy-4-(2-propenyl)-,acetate (15.09%), caryophyllene-(I1) (2,6,10,10-tetramethyl bicyclo [7.2.0] undeca-1,6-diene (13.75%), caryophyllene oxide (3.04%), 2,6,6,9-tetramethyl-1,4,8-cycloundecatriene (1.67%), and copaene (1.33%). The filter paper contact bioassay study showed pronounced pediculicidal activity in the flower bud hexane extract of S. aromaticum. The toxic effect was determined for every five in an 80-min treatment. The result showed percent mortality of 40, 82, and 100 at 5, 10, and 20 min, and the median lethal time (LT(50)) value was 5.83 (0.5 mg/cm(2)); 28, 82, and 100 at 5, 10, and 30 min. (LT(50) = 6.54; 0.25 mg/cm(2)); and 13, 22, 42, 80, and 100 at 5, 10, 20, 40, and 80 min (LT(50) = 18.68; 0.125 mg/cm(2)), respectively. The vapor phase toxicity was tested at 0.25 mg/cm(2). There was a significant difference in pediculicidal activity of S. aromaticum extract against P. humanus capitis between closed- and open-container methods. Adult mortalities were determined for every five in 60 min (closed method) and for every ten in 180 min (open method). The closed method showed the percent mortality was 45, 88, and 100 at 5, 10, and 15 min (LT(50) = 5.39), respectively. In the open-container method, the percent mortality was observed 5, 20, 47, 84, and 100 at 10, 20, 60, 120, and 180 min (LT(50) = 47.91), respectively. The mortality was more effective in the closed containers than in open ones, indicating that the effect of hexane extract was largely a result of action in the vapor phase exhibited fumigant toxicity. Studies of anti-lice activity of extract provide the basis for preliminary conclusions of structure activity relationships; although no clear patterns can yet be drawn. We here attempt to provide a concise compilation of the available information on anti-lice activity of plant extracts and plant-derived compounds.

Chlorantraniliprole as a candidate pesticide used in combination with the attracticides for lepidopteran moths.

PubMed

Liu, Yongqiang; Gao, Yu; Liang, Gemei; Lu, Yanhui

2017-01-01

Methomyl is currently used as a toxicant for the attracticide BioAttract in cotton and vegetables in China. However, methomyl is highly toxic to non-target organisms and a more environmental friendly acceptable alternative is required. Larvae of three lepidopteran insects Helicoverpa armigera, Agrotis ipsilon and Spodoptera litura are important pests of these crops in China. In the present study, the toxicity of 23 commonly used insecticides were tested on H. armigera, then tested the susceptibility of A. ipsilon and S. litura moths to the insecticides which were the most toxic to H. armigera, and the acute toxicity of the most efficacious insecticides were further investigated under laboratory conditions. Chlorantraniliprole, emamectin benzoate, spinetoram, spinosad and methomyl exhibited high levels of toxicity to H. armigera moths with a mortality of 86.67%, 91.11%, 73.33%, 57.78% and 80.00%, respectively, during 24 h period at the concentration of 1 mg a.i. L-1. Among these five insecticides, A. ipsilon and S. litura moths were more sensitive to chlorantraniliprole, emamectin benzoate and methomyl. The lethal time (LT50) values of chlorantraniliprole and methomyl were shorter than emamectin benzoate for all three lepidopteran moth species at 1000 mg a.i. L-1 compared to concentrations of 500, 100 and 1 mg a.i L-1. Chlorantraniliprole was found to have similar levels of toxicity and lethal time on the three lepidopteran moths tested to the standard methomyl, and therefore, can be used as an alternative insecticide to methomyl in the attracticide for controlling these pest species.

Chlorantraniliprole as a candidate pesticide used in combination with the attracticides for lepidopteran moths

PubMed Central

Liu, Yongqiang; Gao, Yu; Liang, Gemei

2017-01-01

Methomyl is currently used as a toxicant for the attracticide BioAttract in cotton and vegetables in China. However, methomyl is highly toxic to non-target organisms and a more environmental friendly acceptable alternative is required. Larvae of three lepidopteran insects Helicoverpa armigera, Agrotis ipsilon and Spodoptera litura are important pests of these crops in China. In the present study, the toxicity of 23 commonly used insecticides were tested on H. armigera, then tested the susceptibility of A. ipsilon and S. litura moths to the insecticides which were the most toxic to H. armigera, and the acute toxicity of the most efficacious insecticides were further investigated under laboratory conditions. Chlorantraniliprole, emamectin benzoate, spinetoram, spinosad and methomyl exhibited high levels of toxicity to H. armigera moths with a mortality of 86.67%, 91.11%, 73.33%, 57.78% and 80.00%, respectively, during 24 h period at the concentration of 1 mg a.i. L-1. Among these five insecticides, A. ipsilon and S. litura moths were more sensitive to chlorantraniliprole, emamectin benzoate and methomyl. The lethal time (LT50) values of chlorantraniliprole and methomyl were shorter than emamectin benzoate for all three lepidopteran moth species at 1000 mg a.i. L-1 compared to concentrations of 500, 100 and 1 mg a.i L-1. Chlorantraniliprole was found to have similar levels of toxicity and lethal time on the three lepidopteran moths tested to the standard methomyl, and therefore, can be used as an alternative insecticide to methomyl in the attracticide for controlling these pest species. PMID:28658277

Identification and characterization of Vibrio harveyi associated with diseased abalone Haliotis diversicolor.

PubMed

Jiang, Qingru; Shi, Liuyang; Ke, Caihuan; You, Weiwei; Zhao, Jing

2013-03-26

Mass mortality of farmed small abalone Haliotis diversicolor occurred in Fujian, China, from 2009 to 2011. Among isolates obtained from moribund abalones, the dominant species AP37 exhibited the strongest virulence. After immersion challenge with 106 CFU ml-1 of AP37, abalone mortalities of 0, 53 and 67% were induced at water temperatures of 20°C, 24°C, and 28°C, respectively. Following intramuscular injection, AP37 showed a low LD50 (median lethal concentration) value of 2.9 × 102 CFU g-1 (colony forming units per gram abalone wet body weight). The LT50 (median lethal time) values were 5.2 h for 1 × 106 CFU abalone-1, 8.4 h for 1 × 105 CFU abalone-1, and 21.5 h for 1 × 104 CFU abalone-1. For further analysis of virulence, AP37 was screened for the production of extracellular factors. The results showed that various factors including presence of flagella and production of extracellular enzymes, such as lipase, phospholipase and haemolysin, could be responsible for pathogenesis. Based on its 16S rRNA gene sequence, strain AP37 showed >98.8% similarity to Vibrio harveyi, V. campbellii, V. parahaemolyticus, V. alginolyticus, V. natriegens and V. rotiferianus, so it could not be identified by this method. However, multi-locus sequence analysis (MLSA) of concatenated sequences, including the rpoD, rctB, gyrB, toxR and pyrH genes, identified strain AP37 as V. harveyi. Phenotypic characters of AP37 were identified by API 20E. In antibiotic susceptibility tests, strain AP37 exhibited susceptibility to 7 antibiotics and resistance to 13. This is the first report of a V. harveyi-related species being linked with the mass mortality of adult abalone H. diversicolor in southern China.

Evaluation of Piper aduncum Linn. Essential Oil (Fam:Piperaceae) against Periplaneta americana (L.).

PubMed

Ling A, I; Sulaiman, S; Othman, H

2009-01-01

The efficacy of Piper aduncum essential oil was evaluated against Periplaneta americana adults and nymphs in the laboratory. The plant essential oil at varying concentrations ranging between 10,000 to 80,000 ppm were placed inside glass beakers, rolled horizontally to ensure the essential oil covers all sides of the beakers and exposed to adults and nymphs of P. americana. Resigen (R) 1ppm was used as positive control and distilled water as negative control. The LT50 and LT90 was obtained using Log Probit programme. Exposure of essential oil to females P. americana at concentrations between 10,000 to 80,000 ppm indicated the LT50 and LT90 values between 5.31 h-189.19 h and 14.90 h-2105.31 h, respectively. Treatment with the same concentrations against males P. americana ,the LT50 and LT90 were 2.08 h-181.73 h and 5.4 h-8460.51 h, respectively. Treatment against the nymphal stage with the same range of concentrations indicated the LT50 and LT 90 of 4.68 h-381.02 h and 28.71 h-5313.36 h, respectively.The nymphs and males were more susceptible than the females cockroaches. Treatment with Resigen (R) at 1ppm indicated much lower LT 50 and LT 90 values of 2.54 h-9.47 h for the females, 1.47 h-4.22 h for the males and 4.69 h-8.92 h for the nymphs.The negative control indicated no mortality for all stages of the cockroach. Piper aduncum essential oil can be used as an alternative natural product for controlling the cockroach Peripatetic americana.

Evaluation of Piper aduncum Linn. Essential Oil (Fam:Piperaceae) against Periplaneta americana (L.)

PubMed Central

Ling A, I; Sulaiman, S; Othman, H

2009-01-01

Background: The efficacy of Piper aduncum essential oil was evaluated against Periplaneta americana adults and nymphs in the laboratory. Methods: The plant essential oil at varying concentrations ranging between 10,000 to 80,000 ppm were placed inside glass beakers, rolled horizontally to ensure the essential oil covers all sides of the beakers and exposed to adults and nymphs of P. americana. Resigen (R) 1ppm was used as positive control and distilled water as negative control. The LT50 and LT90 was obtained using Log Probit programme. Results: Exposure of essential oil to females P. americana at concentrations between 10,000 to 80,000 ppm indicated the LT50 and LT90 values between 5.31 h–189.19 h and 14.90 h–2105.31 h, respectively. Treatment with the same concentrations against males P. americana ,the LT50 and LT90 were 2.08 h–181.73 h and 5.4 h–8460.51 h, respectively. Treatment against the nymphal stage with the same range of concentrations indicated the LT50 and LT 90 of 4.68 h–381.02 h and 28.71 h–5313.36 h, respectively.The nymphs and males were more susceptible than the females cockroaches. Treatment with Resigen (R) at 1ppm indicated much lower LT 50 and LT 90 values of 2.54 h–9.47 h for the females, 1.47 h–4.22 h for the males and 4.69 h–8.92 h for the nymphs.The negative control indicated no mortality for all stages of the cockroach. Conclusion: Piper aduncum essential oil can be used as an alternative natural product for controlling the cockroach Peripatetic americana. PMID:22808375

Ex vivo evaluation of 4 different viscoelastic assays for detecting moderate to severe coagulopathy during liver transplantation.

PubMed

Abuelkasem, Ezeldeen; Mazzeffi, Michael A; Lu, Shu Yang; Planinsic, Raymond M; Sakai, Tetsuro; Tanaka, Kenichi A

2016-04-01

Prolonged prothrombin time (PT) and its ratio are routinely used for the assessment of candidates for liver transplantation (LT), but intraoperative coagulation management of transfusion is hindered by its long turnaround time. Abnormal reaction time (R time) on thromboelastography (TEG) or clotting time (CT) of rotational thromboelastometry (ROTEM) are presumably an alternative, but there is a paucity of clinical data on abnormal R time/CT values compared to PT during LT. After receiving institutional review board approval and informed consent, we obtained blood samples from 36 LT patients for international normalized ratio (INR), factor (F) X level, and viscoelastic tests (EXTEM/INTEM and kaolin/rapid TEG) at baseline and 30 minutes after graft reperfusion. Receiver operating characteristic (ROC) curves were calculated for INR > 1.5 and viscoelastic R time/CT thresholds to assess the ability to diagnose FX deficiency at the moderate (<50%) or severe (<35%) level. The FX deficiency data were calculated using cutoff values of INR (>1.5) and abnormal R time/CT for TEG and ROTEM. Tissue factor (TF)-activated INR and EXTEM-CT performed well in diagnosing FX below 50%, but rapid TEG with combined TF and kaolin activators failed. Improved performance of INTEM-CT in diagnosing FX below 35% underlies multifactorial deficiency involving both intrinsic and common pathways. In conclusion, the differences among different viscoelastic tests and clinical situations should be carefully considered when they are used to guide transfusion during LT. © 2015 American Association for the Study of Liver Diseases.

Susceptibility of Culicidae Mosquitoes to Some Insecticides Recommended by WHO in a Malaria Endemic Area of Southeastern Iran

PubMed Central

Fathian, Mousa; Vatandoost, Hassan; Moosa-Kazemi, Seyed Hassan; Raeisi, Ahmad; Yaghoobi-Ershadi, Mohammad Reza; Oshaghi, Mohammad Ali; Sedaghat, Mohammad Mehdi

2015-01-01

Background: According to the national strategy plan on monitoring of insecticides resistance, this study was carried out to determine the base line susceptibility of the Culicidae mosquitoes to the WHO-recommended insecticides in an endemic focus of malaria in southeastern Iran. Methods: Larval collection was carried out by dipping method and adult collection occurred by suction tube from January to December 2010. The susceptibility test was assessed to DDT 4 %, malathion 5 %, propoxur 0.1 %, deltamethrin 0.05 %, lambda-cyhalothrin 0.05 %, and cyfluthrin 0.15 % at different interval times (discriminative dose) followed by 24 h recovery period. The LT50 and LT90 values were calculated for plotting the regression line using Microsoft office Excel software ver. 2007. Results: Anopheles stephensi was quite resistant to DDT and showed susceptible or tolerant to other insecticides. The LT50 and LT90 values to DDT in this species were 29.07, and 98.26 minutes, respectively. Anopheles culicifacies and Anopheles dthali were found susceptible or tolerant to insecticides. Culex pipiens was found resistance to DDT, propoxur, lambda-cyhalothrin and cyfluthrin whereas observed susceptible to malathion and tolerant to deltamethrin. Ochlerotatus caspius sl. was resistant to DDT, whereas found susceptible to other insecticides. Culisita longiareolata was susceptible to deltamethrin, whereas tolerant to other insecticides. The LT50 and LT90 values of Cs. longiareolata to DDT were 17.82, and 51.26 minutes. Conclusion: We suggested the same study in different parts of the country for monitoring and evaluation of control measures. PMID:26114141

Acaricidal activities of the essential oil from Rhododendron nivale Hook. f. and its main compund, δ-cadinene against Psoroptes cuniculi.

PubMed

Guo, Xiao; Shang, Xiaofei; Li, Bing; Zhou, Xu Zheng; Wen, Hao; Zhang, Jiyu

2017-03-15

In this paper, the acaricidal activities of Rhododendron nivale Hook. f. and its main compound, δ-cadinene were investigated, and the chemical composition of the essential oil was analyzed. The results showed that among aqueous, 70% ethanols, acetic ether, chloroform, petroleum ether and essential oil extracts from the shoots and leaves, the essential oil showed the best in vitro acaricidal activity against adult P. cuniculi, which occurred in a concentration- and time-dependent manner. The median lethal time (LT 50 ) values of four concentrations (33.33-4.17mg/ml) of the essential oil ranged from 1.476 to 25.900h, respectively. After the treatment of P. cuniculi with the essential oil and ivermectin, infected rabbits were free of scabs or secretions in the ear canal by day 20. Then, the percent yield of essential oil from the leaves and shoots was 2.45% (w/w), which includes 50 compounds. The primary component identified was terpenes, and among of compounds identified from the essential oil of R. nivale the highest relative content was δ-cadinene, which also presented the marked acaricidal activity against Psoroptes cuniculi in vitro. These findings provide evidence for the use of acaricides as a traditional medicine and indicate that the essential oil and δ-cadinene could be used to control mites in livestock. Copyright © 2017 Elsevier B.V. All rights reserved.

The effects of elevated water temperature on native juvenile mussels: implications for climate change

USGS Publications Warehouse

Ganser, Alissa M.; Newton, Teresa J.; Haro, Roger J.

2013-01-01

Native freshwater mussels are a diverse but imperiled fauna and may be especially sensitive to increasing water temperatures because many species already may be living near their upper thermal limits. We tested the hypothesis that elevated water temperatures (20, 25, 30, and 35°C) adversely affected the survival and physiology of 2-mo-old juvenile mussels (Lampsilis abrupta, Lampsilis siliquoidea, and Megalonaias nervosa) in 28-d laboratory experiments. The 28-d LT50s (lethal temperature affecting 50% of the population) ranged from 25.3 to 30.3°C across species, and were lowest for L. abrupta and L. siliquoidea. Heart rate of L. siliquoidea was not affected by temperature, but heart rate declined at higher temperatures in L. abrupta and M. nervosa. However, for both of these species, heart rate also declined steadily during the experiment and a strong temperature × time interaction was detected. Juvenile growth was low for all species in all treatments and did not respond directly to temperature, but growth of some species responded to a temperature × time interaction. Responses to thermal stress differed among species, but potential laboratory artifacts may limit applicability of these results to real-world situations. Environmentally relevant estimates of upper thermal tolerances in native mussels are urgently needed to assess the extent of assemblage changes that can be expected in response to global climate change.

Survival of indianmeal moth and navel orangeworm (Lepidoptera: Pyralidae) at low temperatures.

PubMed

Johnson, J A

2007-08-01

Concerns over insect resistance, regulatory action, and the needs of organic processors have generated renewed interest in developing nonchemical alternative postharvest treatments to fumigants used on dried fruits and nuts. Low-temperature storage has been identified as one alternative for the Indianmeal moth, Plodia interpunctella (Hiibner), and navel orangeworm, Amyelois transitella (Walker) (Lepidoptera: Pyralidae), common postharvest pests in California dried fruits and nuts. The response of eggs, nondiapausing larvae, and pupae of both species to exposure to low temperatures (0, 5, and 10 degrees C) was evaluated. Eggs of both species were the least tolerant of low temperatures. At 0 and 5 degrees C, pupae were most tolerant, but at 10 degrees C, nondiapausing larvae of both species were most tolerant, with lethal time (LT)95 values of 127 and 100 d for Indianmeal moth and navel orangeworm, respectively. The response of diapausing Indianmeal moth larvae to subfreezing temperatures also was evaluated. Diapausing larvae were very cold tolerant at -10 degrees C, with LT95 values of 20 and 17 d for long-term laboratory and recently isolated cultures, respectively. Diapausing larvae were far less tolerant at lower temperatures. At -15 degrees C, LT95 values for both cultures were <23 h, and at -20 degrees C, LT95 values were <7 h. Refrigeration temperatures of 0-5 degrees C should be useful in disinfesting product contaminated with nondiapausing insects, with storage times of 3 wk needed for adequate control. Relatively brief storage in commercial freezers, provided that the temperature throughout the product was below -15 degrees C for at least 48 h, also shows potential as a disinfestation treatment, and it is necessary when diapausing Indianmeal moth larvae are present.

Effect of dietary supplementation of l-tryptophan on thermal tolerance and oxygen consumption rate in Cirrhinus mrigala fingerlings under varied stocking density.

PubMed

Tejpal, C S; Sumitha, E B; Pal, A K; Shivananda Murthy, H; Sahu, N P; Siddaiah, G M

2014-04-01

A 60 day feeding trial was conducted to study the effect of dietary l-tryptophan on thermal tolerance and oxygen consumption rate of freshwater fish, mrigala, Cirrhinus mrigala reared under ambient temperature at low and high stocking density. Four hundred eighty fingerlings were distributed into eight experimental groups. Four groups each of low density group (10 fishes/75L water) and higher density group (30 fishes/75L water) were fed a diet containing 0, 0.68, 1.36 or 2.72% l-tryptophan in the diet, thus forming eight experimental groups namely, Low density control (LC) (basal feed +0% l-tryptophan); LT1 (basal feed+0.68% l-tryptophan); LT2 (basal feed+1.36% l-tryptophan); LT3 (basal feed+2.72% l-tryptophan); high density control (HC) (basal feed+0% l-tryptophan); HT1 (basal feed+0.68% l-tryptophan); HT2 (basal feed+1.36% l-tryptophan); and HT3 (basal feed+2.72% l-tryptophan) were fed at 3% of the body weight. The test diets having crude protein 34.33±0.23 to 35.81±0.18% and lipid 423.49±1.76 to 425.85±0.31KCal/100g were prepared using purified ingredients. The possible role of dietary l-tryptophan on thermal tolerance and oxygen consumption rate was assessed in terms of critical thermal maxima (CTMax), critical thermal minima (CTMin), lethal thermal maxima (LTMax) and lethal thermal minima (LTMin). The CTMax, CTMin, LTMax and LTMin values were found to be significantly higher (p<0.05) in the treatment groups with CTMax 42.94±0.037 (LT2); LT Max 43.18±0.070 (LT2); CTMin 10.47±0.088 (LT2) and LTMin 9.42±0.062 (LT3), whereas the control group showed a lower tolerance level. The same trend was observed in the high density group (CTMax 42.09±0.066 (LT3); LTMax 43 23±0.067 (HT3); CTMin 10.98±0.040 (HT3) and LTMin 9.74±0.037 (HT3). However, gradual supplementation of dietary l-tryptophan in the diet significantly reduced the oxygen consumption rate in both the low density group (Y=-26.74x+222.4, r²=0.915) and the high density group (Y=-32.96x+296.5, r²=0.8923). Dietary supplementation of l-tryptophan at a level of 1.36% improved the thermal tolerance level and reduced the oxygen consumption rate in C. mrigala fingerlings. Copyright © 2014 Elsevier Ltd. All rights reserved.

Allelic Variation on Murine Chromosome 11 Modifies Host Inflammatory Responses and Resistance to Bacillus anthracis

PubMed Central

Terra, Jill K.; France, Bryan; Cote, Christopher K.; Jenkins, Amy; Bozue, Joel A.; Welkos, Susan L.; Bhargava, Ragini; Ho, Chi-Lee; Mehrabian, Margarete; Pan, Calvin; Lusis, Aldons J.; Davis, Richard C.; LeVine, Steven M.; Bradley, Kenneth A.

2011-01-01

Anthrax is a potentially fatal disease resulting from infection with Bacillus anthracis. The outcome of infection is influenced by pathogen-encoded virulence factors such as lethal toxin (LT), as well as by genetic variation within the host. To identify host genes controlling susceptibility to anthrax, a library of congenic mice consisting of strains with homozygous chromosomal segments from the LT-responsive CAST/Ei strain introgressed on a LT-resistant C57BL/6 (B6) background was screened for response to LT. Three congenic strains containing CAST/Ei regions of chromosome 11 were identified that displayed a rapid inflammatory response to LT similar to, but more severe than that driven by a LT-responsive allele of the inflammasome constituent NRLP1B. Importantly, increased response to LT in congenic mice correlated with greater resistance to infection by the Sterne strain of B. anthracis. The genomic region controlling the inflammatory response to LT was mapped to 66.36–74.67 Mb on chromosome 11, a region that encodes the LT-responsive CAST/Ei allele of Nlrp1b. However, known downstream effects of NLRP1B activation, including macrophage pyroptosis, cytokine release, and leukocyte infiltration could not fully explain the response to LT or the resistance to B. anthracis Sterne in congenic mice. Further, the exacerbated response in congenic mice is inherited in a recessive manner while the Nlrp1b-mediated response to LT is dominant. Finally, congenic mice displayed increased responsiveness in a model of sepsis compared with B6 mice. In total, these data suggest that allelic variation of one or more chromosome 11 genes in addition to Nlrp1b controls the severity of host response to multiple inflammatory stimuli and contributes to resistance to B. anthracis Sterne. Expression quantitative trait locus analysis revealed 25 genes within this region as high priority candidates for contributing to the host response to LT. PMID:22241984

Bioassay and Scanning Electron Microscopic Observations Reveal High Virulence of Entomopathogenic Fungus, Beauveria bassiana, on the Onion Maggot (Diptera: Anthomyiidae) Adults.

PubMed

Zhang, Hui; Wu, Shengyong; Xing, Zhenlong; Wang, Xiaoqing; Lei, Zhongren

2016-12-01

When flies were dipped in 1 × 10 8 conidia/ml conidia suspensions and then kept in the incubator (22 ± 1 °C, 70 ± 5% RH), scanning electron microscope observations revealed that, at 2 h, the majority of adhering Beauveria bassiana conidia were attached to either the wing surface or the interstitial area between the macrochaetae on the thorax and abdomen of the onion maggot adults. Germ tubes were being produced and had oriented toward the cuticle by 18 h. Penetration of the insect cuticle had occurred by 36 h, and by 48 h, germ tubes had completely penetrated the cuticle. Fungal mycelia had emerged from the insect body and were proliferating after 72 h. The superficial area and structure of the wings and macrochaetae may facilitate the attachment of conidia and enable effective penetration. The susceptibility of adults to 12 isolates, at a concentration of 1 × 10 7 conidia/ml, was tested in laboratory experiments. Eight of the more potent strains caused in excess of 85% adult mortality 8 d post inoculation, while the median lethal time (LT 50 ) of these strains was <6 d. The virulence of the more effective strains was further tested, and the median lethal concentrations (LC 50 ) were calculated by exposing adults to doses ranging from 10 3 -10 7 conidia/ml. The lowest LC 50 value, found in the isolate XJWLMQ-32, for the adults was 3.87 × 10 3 conidia/ml. These results demonstrate that some B. bassiana strains are highly virulent to onion maggot adults and should be considered as potential biocontrol agents against the adult flies. © The Authors 2016. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Should possible recurrence of disease contraindicate liver transplantation in patients with end-stage alveolar echinococcosis? A 20-year follow-up study.

PubMed

Bresson-Hadni, Solange; Blagosklonov, Oleg; Knapp, Jenny; Grenouillet, Frédéric; Sako, Yasuhito; Delabrousse, Eric; Brientini, Marie-Pascale; Richou, Carine; Minello, Anne; Antonino, Anca-Teodora; Gillet, Michel; Ito, Akira; Mantion, Georges André; Vuitton, Dominique Angèle

2011-07-01

Liver transplantation (LT) is currently contraindicated in patients with residual or metastatic alveolar echinococcosis (AE) lesions. We evaluated the long-term course of such patients who underwent LT and were subsequently treated with benzimidazoles. Clinical, imaging, serological, and therapeutic data were collected from 5 patients with residual/recurrent AE lesions who survived for more than 15 years. Since 2004, [(18) F]-2-fluoro-2-deoxyglucose (FDG)-positron emission tomography (PET) images were available, and the levels of serum antibodies (Abs) against Echinococcus multilocularis-recombinant antigens were evaluated. Median survival time after LT was 21 years. These patients were from a prospective cohort of 23 patients with AE who underwent LT: 5 of 8 patients with residual/recurrent AE and 4 of 9 patients without residual/recurrent AE were alive in September 2009. High doses of immunosuppressive drugs, the late introduction of therapy with benzimidazoles, its withdrawal due to side effects, and nonadherence to this therapy adversely affected the prognosis. Anti-Em2(plus) and anti-rEm18 Ab levels and standard FDG-PET enabled the efficacy of therapy on the growth of EA lesions to be assessed. However, meaningful variations in Ab levels were observed below diagnostic cutoff values; and in monitoring AE lesions, images of FDG uptake taken 3 hours after its injection were more sensitive than images obtained 1 hour after its injection. In conclusion, benzimidazoles can control residual/recurrent AE lesions after LT. Using anti-rEm18 or anti-Em2(plus) Ab levels and the delayed acquisition of FDG-PET images can improve the functional assessment of disease activity. The potential recurrence of disease, especially in patients with residual or metastatic AE lesions, should not be regarded as a contraindication to LT when AE is considered to be lethal in the short term. Copyright © 2011 American Association for the Study of Liver Diseases.

Effect of temperature and humidity on pathogenicity of native Beauveria bassiana isolate against Musca domestica L.

PubMed

Mishra, Sapna; Kumar, Peeyush; Malik, Anushree

2015-12-01

Beauveria bassiana HQ917687 virulence to housefly larvae and adult was assessed at different relative humidity, RH (50, 75, 90, and 100 %) and temperature (15, 20, 25, 30, 35, 40, 45 °C) conditions at the fungal dose of 10(8) conidia/ml. Depending on the temperature and RH regime tested, difference in mortality rates of housefly adult and larvae were detected. During assay on adult housefly, 100 % mortality was achieved at RH, 90 and 100 % while the temperature of 30 °C showed maximum mortality at all the tested humidity conditions. Lethal time, LT50 was 2.9 days at 100 % RH. Larval mortality at different humidity conditions varied between 30 and 74 %, with maximum mortality at 100 % RH and 30 °C. Optimum temperature for B. bassiana virulence to housefly larvae was also found to be 30 °C. The interaction between temperature and RH revealed significant effect of RH at moderate temperature range (20-35 °C), while such an interaction was not observed at extreme temperatures. The results obtained in this study have useful implications in understanding the pathogen behavior under actual field conditions. This in turn may help devising suitable entomopathogen release schedules for maximum fungal infection.

Does Resistance to Buprofezin Improve Heat and Cold Tolerance of Laodelphax striatellus (Hemiptera: Delphacidae)?

PubMed

Li, Yongteng; Zhang, Yueliang; Liu, Xiangdong; Guo, Huifang

2017-08-01

There is ample evidence that insecticide resistance causes fitness costs and benefits in pests, while the impact of insecticide resistance on thermotolerance of pests is mostly unclear. The Laodelphax striatellus (Fallén), is an important rice insect pest, which has developed resistance to buprofezin in China. Here, we investigated differences in heat tolerance and cold tolerance among L. striatellus lines with variable buprofezin resistance. The lethal time for 50% of the individuals to die (LT50) at 40 °C increased with an increase in buprofezin resistance level, whereas both the survival rate under -22 °C and the supercooling point of planthoppers did not differ significantly between resistant and susceptible strains. The metabolic enzyme carboxylesterase was found to have an association with buprofezin resistance. Our research showed that buprofezin resistance was positively related with heat tolerance in L. striatellus, but it had no effect on cold tolerance. Insecticide resistance in L. striatellus may therefore have broader implications for the ecology of L. striatellus, and the management of buprofezin resistance in this pest may be challenging. © The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Massage therapy decreases cancer-related fatigue: Results from a randomized early phase trial.

PubMed

Kinkead, Becky; Schettler, Pamela J; Larson, Erika R; Carroll, Dedric; Sharenko, Margaret; Nettles, James; Edwards, Sherry A; Miller, Andrew H; Torres, Mylin A; Dunlop, Boadie W; Rakofsky, Jeffrey J; Rapaport, Mark Hyman

2018-02-01

Cancer-related fatigue (CRF) is a prevalent and debilitating symptom experienced by cancer survivors, yet treatment options for CRF are limited. In this study, we evaluated the efficacy of weekly Swedish massage therapy (SMT) versus an active control condition (light touch [LT]) and waitlist control (WLC) on persistent CRF in breast cancer survivors. This early phase, randomized, single-masked, 6-week investigation of SMT, LT, and WLC enrolled 66 female stage 0-III breast cancer survivors (age range, 32-72 years) who had received surgery plus radiation and/or chemotherapy/chemoprevention with CRF (Brief Fatigue Inventory > 25). The primary outcome was the Multidimensional Fatigue Inventory (MFI), with the National Institutes of Health PROMIS Fatigue scale secondary. Mean baseline MFI scores for 57 evaluable subjects were 62.95 for SMT, 55.00 for LT, and 60.41 for WLC. SMT resulted in a mean (standard deviation) 6-week reduction in MFI total scores of -16.50 (6.37) (n = 20) versus -8.06 (6.50) for LT (n = 20) and an increase of 5.88 (6.48) points for WLC (n = 17) (treatment-by-time P < .0001). The mean baseline PROMIS Fatigue scores were SMT, 22.25; LT, 22.05; and WLC, 23.24. The mean (standard deviation) reduction in PROMIS Fatigue scores was -5.49 (2.53) points for SMT versus -3.24 (2.57) points for LT and -0.06 (1.88) points for WLC (treatment-by-time P = .0008). Higher credibility, expectancy, and preference for SMT than for LT did not account for these results. SMT produced clinically significant relief of CRF. This finding suggests that 6 weeks of a safe, widely accepted manual intervention causes a significant reduction in fatigue, a debilitating sequela for cancer survivors. Cancer 2018;124:546-54. © 2017 American Cancer Society. © 2017 American Cancer Society.

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

Ambrosone, Alfredo; Scotto di Vettimo, Maria Rosaria; Malvindi, Maria Ada

It is generally accepted that silica (SiO{sub 2}) is not toxic. But the increasing use of silica nanoparticles (SiO{sub 2}NPs) in many different industrial fields has prompted the careful investigation of their toxicity in biological systems. In this report, we describe the effects elicited by SiO{sub 2}NPs on animal and cell physiology. Stable and monodisperse amorphous silica nanoparticles, 25 nM in diameter, were administered to living Hydra vulgaris (Cnidaria). The dose-related effects were defined by morphological and behavioral assays. The results revealed an all-or-nothing lethal toxicity with a rather high threshold (35 nM NPs) and a LT50 of 38 h.more » At sub lethal doses, the morphophysiological effects included: animal morphology alterations, paralysis of the gastric region, disorganization and depletion of tentacle specialized cells, increase of apoptotic and collapsed cells, and reduction of the epithelial cell proliferation rate. Transcriptome analysis (RNAseq) revealed 45 differentially expressed genes, mostly involved in stress response and cuticle renovation. Our results show that Hydra reacts to SiO{sub 2}NPs, is able to rebalance the animal homeostasis up to a relatively high doses of SiO{sub 2}NPs, and that the physiological modifications are transduced to gene expression modulation.« less

New insights into the biological effects of anthrax toxins: linking cellular to organismal responses

PubMed Central

Guichard, Annabel; Nizet, Victor; Bier, Ethan

2013-01-01

The anthrax toxins lethal toxin (LT) and edema toxin (ET), are essential virulence factors produced by B. anthracis. These toxins act during two distinct phases of anthrax infection. During the first, prodromal phase, which is often asymptomatic, anthrax toxins act on cells of the immune system to help the pathogen establish infection. Then, during the rapidly progressing (or fulminant) stage of the disease bacteria disseminate via a hematological route to various target tissues and organs, which are typically highly vascularized. As bacteria proliferate in the bloodstream LT and ET begin to accumulate rapidly reaching a critical threshold level that will cause death even when the bacterial proliferation is curtailed by antibiotics. During this final phase of infection the toxins cause an increase in vascular permeability and a decrease in function of target organs including the heart, spleen, kidney, adrenal gland, and brain. In this review, we examine the various biological effects of anthrax toxins, focusing on the fulminant stage of the disease and on mechanisms by which the two toxins may collaborate to cause cardiovascular collapse. We discuss normal mechanisms involved in maintaining vascular integrity and based on recent studies indicating that LT and ET cooperatively inhibit membrane trafficking to cell-cell junctions we explore several potential mechanisms by which the toxins may achieve their lethal effects. We also summarize the effects of other potential virulence factors secreted by B. anthracis and consider the role of toxic factors in the evolutionarily recent emergence of this devastating disease. PMID:21930233

Automatic Threshold Detector Techniques

DTIC Science & Technology

1976-07-15

Averaging CFAR in Non- Stationary Weibull Clutter, " L. Novak, (1974 IEEE Symposium on Information Theory ). 8. "The Weibull Distribution Applied to the... UGTS (K) ,Kml NPTS) 140 DO 153 K~lvNPT9 IF(SIGCSO(K) .LT.0. )SIOCSO(K).1 .E-50 IF(SIOWSO(K) .LT.0. )SIGWSQ(K)-1 .E-50 IF(SIONSG(K) .LT.O. )SIG3NSQCIO-1.E

Effect of a prior intermittent run at vVO2max on oxygen kinetics during an all-out severe run in humans.

PubMed

Billat, V L; Bocquet, V; Slawinski, J; Laffite, L; Demarle, A; Chassaing, P; Koralsztein, J P

2000-09-01

The purpose of this study was to examine the influence of prior intermittent running at VO2max on oxygen kinetics during a continuous severe intensity run and the time spent at VO2max. Eight long-distance runners performed three maximal tests on a synthetic track (400 m) whilst breathing through the COSMED K4 portable telemetric metabolic analyser: i) an incremental test which determined velocity at the lactate threshold (vLT), VO2max and velocity associated with VO2max (vVO2max), ii) a continuous severe intensity run at vLT+50% (vdelta50) of the difference between vLT and vVO2max (91.3+/-1.6% VO2max)preceded by a light continuous 20 minute run at 50% of vVO2max (light warm-up), iii) the same continuous severe intensity run at vdelta50 with a prior interval training exercise (hard warm-up) of repeated hard running bouts performed at 100% of vVO2max and light running at 50% of vVO2max (of 30 seconds each) performed until exhaustion (on average 19+/-5 min with 19+/-5 interval repetitions). This hard warm-up speeded the VO2 kinetics: the time constant was reduced by 45% (28+/-7 sec vs 51+/-37 sec) and the slow component of VO2 (deltaVO2 6-3 min) was deleted (-143+/-271 ml x min(-1) vs 291+/-153 ml x min(-1)). In conclusion, despite a significantly lower total run time at vdelta50 (6 min 19+/-0) min 17 vs 8 min 20+/-1 min 45, p=0.02) after the intermittent warm-up at VO2max, the time spent specifically at VO2max in the severe continuous run at vdelta50 was not significantly different.

Liver transplantation: Fifty years of experience

PubMed Central

Song, Alice Tung Wan; Avelino-Silva, Vivian Iida; Pecora, Rafael Antonio Arruda; Pugliese, Vincenzo; D’Albuquerque, Luiz Augusto Carneiro; Abdala, Edson

2014-01-01

Since 1963, when the first human liver transplantation (LT) was performed by Thomas Starzl, the world has witnessed 50 years of development in surgical techniques, immunosuppression, organ allocation, donor selection, and the indications and contraindications for LT. This has led to the mainstream, well-established procedure that has saved innumerable lives worldwide. Today, there are hundreds of liver transplant centres in over 80 countries. This review aims to describe the main aspects of LT regarding the progressive changes that have occurred over the years. We herein review historical aspects since the first experimental studies and the first attempts at human transplantation. We also provide an overview of immunosuppressive agents and their potential side effects, the evolution of the indications and contraindications of LT, the evolution of survival according to different time periods, and the evolution of methods of organ allocation. PMID:24833866

The slow component of O(2) uptake is not accompanied by changes in muscle EMG during repeated bouts of heavy exercise in humans.

PubMed

Scheuermann, B W; Hoelting, B D; Noble, M L; Barstow, T J

2001-02-15

1. We hypothesized that either the recruitment of additional muscle motor units and/or the progressive recruitment of less efficient fast-twitch muscle fibres was the predominant contributor to the additional oxygen uptake (VO2) observed during heavy exercise. Using surface electromyographic (EMG) techniques, we compared the VO2 response with the integrated EMG (iEMG) and mean power frequency (MPF) response of the vastus lateralis with the VO2 response during repeated bouts of moderate (below the lactate threshold, < LT) and heavy (above the lactate threshold, > LT) intensity cycle ergometer exercise. 2. Seven male subjects (age 29 +/- 7 years, mean +/- S.D.) performed three transitions to a work rate (WR) corresponding to 90 % LT and two transitions to a work rate that would elicit a VO2 corresponding to 50 % of the difference between peak VO2 and the LT (i.e. Delta50 %, > LT1 and > LT2). 3. The VO2 slow component was significantly reduced by prior heavy intensity exercise (> LT1, 410 +/- 196 ml min(-1); > LT2, 230 +/- 191 ml min-1). The time constant (tau), amplitude (A) and gain (DeltaVO2/DeltaWR) of the primary VO2 response (phase II) were not affected by prior heavy exercise when a three-component, exponential model was used to describe the V2 response. 4. Integrated EMG and MPF remained relatively constant and at the same level throughout both > LT1 and > LT2 exercise and therefore were not associated with the VO2 slow component. 5. These data are consistent with the view that the increased O2 cost (i.e. VO2 slow component) associated with performing heavy exercise is coupled with a progressive increase in ATP requirements of the already recruited motor units rather than to changes in the recruitment pattern of slow versus fast-twitch motor units. Further, the lack of speeding of the kinetics of the primary VO2 component with prior heavy exercise, thought to represent the initial muscle VO2 response, are inconsistent with O2 delivery being the limiting factor in V > O2 kinetics during heavy exercise.

Cold Tolerance of Mountain Pine Beetle (Coleoptera: Curculionidae) Eggs From the Historic and Expanded Ranges.

PubMed

Bleiker, K P; Smith, G D; Humble, L M

2017-10-01

Winter mortality is expected to be a key factor determining the ability of mountain pine beetle, Dendroctonus ponderosae Hopkins (Coleoptera: Curculionidae), to expand its range in Canada. We determined the mortality rate and supercooling points of eggs from the beetle's historic range in southern British Columbia as well as the recently expanded range in north-central Alberta and tested if eggs require an extended period of chilling to reach their maximum cold tolerance. We found no effect of population source or acclimation time on egg cold tolerance. Although 50% of eggs can survive brief exposure to -20.5 °C (LT50), storage at 0.3 °C and -7.5 °C for 59 d resulted in 50% and 100% mortality, respectively. Our results indicate that eggs suffer significant prefreeze mortality and are not well-adapted to overwintering: eggs are unlikely to survive winter throughout much of the beetle's range. Our results provide information that can be used to help model the climatic suitability of mountain pine beetle, including how changes in seasonality associated with new or changing climates may affect winter survival. In addition to lower lethal temperatures, it is critical that the duration of exposure to sublethal cold temperatures are considered in a comprehensive index of cold tolerance and incorporated into survival and population models. © The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Substitution of Liothyronine at a 1:5 Ratio for a Portion of Levothyroxine: Effect on Fatigue, Symptoms of Depression, and Working Memory Versus Treatment with Levothyroxine Alone

PubMed Central

Rodriguez, Tom; Lavis, Victor R.; Meininger, Janet Ck.; Kapadia, Asha S.; Stafford, Linda F.

2006-01-01

Background This study was planned at a time when important questions were being raised about the adequacy of using one hormone to treat hypothyroidism instead of two. Methods This trial attempted to replicate prior findings which suggested that substituting 12.5 μg of liothyronine for 50 μg of levothyroxine might improve mood, cognition, and physical symptoms in patients with primary hypothyroidism. Additionally, this trial aimed to extend the above findings to fatigue and to assess for differential effects in subjects with low and high fatigue at baseline. A randomized, double-blind, two-period, crossover design was used. Thirty subjects stabilized on levothyroxine (L-T4) at an endocrinology and diabetes clinic were recruited. Sequence one received their standard L-T4 dose in one capsule and placebo in another. Sequence two received their usual L-T4 dose minus 50 μg in one capsule and 10 μg of liothyronine (L-T3) in the other. At the end of the first six weeks, subjects were crossed over. T tests were used to assess carry-over and treatment effects. Results Twenty-seven subjects completed the trial. Mean L-T4 dose was 121 μg/d (± 26.0) at baseline. There were no significant differences in fatigue and symptoms of depression between treatments. Measures of working memory were unchanged. While on substitution treatment, free thyroxine index was reduced by 0.7 (p<0.001), total serum thyroxine was reduced by 3.0 μg/dl (p<0.001), and total serum triiodothyronine was increased by 20.5 ng/dl (p=0.004). Conclusions With regard to the outcomes measured, substitution of L-T3 at a 1:5 ratio for a portion of baseline L-T4 was no better than treatment with the original dose of L-T4 alone. PMID:16006298

T cell-derived Lymphotoxin is Essential for anti-HSV-1 Humoral Immune Response.

PubMed

Yang, Kaiting; Liang, Yong; Sun, Zhichen; Xue, Diyuan; Xu, Hairong; Zhu, Mingzhao; Fu, Yang-Xin; Peng, Hua

2018-05-09

B cell-derived lymphotoxin (LT) is required for the development of follicular dendritic cell clusters for the formation of primary and secondary lymphoid follicles, but the role of T cell-derived LT in antibody response has not been well demonstrated. We observed that lymphotoxin-β-receptor (LTβR) signaling is essential for optimal humoral immune response and protection against an acute HSV-1 infection. Blocking the LTβR pathway caused poor maintenance of germinal center B (GC-B) cells and follicular helper T (Tfh) cells. Using bone marrow chimeric mice and adoptive transplantation, we determined that T cell-derived LT played an indispensable role in the humoral immune response to HSV-1. Up-regulation of IFNγ by the LTβR-Ig blockade impairs the sustainability of Tfh-like cells, thus leading to an impaired humoral immune response. Our findings have identified a novel role of T cell-derived LT in the humoral immune response against HSV-1 infection. IMPORTANCE Immunocompromised people are susceptible for HSV-1 infection and lethal recurrence, which could be inhibited by anti-HSV-1 humoral immune response in the host. This study sought to explore the role of T cell-derived LT in the anti-HSV-1 humoral immune response using LT-LTβR signaling deficient mice and the LTβR-Ig blockade. The data indicate that the T cell-derived LT may play an essential role in sustaining Tfh-like cells and ensure Tfh-like cells' migration into primary or secondary follicles for further maturation. This study provides insights for vaccine development against infectious diseases. Copyright © 2018 American Society for Microbiology.

Treatment of patients waitlisted for liver transplant with all-oral direct-acting antivirals is a cost-effective treatment strategy in the United States.

PubMed

Ahmed, Aijaz; Gonzalez, Stevan A; Cholankeril, George; Perumpail, Ryan B; McGinnis, Justin; Saab, Sammy; Beckerman, Rachel; Younossi, Zobair M

2017-07-01

All-oral direct acting antivirals (DAAs) have been shown to have high safety and efficacy in treating patients with hepatitis C virus (HCV) awaiting liver transplant (LT). However, there is limited empirical evidence comparing the health and economic outcomes associated with treating patients pre-LT versus post-LT. The objective of this study was to analyze the cost-effectiveness of pre-LT versus post-LT treatment with an all-oral DAA regimen among HCV patients with hepatocellular carcinoma (HCC) or decompensated cirrhosis (DCC). We constructed decision-analytic Markov models of the natural disease progression of HCV in HCC patients and DCC patients waitlisted for LT. The model followed hypothetical cohorts of 1,000 patients with a mean age of 50 over a 30-year time horizon from a third-party US payer perspective and estimated their health and cost outcomes based on pre-LT versus post-LT treatment with an all-oral DAA regimen. Transition probabilities and utilities were based on the literature and hepatologist consensus. Sustained virological response rates were sourced from ASTRAL-4, SOLAR-1, and SOLAR-2. Costs were sourced from RedBook, Medicare fee schedules, and published literature. In the HCC analysis, the pre-LT treatment strategy resulted in 11.48 per-patient quality-adjusted life years and $365,948 per patient lifetime costs versus 10.39 and $283,696, respectively, in the post-LT arm. In the DCC analysis, the pre-LT treatment strategy resulted in 9.27 per-patient quality-adjusted life years and $304,800 per patient lifetime costs versus 8.7 and $283,789, respectively, in the post-LT arm. As such, the pre-LT treatment strategy was found to be the most cost-effective in both populations with an incremental cost-effectiveness ratio of $74,255 (HCC) and $36,583 (DCC). Sensitivity and scenario analyses showed that results were most sensitive to the utility of patients post-LT, treatment sustained virological response rates, LT costs, and baseline Model for End-Stage Liver Disease score (DCC analysis only). The timing of initiation of antiviral treatment for HCV patients with HCC or DCC relative to LT is an important area of clinical and policy research; our results indicate that pre-LT treatment with a highly effective, all-oral DAA regimen provides the best health outcomes and is the most cost-effective strategy for the treatment of HCV patients with HCC or DCC waitlisted for LT. (Hepatology 2017;66:46-56). © 2017 by the American Association for the Study of Liver Diseases.

Diversity of soil fungi in North 24 Parganas and their antagonistic potential against Leucinodes orbonalis Guen. (Shoot and fruit borer of brinjal).

PubMed

Pal, Sujoy; Ghosh, Swapan Kumar

2014-12-01

Soil samples were collected from agricultural fields and gardens in North 24 Parganas, West Bengal, and fungi species were isolated from them. Thirty-one fungal species were isolated with 19 found in agricultural soil and 28 in garden soil. Twenty-eight out of 31 were identified using cultural and microscopic characters, and three were unidentified. The diversity of isolated fungi was calculated by Simpson's diversity index. The garden soil possessed more fungal colonies (750) than agricultural soil (477). In agricultural soil, the dominant fungi were Aspergillus niger, Rhizopus oryzae, and Penicillium expansum, and the dominant fungi of garden soil were A. niger and Fusarium moniliforme. Simpson's diversity index indicated that garden soil had more fungal diversity (0.939) than agricultural soil (0.896). The entomopathogenic capacity of the isolated fungi was tested against the brinjal shoot and fruit borer (Leucinodes orbonalis Guen) which is the major insect pest of brinjal. The isolated fungi were screened against larva of L. orbonalis for their entomopathogenic potential. Beauveria bassiana, A. niger, and P. expansum showed appreciable antagonism to L. orbonalis, and their lethal doses with 50 % mortality (LD50s) were 4.0 × 10(7), 9.06 × 10(7), and 1.50 × 10(8) spore/mL, respectively, and their times taken to reach 50 % mortality (LT50s) were 9.77, 10.56, and 10.60 days, respectively. This work suggests the restriction of chemical pesticide application in agricultural fields to increase fungal diversity. The entomopathogenic efficacy of B. bassiana could be used in agricultural fields to increase fugal diversity and protect the brinjal crop.

Development of an attract-and-infect system to control Rhynchophorus ferrugineus with the entomopathogenic fungus Beauveria bassiana.

PubMed

Dembilio, Óscar; Moya, Pilar; Vacas, Sandra; Ortega-García, Lola; Quesada-Moraga, Enrique; Jaques, Josep A; Navarro-Llopis, Vicente

2018-02-09

A new Beauveria bassiana-based attract and infect device (AID) to control Rhynchophorus ferrugineus Olivier (Coleoptera: Curculionidae) was developed. The virulence and persistence of the fungal formulation used in the AID were evaluated in the laboratory. Semi-field and field trials were carried out to validate the results and establish the potential of this device as a control tool. In laboratory conditions, a 50% lethal time (LT 50 ) of 4.33 days was obtained when adults (7-10 days old) were exposed to the inoculation tunnel (IT) containing 1 × 10 10 conidia g -1 in an oil-based fungal formulation. This formulation maintained conidium viability at 50% for up to 2 months. Moreover, when adults were exposed to 2.5-month field-aged ITs, mortality still reached 50% 40 days after exposure. In addition, no differences were observed between ITs aged in early spring and those aged in summer, suggesting that the fungal formulation is not strongly affected by environmental factors in Mediterranean basin conditions. Semi-field assays showed that the device allowed an easy transit of weevils through the IT, which were effectively attracted and infected. Using the AIDs in 4-ha plot field trials, a reduction of >50% in the percentage of infested sentinel palms was obtained. Based on the results obtained in terms of the efficacy and persistence of this new AID in the field and its potential in reducing R. ferrugineus populations and palm infestation, this device could become a key tool for the management of R. ferrugineus. © 2018 Society of Chemical Industry. © 2018 Society of Chemical Industry.

Weevil x Insecticide: Does 'Personality' Matter?

PubMed

Morales, Juliana A; Cardoso, Danúbia G; Della Lucia, Terezinha Maria C; Guedes, Raul Narciso C

2013-01-01

An insect's behavior is the expression of its integrated physiology in response to external and internal stimuli, turning insect behavior into a potential determinant of insecticide exposure. Behavioral traits may therefore influence insecticide efficacy against insects, compromising the validity of standard bioassays of insecticide activity, which are fundamentally based on lethality alone. By extension, insect 'personality' (i.e., an individual's integrated set of behavioral tendencies that is inferred from multiple empirical measures) may also be an important determinant of insecticide exposure and activity. This has yet to be considered because the behavioral studies involving insects and insecticides focus on populations rather than on individuals. Even among studies of animal 'personality', the relative contributions of individual and population variation are usually neglected. Here, we assessed behavioral traits (within the categories: activity, boldness/shyness, and exploration/avoidance) of individuals from 15 populations of the maize weevil (Sitophilus zeamais), an important stored-grain pest with serious problems of insecticide resistance, and correlated the behavioral responses with the activity of the insecticide deltamethrin. This analysis was performed at both the population and individual levels. There was significant variation in weevil 'personality' among individuals and populations, but variation among individuals within populations accounted for most of the observed variation (92.57%). This result emphasizes the importance of individual variation in behavioral and 'personality' studies. When the behavioral traits assessed were correlated with median lethal time (LT50) at the population level and with the survival time under insecticide exposure, activity traits, particularly the distance walked, significantly increased survival time. Therefore, behavioral traits are important components of insecticide efficacy, and individual variation should be considered in such studies. This is so because population differences provided only crude approximation of the individual personality in a restrained experimental setting likely to restrict individual behavior favoring the transposition of the individual variation to the population.

Reproductive biology of the crocodile shark Pseudocarcharias kamoharai.

PubMed

Oliveira, P; Hazin, F H V; Carvalho, F; Rego, M; Coelho, R; Piercy, A; Burgess, G

2010-05-01

From February 2005 to September 2007, a total of 490 crocodile sharks Pseudocarcharias kamoharai, caught as by-catch in the swordfish and tuna longline fishery that operates in the tropical western Atlantic Ocean, was studied in regard to their reproductive biology. Maximum observed total lengths (L(T)) were 1220 and 1090 mm for females and males respectively, with a high proportion of the catch being composed of mature specimens. Sexual maturity was attained at 760-810 mm L(T) for males (L(T50) = 800 mm) and 870-980 mm L(T) for females (L(T50) = 916 mm). The size at birth was estimated at 415 mm L(T). Temporal variation in gonad morphology and mass suggests that in this region P. kamoharai, an aplacental viviparous species with oophagy, does not show a well-defined reproductive seasonality, with mating and parturition occurring possibly over an extended period of the year. Mean +/-S.D. fecundity was estimated to be 3.9 (+/- 0.6) pups per reproductive cycle.

Changes in ABA and gene expression in cold-acclimated sugar maple.

PubMed

Bertrand, A; Robitaille, G; Castonguay, Y; Nadeau, P; Boutin, R

1997-01-01

To determine if cold acclimation of sugar maple (Acer saccharum Marsh.) is associated with specific changes in gene expression under natural hardening conditions, we compared bud and root translatable mRNAs of potted maple seedlings after cold acclimation under natural conditions and following spring dehardening. Cold-hardened roots and buds were sampled in January when tissues reached their maximum hardiness. Freezing tolerance, expressed as the lethal temperature for 50% of the tissues (LT(50)), was estimated at -17 degrees C for roots, and at lower than -36 degrees C for buds. Approximately ten transcripts were specifically synthesized in cold-acclimated buds, or were more abundant in cold-acclimated buds than in unhardened buds. Cold hardening was also associated with changes in translation. At least five translation products were more abundant in cold-acclimated buds and roots compared with unhardened tissues. Abscisic acid (ABA) concentration increased approximately tenfold in the xylem sap following winter acclimation, and the maximum concentration was reached just before maximal acclimation. We discuss the potential involvement of ABA in the observed modification of gene expression during cold hardening.

Biocontrol of ticks by entomopathogenic nematodes. Research update.

PubMed

Samish, M; Alekseev, E; Glazer, I

2000-01-01

Entomopathogenic nematodes (EPNs) are lethal to ticks even though they do not use their normal propagation cycle within tick cadavers. The tick Boophilus annulatus was found to be far more susceptible to EPNs than Hyalomma excavatum, Rhipicephalus bursa, or Rhipicephalus sanguineus. Ticks seem to be less susceptible to nematodes when feeding on a host. Preimaginal tick stages were less susceptible to nematodes than adult ticks. The mortality rate of unfed females was highest, followed by unfed males, and engorged females. The virulence of nematodes to ticks varied greatly among different nematode strains. In most cases, the Heterorhabditis sp. strains were the most virulent strains tested in petri dishes. In buckets containing sandy soil sprayed with 50 nematodes/cm2 and engorged B. annulatus females, the LT50 of the ticks was less than five days. The addition of manure to soil or a manure extract to petri dishes reduced nematode virulence. Since ticks spend most of their life cycle in the upper humid layer of the ground, and many nematode strains share this same ecological niche, the use of EPNs for biocontrol of ticks appears promising.

Passive Immunotherapy Protects against Enteric Invasion and Lethal Sepsis in a Murine Model of Gastrointestinal Anthrax

PubMed Central

Huang, Bruce; Xie, Tao; Rotstein, David; Fang, Hui; Frucht, David M.

2015-01-01

The principal portal for anthrax infection in natural animal outbreaks is the digestive tract. Enteric exposure to anthrax, which is difficult to detect or prevent in a timely manner, could be exploited as an act of terror through contamination of human or animal food. Our group has developed a novel animal model of gastrointestinal (GI) anthrax for evaluation of disease pathogenesis and experimental therapeutics, utilizing vegetative Bacillus anthracis (Sterne strain) administered to A/J mice (a complement-deficient strain) by oral gavage. We hypothesized that a humanized recombinant monoclonal antibody (mAb) * that neutralizes the protective antigen (PA) component of B. anthracis lethal toxin (LT) and edema toxin (ET) could be an effective treatment. Although the efficacy of this anti-anthrax PA mAb has been shown in animal models of inhalational anthrax, its activity in GI infection had not yet been ascertained. We hereby demonstrate that passive immunotherapy with anti-anthrax PA mAb, administered at the same time as gastrointestinal exposure to B. anthracis, prevents lethal sepsis in nearly all cases (>90%), while a delay of up to forty-eight hours in treatment still greatly reduces mortality following exposure (65%). Moreover, passive immunotherapy protects against enteric invasion, associated mucosal injury and subsequent dissemination by gastrointestinal B. anthracis, indicating that it acts to prevent the initial stages of infection. * Expired raxibacumab being cycled off the Strategic National Stockpile; biological activity confirmed by in vitro assay. PMID:26426050

Passive Immunotherapy Protects against Enteric Invasion and Lethal Sepsis in a Murine Model of Gastrointestinal Anthrax.

PubMed

Huang, Bruce; Xie, Tao; Rotstein, David; Fang, Hui; Frucht, David M

2015-09-29

The principal portal for anthrax infection in natural animal outbreaks is the digestive tract. Enteric exposure to anthrax, which is difficult to detect or prevent in a timely manner, could be exploited as an act of terror through contamination of human or animal food. Our group has developed a novel animal model of gastrointestinal (GI) anthrax for evaluation of disease pathogenesis and experimental therapeutics, utilizing vegetative Bacillus anthracis (Sterne strain) administered to A/J mice (a complement-deficient strain) by oral gavage. We hypothesized that a humanized recombinant monoclonal antibody (mAb) * that neutralizes the protective antigen (PA) component of B. anthracis lethal toxin (LT) and edema toxin (ET) could be an effective treatment. Although the efficacy of this anti-anthrax PA mAb has been shown in animal models of inhalational anthrax, its activity in GI infection had not yet been ascertained. We hereby demonstrate that passive immunotherapy with anti-anthrax PA mAb, administered at the same time as gastrointestinal exposure to B. anthracis, prevents lethal sepsis in nearly all cases (>90%), while a delay of up to forty-eight hours in treatment still greatly reduces mortality following exposure (65%). Moreover, passive immunotherapy protects against enteric invasion, associated mucosal injury and subsequent dissemination by gastrointestinal B. anthracis, indicating that it acts to prevent the initial stages of infection. * Expired raxibacumab being cycled off the Strategic National Stockpile; biological activity confirmed by in vitro assay.

Mapping the epitopes of a neutralizing antibody fragment directed against the lethal factor of Bacillus anthracis and cross-reacting with the homologous edema factor.

PubMed

Thullier, Philippe; Avril, Arnaud; Mathieu, Jacques; Behrens, Christian K; Pellequer, Jean-Luc; Pelat, Thibaut

2013-01-01

The lethal toxin (LT) of Bacillus anthracis, composed of the protective antigen (PA) and the lethal factor (LF), plays an essential role in anthrax pathogenesis. PA also interacts with the edema factor (EF, 20% identity with LF) to form the edema toxin (ET), which has a lesser role in anthrax pathogenesis. The first recombinant antibody fragment directed against LF was scFv 2LF; it neutralizes LT by blocking the interaction between PA and LF. Here, we report that scFv 2LF cross-reacts with EF and cross-neutralizes ET, and we present an in silico method taking advantage of this cross-reactivity to map the epitope of scFv 2LF on both LF and EF. This method identified five epitope candidates on LF, constituted of a total of 32 residues, which were tested experimentally by mutating the residues to alanine. This combined approach precisely identified the epitope of scFv 2LF on LF as five residues (H229, R230, Q234, L235 and Y236), of which three were missed by the consensus epitope candidate identified by pre-existing in silico methods. The homolog of this epitope on EF (H253, R254, E258, L259 and Y260) was experimentally confirmed to constitute the epitope of scFv 2LF on EF. Other inhibitors, including synthetic molecules, could be used to target these epitopes for therapeutic purposes. The in silico method presented here may be of more general interest.

The overwintering biology of the acorn weevil, Curculio glandium in southwestern Ontario.

PubMed

Udaka, Hiroko; Sinclair, Brent J

2014-08-01

The acorn weevil, Curculio glandium, is a widespread predator of acorns in eastern North America that overwinters in the soil as a larva. It is possible that low temperatures limit its northern geographic range, so we determined the cold tolerance strategy, seasonal variation in cold tolerance, and explored the physiological plasticity of overwintering larvae. Weevil larvae were collected from acorns of red and bur oak from Pelee Island, southwestern Ontario in fall 2010 and 2011. C. glandium larvae are freeze avoidant and larvae collected from bur oak acorns had lower supercooling points (SCPs: -7.6±0.36°C, LT50: -7.2°C) than those collected from red oak acorns (SCPs: -6.1±0.40°C, LT50: -6.1°C). In the winter of 2010-2011, SCPs and water content decreased, however these changes did not occur in 2011-2012, when winter soil temperatures fluctuated greatly in the absence of the buffering effect of snow. To examine whether larvae utilize cryoprotective dehydration, larvae from red oak acorns were exposed to -5°C in the presence of ice for seven days. These conditions decreased the SCP without affecting water content, suggesting that SCP and water content are not directly coupled. Finally, long-term acclimation at 0°C for six weeks slightly increased cold tolerance but also did not affect water content. Thus, although larval diet affects cold tolerance, there is limited plasticity after other treatments. The soil temperatures we observed were not close to lethal limits, although we speculate that soil temperatures in northerly habitats, or in years of reduced snow cover, has the potential to cause mortality in the field. Copyright © 2014 Elsevier Ltd. All rights reserved.

The Romanian National Program for Liver Transplantation - 852 Procedures in 815 Patients over 17 Years (2000-2017): A Continuous Evolution to Success.

PubMed

Popescu, Irinel; Ionescu, Mihnea; Braşoveanu, Vladislav; Hrehoreţ, Doina; Copca, Narcis; Lupaşcu, Cristian; Botea, Florin; Dorobanţu, Bogdan; Alexandrescu, Sorin; Grigorie, Mihai; Matei, Emil; Zamfir, Radu; Lungu, Vasile; Tomescu, Dana; Droc, Gabriela; Ungureanu, Daniela; Fota, Ruxandra; Manga, Graţiela; Popescu, Mihai; Popa, Laura; Gheorghe, Liana; Iacob, Speranţa; Pietrăreanu, Corina; Mihailă, Mariana; Mic, Laurenţiu; Constantinescu, Sanda; Gheorghe, Cristian; Cotruta, Bogdan; Lupescu, Ioana; Grasu, Mugur; Boroş, Mirela; Dumitru, Radu; Toma, Mihai; Paslaru, Liliana; Vlad, Laura; Constantinescu, Ileana; Dima, Ileana; Herlea, Vlad; Becheanu, Gabriel; Pecheanu, Cătălin; Sasalovici, Daniela

2017-01-01

Background: Liver transplantation (LT) has become an established treatment for end-stage liver disease, with more than 20.000 procedures yearly worldwide. The aim of this study was to analyze the results of Romanian National Program of LT. Methods: Between April 2000 and April 2017, 817 pts received 852 LTs in Romania. Male/female ratio was 487/330, while adult/pediatric ratio was 753/64, with a mean age of 46 years (median 50 yrs; range 7 months - 68 yrs). Main LT indications were HBV cirrhosis (230 pts; 28.2%), HCC (173 pts; 21.2%), and HCV cirrhosis (137 pts; 16.8%). Waiting time and indications for LT, patient and donor demographics, graft features, surgical procedures, and short and long-term outcomes were analyzed. Results: DDLT was performed in 682 pts (83.9%): whole LT in 662 pts (81%), split LT in 16 pts (2.3%), reduced LT in 2 pts (0.2%), and domino LT in 1 pts (0.1%). LDLT was performed in 135 pts (16.5%): right hemiliver in 93 pts (11.4%), left lateral section in 28 pts (3.4%), left hemiliver in 8 pts (1%), left hemiliver with segment 1 in 4 pts (0.5%), and dual graft LDLT in 2 pts (0.2%). Overall major morbidity rate was 31.4% (268 pts), while perioperative mortality was 7.9% (65 pts). Retransplantation rate was 4.3% (35 pts): 27 whole LTs, 3 reduced LTs, 3 split LTs, and 2 LDLT. Long-term overall 1-, 3-, and 5-year estimated survival rates for patients were 87.9%, 81.5%, and 79.1%, respectively. One-, 3-, and 5-year overall mortality on waiting list also decreased significantly over time from 31.4%, 54.1% and 63.5%, to 4.4%, 13.9% and 23.6%, respectively. Conclusions: The Romanian National program for liver transplantation addresses all causes of acute and chronic liver failure or liver tumors in adults and children, using all surgical techniques, with good long-term outcome. The program constantly evolved over time, leading to decreased mortality rate on the waiting list. Celsius.

A proteome analysis of freezing tolerance in red clover (Trifolium pratense L.).

PubMed

Bertrand, Annick; Bipfubusa, Marie; Castonguay, Yves; Rocher, Solen; Szopinska-Morawska, Aleksandra; Papadopoulos, Yousef; Renaut, Jenny

2016-03-10

Improvement of freezing tolerance of red clover (Trifolium pratense L.) would increase its persistence under cold climate. In this study, we assessed the freezing tolerance and compared the proteome composition of non-acclimated and cold-acclimated plants of two initial cultivars of red clover: Endure (E-TF0) and Christie (C-TF0) and of populations issued from these cultivars after three (TF3) and four (TF4) cycles of phenotypic recurrent selection for superior freezing tolerance. Through this approach, we wanted to identify proteins that are associated with the improvement of freezing tolerance in red clover. Freezing tolerance expressed as the lethal temperature for 50 % of the plants (LT50) increased markedly from approximately -2 to -16 °C following cold acclimation. Recurrent selection allowed a significant 2 to 3 °C increase of the LT50 after four cycles of recurrent selection. Two-dimensional difference gel electrophoresis (2D-DIGE) was used to study variations in protein abundance. Principal component analysis based on 2D-DIGE revealed that the largest variability in the protein data set was attributable to the cold acclimation treatment and that the two genetic backgrounds had differential protein composition in the acclimated state only. Vegetative storage proteins (VSP), which are essential nitrogen reserves for plant regrowth, and dehydrins were among the most striking changes in proteome composition of cold acclimated crowns of red clovers. A subset of proteins varied in abundance in response to selection including a dehydrin that increased in abundance in TF3 and TF4 populations as compared to TF0 in the Endure background. Recurrent selection performed indoor is an effective approach to improve the freezing tolerance of red clover. Significant improvement of freezing tolerance by recurrent selection was associated with differential accumulation of a small number of cold-regulated proteins that may play an important role in the determination of the level of freezing tolerance.

Inhalation toxicology. XII., Comparison of toxicity rankings of six polymers by lethality and by incapacitation in rats.

DOT National Transportation Integrated Search

1991-12-01

Polymeric aircraft cabin materials have the potential to produce toxic gases in fires. Lethality (LC50) in animal models is a standard index to rank polymers on the basis of their combustion product toxicity. However, the use of times-toincapacitatio...

Liver stiffness identifies two different patterns of fibrosis progression in patients with hepatitis C virus recurrence after liver transplantation.

PubMed

Carrión, José A; Torres, Ferran; Crespo, Gonzalo; Miquel, Rosa; García-Valdecasas, Juan-Carlos; Navasa, Miquel; Forns, Xavier

2010-01-01

Significant liver fibrosis (F >or= 2) and portal hypertension (hepatic venous pressure gradient [HVPG] >or= 6 mmHg) at 1 year after liver transplantation (LT) identify patients with severe hepatitis C recurrence. We evaluated whether repeated liver stiffness measurements (LSM) following LT can discriminate between slow and rapid "fibrosers" (fibrosis stage F2-F4 at 1 year after LT). Eighty-four patients who had undergone LT and who were infected with hepatitis C virus (HCV) and 19 LT controls who were not infected with HCV underwent LSM at 3, 6, 9, and 12 months after LT. All HCV-infected patients underwent liver biopsy 12 months after LT (paired HVPG measurements in 74); 31 (37%) were rapid fibrosers. Median LSM (in kilopascal) at months 6, 9, and 12 were significantly higher in rapid fibrosers (9.9, 9.5, 12.1) than in slow fibrosers (6.9, 7.5, 6.6) (P < 0.01 all time points). The slope of liver stiffness progression (kPa x month) in rapid fibrosers (0.42) was significantly greater than in slow fibrosers (0.05) (P < 0.001), suggesting two different speeds of liver fibrosis progression. Figures were almost identical for patients with HVPG >or= 6 mmHg or HVPG < 6 mmHg at 1 year after LT. Multivariate analysis identified donor age, bilirubin level, and LSM as independent predictors of fibrosis progression and portal hypertension in the estimation group (n = 50) and were validated in a second group of 34 patients. The areas under the receiver operating characteristic curve that could identify rapid fibrosers and patients with portal hypertension as early as 6 months after LT were 0.83 and 0.87, respectively, in the estimation group and 0.75 and 0.80, respectively, in the validation group. Early and repeated LSM following hepatitis C recurrence in combination with clinical variables discriminates between rapid and slow fibrosers after LT.

Extracts of the unripe fruit of Ilex paraguariensis as a potential chemical control against the golden apple snail Pomacea canaliculata (Gastropoda, Ampullariidae).

PubMed

Brito, Fabiano Carvalho de; Gosmann, Grace; Oliveira, Guendalina Turcato

2018-02-22

Plant extracts can provide a viable alternative to controlling many crop pests. This study sought to assess the efficacy of vegetable extracts of the unripe fruits of Ilex paraguariensis (yerba maté) for chemical control of the channeled apple snail (Pomacea canaliculata) and of non-target species as the South American catfish (Rhamdia quelen) under laboratory conditions. In P. canaliculata, the LC 50 of the decoction extract was 31.39 mg.L -1 and the LT 50 was over 26 h. The LC 50 of the butanol extract was 24.75 mg.L -1 and the LT 50 was in the range of 28 to 32 h. In juvenile R. quelen, the LC 50 of the decoction was 17.98 mg.L -1 and the LT 50 was in the range of 10-12 h. These extracts are particularly attractive considering the source of compounds and their effectiveness as molluscicides.

Acute Oral Toxicity of Tetrodotoxin in Mice: Determination of Lethal Dose 50 (LD50) and No Observed Adverse Effect Level (NOAEL).

PubMed

Abal, Paula; Louzao, M Carmen; Antelo, Alvaro; Alvarez, Mercedes; Cagide, Eva; Vilariño, Natalia; Vieytes, Mercedes R; Botana, Luis M

2017-02-24

Tetrodotoxin (TTX) is starting to appear in molluscs from the European waters and is a hazard to seafood consumers. This toxin blocks sodium channels resulting in neuromuscular paralysis and even death. As a part of the risk assessment process leading to a safe seafood level for TTX, oral toxicity data are required. In this study, a 4-level Up and Down Procedure was designed in order to determine for the first time the oral lethal dose 50 (LD 50 ) and the No Observed Adverse Effect Level (NOAEL) in mice by using an accurate well-characterized TTX standard.

Edible vaccine protects mice against Escherichia coli heat-labile enterotoxin (LT): potatoes expressing a synthetic LT-B gene.

PubMed

Mason, H S; Haq, T A; Clements, J D; Arntzen, C J

1998-08-01

The authors have designed and constructed a plant-optimize synthetic gene encoding the Escherichia coli heat-labile enterotoxin B subunit (LT-B), for use in transgenic plants as an edible vaccine against enterotoxigenic E. coli. Expression of the synthetic LT-B gene in potato plants under the control of a constitutive promoter yielded increased accumulation of LT-B in leaves and tubers, as compared to the bacterial LT-B gene. The plant-derived LT-B assembled into native pentameric structures as evidenced by its ability to bind ganglioside. The authors demonstrated immunogenicity by feeding mice the raw tubers and comparing the anti-LT-B serum IgG and faecal IgA to that produced in mice gavaged with bacterial LT-B. Mice were fed three weekly doses of 5 g tuber tissue containing either 20 or 50 micrograms LT-B, or gavaged weekly with 5 micrograms of LT-B from recombinant E. coli. One week after the third dose, mice immunized with potato LT-B had higher levels of serum and mucosal anti-LT-B than those gavaged with bacterial LT-B. Mice were challenged by oral administration of 25 micrograms LT, and protection assessed by comparing the gut/carcass mass ratios. Although none of the mice were completely protected, the higher dose potato vaccine compared favourably with the bacterial vaccine. These findings show that an edible vaccine against E. coli LT-B is feasible.

Acute, sublethal, and combination effects of azadirachtin and Bacillus thuringiensis on the cotton bollworm, Helicoverpa armigera

PubMed Central

Abedi, Zahra; Saber, Moosa; Vojoudi, Samad; Mahdavi, Vahid; Parsaeyan, Ehsan

2014-01-01

Abstract The cotton bollworm, Helicoverpa armigera Hübner (Lepidoptera: Noctuidae) is a polyphagous and cosmopolitan insect pest that causes damage to various plants. In this study, the lethal and sublethal effects of azadirachtin and Bacillus thuringiensis Berliner sub sp . kurstaki (Bacillales: Bacillaceae) were evaluated on third instar H. armigera under laboratory conditions. The LC50 values of azadirachtin and Bt were 12.95 and 96.8 µg a.i./mL, respectively. A total mortality of 56.7% was caused on third instar larvae when LC20 values of the insecticides were applied in combination with each other. The LT50 values of azadirachtin and Bt were 4.8 and 3.6 days, respectively. The results of the sublethal study showed that the application of LC30 value of azadirachtin and Bt reduced the larval and pupal weight and increased larval and pupal duration of H. armigera . The longevity and fecundity of female adults were affected significantly by the insecticides. Female fecundity was reduced by the treatments, respectively. The lowest adult emergence ratio and pupation ratio were observed in the azadirachtin treatment. The results indicated that both insecticides have high potential for controlling of the pest. PMID:25373177

[Clonal variability in longevity of the cercariae of Himasthla elongata (Trematoda: Echinostomatidae)].

PubMed

Levakin, I A; Losev, E A; Zavirskiĭ, Ia V; Galaktionov, K V

2013-01-01

The study was carried out on Himasthla elongata cercariae shed by infected Littorina littorea snails. The infected periwinkles were collected from the settlement with the low prevalence of H. elongata. As shown earlier with the use of AFLP (Amplified Fragment Length Polymorphisms) method, rediae groups in all the infected periwinkles of this settlement arise from the infection of a mollusc with a single miracidium. Therefore, the cercariae shed by an infected mollusc have the same genotype or, in other words, represent a clone. The LT50 (the time during which 50% of cercariae perish in the experimental dish) were measured experimentally for cercariae Himasthla elongata belong to different clones. The investigated parameter demonstrated a high level of interclonal variability. Two groups of cercarial clones were identified: one of them was characterized by the high level of intraclonal variability in LT50 and the second, by the low one. It is assumed that the observed heterogeneity may be stipulated by different degrees of mitotic recombinations during formation of different cercarial clones.

Effects of temperature on development, mortality, mating and blood feeding behavior of Culiseta incidens (Diptera: Culicidae).

PubMed

Su, T; Mulla, M S

2001-06-01

Culiseta incidens Thomson is distributed over most of the western USA and Canada northward to Alaska. Because this mosquito is difficult to colonize, its biology has not been well investigated. We colonized this species in 1998 and studied the effects of temperature on various aspects of its life cycle. The time required for egg melanization and the duration of the egg stage were negatively correlated with temperature. The proportion of fertile egg rafts was temperature-independent. An inverse relationship existed between temperature and egg hatch. Molting and stadium duration after hatching were temperature-dependent, with higher temperature accelerating development and molting. Larvae and pupae experienced lower mortality and higher molting success at lower temperatures. Survivorship of adult mosquitoes fed on sugar solution was inversely proportional to temperature, lethal times for 50% mortality (LT50) were greater at the lower temperature than at the higher temperature. Females survived longer than did males at all test temperatures. Because this species is eurygamous, mating only occurred in large cages. Mating success was also affected by temperature. At the test temperatures, 20 degrees C, 25 degrees C and 30 degrees C, mating started from 3-5 days after emergence and reached a peak on days 13-15 after emergence. Maximum mating rates at 20 degrees C and 25 degrees C were higher than at 30 degrees C. Blood feeding, as indicated by cumulative feeding rates, was affected by cage size, mosquito age and temperature. Mosquitoes in large cages exhibited a much higher feeding rate than in small cages. With age, the cumulative blood feeding rate increased, with the highest rate at 25 degrees C, followed by 20 degrees C and 30 degrees C. At all temperatures tested, most of the blood fed females were mated.

New Approach of Beauveria bassiana to Control the Red Palm Weevil (Coleoptera: Curculionidae) by Trapping Technique.

PubMed

Hajjar, M J; Ajlan, A M; Al-Ahmad, M H

2015-04-01

This work is the first study to investigate the efficacy of the commercial formulation of Beauveria bassiana (Broadband) to control adults of red palm weevil (Rhynchophorus ferrugineus (Olivier)). This fungus could be applied as one of the biological tactics in controlling red palm weevil. Bioassay experiments for medium lethal concentrate and medium time to cause death of 50% of red palm weevil adults were carried out. The result showed that the LC50 of B. bassiana (Broadband) was 2.19×10(7) and 2.76×10(6) spores/ml at 9 and 23 d of treatment, respectively. The LT50 was 13.95 and 4.15 d for concentration of 1×10(7) and 1×10(8) spores/ml, respectively, whereas 1×10(9) spores/ml caused 100% mortality after 24 h. Additionally, a red palm weevil pheromone trap was designed to attract the adults to be contaminated with spores of Broadband, which was applied to the sackcloth fabric that coated the internal surfaces of the bucket trap. The mating behavior was studied to determine direct and indirect infection of the spores from male to female and vice versa. The results showed a high efficacy of Broadband suspension at 1×10(9) spores/ml; 40 ml of suspension at this concentration treated to cloth in a trap caused death of contaminated adults with B. bassiana spores directly and indirectly. The 100% mortality was obtained even after 13 d of traps treatment with 40 ml of the suspension at 1×10(9) spores/ml. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Vectorial capacity of Aedes aegypti for dengue virus type 2 is reduced with co-infection of Metarhizium anisopliae.

PubMed

Garza-Hernández, Javier A; Rodríguez-Pérez, Mario A; Salazar, Ma Isabel; Russell, Tanya L; Adeleke, Monsuru A; de Luna-Santillana, Erik de J; Reyes-Villanueva, Filiberto

2013-01-01

Aedes aegypti, is the major dengue vector and a worldwide public health threat combated basically by chemical insecticides. In this study, the vectorial competence of Ae. aegypti co-infected with a mildly virulent Metarhizium anisopliae and fed with blood infected with the DENV-2 virus, was examined. The study encompassed three bioassays (B). In B1 the median lethal time (LT50) of Ae. aegypti exposed to M. anisopliae was determined in four treatments: co-infected (CI), single-fungus infection (SF), single-virus infection (SV) and control (C). In B2, the mortality and viral infection rate in midgut and in head were registered in fifty females of CI and in SV. In B3, the same treatments as in B1 but with females separated individually were tested to evaluate the effect on fecundity and gonotrophic cycle length. Survival in CI and SF females was 70% shorter than the one of those in SV and control. Overall viral infection rate in CI and SV were 76 and 84% but the mortality at day six post-infection was 78% (54% infected) and 6% respectively. Survivors with virus in head at day seven post-infection were 12 and 64% in both CI and SV mosquitoes. Fecundity and gonotrophic cycle length were reduced in 52 and 40% in CI compared to the ones in control. Fungus-induced mortality for the CI group was 78%. Of the survivors, 12% (6/50) could potentially transmit DENV-2, as opposed to 64% (32/50) of the SV group, meaning a 5-fold reduction in the number of infective mosquitoes. This is the first report on a fungus that reduces the vectorial capacity of Ae. aegypti infected with the DENV-2 virus.

Acute Oral Toxicity of Tetrodotoxin in Mice: Determination of Lethal Dose 50 (LD50) and No Observed Adverse Effect Level (NOAEL)

PubMed Central

Abal, Paula; Louzao, M. Carmen; Antelo, Alvaro; Alvarez, Mercedes; Cagide, Eva; Vilariño, Natalia; Vieytes, Mercedes R.; Botana, Luis M.

2017-01-01

Tetrodotoxin (TTX) is starting to appear in molluscs from the European waters and is a hazard to seafood consumers. This toxin blocks sodium channels resulting in neuromuscular paralysis and even death. As a part of the risk assessment process leading to a safe seafood level for TTX, oral toxicity data are required. In this study, a 4-level Up and Down Procedure was designed in order to determine for the first time the oral lethal dose 50 (LD50) and the No Observed Adverse Effect Level (NOAEL) in mice by using an accurate well-characterized TTX standard. PMID:28245573

Braving the attitude of altitude: Caragana jubata at work in cold desert of Himalaya

PubMed Central

Bhardwaj, Pardeep Kumar; Kapoor, Ritu; Mala, Deep; Bhagwat, Geetika; Acharya, Vishal; Singh, Anil Kumar; Vats, Surender Kumar; Ahuja, Paramvir Singh; Kumar, Sanjay

2013-01-01

The present work was conducted to understand the basis of adaptation in Caragana jubata in its niche environment at high altitude cold desert of Himalaya. Molecular data showed predominance of genes encoding chaperones and those involved in growth and development at low temperature (LT), a major cue operative at high altitude. Importantly, these genes expressed in C. jubata in its natural habitat. Their homologues in Arabidopsis thaliana, Oryza sativa, and Glycine max did not exhibit similar trend of gene expression at LT. Constitutive expression and a quick up-regulation of the above genes suggested the ability of C. jubata to adjust its cellular machinery to maintain growth and development in its niche. This was reflected in LT50 (the temperature at which 50% injury occurred) and LT mediated photosynthetic acclimatory response. Such molecular and physiological plasticity enables C. jubata to thrive in the high altitude cold desert of Himalayas. PMID:23289064

Reproductive parameters of the Pacific angel shark Squatina californica (Selachii: Squatinidae).

PubMed

Romero-Caicedo, A F; Galván-Magaña, F; Hernández-Herrera, A; Carrera-Fernández, M

2016-04-01

Reproductive characteristics of the Pacific angel shark, Squatina californica, were evaluated from 420 specimens obtained from the artisanal fishery in La Paz Bay, Gulf of California, Mexico. Females (99 cm, 6000 g) were larger than males (95 cm, 5000 g) in terms of both total length (L(T)) and body mass (M(T)). The overall sex ratio was significantly different from the expected 1:1, suggesting sexual segregation of mature individuals in La Paz Bay. Males had developed reproductive organs and calcified claspers from 72 cm L(T); the median size at maturity (LT50 ) was 75.6 cm. In females, only the left ovary was functional and mature ovarian follicles were present from 77 cm L(T); the estimated LT50 was 77.7 cm. For the 10 gravid females sampled, uterine fecundity was between two and 10 embryos. Mature, non-gravid females with small and large ovarian follicles appeared simultaneously with gravid females with follicles that did not exceed 1.9 cm diameter. © 2016 The Fisheries Society of the British Isles.

Pharmacokinetics of total thyroxine in dogs after administration of an oral solution of levothyroxine sodium.

PubMed

Le Traon, G; Burgaud, S; Horspool, L J I

2008-04-01

Oral L-thyroxine (L-T4) supplementation is used to replace thyroid hormone concentrations in dogs with hypothyroidism. The pharmacokinetics of L-T4 following administration of a solution (Leventa) was investigated in healthy dogs. L-T4 was absorbed fairly rapidly (t(max) 3 h). A mean bioavailability of 22% was calculated following a single oral administration of 40 microg L-T4/kg body weight. Repeated oral administration at the same dose for 14 consecutive days did not lead to any accumulation of T4 in serum. After intravenous administration of L-T4, a serum half-life of 11.6 h was calculated. Food intake concomitant with L-T4 oral administration delayed L-T4 absorption and decreased its rate and extent by about 45%. The relative bioavailability of L-T4 following administration of a tablet formulation was about 50% of that of the L-T4 solution. The pharmacokinetic properties of liquid L-T4 after oral administration support the use of a dose rate of 20 microg/kg once daily, as a starting dose for replacement therapy in dogs with hypothyroidism.

Pediculicidal effect of herbal shampoo against Pediculus humanus capitis in vitro.

PubMed

Watcharawit, R; Soonwera, M

2013-06-01

Human head lice infestation is an important public health problem in Thailand. Lice resistance is increasing, chemical pediculicides have lost their efficacy and thus alternative products such as herbal shampoos have been proposed to treat lice infestation. The present study investigated the efficacy of twenty nine herbal shampoos based on zinbiberaceae plants, piperaceae plants and native plants against human head lice and compared them with malathion shampoo (A-lices shampoo®: 1% w/v malathion) and commercial shampoo (BabiMild Natural'N Mild®) in order to assess their in vitro efficacy. All herbal shampoo were more effective than commercial shampoo with 100% mortality at 60 seconds and LT50 values ranged from 11.30 to 31.97 seconds, meanwhile, commercial shampoo caused 14.0-15.0% mortality and LT50 values ranged from 83.96 to 87.43 seconds. The nine herbal shampoos from Zingiber cassumunar, Piper betle, Piper ribesioides, Averrhoa bilimbi, Clitoria ternatea, Plectranthus amboincus, Myristica fragrans, Tacca chantrieri and Zanthoxylum limonella were more effective pediculicide than malathion shampoo with 100% mortality at 30 seconds and LT50 values ranged from 11.30-13.58 seconds, on the other hand malathion shampoo showed LT50 values ranging from 12.39 to 13.67 seconds. LT50 values indicated the order of pediculicidal activity in the herbal shampoos as Z. cassumunar shampoo > P. betle shampoo > Za. limonella shampoo > Av. bilimbi shampoo > P. ribesioides shampoo > My. fragrans shampoo > T. chantrieri shampoo > Pl. amboincus shampoo. Our data showed that eight of the twenty nine herbal shampoos in this study were of high potential pediculicide to human head lice treatments for Thai children.

The acute toxicity evaluation of a low-temperature hydraulic fluid.

PubMed

Kinkead, E R; Wolfe, R E; Bunger, S K; Leahy, H F

1992-03-01

A low-temperature version of MIL-H-83282 (LT 83282) is a candidate hydraulic fluid to be used as a replacement for the current low-temperature fluid used on Strategic Air Command aircraft. A single neat dose of 0.1 mL LT 83282 into New Zealand White (NZW) rabbit eyes resulted in slight conjunctival irritation for up to 24 hr after treatment in two of nine rabbits. Rinsing the eyes after treatment appeared beneficial. A single treatment of 0.5 mL neat LT 83282 to rabbit skin produced no irritation. A total of 40% of the guinea pigs receiving repeated dermal application of the fluid demonstrated a positive sensitization response. A single oral dose of 5 g LT 83282/kg body weight given to five male and five female Fischer 344 (F-344) rats and a single dermal application of 2 g LT 83282/kg body weight applied to five male and five female NZW rabbits resulted in no deaths. Inhalation exposures to aerosol concentrations of LT 83282 resulted in an LC50 of 2.13 and 1.50 mg/L for male and female F-344 rats, respectively. No clinical signs of acute delayed neurotoxicity were observed in hens twice dosed at limit levels (5 g/kg) and observed for 21 days.

Cold temperature tolerance of apple rootstock trunk and root tissues

USDA-ARS?s Scientific Manuscript database

G.11, G.30, G.41, P.2 and B.9 apple (Malus xdomestica) rootstocks have root tissue hardiness similar to M.26, but G.935 has greater hardiness than M.26 when based on shoot regrowth in ungrafted trees. The LT50 of M.26 and P.2 roots ranged from -12 to -14 degrees C. The LT50 of B.9 was -13 degrees ...

Australian tiger snake (Notechis scutatus) and mexican coral snake (Micruris species) antivenoms prevent death from United States coral snake (Micrurus fulvius fulvius) venom in a mouse model.

PubMed

Wisniewski, Michael S; Hill, Robert E; Havey, Joshua M; Bogdan, Gregory M; Dart, Richard C

2003-01-01

Wyeth-Ayerst has discontinued production of Antivenin (Micrurus fulvius). Currently, there is no other approved coral snake antivenom available in the United States. This study was a randomized, placebo-controlled and blinded determination of the ability of a Mexican Micrurus (coral snake) antivenom and an Australian Notechis (tiger snake) antivenom to prevent lethality from a United States Micrurus fulvius fulvius venom in a mouse model. Venom dosing was based on an LD50 determined for this experiment. Our comparison groups included: (1) M. f. fulvius venom + Micrurus antivenom, (2) M. f. fulvius venom + Notechis antivenom, (3) M. f. fulvius venom + protein control, (4) 0.9% normal saline + protein control, (5) saline + Notechis antivenom, (6) saline + Micrurus antivenom. Venom dose was 5 times the determined LD50. The antivenom amounts were capable of neutralizing 10 times the venom injected (50 times the LD50). The LD50 of M. f. fulvius venom was determined to be 0.85 mg/kg. All mice in both antivenom test groups were protected from lethality for the entire 24-hour observation period. Six of the 7 mice in the venom test group died, with a survival time of 349 +/- 382 minutes (mean +/- s.d.) after the venom injection. All three groups of control mice survived the entire 24-hour observation period. Mexican Micrurus antivenom and Australian Notechis antivenom provide protection from lethality in mice envenomated with a United States M. f. filvius venom.

Larvicidal Activity of Citrus Limonoids against Aedes albopictus Larvae.

PubMed

Bilal, Hazrat; Akram, Waseem; Ali-Hassan, Soaib

2012-12-01

Development of insecticide resistance occurred due to the continuous and misuse of synthetic insecticides therefore, the recent study was conducted to explore eco-friendly plant extracts that have some potential to suppress mosquito larval population. WHO recommended mosquito larval bioassay method for insecticide was used while for the analysis of citrus oils for limonin and nomilin content HPLC was used. Among the two citrus cultivars tested as larvicide against Aedes albopictus, valencia late (Citrus sinensis) was the best in terms of LC(50) (297 ppm), % mortality (97%) and LT(50) (18.49 hours) then freutrall early (Citrus reticulate) with LC(50) (377.4 ppm), % mortality (88%) and LT(50) (31 hours), While nomilin gave lowest LC(50) (121.04 ppm) than limonin (382.22 ppm) after 72 hours of exposure. Valencia late also had more limonin and nomilin (377 μg/ml and 21.19 μg/ml) than freutrall early (5.29 μg/ml and 3.89 μg/ml) respectively. Valencia late showed best results in term of LC(50), LT(50) and percentage mortality against Aedes albopictus as it has more amount of nomilin then freutrall early, however further evaluation in the field conditions is required.

Larvicidal Activity of Citrus Limonoids against Aedes albopictus Larvae

PubMed Central

Bilal, Hazrat; Akram, Waseem; Ali-Hassan, Soaib

2012-01-01

Background: Development of insecticide resistance occurred due to the continuous and misuse of synthetic insecticides therefore, the recent study was conducted to explore eco-friendly plant extracts that have some potential to suppress mosquito larval population. Methods: WHO recommended mosquito larval bioassay method for insecticide was used while for the analysis of citrus oils for limonin and nomilin content HPLC was used. Results: Among the two citrus cultivars tested as larvicide against Aedes albopictus, valencia late (Citrus sinensis) was the best in terms of LC50 (297 ppm), % mortality (97%) and LT50 (18.49 hours) then freutrall early (Citrus reticulate) with LC50 (377.4 ppm), % mortality (88%) and LT50 (31 hours), While nomilin gave lowest LC50 (121.04 ppm) than limonin (382.22 ppm) after 72 hours of exposure. Valencia late also had more limonin and nomilin (377 μg/ml and 21.19 μg/ml) than freutrall early (5.29 μg/ml and 3.89 μg/ml) respectively. Conclusion: Valencia late showed best results in term of LC50, LT50 and percentage mortality against Aedes albopictus as it has more amount of nomilin then freutrall early, however further evaluation in the field conditions is required. PMID:23378967

Effects of Altering Levothyroxine (L-T4) Doses on Quality of Life, Mood, and Cognition in L-T4 Treated Subjects.

PubMed

Samuels, Mary H; Kolobova, Irina; Niederhausen, Meike; Janowsky, Jeri S; Schuff, Kathryn G

2018-05-01

The brain is a critical target organ for thyroid hormone, but it is unclear whether variations in thyroid function within and near the reference range affect quality of life, mood, or cognition. A total of 138 subjects with levothyroxine (L-T4)-treated hypothyroidism and normal thyrotropin (TSH) levels underwent measures of quality of life (36-Item Short Form Health Survey, Underactive Thyroid-Dependent Quality of Life Questionnaire), mood (Profile of Mood States, Affective Lability Scale), and cognition (executive function, memory). They were then randomly assigned to receive an unchanged, higher, or lower L-T4 dose in double-blind fashion, targeting one of three TSH ranges (0.34 to 2.50, 2.51 to 5.60, or 5.61 to 12.0 mU/L). Doses were adjusted every 6 weeks based on TSH levels. Baseline measures were reassessed at 6 months. At the end of the study, by intention to treat, mean L-T4 doses were 1.50 ± 0.07, 1.32 ± 0.07, and 0.78 ± 0.08 μg/kg (P < 0.001), and mean TSH levels were 1.85 ± 0.25, 3.93 ± 0.38, and 9.49 ± 0.80 mU/L (P < 0.001), respectively, in the three arms. There were minor differences in a few outcomes between the three arms, which were no longer significant after correction for multiple comparisons. Subjects could not ascertain how their L-T4 doses had been adjusted (P = 0.55) but preferred L-T4 doses they perceived to be higher (P < 0.001). Altering L-T4 doses in hypothyroid subjects to vary TSH levels in and near the reference range does not affect quality of life, mood, or cognition. L-T4-treated subjects prefer perceived higher L-T4 doses despite a lack of objective benefit. Adjusting L-T4 doses in hypothyroid patients based on symptoms in these areas may not result in significant clinical improvement.

The influence of exercise duration at VO2 max on the off-transient pulmonary oxygen uptake phase during high intensity running activity.

PubMed

Billat, V L; Hamard, L; Koralsztein, J P

2002-12-01

The purpose of this study was to examine the influence of time run at maximal oxygen uptake (VO2 max) on the off-transient pulmonary oxygen uptake phase after supra-lactate threshold runs. We hypothesised: 1) that among the velocities eliciting VO2 max there is a velocity threshold from which there is a slow component in the VO2-off transient, and 2) that at this velocity the longer the duration of this time at VO2 max (associated with an accumulated oxygen kinetics since VO2 can not overlap VO2 max), the longer is the off-transient phase of oxygen uptake kinetics. Nine long-distance runners performed five maximal tests on a synthetic track (400 m) while breathing through the COSMED K4b2 portable, telemetric metabolic analyser: i) an incremental test which determined VO2 max, the minimal velocity associated with VO2 max (vVO2 max) and the velocity at the lactate threshold (vLT), ii) and in a random order, four supra-lactate threshold runs performed until exhaustion at vLT + 25, 50, 75 and 100% of the difference between vLT and vVO2 max (vdelta25, vdelta50, vdelta75, vdelta100). At vdelta25, vdelta50 (= 91.0 +/- 0.9% vVO2 max) and vdelta75, an asymmetry was found between the VO2 on (double exponential) and off-transient (mono exponential) phases. Only at vdelta75 there was at positive relationship between the time run at VO2 max (%tlimtot) and the VO2 recovery time constant (Z = 1.8, P = 0.05). In conclusion, this study showed that among the velocities eliciting VO2 max, vdelta75 is the velocity at which the longer the duration of the time at VO2 max, the longer is the off-transient phase of oxygen uptake kinetics. It may be possible that at vdelta50 there is not an accumulated oxygen deficit during the plateau of VO2 at VO2 max and that the duration of the time at VO2 max during the exhaustive runs at vdelta100, could be too short to induce an accumulating oxygen deficit affecting the oxygen recovery.

Selectivity of recombinant human leukotriene D(4), leukotriene B(4), and lipoxin A(4) receptors with aspirin-triggered 15-epi-LXA(4) and regulation of vascular and inflammatory responses.

PubMed

Gronert, K; Martinsson-Niskanen, T; Ravasi, S; Chiang, N; Serhan, C N

2001-01-01

Aspirin-triggered lipoxin A(4) (ATL, 15-epi-LXA(4)) and leukotriene D(4) (LTD(4)) possess opposing vascular actions mediated via receptors distinct from the LXA(4) receptor (ALX) that is involved in leukocyte trafficking. Here, we identified these receptors by nucleotide sequencing and demonstrate that LTD(4) receptor (CysLT(1)) is induced in human vascular endothelia by interleukin-1beta. Recombinant CysLT(1) receptor gave stereospecific binding with both [(3)H]-LTD(4) and a novel labeled mimetic of ATL ([(3)H]-ATLa) that was displaced with LTD(4) and ATLa ( approximately IC(50) 0.2 to 0.9 nmol/L), but not with a bioinactive ATL isomer. The clinically used CysLT(1) receptor antagonist, Singulair, showed a lower rank order for competition with [(3)H]-ATLa (IC(50) approximately 8.3 nmol/L). In contrast, LTD(4) was an ineffective competitive ligand for recombinant ALX receptor with [(3)H]-ATLa, and ATLa did not compete for [(3)H]-LTB(4) binding with recombinant LTB(4) receptor. Endogenous murine CysLT(1) receptors also gave specific [(3)H]-ATLa binding that was displaced with essentially equal affinity by LTD(4) or ATLa. Systemic ATLa proved to be a potent inhibitor (>50%) of CysLT(1)-mediated vascular leakage in murine skin (200 microg/kg) in addition to its ability to block polymorphonuclear leukocyte recruitment to dorsal air pouch (4 microg/kg). These results indicate that ATL and LTD(4) bind and compete with equal affinity at CysLT(1), providing a molecular basis for aspirin-triggered LXs serving as a local damper of both vascular CysLT(1) signals as well as ALX receptor-regulated polymorphonuclear leukocyte traffic.

Pharmacokinetics of coadministration of levothyroxine sodium and alendronate sodium new effervescent formulation.

PubMed

Bone, H G; Walter, M A; Hurley, M E; Epstein, S

2017-05-01

No clinically important pharmacokinetic interference of alendronate occurred between a new effervescent formulation of alendronate and levothyroxine when coadministered. The combination does not materially affect levothyroxine absorption. Concurrent treatment of osteoporosis with alendronate (Aln) and hypothyroidism with levothyroxine (LT4) may be problematic because both drugs are to be taken separately after fasting overnight. The primary objective was to assess pharmacokinetic interactions between a new effervescent formulation of Aln (Aln-NEF) and LT4. A randomized, open-label, 3-way crossover study was conducted in 30 healthy adults (15 women). Subjects were dosed 3 times, separated by 35 days, after overnight fasts, with Aln-NEF alone (70 mg), LT4 alone (600 μg), or Aln-NEF and LT4 concurrently. Samples were analyzed for plasma Aln and serum LT4. Pharmacokinetic drug-drug interaction was assessed using 90% confidence intervals (CIs) for the test/reference ratio of the geometric means for area under the concentration-time curve from time zero to last measureable time point (AUC 0-t ) and maximum concentration (C max ). Results were compared to the default no-effect boundaries of 80 to 125% for the ratio Aln-NEF and LT4 concurrently/Aln-NEF alone and the ratio Aln-NEF and LT4 concurrently/LT4 alone. Geometric mean ratios (Aln-NEF with LT4/Aln-NEF alone) were 0.927 (90% CI 0.795-1.081) for AUC 0-8 and 0.912 (90% CI 0.773-1.077) for C max , demonstrating LT4 does not appreciably affect the pharmacokinetics of Aln. Geometric mean ratios (LT4 with Aln-NEF/LT4 alone) were 1.049 (90% CI 0.983-1.119) for AUC 0-48 and 1.075 (90% CI 1.006-1.148) for C max , demonstrating LT4 is bioequivalent between the 2 treatments. Coadministration of Aln-NEF and LT4 was well tolerated. There was no clinically important pharmacokinetic interference between the Aln-NEF formulation and LT4. Aln-NEF does not materially affect LT4 absorption.

Locomotor Training Restores Walking in a Nonambulatory Child With Chronic, Severe, Incomplete Cervical Spinal Cord Injury

PubMed Central

Behrman, Andrea L; Nair, Preeti M; Bowden, Mark G; Dauser, Robert C; Herget, Benjamin R; Martin, Jennifer B; Phadke, Chetan P; Reier, Paul J; Senesac, Claudia R; Thompson, Floyd J; Howland, Dena R

2008-01-01

Background and Purpose: Locomotor training (LT) enhances walking in adult experimental animals and humans with mild-to-moderate spinal cord injuries (SCIs). The animal literature suggests that the effects of LT may be greater on an immature nervous system than on a mature nervous system. The purpose of this study was to evaluate the effects of LT in a child with chronic, incomplete SCI. Subject: The subject was a nonambulatory 4½-year-old boy with an American Spinal Injury Association Impairment Scale (AIS) C Lower Extremity Motor Score (LEMS) of 4/50 who was deemed permanently wheelchair-dependent and was enrolled in an LT program 16 months after a severe cervical SCI. Methods: A pretest-posttest design was used in the study. Over 16 weeks, the child received 76 LT sessions using both treadmill and over-ground settings in which graded sensory cues were provided. The outcome measures were ASIA Impairment Scale score, gait speed, walking independence, and number of steps. Result: One month into LT, voluntary stepping began, and the child progressed from having no ability to use his legs to community ambulation with a rolling walker. By the end of LT, his walking independence score had increased from 0 to 13/20, despite no change in LEMS. The child's final self-selected gait speed was 0.29 m/s, with an average of 2,488 community-based steps per day and a maximum speed of 0.48 m/s. He then attended kindergarten using a walker full-time. Discussion and Conclusion: A simple, context-dependent stepping pattern sufficient for community ambulation was recovered in the absence of substantial voluntary isolated lower-extremity movement in a child with chronic, severe SCI. These novel data suggest that some children with severe, incomplete SCI may recover community ambulation after undergoing LT and that the LEMS cannot identify this subpopulation. PMID:18326054

Polyethylene Glycol Camouflaged Earthworm Hemoglobin.

PubMed

Jani, Vivek P; Jelvani, Alborz; Moges, Selamawit; Nacharaju, Parimala; Roche, Camille; Dantsker, David; Palmer, Andre; Friedman, Joel M; Cabrales, Pedro

2017-01-01

Nearly 21 million components of blood and whole blood and transfused annually in the United States, while on average only 13.6 million units of blood are donated. As the demand for Red Blood Cells (RBCs) continues to increase due to the aging population, this deficit will be more significant. Despite decades of research to develop hemoglobin (Hb) based oxygen (O2) carriers (HBOCs) as RBC substitutes, there are no products approved for clinical use. Lumbricus terrestris erythrocruorin (LtEc) is the large acellular O2 carrying protein complex found in the earthworm Lumbricus terrestris. LtEc is an extremely stable protein complex, resistant to autoxidation, and capable of transporting O2 to tissue when transfused into mammals. These characteristics render LtEc a promising candidate for the development of the next generation HBOCs. LtEc has a short half-life in circulation, limiting its application as a bridge over days, until blood became available. Conjugation with polyethylene glycol (PEG-LtEc) can extend LtEc circulation time. This study explores PEG-LtEc pharmacokinetics and pharmacodynamics. To study PEG-LtEc pharmacokinetics, hamsters instrumented with the dorsal window chamber were subjected to a 40% exchange transfusion with 10 g/dL PEG-LtEc or LtEc and followed for 48 hours. To study the vascular response of PEG-LtEc, hamsters instrumented with the dorsal window chamber received multiple infusions of 10 g/dL PEG-LtEc or LtEc solution to increase plasma LtEc concentration to 0.5, then 1.0, and 1.5 g/dL, while monitoring the animals' systemic and microcirculatory parameters. Results confirm that PEGylation of LtEc increases its circulation time, extending the half-life to 70 hours, 4 times longer than that of unPEGylated LtEc. However, PEGylation increased the rate of LtEc oxidation in vivo. Vascular analysis verified that PEG-LtEc showed the absence of microvascular vasoconstriction or systemic hypertension. The molecular size of PEG-LtEc did not change the colloid osmotic pressure or blood volume expansion capacity compared to LtEc, due to LtEc's already large molecular size. Taken together, these results further encourage the development of PEG-LtEc as an O2 carrying therapeutic.

Clinical Characteristics of Transplant-associated Encephalopathy in Children.

PubMed

Lee, Yun Jeong; Yum, Mi Sun; Kim, Eun Hee; Kim, Min Jee; Kim, Kyung Mo; Im, Ho Joon; Kim, Young Hwue; Park, Young Seo; Ko, Tae Sung

2017-03-01

We aimed to analyze characteristics of encephalopathy after both hematopoietic stem cell and solid organ pediatric transplantation. We retrospectively reviewed medical records of 662 pediatric transplant recipients (201 with liver transplantation [LT], 55 with heart transplantation [HT], and 67 with kidney transplantation [KT], 339 with allogeneic hematopoietic stem cell transplantation [HSCT]) who received their graft organs at Asan Medical Center between January 2000 and July 2014. Of the 662 patients, 50 (7.6%) experienced encephalopathy after transplantation. The incidence of encephalopathy was significantly different according to the type of organ transplant: LT, 16/201 (8.0%), HT, 13/55 (23.6%), KT, 5/67 (7.5%), and HSCT, 16/339 (4.7%) (P < 0.001). Drug-induced encephalopathy (n = 14) was the most common encephalopathy for all transplant types, but particularly after HSCT. Hypertensive encephalopathy was the most common after KT and HT, whereas metabolic encephalopathy was the most common after LT. The median time to encephalopathy onset also differed according to the transplant type: 5 days after KT (range 0-491 days), 10 days after HT (1-296 days), 49.5 days after HSCT (9-1,405 days), and 39 days after LT (1-1,092 days) (P = 0.018). The mortality rate among patients with encephalopathy was 42.0% (n = 21/50). Only 5 patients died of neurologic complications. Transplant-associated encephalopathy presented different characteristics according to the type of transplant. Specialized diagnostic approach for neurologic complications specific to the type of transplant may improve survival and quality of life in children after transplantation.

Clinical Characteristics of Transplant-associated Encephalopathy in Children

PubMed Central

2017-01-01

We aimed to analyze characteristics of encephalopathy after both hematopoietic stem cell and solid organ pediatric transplantation. We retrospectively reviewed medical records of 662 pediatric transplant recipients (201 with liver transplantation [LT], 55 with heart transplantation [HT], and 67 with kidney transplantation [KT], 339 with allogeneic hematopoietic stem cell transplantation [HSCT]) who received their graft organs at Asan Medical Center between January 2000 and July 2014. Of the 662 patients, 50 (7.6%) experienced encephalopathy after transplantation. The incidence of encephalopathy was significantly different according to the type of organ transplant: LT, 16/201 (8.0%), HT, 13/55 (23.6%), KT, 5/67 (7.5%), and HSCT, 16/339 (4.7%) (P < 0.001). Drug-induced encephalopathy (n = 14) was the most common encephalopathy for all transplant types, but particularly after HSCT. Hypertensive encephalopathy was the most common after KT and HT, whereas metabolic encephalopathy was the most common after LT. The median time to encephalopathy onset also differed according to the transplant type: 5 days after KT (range 0–491 days), 10 days after HT (1–296 days), 49.5 days after HSCT (9–1,405 days), and 39 days after LT (1–1,092 days) (P = 0.018). The mortality rate among patients with encephalopathy was 42.0% (n = 21/50). Only 5 patients died of neurologic complications. Transplant-associated encephalopathy presented different characteristics according to the type of transplant. Specialized diagnostic approach for neurologic complications specific to the type of transplant may improve survival and quality of life in children after transplantation. PMID:28145649

Non-Lethal Heat Shock of the Asian Green Mussel, Perna viridis, Promotes Hsp70 Synthesis, Induces Thermotolerance and Protects Against Vibrio Infection.

PubMed

Aleng, Nor Afiqah; Sung, Yeong Yik; MacRae, Thomas H; Abd Wahid, Mohd Effendy

2015-01-01

Mild heat stress promotes thermotolerance and protection against several different stresses in aquatic animals, consequences correlated with the accumulation of heat shock protein 70 (Hsp70). The purpose of this study was to determine if non-lethal heat shock (NLHS) of the Asian green mussel, Perna viridis, an aquatic species of commercial value, promoted the production of Hsp70 and enhanced its resistance to stresses. Initially, the LT50 and LHT for P. viridis were determined to be 42°C and 44°C, respectively, with no heat shock induced death of mussels at 40°C or less. Immunoprobing of western blots revealed augmentation of constitutive (PvHsp70-1) and inducible (PvHsp70-2) Hsp70 in tissue from adductor muscle, foot, gill and mantel of P. viridis exposed to 38°C for 30 min followed by 6 h recovery, NLHS conditions for this organism. Characterization by liquid chromatography-tandem mass spectrometry (LC-MS/MS) revealed that PvHsp70-1 and PvHsp70-2 respectively corresponded most closely to Hsp70 from P. viridis and Mytilus galloprovincialis. Priming of adult mussels with NLHS promoted thermotolerance and increased resistance to V. alginolyticus. The induction of Hsp70 in parallel with enhanced thermotolerance and improved protection against V. alginolyticus, suggests Hsp70 functions in P. viridis as a molecular chaperone and as a stimulator of the immune system.

The Royal Free Hospital 'hub-and-spoke network model' delivers effective care and increased access to liver transplantation.

PubMed

Tai, D; Dhar, A; Yusuf, A; Marshall, A; O'Beirne, J; Patch, D; Tsochatzis, E; Alexander, G; Portal, J; Thalheimer, U; Thorburn, D; Kallis, Y; Westbrook, R H

2018-01-01

'Hub-and-spoke' networks may be one solution to reduce the geographical inequality in access to liver transplantation (LT) and the growing demands on, and saturation of, LT centres. It is not clear if such networks improve equity of access, deliver comparable patient outcomes or effect patient satisfaction. Retrospective evaluation of outcomes and patient satisfaction within the Royal Free liver transplant 'hub-and-spoke' network. Patient outcomes in those assessed for LT between September 2011 and 2014 at spoke centres (n = 4) were compared retrospectively with those assessed at the LT hub centre. Patient satisfaction questionnaires were completed and changes in LT referral patterns were explored with data obtained directly from NHS Blood and Transplant (NHSBT). A total of 655 patients (180 spoke; 475 hub) were assessed for LT. Patients referred from spoke centres were more likely to have viral hepatitis as an underlying aetiology (72/180 vs 110/475; P < 0.001), or hepatocellular carcinoma (48/180 vs 60/475; P < 0.001) as an indication for LT and were more likely to be listed for LT when compared with hub patients (139/180 vs 312/475, P = 0.005). Mortality on the waiting list (9/123 vs 25/269, P = 0.57), waiting time to LT (64-days vs 78-days, P = 0.91) and Model for End-Stage liver disease (MELD)/United Kingdom End-Stage Liver Disease (UKELD) score (P = 0.24/0.26) in listed patients were equivalent as were 1- and 3-year patient and graft survival rates. Patient satisfaction rates were high at both types of centre, with significantly more patients preferring 'locally delivered care' at spoke vs hub (11/50 vs 70/73, P≤0.0001). Since the development of formal hub-and-spoke networks data from NHSBT based on postcode confirmed a significant increase in patients undergoing LT (153%) from spoke centres, whereas numbers assessed and transplanted from the hub centre have remained static. Hub-and-spoke LT networks are effective in offering equivalent clinical outcomes, high patient satisfaction and alleviate clinical pressure on the hub centre. They have to potential to help eliminate the geographical disparity in mortality rates from chronic liver disease. Copyright © 2017 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

Portal Hypertension Complications Are Frequently the First Presentation of NAFLD in Patients Undergoing Liver Transplantation Evaluation.

PubMed

Nagpal, Sajan Jiv Singh; Kabbany, Mohammad Nasser; Mohamad, Bashar; Lopez, Rocio; Zein, Nizar N; Alkhouri, Naim

2016-07-01

Nonalcoholic fatty liver disease (NAFLD) is likely to replace Hepatitis C as the leading cause of cirrhosis resulting in liver transplantation (LT) within a few years. Unfortunately, due to the lack of established guidelines for the screening of NAFLD in high-risk populations, many patients present with portal hypertension complications as their first manifestation of NAFLD require a LT evaluation. We aimed to investigate what proportion of patients who underwent LT for NAFLD-cirrhosis had knowledge of their liver disease prior to presenting with portal hypertension complications and to identify differences in clinical parameters between those with and without knowledge of preexisting NAFLD. Consecutive patients who underwent LT for NAFLD-cirrhosis at a tertiary referral center were included in the study. Demographic and clinical data at the time of the first LT evaluation visit were collected, and patient knowledge of previous NAFLD was documented. Ascites, variceal bleeding, hepatic encephalopathy, and thrombocytopenia leading to diagnosis of underlying cirrhosis were considered as the presenting symptoms of portal hypertension. A p < 0.05 was considered statistically significant. A total of 124 subjects who received LT for NAFLD-cirrhosis were included, 58 % (n = 72) were male. At the time of the first LT evaluation visit, 60 % had diabetes, the mean body mass index was 33.2 [28.6, 37.6] kg/m(2), and the mean Model for End-Stage Liver Disease (MELD) score was 14.0 [11.0, 19.0]. More importantly, 85/124 patients (68.5 %) had no knowledge of preexisting NAFLD prior to presentation with symptoms of portal hypertension. The presenting symptoms were new-onset ascites in 61 %, hepatic encephalopathy in 25 %, variceal bleeding in 18 %, thrombocytopenia in 9 %, and other in 9 % (non-exclusive). Patients with no prior knowledge of NAFLD were less likely to have a diagnosis of hypercholesterolemia (30 vs. 50 %, p = 0.035) and had a trend toward having higher MELD scores at the time of the first LT evaluation visit (15 vs. 13.5, p = 0.05) and presenting with encephalopathy (25 vs. 10 %, p = 0.06) compared to those with previous knowledge of NAFLD diagnosis. The majority of patients undergoing liver transplant evaluation for NAFLD-cirrhosis are not aware of underlying NAFLD until they present with features of portal hypertension. New guidelines should consider screening for NAFLD in certain high-risk groups as more effective treatments for NAFLD are emerging.

Effect of tidal regime on the thermal tolerance of the marine gastropod Lunella smaragda (Gmelin 1791).

PubMed

Mortensen, B J D; Dunphy, B J

2016-08-01

The tidal cycle around New Zealand results in spring low tides consistently occurring during the hottest part of the day (mid-afternoon) in north-eastern New Zealand, and during the cooler dawn/dusk periods in the north-west of the country. We hypothesised that due to mid-afternoon spring low tides, intertidal populations residing at north-eastern sites would show greater thermotolerance than their north-west conspecifics. To test this we used the marine gastropod, Lunella smaragda, which were collected from sites on both the East and West coasts of the Auckland region and exposed to an acute heat shock. Thermotolerance was measured as survivorship (LT50), drop down time (time to heat coma) and thermal stability of the anaerobic energy producing enzyme Tauropine dehydrogenase. Furthermore, temperature loggers were deployed at each site so as to record and compare thermal regimes among sites. A strong temperature spike associated with spring low tide was found at all sites, and maximal temperatures of all East coast sites were higher than West coast sites (in some case by up to 10°C). In terms of thermotolerance, mortality of L. smaragda occurred at 42°C leading to 100% mortality at 45°C. However, comparison of LT50 showed snails were equally thermotolerant regardless of site of collection. Similar results were found in TDH thermal stability with animals from all sites showing an approximately 80% decrease in enzyme activity after 10min exposure to 42°C. Whilst drop down times were different among sites these were correlated with animal size as opposed to site of collection. Thus, East coast populations of L. smaragda appear no more thermotolerant than their West coast counterparts. Such a result is concerning as maximal temperatures at East coast sites already exceed the LT50 values of L. smaragda recorded in the lab suggesting these populations have less of a thermal safety margin. Copyright © 2016 Elsevier Ltd. All rights reserved.

Bm91 is an envelope component of ODV but is dispensable for the propagation of Bombyx mori nucleopolyhedrovirus.

PubMed

Tang, Qi; Li, Guohui; Yao, Qin; Chen, Liang; Lv, Peng; Lian, Chaoqun; Chen, Keping

2013-05-01

Orf91 (Bm91) of Bombyx mori nucleopolyhedrovirus (BmNPV) is a highly conserved gene that encodes a predicted 105-amino-acid protein, but its function remains unknown. In the current study, 5'-RACE revealed that the transcription initiation site of Bm91 was - 12 nucleotides upstream of the start codon ATG, transcription of Bm91 was detected from 12 to 96 h postinfection (p.i.) and Bm91 protein was detected from 24 to 96 h p.i. in BmNPV-infected BmN cells. Furthermore, Western blot analysis revealed that Bm91 was in occlusion-derived virus (ODV) but not in budded virus (BV). To investigate the role of Bm91 in baculovirus life cycle, a Bm91-knockout virus was constructed by bacmid recombination in E. coli. Fluorescence and light microscopy showed that the production of BV and occlusion bodies (OBs) in Bm91-deficient-virus-infected BmN cells were similar to those in wild-type-virus-infected ones. Bioassay results showed that genetic deletion of Bm91 did not significantly affect BmNPV infectivity, but extended the median lethal time (LT50). Taken together, these results indicate that Bm91 is not essential for viral propagation in vitro, but absence of the gene may affect the virulence of ODVs in silkworm larvae. Copyright © 2013 Elsevier Inc. All rights reserved.

A Biologically-Based Computational Approach to Drug Repurposing for Anthrax Infection.

PubMed

Bai, Jane P F; Sakellaropoulos, Theodore; Alexopoulos, Leonidas G

2017-03-10

Developing drugs to treat the toxic effects of lethal toxin (LT) and edema toxin (ET) produced by B. anthracis is of global interest . We utilized a computational approach to score 474 drugs/compounds for their ability to reverse the toxic effects of anthrax toxins. For each toxin or drug/compound, we constructed an activity network by using its differentially expressed genes, molecular targets, and protein interactions. Gene expression profiles of drugs were obtained from the Connectivity Map and those of anthrax toxins in human alveolar macrophages were obtained from the Gene Expression Omnibus. Drug rankings were based on the ability of a drug/compound's mode of action in the form of a signaling network to reverse the effects of anthrax toxins; literature reports were used to verify the top 10 and bottom 10 drugs/compounds identified. Simvastatin and bepridil with reported in vitro potency for protecting cells from LT and ET toxicities were computationally ranked fourth and eighth. The other top 10 drugs were fenofibrate, dihydroergotamine, cotinine, amantadine, mephenytoin, sotalol, ifosfamide, and mefloquine; literature mining revealed their potential protective effects from LT and ET toxicities. These drugs are worthy of investigation for their therapeutic benefits and might be used in combination with antibiotics for treating B. anthracis infection.

A Biologically-Based Computational Approach to Drug Repurposing for Anthrax Infection

PubMed Central

Bai, Jane P. F.; Sakellaropoulos, Theodore; Alexopoulos, Leonidas G.

2017-01-01

Developing drugs to treat the toxic effects of lethal toxin (LT) and edema toxin (ET) produced by B. anthracis is of global interest. We utilized a computational approach to score 474 drugs/compounds for their ability to reverse the toxic effects of anthrax toxins. For each toxin or drug/compound, we constructed an activity network by using its differentially expressed genes, molecular targets, and protein interactions. Gene expression profiles of drugs were obtained from the Connectivity Map and those of anthrax toxins in human alveolar macrophages were obtained from the Gene Expression Omnibus. Drug rankings were based on the ability of a drug/compound’s mode of action in the form of a signaling network to reverse the effects of anthrax toxins; literature reports were used to verify the top 10 and bottom 10 drugs/compounds identified. Simvastatin and bepridil with reported in vitro potency for protecting cells from LT and ET toxicities were computationally ranked fourth and eighth. The other top 10 drugs were fenofibrate, dihydroergotamine, cotinine, amantadine, mephenytoin, sotalol, ifosfamide, and mefloquine; literature mining revealed their potential protective effects from LT and ET toxicities. These drugs are worthy of investigation for their therapeutic benefits and might be used in combination with antibiotics for treating B. anthracis infection. PMID:28287432

Accepting multiple simultaneous liver offers does not negatively impact transplant outcomes.

PubMed

Eldeen, Firas Zahr; Mourad, Moustafa Mabrouk; Bhandari, Mayank; Roll, Garrett; Gunson, Bridget; Mergental, Hynek; Bramhall, Simon; Isaac, John; Muiesan, Paolo; Mirza, Darius F; Perera, M Thamara P R

2016-02-01

Impact of performing multiple liver transplants (LT) in a short period of time is unknown. Consecutively performed LT potentially increase complication rates through team fatigue and overutilization of resources and increase ischemia time. We analyzed the impact of undertaking consecutive LT (Consecutive liver transplant, CLT; LT preceded by another transplant performed not more than 12 h before, both transplants grouped together) on outcomes. Of 1702 LT performed, 314 (18.4%) were CLT. Outcome data was compared with solitary LT (SLT; not more than one LT in 12-h period). Recipient, donor, and graft characteristics were evenly matched between SLT and CLT; second LT of CLT group utilized younger donors grafts with longer cold ischemic times (P = 0.015). Implantation and operative time were significantly lower in CLT recipients on intergroup analysis (P = 0.0001 and 0.002, respectively). Early hepatic artery thrombosis (E-HAT) was higher in CLT versus SLT (P = 0.038), despite absolute number of E-HAT being low in all groups. Intragroup analysis demonstrated a trend toward more frequent E-HAT in first LT, compared to subsequent transplants; however, difference did not reach statistical significance (P = 0.135). In era of organ scarcity, CLT performed at high-volume center is safe and allows pragmatic utilization of organs, potentially reducing number of discarded grafts and reducing waiting list mortality. © 2015 Steunstichting ESOT.

The comparative toxicity of operational Air Force hydraulic fluids.

PubMed

Mattie, D R; Hoeflich, T J; Jones, C E; Horton, M L; Whitmire, R E; Godin, C S; Flemming, C D; Andersen, M E

1993-01-01

The subchronic (26 day) oral toxicities of two AF hydraulic fluids (MIL-H-5606 [H5], MIL-H-83282 [H8]), a commercial phosphate ester (PE), and two candidate hydraulic fluids (low temperature version of MIL-H-83282 [LT] and chlorotrifluorethylene oligomers [polyCTFE]) were compared in male F-344 rats. Oral dosing was used in order to quickly compare these fluids to PolyCTFE, the only fluid at the time to have been tested in a 90-day inhalation study. Rats were initially dosed with 1.0 g/kg/day of each fluid. H8 increased alkaline phosphatase (ALKP) while LT produced an anemia and leukocytosis. Exposure to H5 fluid resulted in lymphocytopenia and persistent diuresis. Due to their greater toxicity, resulting in lethality in the first dosing study, only 0.5 g/kg/day of PE and PolyCTFE were administered in the second study. Exposure to PE (0.5 g/kg) resulted in an anemia and decreases in BW (day 10 until day 25), spleen/BW ratio, blood urea nitrogen (BUN), and creatinine (CREAT). PolyCREAT (0.5 g/kg) decreased BW (day 11 to the end of the study) and testicular weight. PolyCTFE (0.5 g/kg) increased relative spleen weights, various clinical chemistry parameters, and triggered a reversible diuresis. PolyCTFE (0.5 g/kg), PE (0.5 g/kg), and H5 produced an increase in absolute and relative liver weights compared to control livers. Peroxisomal beta oxidation, an indicator of peroxisomal proliferation, was significantly increased above control levels in the livers of all rats except the PE (0.5 g/kg) group, where the increase was not significant. Hydrocarbon nephropathy, indicated by increased levels of hyaline droplets in kidney tubules, was severe in H5, mild in H8, LT, and PolyCTFE (0.5 g/kg), and minimal in PE (0.5 g/kg). The MIL-H-83282 fluids (H8 and LT) were the least toxic hydraulic fluids. PolyCTFE and PE were the most toxic, with H5 intermediate.

Investigating energy deposition within cell populations using Monte Carlo simulations.

PubMed

Oliver, Patricia A K; Thomson, Rowan M

2018-06-27

In this work, we develop multicellular models of healthy and cancerous human soft tissues, which are used to investigate energy deposition in subcellular targets, quantify the microdosimetric spread in a population of cells, and determine how these results depend on model details. Monte Carlo (MC) tissue models combining varying levels of detail on different length scales are developed: microscopically-detailed regions of interest (>1500 explicitly-modelled cells) are embedded in bulk tissue phantoms irradiated by photons (20 keV to 1.25 MeV). Specific energy (<i>z</i>; energy imparted per unit mass) is scored in nuclei and cytoplasm compartments using the EGSnrc user-code egs_chamber; specific energy mean, <<i>z</i>>, standard deviation, <i>σ</i>_<i>z</i>, and distribution, <i>f</i>(<i>z</i>,<i>D</i>), are calculated for a variety of macroscopic doses, <i>D</i>. MC-calculated <i>f</i>(<i>z</i>,<i>D</i>) are compared with normal distributions having the same mean and standard deviation. For mGy doses, there is considerable variation in energy deposition (microdosimetric spread) throughout a cell population: <i>e</i>.<i>g</i>., for 30 keV photons irradiating melanoma with 7.5 μm cell radius and 3 μm nuclear radius, <i>σ</i>_<i>z</i>/<<i>z</i>> for nuclear targets is 170%, and the fraction of nuclei receiving no energy deposition, <i>f</i>_<i>z</i>=0, is 0.31 for a dose of 10 mGy. If cobalt-60 photons are considered instead, then <i>σ</i>_<i>z</i>/<<i>z</i>> decreases to 84%, and <i>f</i>_<i>z</i>=0 decreases to 0.036. These results correspond to randomly arranged cells with cell/nucleus sizes randomly sampled from a normal distribution with a standard deviation of 1 μm. If cells are arranged in a hexagonal lattice and cell/nucleus sizes are uniform throughout the population, then <i>σ</i>_<i>z</i>/<<i>z</i>> decreases to 106% and 68% for 30 keV and cobalt-60,respectively; <i>f</i>_<i>z</i>=0 decreases to 0.25 and 0.00094 for 30 keV and cobalt-60, respectively. Thus, specific energy distributions are sensitive to cell/nucleus sizes and their distributions: variations in specific energy deposited over a cell population are underestimated if targets are assumed to be uniform in size compared with more realistic variation in target size. Bulk tissue dose differs from <<i>z</i>> for nuclei (cytoplasms) by up to 21% (12%) across all cell/nucleus sizes, bulk tissues, and incident photon energies, considering a 50 mGy dose level. Overall, results demonstrate the importance of microdosimetric considerations at low doses, and indicate the sensitivity of energy deposition within subcellular targets to incident photon energy, dose level, elemental compositions, and microscopic tissue model. © 2018 Institute of Physics and Engineering in Medicine.

Stabilization of blood methylmalonic acid level in methylmalonic acidemia after liver transplantation.

PubMed

Chen, P W; Hwu, W L; Ho, M C; Lee, N C; Chien, Y H; Ni, Y H; Lee, P H

2010-05-01

Methylmalonic acidemia with complete mutase deficiency (mut(0) type) is an inborn error of metabolism with high mortality and morbidity. LT has been suggested to be a solution to this disease, but elevation of urinary and blood MMA was still observed after LT. In this study, we measured dry blood spot MMA and its precursor propionyl-carnitine (C3-carnitine) for mut(0) patients. The results revealed that when C3-carnitine rose during metabolic stress, MMA rose exponentially (up to 1000 micromol/L) in patients who did not undergo LT. In patients who underwent LT, MMA rose to 100-200 micromol/L when C3-carnitine reached 10-20 micromol/L. However, when C3-carnitine rose further to 40-50 micromol/L, MMA levels just stayed put. Therefore, LT stabilized blood MMA level, though there might be a threshold for blood MMA clearance by the donor liver. This finding should be critical to understand the long-term outcome for LT in methylmalonic acidemia.

Latitudinal variation of freeze tolerance in intertidal marine snails of the genus Melampus (Gastropoda: Ellobiidae).

PubMed

Dennis, A B; Loomis, S H; Hellberg, M E

2014-01-01

Abstract Low temperatures limit the poleward distribution of many species such that the expansion of geographic range can only be accomplished via evolutionary innovation. We have tested for physiological differences among closely related species to determine whether their poleward latitudinal ranges are limited by tolerance to cold. We measured lower temperature tolerance (LT50) among a group of intertidal pulmonate snails from six congeneric species and nine locales. Differences in tolerance are placed in the context of a molecular phylogeny based on one mitochondrial (cytochrome oxidase subunit I) and two nuclear (histone 3 and a mitochondrial phosphate carrier protein) markers. Temperate species from two separate lineages had significantly lower measures of LT50 than related tropical species. Range differences within the temperate zone, however, were not explained by LT50. These results show that multiple adaptations to cold and freezing may have enabled range expansions out of the tropics in Melampus. However, northern range limits within temperate species are not governed by cold tolerance alone.

The lethality test used for estimating the potency of antivenoms against Bothrops asper snake venom: pathophysiological mechanisms, prophylactic analgesia, and a surrogate in vitro assay.

PubMed

Chacón, Francisco; Oviedo, Andrea; Escalante, Teresa; Solano, Gabriela; Rucavado, Alexandra; Gutiérrez, José María

2015-01-01

The potency of antivenoms is assessed by analyzing the neutralization of venom-induced lethality, and is expressed as the Median Effective Dose (ED50). The present study was designed to investigate the pathophysiological mechanisms responsible for lethality induced by the venom of Bothrops asper, in the experimental conditions used for the evaluation of the neutralizing potency of antivenoms. Mice injected with 4 LD50s of venom by the intraperitoneal route died within ∼25 min with drastic alterations in the abdominal organs, characterized by hemorrhage, increment in plasma extravasation, and hemoconcentration, thus leading to hypovolemia and cardiovascular collapse. Snake venom metalloproteinases (SVMPs) play a predominat role in lethality, as judged by partial inhibition by the chelating agent CaNa2EDTA. When venom was mixed with antivenom, there was a venom/antivenom ratio at which hemorrhage was significantly reduced, but mice died at later time intervals with evident hemoconcentration, indicating that other components in addition to SVMPs also contribute to plasma extravasation and lethality. Pretreatment with the analgesic tramadol did not affect the outcome of the neutralization test, thus suggesting that prophylactic (precautionary) analgesia can be introduced in this assay. Neutralization of lethality in mice correlated with neutralization of in vitro coagulant activity in human plasma. Copyright © 2014 Elsevier Ltd. All rights reserved.

[Secondary metabolites, lethality and antimicrobial activity of extracts from three corals and three marine mollusks from Sucre, Venezuela].

PubMed

Ordaz, Gabriel; D'Armas, Haydelba; Yáñez, Dayanis; Hernández, Juan; Camacho, Angel

2010-06-01

The study of biochemical activity of extracts obtained from marine organisms is gaining interest as some have proved to have efficient health or industrial applications. To evaluate lethality and antimicrobial activities, some chemical tests were performed on crude extracts of the octocorals Eunicea sp., Muricea sp. and Pseudopterogorgia acerosa and the mollusks Pteria colymbus, Phyllonotus pomum and Chicoreus brevifrons, collected in Venezuelan waters. The presence of secondary metabolites like alkaloids, unsaturated sterols and pentacyclic triterpenes in all invertebrates, was evidenced. Additionally, sesquiterpenlactones, saponins, tannins, cyanogenic and cardiotonic glycosides were also detected in some octocoral extracts, suggesting that biosynthesis of these metabolites is typical in this group. From the lethality bioassays, all extracts resulted lethal to Artemia salina (LC50<1000 microg/ml) with an increased of lethal activity with exposition time. P. pomum extract showed the highest lethality rate (LC50=46.8 microg/ml). Compared to the octocorals, mollusks extracts displayed more activity and a greater action spectrum against different bacterial strains, whereas octocorals also inhibited some fungi strains growth. Staphylococcus aureus was the most susceptible to the antimicrobial power of the extracts (66.7%), whereas Pseudomonas aeruginosa, Candida albicans and Aspergillus niger were not affected. The antibiosis shown by marine organisms extracts indicates that some of their biosynthesized metabolites are physiologically active, and may have possible cytotoxic potential or as a source of antibiotic components.

Developmental toxicity and risk assessment of nonylphenol to the South American toad, Rhinella arenarum.

PubMed

Mariel, Aronzon Carolina; Alejandra, Babay Paola; Silvia, Pérez Coll Cristina

2014-09-01

The toxicity of Nonylphenol, an emerging pollutant, on the common South American toad Rhinella arenarum was stage and time dependent, thus Median Lethal Concentrations (LC50) for acute (96h), short-term chronic (168h) and chronic exposure (336h) were 1.06; 0.96 and 0.17mgNP/L from embryonic period (S.4), whereas for exposure from larvae (S.25), LC50 remained constant at 0.37mgNP/L from 96h to 168h, decreasing to 0.11mgNP/L at 336h. NOEC-168h for exposure from embryos was 0.025mgNP/L. The Teratogenic Potential (NOEC-lethality/NOEC-sublethal effects) was 23 times higher than the threshold value, indicating a high risk for embryos to be malformed in absence of significant lethality and representing a threat for the species conservation. By comparing with other amphibians, the early development of R. arenarum was very sensitive to NP. The results highlight the relevance of extending the exposure time and look for the most sensitive stage in order to perform the bioassays for conservation purposes. Copyright © 2014 Elsevier B.V. All rights reserved.

Rate of employment after liver transplantation in France: a single-centre study.

PubMed

Rudler, Marika; Rousseau, Géraldine; Lebray, Pascal; Méténier, Océane; Vaillant, Jean-Christophe; Savier, Eric; Eyraud, Daniel; Poynard, Thierry; Thabut, Dominique

2016-02-01

A return to gainful employment is an important outcome parameter after liver transplantation (LT). A recent study in the USA has shown a very high rate of unemployment after LT (75%). To date, there are no available data in France, where the public health insurance programme guarantees financial protection for everyone. The aim of this study was to assess the employment rate after LT in a French LT centre and to determine factors associated with employment after LT. All patients who had undergone liver transplantation at our centre between January 2000 and April 2011 and who met the following criteria responded to a questionnaire: (i) between 18 and 65 years old at the time of LT, (ii) alive 1 year after LT, (iii) alive, not retired and released from the hospital at the time of survey, (iv) French residents who were affiliated with French national health insurance. A total of 345 LTs were performed in 314 patients during the study period. Of the patients, 109 were excluded from the study: 23 had died within the first year after LT, 28 had died at the time of the survey, three were still in the hospital, seven were living in a foreign country, 11 had retired and 37 were older than 65 years after LT. Two hundred five patients were included in the study. The response rate was 76.6% (157/205). Patients responded a mean 6.1 ± 0.9 years after LT, 77.7% were French nationals, 73.2% were men, and the mean age at LT was 48.8 ± 9.9 years. The aetiologies of liver disease were as follows: alcohol 32.5%, hepatitis C 26.1%, alcohol and hepatitis C 3.8%, hepatitis B 15.3%, biliary cirrhosis 5.1%, autoimmune 2.5% and other causes 14.7%. Two years after LT, 43.3% of patients were employed. The demographic variables associated with post-LT employment were male sex (P<0.001), age under 40 years at LT (P=0.02), a sedentary job (P=0.007), raising children under the age of 18 years at the time of LT (P=0.01), a high level of education (P=0.001), not being affiliated with the French universal health coverage or 'CMU' (P=0.001). Only 53.3% of the patients who did not return to work after LT stated that they felt like they had a physical disability. The rate of return to work after LT in France was 43.1%, which was higher than that reported in the US study. However, this rate remains low and policies supporting return to work are needed to help liver recipients who wish to work after LT.

Mechanism of ascaridole activation in Leishmania.

PubMed

Geroldinger, Gerald; Tonner, Matthias; Hettegger, Hubert; Bacher, Markus; Monzote, Lianet; Walter, Martin; Staniek, Katrin; Rosenau, Thomas; Gille, Lars

2017-05-15

Endoperoxides (EP) are an emerging class of drugs which have potential in antiparasitic therapy, but also in other fields. For malaria therapy the EP artemisinin (Art) and its derivatives are successfully used. We have shown in the past that the EP ascaridole (Asc) is useful for the treatment of cutaneous leishmaniasis in a mouse model. Biomimetic experiments suggested that these drugs need activation in the respective target pathogens to exert their function. In spite of this idea, direct activation of EP to radicals inside cells has never been demonstrated. Therefore, this study was initiated to explore the activation of Asc in biomimetic systems and inside Leishmania in comparison to Art. Using electron paramagnetic resonance spectroscopy (EPR) in combination with spin-trapping we identified the secondary alkyl radical intermediates arising from reduction by Fe 2+ in cell-free systems. Combined GC/NMR analysis confirmed the loss of isopropyl residues from Asc during this process as intermediates. This activation of Asc was stimulated by low molecular Fe 2+ complexes or alternatively by hemin in conjunction with thiol reductants, such as cysteine (Cys). In Leishmania tarentolae promastigotes (LtP) as model for pathogenic forms of Leishmania carbon-centered radicals were identified in the presence of Asc by EPR spin-trapping. Both Asc and Art inhibited the viability in LtP with IC 50 values in the low micromolar range while IC 50 values for J774 macrophages were considerably higher. A similar structure without EP bridge (1,4-cineole) resulted in no detectable radicals and possessed much less cytotoxicity in LtP and no selectivity for LtP compared to J774 cells. The Asc-derived radical formation in LtP was inhibited by the iron chelator deferoxamine (DFO), and stimulated by Cys (a suitable reductant for hemin). The IC 50 values for LtP viability in the presence of Asc or Art were increased significantly by the spin trap DMPO, while Cys and DFO increased only IC 50 values for Art. In a heme association assay Asc demonstrated a lower binding affinity to heme than Art. ICP-OES measurements revealed that in LtP the total iron concentrations were twice as high as values in J774 macrophages. Since low molecular iron was important in Asc activation we studied the influence of Asc on the labile iron pool (LIP) in LtP. Low temperature EPR experiments demonstrated that Asc shifts the redox balance of iron in the LIP to its oxidized state. These data demonstrate that univalent cleavage of Asc/Art in LtP is an essential part of their pharmacological mechanism. The structure of the EP determines whether activation by low molecular iron or heme is favored and the availability of these intracellular activators modulates their cytotoxicity. These findings may be helpful for synthesis of new Asc derivatives and understanding the action of EP in other cell types. Copyright © 2017 Elsevier Inc. All rights reserved.

Successful resolution of severe hepatopulmonary syndrome following liver transplantation.

PubMed

Asthana, Sonal; Maguire, Connor; Lou, Lawrence; Meier, Michael; Bain, Vincent; Townsend, Derek R; Townsend, Rex; Lien, Dale; Bigam, David; Kneteman, Norman; Shapiro, Andrew Mark James

2010-04-01

Hepatopulmonary syndrome (HPS) is a complication of portal hypertension, defined by the presence of liver disease, abnormal pulmonary gas exchange and evidence of intrapulmonary vascular dilatations producing a right-to-left intrapulmonary shunt. Liver transplantation (LT) is the treatment of choice; however, severe hypoxemia (PaO(2) < 50 mmHg on room air) is considered a contraindication to LT. This approach disadvantages some patients, particularly young patients with no intrinsic cardio-respiratory disease. We discuss one such patient who improved with LT despite having extremely severe HPS (PaO2 < 29 mmHg).

Detection of warfare agents in liquid foods using the brine shrimp lethality assay.

PubMed

Lumor, Stephen E; Diez-Gonzalez, Francisco; Labuza, Theodore P

2011-01-01

The brine shrimp lethality assay (BSLA) was used for rapid and non-specific detection of biological and chemical warfare agents at concentrations considerably below that which will cause harm to humans. Warfare agents detected include T-2 toxin, trimethylsilyl cyanide, and commercially available pesticides such as dichlorvos, diazinon, dursban, malathion, and parathion. The assay was performed by introducing 50 μL of milk or orange juice contaminated with each analyte into vials containing 10 freshly hatched brine shrimp nauplii in seawater. This was incubated at 28 °C for 24 h, after which mortality was determined. Mortality was converted to probits and the LC(50) was determined for each analyte by plotting probits of mortality against analyte concentration (log(10)). Our findings were the following: (1) the lethal effects of toxins dissolved in milk were observed, with T-2 toxin being the most lethal and malathion being the least, (2) except for parathion, the dosage (based on LC(50)) of analyte in a cup of milk (200 mL) consumed by a 6-y-old (20 kg) was less than the respective published rat LD(50) values, and (3) the BSLA was only suitable for detecting toxins dissolved in orange juice if incubation time was reduced to 6 h. Our results support the application of the BSLA for routine, rapid, and non-specific prescreening of liquid foods for possible sabotage by an employee or an intentional bioterrorist act. Practical Application: The findings of this study strongly indicate that the brine shrimp lethality assay can be adapted for nonspecific detection of warfare agents or toxins in food at any point during food production and distribution.

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

Harris, L.W.; Talbot, B.G.; Lennox, W.J.

A pretreatment for organophosphorus (OP) anticholinesterase (e. g. , soman) intoxication should prevent lethality and convulsions (CNV) at 2 LD50s and be behavioral-decrement-free when given alone. Behavioral-deficit-free pretreatment regimens (PRGs) for guinea pigs consisted of Physostigmine (0.15 mg/kg, im) and adjunct. Adjuncts MG/KG, IM tested were akineton 0.25, aprophen 8, trihexyphenidyl 2, atropine 16, azaprophen 51, BENACTYZINE 1.25, cogentin 4, dextromethorphan 7.5, ethopropazine 12, kemadrin 11, MEMANTINE 5, promethazine 5, scopolamine 0.081 AND CONTROL 2. PRGs were given 30 min before soman (60 ug/kg, sc; 2 LD50S) or other OP agents. Animals were then observed and graded for signs ofmore » intoxication, including CNV at 7 time points and at 24 hr. Physostigmine alone reduced the incidence of CNV and lethality induced by 2 LD50s of soman by 42 and 60%, respectively. All of the PRGs tested abolished lethality and 12 shortened recovery time to 2 hr or less. Also, PRGs including azaprophen or atropine prevented CNV. When selected PRGs were tested against intoxication by sarin, tabun or VX, the efficacy was generally superior to that for soman. The data show that several PRGs are effective against soman intoxication in guinea pigs. Pretreatment, physostigmine, anticholinesterases, soman (GD).« less

Persistence and Viability of Lecanicillium lecanii in Chinese Agricultural Soil

PubMed Central

Peng, De-Liang; Zhou, Jie; Zhang, Xiao-Lin; Zhang, Zhao-Rong; Zhao, Jin-Jin; Wu, Yu-Huan

2015-01-01

The entomopathogenic fungus L. lecanii has been developed as biopesticides and used widely for biological control of several insects in agricultural practice. Due to the lack of isolation/count methods for L. lecanii in soil, the persistence of this fungus in soil appears to have attracted no attention. A selective medium and count method for L. lecanii in soil based on cetyl trimethyl ammonium bromide (CTAB) was developed, and then the persistence and viability of this fungus in soil were investigated under field conditions between 2012 and 2014. The results showed that the rate of recovery for L. lecanii in soil on the selective CTAB medium was satisfactory. The minimum CFUs for L. lecanii on the selective medium (0.5 g/L CTAB) was about 102 conidia/g soil. The L. lecanii density in soil declined quickly in the first month after inoculation with fungal conidia, kept stable for 6 to 10 months, and then decreased gradually until undetectable. L. lecanii could persist for at least 14 months in the agricultural soil of northern China. The colony growth, conidia yield and germination rate on plates, as well as the median lethal concentration or times (LC50 or LT50) to aphids, mycelium growth in aphids and sporulation on aphids of L. lecanii did not change significantly during the persistence in soil. In general, the count method developed here was a very useful tool for monitoring the dynamics of natural or introduced L. lecanii populations in soil, and the data on the persistence of L. lecanii in soil reported here were helpful for biological control and environmental risk assessment. PMID:26375030

Factors contributing to deep supercooling capability and cold survival in dwarf bamboo (Sasa senanensis) leaf blades.

PubMed

Ishikawa, Masaya; Oda, Asuka; Fukami, Reiko; Kuriyama, Akira

2014-01-01

Wintering Sasa senanensis, dwarf bamboo, is known to employ deep supercooling as the mechanism of cold hardiness in most of its tissues from leaves to rhizomes. The breakdown of supercooling in leaf blades has been shown to proceed in a random and scattered manner with a small piece of tissue surrounded by longitudinal and transverse veins serving as the unit of freezing. The unique cold hardiness mechanism of this plant was further characterized using current year leaf blades. Cold hardiness levels (LT20: the lethal temperature at which 20% of the leaf blades are injured) seasonally increased from August (-11°C) to December (-20°C). This coincided with the increases in supercooling capability of the leaf blades as expressed by the initiation temperature of low temperature exotherms (LTE) detected in differential thermal analyses (DTA). When leaf blades were stored at -5°C for 1-14 days, there was no nucleation of the supercooled tissue units either in summer or winter. However, only summer leaf blades suffered significant injury after prolonged supercooling of the tissue units. This may be a novel type of low temperature-induced injury in supercooled state at subfreezing temperatures. When winter leaf blades were maintained at the threshold temperature (-20°C), a longer storage period (1-7 days) increased lethal freezing of the supercooled tissue units. Within a wintering shoot, the second or third leaf blade from the top was most cold hardy and leaf blades at lower positions tended to suffer more injury due to lethal freezing of the supercooled units. LTE were shifted to higher temperatures (2-5°C) after a lethal freeze-thaw cycle. The results demonstrate that the tissue unit compartmentalized with longitudinal and transverse veins serves as the unit of supercooling and temperature- and time-dependent freezing of the units is lethal both in laboratory freeze tests and in the field. To establish such supercooling in the unit, structural ice barriers such as development of sclerenchyma and biochemical mechanisms to increase the stability of supercooling are considered important. These mechanisms are discussed in regard to ecological and physiological significance in winter survival.

Core body temperature as adjunct to endpoint determination in murine median lethal dose testing of rattlesnake venom.

PubMed

Cates, Charles C; McCabe, James G; Lawson, Gregory W; Couto, Marcelo A

2014-12-01

Median lethal dose (LD50) testing in mice is the 'gold standard' for evaluating the lethality of snake venoms and the effectiveness of interventions. As part of a study to determine the murine LD50 of the venom of 3 species of rattlesnake, temperature data were collected in an attempt to more precisely define humane endpoints. We used an 'up-and-down' methodology of estimating the LD50 that involved serial intraperitoneal injection of predetermined concentrations of venom. By using a rectal thermistor probe, body temperature was taken once before administration and at various times after venom exposure. All but one mouse showed a marked, immediate, dose-dependent drop in temperature of approximately 2 to 6°C at 15 to 45 min after administration. The lowest temperature sustained by any surviving mouse was 33.2°C. Surviving mice generally returned to near-baseline temperatures within 2 h after venom administration, whereas mice that did not survive continued to show a gradual decline in temperature until death or euthanasia. Logistic regression modeling controlling for the effects of baseline core body temperature and venom type showed that core body temperature was a significant predictor of survival. Linear regression of the interaction of time and survival was used to estimate temperatures predictive of death at the earliest time point and demonstrated that venom type had a significant influence on temperature values. Overall, our data suggest that core body temperature is a useful adjunct to monitoring for endpoints in LD50 studies and may be a valuable predictor of survival in venom studies.

Effects of BCG infection on the susceptibility of mouse macrophages to endotoxin.

PubMed Central

Peavy, D L; Baughn, R E; Musher, D M; Musher, D M

1979-01-01

Mice infected intravenously with Mycobacterium bovis (BCG) are 100 to 1,000 times more sensitive to the lethal effects of bacterial lipopolysaccharides (LPS). Since BCG infection results in macrophage activation and LPS may cause pathophysiological effects through interaction with this cell type, it was of interest to determine whether macrophages from BCG-infected animals were more susceptible to the toxic effects of LPS in vitro. When LPS-susceptible, C57BL/6 mice were infected with BCG, a significant reduction in the 50% lethal dose of LPS was first observed after 7 days and persisted for several weeks. Macrophages from these animals had greatly increased susceptibility to LPS in vitro, which correlated with the development of acquired cellular resistance as determined by their ability to inhibit the growth of Listeria monocytogenes. In contrast, BCG infection of C3H/HeJ mice, a strain resistant to LPS, did not alter the 50% lethal dose of LPS for these animals or increase the sensitivity of their peritoneal macrophages to LPS in vitro. These results indicate that susceptibility of BCG-infected mice to the lethal effects of LPS parallels the susceptibility of their macrophages in vitro; release of vasoactive substances from LPS-susceptible activated macrophages in vivo may be, in part, responsible for lethality. PMID:378847

Circulating concentrations of free thyroxine after an oral intake of liquid LT4 taken either during fasting conditions or at breakfast.

PubMed

Marina, Michela; Ceda, Gian Paolo; Aloe, Rosalia; Gnocchi, Cecilia; Ceresini, Graziano

2017-01-16

Liquid levothyroxine (LT4) given at breakfast normalizes TSH in hypothyroid patients. However, a few studies are available on circulating free thyroxine (FT4) concentrations after liquid vs solid LT4 preparations. During an "ad interim" analysis on serum FT4 after 200 mcg liquid LT4 consumption while fasting in thyroidectomized thyroid cancer patients, we found that seven subjects fortuitously took liquid LT4 at breakfast. As established in the original protocol, serum FT4 was measured both at baseline as well as at 3 and 4 hours after solid or liquid LT4 consumption. We compared serum profile of FT4 in these subjects with those obtained in other subjects participating in the same study who took liquid LT4 (n. 7 subjects) or solid LT4 (n. 7 subjects) while fasting. The percentage increase of circulating FT4 was calculated at the above reported peak-times over the baseline values. Circulating FT4 increased of about 40% in each group of subjects at both the 3rd and the 4th hour with no difference between these two time points in either group. The maximum FT4 % increase, irrespective of the time point, was 44.62 ± 3.05 (Mean ± SE), 44.84 ± 5.43, and 43.83 ± 1.30 after fasting solid, fasting liquid, and breakfast liquid LT4 consumption, respectively, with no differences among the three groups. Circulating FT4 obtained after 3 and 4 hours from the ingestion of 200 mcg liquid LT4 is not influenced by meal and is comparable with that observed after solid LT4 preparations ingested while fasting.

Effect of the laryngeal tube on the no-flow-time in a simulated two rescuer basic life support setting with inexperienced users.

PubMed

Schröder, J; Bucher, M; Meyer, O

2016-09-01

Intubation with a laryngeal tube (LT) is a recommended alternative to endotracheal intubation during advanced life support (ALS). LT insertion is easy; therefore, it may also be an alternative to bag-mask ventilation (BMV) for untrained personnel performing basic life support (BLS). Data from manikin studies support the influence of LT on no-flow-time (NFT) during ALS. We performed a prospective, randomized manikin study using a two-rescuer model to compare the effects of ventilation using a LT and BMV on NFT during BLS. Participants were trained in BMV and were inexperienced in the use of a LT. There was no significant difference in total NFT with the use of a LT and BMV (LT: mean 83.1 ± 37.3 s; BMV: mean 78.7 ± 24.5 s; p = 0.313), but we found significant differences in the progression of the scenario: in the BLS-scenario, the proportion of time spent performing chest compressions was higher when BMV was used compared to when a LT was used. The quality of chest compressions and the ventilation rate did not differ significantly between the two groups. The mean tidal volume and mean minute volume were significantly larger with the use of a LT compared with the use of BMV. In conclusion, in a two-rescuer BLS scenario, NFT is longer with the use of a LT (without prior training) than with the use of BMV (with prior training). The probable reasons for this result are higher tidal volumes with the use of a LT leading to longer interruptions without chest compressions.

Training Intensity Distribution Over a Four-Year Cycle in Olympic Champion Rowers: Different Roads Lead to Rio.

PubMed

Plews, Daniel J; Laursen, Paul B

2017-09-27

The purpose of this study was to compare the training intensity distribution (TID) of the undefeated world champion male rowing New Zealand (kiwi) pair over a four-year Olympic cycle, across training phases, training years, and between individuals. Training data, including heart rate and boat speed, were recorded in the athletes rowing in the same boat between March 2013 and August 2016, ending with the Rio Olympics final. Progressive exercise tests assessed first (LT 1 ) and second (LT 2 ) lactate thresholds and associated heart rates, to determine the percentage of training performed below, between and above these demarcation points. Training an average of only 12-15 h/wk throughout the Olympic cycle, the mean percent distribution of time (±SD) at each training intensity was 80.4 ± 5.5% LT 2 for Rower A and 67.3 ± 9.0% LT 2 for Rower B. Across the years 2014-2016, Rower A performed most likely more training

Minimizing tacrolimus decreases the risk of new-onset diabetes mellitus after liver transplantation.

PubMed

Song, Jiu-Lin; Gao, Wei; Zhong, Yan; Yan, Lu-Nan; Yang, Jia-Yin; Wen, Tian-Fu; Li, Bo; Wang, Wen-Tao; Wu, Hong; Xu, Ming-Qing; Chen, Zhe-Yu; Wei, Yong-Gang; Jiang, Li; Yang, Jian

2016-02-14

To investigate the impact of minimum tacrolimus (TAC) on new-onset diabetes mellitus (NODM) after liver transplantation (LT). We retrospectively analyzed the data of 973 liver transplant recipients between March 1999 and September 2014 in West China Hospital Liver Transplantation Center. Following the exclusion of ineligible recipients, 528 recipients with a TAC-dominant regimen were included in our study. We calculated and determined the mean trough concentration of TAC (cTAC) in the year of diabetes diagnosis in NODM recipients or in the last year of the follow-up in non-NODM recipients. A cutoff of mean cTAC value for predicting NODM 6 mo after LT was identified using a receptor operating characteristic curve. TAC-related complications after LT was evaluated by χ(2) test, and the overall and allograft survival was evaluated using the Kaplan-Meier method. Risk factors for NODM after LT were examined by univariate and multivariate Cox regression. Of the 528 transplant recipients, 131 (24.8%) developed NODM after 6 mo after LT, and the cumulative incidence of NODM progressively increased. The mean cTAC of NODM group recipients was significantly higher than that of recipients in the non-NODM group (7.66 ± 3.41 ng/mL vs 4.47 ± 2.22 ng/mL, P < 0.05). Furthermore, NODM group recipients had lower 1-, 5-, 10-year overall survival rates (86.7%, 71.3%, and 61.1% vs 94.7%, 86.1%, and 83.7%, P < 0.05) and allograft survival rates (92.8%, 84.6%, and 75.7% vs 96.1%, 91%, and 86.1%, P < 0.05) than the others. The best cutoff of mean cTAC for predicting NODM was 5.89 ng/mL after 6 mo after LT. Multivariate analysis showed that old age at the time of LT (> 50 years), hypertension pre-LT, and high mean cTAC (≥ 5.89 ng/mL) after 6 mo after LT were independent risk factors for developing NODM. Concurrently, recipients with a low cTAC (< 5.89 ng/mL) were less likely to become obese (21.3% vs 30.2%, P < 0.05) or to develop dyslipidemia (27.5% vs 44.8%, P <0.05), chronic kidney dysfunction (14.6% vs 22.7%, P < 0.05), and moderate to severe infection (24.7% vs 33.1%, P < 0.05) after LT than recipients in the high mean cTAC group. However, the two groups showed no significant difference in the incidence of acute and chronic rejection, hypertension, cardiovascular events and new-onset malignancy. A minimal TAC regimen can decrease the risk of long-term NODM after LT. Maintaining a cTAC value below 5.89 ng/mL after LT is safe and beneficial.

Direct measurement of the lethal isotherm for radiofrequency ablation of myocardial tissue.

PubMed

Wood, Mark; Goldberg, Scott; Lau, Melissa; Goel, Aneesh; Alexander, Daniel; Han, Frederick; Feinstein, Shawn

2011-06-01

The lethal isotherm for radiofrequency catheter ablation of cardiac myocardium is widely accepted to be 50°C, but this has not been directly measured. The purpose of this study was to directly measure the tissue temperature at the edge of radiofrequency lesions in real time using infrared thermal imaging. Fifteen radiofrequency lesions of 6 to 240 seconds in duration were applied to the left ventricular surface of isolated perfused pig hearts. At the end of radiofrequency delivery, a thermal image of the tissue surface was acquired with an infrared camera. The lesion was then stained and an optical image of the lesion was obtained. The thermal and optical images were electronically merged to allow determination of the tissue temperature at the edge of the lesion at the end of radiofrequency delivery. By adjusting the temperature overlay display to conform with the edge of the radiofrequency lesion, the lethal isotherm was measured to be 60.6°C (interquartile ranges, 59.7° to 62.4°C; range, 58.1° to 64.2°C). The areas encompassed by the lesion border in the optical image and the lethal isotherm in the thermal image were statistically similar and highly correlated (Spearman ρ=0.99, P<0.001). The lethal isotherm temperature was not related to the duration of radiofrequency delivery or to lesion size (both P>0.64). The areas circumscribed by 50°C isotherms were significantly larger than the areas of the lesions on optical imaging (P=0.002). By direct measurement, the lethal isotherm for cardiac myocardium is near 61°C for radiofrequency energy deliveries <240 seconds in duration. A 50°C isotherm overestimates lesion size. Accurate knowledge of the lethal isotherm for radiofrequency ablation is important to clinical practice as well as mathematical modeling of radiofrequency lesions.

Histological findings in protocol biopsies following pediatric liver transplant: Low incidence of abnormalities at 5 years.

PubMed

Sheikh, Amin; Chau, Kai Y; Evans, Helen M

2018-05-11

Histological abnormalities, including chronic hepatitis, fibrosis, and steatosis, are increasingly reported in liver biopsies of children after LT. These changes may be progressive and represent a form of rejection. Liver biochemistry is often initially normal. Our LT program began in 2002, utilizing tacrolimus and low-dose steroids for the first year post-LT. Patients undergo a protocol biopsy at 1 year post-LT prior to stopping steroids, then at 5 years and every 5 years thereafter. Target tacrolimus levels are 5-8 μg/L and 3-5 μg/L after 3 and 12 months, respectively. Between 2002 and 2009, 51 LT were performed; 50 (98%) and 49 (96%) patients survived for 1 and 5 years, respectively. A total of 43 patients (median age at LT 2.3 years) underwent a protocol biopsy at 1 year (16 male; median time post-LT 12.5 months), and 44 (20 male; median time post-LT 5.1 years) at 5 years. By 5 years, 3 had transferred to adult services; 1 was re-transplanted for graft failure and 1 moved overseas. Biopsies were reviewed by 2 pathologists. Most patients (31/44) were on tacrolimus monotherapy at 5 years. At 1 and 5 years, 29 of 43 (67.5%) and 31 of 44 (71%) biopsies were normal, respectively. Two of 44 had chronic allograft hepatitis at 5 years. Two of 43 and 1 of 44 had isolated fibrosis, 3 of 43 and 3 of 44 steatosis, and 3 of 43 and 4 of 44 acute rejection at 1 and 5 years, respectively. Other findings included predominantly biliary changes (6/43 & 3/44 at 1 and 5 years, respectively). Tacrolimus levels at 5 years were slightly higher than anticipated (median trough level 5.8 μg/L). With an immunosuppressive regimen of tacrolimus and low-dose steroids for 1 year followed by tacrolimus monotherapy thereafter, the majority of PLB were normal and no progressive changes were observed at 5 years. Compared to other LT programs, we have lower rates of chronic allograft hepatitis, steatosis, and fibrosis at 5 years. However, the tacrolimus levels at 5 years were higher than planned and this may have played a role. Further evaluation is also required to determine the potential long-term adverse effects of corticosteroid use on linear growth and bone mineral density. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Potential for hypobaric storage as a phytosanitary treatment: mortality of Rhagoletis pomonella (Diptera: Tephritidae) in apples and effects on fruit quality.

PubMed

Hulasare, Rajshekhar; Payton, Mark E; Hallman, Guy J; Phillips, Thomas W

2013-06-01

The efficacy of low-oxygen atmospheres using low pressure, referred to as hypobaric conditions, to kill egg and third-instar Rhagoletis pomonella (Walsh) in apples was investigated. Infested apples were exposed to 3.33 and 6.67 kPa in glass jars at 25 and 30 degrees C for times ranging from 3 to 120 h. Probit analyses and lethal dose ratio tests were performed to determine differences in lethal time values. Eggs were more tolerant of low pressure compared with third-instar R. pomonella. Mortality of eggs and larvae increased with increase in time of exposure to low pressure and temperature. Lower pressures increased percent mortality of eggs, but these values were not significantly different at the pressures tested in this investigation. The LT99 for R. pomonella eggs at 3.33 kPa was 105.98 and 51.46 h, respectively, at 25 and 30 degrees C, which was a significant effect of the higher temperature on egg mortality. Investigation into consumer acceptance of low-pressure-treated apples was done with 'Red Delicious' and 'Golden Delicious'. Apples exposed to 3.33 kPa at 25 and 30 degrees C for 3 and 5 d were stored at 1 degrees C for 2 wk and presented to a sensory panel for evaluation. The panelists rated treated apples with untreated controls for external and internal appearance and taste. Golden Delicious apples were unaffected for all three sensory factors across both temperatures and exposure times. Although taste was unaffected for Red Delicious, the internal and external appearances deteriorated. Use of low pressure for disinfestation and preservation of apples is a potential nonchemical alternative to chemical fumigants such as methyl bromide and phosphine.

Prophylactic Administration of Bacterially Derived Immunomodulators Improves the Outcome of Influenza Virus Infection in a Murine Model▿

PubMed Central

Norton, Elizabeth B.; Clements, John D.; Voss, Thomas G.; Cárdenas-Freytag, Lucia

2010-01-01

Prophylactic or therapeutic immunomodulation is an antigen-independent strategy that induces nonspecific immune system activation, thereby enhancing host defense to disease. In this study, we investigated the effect of prophylactic immunomodulation on the outcome of influenza virus infection using three bacterially derived immune-enhancing agents known for promoting distinct immunological profiles. BALB/c mice were treated nasally with either cholera toxin (CT), a mutant form of the CT-related Escherichia coli heat-labile enterotoxin designated LT(R192G), or CpG oligodeoxynucleotide. Mice were subsequently challenged with a lethal dose of influenza A/PR/8/34 virus 24 h after the last immunomodulation treatment and either monitored for survival or sacrificed postchallenge for viral and immunological analysis. Treatment with the three immunomodulators prevented or delayed mortality and weight loss, but only CT and LT(R192G) significantly reduced initial lung viral loads as measured by plaque assay. Analysis performed 4 days postinfection indicated that prophylactic treatments with CT, LT(R192G), or CpG resulted in significantly increased numbers of CD4 T cells, B cells, and dendritic cells and altered costimulatory marker expression in the airways of infected mice, coinciding with reduced expression of pulmonary chemokines and the appearance of inducible bronchus-associated lymphoid tissue-like structures in the lungs. Collectively, these results suggest that, despite different immunomodulatory mechanisms, CT, LT(R192G), and CpG induce an initial inflammatory process and enhance the immune response to primary influenza virus challenge while preventing potentially damaging chemokine expression. These studies provide insight into the immunological parameters and immune modulation strategies that have the potential to enhance the nonspecific host response to influenza virus infection. PMID:20053748

Lethal and sub-lethal effects of cyproconazole on freshwater organisms: a case study with Chironomus riparius and Dugesia tigrina.

PubMed

Saraiva, Althiéris S; Sarmento, Renato A; Golovko, Oksana; Randak, Tomas; Pestana, João L T; Soares, Amadeu M V M

2018-04-01

The fungicide cyproconazole (CPZ) inhibits the biosynthesis of ergosterol, an essential sterol component in fungal cell membrane and can also affect non-target organisms by its inhibitory effects on P450 monooxygenases. The predicted environmental concentration of CPZ is up to 49.05 μg/L and 145.89 μg/kg in surface waters and sediments, respectively, and information about CPZ toxicity towards non-target aquatic organisms is still limited. This study aimed to address the lack of ecotoxicological data for CPZ, and thus, an evaluation of the lethal and sub-lethal effects of CPZ was performed using two freshwater invertebrates (the midge Chironomus riparius and the planarian Dugesia tigrina). The estimated CPZ 48 h LC 50 (95% CI) was 17.46 mg/L for C. riparius and 47.38 mg/L for D. tigrina. The emergence time (EmT 50 ) of C. riparius was delayed by CPZ exposure from 0.76 mg/L. On the other hand, planarians showed higher tolerance to CPZ exposure. Sub-lethal effects of CPZ on planarians included reductions in locomotion (1.8 mg/L), delayed photoreceptors regeneration (from 0.45 mg/L), and feeding inhibition (5.6 mg/L). Our results confirm the moderate toxicity of CPZ towards aquatic invertebrates but sub-lethal effects observed also suggest potential chronic effects of CPZ with consequences for population dynamics.

Temperature and humidity effects on off-host survival of the Northern fowl mite (Acari: Macronyssidae) and the chicken body louse (Phthiraptera: Menoponidae).

PubMed

Chen, Brian L; Mullens, Bradley A

2008-04-01

Off-host survival of the northern fowl mite, Ornithonyssus sylviarum (Canestrini & Fanzago) (Acari: Macronyssidae), and the chicken body louse, Menacanthus stramineus (Nitzsch) (Phthiraptera: Menoponidae), was studied at 12 combinations of temperature (15, 21, 27, and 33 degrees C) and humidity (31, 65, and 85% RH). Mite protonymphs and louse third instars survived longer on average than the respective adult stages. Higher temperatures significantly reduced survival of adult and immature stages of both ectoparasites, whereas relative humidity had significant effects on O. sylviarum (especially protonymphs) but not M. stramineus. The LT50 values for adult northern fowl mites ranged from 1.9 (at 33 degrees C, 31%RH) to 8.3 d (at 15 degrees C, 85%RH), LT50 values for mite protonymphs ranged from 2.0 (at 33 degrees C, 31%RH) to 18.1 d (at 15 degrees C, 85%RH), LT50 values for adult lice ranged from 0.5 (at 33 degrees C, 31%RH) to 1.7 d (at 15 degrees C, 65%RH), and LT50 values for nymphal lice ranged from 1.2 (at 33 degrees C, 65%RH) to 3.3 d (at 21 degrees C, 31%RH). Maximum survival of the northern fowl mite was up to 35 d for adults and 29 d for protonymphs. Maximum survival for the chicken body louse was 3.3 d for adults and 5.8 d for nymphs. The data provide minimum guidelines for leaving poultry houses vacant long enough to allow ectoparasites to die before introduction of subsequent new flocks.

The hemostatic profile of recombinant activated factor VII. Can low concentrations stop bleeding in off-label indications?

PubMed Central

2010-01-01

Background High concentrations of recombinant activated factor VII (rFVIIa) can stop bleeding in hemophilic patients. However the rFVIIa dose needed for stopping haemhorrage in off-label indications is unknown. Since thrombin is the main hemostatic agent, this study investigated the effect of rFVIIa and tissue factor (TF) on thrombin generation (TG) in vitro. Methods Lag time (LT), time to peak (TTP), peak TG (PTG), and area under the curve after 35 min (AUCo-35 min) with the calibrated automated thrombography was used to evaluate TG. TG was assayed in platelet-rich plasma (PRP) samples from 29 healthy volunteers under basal conditions and after platelet stimulation with 5.0 μg/ml, 2.6 μg/ml, 0.5 μg/ml, 0.25 μg/ml, and 0.125 μg/ml rFVIIa alone and in normal platelet-poor plasma (PPP) samples from 22 healthy volunteers, rFVIIa in combination with various concentrations of TF (5.0, 2.5, 1.25 and 0.5 pM). Results In PRP activated by rFVIIa, there was a statistically significant increase in TG compared to basal values. A significant TF dose-dependent shortening of LT and increased PTG and AUCo→35 min were obtained in PPP. The addition of rFVIIa increased the effect of TF in shorting the LT and increasing the AUCo→35 min with no effect on PTG but were independent of rFVIIa concentration. Conclusion Low concentrations of rFVIIa were sufficient to form enough thrombin in normal PRP or in PPP when combined with TF, and suggest low concentrations for normalizing hemostasis in off-label indications. PMID:20444280

Experimental and numerical investigation of DNAPL infiltration and spreading in a 2-D sandbox by means of light transmission method

NASA Astrophysics Data System (ADS)

Zheng, F.; Shi, X.; Wu, J.; Gao, Y. W.

2013-12-01

Chlorinated solvents such as trichloroethene (TCE) and tetrachloroethene (PCE) are widespread groundwater contaminants often referred to as dense non-aqueous phase liquids (DNAPLs). Accuracy description of the spreading behavior and configuration for subsurface DNAPL migration is important, especially favourable for design effective remediation strategies. In this study, a 2-D experiment was conducted to investigate the infiltration behavior and spatial distribution of PCE in saturated porous media. Accusand 20/30 mesh sand (Unimin, Le Sueur, MN) was used as the background medium with two 70/80 and 60/70 mesh lenses embedded to simulate heterogeneous conditions. Dyed PCE of 100 ml was released into the flow cell at a constant rate of 2ml/min using a Harvard Apparatus syringe pump with a 50 ml glass syringe for two times, and 5 ml/min water was continuously injected through the inlet at the left side of the sandbox, while kept the same effluent rate at right side to create hydrodynamic condition. A light transmission (LT) system was used to record the migration of PCE and determine the saturation distribution of PCE in the sandbox experiment with a thermoelectrically air-cooled charged-coupled device (CCD) camera. All images were processed using MATLAB to calculate thickness-averaged PCE saturation for each pixel. Mass balance was checked through comparing injected known mounts of PCE with that calculated from LT analysis. Results showed that LT method is effective to delineate PCE migration pathways and quantify the saturation distribution. The relative errors of total PCE volumes calculated by LT analysis at different times were within 15% of the injected PCE volumes. The simulation are conducted using the multiphase modeling software T2VOC, which calibrated by the LT analysis results of three recorded time steps to fit with the complete spatial-temporal distribution of the PCE saturation. Model verification was then performed using the other eight recorded time steps. Simulated results showed that the model could successfully reproduce the migration pathways and distribution configuration observed from the laboratory experiment and LT analysis, excepted for a smaller pool height on the lenses, and a lower saturation values in PCE accumulation area due to local heterogeneities. Due to the influence of water flow, the PCE distribution was asymmetrical, and the PCE distribution area, pool height as well as PCE saturation in the accumulation region at right side was much greater. Acknowledge: This work is financially supported by the National Nature Science Foundation of China grants No. 41030746 and 41172206.

Lethal and sub-lethal effects of five pesticides used in rice farming on the earthworm Eisenia fetida.

PubMed

Rico, Andreu; Sabater, Consuelo; Castillo, María-Ángeles

2016-05-01

The toxicity of five pesticides typically used in rice farming (trichlorfon, dimethoate, carbendazim, tebuconazole and prochloraz) was evaluated on different lethal and sub-lethal endpoints of the earthworm Eisenia fetida. The evaluated endpoints included: avoidance behaviour after an exposure period of 2 days; and mortality, weight loss, enzymatic activities (cholinesterase, lactate dehydrogenase and alkaline phosphatase) and histopathological effects after an exposure period of 14 days. Carbendazim was found to be highly toxic to E. fetida (LC50=2mg/kg d.w.), significantly reducing earthworm weight and showing an avoidance response at soil concentrations that are close to those predicted in rice-fields and in surrounding ecosystems. The insecticide dimethoate showed a moderate acute toxicity (LC50=28mg/kg d.w.), whereas the rest of tested pesticides showed low toxicity potential (LC50 values above 100mg/kg d.w.). For these pesticides, however, weight loss was identified as a sensitive endpoint, with NOEC values approximately 2 times or lower than the calculated LC10 values. The investigated effects on the enzymatic activities of E. fetida and the observed histopathological alterations (longitudinal and circular muscle lesions, edematous tissues, endothelial degeneration and necrosis) proved to be sensitive biomarkers to monitor pesticide contamination and are proposed as alternative measures to evaluate pesticide risks on agro-ecosystems. Copyright © 2016 Elsevier Inc. All rights reserved.

Popularity of Russian information sources of medical education.

PubMed

Vasilyeva, Irina V; Arseniev, Sergey B

2014-01-01

The aim of the present study is to analyze the popularity of information sources of medical educational sites <webmedinfo.ru>, medical information portal <meduniver.com>, medical portal for students <6years.net>, electronic library of medical literature <booksmed.com>, <medliter.ru> and <medbook.net.ru>. Three sites (<www.webmedinfo.ru>, <meduniver.com> and <6years.net>) provide sources of medical literature, educational videos, medical histories, medical papers and medical popular literature. And three other sites (<www.booksmed.com>, <www.medliter.ru> and <www.medbook.net.ru>) provide sources for electronic medical books on various subjects. Using on-line programs Alexa and Cy-pr we have analyzed the website's rating and identified the main data and time-varying data of the sites. Calculated Alexa Rank rating was determined for each site. Our study has shown that the most popular information sources of medical education among the six studied sites for Russian users is <meduniver.com>; the site <booksmed.com> is at the second place referring to the Alexa Rank rating and the site <webmedinfo.ru> is at the second place referring to the citation index in Yandex. The most popular medical site of electronic medical books is <booksmed.com>.

Mechanisms Relevant to the Enhanced Virulence of a Dihydroxynaphthalene-Melanin Metabolically Engineered Entomopathogen

PubMed Central

Tseng, Min-Nan; Chung, Chia-Ling; Tzean, Shean-Shong

2014-01-01

The entomopathogenic fungus Metarhizium anisopliae MA05-169 is a transformant strain that has been metabolically engineered to express dihydroxynaphthalene-melanin biosynthesis genes. In contrast to the wild type strain, the transformant displays a greater resistance to environmental stress and a higher virulence toward target insect host. However, the underlying mechanisms for these characteristics remain unclear; hence experiments were initiated to explore the possible mechanism(s) through physiological and molecular approaches. Although both transformant and wild type strains could infect and share the same insect host range, the former germinated faster and produced more appressoria than the latter, both in vivo and in vitro. The transformant showed a significantly shorter median lethal time (LT50) when infecting the diamondback moth (Plutella xylostella) and the striped flea beetle (Phyllotreta striolata), than the wild type. Additionally, the transformant was more tolerant to reactive oxygen species (ROS), produced 40-fold more orthosporin and notably overexpressed the transcripts of the pathogenicity-relevant hydrolytic enzymes (chitinase, protease, and phospholipase) genes in vivo. In contrast, appressorium turgor pressure and destruxin A content were slightly decreased compared to the wild type. The transformant's high anti-stress tolerance, its high virulence against five important insect pests (cowpea aphid Aphis craccivora, diamondback moth Pl. xylostella, striped flea beetle Ph. striolata, and silverleaf whitefly Bemisia argentifolii) and its capacity to colonize the root system are key properties for its potential bio-control field application. PMID:24662974

Electronic and Thermal Effects in the Insulator-Metal Phase Transition in VO2 Nano-Gap Junctions

DTIC Science & Technology

2014-11-27

VO2 , air, or SiO2, the 2 -0.50 -0.25 0.00 0.25 0.50 0 2 4 6 V Gap V App V o lt ag e (V ) time (ms) t p V I→M V M→I 100 400 700 1000 0.0 2.5 5.0 7.5...Electronic and thermal effects in the insulator-metal phase transition in VO2 nano-gap junctions Arash Joushaghani,1 Junho Jeong,1 Suzanne Paradis,2...Canada (Dated: 27 November 2014) By controlling the thermal transport of VO2 nano-gap junctions using device geometry, contact material, and applied

Pneumonia relevant to lung transplantation and pathogen distribution.

PubMed

He, Xuan; Dai, Hua-Ping; Chen, Qi-Rui; Miao, Jin-Bai; Sun, Bing; Bao, Na; Hu, Bin; Li, Hui; Wu, An-Shi; Ban, Cheng-Jun; Ge, Su-Juan; Wang, Chen; Hou, Sheng-Cai

2013-01-01

Pneumonia is the most common cause of morbidity and mortality in lung transplant (LT) recipients. The aim of the present study was to evaluate the incidence, etiology, risk factors and prognosis of pneumonia in LT recipients. The LT cohort consisted of 28 recipients receiving LT in Beijing Chao-Yang Hospital from August 2005 to April 2011. Data collected included demographic data, underlying disorders, time and type of transplant, follow-up information, date of last follow-up, and patient status. A retrospective analysis was made of observational data that were prospectively collected. Twenty-two patients of 28 LT recipients had 47 episodes of pneumonia throughout the study period. Thirtyeight episodes of pneumonia in 19 recipients occurred post-LT with a median follow-up of 257.5 days (1-2104 days), the incidence of pneumonia was 192.4 episodes per 100 LT/year and its median time of onset was 100.5 days (0-946 days) post-transplantation. Bacteria, virus and fungi accounted for 62%, 16% and 15% of the microbial pathogens, respectively. The most frequent were Pseudomonas aeruginosa (20%), cytomegalovirus (CMV) (15%), and Aspergillus fumigatus (10%). A total of 29% (11/38) of pneumonias occurred in the first month post-LT, and then the incidence decreased gradually. The incidence of CMV pneumonia was 25% (7/28) with a median time of 97 days (10-971 days). More than one bacterial infection and CMV infection were independent risk factors for aspergillus infection. The incidence of pulmonary tuberculosis (TB) was 18% (5/28), and the history of TB was a risk factor for TB relapse. There were 58% (7/12) of recipients who died of infection, and 71% (5/7) of these died in the first year after LT. Pneumonia is still a major cause of morbidity and mortality in LT recipients. The most frequent microorganisms were Pseudomonas aeruginosa, CMV, and Aspergillus fumigates. The incidence of CMV pneumonia decreases with a delayed median time of onset. More than one incidence of bacterial infection and CMV infection are independent risk factors for aspergillus infection. LT recipients are at high risk for TB, and the history of TB is a risk factor for TB relapse.

Hepatic encephalopathy in a liver transplant recipient with stable liver function.

PubMed

Arab, Juan Pablo; Meneses, Luis; Pérez, Rosa M; Arrese, Marco; Benítez, Carlos

2013-04-01

Postshunt hepatic encephalopathy after liver transplantation (LT) is an infrequent condition and is commonly associated with portal occlusion or stenosis and the presence of a patent portosystemic shunt. Portal vein stenosis (PVS) or thrombosis (PVT) are uncommon complications after LT. The overall frequency of both complications is reported to be less than 3%. When PVS or PVT develop early after LT, the occlusion of the portal vein can have catastrophic consequences to the graft including acute liver failure and graft loss. Late PVT/PVS are asymptomatic in approximately 50% of the cases and mainly diagnosed by a routine ultrasound. Symptomatic postshunt hepatic encephalopathy (HE) is a very infrequent condition after LT that has been scarcely reported in the literature. We present here the case of a liver recipient with normal graft function who presented with hepatic encephalopathy 3 months after LT with stable liver function but a severe portal stenosis and the presence of a spontaneous portosystemic shunt whose successful endovascular treatment was followed by the complete resolution of the HE.

Acute, sublethal, and combination effects of azadirachtin and Bacillus thuringiensis on the cotton bollworm, Helicoverpa armigera.

PubMed

Abedi, Zahra; Saber, Moosa; Vojoudi, Samad; Mahdavi, Vahid; Parsaeyan, Ehsan

2014-02-26

The cotton bollworm, Helicoverpa armigera Hübner (Lepidoptera: Noctuidae) is a polyphagous and cosmopolitan insect pest that causes damage to various plants. In this study, the lethal and sublethal effects of azadirachtin and Bacillus thuringiensis Berliner sub sp . kurstaki (Bacillales: Bacillaceae) were evaluated on third instar H. armigera under laboratory conditions. The LC50 values of azadirachtin and Bt were 12.95 and 96.8 µg a.i./mL, respectively. A total mortality of 56.7% was caused on third instar larvae when LC20 values of the insecticides were applied in combination with each other. The LT50 values of azadirachtin and Bt were 4.8 and 3.6 days, respectively. The results of the sublethal study showed that the application of LC30 value of azadirachtin and Bt reduced the larval and pupal weight and increased larval and pupal duration of H. armigera. The longevity and fecundity of female adults were affected significantly by the insecticides. Female fecundity was reduced by the treatments, respectively. The lowest adult emergence ratio and pupation ratio were observed in the azadirachtin treatment. The results indicated that both insecticides have high potential for controlling of the pest. This is an open access paper. We use the Creative Commons Attribution 3.0 license that permits unrestricted use, provided that the paper is properly attributed.

Core Body Temperature as Adjunct to Endpoint Determination in Murine Median Lethal Dose Testing of Rattlesnake Venom

PubMed Central

Cates, Charles C; McCabe, James G; Lawson, Gregory W; Couto, Marcelo A

2014-01-01

Median lethal dose (LD50) testing in mice is the ‘gold standard’ for evaluating the lethality of snake venoms and the effectiveness of interventions. As part of a study to determine the murine LD50 of the venom of 3 species of rattlesnake, temperature data were collected in an attempt to more precisely define humane endpoints. We used an ‘up-and-down’ methodology of estimating the LD50 that involved serial intraperitoneal injection of predetermined concentrations of venom. By using a rectal thermistor probe, body temperature was taken once before administration and at various times after venom exposure. All but one mouse showed a marked, immediate, dose-dependent drop in temperature of approximately 2 to 6 °C at 15 to 45 min after administration. The lowest temperature sustained by any surviving mouse was 33.2 °C. Surviving mice generally returned to near-baseline temperatures within 2 h after venom administration, whereas mice that did not survive continued to show a gradual decline in temperature until death or euthanasia. Logistic regression modeling controlling for the effects of baseline core body temperature and venom type showed that core body temperature was a significant predictor of survival. Linear regression of the interaction of time and survival was used to estimate temperatures predictive of death at the earliest time point and demonstrated that venom type had a significant influence on temperature values. Overall, our data suggest that core body temperature is a useful adjunct to monitoring for endpoints in LD50 studies and may be a valuable predictor of survival in venom studies. PMID:25527024

Lethal and behavioral impacts of diesel and fuel oil on the Antarctic amphipod Paramoera walkeri.

PubMed

Brown, Kathryn E; King, Catherine K; Harrison, Peter L

2017-09-01

Toxicity testing with Antarctic species is required for risk assessment of fuel spills in Antarctic coastal waters. The lethal and sublethal (movement behavior) sensitivities of adults and juveniles of the Antarctic amphipod Paramoera walkeri to the water accommodated fractions (WAFs) of 3 fuels were estimated in extended-duration tests at -1 °C to 21 d. Response of P. walkeri for lethal hydrocarbon concentrations was slow, with 50% lethal concentrations (LC50s) first able to be estimated at 7 d for adults exposed to Special Antarctic Blend diesel (SAB), which had the highest hydrocarbon concentrations of the 3 fuel WAFs. Juveniles showed greater response to marine gas oil (MGO) and intermediate residual fuel oil (IFO 180) at longer exposure durations and were most sensitive at 21 d to IFO 180 (LC50 = 12 μg/L). Adults were initially more sensitive than juveniles; at 21 d, however, juveniles were more than twice as sensitive as adults to SAB (LC50 = 153 μg/L and 377 μg/L, respectively). Significant effects on movement behavior were evident at earlier time points and lower concentrations than was mortality in all 3 fuel WAFs, and juveniles were highly sensitive to sublethal effects of MGO. These first estimates of Antarctic amphipod sensitivity to diesel and fuel oils in seawater contribute to the development of ecologically relevant risk assessments for management of hydrocarbon contamination in the region. Environ Toxicol Chem 2017;36:2444-2455. © 2017 SETAC. © 2017 SETAC.

Minimizing tacrolimus decreases the risk of new-onset diabetes mellitus after liver transplantation

PubMed Central

Song, Jiu-Lin; Gao, Wei; Zhong, Yan; Yan, Lu-Nan; Yang, Jia-Yin; Wen, Tian-Fu; Li, Bo; Wang, Wen-Tao; Wu, Hong; Xu, Ming-Qing; Chen, Zhe-Yu; Wei, Yong-Gang; Jiang, Li; Yang, Jian

2016-01-01

AIM: To investigate the impact of minimum tacrolimus (TAC) on new-onset diabetes mellitus (NODM) after liver transplantation (LT). METHODS: We retrospectively analyzed the data of 973 liver transplant recipients between March 1999 and September 2014 in West China Hospital Liver Transplantation Center. Following the exclusion of ineligible recipients, 528 recipients with a TAC-dominant regimen were included in our study. We calculated and determined the mean trough concentration of TAC (cTAC) in the year of diabetes diagnosis in NODM recipients or in the last year of the follow-up in non-NODM recipients. A cutoff of mean cTAC value for predicting NODM 6 mo after LT was identified using a receptor operating characteristic curve. TAC-related complications after LT was evaluated by χ2 test, and the overall and allograft survival was evaluated using the Kaplan-Meier method. Risk factors for NODM after LT were examined by univariate and multivariate Cox regression. RESULTS: Of the 528 transplant recipients, 131 (24.8%) developed NODM after 6 mo after LT, and the cumulative incidence of NODM progressively increased. The mean cTAC of NODM group recipients was significantly higher than that of recipients in the non-NODM group (7.66 ± 3.41 ng/mL vs 4.47 ± 2.22 ng/mL, P < 0.05). Furthermore, NODM group recipients had lower 1-, 5-, 10-year overall survival rates (86.7%, 71.3%, and 61.1% vs 94.7%, 86.1%, and 83.7%, P < 0.05) and allograft survival rates (92.8%, 84.6%, and 75.7% vs 96.1%, 91%, and 86.1%, P < 0.05) than the others. The best cutoff of mean cTAC for predicting NODM was 5.89 ng/mL after 6 mo after LT. Multivariate analysis showed that old age at the time of LT (> 50 years), hypertension pre-LT, and high mean cTAC (≥ 5.89 ng/mL) after 6 mo after LT were independent risk factors for developing NODM. Concurrently, recipients with a low cTAC (< 5.89 ng/mL) were less likely to become obese (21.3% vs 30.2%, P < 0.05) or to develop dyslipidemia (27.5% vs 44.8%, P <0.05), chronic kidney dysfunction (14.6% vs 22.7%, P < 0.05), and moderate to severe infection (24.7% vs 33.1%, P < 0.05) after LT than recipients in the high mean cTAC group. However, the two groups showed no significant difference in the incidence of acute and chronic rejection, hypertension, cardiovascular events and new-onset malignancy. CONCLUSION: A minimal TAC regimen can decrease the risk of long-term NODM after LT. Maintaining a cTAC value below 5.89 ng/mL after LT is safe and beneficial. PMID:26877618

Evaluation of Dynamic Changes in Rating of Russian Information Sources of Medical Education Sites.

PubMed

Vasilyeva, Irina V; Arseniev, Sergey B

2016-01-01

The aim of the present study is to analyze dynamic changes in the rating of information sources of medical literature in the sites of the following electronic libraries (<rsl.ru>, <rssi.ru>, <elibrary.ru>) and the rating of information sources for electronic medical books (<booksmed.com>, <medliter.ru> <medbook.net.ru>). While using the on-line programs Alexa and Cy-pr, we have analyzed their website's rating and identified basic data and time-varying site data obtained for fourteen months. Alexa Rank rating was calculated for each sitemonthly. Our study has shown that the most popular information sources of medical education among the six studied sites for Russian users is <elibrary.ru>; the site <rssi.ru> is at the second place.

Assessment of Listeria monocytogenes virulence in the Galleria mellonella insect larvae model.

PubMed

Rakic Martinez, Mira; Wiedmann, Martin; Ferguson, Martine; Datta, Atin R

2017-01-01

Several animal models have been used to understand the molecular basis of the pathogenicity, infectious dose and strain to strain variation of Listeria monocytogenes. The greater wax worm Galleria mellonella, as an alternative model, provides some useful advantages not available with other models and has already been described as suitable for the virulence assessment of various pathogens including L. monocytogenes. The objectives of this study are: 1) confirming the usefulness of this model with a wide panel of Listeria spp. including non-pathogenic L. innocua, L. seeligeri, L. welshimeri and animal pathogen L. ivanovii; 2) assessment of virulence of several isogenic in-frame deletion mutants in virulence and stress related genes of L. monocytogenes and 3) virulence assessment of paired food and clinical isolates of L. monocytogenes from 14 major listeriosis outbreaks occurred worldwide between 1980 and 2015. Larvae injected with different concentrations of Listeria were incubated at 37°C and monitored over seven days for time needed to kill 50% of larvae (LT50) and to determine change of bacterial population in G. mellonella, 2 and 24 hours post-inoculation. Non-pathogenic members of Listeria and L. ivanovii showed significantly (P < 0.05) higher LT50 (lower virulence) than the wild type L. monocytogenes strains. Isogenic mutants of L. monocytogenes with the deletions in prfA, plcA, hly, actA and virR genes, also showed significantly (P < 0.05) higher LT50 than the wild type strain at the inoculum of 106CFU/larva. Food isolates had significantly (P < 0.05) lower virulence than the paired clinical isolates, at all three inoculum concentrations. L. monocytogenes strains related to non-invasive (gastroenteritis) outbreaks of listeriosis showed significantly (P < 0.05) lower virulence than isolates of the same serotype obtained from outbreaks with invasive symptoms. The difference, however, was dose and strain- dependent. No significant differences in virulence were observed among the serotype tested in this study.

Assessment of Listeria monocytogenes virulence in the Galleria mellonella insect larvae model

PubMed Central

Rakic Martinez, Mira; Ferguson, Martine; Datta, Atin R.

2017-01-01

Several animal models have been used to understand the molecular basis of the pathogenicity, infectious dose and strain to strain variation of Listeria monocytogenes. The greater wax worm Galleria mellonella, as an alternative model, provides some useful advantages not available with other models and has already been described as suitable for the virulence assessment of various pathogens including L. monocytogenes. The objectives of this study are: 1) confirming the usefulness of this model with a wide panel of Listeria spp. including non-pathogenic L. innocua, L. seeligeri, L. welshimeri and animal pathogen L. ivanovii; 2) assessment of virulence of several isogenic in-frame deletion mutants in virulence and stress related genes of L. monocytogenes and 3) virulence assessment of paired food and clinical isolates of L. monocytogenes from 14 major listeriosis outbreaks occurred worldwide between 1980 and 2015. Larvae injected with different concentrations of Listeria were incubated at 37°C and monitored over seven days for time needed to kill 50% of larvae (LT50) and to determine change of bacterial population in G. mellonella, 2 and 24 hours post-inoculation. Non-pathogenic members of Listeria and L. ivanovii showed significantly (P < 0.05) higher LT50 (lower virulence) than the wild type L. monocytogenes strains. Isogenic mutants of L. monocytogenes with the deletions in prfA, plcA, hly, actA and virR genes, also showed significantly (P < 0.05) higher LT50 than the wild type strain at the inoculum of 106CFU/larva. Food isolates had significantly (P < 0.05) lower virulence than the paired clinical isolates, at all three inoculum concentrations. L. monocytogenes strains related to non-invasive (gastroenteritis) outbreaks of listeriosis showed significantly (P < 0.05) lower virulence than isolates of the same serotype obtained from outbreaks with invasive symptoms. The difference, however, was dose and strain- dependent. No significant differences in virulence were observed among the serotype tested in this study. PMID:28898264

New levothyroxine formulation meeting 95-105% specification over the whole shelf-life: results from two pharmacokinetic trials.

PubMed

Gottwald-Hostalek, Ulrike; Uhl, Wolfgang; Wolna, Peter; Kahaly, George J

2017-02-01

Small levothyroxine (L-T4) dose changes can lead to significant clinical effects. To ensure thyroid hormone levels are safely maintained, authorities are increasingly adopting stricter potency specifications for L-T4, the most stringent of these being 95-105% of the labeled dose over the whole shelf-life. Levothyroxine sodium (Euthyrox, Eutirox, Lévothyrox ) has been reformulated, and two studies performed, to ensure bioequivalence to the currently marketed formulation and dosage form proportionality of the new formulation. The bioequivalence study was an open-label, randomized, single-dose, two-period, two-sequence crossover comparing the highest dosage strengths of the currently marketed and the new L-T4 formulation at a total dose of 600 μg. The dosage form proportionality study was an open-label, randomized, three-period, six-sequence crossover, comparing 50 μg, 100 μg, and 200 μg L-T4 tablets, at a total dose of 600 μg. Blood samples were taken at predefined time intervals. Primary outcomes were area under the curve (AUC) and maximum concentration (C max ) of thyroxine (T4) in plasma. In the bioequivalence study, comparing the T4 profiles for the new and current formulation of L-T4, the geometric least square mean ratio of the baseline-adjusted AUC 0-72,adj was 99.3% (90% confidence interval [CI]: 95.6-103.2) and the C max,adj was 101.7% (90% CI: 98.8-104.6). Bioequivalence was established if the 90% CI lay within the predefined 0.9-1.11 limits. In the dosage form proportionality study, pairwise comparisons ranged from 99.3% to 104.8%, and all 95% CIs were within the predefined CI range (0.8-1.25): the three dose strengths were dosage form proportional. The new formulation of L-T4 meets the most stringent potency specification guidelines, and has been demonstrated to be bioequivalent to the current formulation and to show dosage form proportionality. The new formulation will enable patients to receive a dose fine tuned to their medical needs, contributing to improved safety in the use of L-T4.

The Rate of Core Collapse Supernovae to Redshift 2.5 from the CANDELS and CLASH Supernova Surveys

NASA Astrophysics Data System (ADS)

Strolger, Louis-Gregory; Dahlen, Tomas; Rodney, Steven A.; Graur, Or; Riess, Adam G.; McCully, Curtis; Ravindranath, Swara; Mobasher, Bahram; Shahady, A. Kristin

2015-11-01

The Cosmic Assembly Near-infrared Deep Extragalactic Legacy Survey and Cluster Lensing And Supernova survey with Hubble multi-cycle treasury programs with the Hubble Space Telescope (HST) have provided new opportunities to probe the rate of core-collapse supernovae (CCSNe) at high redshift, now extending to z≈ 2.5. Here we use a sample of approximately 44 CCSNe to determine volumetric rates, RCC, in six redshift bins in the range 0.1\\lt z\\lt 2.5. Together with rates from our previous HST program, and rates from the literature, we trace a more complete history of {R}{CC}(z), with {R}{CC}=0.72+/- 0.06 yr-1 Mpc-3 10-4{h}703 at z\\lt 0.08, and increasing to {3.7}-1.6+3.1 yr-1 Mpc-3 10-4{h}703 to z≈ 2.0. The statistical precision in each bin is several factors better than than the systematic error, with significant contributions from host extinction, and average peak absolute magnitudes of the assumed luminosity functions for CCSN types. Assuming negligible time delays from stellar formation to explosion, we find these composite CCSN rates to be in excellent agreement with cosmic star formation rate density (SFRs) derived largely from dust-corrected rest-frame UV emission, with a scaling factor of k=0.0091+/- 0.0017 {M}⊙ -1, and inconsistent (to \\gt 95% confidence) with SFRs from IR luminous galaxies, or with SFR models that include simple evolution in the initial mass function over time. This scaling factor is expected if the fraction of the IMF contributing to CCSN progenitors is in the 8-50 M⊙ range. It is not supportive, however, of an upper mass limit for progenitors at \\lt 20 {M}⊙ .

Occurrence of thyroxine tablet (Thyradin S(®)) - induced liver dysfunction in a patient with subclinical hypothyroidism.

PubMed

Kang, Shino; Amino, Nobuyuki; Kudo, Takumi; Nishihara, Eijun; Ito, Mitsuru; Hirokawa, Mitsuyoshi; Miyauchi, Akira; Tamada, Daisuke; Yasuda, Takenori

2015-01-01

A 54-year-old woman with subclinical hypothyroidism developed liver dysfunction after increasing dose of levothyroxine (L-T4) in tablet form (Thyradin S(®)) from 25μg to 50μg. Viral hepatitis, autoimmune hepatitis and NASH were ruled out with examinations. After cessation of levothyroxine in 50μg tablet form, liver enzymes gradually returned to normal. She was diagnosed levothyroxine-induced liver injury, based on criteria proposed in DDW-J 2004 workshop. Thyradin S(®) powder 0.01% (here in after referred to as L-T4 in powder form) was tried as an alternative, and liver enzymes have remained within normal range. As for Thyradin S(®) tablet, additives are different for each type of levothyroxine sodium content. The difference of additive is whether Fe2O3 is contained or not: it is not included in Thyradin S(®) 50μg tablet and powder form. Although there are two case reports in the Japanese literature and three case reports in the English literature of liver dysfunction suspected due to L-T4, we cannot find past reports about cases of drug induced liver dysfunction due to Fe2O3 free levothyroxine tablet form. This is a rare case report of drug induced liver injury due to Fe2O3 free levothyroxine tablet form, and administration of L-T4 in powder form may be useful for treatment of cases similar to this one.

Effects of cholinergic and beta-adrenergic blockade on orthostatic tolerance in healthy subjects

NASA Technical Reports Server (NTRS)

Convertino, V. A.; Sather, T. M.

2000-01-01

Cardiovascular responses during a graded lower body negative pressure (LBNP) protocol were compared before and after atropine and propranolol administration to test the hypothesis that both sympathetic and parasympathetic control of cardio-acceleration are associated with syncopal predisposition to orthostatic stress in healthy subjects. Eleven men were categorized into two groups having high (HT, N = 6) or low (LT, N = 5) tolerance based on their total time before the onset of presyncopal symptoms. HT and LT groups were similar in physical characteristics, fitness, and baseline cardiovascular measurements. Atropine treatment had no effect on LBNP tolerance or mean arterial pressure at presyncope, despite an atropine-induced increase in heart rate. Propranolol treatment reduced (p<0.05) LBNP tolerance in both groups. Diminished LBNP tolerance after propranolol administration was associated with reductions in cardiac output, whereas increase in systemic peripheral resistance from baseline to presyncope was unaffected by propranolol. Reduction in cardiac output and LBNP tolerance after beta blockade reflected a chronotropic effect because lower LBNP tolerance for the HT (-50%) and LT (-39%) groups was associated with dramatic reductions (p <0.05) in the magnitude of LBNP-induced tachycardia without significant effects on stroke volume at presyncope. Absence of an atropine-induced difference in cardiac output and systemic peripheral resistance between HT and LT groups failed to support the notion that cardiac vagal withdrawal represents a predominant mechanism that could account for differences in orthostatic tolerance. Because a reduction in LBNP tolerance in both HT and LT groups after propranolol treatment was most closely associated with reduced tachycardia, the data suggest that a primary autonomically mediated mechanism for maintenance of mean arterial pressure and orthostatic tolerance in healthy subjects is beta adrenergic-induced tachycardia.

A cost-effective, community-based, mosquito-trapping scheme that captures spatial and temporal heterogeneities of malaria transmission in rural Zambia

PubMed Central

2014-01-01

Background Monitoring mosquito population dynamics is essential to guide selection and evaluation of malaria vector control interventions but is typically implemented by mobile, centrally-managed teams who can only visit a limited number of locations frequently enough to capture longitudinal trends. Community-based (CB) mosquito trapping schemes for parallel, continuous monitoring of multiple locations are therefore required that are practical, affordable, effective, and reliable. Methods A CB surveillance scheme, with a monthly sampling and reporting cycle for capturing malaria vectors, using Centers for Disease Control and Prevention light traps (LT) and Ifakara Tent Traps (ITT), were conducted by trained community health workers (CHW) in 14 clusters of households immediately surrounding health facilities in rural south-east Zambia. At the end of the study, a controlled quality assurance (QA) survey was conducted by a centrally supervised expert team using human landing catch (HLC), LT and ITT to evaluate accuracy of the CB trapping data. Active surveillance of malaria parasite infection rates amongst humans was conducted by CHWs in the same clusters to determine the epidemiological relevance of these CB entomological surveys. Results CB-LT and CB-ITT exhibited relative sampling efficiencies of 50 and 7%, respectively, compared with QA surveys using the same traps. However, cost per sampling night was lowest for CB-LT ($13.6), followed closely by CB-ITT ($18.0), both of which were far less expensive than any QA survey (HLC: $138, LT: $289, ITT: $269). Cost per specimen of Anopheles funestus captured was lowest for CB-LT ($5.3), followed by potentially hazardous QA-HLC ($10.5) and then CB-ITT ($28.0), all of which were far more cost-effective than QA-LT ($141) and QA-ITT ($168). Time-trends of malaria diagnostic positivity (DP) followed those of An. funestus density with a one-month lag and the wide range of mean DP across clusters was closely associated with mean densities of An. funestus caught by CB-LT (P < 0.001). Conclusions CB trapping schemes appear to be far more affordable, epidemiologically relevant and cost-effective than centrally supervised trapping schemes and may well be applicable to enhance intervention trials and even enable routine programmatic monitoring of vector population dynamics on unprecedented national scales. PMID:24906704

Fumigant Toxicity and Sublethal Effects of Artemisia khorassanica and Artemisia sieberi on Sitotroga cerealella (Lepidoptera: Gelechiidae)

PubMed Central

Abedi, Z; Abdolmaleki, A; Jafary-Jahed, M; Borzoui, E; Mozaffar Mansouri, Seyed

2017-01-01

Abstract Fumigant toxicity and sublethal effects of essential oils from Artemisia khorassanica Podl. and Artemisia sieberi Bess were investigated against adults of Sitotroga cerealella Olivier. To assess the sublethal effects, adult moths were exposed to the LC30 of each essential oil, and life table parameters of the surviving S. cerealella were studied. Higher fumigant toxicity of A. khorassanica (LC50: 7.38 µl/liter air) than A. sieberi (LC50: 9.26 µl/liter air) was observed against S. cerealella. Also, the insecticidal effects of A. khorassanica (LT50: 9.01 h) were faster than A. sieberi (LT50: 14.37 h). A significant extension was observed in the developmental time (egg to adult) of S. cerealella treated with the essential oils. In addition, fecundity of S. cerealella reduced by 25.29 and 35.78% following exposure to sublethal concentrations of A. sieberi and A. khorassanica, respectively. Both tested essential oils caused a significant reduction in the gross and net reproductive rates, intrinsic rate of increase (rm), and finite rate of increase of S. cerealella. The rm values following exposure to A. sieberi, A. khorassanica, and control were 0.098, 0.094, and 0.107 d−1, respectively. The results of this study suggest that tested essential oils have a good potential to apply in integrated pest management of S. cerealella. PMID:29117375

A functional and thromboelastometric-based micromethod for assessing crotoxin anticoagulant activity and antiserum relative potency against Crotalus durissus terrificus venom.

PubMed

Prezoto, B C; Tanaka-Azevedo, A M; Marcelino, J R; Tashima, A K; Nishiduka, E S; Kapronezai, J; Mota, J O; Rocha, M M T; Serino-Silva, C; Oguiura, N

2018-06-15

The assessment of the capacity of antivenoms to neutralize the lethal activity of snake venoms still relies on traditional rodent in vivo lethality assay. ED 50 and LD 50 assays require large quantities of venoms and antivenoms, and besides leading to animal suffering. Therefore, in vitro tests should be introduced for assessing antivenom neutralizing capacity in intermediary steps of antivenom production. This task is facilitated when one key lethal toxin is identified. A good example is crotoxin, a β-neurotoxin phospholipase A 2 -like toxin that presents anticoagulant activity in vitro and is responsible for the lethality of venoms of Crotalus durissus snakes. By using rotational thromboelastometry, we reported recently one sensitive coagulation assay for assessing relative potency of the anti-bothropic serum in neutralizing procoagulant activity of Bothrops jararaca venom upon recalcified factor-XII-deficient chicken plasma samples (CPS). In this study, we stablished conditions for determining relative potency of four batches of the anti-crotalic serum (ACS) (antagonist) in inactivating crotoxin anticoagulant activity in CPS (target) simultaneously treated with one classical activator of coagulation (agonists). The correlation coefficient (r) between values related the ACS potency in inactivating both in vitro crotoxin anticoagulant activity and the in vivo lethality of whole venom (ED 50 ) was 0.94 (p value < 0.05). In conclusion, slowness in spontaneous thrombin/fibrin generation even after recalcification elicit time lapse sufficient for elaboration of one dose-response curve to pro- or anti-coagulant agonists in CPS. We propose this methodology as an alternative and sensitive assay for assessing antivenom neutralizing ability in plasma of immunized horses as well as for in-process quality control. Copyright © 2018 Elsevier Ltd. All rights reserved.

Metformin Does Not Suppress Serum Thyrotropin by Increasing Levothyroxine Absorption

PubMed Central

Al-Alusi, Mostafa A.; Du, Lin; Li, Ning; Yeh, Michael W.; He, Xuemei; Braverman, Lewis E.

2015-01-01

Background: Levothyroxine (LT4) absorption is affected by concomitant ingestion of certain minerals, medications, and foods. It has been hypothesized that metformin may suppress serum thyrotropin (TSH) concentrations by enhancing LT4 absorption or by directly affecting the hypothalamic–pituitary axis. This study examined the effect of metformin ingestion on LT4 absorption, as assessed by serum total thyroxine (TT4) concentrations. Methods: A modified Food and Drug Administration LT4 bioequivalence protocol was applied to healthy, metformin-naïve, euthyroid adult volunteers. Following an overnight fast, 600 μg LT4 was administered orally. Serum TT4 concentrations were measured at baseline and at 0.5, 1, 1.5, 2, 4, and 6 h following LT4 administration. Measurements were performed before and after one week of metformin ingestion (850 mg three times daily). Peak serum TT4 concentrations, time to peak TT4 concentrations, and area under the concentration-time curve (AUC) were calculated. Results: Twenty-six subjects (54% men, 27% white, age 33 ± 10 years) were studied. There were no significant differences in peak serum TT4 concentrations (p = 0.13) and time to peak TT4 concentrations (p = 0.19) before and after one week of metformin use. A trend toward reduced TT4 AUC was observed after metformin ingestion (pre-metformin 3893 ± 568 μg/dL-min, post-metformin 3765 ± 588 μg/dL-min, p = 0.09). Conclusions: LT4 absorption is unchanged by concomitant metformin ingestion. Mechanisms other than increased LT4 absorption may be responsible for the suppressed TSH concentrations observed in patients ingesting both drugs. PMID:26191653

How dead is dead? Qualitative findings from participants of combined traditional and lead-time time trade-off valuations.

PubMed

Al Sayah, Fatima; Mladenovic, Ana; Gaebel, Kathryn; Xie, Feng; Johnson, Jeffrey A

2016-01-01

The EuroQol Valuation Technology (EQ-VT) uses traditional time trade-off (tTTO) for health states better than dead and lead-time TTO (LT-TTO) for states worse than dead to elicit a value (-1.0 to +1.0) for each health state. In the Canadian EQ-5D-5L Valuation study which used the EQVT platform, we observed an unexpected peak in frequency of "0" values and few negative values, particularly in the range of 0 to -0.5. To better understand this finding, we sought to explore respondents' thought processes while valuing a health state, and their understanding of the tTTO and LT-TTO exercises. Qualitative semi-structured interviews were conducted with EQVT task respondents. Questions focused on valuations of health states as: (a) Same as dead in tTTO, (b) Worse than dead in tTTO but changed to same as dead in LT-TTO, (c) Worse than dead in LT-TTO, and (d) Worse than dead in LT-TTO with trading off all 10 years. Data were analyzed using content and thematic analysis. Mean age of participants (N = 70) was 40 ± 18.1 years, 60% female, and 76% Caucasian. Participants provided similar reasons for valuing a health state same as or worse than dead. Many participants expressed confusion about worse than dead valuations, distinction between same as and worse than dead, and the transition from tTTO to LT-TTO. A few indicated that the addition of 10 years of full health in the LT-TTO influenced their valuations. The transition from tTTO to LT-TTO in the EQVT was confusing to participants, whereby some health state valuations around this transition appeared to be arbitrary.

Evaluation of CDC light traps for mosquito surveillance in a malaria endemic area on the Thai-Myanmar border.

PubMed

Sriwichai, Patchara; Karl, Stephan; Samung, Yudthana; Sumruayphol, Suchada; Kiattibutr, Kirakorn; Payakkapol, Anon; Mueller, Ivo; Yan, Guiyun; Cui, Liwang; Sattabongkot, Jetsumon

2015-12-15

Centers for Disease Control and Prevention miniature light traps (CDC-LT) baited with CO2 are a routine tool for adult mosquito sampling used in entomological surveys, and for monitoring and surveillance of disease vectors. The present study was aimed at evaluating the performance of baited and unbaited CDC-LT for indoor and outdoor trapping of endemic mosquito species in northwestern Thailand. CDC-LT (n = 112) with and without dry ice baits were set both indoors and outdoors in 88 selected houses for stretches of 5 consecutive nights per month in 7 villages in Tha Song Yang district, Tak province between January 2011 and March 2013. Individual traps were repeatedly placed in the same location for a median of 6 (range 1-10) times. Mosquitoes were identified by morphological characteristics and classified into blood-fed, empty, male/female and gravid. Absolute mosquito numbers were converted to capture rates (i.e., mosquitoes per trap and year). Capture rates were compared using multilevel negative binomial regression to account for multiple trap placements and adjust for regional and seasonal differences. A total of 6,668 mosquitoes from 9 genera were collected from 576 individual CDC-LT placements. Culex was the predominant captured genus (46%), followed by anopheline mosquitoes (45%). Overall, CO2 baited traps captured significantly more Culex (especially Culex vishnui Theobald) and Anopheles mosquitoes per unit time (adjusted capture rate ratio (aCRR) 1.64 and 1.38, respectively). Armigeres spp. mosquitoes were trapped in outdoor traps with significantly higher frequency (aCRR: 1.50), whereas Aedes albopictus (Skuse) had a tendency to be trapped more frequently indoors (aCRR: 1.89, p = 0.07). Furthermore, capture rate ratios between CO2 baited and non-baited CDC-LT were significantly influenced by seasonality and indoor vs. outdoor trap placement. The present study shows that CDC-LT with CO2 baiting capture significantly more Culex and Anopheles mosquitoes, some of which (e.g., Cx. vishnui, Cx. quinquefasciatus Say, An. minimus s.l. Theobald, An. maculatus s.l. Theobald) represent important disease vectors in Thailand. This study also shows significant differences in the capture efficiency of CDC-LT when placed indoors or outdoors and in different seasons. Our study thus provides important guidelines for more targeted future vector trapping studies on the Thai-Myanmar border, which is an important cross-border malaria transmission region in Thailand.

Laser-Linewidth Effects on the Photon-Phonon Conversion Rate at a Gas-Solid Interface,

DTIC Science & Technology

1986-07-01

eliminate the exp(± iwLt )-dependence and facilitate the appearance of 0(t).20󈧙 We define the density operator a(t) as 0(t) - ei(Lt + *(t))Pgp(t)e i(wLt...specific form of our transformation (3.1) to the rotating frame. We remark that other kinds of transformations 24 , which also eliminate the exp(± iwLt ) time

 Increased hepatocellular carcinoma recurrence in women compared to men with high alpha fetoprotein at liver transplant.

PubMed

Sarkar, Monika; Dodge, Jennifer L; Roberts, John P; Terrault, Norah; Yao, Francis; Mehta, Neil

2016-01-01

 Introduction. Men have higher risk for hepatocellular carcinoma (HCC) than women. Pre liver transplant (LT) alpha fetoprotein (AFP) levels strongly predict post LT HCC recurrence. Though women with HCC have higher AFP, the contribution of AFP level by gender to post LT HCC recurrence is unknown. In this UNOSbased, retrospective cohort study we investigate sex differences in HCC recurrence among LT recipients with MELD exception between 2006-2010. Covariates include race, disease etiology, co-morbidities, AFP at listing and LT, tumor burden, loco-regional therapy, and donor risk index. HCC recurrence was assessed by competing risks regression. Of the eligible cohort (n = 5,002) included 3,872 men and 1,130 women. HCC recurred in 258 men (7%) and 66 women (6%). Median listing AFP was higher in women than men (14 vs. 11 ng/dL, p < 0.001). While no sex difference in overall HCC recurrence was detected (HR 0.9, 95% CI 0.7-1.2, p = 0.38), there was a strong interaction between gender and AFP on recurrence risk (p = 0.02). HCC recurrence was nearly three times higher in women (HR 4.2, 95% CI 2.2-8.2, p < 0.001) than men (HR 1.5, 95% CI 1.1-2.1, p = 0.02) with AFP at LT between 101-500 ng/dL. This study reveals novel sex differences in post LT HCC recurrence, which was nearly three times higher in women than men with high AFP at LT. Pre-LT AFP levels appear to carry a different prognosis in women than men, and a subset of female LT recipients may benefit from more intensive HCC surveillance after LT.

Time-dependent reversal of significant intrapulmonary shunt after liver transplantation.

PubMed

Jin, Xin; Sun, Byung Joo; Song, Jae-Kwan; Roh, Jae-Hyung; Jang, Jeong Yoon; Kim, Dae-Hee; Lim, Young-Suk; Song, Jong-Min; Kang, Duk-Hyun; Lee, Sung Gyu

2018-03-05

Although the association between intrapulmonary shunt (IPS) and liver cirrhosis is clear, data of repeated contrast echocardiography (CE) before and after liver transplantation (LT) to evaluate factors associated with IPS are limited. Hand-agitated saline was used for CE and, by assessing left-chamber opacification, IPS was classified as grade 0 to 4. Grade 3/4 constituted significant IPS and hepatopulmonary syndrome (HPS) was defined as significant IPS with the arterial partial pressure of oxygen < 70 mmHg. Before LT, 253 patients underwent CE and the frequency of significant IPS and HPS were 44% (n = 112) and 7% (n = 17), respectively. Child-Pugh score (odds ratio [OR], 1.345; 95% confidence interval [CI], 1.090 to 1.660; p = 0.006) and arterial oxygen content (OR, 0.838; 95% CI, 0.708 to 0.991; p = 0.039) were independent determinants of significant IPS, whereas direct bilirubin (OR, 1.076; 95% CI, 1.012 to 1.144; p = 0.019) was the only variable associated with HPS. Among 153 patients who underwent successful LT, repeated CE was performed in 97 (63%), which showed significant reductions in IPS grade (from 2.6 ± 1.0 to 1.2 ± 1.3, p < 0.001) and the prevalence of significant IPS (from 56% to 20%, p = 0.038). After adjustment for pre-LT IPS grade, time from LT to repeated CE presented negative linear relationship with post-LT IPS grade (r 2 = 0.366, p < 0.001) and was the only determinant of post-LT IPS grade (OR, 1.009; 95% CI, 1.003 to 1.014; p = 0.004). Repeated CE is useful to evaluate intrapulmonary vascular change before and after LT. Reversal of IPS after successful LT is time-dependent and follow-up duration should be considered for accurate assessment of IPS after LT.

The role of the ligamentum teres in the adult hip: redundant or relevant? A review

PubMed Central

Devitt, Brian M; Arora, Manit

2018-01-01

ABSTRACT The ligamentum teres (LT) has traditionally been described as a redundant structure with no contribution to hip biomechanics or function. There has been renewed interest in the LT as a source of hip pathology due to the high prevalence of LT pathology observed at the time of hip arthroscopy. The LT acts a secondary stabilizer to supplement the work of the capsular ligaments and works in a sling-like manner to prevent subluxation of the hip at the extremes of motion. The presence of free nerve endings within the LT indicates a definite role in pain generation, with the LT undergoing various mechanical and histological adaptations to hip pathology. PMID:29423246

Pharmacodynamics of recombinant activated factor VII and plasma-derived factor VII in a cohort of severe FVII deficient patients.

PubMed

van Geffen, Mark; Mathijssen, Natascha C J; Holme, Pål A; Laros-van Gorkom, Britta A P; van Kraaij, Marian G J; Masereeuw, Roselinde; Peyvandi, Flora; van Heerde, Waander L

2013-07-01

Recombinant activated factor VII (rFVIIa) and plasma-derived factor VII (pdFVII) are used to prevent bleedings in severe FVII deficient patients, despite their short half-lifes. It is suggested that FVII levels of 15-20 IU/dL are sufficient to maintain hemostasis. We analyzed the pharmacodynamic effects of FVII substitution therapy in the Nijmegen Hemostasis Assay (NHA) that simultaneously measures thrombin and plasmin generation. Ten severe FVII deficient patients were treated with 20 μg/kg rFVIIa or 25 IU/kg pdFVII in a cross-over design. Thrombin generation lag-time (TG-LT) was identified as an effect-response parameter. Pharmacodynamic analysis using a maximum effect model showed 50% reduction of the TG-LT effect at ~2 IU/dL FVII activity for both rFVIIa and pdFVII. The FVII activity to obtain TG-LT comparable to the upper limit of normal range in healthy controls (4 min) was given by the effective concentration (ECnormal), showing sufficient hemostasis at 3-4 IU/dL FVII activity. No association was seen between FVII activity and other thrombin or plasmin generation parameters as measured by NHA. In conclusion, 3-4 IU/dL FVII activity seems sufficient to maintain hemostasis in patients with severe FVII deficiency during prophylaxis. These data may suggest a potential value for measurement of TG-LT in the monitoring of FVII(a) therapy. Copyright © 2013 Elsevier Ltd. All rights reserved.

Problem video game playing is related to emotional distress in adolescents.

PubMed

Gonzálvez, María T; Espada, José P; Tejeiro, Ricardo

2017-06-28

Problem use of video games is an increasing risk behaviour. High exposure of adolescents to video games has been linked to a variety of disorders, but the relationship between problem video game playing and emotional welfare is unknown. The aim of the study is to analyse problem video game playing in a sample of adolescents and to determine whether there are differences between online and offline players, in addition to examining its relationship with anxiety and depressive symptomatology. A sample of adolescents (N = 380) completed self-reports measuring video game use and symptoms of anxiety and depression. We found that 7.4% of females and 30% of males can be considered as playing at problem levels. Online players were almost 12 times more likely to play at high frequency than offline players (χ2 (1, 267) = 72.72, p < .001, OR = 11.63, 95% CI [6.31, 21.43]). Males play more frequently, and play more online (χ2 (1, 267) = 50.85, p < .001, OR = 6.74, 95% CI [3.90, 11.64]), with a clear relationship between problem video game playing and anxiety (r = .24; p < .001). In females, there is a relationship between problem video game playing and depression (r = .19; p < .05). Our findings contribute to a better understanding of the psychological variables involved in problem video game playing. The implementation of strategies is suggested in order to prevent pathological gaming and associated problems.

Testing of candidate non-lethal sampling methods for detection of Renibacterium salmoninarum in juvenile Chinook salmon Oncorhynchus tshawytscha

USGS Publications Warehouse

Elliott, Diane G.; McKibben, Constance L.; Conway, Carla M.; Purcell, Maureen K.; Chase, Dorothy M.; Applegate, Lynn M.

2015-01-01

Non-lethal pathogen testing can be a useful tool for fish disease research and management. Our research objectives were to determine if (1) fin clips, gill snips, surface mucus scrapings, blood draws, or kidney biopsies could be obtained non-lethally from 3 to 15 g Chinook salmon Oncorhynchus tshawytscha, (2) non-lethal samples could accurately discriminate between fish exposed to the bacterial kidney disease agent Renibacterium salmoninarum and non-exposed fish, and (3) non-lethal samples could serve as proxies for lethal kidney samples to assess infection intensity. Blood draws and kidney biopsies caused ≥5% post-sampling mortality (Objective 1) and may be appropriate only for larger fish, but the other sample types were non-lethal. Sampling was performed over 21 wk following R. salmoninarum immersion challenge of fish from 2 stocks (Objectives 2 and 3), and nested PCR (nPCR) and real-time quantitative PCR (qPCR) results from candidate non-lethal samples were compared with kidney tissue analysis by nPCR, qPCR, bacteriological culture, enzyme-linked immunosorbent assay (ELISA), fluorescent antibody test (FAT) and histopathology/immunohistochemistry. R. salmoninarum was detected by PCR in >50% of fin, gill, and mucus samples from challenged fish. Mucus qPCR was the only non-lethal assay exhibiting both diagnostic sensitivity and specificity estimates >90% for distinguishing between R. salmoninarum-exposed and non-exposed fish and was the best candidate for use as an alternative to lethal kidney sample testing. Mucus qPCR R. salmoninarum quantity estimates reflected changes in kidney bacterial load estimates, as evidenced by significant positive correlations with kidney R. salmoninaruminfection intensity scores at all sample times and in both fish stocks, and were not significantly impacted by environmentalR. salmoninarum concentrations.

Intraspecific Variation in Pinus Pinaster PSII Photochemical Efficiency in Response to Winter Stress and Freezing Temperatures

PubMed Central

Corcuera, Leyre; Gil-Pelegrin, Eustaquio; Notivol, Eduardo

2011-01-01

As part of a program to select maritime pine (Pinus pinaster Ait.) genotypes for resistance to low winter temperatures, we examined variation in photosystem II activity by chlorophyll fluorescence. Populations and families within populations from contrasting climates were tested during two consecutive winters through two progeny trials, one located at a continental and xeric site and one at a mesic site with Atlantic influence. We also obtained the LT50, or the temperature that causes 50% damage, by controlled freezing and the subsequent analysis of chlorophyll fluorescence in needles and stems that were collected from populations at the continental trial site. P. pinaster showed sensitivity to winter stress at the continental site, during the colder winter. The combination of low temperatures, high solar irradiation and low precipitation caused sustained decreases in maximal photochemical efficiency (Fv/Fm), quantum yield of non-cyclic electron transport (ΦPSII) and photochemical quenching (qP). The variation in photochemical parameters was larger among families than among populations, and population differences appeared only under the harshest conditions at the continental site. As expected, the environmental effects (winter and site) on the photochemical parameters were much larger than the genotypic effects (population or family). LT50 was closely related to the minimum winter temperatures of the population's range. The dark-adapted Fv/Fm ratio discriminated clearly between interior and coastal populations. In conclusion, variations in Fv/Fm, ΦPSII, qP and non-photochemical quenching (NPQ) in response to winter stress were primarily due to the differences between the winter conditions and the sites and secondarily due to the differences among families and their interactions with the environment. Populations from continental climates showed higher frost tolerance (LT50) than coastal populations that typically experience mild winters. Therefore, LT50, as estimated by Fv/Fm, is a reliable indicator of frost tolerance among P. pinaster populations. PMID:22220195

Review and Assessment of Chlorine Mammalian Lethality Data and the Development of a Human Estimate R-1

DTIC Science & Technology

2009-06-01

BR; and Hartman, SE, Ratios as a Size Adjustment in Morphometrics , American Journal of Physical Anthropology. 91: 441-468, 1993. 18 Vanderburgh, PM...C2T was used for the toxic load model. After the median lethal C2T was determined, the geometric mean of all the individual exposure durations (T...was then calculated for each species dataset. The L(C2T)50 was assumed to be associated with this geometric mean time, which was found to equal

Radar observations of a tornado-spawning storm complex in Southeast Brazil and Meso-Eta forecasts of this extreme event

NASA Astrophysics Data System (ADS)

Held, Gerhard; Gomes, Jorge Luis; Gomes, Ana Maria

2014-05-01

During the early afternoon of 22 September 2013, severe storms, accompanied by large hail, damaging winds, heavy precipitation and intense lightning activity, devastated a region in the southeast State of São Paulo. Several extremely intense storm cells moved at up to 80 km/h east-southeastwards, ahead of a strong cold front approaching through Paraná, which created extremely unstable conditions that led to deep convection and overshooting towers up to 18 km. At least one of theses cells spawned a tornado when it reached the town of Taquarituba. The tornado traversed the town from south-southwest to north-northeast and was responsible for 63 people injured and two fatalities. Based on the damage reported, it was at least an F3 according to the Fujita scale. The objective of the present study is to characterize this severe thunderstorm event, using different types of data, and to evaluate the forecasts provided by the Meso-Eta model centered over Bauru. The pre-frontal and frontal convective cells were tracked throughout their life-time by IPMet's Doppler radars, which cover the western and central regions of the State São Paulo, as well as northern Paraná State. Radar volume scans, generated every 7,5 min, were processed with the TITAN (Thunderstorm Identification, Tracking, Analysis and Nowcasting) Software, yielding the following preliminary results: as the storm complex traversed the Paranapanema River, which forms the border between the two states, the cells intensified drastically and shortly before reaching the town of Taquarituba, that particular cell displayed extremely strong radial shear just above the cloud base (about -20 to +35 m/s), which led to the formation of a deep meso-cyclone, from which the tornado spawned and touched down at around 14:30 LT (LT=UT-3h). Cell properties calculated by TITAN showed a drastic increase of VIL (Vertically Integrated Liquid water content) from 13:52 LT (7,9 kg/m2) to a maximum of 61,8 kg/m2 at 14:15 LT. From 14:22 LT to 14:45 LT the VIL dropped to 14,2 kg/m2, indicative of destructive winds reaching the ground, coincident with the tornado touch-down. Simultaneously, the accumulated hail mass aloft increased from 0 to 802 ktons at 14:22 LT, which subsequently dropped to the ground, confirmed by the likewise decrease of VIL. Furthermore, the fact that the 40 dBZ radar reflectivity reached up to 16,6 km at the time of the tornado occurrence was also outstanding, while maximum reflectivities varied between 50 and 60 dBZ during 90 min. The Meso-Eta model is initiated twice daily (00 and 12 UT) for a domain, which amply covers the State of São Paulo at a resolution of 10x10km horizontally and 38 levels from 1000 to 50 hPa. It also computes additional convective parameters (Storm Relative Helicity (SRH), BRN Shear, supercell index, etc), as well as vertical profiles (Skew-T-Log-P) at any specified grid point. Furthermore, each run of the model is executed twice, using the convection parameterization of Betts & Miller and Kain-Fritsch, respectively. Based on the forecast from the 21Sept2013-12UT and 22Sept2013-00UT model runs (+27h & +30h and +15h & +18h, respectively), a warning for very severe storms to occur in the region from Ourinhos to Taquarituba could be emitted during the night before the extreme event. Some of the indicators were: CAPE 3000-4000 J/kg; K Index 38-42; strong wind shear between 500 hPa and 250 hPa (northwest at ±20 m/s to west at 30m/s); Omega at 500 hPa -1,0 to -1,4 Pa/s; Supercell Parameter -1 and SRH 150-200 m2/s2. The time window ranged from 12:00 to 18:00 LT. The Skew-T diagram at 09:00LT at Taquarituba indicated relatively dry air between 600-200hPa, which was quickly moistened as the cold front approached.

Longitudinal structure of the equatorial ionosphere: Time evolution of the four-peaked EIA structure

NASA Astrophysics Data System (ADS)

Lin, C. H.; Hsiao, C. C.; Liu, J. Y.; Liu, C. H.

2007-12-01

Longitudinal structure of the equatorial ionosphere during the 24 h local time period is observed by the FORMOSAT-3/COSMIC (F3/C) satellite constellation. By binning the F3/C radio occultation observations during September and October 2006, global ionospheric total electron content (TEC) maps at a constant local time map (local time TEC map, referred as LT map) can be obtained to monitor the development and subsidence of the four-peaked longitudinal structure of the equatorial ionosphere. From LT maps, the four-peaked structure starts to develop at 0800-1000 LT and becomes most prominent at 1200-1600 LT. The longitudinal structure starts to subside after 2200-2400 LT and becomes indiscernible after 0400-0600 LT. In addition to TEC, ionospheric peak altitude also shows a four-peaked longitudinal structure with variation very similar to TEC during daytime. The four-peaked structure of the ionospheric peak altitude is indiscernible at night. With global local time maps of ionospheric TEC and peak altitude, we compare temporal variations of the longitudinal structure with variations of E × B drift from the empirical model. Our results indicate that the observations are consistent with the hypothesis that the four-peaked longitudinal structure is caused by the equatorial plasma fountain modulated by the E3 nonmigrating tide. Additionally, the four maximum regions show a tendency of moving eastward with propagation velocity of several 10 s m/s.

Lithium-methomyl induced seizures in rats: A new model of status epilepticus?

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

Kaminski, Rafal M.; Blaszczak, Piotr; Dekundy, Andrzej

2007-03-15

Behavioral, electroencephalographic (EEG) and neuropathological effects of methomyl, a carbamate insecticide reversibly inhibiting acetylcholinesterase activity, were studied in naive or lithium chloride (24 h, 3 mEq/kg, s.c.) pretreated male Wistar rats. In naive animals, methomyl with equal potency produced motor limbic seizures and fatal status epilepticus. Thus, the CD50 values (50% convulsant dose) for these seizure endpoints were almost equal to the LD50 (50% lethal dose) of methomyl (13 mg/kg). Lithium pretreated rats were much more susceptible to convulsant, but not lethal effect of methomyl. CD50 values of methomyl for motor limbic seizures and status epilepticus were reduced by lithiummore » pretreatment to 3.7 mg/kg (a 3.5-fold decrease) and 5.2 mg/kg (a 2.5-fold decrease), respectively. In contrast, lithium pretreatment resulted in only 1.3-fold decrease of LD50 value of methomyl (9.9 mg/kg). Moreover, lithium-methomyl treated animals developed a long-lasting status epilepticus, which was not associated with imminent lethality observed in methomyl-only treated rats. Scopolamine (10 mg/kg) or diazepam (10 mg/kg) protected all lithium-methomyl treated rats from convulsions and lethality. Cortical and hippocampal EEG recordings revealed typical epileptic discharges that were consistent with behavioral seizures observed in lithium-methomyl treated rats. In addition, convulsions induced by lithium-methomyl treatment were associated with widespread neurodegeneration of limbic structures. Our observations indicate that lithium pretreatment results in separation between convulsant and lethal effects of methomyl in rats. As such, seizures induced by lithium-methomyl administration may be an alternative to lithium-pilocarpine model of status epilepticus, which is associated with high lethality.« less

Lethal/sublethal responses of Daphnia magna to acute norfloxacin contamination and changes in phytoplankton-zooplankton interactions induced by this antibiotic

NASA Astrophysics Data System (ADS)

Pan, Ying; Yan, Shi-Wei; Li, Ruo-Zhu; Hu, Yi-Wen; Chang, Xue-Xiu

2017-01-01

Although the well-known antibiotic norfloxacin (NOR) is recognized as an important environmental pollutant, little is known about its impacts on ecological processes, particularly on species interactions. In this paper, we quantified Daphnia magna (Crustacea, Cladocera) responses in mortality rate at lethal NOR concentrations (0, 25, 50, 100, 200, 300 and 400 mg L-1), and in heartbeat rate, swimming behavior and feeding rate (on the green alga Chlorella pyrenoidosa) at sublethal NOR concentrations (0, 25, 50 and 100 mg L-1) to determine the effects of this antibiotic in plankton systems. In 96-h-long lethal experiment, mortality rates of D. magna increased significantly with increasing NOR concentration and exposure time. In sublethal experiments, heartbeat rate decreased, while time ratio of vertical to horizontal swimming (TVH) and the duration of quiescence increased in D. magna individuals exposed to increasing NOR concentrations after 4 and 12 h of exposure. These collectively led to decreases in both average swimming ability and feeding rate, consistent with the positive relationship between average swimming ability and feeding rate. Overall, results indicate that, by affecting zooplankton heartbeat rate and behavior, NOR decreased feeding efficiency of D. magna even at low doses, therefore, it might seriously compromise ecosystem health and function.

Struggling to Target: Airpower’s Historical Challenge Continues

DTIC Science & Technology

2002-04-01

targeting. Notes 1 Larry A. Weaver and Robert D. Pollock, “Campaign Planning for the 21st Century,” in Airpower Studies Coursebook , ed. Lt...Around,” in Airpower Studies Coursebook , ed. Lt Colonel Anthony C. Cain, Dr. Doug Peifer, Llewellyn A. Lamar et al. (Maxwell AFB, Ala.: Air Command...In addition, the list of installations considered viable targets increased by 50% during the same timeframe.26 These statistics are only a small

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

Giggleman, M.A.; Fitzpatrick, L.C.; Goven, A.J.

Earthworms, Lumbricus terrestris, exposed for 96 h to filter paper saturated with five nominal concentrations of pentachlorophenol, exhibited a 50% lethal concentration (LC50) of 25.0 {micro}g PCP/cm{sup 2} and corresponding whole worm body burden-based 50% lethal dose (LD50) of 877.7 {micro}g PCP/g dry mass. Linear regression modeling showed that worms increased body concentrations (BC = {micro}g PCP/g dry tissue mass) with increasing exposure concentrations (EC) according to BC = 113.5 + 29.5EC. Phagocytosis of yeast cells by immunoactive coelomocytes was suppressed only at body concentrations (863.3 {micro}g PCP/g dry mass) that approximated the calculated LD50 and overlapped those demonstrating lethality,more » indicating a sharp transition between sublethal and lethal toxicity. An exposure concentration of 15 {micro}g PCP/cm{sup 2} produced significant suppression of phagocytosis of yeast cells by immunoactive coelomocytes. However, the average measured body burden from this group approximated the estimated LD50, indicating a sharp toxic response slope. Exposure to 10 {micro}g PCP/cm{sup 2} with a corresponding body concentration of 501.3 {micro}g PCP/g dry mass did not affect phagocytosis. The importance of body burden data is emphasized.« less

Concentrations of cysteinyl leukotrienes in urine and bronchoalveolar lavage fluid of cats with experimentally induced asthma.

PubMed

Norris, Carol R; Decile, Kendra C; Berghaus, Londa J; Berghaus, Roy D; Walby, William F; Schelegle, Edward S; Hyde, Dallas M; Gershwin, Laurel J

2003-11-01

To evaluate changes in cysteinyl leukotriene (LT) concentrations in urine and bronchoalveolar lavage fluid (BALF) in cats with experimentally induced asthma. 19 cats with experimentally induced asthma and 5 control cats. Cats were sensitized to Bermuda grass or house dust mite allergen, and phenotypic features of asthma were confirmed with intradermal skin testing, evaluation of BALF eosinophil percentages, and pulmonary function testing. A competitive ELISA kit for LTC4, LTD4, and LTE4 was used for quantitative analysis of LTs. Urinary creatinine concentrations and BALF total protein (TP) concentrations were measured, and urinary LT-to-creatinine ratios and BALF LT-to-TP ratios were calculated. Mean urinary LT-to-creatinine ratios did not differ significantly between control cats and allergen-sensitized cats before or after sensitization and challenge exposure with saline (0.9% NaCl) solution or allergen, respectively. In BALF the mean LT-to-TP ratio of control cats did not differ significantly before or after sensitization and challenge exposure with saline. Asthmatic cats had BALF LT-to-TP ratios that were significantly lower than control cats at all time points, whereas ratios for asthmatic cats did not differ significantly among the various time points. Although LTs were readily detectable in urine, no significant increases in urinary LT concentrations were detected after challenge in allergen-sensitized cats. Spot testing of urinary LT concentrations appears to have no clinical benefit for use in monitoring the inflammatory asthmatic state in cats. The possibility that cysteinyl LTs bind effectively to their target receptors in BALF and, thus, decrease free LT concentrations deserves further study.

Prediction of lactate threshold and fixed blood lactate concentrations from 3200-m running performance in male runners.

PubMed

Weltman, A; Snead, D; Seip, R; Schurrer, R; Levine, S; Rutt, R; Reilly, T; Weltman, J; Rogol, A

1987-12-01

To determine the effectiveness of a 3200-m time trial for predicting VO2 and running velocity at lactate threshold (LT), fixed blood lactate concentrations of 2.0, 2.5, and 4.0 mM, and peak, 42 male runners (means age = 31.1 +/- 8.3 years; means ht = 176.8 +/- 6.6 cm; means wt = 70.4 +/- 10.0 kg) completed a VO2 peak/LT test and a 3200-m time trial. The continuous treadmill protocol started at 0% grade 150 m/min and increased 10 m/min every 3 min until exhaustion. Velocity at LT, 2.0, 2.5, and 4.0 mM was determined from individual velocity blood lactate relationships, and VO2 values were determined from individual plots ov VO2 vs velocity. VO2 peak and velocity peak were chosen as the highest values observed. Oxygen uptake at LT, 2.0, 2.5, 4.0 mM, and peak was 52.51, 56.61, 58.31, 61.70, and 64.21 ml/kg.min-1, respectively, while the velocities associated with LT, 2.0, 2.5, 4.0 mM, and peak were 235.5, 251.5, 259.8, 273.5, and 285.5 m/min, respectively. During the 3200-m time trial (means time = 11.28 +/- 0.96 min), 400-m split times and cumulative times were recorded. Twenty-nine subjects were randomly assigned to a validation sample and the remaining subjects were used for cross-validation purposes. Regression analysis revealed that a 3200-m time trial was a good predictor of both VO2 (ml/kg.min-1) and velocity (m/min) at LT, 2.0, 2.5, 4.0 mM, and peak.

Cold tolerance of Littorinidae from southern Africa: intertidal snails are not constrained to freeze tolerance.

PubMed

Sinclair, Brent J; Marshall, David J; Singh, Sarika; Chown, Steven L

2004-11-01

All intertidal gastropods for which cold tolerance strategies have been assessed have been shown to be freeze tolerant. Thus, freeze tolerance is considered an adaptation to the intertidal environment. We investigated the cold tolerance strategies of three species of subtropical and temperate snails (Gastropoda: Littorinidae) to determine whether this group is phylogenetically constrained to freeze tolerance. We exposed 'dry' acclimated and 'wet' rehydrated snails to low temperatures to determine temperature of crystallisation (Tc), lower lethal temperature and LT(50) and to examine the relationship between ice formation and mortality. Tc was lowest in dry Afrolittorina knysnaensis (-13.6+/-0.4 degrees C), followed by dry Echinolittorina natalensis (-10.9+/-0.2 degrees C) and wet A. knysnaensis (-10.2+/-0.2 degrees C) . The Tc of both A. knysnaensis and E. natalensis increased with rehydration, whereas Tc of dry and wet Afrolittorina africana did not differ (-9.6+/-0.2 and -9.0+/-0.2 degrees C respectively). Wet snails of all species exhibited no or low survival of inoculative freezing, whereas dry individuals of A. knysnaensis could survive subzero temperatures above -8 degrees C when freezing was inoculated with ice . In the absence of external ice, Afrolittorina knysnaensis employs a freeze-avoidance strategy of cold tolerance, the first time this has been reported for an intertidal snail, indicating that there is no family-level phylogenetic constraint to freeze tolerance. Echinolittorina natalensis and A. africana both showed pre-freeze mortality and survival of some internal ice formation, but were not cold hardy in any strict sense.

Fumigant Toxicity and Sublethal Effects of Artemisia khorassanica and Artemisia sieberi on Sitotroga cerealella (Lepidoptera: Gelechiidae).

PubMed

Naseri, B; Abedi, Z; Abdolmaleki, A; Jafary-Jahed, M; Borzoui, E; Mozaffar Mansouri, Seyed

2017-09-01

Fumigant toxicity and sublethal effects of essential oils from Artemisia khorassanica Podl. and Artemisia sieberi Bess were investigated against adults of Sitotroga cerealella Olivier. To assess the sublethal effects, adult moths were exposed to the LC30 of each essential oil, and life table parameters of the surviving S. cerealella were studied. Higher fumigant toxicity of A. khorassanica (LC50: 7.38 µl/liter air) than A. sieberi (LC50: 9.26 µl/liter air) was observed against S. cerealella. Also, the insecticidal effects of A. khorassanica (LT50: 9.01 h) were faster than A. sieberi (LT50: 14.37 h). A significant extension was observed in the developmental time (egg to adult) of S. cerealella treated with the essential oils. In addition, fecundity of S. cerealella reduced by 25.29 and 35.78% following exposure to sublethal concentrations of A. sieberi and A. khorassanica, respectively. Both tested essential oils caused a significant reduction in the gross and net reproductive rates, intrinsic rate of increase (rm), and finite rate of increase of S. cerealella. The rm values following exposure to A. sieberi, A. khorassanica, and control were 0.098, 0.094, and 0.107 d-1, respectively. The results of this study suggest that tested essential oils have a good potential to apply in integrated pest management of S. cerealella. © The Author 2017. Published by Oxford University Press on behalf of Entomological Society of America.

Effect of using a laryngeal tube on the no-flow time in a simulated, single-rescuer, basic life support setting with inexperienced users.

PubMed

Meyer, O; Bucher, M; Schröder, J

2016-03-01

The laryngeal tube (LT) is a recommended alternative to endotracheal intubation during advanced life support (ALS). Its insertion is relatively simple; therefore, it may also serve as an alternative to bag mask ventilation (BMV) for untrained personnel performing basic life support (BLS). Data support the influence of LT on the no-flow time (NFT) compared with BMV during ALS in manikin studies. We performed a manikin study to investigate the effect of using the LT for ventilation instead of BMV on the NFT during BLS in a prospective, randomized, single-rescuer study. All 209 participants were trained in BMV, but were inexperienced in using LT; each participant performed BLS during a 4-min time period. No significant difference in total NFT (LT: mean 81.1 ± 22.7 s; BMV: mean 83.2 ± 13.1 s, p = 0.414) was found; however, significant differences in the later periods of the scenario were identified. While ventilating with the LT, the proportion of chest compressions increased significantly from 67.2 to 73.2%, whereas the proportion of chest compressions increased only marginally when performing BMV. The quality of the chest compressions and the associated ventilation rate did not differ significantly. The mean tidal volume and mean minute volume were significantly lower when performing BMV. The NFT was significantly shorter in the later periods in a single-rescuer, cardiac arrest scenario when using an LT without previous training compared with BMV with previous training. A possible explanation for this result may be the complexity and workload of alternating tasks (e.g., time loss when reclining the head and positioning the mask for each ventilation during BMV).

Everolimus immunosuppression reduces the serum expression of fibrosis markers in liver transplant recipients.

PubMed

Fernández-Yunquera, Ainhoa; Ripoll, Cristina; Bañares, Rafael; Puerto, Marta; Rincón, Diego; Yepes, Ismael; Catalina, Vega; Salcedo, Magdalena

2014-06-24

To evaluate the expression of serum fibrosis markers in liver transplantation (LT) recipients on everolimus monotherapy compared to patients on an anti-calcineurin regimen. This cross-sectional case-control study included LT patients on everolimus monotherapy (cases) (E) (n = 30) and matched controls on an anti-calcineurin regimen (calcineurin inhibitors, CNI), paired by etiology of liver disease and time since LT (n = 30). Clinical characteristics, blood tests and elastography were collected. Serum levels of transforming growth factor-β (TGF-β), angiopoietin-1, tumor necrosis factor (TNF), platelet derived growth factor, amino-terminal propeptide of type III procollagen (PIIINP), hyaluronic acid (HA), VCM-1 (ng/mL), interleukin (IL)-10, interferon-inducible protein 10 (IP-10), vascular endothelial growth factor and hepatocyte growth factor (HGF) (pg/mL) were determined by enzyme-linked immunosorbent assay. Expression of these markers between E and CNI was compared. Stratified analysis was done according to factors that may influence liver fibrosis. Variables are described with medians (interquartillic range) or percentages. A total of 60 patients [age: 59 (49-64), hepatitis C virus (HCV): n = 21 (35%), time from LT: 73 mo (16-105)] were included. Patients had been on everolimus for a median of 15 mo. No differences in inflammatory activity, APRI test or liver elastography were found between the groups. No significant differences were observed between the groups in serum levels of PIIINP, metalloproteinase type = 1, angiopoietin, HGF, IP-10, TNF-α, IL-10 and vascular cell adhesion molecule. Patients on E had a lower expression of TGF-β [E: 12.7 (3.7-133.6), CNI: 152.5 (14.4-333.2), P = 0.009] and HA [E: 702.89 (329.4-838.2), CNI: 1513.6 (691.9-1951.4), P = 0.001] than those on CNI. This difference was maintained in the stratified analysis when recipient age is more than 50 years (TFG-β1: P = 0.06; HA: P = 0.005), in patients without active neoplasia (TFG-β1, P = 0.009; HA: P = 0.01), according to time since LT (> than 5 years, TFG-β1: P = 0.001; HA: P = 0.002), related to previous history of biliary complications (HA: P = 0.01) and HCV recurrence (HA: P = 0.004). Liver transplant recipients with everolimus monotherapy had less serum expression of TGF-β y HA than matched patients with anti-calcineurins. This difference remains when classifying patients according to donor age and time since LT. Due to the small sample size, when examining patients with a prior history of biliary complications or recurrent HCV, the difference was non-significant but trends towards the lower expression of TFG-β1 in the everolimus group. Mammalian target of rapamycin (mTOR) plays a role in the transformation of quiescent hepatocellular stellate cell to their active profibrotic state, and experimental models have demonstrated the potential activity of mTOR inhibition in attenuating fibrogenesis. This study supports a possible role of everolimus in liver fibrosis modulation after LT in a clinical setting and suggests that tailoring immunosuppression could avoid fibrosis progression in the allograft.

Everolimus immunosuppression reduces the serum expression of fibrosis markers in liver transplant recipients

PubMed Central

Fernández-Yunquera, Ainhoa; Ripoll, Cristina; Bañares, Rafael; Puerto, Marta; Rincón, Diego; Yepes, Ismael; Catalina, Vega; Salcedo, Magdalena

2014-01-01

AIM: To evaluate the expression of serum fibrosis markers in liver transplantation (LT) recipients on everolimus monotherapy compared to patients on an anti-calcineurin regimen. METHODS: This cross-sectional case-control study included LT patients on everolimus monotherapy (cases) (E) (n = 30) and matched controls on an anti-calcineurin regimen (calcineurin inhibitors, CNI), paired by etiology of liver disease and time since LT (n = 30). Clinical characteristics, blood tests and elastography were collected. Serum levels of transforming growth factor-β (TGF-β), angiopoietin-1, tumor necrosis factor (TNF), platelet derived growth factor, amino-terminal propeptide of type III procollagen (PIIINP), hyaluronic acid (HA), VCM-1 (ng/mL), interleukin (IL)-10, interferon-inducible protein 10 (IP-10), vascular endothelial growth factor and hepatocyte growth factor (HGF) (pg/mL) were determined by enzyme-linked immunosorbent assay. Expression of these markers between E and CNI was compared. Stratified analysis was done according to factors that may influence liver fibrosis. Variables are described with medians (interquartillic range) or percentages. RESULTS: A total of 60 patients [age: 59 (49-64), hepatitis C virus (HCV): n = 21 (35%), time from LT: 73 mo (16-105)] were included. Patients had been on everolimus for a median of 15 mo. No differences in inflammatory activity, APRI test or liver elastography were found between the groups. No significant differences were observed between the groups in serum levels of PIIINP, metalloproteinase type = 1, angiopoietin, HGF, IP-10, TNF-α, IL-10 and vascular cell adhesion molecule. Patients on E had a lower expression of TGF-β [E: 12.7 (3.7-133.6), CNI: 152.5 (14.4-333.2), P = 0.009] and HA [E: 702.89 (329.4-838.2), CNI: 1513.6 (691.9-1951.4), P = 0.001] than those on CNI. This difference was maintained in the stratified analysis when recipient age is more than 50 years (TFG-β1: P = 0.06; HA: P = 0.005), in patients without active neoplasia (TFG-β1, P = 0.009; HA: P = 0.01), according to time since LT (> than 5 years, TFG-β1: P = 0.001; HA: P = 0.002), related to previous history of biliary complications (HA: P = 0.01) and HCV recurrence (HA: P = 0.004). Liver transplant recipients with everolimus monotherapy had less serum expression of TGF-β y HA than matched patients with anti-calcineurins. This difference remains when classifying patients according to donor age and time since LT. Due to the small sample size, when examining patients with a prior history of biliary complications or recurrent HCV, the difference was non-significant but trends towards the lower expression of TFG-β1 in the everolimus group. Mammalian target of rapamycin (mTOR) plays a role in the transformation of quiescent hepatocellular stellate cell to their active profibrotic state, and experimental models have demonstrated the potential activity of mTOR inhibition in attenuating fibrogenesis. CONCLUSION: This study supports a possible role of everolimus in liver fibrosis modulation after LT in a clinical setting and suggests that tailoring immunosuppression could avoid fibrosis progression in the allograft. PMID:25032102

Development and Testing of a Device Capable of Placing Model Piles by Driving and Pushing in the Centrifuge

DTIC Science & Technology

1989-05-01

Cohesion C M /LT 2 5 , D ynamic Time T T 5 "I Wave Speed P L/T7 IT Yield Strength F I/LT2 a I9 i spl acement D L 9 It Area A L2 10 T Permeability K L/T 11...by the square of the dynamic time scale factor (1/n), or I/n2 . The two scaling laws derived are summarized below. The subscripts m and p designate the...4-1(b) depicts the model pile groups and test gravity levels. InUd ~ cial’odel Piles a~ft -to Ri ght--49.3, 5.,3. ana g o d ’iaeIs~ M )uodel Pile

Further Characterization of the Mitigation of Radiation Lethality by Protective Wounding

PubMed Central

Dynlacht, Joseph R.; Garrett, Joy; Joel, Rebecca; Lane, Katharina; Mendonca, Marc S.; Orschell, Christie M.

2017-01-01

There continues to be a major effort in the United States to develop mitigators for the treatment of mass casualties that received high-intensity acute ionizing radiation exposures from the detonation of an improvised nuclear device during a radiological terrorist attack. The ideal countermeasure should be effective when administered after exposure, and over a wide range of absorbed doses. We have previously shown that the administration of a subcutaneous incision of a defined length, if administered within minutes after irradiation, protected young adult female C57BL/6 mice against radiation-induced lethality, and increased survival after total-body exposure to an LD50/30 X-ray dose from 50% to over 90%. We refer to this approach as “protective wounding”. In this article, we report on our efforts to further optimize, characterize and demonstrate the validity of the protective wounding response by comparing the response of female and male mice, varying the radiation dose, the size of the wound, and the timing of wounding with respect to administration of the radiation dose. Both male and female mice that received a subcutaneous incision after irradiation were significantly protected from radiation lethality. We observed that the extent of protection against lethality after an LD50/30 X-ray dose was independent of the size of the subcutaneous cut, and that a 3 mm subcutaneous incision is effective at enhancing the survival of mice exposed to a broad range of radiation doses (LD15–LD100). Over the range of 6.2–6.7 Gy, the increase in survival observed in mice that received an incision was associated with an enhanced recovery of hematopoiesis. The enhanced rate of recovery of hematopoiesis was preceded by an increase in the production of a select group of cytokines. Thus, a thorough knowledge of the timing of the cytokine cascade after wounding could aid in the development of novel pharmacological radiation countermeasures that can be administered several days after the actual radiation exposure. PMID:28437188

Influence of dimethyl dicarbonate on the resistance of Escherichia coli to a combined UV-Heat treatment in apple juice

PubMed Central

Gouma, Maria; Gayán, Elisa; Raso, Javier; Condón, Santiago; Álvarez, Ignacio

2015-01-01

Commercial apple juice inoculated with Escherichia coli was treated with UV-C, heat (55°C) and dimethyl dicarbonate – DMDC (25, 50, and 75 mg/L)-, applied separately and in combination, in order to investigate the possibility of synergistic lethal effects. The inactivation levels resulting from each treatment applied individually for a maximum treatment time of 3.58 min were limited, reaching 1.2, 2.9, and 0.06 log10 reductions for UV, heat, and DMDC (75 mg/L), respectively. However, all the investigated combinations resulted in a synergistic lethal effect, reducing the total treatment time and UV dose, with the synergistic lethal effect being higher when larger concentrations of DMDC were added to the apple juice. The addition of 75 mg/L of DMDC prior to the combined UV-C light treatment at 55°C resulted in 5 log10 reductions after only 1.8 min, reducing the treatment time and UV dose of the combined UV-Heat treatment by 44%. PMID:26042117

78 FR 14241 - Acetonitrile; Community Right-to-Know Toxic Chemical Release Reporting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-05

... 50 values (i.e., the dose of a chemical that is lethal to 50 percent of the test organisms) have been...., the concentration of a chemical that is lethal to 50 percent of the test organisms) of 12,000, 16,000... estimate for acetonitrile in mice was reported to be 2,693 ppm (Ref. 6). A recent study (Ref. 12) reported...

Acute Versus Delayed Magnetic Resonance Imaging and Associated Abnormalities in Traumatic Anterior Shoulder Dislocations

PubMed Central

Orvets, Nathan D.; Parisien, Robert L.; Curry, Emily J.; Chung, Justin S.; Eichinger, Josef K.; Murakami, Akira M.; Li, Xinning

2017-01-01

Background: The delayed management of patients with shoulder instability may increase the prevalence and severity of concomitant intra-articular shoulder injuries resulting from persistent subluxations and dislocations. Hypothesis: Patients with a longer delay from the initial dislocation event to undergoing magnetic resonance imaging (MRI) or magnetic resonance arthrography will demonstrate more subluxations or dislocations and a greater amount of intra-articular shoulder damage. Study Design: Cohort study; Level of evidence, 3. Methods: We performed a retrospective review of 89 patients from a single institution with clinically and radiographically confirmed primary traumatic anterior shoulder dislocations. Patients were divided into 2 groups: those undergoing MRI less than 6 months (n = 44; LT6) or greater than 6 months (n = 45; GT6) from the initial dislocation event. The MRI assessment included evaluation of soft tissue injuries, including the labrum, capsule, rotator cuff, and cartilage damage severity along with bone loss. Results: The delayed MRI group (GT6) demonstrated a greater degree of intra-articular abnormalities compared to the early MRI group (LT6). A greater percentage of superior labral anterior-posterior (SLAP) tears (58% vs 34%, respectively) and cartilage damage (73% vs 27%, respectively) was present in the GT6 group compared to the LT6 group. Cartilage damage was 18% mild, 7% moderate, and 2% severe for the LT6 group as compared to 38% mild, 31% moderate, and 4% severe for the GT6 group. Additionally, more recurrent shoulder dislocations were seen in the GT6 group (n = 6) compared to the LT6 group (n = 2). In the LT6 group, there were more rotator cuff tears (50% vs 24%, respectively) and capsular tears (25% vs 9%, respectively) than the GT6 group. There was no difference in anterior glenoid bone loss, glenoid version, or humeral head subluxation between the 2 groups. Conclusion: Patients who undergo MRI greater than 6 months from the time of primary or initial shoulder dislocation had significantly more recurrent shoulder instability events and demonstrated a greater incidence and severity of intra-articular abnormalities, including SLAP tears, posterior labral tears, and anterior glenoid cartilage damage. PMID:28975132

Liver transplantation with piggyback anastomosis using a linear stapler: a case report.

PubMed

Akbulut, S; Wojcicki, M; Kayaalp, C; Yilmaz, S

2013-04-01

The so-called piggyback technique of liver transplantation (PB-LT) preserves the recipient's caval vein, shortening the warm ischemic time. It can be reduced even further by using a linear stapler for the cavocaval anastomosis. Herein, we have presented a case of a patient undergoing a side-to-side, whole-organ PB-LT for cryptogenic cirrhosis. Upper and lower orifices of the donor caval vein were closed at the back table using a running 5-0 polypropylene suture. Three stay sutures were then placed on caudal parts of both the recipient and donor caval with a 5-mm venotomies. The endoscopic linear stapler was placed upward through the orifices and fired. A second stapler was placed more cranially and fired resulting in a 8-9 cm long cavocavostomy. Some loose clips were flushed away from the caval lumen. The caval anastomosis was performed within 4 minutes; the time needed to close the caval vein stapler insertion orifices (4-0 polypropylene running suture) before reperfusion was 1 minute. All other anastomoses were performed as typically sutured. The presented technique enables one to reduce the warm ischemic time, which can be of particular importance with marginal grafts. Copyright © 2013 Elsevier Inc. All rights reserved.

A literature-based cost analysis of tissue plasminogen activator for prevention of biliary stricture in donation after circulatory death liver transplantation.

PubMed

Jones, J M; Bhutiani, N; Wei, D; Goldstein, L; Jones, C M; Cannon, R M

2018-04-17

This study sought to approximate the cost-effectiveness of tPA utilization for prevention of biliary strictures (PTBS) in donation after circulatory death liver transplantation (DCD-LT). Previously-reported PTBS rates in DCD-LT with and without tPA were used to calculate the number needed to treat (NNT) for prevention of one PTBS. The incremental cost of PTBS was then used to determine the cost effectiveness of tPA for prevention of PTBS. The incidence of PTBS in the setting of tPA administration was 20%, while incidence in patients without tPA use was 43% (p < 0.001). Meta-analysis demonstrated a risk reduction of 15.7%, which translated into a NNT of 6.4. Cost associated with treating 6.4 patients was $50,353. Based on an incremental cost of $81,888 associated with PTBS management, use of tPA in DCD-LT protocols was estimated to save $31,528 per PTBS prevented. Utilization of tPA in DCD-LT protocols represents one possible cost-effective strategy for prevention of PTBS in DCD-LT. Copyright © 2018 Elsevier Inc. All rights reserved.

Decrease of Staphylococcus aureus Virulence by Helcococcus kunzii in a Caenorhabditis elegans Model.

PubMed

Ngba Essebe, Christelle; Visvikis, Orane; Fines-Guyon, Marguerite; Vergne, Anne; Cattoir, Vincent; Lecoustumier, Alain; Lemichez, Emmanuel; Sotto, Albert; Lavigne, Jean-Philippe; Dunyach-Remy, Catherine

2017-01-01

Social bacterial interactions are considered essential in numerous infectious diseases, particularly in wounds. Foot ulcers are a common complication in diabetic patients and these ulcers become frequently infected. This infection is usually polymicrobial promoting cell-to-cell communications. Staphylococcus aureus is the most prevalent pathogen isolated. Its association with Helcococcus kunzii , commensal Gram-positive cocci, is frequently described. The aim of this study was to assess the impact of co-infection on virulence of both H. kunzii and S. aureus strains in a Caenorhabditis elegans model. To study the host response, qRT-PCRs targeting host defense genes were performed. We observed that H. kunzii strains harbored a very low (LT50: 5.7 days ± 0.4) or an absence of virulence (LT50: 6.9 days ± 0.5). In contrast, S. aureus strains (LT50: 2.9 days ± 0.4) were significantly more virulent than all H. kunzii ( P < 0.001). When H. kunzii and S. aureus strains were associated, H. kunzii significantly reduced the virulence of the S. aureus strain in nematodes (LT50 between 4.4 and 5.2 days; P < 0.001). To evaluate the impact of these strains on host response, transcriptomic analysis showed that the ingestion of S. aureus led to a strong induction of defense genes ( lys-5, sodh-1 , and cyp-37B1 ) while H. kunzii did not. No statistical difference of host response genes expression was observed when C. elegans were infected with either S. aureus alone or with S. aureus + H. kunzii . Moreover, two well-characterized virulence factors ( hla and agr ) present in S. aureus were down-regulated when S. aureus were co-infected with H. kunzii . This study showed that H. kunzii decreased the virulence of S. aureus without modifying directly the host defense response. Factor(s) produced by this bacterium modulating the staphylococci virulence must be investigated.

Decrease of Staphylococcus aureus Virulence by Helcococcus kunzii in a Caenorhabditis elegans Model

PubMed Central

Ngba Essebe, Christelle; Visvikis, Orane; Fines-Guyon, Marguerite; Vergne, Anne; Cattoir, Vincent; Lecoustumier, Alain; Lemichez, Emmanuel; Sotto, Albert; Lavigne, Jean-Philippe; Dunyach-Remy, Catherine

2017-01-01

Social bacterial interactions are considered essential in numerous infectious diseases, particularly in wounds. Foot ulcers are a common complication in diabetic patients and these ulcers become frequently infected. This infection is usually polymicrobial promoting cell-to-cell communications. Staphylococcus aureus is the most prevalent pathogen isolated. Its association with Helcococcus kunzii, commensal Gram-positive cocci, is frequently described. The aim of this study was to assess the impact of co-infection on virulence of both H. kunzii and S. aureus strains in a Caenorhabditis elegans model. To study the host response, qRT-PCRs targeting host defense genes were performed. We observed that H. kunzii strains harbored a very low (LT50: 5.7 days ± 0.4) or an absence of virulence (LT50: 6.9 days ± 0.5). In contrast, S. aureus strains (LT50: 2.9 days ± 0.4) were significantly more virulent than all H. kunzii (P < 0.001). When H. kunzii and S. aureus strains were associated, H. kunzii significantly reduced the virulence of the S. aureus strain in nematodes (LT50 between 4.4 and 5.2 days; P < 0.001). To evaluate the impact of these strains on host response, transcriptomic analysis showed that the ingestion of S. aureus led to a strong induction of defense genes (lys-5, sodh-1, and cyp-37B1) while H. kunzii did not. No statistical difference of host response genes expression was observed when C. elegans were infected with either S. aureus alone or with S. aureus + H. kunzii. Moreover, two well-characterized virulence factors (hla and agr) present in S. aureus were down-regulated when S. aureus were co-infected with H. kunzii. This study showed that H. kunzii decreased the virulence of S. aureus without modifying directly the host defense response. Factor(s) produced by this bacterium modulating the staphylococci virulence must be investigated. PMID:28361041

The Italian compassionate use of sofosbuvir in HCV patients waitlisted for liver transplantation: A national real-life experience.

PubMed

Martini, Silvia; Donato, Maria Francesca; Mazzarelli, Chiara; Rendina, Maria; Visco-Comandini, Ubaldo; Filì, Daniela; Gianstefani, Alice; Fagiuoli, Stefano; Melazzini, Mario; Montilla, Simona; Pani, Luca; Petraglia, Sandra; Russo, Pierluigi; Trotta, Maria Paola; Carrai, Paola; Caraceni, Paolo

2018-04-01

This study aimed to assess the real-life clinical and virological outcomes of HCV waitlisted patients for liver transplantation (LT) who received sofosbuvir/ribavirin (SOF/R) within the Italian compassionate use program. Clinical and virological data were collected in 224 patients with decompensated cirrhosis and/or hepatocellular carcinoma (HCC) receiving daily SOF/R until LT or up a maximum of 48 weeks. Of 100 transplanted patients, 51 were HCV-RNA negative for >4 weeks before LT (SVR12: 88%) and 49 negative for <4 weeks or still viraemic at transplant: 34 patients continued treatment after LT (bridging therapy) (SVR12: 88%), while 15 stopped treatment (SVR12: 53%). 98 patients completed SOF/R without LT (SVR12: 73%). In patients with advanced decompensated cirrhosis (basal MELD ≥15 and/or C-P ≥B8), a marked improvement of the scores occurred in about 50% of cases and almost 20% of decompensated patients without HCC reached a condition suitable for inactivation and delisting. These real-life data indicate that in waitlisted patients: (i) bridging antiviral therapy can be an option for patients still viraemic or negative <4 weeks at LT; and (ii) clinical improvement to a condition suitable for delisting can occur even in patients with advanced decompensated cirrhosis. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Prevention and treatment of Clostridium perfringens epsilon toxin intoxication in mice with a neutralizing monoclonal antibody (c4D7) produced in Nicotiana benthamiana.

PubMed

Garcia, J P; Beingesser, J; Bohorov, O; Bohorova, N; Goodman, C; Kim, D; Pauly, M; Velasco, J; Whaley, K; Zeitlin, L; Roy, C J; Uzal, F A

2014-09-01

Epsilon toxin (ETX), produced by Clostridium perfringens types B and D, is among the most lethal toxins known. ETX is a potential bioterrorism threat that was listed as a Category B agent by the U.S. Centers for Disease Control until 2012 and it still remains a toxin of interest for several government agencies. We produced a monoclonal antibody (MAb) against ETX (ETX MAb c4D7) in Nicotiana benthamiana and characterized its preventive and therapeutic efficacy in mice. The ETX preparation used was highly lethal for mice (LD50 = 1.6 μg/kg) and resulted in a mean time from inoculation to death of 18 and 180 min when administered intravenously or intraperitoneally, respectively. High lethal challenge resulted in dramatic increases of a variety of pro-inflammatory cytokines in serum, while lower, but still lethal doses, did not elicit such responses. ETX MAb c4D7 was highly effective prophylactically (ED50 = 0.3 mg/kg; ED100 = 0.8 mg/kg) and also provided protection when delivered 15-30 min post-ETX intoxication. These data suggest that ETX MAb c4D7 may have use as a pre- and post-exposure treatment for ETX intoxication. Copyright © 2014 Elsevier Ltd. All rights reserved.

Performance investigation on dissipative dielectric elastomer generators with a triangular energy harvesting scheme

NASA Astrophysics Data System (ADS)

Fan, Peng; Chen, Hualing; Li, Bo; Wang, Yongquan

2017-11-01

In this letter, a theoretical framework describing an energy harvesting cycle including the loss of tension (LT) process is proposed to investigate the energy harvesting performance of a dielectric elastomer generator (DEG) with a triangular energy harvesting scheme by considering material viscosity and leakage current. As the external force that is applied to the membrane decreases, the membrane is relaxed. When the external force decreases to zero, the condition is known as LT. Then the membrane undergoing LT can further relax, which is referred to as the LT process. The LT process is usually ignored in theoretical analysis but observed from energy harvesting experiments of DEGs. It is also studied how shrinking time and transfer capacitor affect the energy conversion of a DEG. The results indicate that energy density and conversion efficiency can be simultaneously improved by choosing appropriate shrinking time and transfer capacitor to optimize the energy harvesting cycle. The results and methods are expected to provide guidelines for the optimal design and assessment of DEGs.

[Indications of lung transplantation: Patients selection, timing of listing, and choice of procedure].

PubMed

Morisse Pradier, H; Sénéchal, A; Philit, F; Tronc, F; Maury, J-M; Grima, R; Flamens, C; Paulus, S; Neidecker, J; Mornex, J-F

2016-02-01

Lung transplantation (LT) is now considered as an excellent treatment option for selected patients with end-stage pulmonary diseases, such as COPD, cystic fibrosis, idiopathic pulmonary fibrosis, and pulmonary arterial hypertension. The 2 goals of LT are to provide a survival benefit and to improve quality of life. The 3-step decision process leading to LT is discussed in this review. The first step is the selection of candidates, which requires a careful examination in order to check absolute and relative contraindications. The second step is the timing of listing for LT; it requires the knowledge of disease-specific prognostic factors available in international guidelines, and discussed in this paper. The third step is the choice of procedure: indications of heart-lung, single-lung, and bilateral-lung transplantation are described. In conclusion, this document provides guidelines to help pulmonologists in the referral and selection processes of candidates for transplantation in order to optimize the outcome of LT. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Lethal and sub-lethal effects of elevated CO2 concentrations on marine benthic invertebrates and fish.

PubMed

Lee, Changkeun; Hong, Seongjin; Kwon, Bong-Oh; Lee, Jung-Ho; Ryu, Jongseong; Park, Young-Gyu; Kang, Seong-Gil; Khim, Jong Seong

2016-08-01

Concern about leakage of carbon dioxide (CO2) from deep-sea storage in geological reservoirs is increasing because of its possible adverse effects on marine organisms locally or at nearby coastal areas both in sediment and water column. In the present study, we examined how elevated CO2 affects various intertidal epibenthic (benthic copepod), intertidal endobenthic (Manila clam and Venus clam), sub-tidal benthic (brittle starfish), and free-living (marine medaka) organisms in areas expected to be impacted by leakage. Acute lethal and sub-lethal effects were detected in the adult stage of all test organisms exposed to varying concentrations of CO2, due to the associated decline in pH (8.3 to 5.2) during 96-h exposure. However, intertidal organisms (such as benthic copepods and clams) showed remarkable resistance to elevated CO2, with the Venus clam being the most tolerant (LpH50 = 5.45). Sub-tidal species (such as brittle starfish [LpH50 = 6.16] and marine medaka [LpH50 = 5.91]) were more sensitive to elevated CO2 compared to intertidal species, possibly because they have fewer defensive capabilities. Of note, the exposure duration might regulate the degree of acute sub-lethal effects, as evidenced by the Venus clam, which showed a time-dependent effect to elevated CO2. Finally, copper was chosen as a model toxic element to find out the synergistic or antagonistic effects between ocean acidification and metal pollution. Combination of CO2 and Cu exposure enhances the adverse effects to organisms, generally supporting a synergistic effect scenario. Overall, the significant variation in the degree to which CO2 adversely affected organisms (viz., working range and strength) was clearly observed, supporting the general concept of species-dependent effects of elevated CO2.

Liver transplantation may prevent neurodevelopmental deterioration in high-risk patients with urea cycle disorders.

PubMed

Kido, Jun; Matsumoto, Shirou; Momosaki, Ken; Sakamoto, Rieko; Mitsubuchi, Hiroshi; Endo, Fumio; Nakamura, Kimitoshi

2017-09-01

UCDs are among the most common inherited metabolic diseases in Japan. We investigated the clinical manifestations, treatment, and prognoses of 177 patients with UCDs who were evaluated and treated from January 1999 to March 2009 in Japan, using a questionnaire survey. Among these 177 patients, 42 (seven with carbamoyl phosphate synthetase 1 deficiency, 27 with ornithine transcarbamylase deficiency, seven with argininosuccinate synthetase deficiency, and one with arginase 1 deficiency) underwent living-donor LT. Although this study was retrospective and included limited neurodevelopmental information before and after LT, we evaluated whether LT could improve neurodevelopmental outcomes in patients with UCDs. The neurodevelopmental outcomes of patients with a MAC of <300 μmol/L at the time of onset were not significantly different between the LT and non-LT groups (P=.222). LT may have prevented further neurodevelopmental complications in children with MAC ≥300 μmol/L (P=.008) compared with non-transplant management. Therefore, Liver transplant should be considered in patients with UCD with a MAC of ≥300 μmol/L at the time of disease onset. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Analysis of heart rate deflection points to predict the anaerobic threshold by a computerized method.

PubMed

Marques-Neto, Silvio R; Maior, Alex S; Maranhão Neto, Geraldo A; Santos, Edil L

2012-07-01

Many studies have used the heart rate deflection points (HRDPs) during incremental exercise tests, because of their strong correlation with the anaerobic threshold. The aim of this study was to evaluate the profile of the HRDPs identified by a computerized method and compare them with ventilatory and lactate thresholds. Twenty-four professional soccer players (age, 22 ± 5 years; body mass, 74 ± 7 kg; height 177 ± 7 cm) volunteered for the study. The subjects completed a Bruce-protocol incremental treadmill exercise test to volitional fatigue. Heart rate (HR) and alveolar gas exchange were recorded continuously at ≥1 Hz during exercise testing. Subsequently, the time course of the HR was fit by a computer algorithm, and a set of lines yielding the lowest pooled residual sum of squares was chosen as the best fit. This procedure defined 2 HRDPs (HRDP1 and HRDP2). The HR break points averaged 43.9 ± 5.9 and 89.7 ± 7.5% of the VO2peak. The HRDP1 showed a poor correlation with ventilatory threshold (VT; r = 0.50), but HRDP2 was highly correlated to the respiratory compensation (RC) point (r = 0.98). Neither HRDP1 nor HRDP2 was correlated with LT1 (at VO2 = 2.26 ± 0.72 L·min(-1); r = 0.26) or LT2 (2.79 ± 0.59 L·min(-1); r = 0.49), respectively. LT1 and LT2 also were not well correlated with VT (2.93 ± 0.68 L·min(-1); r = 0.20) or RC (3.82 ± 0.60 L·min(-1); r = 0.58), respectively. Although the HR deflection points were not correlated to LT, HRDP2 could be identified in all the subjects and was strongly correlated with RC, consistent with a relationship to cardiorespiratory fatigue and endurance performance.

Modulation of the atmospheric quasi-biweekly oscillation on the diurnal variation of the occurrence frequency of the Tibetan Plateau vortices

NASA Astrophysics Data System (ADS)

Li, Lun; Zhang, Renhe; Wen, Min

2018-06-01

In this study, modulation of the atmospheric quasi-biweekly oscillation (QBWO) on diurnal variation of the occurrence frequency of Tibetan Plateau vortices (TPVs) during May-August of 2000-2009 was investigated. The diurnal variations of the occurrence frequency of the TPVs (OFTPVs) and the related dynamic and thermodynamic features in the positive and negative phases of QBWO were compared. In both the positive and negative phases, the OFTPVs reaches the maximum from evening to midnight (18-00 LT, LT indicates the local time), and minimum from early morning to noon (06-12 LT). At 18 LT, there is strongest convergence at 500 hPa and ascending motion, as well as the most abundant net water vapor budget over the Tibetan Plateau, which is in favor of the precipitation and the related condensation latent heat release, corresponding to the maximum of OFTPVs in 18-00 LT. On the contrary, in the early morning at 06 LT, the conditions are most unfavorable for genesis of TPVs in 06-12 LT. QBWO leads to stronger convergence at 500 hPa, ascending motion as well as more massive water vapor in the positive phases than those in the negative phases, resulting in larger numbers of TPVs occur in all of the four periods of a day (00-06 LT, 06-12 LT, 12-18 LT, and 18-00 LT) in the former. The TPVs generating from the early morning to noon (06-12 LT) are weaker and more sensitive and fragile to the disadvantageous background, while the TPVs occurring from evening to midnight (18-00 LT) are stronger and seem to be well tolerated, leading to more remarkable contrast between the OFTPVs in the negative and positive phases in 06-12 LT than in 18-00 LT.

The dynamic and clinical significance of autoantibodies and immunoglobulins in liver transplant recipients.

PubMed

Stanca, Carmen M; Aloman, Costica; Fiel, Maria Isabel; Raja, Kaiser; Uskudar, Oguz; Florman, Sander; Schiano, Thomas D

2016-03-01

Little is known about autoantibody pattern in liver transplantation (LT). The aim of the study was to examine autoantibodies (AAB) and immunoglobulins in patients with end-stage liver disease before and after LT. Patients with LT who underwent post-LT biopsies between 10/2008 and 8/2011 were enrolled. AAB were assessed at the time of LT and liver biopsy. Demographics, serum immunoglobulins, AAB, and liver histology (explant, post-LT biopsies) were analyzed. Two hundred and twenty patients (M/F 143/77; age at LT 54 (19-73)) were included; AAB and immunoglobulins were evaluated in 76 patients. Length of follow-up from LT was 285 (30-1462) days. Sixty-one percent of patients had hepatitis C (HCV); 83% developed recurrent HCV. A significant decrease in IgG, IgA, IgM (p < 0.001 each), anticardiolipin antibodies IgG and IgM (p = 0.02), and beta-2 microglobulin (p = 0.004) was observed post-LT. HCV patients had higher IgG (p = 0.005), rheumatoid factor (p = 0.044) before LT; elevated IgM was associated with increased inflammation in the explant (p = 0.007). Lower IgG levels and antismooth muscle antibodies were present before LT in a higher percentage in patients who would develop recurrent HCV (p = 0.004, p = 0.077, respectively). In conclusion, AAB change significantly after LT and have a different pattern in HCV. Some immunological markers are associated with HCV recurrence and advanced inflammation on explant. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Differences in susceptibility of inbred mice to Bacillus anthracis.

PubMed Central

Welkos, S L; Keener, T J; Gibbs, P H

1986-01-01

Animal species differ in their resistance both to infection by Bacillus anthracis and to anthrax toxin. A mouse model was developed to study the basis of the host differences and the pathogenesis of infection. When mice were infected with the virulent B. anthracis strain Vollum 1B, low 50% lethal dose (LD50) values (5 to 30 spores) were found for all 10 strains of inbred mice tested. However, analysis of time-to-death data revealed significant differences among the strains, which could be divided into three groups: most susceptible (A/J and DBA/2J); least susceptible (CBA/J, BALB/cJ, and C57BR/cdJ); and intermediate (the remaining five strains). In contrast, the mice were distinctly susceptible or resistant to lethal infection by the toxigenic, nonencapsulated Sterne vaccine strain. The LD50 for the susceptible A/J and DBA/2J mice was approximately 10(3) spores of the Sterne strain, whereas the remaining eight relatively resistant strains were killed only by 10(6) or more spores. F1 hybrid and backcross studies suggested that resistance to the Sterne strain is determined by a single dominant gene or gene complex. Mice lethally infected with B. anthracis showed an acute course of infection, characterized by extensive gelatinous edema and large concentrations of bacilli in the blood and organs (e.g., 10(9) CFU/g of spleen). The susceptibility of A/J and CBA/J mice to intravenously injected anthrax toxin components appeared to differ from their susceptibility to infection. The toxin LD50 values for both strains were similar. However, CBA/J mice died sooner than did A/J mice, with mean time to death of 0.9 and 3.7 days, respectively, in mice given 4 LD50 of toxin. The mouse model appears to be useful in studies on host resistance to anthrax and on the pathogenesis of the infection. PMID:3081444

Arctic skate Amblyraja hyperborea preys on remarkably large glacial eelpouts Lycodes frigidus.

PubMed

Byrkjedal, I; Christiansen, J S; Karamushko, O V; Langhelle, G; Lynghammar, A

2015-01-01

During scientific surveys on the continental slopes north-west of Spitsbergen and off north-east Greenland (c. 600 and 1000 m depths), two female Arctic skates Amblyraja hyperborea were caught while swallowing extraordinary large individuals of glacial eelpout Lycodes frigidus. The total length (LT) of the prey constituted 50 and 80% of the LT of the skates, which reveal that A. hyperborea are capable predators of fishes of surprisingly large relative size. © 2014 The Fisheries Society of the British Isles.

Lymphatic involution and early mortality in the young chicken produced by 2.2 GeV protons

NASA Technical Reports Server (NTRS)

Montour, J. L.; Shellabarger, C. J.

1972-01-01

Young single-comb white Leghorn cockerels were subjected to single acute doses of either 2.2 GeV protons or 250 kVp X-rays. Since young chickens exposed in the lethal range die within 48 hours of exposure, an hourly tabulation of deaths was recorded for this length of time after exposure. Animals which were exposed to sublethal doses were killed five days after exposure and their major lymphatic organs, (thymus, bursa, and spleen), removed and weighed. In the lethal range, animals exposed to 2.2 GeV protons died sooner than those receiving similar doses of X-rays, but total mortality was similar in each case at similar dose levels. The 48 hour LD sub 50 was determined to be 710 rad. Measured five days after exposure, 50% depression ED sub 50 for lymphatic organs occurred as follows: (1) thymus, 350 rad; (2) pursa, 500 rad, and (3) spleen, 450 rad. In all case R.B.E. values were not different from unity.

Clearance of hepatitis C virus after living-donor liver transplantation in spite of residual viremia on end date of interferon therapy before transplantation

PubMed Central

Ichikawa, Tatsuki; Nakao, Kazuhiko; Hamasaki, Keisuke; Honda, Takuya; Shibata, Hidetaka; Akahoshi, Mana; Eguchi, Susumu; Takatsuki, Mitsuhisa; Kanematsu, Takashi; Eguchi, Katsumi

2007-01-01

Interferon (IFN) therapy is the only treatment strategy for hepatitis C virus (HCV) infection after liver transplantation (LT), but prophylactic and treatable IFN therapy after LT has been shown to be insufficient due to the adverse effects of IFN and rivabirin. In this paper, we describe the disappearance of HCV after LT without IFN therapy in the presence of residual viremia on the day of LT. We herein report our findings since this is considered an important case for the anti-HCV strategy of post LT. A 60-year old woman with LC and HCC was referred to Nagasaki University Hospital in August 2004. After she underwent LT on February 18, 2005, we injected peg-IFN-α-2a the 11th time at 18 wk and HCV-RNA was still positive in the serum at LT. The serum HCV-RNA was negative one month after operation and subsequently dissolved 15 mo after operation without IFN therapy. As a result, we speculate that if HCV-RNA is positive while HCV core antigen is negative before LT, then it may lead to clearance of HCV after LT. Therefore long acting peg-IFN-α-2a is thus considered a potentially effective agent for the treatment of HCV-related cirrhosis before LT. PMID:17696240

Pre-acclimation to low ammonia improves ammonia handling in common carp (Cyprinus carpio) when exposed subsequently to high environmental ammonia.

PubMed

Shrivastava, Jyotsna; Sinha, Amit Kumar; Datta, Surjya Narayan; Blust, Ronny; De Boeck, Gudrun

2016-11-01

We tested whether exposing fish to low ammonia concentrations induced acclimation processes and helped fish to tolerate subsequent (sub)lethal ammonia exposure by activating ammonia excretory pathways. Common carp (Cyprinus carpio) were pre-exposed to 0.27mM ammonia (∼10% 96h LC 50 ) for 3, 7 and 14days. Thereafter, each of these pre-exposed and parallel naïve groups were exposed to 1.35mM high environmental ammonia (HEA, ∼50% 96h LC 50 ) for 12h and 48h to assess the occurrence of ammonia acclimation based on sub-lethal end-points, and to lethal ammonia concentrations (2.7mM, 96h LC 50 ) in order to assess improved survival time. Results show that fish pre-exposed to ammonia for 3 and 7days had a longer survival time than the ammonia naïve fish. However, this effect disappeared after prolonged (14days) pre-exposure. Ammonia excretion rate (J amm ) was strongly inhibited (or even reversed) in the unacclimated groups during HEA. On the contrary, after 3days the pre-exposure fish maintained J amm while after 7days these pre-acclimated fish were able to increase J amm efficiently. Again, this effect disappeared after 14days of pre-acclimation. The efficient ammonia efflux in pre-acclimated fish was associated with the up-regulation of branchial mRNA expression of ammonia transporters and exchangers. Pre-exposure with ammonia for 3-7days stimulated an increment in the transcript level of gill Rhcg-a and Rhcg-b mRNA relative to the naïve control group and the up-regulation of these two Rhcg homologs was reinforced during subsequent HEA exposure. No effect of pre-exposure was noted for Rhbg. Relative to unacclimated fish, the transcript level of Na + /H + exchangers (NHE-3) was raised in 3-7days pre-acclimated fish and remained higher during the subsequent HEA exposure while gill H + -ATPase activities and mRNA levels were not affected by pre-acclimation episodes. Likewise, ammonia pre-acclimated fish with or without HEA exposure displayed pronounced up-regulation in Na + /K + -ATPase activity and mRNA expression relative to the corresponding ammonia naïve groups. Overall, these data suggest that ammonia acclimation was evident for both lethal and the sub-lethal endpoints through priming mechanisms in ammonia excretory transcriptional processes, but these acclimation effects were transient and disappeared after prolonged pre-exposure. Copyright © 2016 Elsevier B.V. All rights reserved.

Psycho-social outcome in liver transplanted children: beware of emotional self-assessment!

PubMed

Calinescu, Ana Maria; McLin, Valérie A; Belli, Dominque; Wildhaber, Barbara E

2012-08-10

Psycho-social outcome in children after liver transplantation (LT) is known to be inferior to age-related peers. Yet, when children and their parents are questioned by their nurse or physician about the child's psycho-social well-being, the answers usually are very positive. We hypothesized that patients and their parents after LT report their psycho-social well-being too enthusiastically when enquired by their personal care takers. LT at the Children's University Hospital of Geneva 1992-2007, age >3 years, <16 years, time after LT >2 years. Children and their parents were questioned by their well-known, familiar nurse at the annual follow up visit about their personal well-being. To allow for evaluation of answers, scores (good, medium, bad) were attributed to the different questions. 46 children were included in the study. Mean age at enquiry was 9.7 years (SD 4 years), mean time after LT was 7.5 years (SD 4.2 years). The different themes were reported as good for: parent-child relationship (83%), relationship with peers (98%), relation with siblings (39%), sport activities (54%), play activities (78%), school performance (87%), expression skills (67%), and general behavior (89%). Most of our LT children and their parents consider, during a personal interview with a closely related, familiar nurse, that the child's psycho-social outcome is good. Yet, it is generally acknowledged that children after LT have negatively altered psycho-social outcomes. Thus, emotionally influenced reports about psycho-social outcome in children after LT must be looked at with care.

Synthesis of silver and gold nanoparticles using Jasminum nervosum leaf extract and its larvicidal activity against filarial and arboviral vector Culex quinquefasciatus Say (Diptera: Culicidae).

PubMed

Lallawmawma, H; Sathishkumar, Gnanasekar; Sarathbabu, Subburayan; Ghatak, Souvik; Sivaramakrishnan, Sivaperumal; Gurusubramanian, Guruswami; Kumar, Nachimuthu Senthil

2015-11-01

Silver and gold nanoparticles of Jasminum nervosum L. had unique optical properties such as broad absorbance band in the visible region of the electromagnetic spectrum. Characterization of the nanoparticles using UV spectrophotometer, Fourier transform infrared spectroscopy, X-ray diffraction, and transmission electron microscopy confirmed that the particles were silver (AgNPs) and gold (AuNPs) ranging between 4-22 and 2-20 nm with an average particles size of 9.4 and 10 nm, respectively. AgNPs and AuNPs of J. nervosum had high larvicidal activity on the filarial and arboviral vector, Culex quinquefasciatus, than the leaf aqueous extract. Observed lethal concentrations (LC50 and LC95) against the third instar larvae were 57.40 and 144.36 μg/ml for AgNPs and 82.62 and 254.68 μg/ml for AuNPs after 24 h treatment, respectively. The lethal time to kill 50% of C. quinquefasciatus larvae were 2.24 and 4.51 h at 150 μg/ml of AgNPs and AuNPs, respectively, while in the case of aqueous leaf extract of J. nervosum it was 9.44 h at 500 μg/ml (F 2,14 = 397.51, P < 0.0001). The principal component analysis plot presented differential clustering of the aqueous leaf extract, AgNP and AuNPs in relation to lethal dose and lethal time. It is concluded from the present findings that the biosynthesised AgNPs and AuNPs using leaf aqueous extract of J. nervosum could be an environmentally safer nanobiopesticide, and provided potential larvicidal effect on C. quinquefasciatus larvae which could be used for prevention of several dreadful diseases.

Defining the determinants of endurance running performance in the heat

PubMed Central

James, Carl A.; Hayes, Mark; Willmott, Ashley G. B.; Gibson, Oliver R.; Schlader, Zachary J.; Maxwell, Neil S.

2017-01-01

ABSTRACT In cool conditions, physiologic markers accurately predict endurance performance, but it is unclear whether thermal strain and perceived thermal strain modify the strength of these relationships. This study examined the relationships between traditional determinants of endurance performance and time to complete a 5-km time trial in the heat. Seventeen club runners completed graded exercise tests (GXT) in hot (GXTHOT; 32°C, 60% RH, 27.2°C WBGT) and cool conditions (GXTCOOL; 13°C, 50% RH, 9.3°C WBGT) to determine maximal oxygen uptake (V̇O2max), running economy (RE), velocity at V̇O2max (vV̇O2max), and running speeds corresponding to the lactate threshold (LT, 2 mmol.l−1) and lactate turnpoint (LTP, 4 mmol.l−1). Simultaneous multiple linear regression was used to predict 5 km time, using these determinants, indicating neither GXTHOT (R2 = 0.72) nor GXTCOOL (R2 = 0.86) predicted performance in the heat as strongly has previously been reported in cool conditions. vV̇O2max was the strongest individual predictor of performance, both when assessed in GXTHOT (r = −0.83) and GXTCOOL (r = −0.90). The GXTs revealed the following correlations for individual predictors in GXTHOT; V̇O2max r = −0.7, RE r = 0.36, LT r = −0.77, LTP r = −0.78 and in GXTCOOL; V̇O2max r = −0.67, RE r = 0.62, LT r = −0.79, LTP r = −0.8. These data indicate (i) GXTHOT does not predict 5 km running performance in the heat as strongly as a GXTCOOL, (ii) as in cool conditions, vV̇O2max may best predict running performance in the heat. PMID:28944273

Reversible non-ischaemic cardiomyopathy and left ventricular dysfunction after liver transplantation: a single-centre experience.

PubMed

Yataco, Maria L; Difato, Thomas; Bargehr, Johannes; Rosser, Barry G; Patel, Tushar; Trejo-Gutierrez, Jorge F; Pungpapong, Surakit; Taner, C Burcin; Aranda-Michel, Jaime

2014-07-01

Non-ischaemic cardiomyopathy (NIC) is an early complication of liver transplantation (LT). Our aims were to define the prevalence, associated clinical factors, and prognosis of this condition. A retrospective study was performed on patients undergoing LT at our institution from January 2005 to December 2012. Patients who developed NIC were identified. Data collected included demographic and clinical data. A total 1460 transplants were performed in this period and seventeen patients developed NIC. Pretransplant median QTc interval was 459 (range, 405-530), and median E/A ratio was 1 (range, 0.71-1.67). Fourteen patients (82%) were severely malnourished and required nutritional support. Thirteen patients (76%) had renal insufficiency. Median time to onset was 2 days post-transplant (range, 0-20). Echocardiograms showed global left ventricular hypokinesis and a decrease in ejection fraction (EF) from a median of 65% (range, 50-81) pretransplant to a median of 21% (range, 15-32). Median raw model for end-stage liver disease (MELD) score was 29 in patients with NIC vs. 18 in patients without cardiomyopathy (P = 0.01). There was no significant difference between recipients with NIC vs. recipients without cardiomyopathy regarding donor age, donor risk index, and cold and warm ischaemia time. Recovery of cardiac function occurred in 16 patients, with a median EF of 44% (range, 25-65%) at the time of discharge. The last echocardiogram available showed a median EF of 59% (range, 49-73%). One-year survival of NIC patients was 94.1%. Non-ischaemic cardiomyopathy is a rare complication after LT. Patients with NIC are critically ill, with high MELD score, and severe malnutrition. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Practical Advice on Calculating Confidence Intervals for Radioprotection Effects and Reducing Animal Numbers in Radiation Countermeasure Experiments

PubMed Central

Landes, Reid D.; Lensing, Shelly Y.; Kodell, Ralph L.; Hauer-Jensen, Martin

2014-01-01

The dose of a substance that causes death in P% of a population is called an LDP, where LD stands for lethal dose. In radiation research, a common LDP of interest is the radiation dose that kills 50% of the population by a specified time, i.e., lethal dose 50 or LD50. When comparing LD50 between two populations, relative potency is the parameter of interest. In radiation research, this is commonly known as the dose reduction factor (DRF). Unfortunately, statistical inference on dose reduction factor is seldom reported. We illustrate how to calculate confidence intervals for dose reduction factor, which may then be used for statistical inference. Further, most dose reduction factor experiments use hundreds, rather than tens of animals. Through better dosing strategies and the use of a recently available sample size formula, we also show how animal numbers may be reduced while maintaining high statistical power. The illustrations center on realistic examples comparing LD50 values between a radiation countermeasure group and a radiation-only control. We also provide easy-to-use spreadsheets for sample size calculations and confidence interval calculations, as well as SAS® and R code for the latter. PMID:24164553

Treatment carryover impacts on effectiveness of intraocular pressure lowering agents, estimated by a discrete event simulation model.

PubMed

Denis, P; Le Pen, C; Umuhire, D; Berdeaux, G

2008-01-01

To compare the effectiveness of two treatment sequences, latanoprost-latanoprost timolol fixed combination (L-LT) versus travoprost-travoprost timolol fixed combination (T-TT), in the treatment of open-angle glaucoma (OAG) or ocular hypertension (OHT). A discrete event simulation (DES) model was constructed. Patients with either OAG or OHT were treated first-line with a prostaglandin, either latanoprost or travoprost. In case of treatment failure, patients were switched to the specific prostaglandin-timolol sequence LT or TT. Failure was defined as intraocular pressure higher than or equal to 18 mmHg at two visits. Time to failure was estimated from two randomized clinical trials. Log-rank tests were computed. Linear functions after log-log transformation were used to model time to failure. The time horizon of the model was 60 months. Outcomes included treatment failure and disease progression. Sensitivity analyses were performed. Latanoprost treatment resulted in more treatment failures than travoprost (p<0.01), and LT more than TT (p<0.01). At 60 months, the probability of starting a third treatment line was 39.2% with L-LT versus 29.9% with T-TT. On average, L-LT patients developed 0.55 new visual field defects versus 0.48 for T-TT patients. The probability of no disease progression at 60 months was 61.4% with L-LT and 65.5% with T-TT. Based on randomized clinical trial results and using a DES model, the T-TT sequence was more effective at avoiding starting a third line treatment than the L-LT sequence. T-TT treated patients developed less glaucoma progression.

A COMPARISON OF THE LETHAL AND SUBLETHAL TOXICITY OF ORGANIC CHEMICAL MIXTURES TO THE FATHEAD MINNOW (PIMEPHALES PROMELAS)

EPA Science Inventory

The joint toxic effects of known binary and multiple organic chemical mixtures to the fathead minnow (Pimephales promelas) were defined at both the 96-h 50% lethal effect concentration (LC50) and sublethal (32-d growth) response levels for toxicants with a narcosis I, narcosis II...

The Evolution of the Faint End of the UV Luminosity Function during the Peak Epoch of Star Formation (1 < z < 3)

NASA Astrophysics Data System (ADS)

Alavi, Anahita; Siana, Brian; Richard, Johan; Rafelski, Marc; Jauzac, Mathilde; Limousin, Marceau; Freeman, William R.; Scarlata, Claudia; Robertson, Brant; Stark, Daniel P.; Teplitz, Harry I.; Desai, Vandana

2016-11-01

We present a robust measurement of the rest-frame UV luminosity function (LF) and its evolution during the peak epoch of cosmic star formation at 1\\lt z\\lt 3. We use our deep near-ultraviolet imaging from WFC3/UVIS on the Hubble Space Telescope and existing Advanced Camera for Surveys (ACS)/WFC and WFC3/IR imaging of three lensing galaxy clusters, Abell 2744 and MACS J0717 from the Hubble Frontier Field survey and Abell 1689. Combining deep UV imaging and high magnification from strong gravitational lensing, we use photometric redshifts to identify 780 ultra-faint galaxies with {M}{UV}\\lt -12.5 AB mag at 1\\lt z\\lt 3. From these samples, we identified five new, faint, multiply imaged systems in A1689. We run a Monte Carlo simulation to estimate the completeness correction and effective volume for each cluster using the latest published lensing models. We compute the rest-frame UV LF and find the best-fit faint-end slopes of α =-1.56+/- 0.04, α =-1.72+/- 0.04, and α =-1.94+/- 0.06 at 1.0\\lt z\\lt 1.6, 1.6\\lt z\\lt 2.2, and 2.2\\lt z\\lt 3.0, respectively. Our results demonstrate that the UV LF becomes steeper from z˜ 1.3 to z˜ 2.6 with no sign of a turnover down to {M}{UV}=-14 AB mag. We further derive the UV LFs using the Lyman break “dropout” selection and confirm the robustness of our conclusions against different selection methodologies. Because the sample sizes are so large and extend to such faint luminosities, the statistical uncertainties are quite small, and systematic uncertainties (due to the assumed size distribution, for example) likely dominate. If we restrict our analysis to galaxies and volumes above \\gt 50 % completeness in order to minimize these systematics, we still find that the faint-end slope is steep and getting steeper with redshift, though with slightly shallower (less negative) values (α =-1.55+/- 0.06, -1.69 ± 0.07, and -1.79 ± 0.08 for z˜ 1.3, 1.9, and 2.6, respectively). Finally, we conclude that the faint star-forming galaxies with UV magnitudes of -18.5\\lt {M}{UV}\\lt -12.5 covered in this study produce the majority (55%-60%) of the unobscured UV luminosity density at 1\\lt z\\lt 3. Some of the data presented herein were obtained at the W.M. Keck Observatory, which is operated as a scientific partnership among the California Institute of Technology, the University of California, and the National Aeronautics and Space Administration. The Observatory was made possible by the generous financial support of the W.M. Keck Foundation.

Red-Light-Running Crashes' Classification, Comparison, and Risk Analysis Based on General Estimates System (GES) Crash Database.

PubMed

Zhang, Yuting; Yan, Xuedong; Li, Xiaomeng; Wu, Jiawei; Dixit, Vinayak V

2018-06-19

Red-light running (RLR) has been identified as one of the prominent contributing factors involved in signalized intersection crashes. In order to reduce RLR crashes, primarily, a better understanding of RLR behavior and crashes is needed. In this study, three RLR crash types were extracted from the general estimates system (GES), including go-straight (GS) RLR vehicle colliding with go-straight non-RLR vehicle, go-straight RLR vehicle colliding with left-turn (LT) non-RLR vehicle, and left-turn RLR vehicle colliding with go-straight non-RLR vehicle. Then, crash features within each crash type scenario were compared, and risk analyses of GS RLR and LT RLR were also conducted. The results indicated that for the GS RLR driver, the speed limit displayed the highest effects on the percentages of GS RLR collision scenarios. For the LT RLR driver, the number of lanes displayed the highest effects on the percentages of LT RLR collision scenarios. Additionally, the drivers who were older than 50 years, distracted, and had a limited view were more likely to be involved in LT RLR accidents. Furthermore, the speeding drivers were more likely to be involved in GS RLR accidents. These findings could give a comprehensive understanding of RLR crash features and propensities for each RLR crash type.

Placement of Intubating Laryngeal Mask Airway Is Easier than Placement of Laryngeal Tube during Manual In-Line Stabilisation of The Neck

PubMed Central

Komatsu, R.; Nagata, O.; Kamata, K.; Yamagata, K.; Sessler, D.I.; Ozaki, M.

2005-01-01

Summary We compared the usefulness of the laryngeal tube (LT) with the intubating laryngeal mask airway (ILMA) in 51 patients whose necks were stabilised by manual in-line traction. After induction of anaesthesia and neuromuscular block, the LT and ILMA were inserted consecutively in a randomised, crossover design. During pressure-controlled ventilation (20 cmH2O inspiratory pressure), we measured insertion attempts, time to establish positive-pressure ventilation, tidal volume, gastric insufflation, and minimum airway pressure at which gas leaked around the cuff. Data were compared using Wilcoxon signed-rank tests; P<0.05 was considered significant. Insertion was more difficult with the LT (successful at first attempt in 16 patients) than with the ILMA (successful at first attempt in 42 patients, P<0.0001). Time required for insertion was longer for the LT (28 [23–35] sec, median [interquartile range]) than the ILMA (20 [15–25] sec, P=0.0009). Tidal volume was less for the LT (440 [290–670] ml) than the ILMA. (630 [440–750] ml, P=0.013). Minimum airway pressure at which gas leak occurred and incidence of gastric insufflation were similar with two devices. In patients whose necks were stabilised with manual in-line traction, insertion of the ILMA was easier and quicker than insertion of the LT and tidal volume was greater with the ILMA than the LT. PMID:15644005

Review article: liver transplantation for hepatocellular carcinoma - a critical appraisal of the current worldwide listing criteria.

PubMed

Menon, K V; Hakeem, A R; Heaton, N D

2014-10-01

Liver transplantation (LT) plays an important role in the management of patients with hepatocellular carcinoma (HCC). Although early results following LT for HCC were poor, since the introduction of the Milan criteria in 1996 morphological criteria have since been well established. Thereafter, various expansions of the Milan criteria were introduced worldwide. Listing criteria for LT for HCC in the United Kingdom (UK) initially conformed to the Milan criteria but were re-defined in 2009 by expansion of the Milan criteria. To look at the evidence in literature on listing criteria and management of HCC worldwide in comparison with the UK. Secondly, we aim to review worldwide vs. UK literature on prioritisation models, loco-regional therapy protocols and role of alpha-fetoprotein (AFP) in LT for HCC. An electronic literature search with Medline was carried out to identify articles related to LT for HCC. Although various expansions of the Milan criteria have been described, they remain the gold standard against which other criteria are measured. The UK criteria are an expansion of the Milan criteria that go beyond Milan and University of California, San Francisco (UCSF) criteria. The current UK listing criteria for LT for HCC when compared to the worldwide criteria have a worse survival benefit (projected 5-year survival between 35-50%) when plotted on the metroticket calculator. In keeping with most transplant centres worldwide, the UK have adopted expansions to Milan to allow more patients to benefit from LT. However, currently, as it stands the UK criteria when plotted in the modification of the Metroticket model project worse survival that would seem unjustified. © 2014 John Wiley & Sons Ltd.

Alterations of intercellular junctions in peritoneal mesothelial cells from patients undergoing dialysis: effect of retinoic Acid.

PubMed

Retana, Carmen; Sanchez, Elsa; Perez-Lopez, Alejandro; Cruz, Armando; Lagunas, Jesus; Cruz, Carmen; Vital, Socorro; Reyes, Jose L

2015-01-01

Dialysis patients are classified according to their peritoneal permeability as low transporter (LT, low solute permeability) or high transporter (HT, high solute permeability). Tight junction (TJ) proteins are critical to maintain ions, molecules and water paracellular transport through peritoneum. Exposure to peritoneal dialysis solutions causes damage to TJ in human peritoneal mesothelial cells (HPMCs). We analyzed the quantity, distribution and function of TJ proteins: claudin-1, -2 and -8, ZO-1 and occludin, in HPMC cultures from LT and HT patients. Since all-trans retinoic acid (ATRA) might modify the expression of TJ proteins, we studied its effect on HPMCs. Control HPMCs were isolated from human omentum, while HT or LT cells were obtained from dialysis effluents. Cells were cultured in presence of ATRA 0, 50 or 100 nM. Transepithelial electrical resistance (TER) measurement, immunostaining and Western blot analyses were performed. HT exhibited lower TER than control and LT monolayers. Immunofluorescence for TJ was weak and discontinuous along the cell contour, in LT and HT. Furthermore, claudin-1, occludin and ZO-1 expressions were decreased. In all groups, claudin-2 was localized at nuclei. We observed that ATRA improved TJ distribution and increased TJ expression in HT. This retinoid did not modify claudin-2 and -8 expressions. All-trans retinoic acid decreased TER in HT, but had no effect in LT. Tight junctions were altered in HPMCs from dialyzed patients. The HT monolayer has lower TER than LT, which might be associated with the peritoneal permeability in these patients. ATRA might be a therapeutic alternative to maintain mesothelial integrity, since it improved TJ localization and expression. Copyright © 2015 International Society for Peritoneal Dialysis.

Alterations of Intercellular Junctions in Peritoneal Mesothelial Cells from Patients Undergoing Dialysis: Effect of Retinoic Acid

PubMed Central

Retana, Carmen; Sanchez, Elsa; Perez-Lopez, Alejandro; Cruz, Armando; Lagunas, Jesus; Cruz, Carmen; Vital, Socorro; Reyes, Jose L.

2015-01-01

♦ Background: Dialysis patients are classified according to their peritoneal permeability as low transporter (LT, low solute permeability) or high transporter (HT, high solute permeability). Tight junction (TJ) proteins are critical to maintain ions, molecules and water paracellular transport through peritoneum. Exposure to peritoneal dialysis solutions causes damage to TJ in human peritoneal mesothelial cells (HPMCs). We analyzed the quantity, distribution and function of TJ proteins: claudin-1, -2 and -8, ZO-1 and occludin, in HPMC cultures from LT and HT patients. Since all-trans retinoic acid (ATRA) might modify the expression of TJ proteins, we studied its effect on HPMCs. ♦ Methods: Control HPMCs were isolated from human omentum, while HT or LT cells were obtained from dialysis effluents. Cells were cultured in presence of ATRA 0, 50 or 100 nM. Transepithelial electrical resistance (TER) measurement, immunostaining and Western blot analyses were performed. ♦ Results: HT exhibited lower TER than control and LT monolayers. Immunofluorescence for TJ was weak and discontinuous along the cell contour, in LT and HT. Furthermore, claudin-1, occludin and ZO-1 expressions were decreased. In all groups, claudin-2 was localized at nuclei. We observed that ATRA improved TJ distribution and increased TJ expression in HT. This retinoid did not modify claudin-2 and -8 expressions. All-trans retinoic acid decreased TER in HT, but had no effect in LT. ♦ Conclusions: Tight junctions were altered in HPMCs from dialyzed patients. The HT monolayer has lower TER than LT, which might be associated with the peritoneal permeability in these patients. ATRA might be a therapeutic alternative to maintain mesothelial integrity, since it improved TJ localization and expression. PMID:24584604

A statistical analysis of equatorial plasma bubble structures based on an all-sky airglow imager network in China

NASA Astrophysics Data System (ADS)

Sun, Longchang; Xu, Jiyao; Wang, Wenbin; Yuan, Wei; Li, Qinzeng; Jiang, Chaowei

2016-11-01

This paper investigates the statistical features of equatorial plasma bubbles (EPBs) using airglow images from 2012 to 2014 from a ground-based network of four imagers in the equatorial region of China. It is found that (1) EPBs mainly occur during 21:00-00:00 local time (LT) in equinoxes. There is an asymmetry in occurrence rates between March (June) and September equinoxes (December solstices). (2) Most EPBs occur in groups of two to six depletions. The distance between adjacent EPB depletions is 100-700 km, and the average is 200-300 km. The zonal extension of an EPB group is usually less than 1500 km but can reach 3000 km. (3) EPBs usually have a maximum drift velocity near 100 m/s at 21:00-22:00 LT in 9.5° ± 1.5° geomagnetic latitude and then decrease to 50-70 m/s toward sunrise. (4) The averaged westward tilt angle of most EPBs (with respect to the geographic north-south) increased from 5°-10° to 23°-30° with LT between 20:00 and 03:00 LT, then decreasing to 10°-20° toward sunrise. (5) When 90 < F10.7 < 140, the maximum magnetic latitudinal extension (PMLE) is usually lower than 15.0° (apex height 725 km), but it can reach 23.0° (apex height 1330 km) when F10.7 > 140. The maximum PMLE increases by 3.4°-5.5° when F10.7 changes from 90 to 190. (6) The EPB occurrence patterns and zonal drift velocities are significantly different from those at Kolhapur, India, which locates west to our stations by 20.0°-32.0° in longitude.

Efficacy of osteopathic manipulation as an adjunctive treatment for hospitalized patients with pneumonia: a randomized controlled trial

PubMed Central

2010-01-01

Background The Multicenter Osteopathic Pneumonia Study in the Elderly (MOPSE) is a registered, double-blinded, randomized, controlled trial designed to assess the efficacy of osteopathic manipulative treatment (OMT) as an adjunctive treatment in elderly patients with pneumonia. Methods 406 subjects aged ≥ 50 years hospitalized with pneumonia at 7 community hospitals were randomized using concealed allocation to conventional care only (CCO), light-touch treatment (LT), or OMT groups. All subjects received conventional treatment for pneumonia. OMT and LT groups received group-specific protocols for 15 minutes, twice daily until discharge, cessation of antibiotics, respiratory failure, death, or withdrawal from the study. The primary outcomes were hospital length of stay (LOS), time to clinical stability, and a symptomatic and functional recovery score. Results Intention-to-treat (ITT) analysis (n = 387) found no significant differences between groups. Per-protocol (PP) analysis (n = 318) found a significant difference between groups (P = 0.01) in LOS. Multiple comparisons indicated a reduction in median LOS (95% confidence interval) for the OMT group (3.5 [3.2-4.0] days) versus the CCO group (4.5 [3.9-4.9] days), but not versus the LT group (3.9 [3.5-4.8] days). Secondary outcomes of duration of intravenous antibiotics and treatment endpoint were also significantly different between groups (P = 0.05 and 0.006, respectively). Duration of intravenous antibiotics and death or respiratory failure were lower for the OMT group versus the CCO group, but not versus the LT group. Conclusions ITT analysis found no differences between groups. PP analysis found significant reductions in LOS, duration of intravenous antibiotics, and respiratory failure or death when OMT was compared to CCO. Given the prevalence of pneumonia, adjunctive OMT merits further study. PMID:20302619

Acute toxicity of fipronil to the stingless bee Scaptotrigona postica Latreille.

PubMed

Jacob, Cynthia Renata Oliveira; Soares, Hellen Maria; Carvalho, Stephan Malfitano; Nocelli, Roberta Cornélio Ferreira; Malaspina, Osmar

2013-01-01

Fipronil is an insecticide widely used to control a great number of pests, thus the aim of this study was to determine the lethal dose and lethal concentration (LD(50) and LC(50)) of this insecticide to the stingless bees Scaptotrigona postica Latreille, 1807. The LD(50) and LC(50) values obtained after 24 h of exposition were of 0.54 ng a.i./bee and 0.24 ng a.i./μL diet, respectively. These values were considered highly toxic to stingless bees.

Relative toxicity of the pyrolysis products from some thermoplastic and thermoset polymers

NASA Technical Reports Server (NTRS)

Kourtides, D. A.; Gilwee, W. J., Jr.; Hilado, C. J.

1978-01-01

Relative toxicity data on the pyrolysis products of a variety of thermoplastic and thermoset polymers are presented. The data are presented in terms of time to incapacitation and time to death with a fixed sample weight of 1.0 g, and in terms of the apparent lethal concentration required to produce 50 percent mortality within a fixed exposure period of 30 min.

ITALIAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS STATEMENT-REPLACEMENT THERAPY FOR PRIMARY HYPOTHYROIDISM: A BRIEF GUIDE FOR CLINICAL PRACTICE.

PubMed

Guglielmi, Rinaldo; Frasoldati, Andrea; Zini, Michele; Grimaldi, Franco; Gharib, Hossein; Garber, Jeffrey R; Papini, Enrico

2016-11-01

Hypothyroidism requires life-long thyroid hormone replacement therapy in most patients. Oral levothyroxine (LT4) is an established safe and effective treatment for hypothyroidism, but some issues remain unsettled. The Italian Association of Clinical Endocrinologists appointed a panel of experts to provide an updated statement for appropriate use of thyroid hormone formulations for hypothyroidism replacement therapy. The American Association of Clinical Endocrinologists' protocol for standardized production of clinical practice guidelines was followed. LT4 is the first choice in replacement therapy. Thyroid-stimulating hormone (TSH) should be maintained between 1.0 and 3.0 mIU/L in young subjects and at the upper normal limit in elderly or fragile patients. Achievement of biochemical targets, patient well-being, and adherence to treatment should be addressed. In patients with unstable serum TSH, a search for interfering factors and patient compliance is warranted. Liquid or gel formulations may be considered in subjects with hampered LT4 absorption or who do not allow sufficient time before or after meals and LT4 replacement. Replacement therapy with LT4 and L-triiodothyronine (LT3) combination is generally not recommended. A trial may be considered in patients with normal values of serum TSH who continue to complain of symptoms of hypothyroidism only after co-existent nonthyroid problems have been excluded or optimally managed. LT3 should be administered in small (LT4:LT3 ratio, 10:1 to 20:1) divided daily doses. Combined therapy should be avoided in elderly patients or those with cardiac risk factors and in pregnancy. LT4 therapy should be aimed at resolution of symptoms of hypothyroidism, normalization of serum TSH, and improvement of quality of life. In selected cases, the use of liquid LT4 formulations or combined LT4/LT3 treatment may be considered to improve adherence to treatment or patient well-being. AACE = American Association of Clinical Endocrinologists FT3 = free triiodothyronine FT4 = free thyroxine LT3 = levotriiodothyronine LT4 = levothyroxine MeSH = medicine medical subject headings QoL = quality of life TSH = thyroid-stimulating hormone.

Statistical evidence of seismo-ionospheric precursors of the GPS total electron content in China

NASA Astrophysics Data System (ADS)

Chen, Yuh-Ing; Huang, Chi-Shen; Liu, Jann-Yenq

2015-04-01

Evidence of the seismo-ionospheric precursor (SIP) is reported by statistically investigating the relationship between the total electron content (TEC) in global ionosphere map (GIM) and 56 M≥6.0 earthquakes during 1998-2013 in China. A median-based method together with the z test is employed to examine the TEC variations 30 days before and after the earthquake. It is found that the TEC significantly decreases 0600-1000 LT 1-6 days before the earthquake, and anomalously increases in 3 time periods of 1300-1700 LT 12-15 days; 0000-0500 LT 15-17 days; and 0500-0900 LT 22-28 days before the earthquake. The receiver operating characteristic (ROC) curve is then used to evaluate the efficiency of TEC for predicting M≥6.0 earthquakes in China during a specified time period. Statistical results suggest that the SIP is the significant TEC reduction in the morning period of 0600-1000 LT. The SIP is further confirmed since the area under the ROC curve is positively associated with the earthquake magnitude.

Statistical evidences of seismo-ionospheric precursors applying receiver operating characteristic (ROC) curve on the GPS total electron content in China

NASA Astrophysics Data System (ADS)

Chen, Yuh-Ing; Huang, Chi-Shen; Liu, Jann-Yenq

2015-12-01

Evidence of the seismo-ionospheric precursor (SIP) is reported by statistically investigating the relationship between the total electron content (TEC) in global ionosphere map (GIM) and 56 M ⩾ 6.0 earthquakes during 1998-2013 in China. A median-based method together with the z test is employed to examine the TEC variations 30 days before and after the earthquake. It is found that the TEC significantly decreases 0600-1000 LT 1-6 days before the earthquake, and anomalously increases in 3 time periods of 1300-1700 LT 12-15 days; 0000-0500 LT 15-17 days; and 0500-0900 LT 22-28 days before the earthquake. The receiver operating characteristic (ROC) curve is then used to evaluate the efficiency of TEC for predicting M ⩾ 6.0 earthquakes in China during a specified time period. Statistical results suggest that the SIP is the significant TEC reduction in the morning period of 0600-1000 LT. The SIP is further confirmed since the area under the ROC curve is positively associated with the earthquake magnitude.

Upper temperature tolerance of loach minnow under acute, chronic, and fluctuating thermal regimes

USGS Publications Warehouse

Widmer, A.M.; Carveth, C.J.; Bonar, Scott A.; Simms, J.R.

2006-01-01

We used four methods to estimate the upper lethal temperature of loach minnow Rhinichthys cobitis: the lethal thermal method (LTM), chronic lethal method (CLM), acclimated chronic exposure (ACE) method with static temperatures, and ACE method with diel temperature fluctuations. The upper lethal temperature of this species ranged between 32??C and 38??C, depending on the method and exposure time; however, temperatures as low as 28??C resulted in slowed growth compared with the control groups. In LTM trials, we increased temperatures 0.3??C/min and death occurred at 36.8 ?? 0.2??C (mean ?? SE) for fish (37-19 mm total length) acclimated to 30??C and at 36.4 ?? 0.07??C for fish acclimated to 25??C. In CLM trials, temperatures were increased more slowly (1??C/d), allowing fish to acclimate. Mean temperature at death was 33.4 ?? 0.1??C for fish 25-35 mm and 32.9 ?? 0.4??C for fish 45-50 mm. In the ACE experiment with static temperatures, we exposed fish for 30 d to four constant temperatures. No fish (20-40 mm) survived beyond 30 d at 32??C and the 30-d temperature lethal to 50% of the test animals was 30.6??C. Growth at static 28??C and 30??C was slower than growth at 25??C, suggesting that fish were stressed at sublethal temperatures. In ACE trials with diel temperature fluctuations of 4,6, and 10??C and a 32??C peak temperature, over 80% of fish (20-40 mm) survived 30 d. Although brief exposures to 32??C were not lethal, the growth of fish in the three fluctuating-temperature treatments was significantly less than the growth at the ambient temperature (25-29??C). To minimize thermal stress and buffer against temperature spikes, we recommend that loach minnow habitat be managed to avoid water temperatures above 28??C. ?? Copyright by the American Fisheries Society 2006.

Self-management and self-efficacy status in liver recipients.

PubMed

Xing, Lei; Chen, Qin-Yun; Li, Jia-Ning; Hu, Zhi-Qiu; Zhang, Ye; Tao, Ran

2015-06-01

Liver transplantation (LT) is a viable treatment for patients with end-stage chronic liver diseases. The main aim of LT is to prolong life and improve life quality. However, although survival after LT continues to improve, some aspects of recipient's health-related quality of life such as self-management and self-efficacy have been largely ignored. A total of 124 LT recipients were included in this study. Questionnaires for general health status information and a "Self-Management Questionnaire for Liver Transplantation Recipients" modified from the Chinese version of "Chronic Disease Self-Management Program Questionnaire Code Book" were used in the survey. Data were collected by self-administered questionnaires. The overall status of self-management in LT recipients was not optimistic. The major variables affecting the self-management of LT recipients were marital status, educational level and employment. The overall status of self-efficacy in LT recipients was around the medium-level. Postoperative time and self-assessment of overall health status were found as the factors impacting on self-efficacy. The self-management behavior of LT recipients needs to be improved. The health care professionals need to offer targeted health education to individual patients, help them to establish healthy lifestyle, enhance physical activity and improve self-efficacy. The development of the multilevel and multifaceted social support system will greatly facilitate the self-management in LT patients.

HSP70 expression in Biomphalaria glabrata snails exposed to cadmium.

PubMed

da Silva Cantinha, Rebeca; Borrely, Sueli Ivone; Oguiura, Nancy; de Bragança Pereira, Carlos Alberto; Rigolon, Marcela M; Nakano, Eliana

2017-06-01

In this study, the effects of the heavy metal cadmium on the stress protein HSP70 are investigated in freshwater mollusks Biomphalaria glabrata. Adult snails were exposed for 96h to CdCl 2 at concentrations ranging from 0.09 to 0.7mgL -1 (LC 50/96h =0.34 (0.30-0.37). Time and concentration-dependent increases in the expression of HSP70 were observed at sub-lethal levels in the immunoblotting assay. Further, an increased survival to a lethal heat shock was observed in animals pre-exposed to a nonlethal concentration of cadmium, evidencing the induction of acquired tolerance. The present study demonstrated the inducibility of B. glabrata HSP70 by cadmium, a relevant environmental contaminant, at non-lethal levels, providing evidences that the assessment of HSP70 in B. glabrata can be regarded as a suitable biomarker for ecotoxicological studies. Copyright © 2017 Elsevier Inc. All rights reserved.

Decreasing incidence of symptomatic Epstein-Barr virus disease and posttransplant lymphoproliferative disorder in pediatric liver transplant recipients: report of the studies of pediatric liver transplantation experience.

PubMed

Narkewicz, Michael R; Green, Michael; Dunn, Stephen; Millis, Michael; McDiarmid, Susan; Mazariegos, George; Anand, Ravinder; Yin, Wanrong

2013-07-01

Posttransplant lymphoproliferative disorder (PTLD) causes significant morbidity and mortality in pediatric recipients of liver transplantation (LT). Describe the incidence of PTLD and symptomatic Epstein-Barr virus (SEBV) disease in a large multicenter cohort of children who underwent LT with a focus on the risk factors and changes in incidence over time. SEBV and PTLD were prospectively determined in 2283 subjects who had undergone LT for the first time with at least 1 year of follow-up in the Studies of Pediatric Liver Transplantation database. SEBV was defined with specific criteria, and PTLD required tissue confirmation. The incidence of SEBV and PTLD was determined with a Kaplan-Meier analysis. Univariate and multivariate modeling of risk factors was performed with standard methods. SEBV occurred in 199 patients; 174 (87.4%) were EBV-negative at LT. Seventy-five patients developed PTLD, and 64 (85.3%) of these patients were EBV-negative at LT. Among the 2048 patients with at least 2 years of follow-up, 8.3% developed SEBV by the second year after LT, and 2.8% developed PTLD. There were lower rates of SEBV (5.9% versus 11.3%, P < 0.001) and PTLD (1.7% versus 4.2%, P = 0.001) in 2002-2007 versus 1995-2001. In 2002-2007, tacrolimus and cyclosporine trough blood levels in the first year after LT were significantly lower, and fewer children were receiving steroids. Biliary atresia, and recipient EBV status were correlated. In a multivariate analysis, era of LT, recipient EBV status, and frequent rejection episodes were associated with SEBV and PTLD. The incidence of SEBV and PTLD is decreasing in pediatric LT recipients concomitantly with a reduction in immunosuppression. Younger recipients and those with multiple rejections remain at higher risk for SEBV and PTLD. © 2013 American Association for the Study of Liver Diseases.

Karnofsky Performance Status Before and After Liver Transplantation Predicts Graft and Patient Survival.

PubMed

Thuluvath, Paul J; Thuluvath, Avesh J; Savva, Yulia

2018-06-05

The Karnofsky Performance Status (KPS) has been used for almost 70 years for clinical assessment of patients. Our objective was to determine whether KPS is an independent predictor of post-liver transplant (LT) survival after adjusting for known confounders. Adult patients listed with UNOS from 2006 to 2016 were grouped patients into low (10-40%, n=15,103), intermediate (50-70%, n=22,183) and high (80-100%, n=13,131) KPS based on KPS scores at the time of LT after excluding those on ventilators or life support. We determined the trends in KPS before and after LT, and survival probabilities based on KPS. There was a decline in KPS scores between listing and LT and there was significant improvement after LT. The graft and patient survival differences were significantly lower (p<0.0001) in those with low KPS. After adjusting for other confounders, the hazard ratios (HR) for graft failure were 1.17 (1.12-1.22, p <0.01) for the intermediate and 1.38 (1.31-1.46, p <0.01) for the low group. Similarly, HR for patient failure were 1.18 (1.13-1.24, p <0.01) for the intermediate and 1.43 (1.35-1.52, p <0.01) for the low group. Other independent negative predictors for graft and patient survival were older age, Black ethnicity, presence of hepatic encephalopathy and donor risk index. Those who did not show significant improvements in post-LT KPS scores had poorer outcomes in all three KPS groups, but it was most obvious in the low KPS group with 1-year patient survival of 33%. The KPS, before and after LT, is an independent predictor of graft and patient survival after adjusting for other important predictors of survival. The overall health of liver transplant recipients could be assessed by a simple clinical assessment tool called Karnofsky Performance Status which assess an individual's overall functional status on 11-point scale, in increments of 10, where a score of 0 is considered dead and 100 is considered perfect health. In this study, using a large dataset, we show that the performance status before and after liver transplant could have an effect on survival. More importantly, those who have low performance status before transplant and do not show an improvement in performance status between 3-12 months after liver transplant have very poor survival. Copyright © 2018. Published by Elsevier B.V.

Correlation between ocular parameters and amplitude of accommodation

PubMed Central

Abraham, Lekha Mary; Kuriakose, Thomas; Sivanandam, Viswanathan; Venkatesan, Nithya; Thomas, Ravi; Muliyil, Jayaprakash

2010-01-01

Aim: To study the relationship between ocular parameters and amplitude of accommodation (AA) in the peri-presbyopic age group (35–50 years). Materials and Methods: Three hundred and sixteen right eyes of consecutive patients in the age group 35–50 years, who attended our outpatient clinic, were studied. Emmetropes, hypermetropes and myopes with best-corrected visual acuity of 20/20, J1 in both eyes were included. The AA was calculated by measuring the near point of accommodation. The axial length (AL), central anterior chamber depth (CACD) and lens thickness (LT) were also measured. Results: There was moderate correlation (Pearson’s correlation coefficient r = 0.56) between AL and AA as well as between CACD and AA (r = 0.53) in myopes in the age group 35–39 years. In the other age groups and the groups taken as a whole, there was no correlation. In hypermetropes and emmetropes, there was no correlation between AA and the above ocular parameters. No significant correlation existed between LT and AA across different age groups and refractive errors. Conclusion: There was no significant correlation between AA and ocular parameters like anterior chamber depth, AL and LT. PMID:20952831

Developmental toxicity of p,p'-dichlorodiphenyltrichloroethane, 2,4,6-trinitrotoluene, their metabolites, and benzo[a]pyrene in Xenopus laevis embryos.

PubMed

Saka, Masahiro

2004-04-01

Since 1995, high incidences of deformed frogs have been documented in Kitakyushu, Japan. In this area, relatively high concentrations of DDT, trinitrotoluene (TNT), their metabolites (p,p'-dichlorodiphenyldichloroethylene [DDE], p,p'-dichlorodiphenyldichloroethane [DDD], 2-amino-4,6-dinitrotoluene [2ADNT], and 4-amino-2,6-dinitrotoluene [4ADNT]), and benzo[a]pyrene [BaP]) have been identified from field samples. I used a standardized assay with Xenopus laevis embryos (frog embryo teratogenesis assay--Xenopus, FETAX) to examine the developmental toxicity of these compounds. Both DDE and BaP were considered nearly nontoxic in embryonic development because they induced low (< 10%) mortality and malformation incidence even at the highest concentrations tested (DDE, 393 microM; BaP, 13.2 microM). The DDD (96-h median lethal concentration [LC50] = 44.1 microM, 96-h median effective concentration [EC50] for malformation = 14.9 microM) was more lethal and teratogenic than its parent compound, DDT (96-h LC50 = 101 microM, 96-h EC50 = 41.5 microM). Predominant symptoms observed were axial malformations (DDT and DDD) and irregular gut coiling (DDT). However, DDT and DDD should not act as major lethal or teratogenic toxicants in the aquatic environment within a short-term exposure via water because their 96-h LC50 and 96-h EC50 values were extremely high, considering their low solubility in water. The TNT (96-h LC50 = 16.7 microM) was more lethal than 2ADNT (96-h LC50 = 166 microM) or 4ADNT (96-h LC50 = 115 microM). Although 4ADNT (96-h EC50 = 85.8 microM) induced various tadpole malformations, it was a weak teratogen compared with TNT (96-h EC50 = 9.78 microM) and 2ADNT (96-h EC50 = 16.9 microM). The most typical malformations observed were axial malformations, eye abnormalities (TNT), edema, and irregular gut coiling (2ADNT and 4ADNT). The 96-h LC50 and 96-h EC50 values of TNT, 2ADNT, and 4ADNT were lower than their saturated concentrations in water. Therefore, these nitroaromatic compounds may show lethal or teratogenic effects on aquatic animals if their habitats are severely contaminated with TNT.

The effects of red tide (Karenia brevis) on reflex impairment and mortality of sublegal Florida stone crabs, Menippe mercenaria.

PubMed

Gravinese, Philip M; Kronstadt, Stephanie M; Clemente, Talib; Cole, Cody; Blum, Patricia; Henry, Michael S; Pierce, Richard H; Lovko, Vincent J

2018-06-01

The Florida stone crab, Menippe mercenaria, is a major commercial fishery that occurs primarily along Florida's west coast, where harmful algal blooms of Karenia brevis frequently develop. To determine sublethal and lethal effects of K. brevis on M. mercenaria, we exposed sublegal stone crabs to three seawater treatments in laboratory conditions: no K. brevis (control), a low-toxin K. brevis strain (Wilson LT), and a toxic K. brevis (New Pass strain). Total food consumed, reflex impairment and survivorship of each crab was monitored throughout the nine-day experiment. Crabs in the toxic treatment consumed 67% less food. The probability of an individual losing a reflex significantly increased with time (days), and there was a 42% decrease in survivorship in the toxic treatment. This is the first study to demonstrate negative effects of K. brevis on the stone crab, presenting the critical need of further investigation to fully understand how red tide may impact sustainability of the fishery. Copyright © 2018 Elsevier Ltd. All rights reserved.

Characteristics of the low latitude ionospheric storm in the East-Asian region

NASA Astrophysics Data System (ADS)

Zhao, B.; Wan, W.; Liu, L.

2009-04-01

First, an classification of ionospheric storm effects in the sub-equatorial ionization anomaly(SEIA) region at 120°E has been performed through the analysis of ionogram data at two ionosonde stations, Wuhan (114.4°, 30.5°) and Chung-Li (121.2°, 25°), and total electron content (TEC) derived from GPS network distributed around 120°E during the year 1999-2004. Three types of negative phase are identified. One is shown to be varied in phase of F-layer height variation and the other two out of phase. Two types of positive phase are also found. The mechanisms to cause these types of ionospheric effects has been considered to be related with storm meridional thermospheric wind including traveling atmosphere disturbance(TAD), electric fields and composition changes. Then based on the 50 years of ionosonde and 8 years of global ionospheric maps (GIMs) data, features of low latitude ionospheric storm were obtained. Results shows that positive phases during 18:00-2400 LT with its center near the 21:00 LT and 24:00-08:00 LT with its center near the sunrise time have predomination in controlling the storm behavior at low latitudes. It is shown that the distortion of EIA under the effects of the above factors have significant influence on the behavior of SEIA ionogram parameters.

Filgrastim Improves Survival in Lethally Irradiated Nonhuman Primates

PubMed Central

Farese, Ann M.; Cohen, Melanie V.; Katz, Barry P.; Smith, Cassandra P.; Gibbs, Allison; Cohen, Daniel M.; MacVittie, Thomas J.

2015-01-01

Treatment of individuals exposed to potentially lethal doses of radiation is of paramount concern to health professionals and government agencies. We evaluated the efficacy of filgrastim to increase survival of nonhuman primates (NHP) exposed to an approximate mid-lethal dose (LD50/60) (7.50 Gy) of LINAC-derived photon radiation. Prior to total-body irradiation (TBI), nonhuman primates were randomized to either a control (n =22) or filgrastim-treated (n =24) cohorts. Filgrastim (10 μg/kg/d) was administered beginning 1 day after TBI and continued daily until the absolute neutrophil count (ANC) was >1,000/μL for 3 consecutive days. All nonhuman primates received medical management as per protocol. The primary end point was all cause overall mortality over the 60 day in-life study. Secondary end points included mean survival time of decedents and all hematologic-related parameters. Filgrastim significantly (P < 0.004) reduced 60 day overall mortality [20.8% (5/24)] compared to the controls [59.1% (13/22)]. Filgrastim significantly decreased the duration of neutropenia, but did not affect the absolute neutrophil count nadir. Febrile neutropenia (ANC <500/μL and body temperature ≥103°F) was experienced by 90.9% (20/22) of controls compared to 79.2% (19/24) of filgrastim-treated animals (P = 0.418). Survival was significantly increased by 38.3% over controls. Filgrastim, administered at this dose and schedule, effectively mitigated the lethality of the hematopoietic subsyndrome of the acute radiation syndrome. PMID:23210705

Fertility after implementation of long- and short-term progesterone-based ovulation synchronization protocols for fixed-time artificial insemination in beef heifers.

PubMed

Kasimanickam, R; Schroeder, S; Hall, J B; Whittier, W D

2015-04-15

Two experiments were conducted to evaluate the effect of long-term (LT; a 14-day controlled internal drug release insert [CIDR]-PGF2α [PGF]-GnRH) and short-term (ST; 5-day CO-Synch + CIDR) progesterone-based protocols on pregnancy rate to fixed-time artificial insemination (FTAI) in beef heifers. In experiment 1, Angus cross beef heifers (N = 1887) at nine locations received a body condition score and a reproductive tract score (RTS). Within the herd, heifers were randomly assigned to LT-72 and ST-56 protocol groups. Heifers in the LT-72 group received a CIDR from Days 0 to 14, followed by 25 mg of PGF 16 days later (Day 30). Heifers in the ST-56 group received a CIDR and 100 μg of gonadorelin hydrochloride (GnRH) on Day 25 followed by 25 mg of PGF at CIDR removal on Day 30 and a second dose of PGF 6 hours later (Day 30). Artificial insemination was performed at 56 hours (Day 32) after CIDR removal for the ST-56 group and at 72 hours (Day 33) after CIDR removal for the LT-72 group, and all heifers were given GnRH (100 μg, intramuscular) at the time of AI. In experiment 2, Angus cross beef heifers (N = 718) at four locations received a body condition score and an RTS. Within the herd, heifers were randomly assigned to LT-72 and ST-72 protocol groups. The protocol was similar to experiment 1 except that AI was performed at 72 hours after CIDR removal for both LT-72 and ST-72 groups. In experiment 1, no difference in AI pregnancy rates between the LT-72 and ST-56 groups was observed (54.5% [489 of 897] and 55.5% [549 of 990], respectively; P = 0.92) after accounting for the RTS. The AI pregnancy rates for heifers with RTS 3 or less, 4, and 5 were 52.6%, 53.6%, and 59.9%, respectively (P < 0.05). In experiment 2, controlling for the RTS, no difference in AI pregnancy rates was observed between the LT-72 and ST-72 groups, 56.9% (198 of 347) and 57.8% (214 of 371), respectively (P = 0.87). The AI pregnancy rates for heifers with RTS 3 or less, 4, and 5 were 49.3%, 58.4%, and 62.1%, respectively (P < 0.05). In conclusion, heifers synchronized for fixed-time AI with LT and ST protocols resulted in a similar AI pregnancy rate. Approximately, 55% of the herd was pregnant to one insemination in 33 days with the LT protocol compared with just 8 days with the ST protocol. Copyright © 2015 Elsevier Inc. All rights reserved.

Variation in the biochemical response to l-thyroxine therapy and relationship with peripheral thyroid hormone conversion efficiency

PubMed Central

Midgley, John E M; Larisch, Rolf; Dietrich, Johannes W; Hoermann, Rudolf

2015-01-01

Several influences modulate biochemical responses to a weight-adjusted levothyroxine (l-T4) replacement dose. We conducted a secondary analysis of the relationship of l-T4 dose to TSH and free T3 (FT3), using a prospective observational study examining the interacting equilibria between thyroid parameters. We studied 353 patients on steady-state l-T4 replacement for autoimmune thyroiditis or after surgery for malignant or benign thyroid disease. Peripheral deiodinase activity was calculated as a measure of T4–T3 conversion efficiency. In euthyroid subjects, the median l-T4 dose was 1.3 μg/kg per day (interquartile range (IQR) 0.94,1.60). The dose was independently associated with gender, age, aetiology and deiodinase activity (all P<0.001). Comparable FT3 levels required higher l-T4 doses in the carcinoma group (n=143), even after adjusting for different TSH levels. Euthyroid athyreotic thyroid carcinoma patients (n=50) received 1.57 μg/kg per day l-T4 (IQR 1.40, 1.69), compared to 1.19 μg/kg per day (0.85,1.47) in autoimmune thyroiditis (P<0.01, n=76) and 1.08 μg/kg per day (0.82, 1.44) in patients operated on for benign disease (P< 0.01, n=80). Stratifying patients by deiodinase activity categories of <23, 23–29 and >29 nmol/s revealed an increasing FT3–FT4 dissociation; the poorest converters showed the lowest FT3 levels in spite of the highest dose and circulating FT4 (P<0.001). An l-T4-related FT3–TSH disjoint was also apparent; some patients with fully suppressed TSH failed to raise FT3 above the median level. These findings imply that thyroid hormone conversion efficiency is an important modulator of the biochemical response to l-T4; FT3 measurement may be an additional treatment target; and l-T4 dose escalation may have limited success to raise FT3 appropriately in some cases. PMID:26335522

The effect of the hypohydration on the lactate threshold in a hot and humid environment.

PubMed

Papadopoulos, C; Doyle, J; Rupp, J; Brandon, L; Benardot, D; Thompson, W

2008-09-01

The purpose of this study was to investigate the effect of hypohydration (HH) on the lactate threshold (LT) in a hot and humid environment. Ten apparently healthy males (age 25+/-3 yrs; height 1.8+/-0.04 m; mass 78+/-12 kg; VO2peak 3.7+/-0.4 L/min) underwent four randomly assigned maximal treadmill tests. Two trials were at room temperature (22+/-1 degrees C; RH = 50%) under two different hydration conditions: euhydrated (EH-RM) and hypohydrated (HH-RM), and two trials were performed in a warm chamber (37+/-0.5 degrees C; RH = 70%) under two different hydration conditions: euhydrated (EH-HT) and hypohydrated (HH-HT). The desired HH level (2-4%) was accomplished in the 24+ hours before testing by fluid restriction. Mean HH was 2.6+/-1.0% body weight. Capillary blood samples were collected at the end of each stage and analyzed for lactic acid (LA). LA concentrations were plotted for each exercise stage, and the LT was determined by visual inspection as the highest exercise stage at which blood LA concentration began to increase above each individual's resting levels. LT and body temperature were analyzed with a two-way repeated measures ANOVA (P < 0.05). During the trials in the warm chamber, the LT occurred at a significantly earlier stage compared to the thermoneutral environment (4.4+/-0.09 vs 5.8+/-0.10) and with a significantly lower oxygen consumption (2.38+/-0.09 L.min(-1) vs 2.86+/-0.13 L.min(-1)). Body temperature at the LT was significantly higher in the heat trials compared to room temperature (38.7+/-0.12 degrees C vs 37.6+/-0.14 degrees C). LT determination was not significantly altered by hydration. These results suggest that during progressive incremental maximal treadmill exercise, moderate HH does not affect the LT, whereas exercise in a hot and humid environment induces a downward shift in the LT. The elevated body temperature during the heat trials suggests that body temperature may affect running performance associated with the LT.

International Symposium on Mechanism of Cyanide Toxicity and Antagonism (1st), Proceedings Held on 15-19 August 1982.

DTIC Science & Technology

1983-10-01

intraventricular contents, and toxicologically significant concentrations of cyanide could still be measured at 3 weeks STORAGE TIME DAYS) in blood samples ...thi- rhod~,iit m lt~ tilt, h v - lt i~ tni ii t iituMtil tmn 1 hu’I-huct~ irt, ig thtu t\\ttlottiimmtii.tt rtighl% equ~.il %i/emiid thc toinnt tig...loopr’ tnbth’id’ wt~hlu ~ Ih l vmhttiblliii thtu unity o~th t * ’ it thu- tjrt~ikt’ tit thc m lt t lt , l I lit it ttvt’ ’itc’ Io,,-~ it, tlt, thgUrt’ 11

Vitamin D status of human immunodeficiency virus-positive patients with advanced liver disease enrolled in the solid organ transplantation in HIV: multi-site study.

PubMed

Branch, Andrea D; Barin, Burc; Rahman, Adeeb; Stock, Peter; Schiano, Thomas D

2014-02-01

An optimal vitamin D status may benefit liver transplantation (LT) patients. Higher levels of 25-hydroxyvitamin D [25(OH)D] mitigate steroid-induced bone loss after LT, correlate with better hepatitis C virus treatment responses, and increase graft survival. This study investigated 25(OH)D levels and assessed strategies for vitamin D deficiency prevention in human immunodeficiency virus (HIV)-positive patients with advanced liver disease who were enrolled in the Solid Organ Transplantation in HIV: Multi-Site Study. 25(OH)D was measured in banked specimens from 154 LT candidates/recipients with the DiaSorin assay; deficiency was defined as a 25(OH)D level < 20 ng/mL. Information about vitamin D supplement use after LT was obtained from medication logs and via surveys. Logistic regression, Cox regression, and linear repeated measures analyses were performed with SAS software. We found that none of the 17 academic medical centers in the United States routinely recommended vitamin D supplements before LT, and only a minority (4/17) recommended vitamin D supplements to all patients after LT. Seventy-one percent of the 139 patients with pre-LT values had vitamin D deficiency, which was significantly associated with cirrhosis (P = 0.01) but no other variable. The vitamin D status improved modestly after LT; however, the status was deficient for 40% of the patients 1 year after LT. In a multivariate linear repeated measures model, a higher pre-LT 25(OH)D level (P < 0.001), specimen collection in the summer (P < 0.001), a routine vitamin D supplementation strategy after LT (P < 0.001), and the time elapsing since LT (P = 0.01) were significantly associated with increases in the post-LT 25(OH)D level; black race was associated with a decreased level (P = 0.02). In conclusion, the majority of patients awaiting LT were vitamin D deficient, and approximately half were vitamin D deficient after LT. More extensive use of vitamin D supplements, more sun exposure, or both are needed to prevent this deficiency in HIV-positive LT candidates and recipients. © 2013 American Association for the Study of Liver Diseases.

Comparison of toxicity rankings of six aircraft cabin polymers by lethality and by incapacitation in rats.

PubMed

Sanders, D C; Endecott, B R; Chaturvedi, A K

1992-10-01

Polymeric aircraft cabin materials have the potential to produce toxic gases in fires. Lethality (LC50) in animal models is a standard index to rank polymers on the basis of their combustion toxicity. However, the use of times-to-incapacitation (ti) may be more realistic for predicting relative escape times from a fire. Therefore, LC50 and ti for polymers, polyamide (I), polystyrene (II), Nylon 6/6 (III), polysulfone (IV), polyethylene (V) and chlorinated polyethylene (VI), of different chemical classes were determined and compared. Male rats, 12/fuel loading, were exposed to the pyrolysis products from selected weights of each polymer for 30 min in a 265-L combustion/exposure system, and LC50 values were determined following a 14-d observation period. For each polymer, ti was measured at 16 g and at its respective LC50 using the inability of rats (n greater than or equal to 12) to walk in rotating cages as a criterion for incapacitation. LC50 (45.7-87.5 mg/L) of the polymers had the order of I less than II approximately III less than IV less than V less than VI, while their ti (6.6-21.1 min) at 16 g (60 mg/L) had the order of III approximately I less than V approximately II less than VI less than IV. Based on ti at LC50, polymers were grouped into III & V; I, II & VI; and IV. LC50 and ti did not exhibit the same relative toxic hazard rankings for these polymers; ti were also not equal at the LC50 concentrations. These findings demonstrate the possible involvement of different mechanisms of action for the combustion products of these polymers at the selected end points.

DNA methyltransferases contribute to the fungal development, stress tolerance and virulence of the entomopathogenic fungus Metarhizium robertsii.

PubMed

Wang, Yulong; Wang, Tiantian; Qiao, Lintao; Zhu, Jianyu; Fan, Jinrui; Zhang, Tingting; Wang, Zhang-Xun; Li, Wanzhen; Chen, Anhui; Huang, Bo

2017-05-01

DNA methylation is an important epigenetic mark in mammals, plants, and fungi and depends on multiple genetic pathways involving de novo and maintenance DNA methyltransferases (DNMTases). Metarhizium robertsii, a model system for investigating insect-fungus interactions, has been used as an environmentally friendly alternative to chemical insecticides. However, little is known concerning the molecular basis for DNA methylation. Here, we report on the roles of two DNMTases (MrRID and MrDIM-2) by characterizing ΔMrRID, ΔMrDIM-2, and ΔRID/ΔDIM-2 mutants. The results showed that approximately 71, 10, and 8% of m C sites remained in the ΔMrRID, ΔMrDIM-2, and ΔRID/ΔDIM-2 strains, respectively, compared with the wild-type (WT) strain. Further analysis showed that MrRID regulates the specificity of DNA methylation and MrDIM-2 is responsible for most DNA methylation, implying an interaction or cooperation between MrRID and MrDIM-2 for DNA methylation. Moreover, the ΔMrDIM-2 and ΔRID/ΔDIM-2 strains showed more defects in radial growth and conidial production compared to the WT. Under ultraviolet (UV) irradiation or heat stress, an obvious reduction in spore viability was observed for all the mutant strains compared to the WT. The spore median lethal times (LT 50 s) for the ΔMrDIM-2 and ΔRID/ΔDIM-2 strains in the greater wax moth, Galleria mellonella, were decreased by 47.7 and 65.9%, respectively, which showed that MrDIM-2 is required for full fungal virulence. Our data advances the understanding of the function of DNMTase in entomopathogenic fungi, which should contribute to future epigenetic investigations in fungi.

Clinical Outcomes of Lung Transplantation in Patients with Telomerase Mutations

PubMed Central

Tokman, Sofya; Singer, Jonathan P.; Devine, Megan S.; Westall, Glen P.; Aubert, John-David; Tamm, Michael; Snell, Gregory I.; Lee, Joyce S.; Goldberg, Hilary J.; Kukreja, Jasleen; Golden, Jeffrey A.; Leard, Lorriana E.; Garcia, Christine K.; Hays, Steven R.

2017-01-01

Background Successful lung transplantation (LT) for patients with pulmonary fibrosis from telomerase mutations is limited by systemic complications of telomerase dysfunction including myelosuppression, cirrhosis, and malignancy. We describe clinical outcomes among 14 LT recipients with telomerase mutations. Methods Subjects underwent LT between February 2005 and April 2014 at 5 LT centers. We abstracted data from medical records, focusing on outcomes reflecting post-LT treatment effects likely to be complicated by telomerase mutations. Results The median age of subjects was 60.5 years (IQR 52.0–62.0), 64.3% were male, and the mean post-LT observation time was 3.2 years (SD ±2.9). Eleven subjects had a mutation in telomerase reverse transcriptase, 2 in telomerase RNA component, and 1 had an uncharacterized mutation. Ten subjects were leukopenic post-LT; leukopenia prompted cessation of mycophenolate mofetil in 5 and treatment with filgrastim in 4. Six subjects had recurrent lower respiratory tract infections (LRTI), 7 had acute cellular rejection (ACR) (A1), and 4 developed chronic lung allograft dysfunction (CLAD). Ten LT recipients developed chronic renal insufficiency and 8 experienced acute, reversible renal failure. Three developed cancer, none had cirrhosis. Thirteen subjects were alive at data censorship. Conclusions The clinical course for LT recipients with telomerase mutations is complicated by renal disease, leukopenia prompting a change in the immunosuppressive regimen, and recurrent LTRI. In contrast, cirrhosis was absent, ACR was mild, and development of CLAD was comparable to other LT populations. While posing challenges, lung transplantation may be feasible for patients with pulmonary fibrosis due to telomerase mutations. PMID:26169663

Role of Abscisic Acid in the Induction of Freezing Tolerance in Brassica napus Suspension-Cultured Cells 1

PubMed Central

Johnson-Flanagan, Anne M.; Huiwen, Zhong; Thiagarajah, Mohan R.; Saini, Hargurdeep S.

1991-01-01

Brassica napus suspension-cultured cells could be hardened in 6 days at 25°C by the addition of mefluidide or ABA to the culture medium. Cells treated with mefluidide (10 milligrams per liter) or ABA (50 micromolar) attained an LT50 of −17.5°C or −18°C, respectively, while the LT50 for the comparable nonhardened control (sucrose) was −10°C. The increased freezing tolerance of mefluidide-treated cells was paralleled by a 4- to 23-fold increase in ABA, as measured by gas-liquid chromatography using electron capture detection. Application of 1 milligram per liter of fluridone, an inhibitor of abscisic acid biosynthesis, prevented the mefluidide-induced increase in freezing tolerance and the accumulation of ABA. Both these inhibitory effects of fluridone were overridden by 50 micromolar ABA in the culture medium. On the basis of these results, we concluded that increased ABA levels are important for the induction of freezing tolerance in suspension-cultured cells. PMID:16668089

BRP-187: A potent inhibitor of leukotriene biosynthesis that acts through impeding the dynamic 5-lipoxygenase/5-lipoxygenase-activating protein (FLAP) complex assembly.

PubMed

Garscha, Ulrike; Voelker, Susanna; Pace, Simona; Gerstmeier, Jana; Emini, Besa; Liening, Stefanie; Rossi, Antonietta; Weinigel, Christina; Rummler, Silke; Schubert, Ulrich S; Scriba, Gerhard K E; Çelikoğlu, Erşan; Çalışkan, Burcu; Banoglu, Erden; Sautebin, Lidia; Werz, Oliver

2016-11-01

The pro-inflammatory leukotrienes (LTs) are formed from arachidonic acid (AA) in activated leukocytes, where 5-lipoxygenase (5-LO) translocates to the nuclear envelope to assemble a functional complex with the integral nuclear membrane protein 5-LO-activating protein (FLAP). FLAP, a MAPEG family member, facilitates AA transfer to 5-LO for efficient conversion, and LT biosynthesis critically depends on FLAP. Here we show that the novel LT biosynthesis inhibitor BRP-187 prevents the 5-LO/FLAP interaction at the nuclear envelope of human leukocytes without blocking 5-LO nuclear redistribution. BRP-187 inhibited 5-LO product formation in human monocytes and polymorphonuclear leukocytes stimulated by lipopolysaccharide plus N-formyl-methionyl-leucyl-phenylalanine (IC 50 =7-10nM), and upon activation by ionophore A23187 (IC 50 =10-60nM). Excess of exogenous AA markedly impaired the potency of BRP-187. Direct 5-LO inhibition in cell-free assays was evident only at >35-fold higher concentrations, which was reversible and not improved under reducing conditions. BRP-187 prevented A23187-induced 5-LO/FLAP complex assembly in leukocytes but failed to block 5-LO nuclear translocation, features that were shared with the FLAP inhibitor MK886. Whereas AA release, cyclooxygenases and related LOs were unaffected, BRP-187 also potently inhibited microsomal prostaglandin E 2 synthase-1 (IC 50 =0.2μM), another MAPEG member. In vivo, BRP-187 (10mg/kg) exhibited significant effectiveness in zymosan-induced murine peritonitis, suppressing LT levels in peritoneal exudates as well as vascular permeability and neutrophil infiltration. Together, BRP-187 potently inhibits LT biosynthesis in vitro and in vivo, which seemingly is caused by preventing the 5-LO/FLAP complex assembly and warrants further preclinical evaluation. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect of a passive exhalation port on tracheostomy ventilation in amyotrophic lateral sclerosis patients: a randomized controlled trial.

PubMed

Vianello, Andrea; Arcaro, Giovanna; Molena, Beatrice; Iovino, Silvia; Gallan, Federico; Turato, Cristian; Marchese-Ragona, Rosario

2018-02-01

Amyotrophic lateral sclerosis (ALS) patients often require long-term tracheostomy ventilation (LT-TV) because of progressive ventilatory failure. Although widely used for non-invasive ventilation (NIV), passive exhalation port systems have not been gaining popularity for TV because of the possibility of carbon dioxide (CO 2 ) rebreathing. The current study set out to investigate the effect of a Whisper Swivel connector in comparison to an active exhalation valve on gas exchange and symptoms in ALS patients requiring LT-TV. A prospective randomized controlled trial was carried out to compare the clinical outcome of ten ALS patients receiving LT-TV by means of a Trilogy 100 ventilator with a Whisper Swivel passive exhalation port (group A) and of 10 ALS patients connected to an Airox Legendair ventilator with an active exhalation valve (group B). The study's main outcome measure was CO 2 retention at the 30-day follow-up assessment. One patient in each of the two cohorts showed significant CO 2 retention. At the 30-day assessment, scores on the following measures were not significantly different in the two groups: the Borg dyspnea scale {2 [1-3] vs. 1 [1-3]; P=0.2891}, the visual analogue scale (VAS) dyspnea {20 [10-85] vs. 20 [0-50]; P=0.8571}, the Epworth sleepiness scale (ESS) {8 [4-10] vs. 5.5 [0-12]; P=0.1443}, the EuroQol-VAS (EQ-VAS) {55 [50-80] vs. 50 [30-80]; P=0.4593} and the relative stress scale (RSS) {49 [30-65] vs. 52 [25-64]; P=0.8650}. At the 3-month follow-up assessment, the numbers of hospitalizations and deaths were likewise similar in the two groups. The efficacy of the Whisper Swivel connector is similar to that of an active exhalation valve in ALS patients undergoing LT-TV.

An improved brine shrimp larvae lethality microwell test method.

PubMed

Zhang, Yi; Mu, Jun; Han, Jinyuan; Gu, Xiaojie

2012-01-01

This article described an improved brine shrimp larvae lethality microwell test method. A simply designed connecting vessel with alternative photoperiod was used to culture and collect high yield of active Artemia parthenogenetica nauplii for brine shrimp larvae lethality microwell test. Using this method, pure A. parthenogenetica nauplii suspension was easily cultured and harvested with high density about 100-150 larvae per milliliter and the natural mortality was reduced to near zero by elimination of unnecessary artificial disturbance. And its sensitivity was validated by determination of LC(50)-24 h of different reference toxicants including five antitumor agents, two pesticides, three organic pollutants, and four heavy metals salts, most of which exhibited LC(50)-24 h between 0.07 and 58.43 mg/L except for bleomycin and mitomycin C with LC(50)-24 h over 300 mg/L.

Time-to-death approach to reveal chronic and cumulative toxicity of a fungicide for honeybees not revealed with the standard ten-day test.

PubMed

Simon-Delso, Noa; San Martin, Gilles; Bruneau, Etienne; Hautier, Louis

2018-05-08

Synthetic fungicides are pesticides widely used in agriculture to control phytopathogenic fungi. The systemicity, persistency and intense application of some of these fungicides, such as boscalid, leads to long periods of exposure for honeybees via contaminated water, pollen and nectar. We exposed adult honeybees in the lab to food contaminated with boscalid for 33 days instead of the standard 10-day test. Most of the toxic effects were observed after 10 days. The median time to death (LT 50 ) ranged from 24.9 days (lowest concentration) to 7.1 days (highest concentration) and was significantly shorter in all cases than with the control (32.0 days). The concentration and dietary doses of boscalid inducing 50% mortality (LC 50 and LDD 50 , respectively) decreased strongly with the time of exposure: LC 50  = 14,729 and 1,174 mg/l and LDD 50  = 0.318 and 0.0301 mg bee -1 day -1 at days 8 and 25, respectively. We found evidence of reinforced toxicity when exposure is prolonged, but with an unusual pattern: no cumulative toxicity is observed until 17-18 days, when a point of inflexion appears that suggests a reduced capacity of bees to deal with the toxicant. Our results show the importance of time-to-death experiments rather than fixed-duration studies for evaluating chronic toxicity.

Local H i emissivity measured with FERMI-LAT and implications for Cosmic-ray spectra

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

Casandjian, Jean -Marc

Cosmic-ray (CR) electrons and nuclei interact with the Galactic interstellar gas and produce high-energy γ-rays. The γ-ray emission rate per hydrogen atom, called emissivity, provides a unique indirect probe of the CR flux. We present the measurement and the interpretation of the emissivity in the solar neighborhood for γ-ray energy from 50 MeV to 50 GeV. We analyzed a subset of 4 yr of observations from the Large Area Telescope (LAT) aboard the Fermi Gamma-ray Space Telescope ( Fermi) restricted to absolute latitudesmore » $$10^\\circ \\lt | b| \\lt 70^\\circ $$. From a fit to the LAT data including atomic, molecular, and ionized hydrogen column density templates, as well as a dust optical depth map, we derived the emissivities, the molecular hydrogen–to–CO conversion factor $${X}_{\\mathrm{CO}}=(0.902\\pm 0.007)\\times {10}^{20}$$ cm–2 (K km s–1)–1, and the dust-to-gas ratio $${X}_{\\mathrm{DUST}}=(41.4\\pm 0.3)\\times {10}^{20}$$ cm–2 mag–1. Moreover, we detected for the first time γ-ray emission from ionized hydrogen. We compared the extracted emissivities to those calculated from γ-ray production cross sections and to CR spectra measured in the heliosphere. We observed that the experimental emissivities are reproduced only if the solar modulation is accounted for. This provides a direct detection of solar modulation observed previously through the anticorrelation between CR fluxes and solar activity. Lastly, we fitted a parameterized spectral form to the heliospheric CR observations and to the Fermi-LAT emissivity and obtained compatible local interstellar spectra for proton and helium kinetic energy per nucleon between between 1 and 100 GeV and for electron–positrons between 0.1 and 100 GeV.« less

Local H i emissivity measured with FERMI-LAT and implications for Cosmic-ray spectra

DOE PAGES

Casandjian, Jean -Marc

2015-06-20

Cosmic-ray (CR) electrons and nuclei interact with the Galactic interstellar gas and produce high-energy γ-rays. The γ-ray emission rate per hydrogen atom, called emissivity, provides a unique indirect probe of the CR flux. We present the measurement and the interpretation of the emissivity in the solar neighborhood for γ-ray energy from 50 MeV to 50 GeV. We analyzed a subset of 4 yr of observations from the Large Area Telescope (LAT) aboard the Fermi Gamma-ray Space Telescope ( Fermi) restricted to absolute latitudesmore » $$10^\\circ \\lt | b| \\lt 70^\\circ $$. From a fit to the LAT data including atomic, molecular, and ionized hydrogen column density templates, as well as a dust optical depth map, we derived the emissivities, the molecular hydrogen–to–CO conversion factor $${X}_{\\mathrm{CO}}=(0.902\\pm 0.007)\\times {10}^{20}$$ cm–2 (K km s–1)–1, and the dust-to-gas ratio $${X}_{\\mathrm{DUST}}=(41.4\\pm 0.3)\\times {10}^{20}$$ cm–2 mag–1. Moreover, we detected for the first time γ-ray emission from ionized hydrogen. We compared the extracted emissivities to those calculated from γ-ray production cross sections and to CR spectra measured in the heliosphere. We observed that the experimental emissivities are reproduced only if the solar modulation is accounted for. This provides a direct detection of solar modulation observed previously through the anticorrelation between CR fluxes and solar activity. Lastly, we fitted a parameterized spectral form to the heliospheric CR observations and to the Fermi-LAT emissivity and obtained compatible local interstellar spectra for proton and helium kinetic energy per nucleon between between 1 and 100 GeV and for electron–positrons between 0.1 and 100 GeV.« less

Antimicrobial and cytotoxic constituents from leaves of Sapium baccatum.

PubMed

Ahmed, Yunus; Sohrab, Md Hossain; Al-Reza, Sharif M; Tareq, Faqir Shahidulla; Hasan, Choudhury M; Sattar, M A

2010-02-01

Six compounds, namely, Lupeol (1), Betulin (2), beta-Taraxerol (3), Taraxerone (4), Stigmasterol (5) and beta-Sitosterol (6) were isolated from the petroleum ether extract of the leaves of Sapium baccatum based on spectroscopic evidence. Lupeol (1), Betulin (2) and Stigmasterol (5) were isolated for the first time from this plant. The cytotoxic potential of the different solvent extracts (methanol, petroleum ether, carbon-tetrachloride and dichloromethane); six column fractions (F-4, F-7, F-10, F-12, F-18 and F-22) of petroleum ether extract and three pure compounds 1, 4 and 6 were determined by using brine shrimp lethality bioassay. The LC50 of all the tested samples were showed to be lethal to brine shrimp nauplii. However, petroleum ether, carbon-tetrachloride extract, column fractions F-4 and F-18 of petroleum ether extract and pure compound 6 showed quite potent activity in brine shrimp lethality bioassay with LC50 1.33, 1.35, 1.40, 1.58 and 1.58 microg/ml, respectively. These result suggested that they might be contain antitumor or pesticidal activity. Further, the methanol extract and four column fractions (F-7, F-12, F-18 and F-22) of petroleum ether showed significant activity against the tested microorganisms. Copyright 2009 Elsevier Ltd. All rights reserved.

GPS TEC near the crest of the EIA at 95°E during the ascending half of solar cycle 24 and comparison with IRI simulations

NASA Astrophysics Data System (ADS)

Bhuyan, Pradip Kumar; Hazarika, Rumajyoti

2013-10-01

Total electron content (TEC) data obtained from GPS dual frequency measurements during the ascending half of the solar cycle 24 from 2009 to 2012 over Dibrugarh (27.5°N, 94.9°E; 17.6°N MLAT) have been used to study the diurnal, seasonal, annual and solar cycle variation of TEC. The measurements reported here are for the first time from the location situated at the poleward edge of the northern equatorial ionization anomaly (EIA) and within the peak region of the longitudinal wave number 4 (WN4) structure in EIA crest TEC. TEC exhibits a minimum around 0600 LT and diurnal maximum around 1300-1600 LT. In the low and moderate solar activity years 2009-2010 and 2010-2011, average daytime (1000-1600 LT) TEC in summer was higher (25.4 and 36.6 TECU) compared to that in winter (21.5 and 26.1 TECU). However, at the peak of the solar cycle in 2011-2012, reversal in the level of ionization between winter and summer takes place and winter TEC becomes higher (50.6 TECU) than that in summer (45.0 TECU). Further, TEC in spring (34.1, 49.9 and 63.3 TECU respectively in 2009-10, 2010-11 and 2011-12) is higher than that in autumn (24.2, 32.3 and 51.9 TECU respectively) thus showing equinoctial asymmetry in all the years of observation. The winter anomaly in high solar activity years and equinoctial asymmetry all throughout may be largely attributed to changes in the thermospheric O/N2 density ratio. A winter to summer delay of ˜1 h in the time of occurrence of the diurnal maximum has also been observed. Daytime maximum TEC bears a nonlinear relationship with F10.7 cm solar flux. TEC increases linearly with F10.7 cm solar flux initially up to about 140 sfu (1 sfu = 10-22 W m-2 Hz-1) after which it tends to saturate. On the contrary, TEC increases linearly with solar EUV flux (photons cm-2 s-1, 0.5-50 nm) during the same period. TEC predicted by the IRI 2012 are lower than the measured TEC for nearly 90% of the time.

Delayed and time-cumulative toxicity of imidacloprid in bees, ants and termites

PubMed Central

Rondeau, Gary; Sánchez-Bayo, Francisco; Tennekes, Henk A.; Decourtye, Axel; Ramírez-Romero, Ricardo; Desneux, Nicolas

2014-01-01

Imidacloprid, one of the most commonly used insecticides, is highly toxic to bees and other beneficial insects. The regulatory challenge to determine safe levels of residual pesticides can benefit from information about the time-dependent toxicity of this chemical. Using published toxicity data for imidacloprid for several insect species, we construct time-to-lethal-effect toxicity plots and fit temporal power-law scaling curves to the data. The level of toxic exposure that results in 50% mortality after time t is found to scale as t1.7 for ants, from t1.6 to t5 for honeybees, and from t1.46 to t2.9 for termites. We present a simple toxicological model that can explain t2 scaling. Extrapolating the toxicity scaling for honeybees to the lifespan of winter bees suggests that imidacloprid in honey at 0.25 μg/kg would be lethal to a large proportion of bees nearing the end of their life. PMID:24993452

Sub-optimal pH Preadaptation Improves the Survival of Lactobacillus plantarum Strains and the Malic Acid Consumption in Wine-Like Medium

PubMed Central

Succi, Mariantonietta; Pannella, Gianfranco; Tremonte, Patrizio; Tipaldi, Luca; Coppola, Raffaele; Iorizzo, Massimo; Lombardi, Silvia Jane; Sorrentino, Elena

2017-01-01

Forty-two oenological strains of Lb. plantarum were assessed for their response to ethanol and pH values generally encountered in wines. Strains showed a higher variability in the survival when exposed to low pH (3.5 or 3.0) than when exposed to ethanol (10 or 14%). The study allowed to individuate the highest ethanol concentration (8%) and the lowest pH value (4.0) for the growth of strains, even if the maximum specific growth rate (μmax) resulted significantly reduced by these conditions. Two strains (GT1 and LT11) preadapted to 2% ethanol and cultured up to 14% of ethanol showed a higher growth than those non-preadapted when they were cultivated at 8% of ethanol. The evaluation of the same strains preadapted to low pH values (5.0 and 4.0) and then grown at pH 3.5 or 3.0 showed only for GT1 a sensitive μmax increment when it was cultivated in MRS at pH 3 after a preadaptation to pH 5.0. The survival of GT1 and LT11 was evaluated in Ringer's solution at 14% ethanol after a long-term adaptation in MRS with 2% ethanol or in MRS with 2% ethanol acidified at pH 5.0 (both conditions, BC). Analogously, the survival was evaluated at pH 3.5 after a long-term adaptation in MRS at pH 5.0 or in MRS BC. The impact of the physiologic state (exponential phase vs stationary phase) on the survival was also evaluated. Preadapted cells showed the same behavior of non-preadapted cells only when cultures were recovered in the stationary phase. Mathematical functions were individuated for the description of the survival of GT1 and LT11 in MRS at 14% ethanol or at pH 3.5. Finally, a synthetic wine (SW) was used to assess the behavior of Lb. plantarum GT1 and LT11 preadapted in MRS at 2% ethanol or at pH 5.0 or in BC. Only GT1 preadapted to pH 5.0 and collected in the stationary phase showed constant values of microbial counts after incubation for 15 days at 20°C. In addition, after 15 days the L-malic acid resulted completely degraded and the pH value increased of about 0.3 units. PMID:28382030

Alpha-Fetoprotein Slope >7.5 ng/mL per Month Predicts Microvascular Invasion and Tumor Recurrence After Liver Transplantation for Hepatocellular Carcinoma.

PubMed

Giard, Jeanne-Marie; Mehta, Neil; Dodge, Jennifer L; Roberts, John P; Yao, Francis Y

2018-05-01

Rising alpha-fetoprotein (AFP) is a potential marker of worse prognosis after liver transplant (LT) for hepatocellular carcinoma (HCC), but prior studies relied on only 2 data points and were imprecise in assessing AFP slope. The aim of this study was to examine the association between AFP slope and post-LT HCC recurrence, with AFP slope estimated from multiple data points over time. Our cohort included 336 patients undergoing LT with Model for End Stage Liver Disease exception for HCC within Milan criteria from 2003 to 2013. Most (98%) had pre-LT locoregional therapy. AFP slope was estimated by fitting a regression line to the AFP levels over time. The 1- and 5-year post-LT survivals were 94% and 77% and 1- and 5-year recurrence-free probabilities were 95% and 86%, respectively. In univariate analysis, HCC recurrence was significantly associated with microvascular invasion (hazard ratio [HR], 13.1; P<0.001), tumor grade (HR, 1.8; P<0.001), pathologic stage >Milan criteria (HR, 8.9; P<0.001), 3 tumor nodules (HR, 5.5; P=0.002), AFP slope greater than 7.5 ng/mL per month (HR, 3.9; P=0.005), and female sex (HR, 2.3; P=0.01). In multivariable analysis of factors known before LT, 3 tumor nodules (HR, 7.6; P<0.001), female sex (HR, 2.5; P=0.01), and AFP slope >7.5 (HR, 3.0; P=0.03) were significantly associated with HCC recurrence. AFP slope greater than 7.5 was also associated with microvascular invasion (odds ratio, 6.8; P=0.008). AFP slope increasing greater than 7.5 ng/mL per month despite locoregional therapy is associated with post-LT HCC recurrence and may serve as a surrogate for microvascular invasion. These findings support incorporating changes in the AFP into candidate selection for LT.

Endotracheal Intubation with the King Laryngeal Tube™ In Situ Using Video Laryngoscopy and a Bougie: A Retrospective Case Series and Cadaveric Crossover Study.

PubMed

Dodd, Kenneth W; Kornas, Rebecca L; Prekker, Matthew E; Klein, Lauren R; Reardon, Robert F; Driver, Brian E

2017-04-01

Removal of a functioning King laryngeal tube (LT) prior to establishing a definitive airway increases the risk of a "can't intubate, can't oxygenate" scenario. We previously described a technique utilizing video laryngoscopy (VL) and a bougie to intubate around a well-seated King LT with the balloons deflated; if necessary, the balloons can be rapidly re-inflated and ventilation resumed. Our objective is to provide preliminary validation of this technique. Emergency physicians performed all orotracheal intubations in this two-part study. Part 1 consisted of a historical analysis of VL recordings from emergency department (ED) patients intubated with the King LT in place over a two-year period at our institution. In Part 2, we analyzed VL recordings from paired attempts at intubating a cadaver, first with a King LT in place and then with the device removed, with each physician serving as his or her own control. The primary outcome for all analyses was first-pass success. There were 11 VL recordings of ED patients intubated with the King LT in place (Part 1) and 11 pairs of cadaveric VL recordings (Part 2). The first-pass success rate was 100% in both parts. In Part 1, the median time to intubation was 43 s (interquartile range [IQR] 36-60 s). In Part 2, the median time to intubation was 23 s (IQR 18-35 s) with the King LT in place and 17 s (IQR 14-18 s) with the King LT removed. Emergency physicians successfully intubated on the first attempt with the King LT in situ. The technique described in this proof-of-concept study seems promising and merits further validation. Copyright © 2016 Elsevier Inc. All rights reserved.

Restricting liver transplant recipients to younger donors does not increase the wait-list time or the dropout rate: the hepatitis C experience.

PubMed

Flemming, Jennifer A; Vagefi, Parsia A; Freise, Chris E; Yao, Francis Y; Terrault, Norah A

2014-10-01

Older donor age is associated with lower graft and patient survival among all recipients of liver transplantation (LT). Among patients with hepatitis C virus (HCV), donor age is one of the strongest predictors of fibrosis severity and graft loss. We evaluated the implementation of a donor age restriction policy for LT patients with HCV at a single center and the effects that this policy had on wait-list (WL) and post-LT outcomes for HCV and non-HCV patients. This was a cohort study of 2388 WL patients and 1015 LT recipients between March 2002 and January 2013 and reflected 3 different eras of donor age policies. With the donor age restriction, the median donor age was reduced in LT recipients with HCV versus LT recipients without HCV (30 versus 48 years, P < 0.001) without differences in the WL time (10.6 versus 8.0 months, P = 0.23). According to a competing risks regression, those with HCV and those without HCV had lower subhazard ratios (SHRs) of dropout or death on the WL during the donor age restriction era versus the era without donor age restriction [SHR = 0.68 (P < 0.01) and SHR = 0.64 (P = 0.01), respectively]. No differences were seen in early post-LT survival for patients with or without HCV between eras (P = 0.7 and P = 0.88, respectively). In conclusion, we show that donor age restriction for HCV results in a lower donor age for HCV recipients without obvious adverse WL consequences. Although additional studies are needed, our results demonstrate the feasibility of donor age restriction for LT recipients with HCV, and such information may be relevant to programs with limited access to new antiviral therapies for which modifying the risk of severe disease remains of paramount importance. © 2014 American Association for the Study of Liver Diseases.

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

Gustafsson, Karin; Heffner, Garrett; Wenzel, Pamela L.

The widely expressed adaptor protein Shb has previously been reported to contribute to T cell function due to its association with the T cell receptor and furthermore, several of Shb's known interaction partners are established regulators of blood cell development and function. In addition, Shb deficient embryonic stem cells displayed reduced blood cell colony formation upon differentiation in vitro. The aim of the current study was therefore to explore hematopoietic stem and progenitor cell function in the Shb knockout mouse. Shb deficient bone marrow contained reduced relative numbers of long-term hematopoietic stem cells (LT-HSCs) that exhibited lower proliferation rates. Despitemore » this, Shb knockout LT-HSCs responded promptly by entering the cell cycle in response to genotoxic stress by 5-fluorouracil treatment. In competitive LT-HSC transplantations, Shb null cells initially engrafted as well as the wild-type cells but provided less myeloid expansion over time. Moreover, Shb knockout bone marrow cells exhibited elevated basal activities of focal adhesion kinase/Rac1/p21-activated kinase signaling and reduced responsiveness to Stem Cell Factor stimulation. Consequently, treatment with a focal adhesion kinase inhibitor increased Shb knockout LT-HSC proliferation. The altered signaling characteristics thus provide a plausible mechanistic explanation for the changes in LT-HSC proliferation since these signaling intermediates have all been shown to participate in LT-HSC cell cycle control. In summary, the loss of Shb dependent signaling in bone marrow cells, resulting in elevated focal adhesion kinase activity and reduced proliferative responses in LT-HSCs under steady state hematopoiesis, confers a disadvantage to the maintenance of LT-HSCs over time. -- Highlights: • Shb is an adaptor protein operating downstream of tyrosine kinase receptors. • Shb deficiency reduces hematopoietic stem cell proliferation. • The proliferative effect of Shb occurs via increased focal adhesion kinase activity. • Shb is critical for the long-term maintenance of the hematopoietic stem cell pool.« less

Development of ELISA-detected anti-HLA antibodies precedes the development of bronchiolitis obliterans syndrome and correlates with progressive decline in pulmonary function after lung transplantation.

PubMed

Jaramillo, A; Smith, M A; Phelan, D; Sundaresan, S; Trulock, E P; Lynch, J P; Cooper, J D; Patterson, G A; Mohanakumar, T

1999-04-27

Development of anti-HLA antibodies after lung transplantation (LT) is thought to play an important role in the etiology of bronchiolitis obliterans syndrome (BOS). However, a cause-effect relationship between anti-HLA antibodies and BOS has not been established. This study was conducted to determine the temporal relationship between the development of anti-HLA antibodies and BOS after LT, and to determine the antigenic specificity of the antibodies developed in BOS patients. Sera from 15 BOS+ LT patients and 12 BOS- LT patients were obtained before LT and collected again at 6, 12, 24, 36, and 48 months after LT. Anti-HLA antibodies were detected by the PRA-STAT ELISA system and by complement-dependent cytotoxicity assays. Anti-HLA reactivity was further characterized by flow cytometry and absorption/elution with human platelets. When analyzed by ELISA, 10 of 15 BOS+ patients developed anti-HLA antibodies, whereas 0 of 12 BOS- patients developed anti-HLA antibodies (P<0.001). When analyzed by complement-dependent cytotoxicity, only 2 of 15 BOS+ patients developed anti-HLA antibodies and 1 of 12 BOS- patients developed anti-HLA antibodies (P = 0.99). There was a significant difference of 20.1 months between the time of anti-HLA antibody detection and the time of BOS diagnosis (P = 0.005). A progressive decrease in pulmonary function correlated with a progressive increase in the anti-HLA reactivity 36 months after LT. The anti-HLA reactivity was directed to one of the donor HLA class I antigens and to other unrelated HLA class I antigens. No anti-HLA reactivity was found against HLA class II molecules. Our study indicates that anti-HLA class I antibodies play an important role in the pathogenesis of BOS and that monitoring of anti-HLA class I antibody development by a highly sensitive assay such as the PRA-STAT ELISA after LT can provide an early identification of an important subset of LT patients with an increased risk of developing BOS.

Thermal annealing and pressure effects on BaFe_2-xCo_xAs₂ single crystals.

PubMed

Shin, Dongwon; Jung, Soon-Gil; Prathiba, G; Seo, Soonbeom; Choi, Ki-Young; Kim, Kee Hoon; Park, Tuson

2017-11-26

We investigate the pressure and thermal annealing effects on BaFe_2-<i>x</i>Co_<i>x</i>As₂ (Co-Ba122) single crystals with <i>x</i> = 0.1 and 0.17 via electrical transport measurements. The thermal annealing treatment not only enhances the superconducting transition temperature (<i>T</i>_c) from 9.6 to 12.7 K for <i>x</i> = 0.1 and from 18.1 to 21.0 K for <i>x</i> = 0.17, but also increases the antiferromagnetic transition temperature (<i>T</i>_N). Simultaneous enhancement of <i>T</i>_c and <i>T</i>_N by the thermal annealing treatment indicates that thermal annealing could substantially improve the quality of the Co-doped Ba122 samples. Interestingly, <i>T</i>_c of the Co-Ba122 compounds shows a scaling behavior with a linear dependence on the resistivity value at 290 K, irrespective of tuning parameters, such as chemical doping, pressure, and thermal annealing. These results not only provide an effective way to access the intrinsic properties of the BaFe₂As₂ system, but also may shed a light on designing new materials with higher superconducting transition temperature. © 2017 IOP Publishing Ltd.

Liver Transplantation in Hepatitis C-Infected Patients: Experience From a South American Transplant Center.

PubMed

Caicedo, L A; Delgado, A; Garcia, V H; Aristizabal, A M; Gomez, C; Jiménez, D F; Sepulveda, M; García, J A; Rosso, F; Castro, A M; Alcazar, K; Villegas, J I; Serrano, O; Echeverri, G J

2018-03-01

Around 2.4% of the world's population is infected with hepatitis C virus (HCV), and it is the most common cause of liver transplantation (LT) in the world. Latin America (LA), with nearly 9% of the world population, has had a continuous increase in the number of LTs per year. Yet, due to the lack of mandatory data collection and a well-developed health-care system, access to transplantation is limited in most LA countries. We report the first LA experience of HCV-infected LT patients. We performed a retrospective cohort study by reviewing the medical histories of all HCV-infected LT patients between 1996 and 2016 who acquired HCV before their LT, at the Fundación Valle del Lilí, Cali, Colombia. Between January 1996 and December 2015, a total of 770 LTs were performed, of which 75 had a cirrhotic liver due to HCV infection. With a median follow-up time of 24.4 months (interquartile range [IQR] 4.7-61.2 months), patient survival was 44.9% and 66.9% for the time periods 1996-2006 and 2007-2015, respectively. Hepatocellular carcinoma (HCC) was present in 30.6% of the patients, and overall postoperative complications had an incidence of 80%. This is the first report of LT in HCV-infected patients in Colombia and in LA. Our results are comparable to those of other transplant centers worldwide with regard to postoperative complications and patient survival. Patients with LT in the 1996-2006 time frame had higher morbidity and mortality. Studies including larger numbers of patients are needed to determine the reason for this finding. Copyright © 2018 Elsevier Inc. All rights reserved.

Lethal levels of selected water quality variables to larval and juvenile Lost River and shortnose suckers

USGS Publications Warehouse

Saiki, M.K.; Monda, D.P.; Bellerud, B.L.

1999-01-01

Resource managers hypothesize that occasional fish kills during summer-early fall in Upper Klamath Lake, Oregon, may be linked to unfavorable water quality conditions created by massive algal blooms. In a preliminary effort to address this concern, short-term (96-h-long) laboratory tests were conducted with larval and juvenile Lost River (Deltistes luxatus) and shortnose (Chasmistes brevirostris) suckers to determine the upper median lethal concentrations (LC50s; also referred to as median tolerance limits) for pH, un-ionized ammonia, and water temperature, and the lower LC50s for dissolved oxygen. The mean LC50s varied among species and life stages as follows: for pH, 10.30-10.39; for un-ionized ammonia, 0.48-1.06 mg litre-1; for temperature, 30.35-31.82??C; and for dissolved oxygen, 1.34-2.10 mg litre-1. Comparisons of 95% confidence limits indicated that, on average, the 96-h LC50s were not significantly different from those computed for shorter exposure times (i.e., 24 h, 48 h, and 72 h). According to two-way analysis of variance, LC50s for the four water quality variables did not vary significantly (p > 0.05) between fish species. However, LC50s for pH (exposure times of 24 h and 48 h) and dissolved oxygen (exposure times of 48 h, 72 h, and 96 h) differed significantly (p ??? 0.05) between life stages, whereas LC50s for un-ionized ammonia and water temperature did not exhibit significant differences. In general, larvae were more sensitive than juveniles to high pH and low dissolved oxygen concentrations. When compared to ambient water quality conditions in Upper Klamath Lake, our results strongly suggest that near-anoxic conditions associated with the senescence phase of algal blooms are most likely to cause high mortalities of larval and juvenile suckers.

The Optimal Timing of Hepatitis C Therapy in Transplant Eligible Patients With Child B and C Cirrhosis: A Cost-Effectiveness Analysis.

PubMed

Tapper, Elliot B; Hughes, Michael S; Buti, Maria; Dufour, Jean-Francois; Flamm, Steve; Firdoos, Saima; Curry, Michael P; Afdhal, Nezam H

2017-05-01

Ledipasvir (LDV)/sofosbuvir (SOF) has demonstrated high efficacy, safety, and tolerability in hepatitis C virus (HCV)-infected patients. There is limited data, however, regarding the optimal timing of therapy in the context of possible liver transplantation (LT). We compared the cost-effectiveness of 12 weeks of HCV therapy before or after LT or nontreatment using a decision analytical microsimulation state-transition model for a simulated cohort of 10 000 patients with HCV Genotype 1 or 4 with Child B or C cirrhosis. All model parameters regarding the efficacy of therapy, adverse events and the effect of therapy on changes in model for end-stage liver disease (MELD) scores were derived from the SOLAR-1 and 2 trials. The simulations were repeated with 10 000 samples from the parameter distributions. The primary outcome was cost (2014 US dollars) per quality adjusted life year. Treatment before LT yielded more quality-adjusted life year for less money than treatment after LT or nontreatment. Treatment before LT was cost-effective in 100% of samples at a willingness-to-pay threshold of US $100 000 in the base-case and when the analysis was restricted to Child B alone, Child C, or MELD > 15. Treatment before transplant was not cost-effective when MELD was 6-10. In sensitivity analyses, the MELD after which treatment before transplant was cost-effective was 13 and the maximum cost of LDV/SOF therapy at which treatment before LT is cost-effective is US $177 381. From a societal perspective, HCV therapy using LDV/SOF with ribavirin before LT is the most cost-effective strategy for patients with decompensated cirrhosis and MELD score greater than 13.

Stage-dependent teratogenic and lethal effects exerted by ultraviolet B radiation on Rhinella (Bufo) arenarum embryos.

PubMed

Castañaga, Luis A; Asorey, Cynthia M; Sandoval, María T; Pérez-Coll, Cristina S; Argibay, Teresa I; Herkovits, Jorge

2009-02-01

The adverse effects of ultraviolet B radiation from 547.2 to 30,096 J/m2 on morphogenesis, cell differentiation, and lethality of amphibian embryos at six developmental stages were evaluated from 24 up to 168 h postexposure. The ultraviolet B radiation lethal dose 10, 50, and 90 values were obtained for all developmental stages evaluated. The lethal dose 50 values, considered as the dose causing lethality in the 50% of the organisms exposed, in J/m2 at 168 h postexposure, ranged from 2,307 to 18,930; gill circulation and blastula were the most susceptible and resistant stages, respectively. Ultraviolet B radiation caused malformations in all developmental stages but was significantly more teratogenic at the gill circulation and complete operculum stages. Moreover, at the gill circulation stage, even the lowest dose (547.2 J/m2) resulted in malformations to 100% of embryos. The most common malformations were persistent yolk plug, bifid spine, reduced body size, delayed development, asymmetry, microcephaly and anencephaly, tail and body flexures toward the irradiated side, agenesia or partial gill development, abnormal pigment distribution, and hypermotility. The stage-dependent susceptibility to ultraviolet B radiation during amphibian embryogenesis could be explained in the framework of evoecotoxicology, considering ontogenic features as biomarkers of environmental signatures of living forms ancestors during the evolutionary process. The stage-dependent susceptibility to ultraviolet B radiation on Rhinella (Bufo) arenarum embryos for both lethal and teratogenic effects could contribute to a better understanding of the role of the increased ultraviolet B radiation on worldwide amphibian populations decline.

Younger rats are more susceptible to the lethal effects of sarin than adult rats: 24 h LC50 for whole-body (10 and 60 min) exposures.

PubMed

Wright, Linnzi K M; Lumley, Lucille A; Lee, Robyn B; Taylor, James T; Miller, Dennis B; Muse, William T; Emm, Edward J; Whalley, Christopher E

2017-04-01

Chemical warfare nerve agents (CWNA) inhibit acetylcholinesterase and are among the most lethal chemicals known to man. Children are predicted to be vulnerable to CWNA exposure because of their smaller body masses, higher ventilation rates and immature central nervous systems. While a handful of studies on the effects of CWNA in younger animals have been published, exposure routes relevant to battlefield or terrorist situations (i.e. inhalation for sarin) were not used. Thus, we estimated the 24 h LC 50 for whole-body (10 and 60 min) exposure to sarin using a stagewise, adaptive dose design. Specifically, male and female Sprague-Dawley rats were exposed to a range of sarin concentrations (6.2-44.0 or 1.6-12.5 mg/m³) for either 10 or 60 min, respectively, at six different times during their development (postnatal day [PND] 7, 14, 21, 28, 42 and 70). For male and female rats, the lowest LC 50 values were observed for PND 14 and the highest LC 50 values for PND 28. Sex differences were observed only for PND 42 for the 10 min exposures and PND 21 and 70 for the 60 min exposures. Thus, younger rats (PND 14) were more susceptible than older rats (PND 70) to the lethal effects of whole-body exposure to sarin, while adolescent (PND 28) rats were the least susceptible and sex differences were minimal. These results underscore the importance of controlling for the age of the animal in research on the toxic effects associated with CWNA exposure.

--No Title--

Science.gov Websites

;ZTolerance>0.0010.001true< EPSG 7.4.1 Simple 4 FALSE 1527 TRUE FALSE TX_50m_wind Feature Class 1527 FID FID OID 4 0 0 Internal

Passive dosing of polycyclic aromatic hydrocarbon (PAH) mixtures to terrestrial springtails: linking mixture toxicity to chemical activities, equilibrium lipid concentrations, and toxic units.

PubMed

Schmidt, Stine N; Holmstrup, Martin; Smith, Kilian E C; Mayer, Philipp

2013-07-02

A 7-day mixture toxicity experiment with the terrestrial springtail Folsomia candida was conducted, and the effects were linked to three different mixture exposure parameters. Passive dosing from silicone was applied to tightly control exposure levels and compositions of 12 mixture treatments, containing the polycyclic aromatic hydrocarbons (PAHs) naphthalene, phenanthrene, and pyrene. Springtail lethality was then linked to sum chemical activities (∑a), sum equilibrium lipid concentrations (∑C(lipid eq.)), and sum toxic units (∑TU). In each case, the effects of all 12 mixture treatments could be fitted to one sigmoidal exposure-response relationship. The effective lethal chemical activity (La50) of 0.027 was well within the expected range for baseline toxicity of 0.01-0.1. Linking the effects to the lipid-based exposure parameter yielded an effective lethal concentration (LC(lipid eq 50)) of 133 mmol kg(-1) lipid in good correspondence with the lethal membrane burden for baseline toxicity (40-160 mmol kg(-1) lipid). Finally, the effective lethal toxic unit (LTU50) of 1.20 was rather close to the expected value of 1. Altogether, passive dosing provided tightly controlled mixture exposure in terms of both level and composition, while ∑a, ∑C(lipid eq.), and ∑TU allowed baseline toxicity to be linked to mixture exposure.

Head and neck and esophageal cancers after liver transplant: results from a multicenter cohort study. Italy, 1997-2010.

PubMed

Piselli, Pierluca; Burra, Patrizia; Lauro, Augusto; Baccarani, Umberto; Ettorre, Giuseppe M; Vizzini, Giovanni B; Rendina, Maria; Rossi, Massimo; Tisone, Giuseppe; Zamboni, Fausto; Bortoluzzi, Ilaria; Pinna, Antonio D; Risaliti, Andrea; Galatioto, Laura; Vennarecci, Giovanni; Di Leo, Alfredo; Nudo, Francesco; Sforza, Daniele; Fantola, Giovanni; Cimaglia, Claudia; Verdirosi, Diana; Virdone, Saverio; Serraino, Diego

2015-07-01

This study quantified the risk of head and neck (HN) and esophageal cancers in 2770 Italian liver transplant (LT) recipients. A total of 186 post-transplant cancers were diagnosed-including 32 cases of HN cancers and nine cases of esophageal carcinoma. The 10-year cumulative risk for HN and esophageal carcinoma was 2.59%. Overall, HN cancers were nearly fivefold more frequent in LT recipients than expected (standardized incidence ratios - SIR=4.7, 95% CI: 3.2-6.6), while esophageal carcinoma was ninefold more frequent (SIR=9.1, 95% CI: 4.1-17.2). SIRs ranged from 11.8 in LT with alcoholic liver disease (ALD) to 1.8 for LT without ALD for HN cancers, and from 23.7 to 2.9, respectively, for esophageal carcinoma. Particularly elevated SIRs in LT with ALD were noted for carcinomas of tongue (23.0) or larynx (13.7). Our findings confirmed and quantified the large cancer excess risk in LT recipients with ALD. The risk magnitude and the prevalence of ALD herein documented stress the need of timely and specifically organized programs for the early diagnosis of cancer among LT recipients, particularly for high-risk recipients like those with ALD. © 2015 Steunstichting ESOT.

The effects of finishing diet and postmortem ageing on the eating quality of the M. longissimus thoracis of electrically stimulated Brahman steer carcasses.

PubMed

Bruce, H L; Stark, J L; Beilken, S L

2004-06-01

Beef from cattle finished on grass will be of similar quality to that from cattle finished on grain when their carcasses are processed using best practice protocols. To test this hypothesis, carcasses of twenty Brahman steers, finished to 400 kg live weight on either Buffel grass pasture (n=10) or grain (n=10), were electrically stimulated with 400 V for 50 s 45 min postmortem, and their beef quality assessed 1 and 14 days postmortem. Hot weight, rump subcutaneous fat thickness and animal rate of growth in the 205 days preceding slaughter were recorded for each carcass as potential influences on beef quality. Quality of the M. longissimus thoracis (LT) at 1 and 14 days postmortem was evaluated using peak Warner-Bratzler shear force, compression, pH, cooking loss and taste panel acceptability, as well as by moisture and crude fat contents measured at 1 day postmortem. Results showed that steers finished on pasture grew the slowest and had the least subcutaneous fat at the same carcass weight. LT from carcasses of steers finished on pasture also had the shortest mean sarcomere lengths, suggesting these muscles may have been cold-affected, but there was no effect of diet on peak shear force. LT from carcasses of steers finished on pasture had the highest mean compression value, possibly because of increased collagen cross-linking associated with slow growth or increased exercise. Ageing significantly decreased LT peak shear force and compression values and increased cooking loss, L (∗), a (∗) and b (∗) values. Taste panellists rated the aged, grass-finished beef the most tender and the best quality; however, the taste panel in this study may have favoured LT from grass-finished steers because it was significantly juicier than LT from the grain-finished steer carcasses. These results indicated that carcass composition and processing conditions interact to exert a greater effect on LT toughness and sensory acceptability than finishing diet. Ageing LT from steers finished on grass improved its colour, and thus may enhance its consumer acceptability.

Relationship between mosquito (Diptera: Culicidae) landing rates on a human subject and numbers captured using CO2-baited light traps.

PubMed

Barnard, D R; Knue, G J; Dickerson, C Z; Bernier, U R; Kline, D L

2011-06-01

Capture rates of insectary-reared female Aedes albopictus (Skuse), Anopheles quadrimaculatus Say, Culex nigripalpus Theobald, Culex quinquefasciatus Say and Aedes triseriatus (Say) in CDC-type light traps (LT) supplemented with CO2 and using the human landing (HL) collection method were observed in matched-pair experiments in outdoor screened enclosures. Mosquito responses were compared on a catch-per-unit-effort basis using regression analysis with LT and HL as the dependent and independent variables, respectively. The average number of mosquitoes captured in 1 min by LT over a 24-h period was significantly related to the average number captured in 1 min by HL only for Cx. nigripalpus and Cx. quinquefasciatus. Patterns of diel activity indicated by a comparison of the mean response to LT and HL at eight different times in a 24-h period were not superposable for any species. The capture rate efficiency of LT when compared with HL was ≤15% for all mosquitoes except Cx. quinquefasciatus (43%). Statistical models of the relationship between mosquito responses to each collection method indicate that, except for Ae. albopictus, LT and HL capture rates are significantly related only during certain times of the diel period. Estimates of mosquito activity based on observations made between sunset and sunrise were most precise in this regard for An. quadrimaculatus and Cx. nigripalpus, as were those between sunrise and sunset for Cx. quinquefasciatus and Ae. triseriatus.

Living Donor Liver Transplantation for Acute Liver Failure : Comparing Guidelines on the Prediction of Liver Transplantation.

PubMed

Yoshida, Kazuhiro; Umeda, Yuzo; Takaki, Akinobu; Nagasaka, Takeshi; Yoshida, Ryuichi; Nobuoka, Daisuke; Kuise, Takashi; Takagi, Kosei; Yasunaka, Tetsuya; Okada, Hiroyuki; Yagi, Takahito; Fujiwara, Toshiyoshi

2017-10-01

Determining the indications for and timing of liver transplantation (LT) for acute liver failure (ALF) is essential. The King's College Hospital (KCH) guidelines and Japanese guidelines are used to predict the need for LT and the outcomes in ALF. These guidelines' accuracy when applied to ALF in different regional and etiological backgrounds may differ. Here we compared the accuracy of new (2010) Japanese guidelines that use a simple scoring system with the 1996 Japanese guidelines and the KCH criteria for living donor liver transplantation (LDLT). We retrospectively analyzed 24 adult ALF patients (18 acute type, 6 sub-acute type) who underwent LDLT in 1998-2009 at our institution. We assessed the accuracies of the 3 guidelines' criteria for ALF. The overall 1-year survival rate was 87.5%. The new and previous Japanese guidelines were superior to the KCH criteria for accurately predicting LT for acute-type ALF (72% vs. 17%). The new Japanese guidelines could identify 13 acute-type ALF patients for LT, based on the timing of encephalopathy onset. Using the previous Japanese guidelines, although the same 13 acute-type ALF patients (72%) had indications for LT, only 4 patients were indicated at the 1st step, and it took an additional 5 days to decide the indication at the 2nd step in the other 9 cases. Our findings showed that the new Japanese guidelines can predict the indications for LT and provide a reliable alternative to the previous Japanese and KCH guidelines.

Diabetes mellitus may affect the long-term survival of hepatitis B virus-related hepatocellular carcinoma patients after liver transplantation.

PubMed

Zhang, Qing; Deng, Yong-Lin; Liu, Chang; Huang, Li-Hong; Shang, Lei; Chen, Xin-Guo; Wang, Le-Tian; Du, Jin-Zan; Wang, Ying; Wang, Pei-Xiao; Zhang, Hui; Shen, Zhong-Yang

2016-11-21

To determine whether diabetes mellitus (DM) affects prognosis/recurrence after liver transplantation (LT) for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). A retrospective study was conducted between January 2000 and August 2013 on 1631 patients with HBV-related HCC who underwent LT with antiviral prophylaxis. Patient data were obtained from the China Liver Transplant Registry (https://www.cltr.org/). To compare the outcomes and tumor recurrence in the HBV-related HCC patients with or without DM, statistical analyses were conducted using χ 2 tests, Mann-Whitney tests, the Kaplan-Meier method, log-rank tests and multivariate step-wise Cox regression analysis. Univariate analysis of 1631 patients who underwent LT found overall 1-, 3- and 5-year survival rates of 79%, 73% and 71% respectively in the DM patients, and 84%, 78% and 76% in the non-DM patients respectively. Overall survival rate differences after LT between the two groups were significant ( P = 0.041), but recurrence-free survival rates were not ( P = 0.096). By stratified analysis, the overall survival rates in DM patients for age > 50 years ( P = 0.002), the presence of vascular invasion ( P = 0.096), tumors ≤ 3 cm ( P = 0.047), two to three tumor nodules ( P = 0.007), Child-Pugh grade B ( P = 0.018), and pre-LT alanine aminotransferase levels between 40 and 80 IU/L ( P = 0.017) were significantly lower than in non-DM patients. Additionally, serum α-fetoprotein level > 2000 ng/mL ( P = 0.052) was associated with a significant survival difference trend between DM and non-DM patients. Multivariate analysis showed that the presence of DM ( P < 0.001, HR = 1.591; 95%CI: 1.239-2.041) was an independent predictor associated with poor survival after LT. HBV-related HCC patients with DM have decreased long-term overall survival and poor LT outcomes. Prevention strategies for HCC patients with DM are recommended.

Determination of hepatocellular carcinoma grade by needle biopsy is unreliable for liver transplant candidate selection.

PubMed

Court, Colin M; Harlander-Locke, Michael P; Markovic, Daniela; French, Samuel W; Naini, Bita V; Lu, David S; Raman, Steven S; Kaldas, Fady M; Zarrinpar, Ali; Farmer, Douglas G; Finn, Richard S; Sadeghi, Saeed; Tomlinson, James S; Busuttil, Ronald W; Agopian, Vatche G

2017-09-01

The objective of this article is to evaluate the utility of preoperative needle biopsy (PNB) grading of hepatocellular carcinoma (HCC) as a biomarker for liver transplantation (LT) candidate selection. Given the prognostic significance of HCC tumor grade, PNB grading has been proposed as a biomarker for LT candidate selection. Clinicopathologic characteristics of HCC LT recipients (1989-2014) with a PNB were analyzed, and the concordance of PNB grade to explant grade and vascular invasion was assessed to determine whether incorporation of PNB grade to accepted transplant criteria improved candidate selection. Of 965 patients undergoing LT for HCC, 234 (24%) underwent PNB at a median of 280 days prior to transplant. Grade by PNB had poor concordance to final explant pathology (κ = 0.22; P = 0.003), and low sensitivity (29%) and positive predictive value (35%) in identifying poorly differentiated tumors. Vascular invasion was predicted by explant pathologic grade (r s = 0.24; P < 0.001) but not PNB grade (r s = -0.05; P = 0.50). Increasing explant pathology grade (P = 0.02), but not PNB grade (P = 0.65), discriminated post-LT HCC recurrence risk. The incorporation of PNB grade to the established radiologic Milan criteria (MC) did not result in improved prognostication of post-LT recurrence (net reclassification index [NRI] = 0%), whereas grade by explant pathology resulted in significantly improved reclassification of risk (NRI = 19%). Preoperative determination of HCC grade by PNB has low concordance with explant pathologic grade and low sensitivity and positive predictive value in identifying poorly differentiated tumors. PNB grade did not accurately discriminate post-LT HCC recurrence and had no utility in improving prognostication compared with the MC alone. Incorporation of PNB to guide transplant candidate selection appears unjustified. Liver Transplantation 23 1123-1132 2017 AASLD. © 2017 by the American Association for the Study of Liver Diseases.

Delayed rearterialization unlikely leads to nonanastomotic stricture but causes temporary injury on bile duct after liver transplantation.

PubMed

Liu, Yang; Wang, Jiazhong; Yang, Peng; Lu, Hongwei; Lu, Le; Wang, Jinlong; Li, Hua; Duan, Yanxia; Wang, Jun; Li, Yiming

2015-03-01

Nonanastomotic strictures (NAS) are common biliary complications after liver transplantation (LT). Delayed rearterialization induces biliary injury in several hours. However, whether this injury can be prolonged remains unknown. The correlation of this injury with NAS occurrence remains obscure. Different delayed rearterialization times were compared using a porcine LT model. Morphological and functional changes in bile canaliculus were evaluated by transmission electron microscopy and real-time PCR. Immunohistochemistry and TUNEL were performed to validate intrahepatic bile duct injury. Three months after LT was performed, biliary duct stricture was determined by cholangiography; the tissue of common bile duct was detected by real-time PCR. Bile canaliculi were impaired in early postoperative stage and then exacerbated as delayed rearterialization time was prolonged. Nevertheless, damaged bile canaliculi could fully recover in subsequent months. TNF-α and TGF-β expressions and apoptosis cell ratio increased in the intrahepatic bile duct only during early postoperative period in a time-dependent manner. No abnormality was observed by cholangiography and common bile duct examination after 3 months. Delayed rearterialization caused temporary injury to bile canaliculi and intrahepatic bile duct in a time-dependent manner. Injury could be fully treated in succeeding months. Solo delayed rearterialization cannot induce NAS after LT. © 2014 The Authors. Transplant International published by John Wiley & Sons Ltd on behalf of Steunstichting ESOT.

Correlation of Lethal Concentrations of Heavy Metals with Tissue Levels of Earthworms

DTIC Science & Technology

1988-08-01

mentioned in the contract i.e. mercury , arsenic, ’cadmium and copper. We will find out the 50 % lethal concentrations (LC50) and the smallest...concentrations, blanks, and background worm stock has been limited to copper and cadmium. In fact, mercury and arsenic request special analytical device...the other boxes but without toxic components. Contaminants to study are heavy metals : cadmium, copper and mercury , and arsenic. We chose following

Oxychlordane, HCS-3260, and nonachlor in birds: Lethal residues and loss rates

USGS Publications Warehouse

Stickel, L.F.; Stickel, W.H.; Dyrland, R.A.; Hughes, D.L.

1983-01-01

Oxychlordane reached lethal levels in birds given dietary dosages of HCS-3260 (70.75% cis-chlordane and 23.51% trans-chlordane) at 6 levels from 50 to 500 ppm. Oxychlordane ranged from 9.4 to 22.1 ppm in brains of cowbirds (Molothrus ater ) grackles (Quiscalus quiscula , and red-winged blackbirds (Agelaius phoeniceus ) that died on dosage and from 1.3 to 4.8 ppm in sacrificed birds, providing a clear diagnostic separation. Among starlings (Sturnus vulgaris ) however, oxychlordane ranged from 5.0 to 19.1 ppm in brains of birds that died, significantly lower than in the other species, and from 1.4 to 10.5 ppm in sacrificed birds, overlapping the levels in those that died. Lethal levels, therefore, begin near 5.0 ppm, as in a previous study in which oxychlordane itself was fed, but the data from starlings emphasizes the need for confirmatory necropsy findings in diagnosis of poisoning.

Pharmacokinetics of total thyroxine after repeated oral administration of levothyroxine solution and its clinical efficacy in hypothyroid dogs.

PubMed

van Dijl, I C; Le Traon, G; van de Meulengraaf, B D A M; Burgaud, S; Horspool, L J I; Kooistra, H S

2014-01-01

Oral levothyroxine (l-T4 ) supplementation is commonly used to treat hypothyroid dogs. Investigate the plasma profile and pharmacokinetics of total thyroxine (tT4 ) after PO administration of a l-T4 solution and its clinical efficacy in hypothyroid dogs. Ten dogs with naturally occurring hypothyroidism. After hypothyroidism diagnosis and supplementation with l-T4 solution PO q24h at 20 μg/kg BW for minimum 4 weeks, the plasma profile and pharmacokinetics of tT4 were determined over 34 hours and the clinical condition of the dogs was evaluated. Before dosing for pharmacokinetic evaluation, mean tT4 concentration was 23 ± 9 nmol/L. l-T4 was absorbed rapidly (tmax , 5 hours), reaching a mean maximal tT4 concentration of 56 ± 11 nmol/L. The apparent terminal half-life was 11.8 hours. Clinical signs of hypothyroidism improved or resolved in all dogs after 4 weeks of treatment. The dosage of 20 μg/kg PO q24h was judged appropriate in 5 dogs, and 4 dogs required slight increases (9-16%). Twice daily treatment, with a 30% increase in dosage, was necessary for 1 dog. The pharmacokinetics of l-T4 in hypothyroid dogs was similar to that reported in healthy euthyroid dogs. Clinical and hormonal responses to l-T4 solution were rapid in all dogs. The starting dosage of 20 μg/kg PO q24h was suitable for maintenance supplementation in 50% of the dogs, minor dosage modification was required in 4 other dogs, and treatment q12h was required in 1 dog. Copyright © 2014 by the American College of Veterinary Internal Medicine.

Effects of levothyroxine on learning and memory deficits in a rat model of Alzheimer's disease: the role of BDNF and oxidative stress.

PubMed

Bavarsad, Kowsar; Hadjzadeh, Mousa-Al-Reza; Hosseini, Mahmoud; Pakdel, Roghayeh; Beheshti, Farimah; Bafadam, Soleyman; Ashaari, Zeinab

2018-06-21

The effect of levothyroxine (L-T4) on the learning and memory impairment induced by streptozotocin (STZ) and brain tissue oxidative damage in rats was evaluated. An animal model of the Alzheimer's disease (AD) was established by intracerebroventricular injection of STZ (3 mg/kg) in male Wistar rats (250 ± 50 g). After that, the rats were treated for 3 weeks with L-T4 (10, 100 μg/kg) or normal saline. Passive avoidance (PA) learning and spatial memory were evaluated using shuttle box and Morris water maze (MWM), respectively. Finally, the rats were euthanized, their blood samples were collected for further thyroxine assessment and their brains were removed after decapitation in order to measure the oxidative stress parameters and brain-derived neurotrophic factor (BDNF). In the MWM, latency (s) increased in the AD rats compared with the normal control group while it decreased in the 10 μg/kg L-T4 injected AD rats compared with the AD group. In the PA, the latency for entering the dark compartment was lower in the AD group than in the normal control group and it decreased in the 10 μg/kg L-T4 injected AD rats. The low dose of L-T4 (10 μg/kg) reduced malondialdehyde concentration but increased thiols concentration, superoxide dismutase, catalase activities and BDNF level in hippocampal tissues of the AD rats. Injection of L-T4 (10 μg/kg) alleviated memory deficits and also improved factors of oxidative stress and BDNF level in the STZ-induced AD rats.

Mixed Model Association with Family-Biased Case-Control Ascertainment.

PubMed

Hayeck, Tristan J; Loh, Po-Ru; Pollack, Samuela; Gusev, Alexander; Patterson, Nick; Zaitlen, Noah A; Price, Alkes L

2017-01-05

Mixed models have become the tool of choice for genetic association studies; however, standard mixed model methods may be poorly calibrated or underpowered under family sampling bias and/or case-control ascertainment. Previously, we introduced a liability threshold-based mixed model association statistic (LTMLM) to address case-control ascertainment in unrelated samples. Here, we consider family-biased case-control ascertainment, where case and control subjects are ascertained non-randomly with respect to family relatedness. Previous work has shown that this type of ascertainment can severely bias heritability estimates; we show here that it also impacts mixed model association statistics. We introduce a family-based association statistic (LT-Fam) that is robust to this problem. Similar to LTMLM, LT-Fam is computed from posterior mean liabilities (PML) under a liability threshold model; however, LT-Fam uses published narrow-sense heritability estimates to avoid the problem of biased heritability estimation, enabling correct calibration. In simulations with family-biased case-control ascertainment, LT-Fam was correctly calibrated (average χ 2 = 1.00-1.02 for null SNPs), whereas the Armitage trend test (ATT), standard mixed model association (MLM), and case-control retrospective association test (CARAT) were mis-calibrated (e.g., average χ 2 = 0.50-1.22 for MLM, 0.89-2.65 for CARAT). LT-Fam also attained higher power than other methods in some settings. In 1,259 type 2 diabetes-affected case subjects and 5,765 control subjects from the CARe cohort, downsampled to induce family-biased ascertainment, LT-Fam was correctly calibrated whereas ATT, MLM, and CARAT were again mis-calibrated. Our results highlight the importance of modeling family sampling bias in case-control datasets with related samples. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Mosquito larvicidal activity of botanical-based mosquito repellents.

PubMed

Zhu, Junwei; Zeng, Xiaopeng; O'Neal, Megan; Schultz, Gretchen; Tucker, Brad; Coats, Joel; Bartholomay, Lyric; Xue, Rui-De

2008-03-01

The larvicidal activity of 4 plant essential oils--innamon oil, lemon eucalyptus oil, sandalwood oil, and turmeric oil--previously reported as insect repellents was evaluated in the laboratory against 4th instars of Aedes albopictus, Ae. aegypti, and Culex pipiens. Sandalwood oil appeared to be the most effective of the larvicides, killing larvae of all 3 mosquito species in relatively short times. The values of LT50 and LT90 at the application dosage (0.2 mg/ml) were 1.06 +/- 0.11 and 3.24 +/- 0.14 h for Ae. aegypti, 1.82 +/- 0.06 and 3.33 +/- 0.48 h for Ae. albopictus, and 1.55 +/- 0.07 and 3.91 +/- 0.44 h for Cx. pipiens, respectively. Chemical compositions of these essential oils were also studied, and the lavicidal activity of their major ingredient compounds was compared with that of each of the essential oils. The acute toxicity of the 4 essential oils to fathead minnows was also evaluated. The safe use of these natural plant essential oils in future applications of mosquito control was discussed.

Lethal Zika Virus Disease Models in Young and Older Interferon α/β Receptor Knock Out Mice.

PubMed

Marzi, Andrea; Emanuel, Jackson; Callison, Julie; McNally, Kristin L; Arndt, Nicolette; Chadinha, Spencer; Martellaro, Cynthia; Rosenke, Rebecca; Scott, Dana P; Safronetz, David; Whitehead, Stephen S; Best, Sonja M; Feldmann, Heinz

2018-01-01

The common small animal disease models for Zika virus (ZIKV) are mice lacking the interferon responses, but infection of interferon receptor α/β knock out (IFNAR -/- ) mice is not uniformly lethal particularly in older animals. Here we sought to advance this model in regard to lethality for future countermeasure efficacy testing against more recent ZIKV strains from the Asian lineage, preferably the American sublineage. We first infected IFNAR -/- mice subcutaneously with the contemporary ZIKV-Paraiba strain resulting in predominantly neurological disease with ~50% lethality. Infection with ZIKV-Paraiba by different routes established a uniformly lethal model only in young mice (4-week old) upon intraperitoneal infection. However, intraperitoneal inoculation of ZIKV-French Polynesia resulted in uniform lethality in older IFNAR -/- mice (10-12-weeks old). In conclusion, we have established uniformly lethal mouse disease models for efficacy testing of antivirals and vaccines against recent ZIKV strains representing the Asian lineage.

Experimental Respiratory Infection of Marmosets (Callithrix jacchus) With Ebola Virus Kikwit.

PubMed

Smither, Sophie J; Nelson, Michelle; Eastaugh, Lin; Nunez, Alejandro; Salguero, Francisco J; Lever, Mark S

2015-10-01

Ebola virus (EBOV) causes a highly infectious and lethal hemorrhagic fever in primates with high fatality rates during outbreaks and EBOV may be exploited as a potential biothreat pathogen. There is therefore a need to develop and license appropriate medical countermeasures against this virus. To determine whether the common marmoset (Callithrix jacchus) would be an appropriate model to assess vaccines or therapies against EBOV disease (EVD), initial susceptibility, lethality and pathogenesis studies were performed. Low doses of EBOV-Kikwit, between 4 and 27 times the 50% tissue culture infectious dose, were sufficient to cause a lethal, reproducible infection. Animals became febrile between days 5 and 6, maintaining a high fever before succumbing to EVD between 6 and 8 days after challenge. Typical signs of EVD were observed. Pathogenesis studies revealed that virus was isolated from the lungs of animals beginning on day 3 after challenge and from the liver, spleen and blood beginning on day 5. The most striking features were observed in animals that succumbed to infection, including high viral titers in all organs, increased levels of liver function enzymes and blood clotting times, decreased levels of platelets, multifocal moderate to severe hepatitis, and perivascular edema. © Crown copyright 2015.

West Europe Report

DTIC Science & Technology

1985-07-15

Lisbon TAL & QUAL in Portuguese 17 May 85 p 3 [Text] Manuel da Costa Bras, Lt Col in the reserves and High Commissioner against Corruption, is facing...people around Gen Eanes, starting with Lt Col Melo Antunes. The PRD itself has already announced many times that it would not oppose such an

Replication Stress and Mitotic Dysfunction in Cells Expressing Simian Virus 40 Large T Antigen

PubMed Central

Hu, Liang; Filippakis, Harilaos; Huang, Haomin; Yen, Timothy J.

2013-01-01

We previously demonstrated that simian virus 40 (SV40) large T antigen (LT) binds to the Bub1 kinase, a key regulator of the spindle checkpoint and chromosome segregation. Bub1 mutations or altered expression patterns are linked to chromosome missegregation and are considered to be a driving force in some human cancers. Here we report that LT, dependent on Bub1 binding, causes micronuclei, lagging chromatin, and anaphase bridges, which are hallmarks of chromosomal instability (CIN) and Bub1 insufficiency. Using time-lapse microscopy, we demonstrate that LT imposes a Bub1 binding-dependent delay in the metaphase-to-anaphase transition. Kinetochore fibers reveal that LT, via Bub1 binding, causes aberrant kinetochore (KT)-microtubule (MT) attachments and a shortened interkinetochore distance, consistent with a lack of tension. Previously, we showed that LT also induces the DNA damage response (DDR) via Bub1 binding. Using inducible LT cell lines, we show that an activated DDR was observed before the appearance of anaphase bridges and micronuclei. Furthermore, LT induction in serum-starved cells demonstrated γ-H2AX accumulation in cells that had not yet entered mitosis. Thus, DDR activation can occur independently of chromosome segregation defects. Replication stress pathways may be responsible, because signatures of replication stress were observed, which were attenuated by exogenous supplementation with nucleosides. Our observations allow us to propose a model that explains and integrates the diverse manifestations of genomic instability induced by LT. PMID:24067972

[Surgical correction of the intraabdominal hypertension in patients with colon cancer].

PubMed

Aliev, S A

2012-01-01

The experience of treatment of 48 patients with colon cancer, complicated with bowe obstruction, colon perforation, abdominal sepsis and intraabdominal hypertension was analyzed. Men were 18, women - 30. Patients' age ranged 24-85 years. 31 patients (64.6%) had the 3rd stage (T4N2M0) of the disease by the time of the diagnosis. Tumor perforation was registered in 35 patients, the rest 13 had suprastenotic perforation. 39 patients developed SIRS and abdominal sepsis. The method of intraoperative "closed" colon decompression and intraluminar colon irrigation with the original modification of vacuum aspiration-irrigation device was introduced, as well as the modified method of end colostomy. Radical treatment was performed in 36 (78.3%) patients, 10 patients received palliative treatment and 2 patients could not be operated on. The postoperative lethality rate was 45.6%, the overall - 47.9%. The suggested method of colon decompression allowed to decrease the postoperative lethality rate from 47.7 to 45.6%, and the overall lethality rate from 50 to 47.9%.

Acute Lethality after Fast-Neutron and X-Irradiation of Tribolium confusum

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

Glenn, Norman D.; Ducoff, Howard S.

1976-01-01

The acute lethal effects of fast neutrons and of X-rays on adults and larvae of T. confusum are compared. The time course of mortality of adults of the Oklahoma strain was the same after midlethal doses of neutrons and X-rays, although the neutrons were about twice as effective as X-rays in producing lethality, based on LD 50(35). The neutron RBE for adults of the Ebony mutant strain was also about 2, but that for Oklahoma larvae was about 3.85. Larvae surviving midlethal doses of neutrons showed a tendency toward wing abnormalities and delayed pupation. Dose-fractionation recovery with neutron doses inmore » the midlethal range was not detectable in the adults or in the larvae. A considerable sparing effect of dose fractionation was found in X-irradiated adults. Finally, also presented are techniques for using a beam port of a Triga research reactor for fast-neutron irradiation and a method of neutron and gamma dosimetry.« less

Direct comparison of oligochaete erythrocruorins as potential blood substitutes

PubMed Central

Zimmerman, Devon; DiIusto, Matthew; Dienes, Jack; Abdulmalik, Osheiza

2017-01-01

Abstract While many blood substitutes are based on mammalian hemoglobins (e.g., human hemoglobin, HbA), the naturally extracellular hemoglobins of invertebrates (a.k.a. erythrocruorins, Ecs) are intriguing alternative oxygen carriers. Specifically, the erythrocruorin of Lumbricus terrestris has been shown to effectively deliver oxygen in mice and rats without the negative side effects observed with HbA. In this study, the properties of six oligochaete Ecs (Lumbricus terrestris, Eisenia hortensis, Eisenia fetida, Eisenia veneta, Eudrilus eugeniae, and Amynthas gracilis) were compared in vitro to identify the most promising blood substitute candidate(s). Several metrics were used to compare the Ecs, including their oxidation rates, dissociation at physiological pH, thermal stability, and oxygen transport characteristics. Overall, the Ecs of Lumbricus terrestris (LtEc) and Eisenia fetida (EfEc) were identified as promising candidates, since they demonstrated high thermal and oligomeric stability, while also exhibiting relatively low oxidation rates. Interestingly, the O2 affinity of LtEc (P 50 = 26.25 mmHg at 37 °C) was also observed to be uniquely lower than EfEc and all of the other Ecs (P 50 = 9.29–13.62 mmHg). Subsequent alignment of the primary sequences of LtEc and EfEc revealed several significant amino acid substitutions within the D subunit interfaces that may be responsible for this significant change in O2 affinity. Nonetheless, these results show that LtEc and EfEc are promising potential blood substitutes that are resistant to oxidation and denaturation, but additional experiments will need to be conducted to determine their safety, efficacy, and the effects of their disparate oxygen affinities in vivo. PMID:29313031

Influence of Route of Administration on Immediate and Extended Protection in Rats Immunized with Escherichia coli Heat-Labile Enterotoxin

PubMed Central

Klipstein, Frederick A.; Engert, Richard F.

1980-01-01

The effect of route of administration, dosage, and number of boosts employed during immunization with the polymyxin-release form of Escherichia coli heat-labile (LT) enterotoxin on the degree and duration of protection afforded was evaluated in rats which were challenged by the ligated loop technique. Increasing the boosting dosage by fivefold from 50 to 250 μg resulted in a marked increase in protection against challenge with toxin in rats immunized either just by the parenteral route (i.p./i.p.) or by a parenteral prime, followed by peroral boosts (i.p./p.o.) in rats pretreated with cimetidine to ablate gastric secretions; such was not the case, however, even with a 50-fold increase in dosage in rats immunized just by the peroral route (p.o./p.o.). Four weekly peroral boosts were required to achieve the strongest degree of protection. Increasing the boosting dosage also increased the degree of protection against challenge with viable LT+/ST− and LT+/ST+ strains (ST indicates heat-stable enterotoxin) in rats immunized by the i.p./p.o., but not by the i.p./i.p., route; no protection was evident against an LT−/ST+ strain. Protection was lost within 3 weeks after immunization in rats immunized by the i.p./i.p. route. In contrast, protection was extended over the 3-month observation period in those immunized by the i.p./p.o. route; the degree of protection was enhanced in rats which received an additional boost at 2 months. These observations establish the fact that immunization with LT is similar to that with cholera toxin in that arousal of the local immune intestinal response by means of peroral immunization provides maximal extended protection. PMID:6987180

Assessment of levothyroxine sodium bioavailability: recommendations for an improved methodology based on the pooled analysis of eight identically designed trials with 396 drug exposures.

PubMed

Walter-Sack, Ingeborg; Clanget, Christof; Ding, Reinhard; Goeggelmann, Christoph; Hinke, Vera; Lang, Matthias; Pfeilschifter, Johannes; Tayrouz, Yorki; Wegscheider, Karl

2004-01-01

Assessment of dosage form performance in delivering endogenous compounds, such as hormones, in vivo requires a specific approach. Assessment of relative bioavailability of levothyroxine sodium (L-T4) from eight solid preparations, compared with a liquid formulation, by using pharmacological doses, and critical evaluation of trial methodology based on the pooled analysis of individual data. Eight open-label, randomised, single-dose, crossover phase I studies using eight solid L-T4 dosage forms (25, 50, 75, 100, 125, 150, 175, 200 microg per tablet; administered total doses 600, 625 or 700 microg) and a liquid formulation; assessment of relative bioavailability by 90% confidence intervals for the relative area under the concentration-time curve (AUC) of total thyroxine (TT4), i.e. protein-bound plus free thyroxine, calculated by using the recommended log AUC four-way analysis of variance models for crossover designs. For the pooled analysis, general linear models were applied to assess the validity of model assumptions, to identify potential sources of effect modification, to discuss alternative modelling approaches with respect to endogenous hormone secretion and to give recommendations for future designs and sample sizes. One hundred and sixty-nine healthy males; 29 of these individuals participating in two studies. Single oral doses of L-T4 tablets and the liquid formulation administered after fasting, separated by at least 6 weeks; a total of 396 drug exposures. TT4 AUC from 0 to 48 hours and peak plasma concentration with and without baseline correction. Each study demonstrated equivalence of the tablets to the drinking solution, independent of the chosen analysis model. Sequence effects that could devalidate the chosen crossover approach were not found. Period effects with changing directions that could best be explained by seasonal variation were detected. While the pre-specified method of baseline correction of simply subtracting individual time-zero TT4 values was disadvantageous, the analysis of total AUC could be improved considerably by covariate adjustment for baseline TT4. With this approach, sample sizes could have been substantially reduced or, alternatively, the recommended equivalence ranges could be reduced to +/-6%. Using a single pharmacological dose of L-T4 in two-period crossover designs is a safe and reliable procedure to assess L-T4 dosage form performance. With an adequate statistical modelling approach, the design is efficient and allows general conclusions with moderate sample sizes.

Complement

MedlinePlus

... activity (CH50, CH100) looks at the overall activity of the complement system. In most cases, other tests that are more ... Church SE, Fremeaux-Bacchi V, Roumenina LT. Complement system part I - molecular mechanisms of activation and regulation. Front Immunol . 2015;6:262. ...

Assessment of School Readiness in Chronic Cholestatic Liver Disease: A Pilot Study Examining Children with and without Liver Transplantation.

PubMed

Gold, Anna; Rogers, Alaine; Cruchley, Elizabeth; Rankin, Stephanie; Parmar, Arpita; Kamath, Binita M; Avitzur, Yaron; Ng, Vicky Lee

2017-01-01

Background. Assessment of school readiness evaluates physical, social-emotional, and neuropsychological domains essential for educational success. Cognitive testing of preschool aged children with chronic liver disease may guide more timely interventions and focused efforts by health care providers. Patients and Methods. Children with chronic cholestatic liver disease diagnosed as an infant and still with their native liver (NL) and children who received a liver transplant (LT) before age of 2 years underwent testing with a battery of well-validated pediatric psychometric measures. Results. Eighteen (13 LT, 5 NL) patients (median age of 4.45 and 4.05 years, resp.) were tested. Median Full-Scale IQ was 98 (range 102-116) for LT and 116 [(range 90-106), p = 0.35, NS] for NL subjects. LT recipients had significantly greater visual based difficulties, poorer caregiver rated daily living skills ( p = 0.04), and higher levels of executive function based difficulties (e.g., inattention, inhibition). Conclusion. This pilot study highlights the risk of neuropsychological difficulties in early school age children who were under 2 years of age at time of LT. Comprehensive early school age assessment should integrate psychometric measures to identify children at greatest risk, thus allowing for proactive educational intervention.

The efficacy of direct anti-HCV drugs improves early post-liver transplant survival and induces significant changes in waiting list composition.

PubMed

Crespo, Gonzalo; Trota, Núria; Londoño, Maria-Carlota; Mauro, Ezequiel; Baliellas, Carme; Castells, Lluís; Castellote, Jose; Tort, Jaume; Forns, Xavier; Navasa, Miquel

2018-07-01

The efficacy of direct-acting antivirals (DAAs) has dramatically changed the prognosis of patients with chronic hepatitis C. We aimed to evaluate the impact of DAA therapy on the composition of the liver transplant (LT) waiting list and the early post-transplant survival. We evaluated all patients admitted to the waiting list for a primary LT between 1st January 2008 and 31st of December 2016 in Catalonia, Spain. Time span was divided into two periods according to the availability of different antiviral therapies: 2008-2013 (interferon-based therapies) and 2014-2016 (DAA). Changes in the indications of LT and the aetiology of liver disease, as well as post-LT patient survival, were evaluated according to the year of inclusion and transplantation, respectively. We included 1,483 patients. Admissions in the waiting list for hepatitis C virus (HCV)-related liver disease decreased significantly, from 47% in 2008-2013 to 35% in 2014-2016 (p <0.001), particularly because of a reduction in patients with decompensated cirrhosis. In contrast, NASH-related inclusions increased from 4% to 7% (p = 0.003). Three-year post-LT patient survival increased significantly in the second period in the whole cohort (82% vs. 91%, p = 0.002), because of better survival in anti-HCV positive patients (76% vs. 91%, p = 0.001), but not in anti-HCV negative patients (88% vs. 91% p = 0.359). Anti-HCV positive serology, the time period of 2008-2013 and higher donor age were independently associated with post-LT mortality in the whole cohort; while time period and donor age were independently associated with post-LT mortality in anti-HCV positive recipients. The high efficacy of DAAs is associated with significant changes in the composition of the LT waiting list and, more importantly, results in improved post-transplant survival. The efficacy of the new direct-acting antivirals is associated with a significant improvement in survival of patients undergoing liver transplantation because of hepatitis C virus-related liver disease. In addition, it has decreased the number of patients with hepatitis C that need a liver transplant. Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Japanese Studies on Manchuria. Volume 11. Part 3. Book B. Small Wars and Border Problems, The Nomonhan Incident

DTIC Science & Technology

1956-09-05

Section (Operations) : Col. Masao Terada Senior Operations Staff Officer s Lt. Col. Takuahiro Hattori 174 Oparatlons ataff Offleart t Lt...2 cos, aprx 10 tks ea) and the 4th Tk Regt (Lt. Col. Tamada ; Type 95 It tks, 3 cos, aprr 10 vks eaj. — Ed. 260 t ! ^ ’if1! jflfl Ist...Col, Tamada ) was killed in action. At .out the same time, on the right flank, the 3d Tank Regiment (medium armor) pene- trated the enemy’s

Recognition of predictors for mid-long term runoff prediction based on lasso

NASA Astrophysics Data System (ADS)

Xie, S.; Huang, Y.

2017-12-01

Reliable and accuracy mid-long term runoff prediction is of great importance in integrated management of reservoir. And many methods are proposed to model runoff time series. Almost all forecast lead times (LT) of these models are 1 month, and the predictors are previous runoff with different time lags. However, runoff prediction with increased LT, which is more beneficial, is not popular in current researches. It is because the connection between previous runoff and current runoff will be weakened with the increase of LT. So 74 atmospheric circulation factors (ACFs) together with pre-runoff are used as alternative predictors for mid-long term runoff prediction of Longyangxia reservoir in this study. Because pre-runoff and 74 ACFs with different time lags are so many and most of these factors are useless, lasso, which means `least absolutely shrinkage and selection operator', is used to recognize predictors. And the result demonstrates that 74 ACFs are beneficial for runoff prediction in both validation and test sets when LT is greater than 6. And there are 6 factors other than pre-runoff, most of which are with big time lag, are selected as predictors frequently. In order to verify the effect of 74 ACFs, 74 stochastic time series generated from normalized 74 ACFs are used as input of model. The result shows that these 74 stochastic time series are useless, which confirm the effect of 74 ACFs on mid-long term runoff prediction.

The Epidemiology and Clinical Features of Clostridium difficile Infection in Liver Transplant Recipients.

PubMed

Sullivan, Timothy; Weinberg, Alan; Rana, Meenakshi; Patel, Gopi; Huprikar, Shirish

2016-09-01

Clostridium difficile infection (CDI) is common after liver transplantation (LT); however, few studies have examined the risk factors, clinical manifestations, and outcomes of CDI in this population. A retrospective study of adults who underwent LT between January 1, 2011, and April 4, 2013, at The Mount Sinai Hospital was conducted. Potential risk factors were evaluated via univariate and multivariable analysis to determine predictors of CDI in this population. The clinical manifestations of CDI and patient outcomes were also reviewed. Clostridium difficile infection occurred in 27 (14%) of 192 patients after LT. In multivariable analysis, CDI was associated with having a model for end-stage liver disease score of 20 or greater (hazards ratio, 2.90; 95% confidence interval, 1.29-6.52; P = 0.010), and receiving a LT from a living donor (hazards ratio, 3.77; 95% confidence interval, 1.47-9.67; P = 0.006). Forty-one percent of CDI cases occurred within 1 week of LT. Seven percent of patients with CDI had a serum white blood cell count greater than 12 000 cells per μL, and 26% had a temperature greater than 38.0°C. After treatment 6 (22%) patients developed CDI relapse, and all were successfully treated. No patients died of CDI after a mean follow-up time of 1.8 years; however, overall survival was significantly lower among those with CDI (78% vs 92%; P = 0.033). Clostridium difficile infection after LT was associated with higher model for end-stage liver disease scores and receiving a LT from a living donor. Clostridium difficile infection often occurred soon after LT and was infrequently associated with leukocytosis or fever. Clostridium difficile infection in LT recipients was associated with lower overall survival.

Is the Functional Threshold Power (FTP) a Valid Surrogate of the Lactate Threshold?

PubMed

Valenzuela, Pedro L; Morales, Javier S; Foster, Carl; Lucia, Alejandro; de la Villa, Pedro

2018-05-10

This study aimed to analyze the relationship between the Functional Threshold Power (FTP) and the Lactate Threshold (LT). 20 male cyclists performed an incremental test in which the LT was determined. At least 48 h later, they performed a 20-minute time trial and 95% of the mean power output (P20) was defined as FTP. Participants were divided into recreational (Peak Power Output [PPO] < 4.5 W∙kg -1 , n=11) or trained cyclists (PPO > 4.5 W∙kg -1 , n=9) according to their fitness status. The FTP (240 ± 35 W) was overall not significantly different (effect size[ES]=0.20, limits of agreement [LoA]=-2.4 ± 11.5%) from the LT (246 ± 24 W), and both markers were strongly correlated (r=0.95, p<0.0001). Accounting for the participants' fitness status, no significant differences were found between FTP and LT ([ES]=0.22; LoA=2.1 ± 7.8%) in TC, but FTP was significantly lower than the LT (p=0.0004, ES=0.81; LoA=-6.5 ± 8.3%) in RC. A significant relationship was found between relative PPO and the bias between FTP and the LT markers (r=0.77, p<0.0001). The FTP is a valid field test-based marker for the assessment of endurance fitness. However, caution should be taken when using the FTP interchangeably with the LT as the bias between markers seems to depend on the athletes' fitness status. Whereas the FTP provides a good estimate of the LT in trained cyclists, in recreational cyclists FTP may underestimate LT.

Clinical efficacy and pharmacokinetics of levothyroxine suppository in patients with hypothyroidism.

PubMed

Kashiwagura, Yasuharu; Uchida, Shinya; Tanaka, Shimako; Watanabe, Hiroshi; Masuzawa, Masahiro; Sasaki, Tadanori; Namiki, Noriyuki

2014-01-01

This study aimed to elucidate the clinical efficacy and pharmacokinetics of levothyroxine (LT4) suppository, thus, we examined the pharmacokinetics of thyroxine (T4) after the administration of the suppository in thyroidectomized rats and examined dose and the levels of free T4 (FT4) in patients with hypothyroidism receiving suppositories. Thyroidectomized rats were administered with LT4 solution and LT4 suppository (30 µg/kg), and plasma T4 concentrations were measured using LC/MS. The AUC0-168 of T4 after rectal administration of the LT4 suppository was 64% lower than these values after oral administration. To evaluate clinical effect of LT4 suppository, we enrolled 6 Japanese patients with hypothyroidism (2 men and 4 women; age, 68.2±13.5 years) who were administered LT4 suppository at Kameda Medical Center from 2007 to 2013 in this case series. The FT4 level during the administration of suppositories was significantly lower than that during the administration of tablets (0.657±0.183 ng/dL vs. 1.25±0.51 ng/dL, p=0.034). The FT4/dose ratio for the suppository was significantly 44% lower than that for the tablet (p=0.020). In conclusion, although the bioavailability of LT4 is lower after administration of the suppository than after the oral formulation, it was suggested that T4 levels can be maintained in patients with hypothyroidism by administering LT4 suppositories at a dose 1.8 times higher than that of the tablet. Thus, the administration of LT4 suppository can be an alternative for treatment with oral medication in clinical practice.

50 CFR 21.43 - Depredation order for blackbirds, cowbirds, grackles, crows, and magpies.

Code of Federal Regulations, 2013 CFR

2013-10-01

...-lethal methods before you may use lethal control. (b) In most cases, if you use a firearm to kill... about your control operations. (d) You may kill birds under this order only in a way that complies with...

50 CFR 21.43 - Depredation order for blackbirds, cowbirds, grackles, crows, and magpies.

Code of Federal Regulations, 2014 CFR

2014-10-01

...-lethal methods before you may use lethal control. (b) In most cases, if you use a firearm to kill... about your control operations. (d) You may kill birds under this order only in a way that complies with...

50 CFR 21.43 - Depredation order for blackbirds, cowbirds, grackles, crows, and magpies.

Code of Federal Regulations, 2012 CFR

2012-10-01

...-lethal methods before you may use lethal control. (b) In most cases, if you use a firearm to kill... about your control operations. (d) You may kill birds under this order only in a way that complies with...

Assessing Toxicity of Obscurant Grade Pan-Based Carbon Fiber Aquatic Species Chronic Tests

DTIC Science & Technology

2004-12-01

ASSESSING TOXICITY OF OBSCURANT GRADE PAN-BASED CARBON FIBER: AQUATIC SPECIES CHRONIC TESTS N. A. Chester, M. V. Haley, C. W. Kurnas and R. T...with minimal restrictions. To this end we are investigating the toxicity of PAN-based carbon fibers to the aquatic species Ceriodaphnia dubia (water... toxicity methods to provide ecotoxicological results for both lethal and sub-lethal parameters, including LC50 (24-, 48- and 96-h), IC50, EC20, and

Evaluation of Caenorhabditis elegans as an acute lethality and a neurotoxicity screening model

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

Williams, P.L.

1988-01-01

This investigation evaluated C. elegans as a lethality and neurotoxicity screening model. The lethality experiments were performed in both agar and an aquatic medium. The salts of 8 metals (Hg, Be, Al, Cu, Zn, Pb, Cd, and Sr) were used in the agar studies and the salts of 14 metals (Ag, Hg, Cu, Be, Al, Pb, Cr, As, Tl, Zn, Cd, Ni, Sr, and Sb) were used in the aquatic tests. In each of these tests an LC50 value was determined. The data from the agar plates were compared to the published mammalian oral LD50 values for salts of themore » same metals. Within this set of chemicals C. elegans was found to be a predictor of mammalian acute lethality, generating LC50 values parallel to the rat and mouse LD50 values. The aquatic data were compared to data from EPA Ambient Water Quality Criteria documents. C. elegans was found to be less sensitive than Daphnia but generally more sensitive than the other invertebrate organisms that are presently used. The neurotoxicity testing also was performed in both agar and an aquatic media. The testing in agar was conducted with the salts of 4 metals (Cu, Be, Pb, and Hg) and 2 organophosphate pesticides (malathion and vapona). The studies in an aquatic medium tested the salts of 4 metals (Cu, Be, Pb, and Hg).« less

Lactate-related factors as a critical determinant of endurance.

PubMed

Tanaka, K

1990-04-01

Many interrelated physiological and/or morphological factors have been demonstrated to influence endurance exercise performance. Some of these factors include skeletal musculature, running economy, maximal oxygen uptake (VO2max), maximal steady state (MSS), onset of blood lactate accumulation (OBLA), onset of plasma lactate accumulation (OPLA), and anaerobic (or lactate) threshold (AT or LT). The present paper focuses mainly on VO2max, MSS, OBLA, OPLA and LT, all of which have been postulated as a prerequisite in endurance exercise success. This paper consists of: (1) significance of La-related variables, (2) longitudinal studies, (3) comments, and (4) conclusion. Briefly, it is suggested that estimation of endurance exercise potential could be obtained with relatively high precision using laboratoriously measured La-related variables. The most critical determinant of endurance exercise performance such as marathon time is considered running velocity (V) at which LT is detected (V / LT), VO2 / LT, or V / MSS, while V / OBLA appears to be the best predictor of performance in endurance events of 16 km or shorter distances.

Effects of short- and long-term exposures to copper on lethal and reproductive endpoints of the harpacticoid copepod Tigriopus fulvus.

PubMed

Biandolino, Francesca; Parlapiano, Isabella; Faraponova, Olga; Prato, Ermelinda

2018-01-01

The long-term exposure provides a realistic measurement of the effects of toxicants on aquatic organisms. The harpacticoid copepod Tigriopus fulvus has a wide geographical distribution and is considered as an ideal model organism for ecotoxicological studies for its good sensitivity to different toxicants. In this study, acute, sub-chronic and chronic toxicity tests based on lethal and reproductive responses of Tigriopus fulvus to copper were performed. The number of moults during larval development was chosen as an endpoint for sub-chronic test. Sex ratio, inhibitory effect on larval development, hatching time, fecundity, brood number, nauplii/brood, total newborn production, etc, were calculated in the chronic test (28d). Lethal effect of copper to nauplii showed the LC50-48h of 310 ± 72µgCu/L (mean ± sd). It was observed a significant inhibition of larval development at sublethal copper concentrations, after 4 and 7 d. After 4d, the EC50 value obtained for the endpoint in "moult naupliar reduction" was of 55.8 ± 2.5µgCu/L (mean ± sd). The EC50 for the inhibition of naupliar development into copepodite stage, was of 21.7 ± 4.4µgCu/L (mean ± sd), after 7 days. Among the different traits tested, copper did not affect sex ratio and growth, while fecundity and total nauplii production were the most sensitive endpoints. The reproductive endpoints offer the advantage of being detectable at very low pollutant concentrations. Copyright © 2017 Elsevier Inc. All rights reserved.

Role of glucose-6-phosphate dehydrogenase in freezing-induced freezing resistance of Populus suaveolens.

PubMed

Lin, Shan-Zhi; Zhang, Zhi-Yi; Liu, Wen-Feng; Lin, Yuan-Zhen; Zhang, Qian; Zhu, Bao-Qing

2005-02-01

To explore the role of glucose-6-phosphate dehydrogenase (G6PDH, EC 1.1.1.49) in the enhancement of freezing resistance induced by freezing acclimation, G6PDH was purified from the leaves of 8-week-old Populus suaveolens cuttings. The G6PDH activity in the absence or the presence of reduced dithiothreitol (DTT(red)) were determined, and the changes in superoxide dismutase (SOD), peroxides (POD) and cytosolic G6PDH activities, malondial-dehyde (MDA) content as well as freezing resistance (expressed as LT(50)) of P. suaveolens cuttings during freezing acclimation at -20 degrees C were investigated. The results showed that the purified G6PDH was probably located in the cytosol of P. suaveolens. Freezing acclimation increased the activities of SOD, POD and cytosolic G6PDH, and decreased the MDA content and LT(50) of cuttings, while 2 d of de-acclimation at 25 degrees C resulted in a decrease in SOD, POD and cytosolic G6PDH activities, and caused an increase in MDA content and LT(50). The change in cytosolic G6PDH activity was found to be closely correlated to the levels of SOD, POD and MDA, and to the degree of freezing resistance of cuttings during freezing acclimation. It is suggested that the enhancement of freezing resistance of cuttings induced by freezing acclimation is related to the distinct increase in cytosolic G6PDH activity, which may be involved in the activation of SOD and POD, and the induction of freezing resistance of cuttings.

Susceptibility of Blastomyces dermatitidis strains to products of oxidative metabolism.

PubMed

Sugar, A M; Chahal, R S; Brummer, E; Stevens, D A

1983-09-01

Three strains of Blastomyces dermatitidis which differ in their virulence for mice were exposed in their yeast form to various components of the peroxidase-hydrogen peroxide-halide system. Susceptibility to H2O2 alone correlated with virulence, with the most virulent strain (ATCC 26199) least susceptible (50% lethal dose, greater than 50 mM) and an avirulent strain (ATCC 26197) most susceptible (50% lethal dose less than 3.3 mM). A strain of intermediate virulence (ATCC 26198) was of intermediate susceptibility (50% lethal dose, 11.5 mM). The addition of a nontoxic concentration of KI (5 X 10(-4) M) did not increase H2O2 toxicity. However, the addition of either myeloperoxidase or horseradish peroxidase and KI markedly decreased the amount of H2O2 required to kill the organisms, with 100 +/- 0% of all strains killed at 5 X 10(-5) M H2O2 and 97 +/- 4, 100 +/- 0, and 94 +/- 8% of ATCC 26199, ATCC 26198, and ATCC 26197 killed, respectively, at 5 X 10(-6) M H2O2. Kinetic studies with H2O2 alone revealed a delayed onset of killing, but virtually 100% of organisms were killed by 120 min of exposure in all strains. By comparison, the peroxidase-hydrogen peroxide-halide system was 100% lethal for all strains at 1 min. The relatively high concentrations of H2O2 required to kill the yeast phase of B. dermatitidis suggest that H2O2 alone does not account for host resistance to the organism. However, the rapidly lethal effect of the peroxidase-hydrogen peroxide-halide system at physiologically relevant concentrations suggests that this may be one mechanism of host defense to B. dermatitidis.

Active retroreflector with in situ beam analysis to measure the rotational orientation in conjunction with a laser tracker

NASA Astrophysics Data System (ADS)

Hofherr, O.; Wachten, C.; Müller, C.; Reinecke, H.

2013-04-01

High precision optical non-contact position measurement is a key technology in modern engineering. Laser trackers (LT) can determine accurately x-y-z coordinates of passive retroreflectors. Next-generation systems answer the additional need to measure an object`s rotational orientation (pitch, yaw, roll). These devices are based either on photogrammetry or on enhanced retroreflectors. However, photogrammetry relies on costly camera systems and time-consuming image processing. Enhanced retroreflectors analyze the LT`s beam but are restricted in roll angle measurements. In the past we have presented a new method [1][2] to measure all six degrees of freedom in conjunction with a LT. Now we dramatically optimized the method and designed a new prototype, e.g. taking into consideration optical alignment, reduced power loss, highly optimized measuring signals and higher resolution. A method is described that allows compensating the influence of the LT's beam offset during tracking the active retroreflector. We prove the functionality of the active retroreflector with the LT and, furthermore, demonstrate the capability of the system to characterize the tracking behavior of a LT. The measurement range for the incident laser beam is +/-12° with a resolution of 0.6".

Magnetic and electronic properties of the Cu-substituted Weyl semimetal candidate ZrCo₂Sn.

PubMed

Kushwaha, S K; Wang, Zhijun; Kong, Tai; Cava, Robert

2018-01-04

We report that the partial substitution of Cu for Co has a significant impact on the magnetic properties of the Heusler-phase Weyl fermion candidate ZrCo₂Sn. Polycrystalline samples of ZrCo_2-<i>x</i>Cu_<i>x</i>Sn (<i>x</i> = 0.0 to 1.0) exhibited a linearly decreasing ferromagnetic transition temperature and similarly decreasing saturated magnetic moment on increasing Cu substitution x. Materials with Cu contents near <i>x</i> = 1 and several other quaternary materials synthesized at the same <i>x</i> (ZrCo<i>T</i>'Sn (<i>T</i>' = Rh, Pd, Ni)) display what appears to be non-ferromagnetic magnetization behavior with spin glass characteristics. Electronic structure calculations suggest that the half-metallic nature of unsubstituted ZrCo₂Sn is disrupted significantly by the Cu substitutions, leading to the breakdown of the magnetization vs. electron count guidelines usually followed by Heusler phases, and a more typical metallic non-spin-polarized electronic structure at high <i>x</i>. © 2018 IOP Publishing Ltd.

Do Ligamentum Teres Tears Portend Inferior Outcomes in Patients With Borderline Dysplasia Undergoing Hip Arthroscopic Surgery? A Match-Controlled Study With a Minimum 2-Year Follow-up.

PubMed

Chaharbakhshi, Edwin O; Perets, Itay; Ashberg, Lyall; Mu, Brian; Lenkeit, Christopher; Domb, Benjamin G

2017-09-01

Arthroscopic surgery in borderline dysplastic hips remains controversial, but the role of the ligamentum teres (LT) has not been studied in this setting. Borderline dysplastic patients with LT tears have worse short-term outcomes than those without LT tears. Cohort study; Level of evidence, 3. Data were prospectively collected on patients who underwent arthroscopic surgery between February 2008 and April 2014. The inclusion criteria were borderline dysplasia (lateral center-edge angle [LCEA], 18°-25°) and labral tears; arthroscopic treatments including labral preservation and capsular plication; and preoperative patient-reported outcome scores including the modified Harris Hip Score (mHHS), Non-Arthritic Hip Score (NAHS), Hip Outcome Score-Sport-Specific Subscale, and visual analog scale for pain. Patients were excluded for preoperative Tönnis osteoarthritis grade >0, workers' compensation claims, previous ipsilateral hip surgery and conditions, or frank dysplasia (LCEA <18°). Patients with LT tears were pair-matched to patients without tears for sex, age at surgery ±10 years, body mass index (<30 kg/m 2 vs ≥30 kg/m 2 ), labral treatment type, and microfracture. Of 68 eligible patients, 63 (93%) had a minimum 2-year follow-up, and 30 (48%) had LT tears. Twenty patients in each group were pair-matched. The mean follow-up time was 54.3 months (range, 24.2-83.8 months) for the LT tear group and 38.6 months (range, 24.6-70.6 months) for the control group ( P = .002). Ninety percent were female. There were no significant differences regarding demographics or intra-operative procedures. The LT tear group trended toward lower postoperative mHHS ( P = .09) and NAHS ( P = .09) values. Mean satisfaction was 8.1 for the LT tear group and 7.9 for the control group. Preoperative and follow-up scores were not significantly different between the groups. The LT tear group had 5 revisions, with 1 revision in the control group. Three patients (15%) in the LT tear group underwent total hip arthroplasty (THA); no patients in the control group required THA. In borderline dysplastic patients undergoing hip arthroscopic surgery with labral treatment and capsular plication, LT tears may indicate advanced instability and portend slightly inferior outcomes when compared with a match-controlled group. Borderline dysplastic patients with LT tears may have increased propensities toward revision arthroscopic surgery and conversion to THA. LT tears in these patients may warrant consideration for additional procedures including periacetabular osteotomy and LT reconstruction.

Impact of pretransplant rifaximin therapy on early post-liver transplant infections.

PubMed

Esfeh, Jamak Modaresi; Hanouneh, Ibrahim A; Koval, Christine E; Kovacs, Christopher; Dalal, Deepan S; Ansari-Gilani, Kianoush; Confer, Bradley D; Eghtesad, Bijan; Zein, Nizar N; Menon, K V Narayanan

2014-05-01

Bacterial and fungal infections are major causes of morbidity and mortality after liver transplantation (LT). The role of intestinal decontamination in the prevention of post-LT infections is controversial. Rifaximin is widely used for the treatment of hepatic encephalopathy. The effect of rifaximin on post-LT infections is unknown. The aim of our study was to determine the effect of rifaximin therapy in the pretransplant period on early bacterial infections (EBIs) and fungal infections within the first 30 days after LT. All adult patients who underwent LT at our institution (January 2009 to July 2011) were included in this retrospective cohort study. Patients receiving antibiotics other than pretransplant protocol antibiotics were excluded. Patients were stratified into 2 groups based on the presence or absence of rifaximin therapy for at least 2 days before LT. Infections were defined by the isolation of any bacterial or fungal organisms within 30 days of LT. Multivariate regression analysis, Student t tests, and Pearson's chi-square tests were used to compare the 2 groups. Two hundred sixty-eight patients were included, and 71 of these patients (26.5%) were on rifaximin at the time of LT. The 2 groups were comparable with respect to age, sex, race, and Model for End-Stage Liver Disease score. There were no significant differences in the rates of EBIs (30% for the non-rifaximin group and 25% for the rifaximin group, P = 0.48) or fungal infections between the 2 groups. There was no increase in antimicrobial resistance among the infecting organisms. There was no difference in survival between the rifaximin and non-rifaximin groups (98% versus 97%, P = 0.36). In conclusion, the use of rifaximin in the pre-LT period was not associated with an increased risk of bacterial or fungal infections in the early post-LT period. © 2014 American Association for the Study of Liver Diseases.

What Are Reasons for the Large Gender Differences in the Lethality of Suicidal Acts? An Epidemiological Analysis in Four European Countries

PubMed Central

Heinrichs, Katherina; Székely, András; Tóth, Mónika Ditta; Coyne, James; Quintão, Sónia; Arensman, Ella; Coffey, Claire; Maxwell, Margaret; Värnik, Airi; van Audenhove, Chantal; McDaid, David; Sarchiapone, Marco; Schmidtke, Armin; Genz, Axel; Gusmão, Ricardo; Hegerl, Ulrich

2015-01-01

Background In Europe, men have lower rates of attempted suicide compared to women and at the same time a higher rate of completed suicides, indicating major gender differences in lethality of suicidal behaviour. The aim of this study was to analyse the extent to which these gender differences in lethality can be explained by factors such as choice of more lethal methods or lethality differences within the same suicide method or age. In addition, we explored gender differences in the intentionality of suicide attempts. Methods and Findings Methods. Design: Epidemiological study using a combination of self-report and official data. Setting: Mental health care services in four European countries: Germany, Hungary, Ireland, and Portugal. Data basis: Completed suicides derived from official statistics for each country (767 acts, 74.4% male) and assessed suicide attempts excluding habitual intentional self-harm (8,175 acts, 43.2% male). Main Outcome Measures and Data Analysis. We collected data on suicidal acts in eight regions of four European countries participating in the EU-funded “OSPI-Europe”-project (www.ospi-europe.com). We calculated method-specific lethality using the number of completed suicides per method * 100 / (number of completed suicides per method + number of attempted suicides per method). We tested gender differences in the distribution of suicidal acts for significance by using the χ2-test for two-by-two tables. We assessed the effect sizes with phi coefficients (φ). We identified predictors of lethality with a binary logistic regression analysis. Poisson regression analysis examined the contribution of choice of methods and method-specific lethality to gender differences in the lethality of suicidal acts. Findings Main Results Suicidal acts (fatal and non-fatal) were 3.4 times more lethal in men than in women (lethality 13.91% (regarding 4106 suicidal acts) versus 4.05% (regarding 4836 suicidal acts)), the difference being significant for the methods hanging, jumping, moving objects, sharp objects and poisoning by substances other than drugs. Median age at time of suicidal behaviour (35–44 years) did not differ between males and females. The overall gender difference in lethality of suicidal behaviour was explained by males choosing more lethal suicide methods (odds ratio (OR) = 2.03; 95% CI = 1.65 to 2.50; p < 0.000001) and additionally, but to a lesser degree, by a higher lethality of suicidal acts for males even within the same method (OR = 1.64; 95% CI = 1.32 to 2.02; p = 0.000005). Results of a regression analysis revealed neither age nor country differences were significant predictors for gender differences in the lethality of suicidal acts. The proportion of serious suicide attempts among all non-fatal suicidal acts with known intentionality (NFSAi) was significantly higher in men (57.1%; 1,207 of 2,115 NFSAi) than in women (48.6%; 1,508 of 3,100 NFSAi) (χ2 = 35.74; p < 0.000001). Main limitations of the study Due to restrictive data security regulations to ensure anonymity in Ireland, specific ages could not be provided because of the relatively low absolute numbers of suicide in the Irish intervention and control region. Therefore, analyses of the interaction between gender and age could only be conducted for three of the four countries. Attempted suicides were assessed for patients presenting to emergency departments or treated in hospitals. An unknown rate of attempted suicides remained undetected. This may have caused an overestimation of the lethality of certain methods. Moreover, the detection of attempted suicides and the registration of completed suicides might have differed across the four countries. Some suicides might be hidden and misclassified as undetermined deaths. Conclusions Men more often used highly lethal methods in suicidal behaviour, but there was also a higher method-specific lethality which together explained the large gender differences in the lethality of suicidal acts. Gender differences in the lethality of suicidal acts were fairly consistent across all four European countries examined. Males and females did not differ in age at time of suicidal behaviour. Suicide attempts by males were rated as being more serious independent of the method used, with the exceptions of attempted hanging, suggesting gender differences in intentionality associated with suicidal behaviour. These findings contribute to understanding of the spectrum of reasons for gender differences in the lethality of suicidal behaviour and should inform the development of gender specific strategies for suicide prevention. PMID:26147965

The effect of light exposure on insomnia and nocturnal movement in Parkinson's disease: an open label, retrospective, longitudinal study.

PubMed

Martino, Jessica K; Freelance, Christopher B; Willis, Gregory L

2018-04-01

Insomnia, hypersomnia and REM Sleep Behavior Disorder (RSBD) during sleep are major problems for patients suffering from Parkinson's disease (PD) but they are also used to predict its onset. While these secondary symptoms detract from the quality of life in PD patients, few treatment options are available due to limited efficacy or risk of complicating the treatment regimen. Light therapy (LT) has been suggested as a strategy for sleep disorders but it has only been implemented recently for use in PD. An open label, retrospective study was undertaken where PD patients had been undergoing LT, using polychromatic light, for four months to 15 years prior. It was found that 1 h exposure to light, just prior to retiring, significantly improved insomnia and reduced RSBD in as little as one month after commencing LT. In addition, the improvement was maintained as long as LT was continued over a four to six year period. The efficacy of LT in alleviating these sleep related conditions was not compromised by time since diagnosis or age of the patient. These results intimate the value of long term application of non-invasive techniques such as LT for treating sleep disorders in PD and justify further controlled trials on the long term efficacy of LT. Copyright © 2018 Elsevier B.V. All rights reserved.

Liver transplantation for Wilson disease.

PubMed

Catana, Andreea M; Medici, Valentina

2012-01-27

The aim of this paper is to review the current status of liver transplantation (LT) for Wilson disease (WD), focusing on indications and controversies, especially in patients with neuropsychiatric disease, and on identification of acute liver failure (ALF) cases related to WD. LT remains the treatment of choice for patients with ALF, as initial presentation of WD or when anti-copper agents are stopped, and for patients with chronic liver disease progressed to cirrhosis, unresponsive to chelating medications or not timely treated with copper chelating agents. The indication for LT in WD remains highly debated in patients with progressive neurological deterioration and failure to improve with appropriate medical treatment. In case of Wilsonian ALF, early identification is key as mortality is 100% without emergency LT. As many of the copper metabolism parameters are believed to be less reliable in ALF, simple biochemical tests have been proposed for diagnosis of acute WD with good sensitivity and specificity. LT corrects copper metabolism and complications resulting from WD with excellent 1 and 5 year survival. Living related liver transplantation represents an alternative to deceased donor LT with excellent long-term survival, without disease recurrence. Future options may include hepatocyte transplantation and gene therapy. Although both of these have shown promising results in animal models of WD, prospective human studies are much needed to demonstrate their long-term beneficial effects and their potential to replace the need for medical therapy and LT in patients with WD.

Family strain and its relation to psychosocial dysfunction in children and adolescents after liver transplantation.

PubMed

Kaller, T; Petersen, I; Petermann, F; Fischer, L; Grabhorn, E; Schulz, K-H

2014-12-01

Parental functioning is essential to children's development. Therefore, this cross-sectional single-center study examined the prevalence of family strain in 181 parents and its associations to psychosocial functioning in their children after LT. Median age at LT was one yr. Mean time elapsed since LT was 5.8 yr. The IFS, and the SDQ were applied to parents. Family strain in the present sample was comparable to that in the German normative group of families with a chronically ill or disabled child, but families of LT recipients showed a significantly higher financial impact, impact on coping, and impact on siblings (p < 0.001). Younger age of patients at survey, a more severe clinical course, child's restrictions, and financial losses following LT were determined as significant predictors of family strain (R(2)  = 0.42). Parents reported less family strain after living-related compared with deceased donation. Family strain was significantly correlated to psychosocial dysfunction in children post-LT. Present findings demonstrate a risk of maladjustment to the post-LT condition in families. They emphasize the importance of psychological assessment of parents and patients during transplant and follow-up to ensure the best achievable long-term outcome of patients. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Patent foramen ovale in liver transplant recipients does not negatively impact short-term outcomes.

PubMed

Werlang, Monia E; Palmer, William C; Boyd, Evelyn A; Cangemi, David J; Harnois, Denise M; Taner, Cemal B; Stancampiano, Fernando F

2016-01-01

Patent foramen ovale (PFO) is a common atrial septal defect that is largely asymptomatic and often undiagnosed. The impact of a PFO in patients undergoing liver transplantation (LT) is unknown. Assess the impact of PFO and physiologic intrapulmonary shunt (IPS) on the perioperative outcomes of patients who underwent LT. We performed a retrospective, intention-to-treat analysis of patients with PFO and controls without PFO who underwent LT at Mayo Clinic in Florida between 2008 and 2013. Patients with physiologic IPS were also analyzed. The cohorts were compared for baseline characteristics, length of stay in the intensive care unit (ICU), postoperative oxygen requirements, 30-d cerebrovascular accidents, and mortality. Of the 935 patients who underwent LT, 10.4% had proven PFO by pre-LT echocardiogram. Control patients (n = 101) were statistically older than PFO and IPS (n = 56) patients, but similar in sex, BMI, Model for End-stage Liver Disease score, American Society of Anesthesiologist score, and left ventricular ejection fraction. PFO and IPS patients had similar length of stay in the ICU, mechanical ventilation times, post-LT oxygen requirements, and 30-d mortality compared to controls. Subgroup analysis showed similar outcomes for large PFO and IPS patients to controls. The presence of PFO did not have a negative impact on perioperative LT outcomes. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Magnetization, resistivity, specific heat and ab initio calculations of Gd₅Sb₃.

PubMed

Samatham, S Shanmukharao; Patel, Akhilesh Kumar; Lukoyanov, Alexey V; Suresh, K G

2018-06-07

We report on the combined results of structural, magnetic, transport and calorimetric properties of Mn₅Si₃-type hexagonal Gd₅Sb₃, together with <i>ab-initio</i> calculations. It exhibits a ferromagnetic (FM)-like transition at 265 K, antiferromagnetic (AFM) Néel transition at 95.5 K followed by a spin-orientation transition at 62 K. The system is found to be in AFM state down to 2 K in a field of 70 kOe. The FM-AFM phase coexistence is not noticeable despite large positive Curie-Weiss temperature (θ_CW = 223.5 ± 0.2 K). Instead, low-temperature AFM and high-temperature FM-like phases are separated in large temperatures. Temperature-magnetic field (<i>H</i>-<i>T</i>) phase diagram reveals field-driven complex magnetic phases. Within the AFM phase, the system is observed to undergo field-driven spin-orientation transitions. Field-induced tricritical and quantum critical points appear to be absent due to strong AFM nature and by the intervention of FM-like state between paramagnetic and AFM states, respectively. The metallic behavior of the compound is inferred from resistivity along with large Sommerfeld parameter. However, no sign of strong electron-correlations is reasoned from the Kadowaki-Wood's ratio <i>A</i>/γ² ∼ 1.9×10^-6 μΩ.cm.(mol.K)²(mJ)^-2, despite heavy γ. Essentially, <i>ab initio</i> calculations accounting for electronic correlations confirm AFM nature of low-temperature magnetic state in Gd₅Sb₃ and attainable FM ordering in agreement with experimental data. © 2018 IOP Publishing Ltd.

Overwork accelerates thrombotic reaction: implications for the pathogenesis of Karoshi.

PubMed

Otsui, Kazunori; Yamamoto, Junichiro; Inoue, Nobutaka

2018-02-01

Work-related stressors are potential causes of cardiovascular diseases (CVDs) and stroke; however, the pathophysiological mechanisms by which occupational stress induces and exacerbates CVDs remain unclear. The global thrombosis test (GTT) is a novel in vitro assay for evaluating both thrombotic reactions and subsequent thrombolysis. The time required to form an occlusive thrombus with the GTT, called as the occlusion time (OT), and the time to lyse the thrombus, the lysis time (LT), are markers of thrombotic and thrombolytic reactions, respectively. We investigated the impact of work-related stress on the thrombotic and thrombolytic reactions in 46 healthy medical residents. Off-duty or on-duty blood samples were collected on the mornings of non-work days or after the night duty on the emergent room respectively. The duration of sleep was significantly shorter during night duty than during off-duty nights [2.25 (1.0, 3.0) h vs. 6.0 (5.0, 7.0) h; p < 0.001]. Baseline OT was 310.3 (260.9, 437.7) s. whereas the on-duty OT was significantly shortened [284.2 (230.5, 355.8) s; p < 0.01]. LT was significantly prolonged during overwork conditions compared with off-duty conditions [1547 (1346, 1908) s vs. 1470 (1219, 1692) s; p < 0.05]. Overwork accelerates the thrombotic reactions. These reactions might explain the pathogenesis of overwork-related CVDs. The GTT is a good tool for evaluating of the level of fatigue.

Acute toxicity of organophosphorus compounds in guinea pigs is sex- and age-dependent and cannot be solely accounted for by acetylcholinesterase inhibition.

PubMed

Fawcett, William P; Aracava, Yasco; Adler, Michael; Pereira, Edna F R; Albuquerque, Edson X

2009-02-01

This study was designed to test the hypothesis that the acute toxicity of the nerve agents S-[2-(diisopropylamino)ethyl]-O-ethyl methylphosphonothioate (VX), O-pinacolyl methylphosphonofluoridate (soman), and O-isopropyl methylphosphonofluoridate (sarin) in guinea pigs is age- and sex-dependent and cannot be fully accounted for by the irreversible inhibition of acetylcholinesterase (AChE). The subcutaneous doses of nerve agents needed to decrease 24-h survival of guinea pigs by 50% (LD(50) values) were estimated by probit analysis. In all animal groups, the rank order of LD(50) values was sarin > soman > VX. The LD(50) value of soman was not influenced by sex or age of the animals. In contrast, the LD(50) values of VX and sarin were lower in adult male than in age-matched female or younger guinea pigs. A colorimetric assay was used to determine the concentrations of nerve agents that inhibit in vitro 50% of AChE activity (IC(50) values) in guinea pig brain extracts, plasma, red blood cells, and whole blood. A positive correlation between LD(50) values and IC(50) values for AChE inhibition would support the hypothesis that AChE inhibition is a major determinant of the acute toxicity of the nerve agents. However, such a positive correlation was found only between LD(50) values and IC(50) values for AChE inhibition in brain extracts from neonatal and prepubertal guinea pigs. These results demonstrate for the first time that the lethal potencies of some nerve agents in guinea pigs are age- and sex-dependent. They also support the contention that mechanisms other than AChE inhibition contribute to the lethality of nerve agents.

Croton grewioides Baill. (Euphorbiaceae) Shows Antidiarrheal Activity in Mice

PubMed Central

da Silva, Anne Dayse Soares; de Melo e Silva, Karoline; Neto, José Clementino; Costa, Vicente Carlos de Oliveira; Pessôa, Hilzeth de Luna F.; Tavares, Josean Fechine; da Silva, Marcelo Sobral; Cavalcante, Fabiana de Andrade

2016-01-01

Based on chemotaxonomy, we decided to investigate the possible antidiarrheal activity in mice of a crude ethanolic extract obtained from aerial parts of Croton grewioides (CG-EtOH). We tested for any possible toxicity in rat erythrocytes and acute toxicity in mice. Antidiarrheal activity was assessed by determining the effect of CG-EtOH on defecation frequency, liquid stool, intestinal motility and intestinal fluid accumulation. CG-EtOH showed no in vitro cytotoxicity and was not orally lethal. In contrast, the extract given intraperitoneally (at 2000 mg/kg) was lethal, but only in females. CG-EtOH produced a significant and equipotent antidiarrheal activity, both in defecation frequency (ED50 = 106.0 ± 8.1 mg/kg) and liquid stools (ED50 = 105.0 ± 9.2 mg/kg). However, CG-EtOH (125 mg/kg) decreased intestinal motility by only 22.7% ± 4.4%. Moreover, extract markedly inhibited the castor oil-induced intestinal contents (ED50 = 34.6 ± 5.4 mg/kg). We thus conclude that CG-EtOH is not orally lethal and contains active principles with antidiarrheal activity, and this effect seems to involve mostly changes in intestinal secretion. SUMMARY CG-EtOH showed no in vitro cytotoxicity and was not orally lethal. In contrast, the extract given intraperitoneally (at 2000 mg/kg) was lethal, but only in females.CG-EtOH probably contains active metabolites with antidiarrheal activity.CG-EtOH reduced the frequency and number of liquid stools.Metabolites presents in the CG-EtOH act mainly by reducing intestinal fluid and, to a lesser extent, reducing intestinal motility. Abbreviations Used: CG-EtOH: crude ethanolic extract obtained from the aerial parts of C. grewioides; WHO: World Health Organization; ED50: dose of a drug that produces 50% of its maximum effect; Emax: maximum effect PMID:27365990

Abscisic acid induced freezing tolerance in chilling-sensitive suspension cultures and seedlings of rice

PubMed Central

2013-01-01

Background The role of abscisic acid (ABA) as a possible activator of cold acclimation process was postulated since endogenous levels of ABA increase temporarily or constitutively during cold-hardening. Exogenous application of ABA has been known to induce freezing tolerance at ambient temperatures in in vitro systems derived from cold hardy plants. Yet, some cell cultures acquired much greater freezing tolerance by ABA than by cold whilst maintaining active growth. This raises questions about the relationships among ABA, cold acclimation and growth cessation. To address this question, we attempted to 1) determine whether exogenous ABA can confer freezing tolerance in chilling-sensitive rice suspension cells and seedlings, which obviously lack the mechanisms to acquire freezing tolerance in response to cold; 2) characterize this phenomenon by optimizing the conditions and compare with the case of cold hardy bromegrass cells. Results Non-embryogenic suspension cells of rice suffered serious chilling injury when exposed to 4°C. When incubated with ABA at the optimal conditions (0.5-1 g cell inoculum, 75 μM ABA, 25-30°C, 7–10 days), they survived slow freezing (2°C/h) to −9.0 ~ −9.3°C (LT50: 50% killing temperature) while control cells were mostly injured at −3°C (LT50: -0.5 ~ −1.5°C). Ice-inoculation of the cell suspension at −3°C and survival determination by regrowth confirmed that ABA-treated rice cells survived extracellular freezing at −9°C. ABA-induced freezing tolerance did not require any exposure to cold and was best achieved at 25-30°C where the rice cells maintained high growth even in the presence of ABA. ABA treatment also increased tolerance to heat (43°C) as determined by regrowth. ABA-treated cells tended to have more augmented cytoplasm and/or reduced vacuole sizes compared to control cultures with a concomitant increase in osmolarity and a decrease in water content. ABA-treated (2–7 days) in vitro grown seedlings and their leaves survived slow freezing to −3°C with only marginal injury (LT50: -4°C) whereas untreated seedlings were killed at −3°C (LT50: -2°C). Conclusions The results indicate that exogenous ABA can induce some levels of freezing tolerance in chilling-sensitive rice cells and seedlings, probably by eliciting mechanisms different from low temperature-induced cold acclimation. PMID:24004611

Affective stress responses during leisure time: Validity evaluation of a modified version of the Stress-Energy Questionnaire.

PubMed

Hadžibajramović, Emina; Ahlborg, Gunnar; Håkansson, Carita; Lundgren-Nilsson, Åsa; Grimby-Ekman, Anna

2015-12-01

Psychosocial stress at work is one of the most important factors behind increasing sick-leave rates. In addition to work stressors, it is important to account for non-work-related stressors when assessing stress responses. In this study, a modified version of the Stress-Energy Questionnaire (SEQ), the SEQ during leisure time (SEQ-LT) was introduced for assessing the affective stress response during leisure time. The aim of this study was to investigate the internal construct validity of the SEQ-LT. A second aim was to define the cut-off points for the scales, which could indicate high and low levels of leisure-time stress and energy, respectively. Internal construct validity of the SEQ-LT was evaluated using a Rasch analysis. We examined the unidimensionality and other psychometric properties of the scale by the fit to the Rasch model. A criterion-based approach was used for classification into high and low stress/energy levels. The psychometric properties of the stress and energy scales of the SEQ-LT were satisfactory, having accommodated for local dependency. The cut-off point for low stress was proposed to be in the interval between 2.45 and 3.02 on the Rasch metric score; while for high stress, it was between 3.65 and 3.90. The suggested cut-off points for the low and high energy levels were values between 1.73-1.97 and 2.66-3.08, respectively. The stress and energy scale of the SEQ-LT satisfied the measurement criteria defined by the Rasch analysis and it provided a useful tool for non-work-related assessment of stress responses. We provide guidelines on how to interpret the scale values. © 2015 the Nordic Societies of Public Health.

Longitudinal Analysis of the Intestinal Microbiota in Liver Transplantation.

PubMed

Kato, Karin; Nagao, Miki; Miyamoto, Kentaro; Oka, Kentaro; Takahashi, Motomichi; Yamamoto, Masaki; Matsumura, Yasufumi; Kaido, Toshimi; Uemoto, Shinji; Ichiyama, Satoshi

2017-04-01

Increasing evidence suggests that the intestinal microbiota plays an important role in liver diseases. However, the dynamics of the intestinal microbiota during liver transplantation (LT) and its potential role in clinical course remain unknown. We prospectively analyzed the intestinal microbiota of 38 patients who underwent LT in Kyoto University Hospital. We characterized the microbial compositions of fecal specimens from LT patients using a metagenomics approach by an Illumina MiSeq platform. We analyzed the diversity of microbiota sequentially from pretransplantation until 2 months after LT and also compared the microbiota during an episode of acute cellular rejection (ACR) and bloodstream infections (BSI) to the microbial composition of time-matched fecal specimens obtained from patients who did not experience ACR or BSI, respectively. Three hundred twenty fecal specimens were analyzed. Dynamic changes were observed in the microbial composition of LT recipients during the perioperative period. Over the course of LT, the mean diversity index decreased during the first 3 weeks after LT and gradually increased during our observation period. The loss of intestinal microbiota diversity was associated with high Child-Pugh scores, high model for end-stage liver disease scores, ACR, and BSI. At the family level, Bacteroides , Enterobacteriaceae , Streptococcaceae, and Bifidobacteriaceae were increased whereas Enterococcaceae , Lactobacillaceae , Clostridiaceae , Ruminococcaceae, and Peptostreptococcaceae were decreased in ACR patients. The microbiota of LT patients was associated with the severity of liver diseases and the presence of ACR and BSI. These results lay the groundwork for more comprehensive investigations of microbiota characteristics to identify diagnostic markers for transplant health and to guide intervention strategies to improve transplant outcomes.

Transfiguring structural, optical and dielectric properties of cadmium thiourea acetate crystal by the addition of L-threonine for laser assisted device applications

NASA Astrophysics Data System (ADS)

Kulkarni, Rupali B.; Anis, Mohd; Hussaini, S. S.; Shirsat, Mahendra D.

2018-03-01

Present investigation reports the growth of pure and L-threonine (LT) doped cadmium thiourea acetate (CTA) crystals by slow solution evaporation technique followed by structural, optical and dielectric characterization studies. A bulk single crystal of LT-CTA has been grown at temperature 38 °C. The single crystal x-ray diffraction technique has been employed to confirm the structural parameters of pure and LT doped CTA crystals. The increase in optical transparency of LT-CTA crystal was ascertained in the range of 200 to 900 nm using UV-visible spectral analysis. The widened optical band gap of the LT-CTA crystal is found to be 4.7 eV. Pure and doped crystals are subjected to FT-IR analysis to indicate the presence of functional groups quantitatively. Appreciable enhancement in second harmonic generation (SHG) efficiency of LT-CTA crystal with reference to parent CTA was confirmed from Kurtz-Perry SHG test (1.31 times of CTA crystal). The assertive influence of LT on electrical properties of grown crystals has been investigated in the temperature range 35 °C-120 °C. Electronic purity and the color centered photoluminescence emission nature of pure and IA-CTA crystals were justified by luminescence analysis. With the aid of single beam Z-scan analysis, the Kerr lensing nonlinearity was identified and the magnitude of TONLO parameters has been determined. The cubic susceptibility (χ3) and figure of merit (FOM) was found to be 4.81 × 10-4esu and 978.35. Results vitalize LT-CTA for laser stabilization systems.

Longitudinal Analysis of the Intestinal Microbiota in Liver Transplantation

PubMed Central

Kato, Karin; Nagao, Miki; Miyamoto, Kentaro; Oka, Kentaro; Takahashi, Motomichi; Yamamoto, Masaki; Matsumura, Yasufumi; Kaido, Toshimi; Uemoto, Shinji; Ichiyama, Satoshi

2017-01-01

Background Increasing evidence suggests that the intestinal microbiota plays an important role in liver diseases. However, the dynamics of the intestinal microbiota during liver transplantation (LT) and its potential role in clinical course remain unknown. Methods We prospectively analyzed the intestinal microbiota of 38 patients who underwent LT in Kyoto University Hospital. We characterized the microbial compositions of fecal specimens from LT patients using a metagenomics approach by an Illumina MiSeq platform. We analyzed the diversity of microbiota sequentially from pretransplantation until 2 months after LT and also compared the microbiota during an episode of acute cellular rejection (ACR) and bloodstream infections (BSI) to the microbial composition of time-matched fecal specimens obtained from patients who did not experience ACR or BSI, respectively. Results Three hundred twenty fecal specimens were analyzed. Dynamic changes were observed in the microbial composition of LT recipients during the perioperative period. Over the course of LT, the mean diversity index decreased during the first 3 weeks after LT and gradually increased during our observation period. The loss of intestinal microbiota diversity was associated with high Child-Pugh scores, high model for end-stage liver disease scores, ACR, and BSI. At the family level, Bacteroides, Enterobacteriaceae, Streptococcaceae, and Bifidobacteriaceae were increased whereas Enterococcaceae, Lactobacillaceae, Clostridiaceae, Ruminococcaceae, and Peptostreptococcaceae were decreased in ACR patients. Conclusions The microbiota of LT patients was associated with the severity of liver diseases and the presence of ACR and BSI. These results lay the groundwork for more comprehensive investigations of microbiota characteristics to identify diagnostic markers for transplant health and to guide intervention strategies to improve transplant outcomes. PMID:28405600

An Online Survey of Hypothyroid Patients Demonstrates Prominent Dissatisfaction.

PubMed

Peterson, Sarah J; Cappola, Anne R; Castro, M Regina; Dayan, Colin M; Farwell, Alan P; Hennessey, James V; Kopp, Peter A; Ross, Douglas S; Samuels, Mary H; Sawka, Anna M; Taylor, Peter N; Jonklaas, Jacqueline; Bianco, Antonio C

2018-06-01

Approximately 15% more patients taking levothyroxine (LT4) report impaired quality of life compared to controls. This could be explained by additional diagnoses independently affecting quality of life and complicating assignment of causation. This study sought to investigate the underpinnings of reduced quality of life in hypothyroid patients and to provide data for discussion at a symposium addressing hypothyroidism. An online survey for hypothyroid patients was posted on the American Thyroid Association Web site and forwarded to multiple groups. Respondents were asked to rank satisfaction with their treatment for hypothyroidism and their treating physician. They also ranked their perception regarding physician knowledge about hypothyroidism treatments, need for new treatments, and life impact of hypothyroidism on a scale of 1-10. Respondents reported the therapy they were taking, categorized as LT4, LT4 and liothyronine (LT4 + LT3), or desiccated thyroid extract (DTE). They also reported sex, age, cause of hypothyroidism, duration of treatment, additional diagnoses, and prevalence of symptoms. A total of 12,146 individuals completed the survey. The overall degree of satisfaction was 5 (interquartile range [IQR] = 3-8). Among respondents without self-reported depression, stressors, or medical conditions (n = 3670), individuals taking DTE reported a higher median treatment satisfaction of 7 (IQR = 5-9) compared to other treatments. At the same time, the LT4 treatment group exhibited the lowest satisfaction of 5 (IQR = 3-7), and for the LT4 + LT3 treatment group, satisfaction was 6 (IQR = 3-8). Respondents taking DTE were also less likely to report problems with weight management, fatigue/energy levels, mood, and memory compared to those taking LT4 or LT4 + LT3. A subset of patients with hypothyroidism are not satisfied with their current therapy or their physicians. Higher satisfaction with both treatment and physicians is reported by those patients on DTE. While the study design does not provide a mechanistic explanation for this observation, future studies should investigate whether preference for DTE is related to triiodothyronine levels or other unidentified causes.

Antifungal catheter lock therapy for the management of a persistent Candida albicans bloodstream infection in an adult receiving hemodialysis.

PubMed

Paul DiMondi, V; Townsend, Mary L; Johnson, Melissa; Durkin, Michael

2014-07-01

Antifungal catheter lock therapy (AfLT) with liposomal amphotericin B has been used in the treatment of pediatric central line infections caused by Candida species; however, reports describing the use of liposomal amphotericin B lock therapy in the adult hemodialysis patient population are lacking. Management of central line-associated candidemia with systemic therapy alone is often challenging due to the propensity of Candida species to form biofilms on foreign bodies. We describe a 64-year-old woman who was receiving hemodialysis 3 times/week and was hospitalized with persistent fungemia. Despite receiving intravenous micafungin, she had multiple positive blood cultures for Candida albicans, which finally cleared after 7 days. Her double-lumen catheter was considered the most likely nidus of infection. Although catheter removal would have been preferred, this was not possible given her vasculopathy, history of multiple bloodstream infections, and lack of other available sites for vascular access. Catheter exchange was performed, and liposomal amphotericin B AfLT was administered in combination with intravenous micafungin for a total of 6 days. During this time, the patient experienced no discernible adverse effects secondary to AfLT. At discharge, AfLT was discontinued, and intravenous micafungin was changed to oral fluconazole. After 6 months of treatment, the patient remained culture negative and maintained her dialysis access. To our knowledge, this is the first case report of liposomal amphotericin B catheter lock therapy used to manage a persistent C. albicans bloodstream infection in an adult receiving hemodialysis. AfLT is a novel concept for treating catheter-associated fungal infections. Liposomal amphotericin B was chosen based on its favorable in vitro activity against Candida species biofilms in catheter lock environments. We identified several barriers to implementing AfLT, and these issues may prohibit the use of AfLT. This case report illustrates the benefits and challenges of managing catheter-associated fungal infections with AfLT. Further study is required to examine the efficacy, safety, and feasibility of this approach. © 2014 Pharmacotherapy Publications, Inc.

Reproductive biology of the southern thorny skate Amblyraja doellojuradoi (Chondrichthyes, Rajidae).

PubMed

Delpiani, G

2016-04-01

The total lengths (L(T)) of 193 males (209-556 mm) and 130 females (275-515 mm) of Amblyraja doellojuradoi, a commercial by-catch species on the Argentinean continental shelf, which are increasingly retained, were analysed. No sexual dimorphism was observed in the L(T) at which 50% of individuals were sexually mature; males matured at 448 mm and females at 411 mm, c. 80 and 82% of maximum L(T). The hepato-somatic index was similar among sexes, but significantly different between maturity stages, being lower in mature than immature specimens. Males had no seasonal difference in the hepato-somatic index and females had the lowest index in autumn. The gonado-somatic index was lower in males than in females and significantly higher in mature than immature specimens of both sexes. Males had the highest index in autumn and females had no seasonal difference. Collectively, these results would indicate that A. doellojuradoi breeds in autumn. © 2016 The Fisheries Society of the British Isles.

Assessment of physical fatigability and fatigue perception in myasthenia gravis.

PubMed

Jordan, Berit; Mehl, Theresa; Schweden, Tabea L K; Menge, Uwe; Zierz, Stephan

2017-05-01

Fatigue includes both performance fatigability and fatigue perception. In 32 stable patients with generalized myasthenia gravis (MG) and 17 controls, time-dependent physical performance was assessed by the arm movement test (AMT) and 6-minute walk test (6MWT). MG patients presented with low quantitative MG scores (mean 0.5, SD 0.5) and without pathologic decrement. Fatigability was based on calculation of linear trend (LT) reflecting dynamic performance within subsequent constant time intervals. Perception of physical fatigue was analyzed using fatigue questionnaires. MG patients showed a negative LT in both AMT and 6MWT, significantly differing from stable performance in controls. LT inversely correlated with elevation of acetylcholine receptor antibodies (r = -0.59, P < 0.005) but not with quantitative MG score and fatigue perception. LT allows quantification of fatigability as an objective measurement of decline in individual performance, even in patients without obvious neuromuscular deficits in routine testing. The missing correlation of experienced fatigue supports the multidimensional fatigue model. Muscle Nerve 55: 657-663, 2017. © 2016 Wiley Periodicals, Inc.

The exercise and affect relationship: evidence for the dual-mode model and a modified opponent process theory.

PubMed

Markowitz, Sarah M; Arent, Shawn M

2010-10-01

This study examined the relationship between exertion level and affect using the framework of opponent-process theory and the dual-mode model, with the Activation-Deactivation Adjective Checklist and the State Anxiety Inventory among 14 active and 14 sedentary participants doing 20 min of treadmill exercise at speeds of 5% below, 5% above, and at lactate threshold (LT). We found a significant effect of time, condition, Time × Condition, and Time × Group, but no group, Group × Condition, or Time × Group × Condition effects, such that the 5% above LT condition produced a worsening of affect in-task compared with all other conditions whereas, across conditions, participants experienced in-task increases in energy and tension, and in-task decreases in tiredness and calmness relative to baseline. Posttask, participants experienced mood improvement (decreased tension, anxiety, and increased calmness) across conditions, with a 30-min delay in the above LT condition. These results partially support the dual-mode model and a modified opponent-process theory.

Acute toxicity of ibogaine and noribogaine.

PubMed

Kubiliene, Asta; Marksiene, Rūta; Kazlauskas, Saulius; Sadauskiene, Ilona; Razukas, Almantas; Ivanov, Leonid

2008-01-01

To evaluate acute toxic effect of ibogaine and noribogaine on the survival of mice and determine median lethal doses of the substances mentioned. White laboratory mice were used for the experiments. Ibogaine and noribogaine were administered intragastrically to mice via a stomach tube. Control animals received the same volume of saline. The median lethal dose was calculated with the help of a standard formula. To determine the median lethal dose of ibogaine, the doses of 100, 300, 400, and 500 mg/kg were administered intragastrically to mice. The survival time of mice after the drug administration was recorded, as well as the number of survived mice in each group. Upon administration of ibogaine at a dose of 500 mg/kg, all mice in this dose group died. Three out of four mice died in the group, which received 300 mg/kg of ibogaine. No mouse deaths were observed in the group, which received 100 mg/kg of ibogaine. The determined LD(50) value of ibogaine equals to 263 mg/kg of body mass. In order to determine the median lethal dose of noribogaine, the doses of 300, 500, 700, and 900 mg/kg were administered to mice intragastrically. Noribogaine given at a dose of 500 mg/kg had no impact on the mouse survival. The increase of noribogaine dose to 700 mg/kg of mouse body mass led to the death of three out of four mice in the group. Upon administration of noribogaine at a dose of 900 mg/kg, all mice in this group died. The LD(50) value of noribogaine in mice determined on the basis of the number of dead mice and the size of the doses used equals to 630 mg/kg of mouse body mass. The behavior of mice was observed upon administration of ibogaine or noribogaine. Low doses of ibogaine and noribogaine had no impact on the mouse behavior. External effects (convulsions, nervous behaviour, limb paralysis) were observed only when substances were administrated at higher doses. It has been determined that the median lethal dose of ibogaine and noribogaine equals to 263 mg and 630 mg/kg of mouse body mass, respectively. The toxicity of ibogaine is 2.4 times higher than that of noribogaine.

Nonmuscarinic Neurotoxicity of Oxotremorine,

DTIC Science & Technology

The ability of various treatments to prevent peripheral parasympathetic actions, central effects and lethality of the muscarinic agonist oxotremorine ...was studied in rats. The percentage of animals exhibiting effects of oxotremorine was dose and time dependent. Doses of oxotremorine in excess of 5...salivation were not present in atropine-treated rats. In the presence of 40 mg/ kg of atropine, ED50 values for oxotremorine were shifted more that 12

Periodic magnetopause oscillations observed with the GOES satellites on March 24, 1991

NASA Technical Reports Server (NTRS)

Cahill, L. J., Jr.; Winckler, J. R.

1992-01-01

The GOES 6 and 7 satellites were in the dayside magnetosphere late on March 24, 1991, when the magnetopause moved in to geosynchronous orbit. Observations on GOES 6 near 1030 local time (LT) indicated six inward and outward periodic movements of the magnetopause past the satellite over a 30-min interval. Later the magnetopause moved farther in, placing GOES 6 (1100 LT) in the magnetosheath and then moving in past GOES 7, near 1245 LT. The periodic oscillations of the magnetopause at GOES 6 suggest surface waves propagating toward the dawn flank of the magnetopause.

Physiological and training characteristics of recreational marathon runners.

PubMed

Gordon, Dan; Wightman, Sarah; Basevitch, Itay; Johnstone, James; Espejo-Sanchez, Carolina; Beckford, Chelsea; Boal, Mariette; Scruton, Adrian; Ferrandino, Mike; Merzbach, Viviane

2017-01-01

The aim of this study was to examine the physical and training characteristics of recreational marathon runners within finish time bandings (2.5-3 h, 3-3.5 h, 3.5-4 h, 4-4.5 h and >4.5 h). A total of 97 recreational marathon runners (age 42.4 ± 9.9 years; mass 69.2 ± 11.3 kg; stature 172.8 ± 9.1 cm), with a marathon finish time of 229.1 ± 48.7 min, of whom n = 34 were female and n = 63 were male, completed an incremental treadmill test for the determination of lactate threshold (LT1), lactate turn point (LT2) and running economy (RE). Following a 7-min recovery, they completed a test to volitional exhaustion starting at LT2 for the assessment of [Formula: see text]. In addition, all participants completed a questionnaire gathering information on their current training regimes exploring weekly distances, training frequencies, types of sessions, longest run in a week, with estimations of training speed, and load and volume derived from these data. Training frequency was shown to be significantly greater for the 2.5-3 h group compared to the 3.5-4 h runners ( P < 0.001) and >4.5 h group ( P = 0.004), while distance per session (km·session -1 ) was significantly greater for the 2.5-3 h group (16.1 ± 4.2) compared to the 3.5-4 h group (15.5 ± 5.2; P = 0.01) and >4.5 h group (10.3 ± 2.6; P = 0.001). Race speed correlated with LT1 ( r = 0.791), LT2 ( r = 0.721) and distance per session ( r = 0.563). The data highlight profound differences for key components of marathon running ([Formula: see text], LT1, LT2, RE and % [Formula: see text]) within a group of recreational runners with the discriminating training variables being training frequency and the absolute training speed.

Health-related quality of life and employment status of liver transplant patients.

PubMed

Aberg, Fredrik; Rissanen, Anne M; Sintonen, Harri; Roine, Risto P; Höckerstedt, Krister; Isoniemi, Helena

2009-01-01

Health-related quality of life (HRQoL) is one preferable outcome measure of medical interventions such as liver transplantation (LT). The aim of this study was to compare HRQoL of LT patients with that of the general population and to assess the employment status of LT patients. HRQoL was measured with the 15D instrument, a validated, non-disease-specific, 15-dimensional, self-administered HRQoL instrument. The questionnaire was sent to all adult LT patients in Finland (401 patients) alive in June 2007. The response rate was 89% (353 patients). The results were compared to those of 6050 age-standardized and gender-standardized controls from the general population. LT patients (mean age, 55 years; range, 20-82) had slightly worse HRQoL scores than the general population (mean 15D score, 0.889 versus 0.907; P < 0.002). Survival time and retransplantation did not affect HRQoL significantly in age-adjusted and gender-adjusted analyses. HRQoL decreased with increasing age (P < 0.0001). Patients transplanted for acute liver failure (ALF) or chronic liver disease (CLD) had significantly worse HRQoL than the general population (P = 0.014 and P = 0.040). Forty-four percent of working-age patients were employed at the time of the study. Persons that were employed had significantly better HRQoL than those unemployed (15D scores, 0.934 versus 0.859; P < 0.0001). Eighty-seven percent of patients experienced improved working capacity after LT. Early retirement was the most common cause of unemployment (56% of unemployed patients), and those patients presented with worse HRQoL than patients unemployed for other reasons. In conclusion, HRQoL of LT patients is very close to that of the general population. Older age, CLD, and ALF impair HRQoL. Employment is an indicator of HRQoL. Copyright 2008 AASLD.

Cognitive-behavioral therapy vs. light therapy for preventing winter depression recurrence: study protocol for a randomized controlled trial.

PubMed

Rohan, Kelly J; Evans, Maggie; Mahon, Jennifer N; Sitnikov, Lilya; Ho, Sheau-Yan; Nillni, Yael I; Postolache, Teodor T; Vacek, Pamela M

2013-03-21

Seasonal affective disorder (SAD) is a subtype of recurrent depression involving major depressive episodes during the fall and/or winter months that remit in the spring. The central public health challenge in the management of SAD is prevention of winter depression recurrence. Light therapy (LT) is the established and best available acute SAD treatment. However, long-term compliance with daily LT from first symptom through spontaneous springtime remission every fall/winter season is poor. Time-limited alternative treatments with effects that endure beyond the cessation of acute treatment are needed to prevent the annual recurrence of SAD. This is an NIMH-funded R01-level randomized clinical trial to test the efficacy of a novel, SAD-tailored cognitive-behavioral group therapy (CBT) against LT in a head-to-head comparison on next winter outcomes. This project is designed to test for a clinically meaningful difference between CBT and LT on depression recurrence in the next winter (the primary outcome). This is a concurrent two-arm study that will randomize 160 currently symptomatic community adults with major depression, recurrent with seasonal pattern, to CBT or LT. After 6 weeks of treatment in the initial winter, participants are followed in the subsequent summer, the next winter, and two winters later. Key methodological issues surround timing study procedures for a predictably recurrent and time-limited disorder with a focus on long-term outcomes. The chosen design answers the primary question of whether prior exposure to CBT is associated with a substantially lower likelihood of depression recurrence the next winter than LT. This design does not test the relative contributions of the cognitive-behavioral treatment components vs. nonspecific factors to CBT's outcomes and is not adequately powered to test for differences or equivalence between cells at treatment endpoint. Alternative designs addressing these limitations would have required more patients, increased costs, and reduced power to detect a difference in the primary outcome. Clinicaltrials.gov identifier NCT01714050.

Serial Monitoring of Immune Markers Being Represented Regulatory T Cell/T Helper 17 Cell Ratio: Indicating Tolerance for Tapering Immunosuppression after Liver Transplantation

PubMed Central

Jhun, JooYeon; Lee, Seung Hoon; Lee, Soon Kyu; Kim, Hee Yeon; Jung, Eun Sun; Kim, Dong Goo; Choi, JeongWon; Bae, Si Hyun; Yoon, Seung Kew; Chung, Byung Ha; Yang, Chul Woo; Cho, Mi-La; Choi, Jong Young

2018-01-01

Recipients of liver transplantation (LT) require long-term immunosuppressive drug treatment, but lifelong immunosuppressive treatment has severe side effects. It is known that some LT recipients develop immune tolerance, and although the development of such operational tolerance should allow a decrease in the burden of immunosuppressive drug treatment, the factors that indicate operational tolerance are not clear. This study aimed to monitor immunological markers over time in LT recipients to identify those markers indicating the development of operational tolerance. We performed a prospective pilot study measuring immune markers, including the ratio of regulatory T (Treg) and T helper (Th) 17 cells in peripheral blood in the 14 most immunologically stable patients among 70 clinically stable LT recipients. The doses of immunosuppressive drugs given to these 14 LT recipients were tapered over time and they were monitored for immunological markers related to the development of immune tolerance. As the doses of immunosuppressive drugs were reduced, the Treg/Th17, Th1/Th17, and CD8/Th17 ratio in tolerant recipients was significantly increased compared with that of nontolerant recipients. These results suggest that monitoring of changes in the immune makers, including Treg/Th17 ratio during tapering of immunosuppression may allow prediction of the development of tolerance. PMID:29545795

Einstein’s sigh: hidden symmetry in Einstein’s derivation of the Lorentz transformation

NASA Astrophysics Data System (ADS)

Chao, Sheng D.

2017-03-01

‘Das hätte ich einfacher sagen können (I could have said that more simply).’ was Einstein’s sigh when he had a chance to remark on his own derivation of the Lorentz transformation (LT) in the 1905 seminal paper. In fact, in a popular science exposition of the theory of relativity Einstein did provide such a simple derivation of the LT. It is a curious historical fact that the latter derivation was presented in 1916, while Einstein’s remark was made in 1943. Was the 1916 derivation simple enough to relieve his sigh? Had he expected an even simpler derivation beyond his thoughts? In this paper, Einstein’s simple derivation of the LT is revisited and analysed. We show that the LT can be obtained from a symmetry principle hidden in Einstein’s logical reasoning. First, the relativity principle can be restated as a mirror principle based on the space-time exchange-inversion operation. Second, the assumed constancy of the speed of light (Einstein’s second postulate) can be derived by using the velocity reciprocity property, which is a deductive result of the space-time homogeneity and the space isotropy. Therefore, Einstein could have presented his derivation of the LT more simply, thus turning Einstein’s sigh of regret into a sigh of relief.

Effect of temperature and heating rate on apparent lethal concentrations of pyrolysis products

NASA Technical Reports Server (NTRS)

Hilado, C. J.; Solis, A. N.; Marcussen, W. H.; Furst, A.

1976-01-01

The apparent lethal concentrations for 50 percent of the test animals of the pyrolysis products from twelve polymeric materials were studied as a function of temperature and heating rate. The materials were polyethylene, nylon 6, ABS, polycarbonate, polyether sulfone, polyaryl sulfone, wool fabric, aromatic polyamide fabric, polychloroprene foam, polyvinyl fluoride film, Douglas fir, and red oak. The apparent lethal concentration values of most materials vary significantly with temperature and heating rate. The apparent lethal concentration values, based on weight of sample charged, appears to effectively integrate the thermophysical, thermochemical, and physiological responses from a known quantity of material under specified imposed conditions.

Chemical reaction of atomic oxygen with evaporated films of copper, part 4

NASA Technical Reports Server (NTRS)

Fromhold, A. T.; Williams, J. R.

1990-01-01

Evaporated copper films were exposed to an atomic oxygen flux of 1.4 x 10(exp 17) atoms/sq cm per sec at temperatures in the range 285 to 375 F (140 to 191 C) for time intervals between 2 and 50 minutes. Rutherford backscattering spectroscopy (RBS) was used to determine the thickness of the oxide layers formed and the ratio of the number of copper to oxygen atoms in the layers. Oxide film thicknesses ranged from 50 to 3000 A (0.005 to 0.3 microns, or equivalently, 5 x 10(exp -9) to 3 x 10(exp -7); it was determined that the primary oxide phase was Cu2O. The growth law was found to be parabolic (L(t) varies as t(exp 1/2)), in which the oxide thickness L(t) increases as the square root of the exposure time t. The analysis of the data is consistent with either of the two parabolic growth laws. (The thin-film parabolic growth law is based on the assumption that the process is diffusion controlled, with the space charge within the growing oxide layer being negligible. The thick-film parabolic growth law is also based on a diffusion controlled process, but space-charge neutrality prevails locally within very thick oxides.) In the absence of a voltage measurement across the growing oxide, a distinction between the two mechanisms cannot be made, nor can growth by the diffusion of neutral atomic oxygen be entirely ruled out. The activation energy for the reaction is on the order of 1.1 eV (1.76 x 10(exp -19) joule, or equivalently, 25.3 kcal/mole).

Effect of dysprosium and lutetium metal buffer layers on the resistive switching characteristics of Cu-Sn alloy-based conductive-bridge random access memory.

PubMed

Vishwanath, Sujaya Kumar; Woo, Hyunsuk; Jeon, Sanghun

2018-06-18

Conductive-bridge random access memory (CBRAM) has become one of the most suitable candidates for non-volatile memory in next-generation information and communication technology. The resistive switching mechanism of CBRAM depends on the formation/annihilation of the conductive filament (CF) between the active metal electrode and the inert electrode. However, excessive ion injection from the active electrode into the solid electrolyte is reduces the uniformity and reliability of the resistive switching devices. To solve this problem, we investigated the resistive switching characteristics of a modified active electrode with different compositions of Cu_x-Sn_{_1-x}(0.13 < X < 0.55). The resistive switching characteristics were further improved by inserting a dysprosium (Dy) or lutetium (Lu) buffer layer at the interface of Cu_x-Sn_1-x/Al₂O₃. Electrical analysis of the optimal Cu_0.27-Sn_0.73/Lu-based CBRAM exhibited stable resistive switching behavior with low operation voltage (SET: 0.7 V and RESET: -0.3 V), a high on/off resistive ratio (10⁶), cyclic endurance (>10⁴), and long-term retention (85℃/10 years). To achieve these performance parameters, CFs were locally formed inside the electrolyte using a modified CuSn active electrode, and the amount of Cu-ion injection was reduced by inserting the Dy or Lu buffer layer between the CuSn active electrode and the electrolyte. In particular, conductive-atomic force microscopy results at the Dy/ or Lu/Al₂O₃ interface directly showed and defined the diameter of the CF. © 2018 IOP Publishing Ltd.

76 FR 61344 - Endangered and Threatened Species; Take of Anadromous Fish

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-04

... and Threatened Species; Take of Anadromous Fish AGENCY: National Marine Fisheries Service (NMFS... to the ESA and NMFS regulations (50 CFR parts 222-226) governing listed fish and wildlife permits... fish captured. Permit 15824 does not authorize any non- lethal or lethal take of adult ESA-listed...

Ebola GP-specific monoclonal antibodies protect mice and guinea pigs from lethal Ebola virus infection.

PubMed

Qiu, Xiangguo; Fernando, Lisa; Melito, P Leno; Audet, Jonathan; Feldmann, Heinz; Kobinger, Gary; Alimonti, Judie B; Jones, Steven M

2012-01-01

Ebola virus (EBOV) causes acute hemorrhagic fever in humans and non-human primates with mortality rates up to 90%. So far there are no effective treatments available. This study evaluates the protective efficacy of 8 monoclonal antibodies (MAbs) against Ebola glycoprotein in mice and guinea pigs. Immunocompetent mice or guinea pigs were given MAbs i.p. in various doses individually or as pools of 3-4 MAbs to test their protection against a lethal challenge with mouse- or guinea pig-adapted EBOV. Each of the 8 MAbs (100 µg) protected mice from a lethal EBOV challenge when administered 1 day before or after challenge. Seven MAbs were effective 2 days post-infection (dpi), with 1 MAb demonstrating partial protection 3 dpi. In the guinea pigs each MAb showed partial protection at 1 dpi, however the mean time to death was significantly prolonged compared to the control group. Moreover, treatment with pools of 3-4 MAbs completely protected the majority of animals, while administration at 2-3 dpi achieved 50-100% protection. This data suggests that the MAbs generated are capable of protecting both animal species against lethal Ebola virus challenge. These results indicate that MAbs particularly when used as an oligoclonal set are a potential therapeutic for post-exposure treatment of EBOV infection.

Association of donor and recipient SUMO4 rs237025 genetic variant with new-onset diabetes mellitus after liver transplantation in a Chinese population.

PubMed

Zhang, Tao; Liu, Yuan; Hu, Yibo; Zhang, Xiaoqing; Zhong, Lin; Fan, Junwei; Peng, Zhihai

2017-09-05

New-onset diabetes mellitus (NODM) is a common complication after liver transplantation (LT). The small ubiquitin-like modifier 4 (SUMO4) rs237025 polymorphism has been reported to be associated with type 2 diabetes mellitus (T2DM). In this study, we aimed to evaluate the association of donor and recipient SUMO4 rs237025 polymorphisms with NODM and the long-term consequences of NODM after LT. A total of 126 liver transplant patients were enrolled in the study. One single nucleotide polymorphism, SUMO4 rs237025, was genotyped in both donors and recipients. Both donor and recipient SUMO4 rs237025 polymorphisms were found to be significantly associated with NODM after LT. In multivariate analysis, recipient age>50 years, tacrolimus trough concentrations>10ng/mL at 1month after LT, donor and recipient rs237025 genetic variant, and the combined donor and recipient rs237025 genetic variant were independent predictive factors of NODM. Area under the receiver operating characteristic curve (AUROC) analysis indicated the higher predictive ability of the model containing combined donor and recipient rs237025 polymorphisms than the clinical model (p=0.046). Furthermore, Kaplan-Meier survival analysis demonstrated that NODM was related to significantly poorer patient survival in comparison with non-NODM patients (p=0.041). Both donor and recipient SUMO4 rs237025 polymorphisms contribute to the development of NODM after LT and NODM is a frequent complication that negatively affects patient survival. Copyright © 2017. Published by Elsevier B.V.

Toxicological Evaluation of Essential Oil From the Leaves of Croton argyrophyllus (Euphorbiaceae) on Aedes aegypti (Diptera: Culicidae) and Mus musculus (Rodentia: Muridae).

PubMed

Cruz, R C D; Silva, S L C E; Souza, I A; Gualberto, S A; Carvalho, K S; Santos, F R; Carvalho, M G

2017-07-01

Plant-derived essential oils can be used as insecticides for vector control. However, to establish their safety, it is necessary to perform toxicological studies. Herein, we evaluated the chemical composition and insecticidal activity of the essential oil from the leaves of Croton argyrophyllus on the third- and fourth-instar larvae and adult Aedes aegypti (L., 1762). We also evaluated the acute toxicity of the essential oil in adult female Mus musculus. The lethal concentration 50 (LC50) and 90 (LC90) of C. argyrophyllus essential oil on larvae of Ae. aegypti were 0.31 and 0.70 mg ml-1, respectively, and 5.92 and 8.94 mg ml-1, respectively, on Ae. aegypti adults. The major components of the essential oil were spathulenol (22.80%), (E)-caryophyllene (15.41%), α-pinene (14.07%), and bicyclogermacrene (10.43%). It also displayed acute toxicity in adults of Mus musculus; the intraperitoneal and oral lethal dose 50 (LD50) were 2,000 mg kg-1 and 2,500 mg kg-1, respectively. The results showed that the essential oil from C. argyrophyllus leaves has insecticidal activity on Ae. aegypti larvae and adults at an average lethal concentration below the median lethal dose needed to cause acute toxicity in the common mouse. © The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Comparative toxicity of diphacinone to northern bobwhite (Colinus virginianus) and American kestrels (Falco sparverius)

USGS Publications Warehouse

Rattner, Barnett A.; Horak, Katherine E.; Warner, Sarah E.; Day, Daniel D.; Johnston, John J.

2010-01-01

The acute oral toxicity of the anticoagulant rodenticide diphacinone was found to be about 20 times greater to American kestrels (LD50=97 mg/kg) than to northern bobwhite (LD50=2,014 mg/kg). Several precise and sensitive clotting assays (prothrombin time, Russell's Viper venom time, thrombin clotting time) were adapted for use in these species, and this combination of assays is recommended to detect effects of diphacinone and other rodenticides on coagulation. Oral administration of diphacinone over a range of doses (sublethal to the extrapolated LD15) prolonged prothrombin time and Russell's Viper venom time within 24 to 48 hrs post-exposure. Prolongation of in vitro clotting time reflects impaired coagulation complex activity and was detected before or at the onset of overt signs of toxicity and lethality. These data will assist in the development of a pharmacodynamic model to assess and predict rodenticide toxicity to non-target avian species.

Probing in-plane anisotropy in fewlayer ReS₂ using low frequency noise measurement.

PubMed

Mitra, Richa; Jariwala, Bhakti; Bhattacharya, Arnab; Das, Anindya

2018-01-31

ReS₂, a layered two-dimensional material popular for its in-plane anisotropic properties is emerging as one of the potential candidates for flexible electronics and ultrafast optical applications. It is an n-type semiconducting material having a layer independent bandgap of 1.55 eV. In this paper we have characterized the intrinsic electronic noise level of fewlayer ReS₂ for the first time. Fewlayer ReS₂ FET devices show 1/f nature of noise for frequency ranging over three orders of magnitude. We have also observed that not only the electrical response of the material is anisotropic; the noise level is also direction dependent. In fact the noise is found to be more sensitive towards the anisotropy. This fact has been explained by evoking the theory where the Hooge parameter is not a constant quantity, but has a distinct power law dependence on mobility along the two axes direction. The anisotropy in 1/f noise measurement will pave the way to quantify the anisotropic nature of two-dimensional (2D) materials, which will be helpful for the design of low noise transistor in future. © 2018 IOP Publishing Ltd.

Hepatitis C and liver transplantation.

PubMed

Martini, Silvia

2018-06-01

Hepatitis C virus (HCV)-related liver disease represents the leading indication for liver transplantation (LT) in the USA and Europe and HCV recurrence is universal in recipients who are viremic at LT. Until a few years ago, pegylated-interferon in association with ribavirin was the only therapeutic strategy, usable only in compensated cirrhotic patients, in order to prevent post-LT viral recurrence. The recent advent of direct-acting antiviral agents (DAAs) has dramatically increased the chances of curative treatment for the transplant population and the debate about which should be the best time for treating the infection is still open: whether to pursue HCV eradication 1) before LT, in order to improve liver function, delist some patients and prevent graft infection; or 2) as early as possible after LT, rather than 3) waiting for hepatitis C recurrence before starting treatment. In addition, in the DAA era, the use of HCV-positive donors may represent a potential approach to safely expanding the donor pool. As more HCV patients achieve cure with DAA regimens, the LT trend for HCV in the future would be expected to mimic the trend observed for hepatitis B virus in the past decade and in the United States, during the DAA-period 2014-2015, the rate of LT wait-listing for HCV complicated by decompensated cirrhosis has already decreased by 32%. This review summarizes the published data and emphasizes DAA treatment applicability to patients with decompensated cirrhosis and to liver transplant recipients.

Liver transplantation for Wilson disease

PubMed Central

Catana, Andreea M; Medici, Valentina

2012-01-01

The aim of this paper is to review the current status of liver transplantation (LT) for Wilson disease (WD), focusing on indications and controversies, especially in patients with neuropsychiatric disease, and on identification of acute liver failure (ALF) cases related to WD. LT remains the treatment of choice for patients with ALF, as initial presentation of WD or when anti-copper agents are stopped, and for patients with chronic liver disease progressed to cirrhosis, unresponsive to chelating medications or not timely treated with copper chelating agents. The indication for LT in WD remains highly debated in patients with progressive neurological deterioration and failure to improve with appropriate medical treatment. In case of Wilsonian ALF, early identification is key as mortality is 100% without emergency LT. As many of the copper metabolism parameters are believed to be less reliable in ALF, simple biochemical tests have been proposed for diagnosis of acute WD with good sensitivity and specificity. LT corrects copper metabolism and complications resulting from WD with excellent 1 and 5 year survival. Living related liver transplantation represents an alternative to deceased donor LT with excellent long-term survival, without disease recurrence. Future options may include hepatocyte transplantation and gene therapy. Although both of these have shown promising results in animal models of WD, prospective human studies are much needed to demonstrate their long-term beneficial effects and their potential to replace the need for medical therapy and LT in patients with WD. PMID:22312450

Cysteinyl leukotrienes C4 and D4 downregulate human mast cell expression of toll-like receptors 1 through 7.

PubMed

Karpov, V; Ilarraza, R; Catalli, A; Kulka, M

2018-01-01

Cysteinyl leukotrienes (CysLT) are potent inflammatory lipid molecules that mediate some of the pathophysiological responses associated with asthma such as bronchoconstriction, vasodilation and increased microvascular permeability. As a result, CysLT receptor antagonists (LRA), such as montelukast, have been used to effectively treat patients with asthma. We have recently shown that mast cells are necessary modulators of innate immune responses to bacterial infection and an important component of this innate immune response may involve the production of CysLT. However, the effect of LRA on innate immune receptors, particularly on allergic effector cells, is unknown. This study determined the effect of CysLT on toll-like receptor (TLR) expression by the human mast cell line LAD2. Real-time PCR analysis determined that LTC4, LTD4 and LTE4 downregulated mRNA expression of several TLR. Specifically in human CD34+-derived human mast cells (HuMC), LTC4 inhibited expression of TLR1, 2, 4, 5, 6 and 7 while LTD4 inhibited expression of TLR1-7. Montelukast blocked LTC4-mediated downregulation of all TLR, suggesting that these effects were mediated by activation of the CysLT1 receptor (CysLT1R). Flow cytometry analysis confirmed that LTC4 downregulated surface expression of TLR2 which was blocked by montelukast. These data show that CysLT can modulate human mast cell expression of TLR and that montelukast may be beneficial for innate immune responses mediated by mast cells.

Occurrence of biogenic amines in beers produced with malted organic Emmer wheat (Triticum dicoccum).

PubMed

Mozzon, Massimo; Boselli, Emanuele; Obiedziński, Mieczysław W; Frega, Natale G

2015-01-01

Because several groups of microorganisms are able to decarboxylate amino acids, the presence of biogenic amines (BA) can be seen as an index of the microbiological quality of the brewing process. BAs were quantified for the first time in the intermediate products and craft beers produced with malted organic Emmer wheat (Triticum dicoccum) in a small size brewery in order to assess the possible presence of critical control points related to biological hazard in the brewing process. BA levels in beers produced exclusively from malted organic Emmer wheat were between 15.4 and 25.2 mg l(-1) in the samples of light beer (Lt) and between 8.9 and 15.3 mg l(-1) in double malt beers (DM) ready for consumption (the beers stored for 90 days at 1-2°C). Cadaverine and tyramine were the main BAs in the Lt and DM beers, respectively. Increased concentrations of BAs seemed to be more related to the heat treatment of the processing product during mashing and wort boiling, rather than to the fermentation process. Much lower concentrations were found in finished beers obtained from 50% malted organic Emmer wheat and 50% malted barley (up to 3.2 mg l(-1)) or from 30% malted Emmer wheat (up to 8.3 mg l(-1)). Thus, Emmer wheat malt can be a useful alternative to wheat and spelt for the production of beer with a limited content of BA, if the processing technology is kept under control.

Tape Casting of High-Performance Low-Temperature Solid Oxide Cells with Thin La0.8Sr0.2Ga0.8Mg0.2O3-δ Electrolytes and Impregnated Nano Anodes.

PubMed

Gao, Zhan; Wang, Hongqian; Miller, Elizabeth; Liu, Qinyuan; Senn, Daniel; Barnett, Scott

2017-03-01

Low-temperature solid oxide cells (LT-SOCs), operating at 400 to 650 °C, have great potential for commercialization since they can provide lower cost and improved long-term durability. Low operating temperature can also enable high round-trip efficiency of SOCs as reversible energy storage devices. This paper describes Sr 0.8 La 0.2 TiO 3-α (SLT) anode supported LT-SOC with thin La 0.8 Sr 0.2 Ga 0.8 Mg 0.2 O 3-δ (LSGM) electrolyte made by tape casting, with screen printed La 0.6 Sr 0.4 Fe 0.8 Co 0.2 O 3-δ (LSCF) cathode and impregnated Ni anode. Optimization of the anode functional layers is described; the best anodes had 68 vol % LSGM and 12.3 vol % Ni and yielded maximum power density of 1.6 Wcm -2 with a cell area specific resistance (ASR) of 0.21 Ωcm 2 at 650 °C. Most of the cell ASR was associated with the cathode. Reversible electrolysis and fuel cell operation yielded similar characteristics with both 50% H 2 -50% H 2 O and syngas fuel. Life testing over 500 h showed that the cathode impedance stabilized after an initial break-in period; the ohmic and anode resistances, though relatively small, increased slightly with time.

Aroclor 1254 residues in birds: Lethal levels and loss rates

USGS Publications Warehouse

Stickel, W.H.; Stickel, L.F.; Dyrland, R.A.; Hughes, D.L.

1984-01-01

Lethal residues of polychlorinated biphenyls (PCBs) were determined experimentally in four species of wild birds (male common grackles (Quiscalus quiscula ), immature female red-winged blackbirds (Agelaius phoeniceus ), adult male brown-headed cowbirds (Molothrus ater ) and immature female starlings (Sturnus vulgaris)) given dietary dosage of 1,500 ppm of Aroclor 1254) until one-half had died, sacrificing the survivors, chemically analyzing the tissues, and comparing results in dead birds and survivors. For all species, residues of 310 ppm or higher in the brain showed increasing likelihood of death from PCB poisoning. Residues in dead birds did not differ among species except for starlings (Sturnus vulgaris ), which averaged slightly lower than the others. However, the species differed in the length of time to 50% mortality and in the levels of PCBs in brains at sacrifice.

Liver transplantation of hepatitis B surface antigen positive donors to hepatitis B core antibody recipients: analysis of 27 patients.

PubMed

Krishnamoorthi, R; Manickam, P; Cappell, M S

2014-06-01

Shortage of donor livers is the major limiting factor for liver transplantation (LT). While livers from patients with past infection of Hepatitis-B (HBcAb+) are commonly used as donors, scant data exists on outcomes following transplantation of HBsAg+ donor livers. The impact of donor HBsAg positivity on recipient survival is currently analyzed. Post hoc analysis of all adults undergoing LT from October 1987-September 2010 registered in United Network for Organ Sharing/Organ Procurement and Transplantation Network, a concurrent, limited access database of all American LT recipients. Only recipients who were HBcAb+ were analyzed. LTs with missing donor or recipient serologic parameters for Hepatitis-B were excluded. Significant predictors of survival were determined by univariate analysis. Cox proportional hazards model was used to determine independent risk predictors in the multivariate analysis. The population consisted of 13,329 LT recipients. The mean age of donors and recipients were 40±16 years and 52±9 years respectively. The mean follow-up was 3.7 years. Study population included 27 recipients transplanted with HBsAg+ grafts, of whom 7 (28%) died. Outcomes were adjusted for donor age, recipient age, donor gender, recipient gender, type of LT, MELD score, HCV status, previous LT, and cold ischemic time. On multivariate analysis, LT recipient outcomes were not significantly different for HBsAg+ donors versus donors without prior hepatitis B infection (HR: 1.14, 95% CI: 0.93-1.39, P=0.17). Kaplan-Meier curves revealed no significant survival difference between the two groups. These results suggest that donor HBsAg positivity did not affect overall survival of LT recipients. These findings could potentially expand the pool of liver donors.

Medication adherence and rejection rates in older versus younger adult liver transplant recipients

PubMed Central

Leven, Emily A.; Annunziato, Rachel; Helcer, Jacqueline; Lieber, Sarah R.; Knight, Christopher S.; Wlodarkiewicz, Catherine; Soriano, Rainier P.; Florman, Sander S.; Schiano, Thomas D.; Shemesh, Eyal

2017-01-01

A growing number of older adults are undergoing liver transplantation (LT) in the US. In some settings, it is thought that adherence declines with age. This retrospective study examined adherence and clinical outcomes in older versus younger adult LT recipients. Medical records of adult LT recipients from 2009–2012 from a single urban center were reviewed. The medication level variability index (MLVI) was the pre-defined primary outcome, with nonadherence defined as MLVI >2.5. The secondary outcome was incidence of rejection. Outcomes were evaluated starting one year post-LT until 2015. 42/248 patients were ≥65 at transplant. Older adults had significantly better adherence than younger ones (65% ≥65 were adherent vs. 42% younger adults; Chi-Square two-tailed p=0.02). Survival analyses of rejection between age groups censored by time since transplant showed no difference among the four age groups (χ2 = 0.84, p=0.84). Older age was not found to be a risk factor for reduced adherence or graft rejection in patients surviving at least one year post-LT. PMID:28370346

Insights into the CuO nanoparticle ecotoxicity with suitable marine model species.

PubMed

Rotini, A; Gallo, A; Parlapiano, I; Berducci, M T; Boni, R; Tosti, E; Prato, E; Maggi, C; Cicero, A M; Migliore, L; Manfra, L

2018-01-01

Metal oxide nanoparticles, among them copper oxide nanoparticles (CuO NPs), are widely used in different applications (e.g. batteries, gas sensors, superconductors, plastics and metallic coatings), increasing their potential release in the environment. In aquatic matrix, the behavior of CuO NPs may strongly change, depending on their surface charge and some physical-chemical characteristics of the medium (e.g. ionic strength, salinity, pH and natural organic matter content). Ecotoxicity of CuO NPs to aquatic organisms was mainly studied on freshwater species, few tests being performed on marine biota. The aim of this study was to assess the toxicity of CuO NPs on suitable indicator species, belonging to the ecologically relevant level of consumers. The selected bioassays use reference protocols to identify Effect/Lethal Concentrations (E(L)C), by assessing lethal and sub-lethal endpoints. Mortality tests were performed on rotifer (Brachionus plicatilis), shrimp (Artemia franciscana) and copepod (Tigriopus fulvus). While moult release failure and fertilization rate were studied, as sub-lethal endpoints, on T. fulvus and sea urchin (Paracentrotus lividus), respectively. The size distribution and sedimentation rates of CuO NPs, together with the copper dissolution, were also analyzed in the exposure media. The CuO NP ecotoxicity assessment showed a concentration-dependent response for all species, indicating similar mortality for B. plicatilis (48hLC 50 = 16.94 ± 2.68mg/l) and T. fulvus (96hLC 50 = 12.35 ± 0.48mg/l), followed by A. franciscana (48hLC 50 = 64.55 ± 3.54mg/l). Comparable EC 50 values were also obtained for the sub-lethal endpoints in P. lividus (EC 50 = 2.28 ± 0.06mg/l) and T. fulvus (EC 50 = 2.38 ± 0.20mg/l). Copper salts showed higher toxicity than CuO NPs for all species, with common sensitivity trend as follows: P. lividus ≥ T. fulvus (sublethal endpoint) ≥ B. plicatilis >T. fulvus (lethal endpoint) >A. franciscana. CuO NP micrometric aggregates and high sedimentation rates were observed in the exposure media, with different particle size distributions depending on the medium. The copper dissolution was about 0.16% of the initial concentration, comparable to literature values. The integrated ecotoxicological-physicochemical approach was used to better describe CuO NP toxicity and behavior. In particular, the successful application of ecotoxicological reference protocols allowed to produce reliable L(E)C data useful to identify thresholds and assess potential environmental hazard due to NPs. Copyright © 2017 Elsevier Inc. All rights reserved.

Neutralization Capacity of Monovalant Antivenom Against Existing Lethal Scorpions in the Turkish Scorpiofauna

PubMed Central

Ozkan, Ozcan; Yağmur, Ersen Aydın

2017-01-01

In this study, Mesobuthus gibbosus and Mesobuthus eupeus eupeus venom samples were compared for lethality, in-vivo effects and proteins. Neutralization capacity of monovalent Androctonus crassicauda antivenom (RSHA anti-Ac) was tested against the lethal effects of the venoms. Venom was obtained from mature scorpions by electrical stimulation of the telson. The lethality of the venom and potency of Horse RSHA anti-Ac were determined in Swiss mice. The protein profiles of the scorpion venoms were analysed by NuPAGE® 4–12% gradient Bis-Tris gel followed by Coomassie blue staining. Western blotting was performed to determine immunogenic compounds in the venom samples. The median lethal doses of M. e. eupeus, M.gibbosus scorpion and A.crassicauda venoms were determined to be 1.92 mg/kg by i.v. injection route, 0.67 mg/kg and 0.24 mg/kg by s.c. injection route, respectively. A.crassicauda (Olivier, 1807) venom was used as control. One millilitre of the RSHA anti-Ac neutralises 23 LD50 of M. e. eupeus, 32 LD50 of M.gibbosus and 42 LD50 of A. crassicauda venom in mice. Analysis of electrophoresis indicates that three scorpion venoms posses low molecular weight proteins. Immunoblotting indicated that RSHA anti-Ac strongly reacted with both the specific venom and Mesobuthus species venoms which have antigenic similarity. The result of our study showed that M.e. eupeus and M.gibbosus could be medically important scorpions for humans, particullary children. The RSHA anti-Ac can be used in the treatment of envenomation by M. e.eupeus and M.gibbosus scorpion stings. PMID:28979319

Heart Rate Variability during Simulated Hemorrhage with Lower Body Negative Pressure in High and Low Tolerant Subjects.

PubMed

Hinojosa-Laborde, Carmen; Rickards, Caroline A; Ryan, Kathy L; Convertino, Victor A

2011-01-01

Heart rate variability (HRV) decreases during hemorrhage, and has been proposed as a new vital sign to assess cardiovascular stability in trauma patients. The purpose of this study was to determine if any of the HRV metrics could accurately distinguish between individuals with different tolerance to simulated hemorrhage. Specifically, we hypothesized that (1) HRV would be similar in low tolerant (LT) and high tolerant (HT) subjects at presyncope when both groups are on the verge of hemodynamic collapse; and (2) HRV could distinguish LT subjects at presyncope from hemodynamically stable HT subjects (i.e., at a submaximal level of hypovolemia). Lower body negative pressure (LBNP) was used as a model of hemorrhage in healthy human subjects, eliciting central hypovolemia to the point of presyncopal symptoms (onset of hemodynamic collapse). Subjects were classified as LT if presyncopal symptoms occurred during the -15 to -60 mmHg levels of LBNP, and HT if symptoms occurred after LBNP of -60 mmHg. A total of 20 HRV metrics were derived from R-R interval measurements at the time of presyncope, and at one level prior to presyncope (submax) in LT and HT groups. Only four HRV metrics (Long-range Detrended Fluctuation Analysis, Forbidden Words, Poincaré Plot Descriptor Ratio, and Fractal Dimensions by Curve Length) supported both hypotheses. These four HRV metrics were evaluated further for their ability to identify individual LT subjects at presyncope when compared to HT subjects at submax. Variability in individual LT and HT responses was so high that LT responses overlapped with HT responses by 85-97%. The sensitivity of these HRV metrics to distinguish between individual LT from HT subjects was 6-33%, and positive predictive values were 40-73%. These results indicate that while a small number of HRV metrics can accurately distinguish between LT and HT subjects using group mean data, individual HRV values are poor indicators of tolerance to hypovolemia.

Scapular muscle activity in a variety of plyometric exercises.

PubMed

Maenhout, Annelies; Benzoor, Maya; Werin, Maria; Cools, Ann

2016-04-01

Plyometric shoulder exercises are commonly used to progress from slow analytical strength training to more demanding high speed power training in the return to play phase after shoulder injury. The aim of this study was first, to investigate scapular muscle activity in plyometric exercises to support exercise selection in practice and second, to enhance understanding of how scapular muscles are recruited during the back and forth movement phase of these exercises. Thirty-two healthy subjects performed 10 plyometric exercises while surface EMG-activity of the scapular muscles (upper (UT), middle (MT) and lower trapezius (LT) and serratus anterior (SA)) was registered. A high speed camera tracked start and end of the back and forth movement. Mean scapular EMG activity during the 10 exercises ranged from 14.50% to 76.26%MVC for UT, from 15.19% to 96.55%MVC for MT, from 13.18% to 94.35%MVC for LT and from 13.50% to 98.50%MVC for SA. Anova for repeated measures showed significant differences in scapular muscle activity between exercises (p<0.001) and between the back and forth movement (p<0.001) within exercises. Plyometric shoulder exercises require moderate (31-60%MVC) to high (>60%MVC) scapular muscle activity. Highest MT/LT activity was present in prone plyometric external rotation and flexion. Highest SA activity was found in plyometric external rotation and flexion with Xco and plyometric push up on Bosu. Specific exercises can be selected that recruit minimal levels of UT activity (<15%): side lying plyometric external rotation and horizontal abduction or plyometric push up on the Bosu. The results of this study support exercise selection for clinical practice. Copyright © 2016 Elsevier Ltd. All rights reserved.

Is sexual reproduction of high-mountain plants endangered by heat?

PubMed

Ladinig, Ursula; Pramsohler, Manuel; Bauer, Ines; Zimmermann, Sonja; Neuner, Gilbert; Wagner, Johanna

2015-04-01

Strong solar irradiation in combination with still air and dry soil can cause prostrate high-mountain plants to heat up considerably and ultimately suffer heat damage. Such heat damage has been repeatedly shown for vegetative structures, but not for reproductive structures, which we expected to be particularly vulnerable to heat. Heat effects on cold-adapted plants may increase with rising global temperatures and the predicted increase in heat waves. We have tested the heat tolerance of reproductive versus vegetative shoots at different reproductive stages, comparing ten common plant species from different elevation belts in the European Alps. Plant samples were exposed to temperatures in 2-K steps of 30 min each between 42 and 56 °C. Heat damage was assessed by visual rating and vital staining. Reproductive shoots were on average 2.5 K less heat tolerant (LT50, i.e. the mean temperature causing 50 % heat damage, 47.2 °C) than vegetative shoots (mean LT50 49.7 °C). Initial heat injuries (mean LT10) were observed at 43-45 °C in heat-susceptible species and at 45-47 °C in more heat-tolerant species, in at least one reproductive stage. Generally, heat tolerance was significantly higher during fruiting than during the bud stages and anthesis. Prostrate species with acaulescent buds and flowers tolerated heat better than those with caulescent buds and flowers. Petals were the most heat-susceptible plant structure and mature pollen the most heat tolerant. Based on these data, heat tolerance of reproductive structures appears to be adapted to the prevailing maximum temperatures which the plants experience during different reproductive stages in their environment. During hot spells, however, heat tolerance thresholds may be exceeded. More frequent heat waves would decrease the reproductive output and, consequently, the competitiveness of heat-susceptible species.

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

Herkovits, J.; Herkovits, F.D.; Fernandez, A.

The identification of mercurium hazard for Cnesterodon decemmaculatus and Bufo arenarum (embryos) was evaluated in a renewal toxicity test system at 20 C and informed as LC100, LC50 and NOEC for 24 and up till 96 hours of exposure (acute Toxicity Profile -- TPa -- for mercurium). On addition the beneficial effect of zinc against the lethal effect of mercurium is reported. The test with fish were conducted maintaining 10 individuals in 1 L of EPA water (by quadruplicate) in six concentrations of Hg plus controls, while for amphibian, batches of 10 Bufo arenarum embryos at stage 25 (by quadruplicate)more » were maintained in 40 ml of Holtfreter`s solution in six concentration of Hg + (HgCl) plus controls. The LC100, LC50 and NOEC for fishes expressed in Hg (+) mg/L were: 0.60, 0.25 and 0.10 for 24 hours of exposure. These values increased very slightly at least up till 96 hours of exposure. Therefore, Bufo arenarum seems to be about three times more sensitive than Cnesterodon decemmaculatus to mercurium. By means of simultaneous mercurium-zinc treatment (ZnSO4) the lethal effect of mercurium could be reduced in amphibians up till 100% with 18 mg Zn2+/L, while for the fish the best result obtained was a reduction of about 50% of lethality within the first 96 hours of treatment with 20 mg Zn2+/L. As a whole the results point out the high susceptibility of amphibian embryos to xenobiotics, the beneficial effect of zinc against embryos to xenobiotics, the beneficial effect of zinc against toxicity exerted by Hg and the need of biological test systems for recording the combined effects of substances released to the environment.« less

Comparative sensitivity of the cnidarian Exaiptasia pallida and a standard toxicity test suite: testing whole effluents intended for ocean disposal.

PubMed

Howe, P L; Reichelt-Brushett, A J; Krassoi, R; Micevska, T

2015-09-01

The sea anemone Exaiptasia pallida (formally Aiptasia pulchella) has been identified as a valuable test species for tropical marine ecotoxicology. Here, the sensitivities of newly developed endpoints for E. pallida to two unidentified whole effluents were compared to a standard suite of temperate toxicity test species and endpoints that are commonly used in toxicological risk assessments for tropical marine environments. For whole effluent 1 (WE1), a 96-h lethal concentration 50 % (LC50) of 40 (95 % confidence intervals, 30-54) % v/v and a 12-day LC50 of 12 (9-15) % v/v were estimated for E. pallida, exhibiting a significantly higher sensitivity than standard sub-lethal endpoints in Allorchestes compressa (96-h effective concentration 50 % (EC50) of >100 % v/v for immobilisation) and Hormosira banksii (72-h EC50 of >100 % v/v for germination), and a similar sensitivity to Mytilus edulis galloprovincialis larval development with a 48-h LC50 of 29 (28-30) % v/v. Sub-lethal effects of whole effluent 2 (WE2) on E. pallida pedal lacerate development resulted in an 8-day EC50 of 7 (3-11) % v/v, demonstrating comparable sensitivity of this endpoint to standardised sub-lethal endpoints in H. banksii (72-h EC50 of 11 (10-11) % v/v for germination), M. edulis galloprovincialis (48-h EC50 for larval development of 12 (9-14) % v/v) and Heliocidaris tuberculata (1-h EC50 of 13 (12-14) % v/v for fertilisation; 72-h EC50 of 26 (25-27) % v/v for larval development) and a significantly higher sensitivity than A. compressa immobilisation (96-h EC50 of >100 % v/v). The sensitivity of E. pallida compared to a standard test species suite highlights the value in standardising the newly developed toxicity test methods for inclusion in routine toxicological risk assessment of complex whole effluents. Importantly, this species provides an additional taxonomic group to the test species that are currently available for tropical marine ecotoxicology and, being a cnidarian, may represent important tropical marine environments including coral reefs.

Liquid L-thyroxine versus tablet L-thyroxine in patients on L- thyroxine replacement or suppressive therapy: a meta-analysis.

PubMed

Laurent, Irakoze; Tang, Siying; Astère, Manirakiza; Wang, Kan Ran; Deng, Shuhua; Xiao, Ling; Li, Qi Fu

2018-03-23

To compare the effectiveness of liquid L-T4 (L-thyroxine) and tablet L-T4 in patients on L-T4 replacement or suppressive therapy. The Cochrane Library, PubMed, Embase, and Web of Science databases were searched to identify relevant articles. All prospective or randomized controlled studies (RCTs) comparing liquid L-T4 and tablet L-T4 in patients on L-T4 replacement or suppressive therapy were included in the analysis. Overall, the initial search of the four databases identified 1278 published studies; of these, eight studies were ultimately included in the meta-analysis. TSH (thyroid stimulating hormone) levels were significantly suppressed in patients on liquid L-T4 compared with those on tablet L-T4, in patients on L-T4 suppressive therapy with L-T4 malabsorption (Mean Difference (MD) = -2.26, 95% Confidence Interval (CI): -3.59, -0.93; P = 0.0009)). However, liquid L-T4 and tablet L-T4 did not show a statistically significant difference in patients on L-T4 suppressive therapy without malabsorption (MD = 0.08, 95% CI: -0.31, 0.47; P = 0.69). TSH levels were significantly normalized in patients on liquid L-T4 compared with those on tablet L-T4, in Patients on L-T4 replacement therapy with L-T4 malabsorption (MD = -3.20, 95% CI: -5.08, -1.32; P = 0.0009). However, liquid L-T4 and tablet L-T4 did not show a statistically significant difference in patients on L-T4 replacement therapy without malabsorption (MD = 0.91, 95% CI: -0.03, 1.86; P = 0.06). Liquid L-T4 is more efficient than tablet L-T4 in patients on L-T4 replacement or suppressive therapy with malabsorption. No significant differences were observed in patients without malabsorption. Further studies should be conducted to verify these findings.

Physical-Chemical Basis of the Protection of Slowly Frozen Human Erythrocytes by Glycerol

PubMed Central

Rall, W. F.; Mazur, Peter; Souzu, Hiroshi

1978-01-01

One theory of freezing damage suggests that slowly cooled cells are killed by being exposed to increasing concentrations of electrolytes as the suspending medium freezes. A corollary to this view is that protective additives such as glycerol protect cells by acting colligatively to reduce the electrolyte concentration at any subzero temperature. Recently published phase-diagram data for the ternary system glycerol-NaCl-water by M. L. Shepard et al. (Cryobiology, 13:9-23, 1976), in combination with the data on human red cell survival vs. subzero temperature presented here and in the companion study of Souzu and Mazur (Biophys. J., 23:89-100), permit a precise test of this theory. Appropriate liquidus phase-diagram information for the solutions used in the red cell freezing experiments was obtained by interpolation of the liquidus data of Shepard and his co-workers. The results of phase-diagram analysis of red cell survival indicate that the correlation between the temperature that yields 50% hemolysis (LT50) and the electrolyte concentration attained at that temperature in various concentrations of glycerol is poor. With increasing concentrations of glycerol, the cells were killed at progressively lower concentrations of NaCl. For example, the LT50 for cells frozen in the absence of glycerol corresponds to a NaCl concentration of 12 weight percent (2.4 molal), while for cells frozen in 1.75 M glycerol in buffered saline the LT50 corresponds to 3.0 weight percent NaCl (1.3 molal). The data, in combination with other findings, lead to two conclusions: (a) The protection from glycerol is due to its colligative ability to reduce the concentration of sodium chloride in the external medium, but (b) the protection is less than that expected from colligative effects; apparently glycerol itself can also be a source of damage, probably because it renders the red cells susceptible to osmotic shock during thawing. PMID:667300

Acute Variceal Bleeding: Does Octreotide Improve Outcomes in Patients with Different Functional Hepatic Reserve?

PubMed

Monreal-Robles, Roberto; Cortez-Hernández, Carlos A; González-González, José A; Abraldes, Juan G; Bosques-Padilla, Francisco J; Silva-Ramos, Héctor N; García-Flores, Jorge A; Maldonado-Garza, Héctor J

2018-01-01

Current guidelines do not differentiate in the utilization of vasoactive drugs in patients with cirrhosis and acute variceal bleeding (AVB) depending on liver disease severity. In this retrospective study, clinical outcomes in 100 patients receiving octreotide plus endoscopic therapy (ET) and 216 patients with ET alone were compared in terms of failure to control bleeding, in-hospital mortality, and transfusion requirements stratifying the results according to liver disease severity by Child-Pugh (CP) score and MELD. In patients with CP-A or those with MELD < 10 octreotide was not associated with a better outcome compared to ET alone in terms of hospital mortality (CP-A: 0.0 vs. 0.0%; MELD < 10: 0.0 vs. 2.9%, p = 1.00), failure to control bleeding (CP-A: 8.7 vs. 3.7%, p = 0.58; MELD < 10: 5.3 vs. 4.3%, p = 1.00) and need for transfusion (CP-A: 39.1 vs. 61.1%, p = 0.09; MELD < 10: 63.2 vs. 62.9%, p = 1.00). Those with severe liver dysfunction in the octreotide group showed better outcomes compared to the non-octreotide group in terms of hospital mortality (CP-B/C: 3.9 vs. 13.0%, p = 0.04; MELD ≥ 10: 3.9 vs. 13.3%, p = 0.03) and need for transfusion (CP-B/C: 58.4 vs. 71.6%, p = 0.05; MELD ≥ 10: 50.6 vs. 72.7%, p < 0.01). In multivariate analysis, octreotide was independently associated with in-hospital mortality (p = 0.028) and need for transfusion (p = 0.008) only in patients with severe liver dysfunction (CP-B/C or MELD ≥ 10). Patients with cirrhosis and AVB categorized as CP-A or MELD < 10 had similar clinical outcomes during hospitalization whether or not they received octreotide.

Stable High-Performance Perovskite Solar Cells Based on Inorganic Electron Transporting Bi-layers.

PubMed

Gu, Hao; Zhao, Chen; Zhang, Yiqiang; Shao, Guosheng

2018-06-27

As one of the significant electron transporting materials (ETM) in efficient planar heterojunction perovskite solar cells (PSCs), SnO₂ can collect/transfer photo-generated carriers produced in perovskite active absorbers and suppress the carrier recombination at interfaces. In this study, we demonstrate that mild solution-processed SnO₂ compact layer can be an eminent ETM for planar heterojunction PSCs. Here, the device based on chemical-bath-deposited SnO₂ electron transporting layer (ETL) exhibits a power conversion efficiency (PCE) of 16.10% and with obvious hysteresis effect (hysteresis index=19.5%), owing to the accumulation and recombination of charge carriers at SnO₂/perovskite interface. In order to improve the carrier dissociation and transport process, an ultrathin TiO₂ film was deposited on the top of SnO₂ ETL passivating nonradiative recombination center. The corresponding device based on TiO₂@SnO₂ electron transporting bi-layer (ETBL) exhibited a high PCE (17.45%) and a negligible hysteresis effect (hysteresis index=1.5%). These findings indicate that this facile solution-processed TiO₂@SnO₂ ETBL paves a scalable and inexpensive way for fabricating hysteresis-less and high-performance PSCs. © 2018 IOP Publishing Ltd.

The use of synthetic and natural vitamin D sources in pig diets to improve meat quality and vitamin D content.

PubMed

Duffy, Sarah K; Kelly, Alan K; Rajauria, Gaurav; Jakobsen, Jette; Clarke, Louise C; Monahan, Frank J; Dowling, Kirsten G; Hull, George; Galvin, Karen; Cashman, Kevin D; Hayes, Aoife; O'Doherty, John V

2018-09-01

This study investigated the effects of synthetic and natural sources of vitamin D biofortification in pig diets on pork vitamin D activity and pork quality. One hundred and twenty pigs (60 male, 60 female) were assigned to one of four dietary treatments for a 55 d feeding period. The dietary treatments were (1)50 μg vitamin D₃/kg of feed; (2)50 μg of 25-hydroxvitamin D₃/kg of feed (25-OH-D₃); (3)50 μg vitamin D₂/kg of feed; (4)50 μg vitamin D₂-enriched mushrooms/kg of feed (Mushroom D₂). The pigs offered the 25-OH-D₃ diet exhibited the highest (P < 0.001) serum total 25-hydroxyvitamin D concentration and subsequently exhibited the highest (P < 0.05) Longissimus thoracis (LT) total vitamin D activity. Mushroom D 2 and 25-OH-D 3 supplementation increased pork antioxidant status. The vitamin D₂-enriched mushrooms improved (P < 0.05) pig performance, carcass weight and LT colour. In conclusion, 25-OH-D₃ is the most successful source for increasing pork vitamin D activity, while Mushroom D 2 may be a new avenue to improve animal performance and pork quality. Copyright © 2018 Elsevier Ltd. All rights reserved.

Toxicity and mutagenicity of hymenoxon, sequiterpene lactone.

PubMed

Jones, D H; Kim, H L

1981-12-01

The oral LD50 of hymenoxon in Swiss white mice was found to be 241 +/- 37 mg/kg. No significant sex differences were observed. Pretreatment of male mice for 3 days using doses of 50 and 100 mg/kg hymenoxon failed to alter significantly pentobarbital sleeping time. Hymenoxon was found to be a direct-acting mutagen in the Salmonella/mammalian microsome test. Urine samples obtained from hymenoxon-treated mice were found to be negative activity when tested directly and when incubated with beta-glucuronidase. Hymenoxon did not produce lethal DNA damage as measured in the Escherichia coli polA or Bacillus subtilis recombinational assays.

Characterization and Demonstration of the Value of a Lethal Mouse Model of Middle East Respiratory Syndrome Coronavirus Infection and Disease.

PubMed

Tao, Xinrong; Garron, Tania; Agrawal, Anurodh Shankar; Algaissi, Abdullah; Peng, Bi-Hung; Wakamiya, Maki; Chan, Teh-Sheng; Lu, Lu; Du, Lanying; Jiang, Shibo; Couch, Robert B; Tseng, Chien-Te K

2016-01-01

Characterized animal models are needed for studying the pathogenesis of and evaluating medical countermeasures for persisting Middle East respiratory syndrome-coronavirus (MERS-CoV) infections. Here, we further characterized a lethal transgenic mouse model of MERS-CoV infection and disease that globally expresses human CD26 (hCD26)/DPP4. The 50% infectious dose (ID50) and lethal dose (LD50) of virus were estimated to be <1 and 10 TCID50 of MERS-CoV, respectively. Neutralizing antibody developed in the surviving mice from the ID50/LD50 determinations, and all were fully immune to challenge with 100 LD50 of MERS-CoV. The tissue distribution and histopathology in mice challenged with a potential working dose of 10 LD50 of MERS-CoV were subsequently evaluated. In contrast to the overwhelming infection seen in the mice challenged with 10(5) LD50 of MERS-CoV, we were able to recover infectious virus from these mice only infrequently, although quantitative reverse transcription-PCR (qRT-PCR) tests indicated early and persistent lung infection and delayed occurrence of brain infection. Persistent inflammatory infiltrates were seen in the lungs and brain stems at day 2 and day 6 after infection, respectively. While focal infiltrates were also noted in the liver, definite pathology was not seen in other tissues. Finally, using a receptor binding domain protein vaccine and a MERS-CoV fusion inhibitor, we demonstrated the value of this model for evaluating vaccines and antivirals against MERS. As outcomes of MERS-CoV infection in patients differ greatly, ranging from asymptomatic to overwhelming disease and death, having available both an infection model and a lethal model makes this transgenic mouse model relevant for advancing MERS research. Fully characterized animal models are essential for studying pathogenesis and for preclinical screening of vaccines and drugs against MERS-CoV infection and disease. When given a high dose of MERS-CoV, our transgenic mice expressing hCD26/DPP4 viral receptor uniformly succumbed to death within 6 days, making it difficult to evaluate host responses to infection and disease. We further characterized this model by determining both the ID50 and the LD50 of MERS-CoV in order to establish both an infection model and a lethal model for MERS and followed this by investigating the antibody responses and immunity of the mice that survived MERS-CoV infection. Using the estimated LD50 and ID50 data, we dissected the kinetics of viral tissue distribution and pathology in mice challenged with 10 LD50 of virus and utilized the model for preclinical evaluation of a vaccine and drug for treatment of MERS-CoV infection. This further-characterized transgenic mouse model will be useful for advancing MERS research. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Double Versus Single Tendon Transfers to Improve Shoulder Function in Brachial Plexus Birth Palsy.

PubMed

Greenhill, Dustin A; Smith, William R; Ramsey, F V; Kozin, Scott H; Zlotolow, Dan A

2017-03-27

In children with brachial plexus birth palsy (BPBP) undergoing tendon transfers to augment shoulder external rotation, it is unclear whether transfer of the latissimus dorsi with its combined latissimus dorsi and teres major (cLT) versus isolated teres major (iTM) tendon transfer yield different outcomes. Records of patients with BPBP who underwent shoulder tendon transfers to augment external rotation were retrospectively reviewed. Transfer type (cLT or iTM) was considered indiscriminate by virtue of surgeon preference. Modified Mallet Scale (mMS) and Active Movement Scale scores were recorded. Patients with <12 months' follow-up, C7 or lower palsy, humeral osteotomy, shoulder procedure(s) within 8 months, microsurgery within 1 year, or recurrent glenohumeral subluxation confirmed by postoperative imaging were excluded. Matched cohorts were identified within each tendon transfer group to yield similar preoperative shoulder function and glenohumeral alignment status. Outcomes for all tendon transfers as well as differences between cLT and iTM cohorts were analyzed. Among 121 cLT and 34 iTM transfers, 49 cLT and 14 iTM met the inclusion criteria. Subsequent matching of cohorts yielded 28 patients (14 cLT and 14 iTM). Average age at time of transfer was 3.0±1.4 years. Follow-up averaged 4.1±3.1 years. There were no statistically significant preoperative differences between cohorts, thus matching criteria were validated. Regardless of tendon(s) transferred, mMS external rotation improved (2.2 to 3.5, P<0.001), whereas mMS internal rotation decreased (3.8 to 3.2, P<0.001). When comparing matched cohorts, cLT transfer produced a greater mMS external rotation improvement than iTM (2.1 vs. 1.5, respectively; P=0.025). Loss of midline function (defined as mMS external rotation <3) occurred in 5 (35.7%) cLT and 2 (14.3%) iTM patients. Both cLT or iTM transfer are effective at augmenting shoulder external rotation in children with C5-C6 BPBP. Furthermore, cLT transfers may yield a larger improvement in external rotation in certain patients. However, both techniques slightly decrease shoulder internal rotation. Given that more total cLT patients lost midline function among matched cohorts, iTM transfer may still be considered when limited midline function is a concern. Level III.

Determination of the median lethal dose of botulinum serotype E in channel catfish fingerlings

USDA-ARS?s Scientific Manuscript database

The median lethal dose of botulinum serotype E in 5.3-g channel catfish Ictalurus punctatus fingerlings was determined. Five tanks (five fish/tank) were assigned to each of the following treatment groups: 70, 50, 35, 25, or 15 pg of purified botulinum serotype E. Fish were injected intracoelomically...

Effect of treatment with interferon-gamma and concanavalin A on the course of infection of mice with Salmonella typhimurium strain LT-2

NASA Technical Reports Server (NTRS)

Gould, Cheryl L.; Sonnenfeld, Gerald

1987-01-01

The effect of pretreatment of mice with 34 units/day, for five days, of interferon-gamma (IFN-gamma) on the course of infection with LD50 of Salmonella typhimurium strain LT-2 was assessed, using two IFN preparations: (1) a hybridoma supernatant fluid containing concanavalin-A-induced IFN-gamma activity and (2) pure murine IFN-gamma produced by recombinant DNA technology. The hybridoma supernatant-treated Salmonella-infected mice were found to die faster than mice treated only with Salmonella. Pure murine IFN-gamma was found to protect infected mice significantly, with 95 percent of mice surviving LD50 infection. In contrast, the Salmonella-infected mice treated with hybridoma supernatant were found to die faster than the Salmonella-infected untreated controls. Mice treated with concanavalin A alone prior to infection with S. typhimurium died more quickly than the untreated infected controls, suggesting that contamination with concanavalin A had a detrimental effect on mice survival.

Toxicity and fate of two munitions constituents in spiked sediment exposures with the marine amphipod Eohaustorius estuarius.

PubMed

Rosen, Gunther; Lotufo, Guilherme R

2005-11-01

The lethal toxicity of the explosive compounds 14C-labeled 2,4,6-trinitrotoluene (TNT) and nonradiolabeled hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) to the estuarine amphipod Eohaustorius estuarius was investigated in 10-d spiked sediment exposures. The 10-d median lethal concentration (LC50) was determined using the sum molar initial concentration of TNT, aminodinitrotoluenes (ADNTs), and diaminonitrotoluenes (DANTs), as determined by high-performance liquid chromatography (HPLC), and collectively referred to as HPLC-TNT*. Despite expectations of higher toxicity in sandy sediment (Yaquina Bay [YB], OR, USA) compared to relatively fine-grained sediment (San Diego Bay [SDB], CA, USA), LC50 values were similar: 159 and 125 micromol/kg, for YB and SDB sediments, respectively. When expressed as the sum of TNT and all its degradation products (14C-TNT*), LC50s were approximately two times the corresponding LC50s determined by HPLC. The HPLC-TNT* fraction likely corresponds to the most bioavailable and toxic transformation products. The concentrations of 14C-TNT* in tissues were substantially higher than those for HPLC-TNT*, suggesting that compounds other than TNT and its major aminated transformation products were prevalent. Critical body residues were similar for exposures to SDB (11.7 micromol/kg) and YB sediments (39.4 micromol/kg), despite marked differences in the nature of compounds available for uptake in the exposure media. The critical body residues for E. estuarius are lower than those reported for other aquatic invertebrates (83-172 micromol/kg). Unlike observations for TNT, RDX was only loosely associated with SDB sediment, with near complete recovery of the parent compound by chemical analysis. Exposure to RDX did not result in significant mortality even at the highest measured sediment concentration of 10,800 micromol/kg dry weight, nor tissue concentrations as high as 96 micromol/kg wet weight. The lack of RDX lethal effects in this study is consistent with results reported for other invertebrate species.

Impact of acute alcohol consumption on lethality of suicide methods.

PubMed

Park, C Hyung Keun; Yoo, Seong Ho; Lee, Jaewon; Cho, Sung Joon; Shin, Min-Sup; Kim, Eun Young; Kim, Se Hyun; Ham, Keunsoo; Ahn, Yong Min

2017-05-01

The influence of acute alcohol consumption on the factors related to suicide remains understudied. Thus, the present study investigated the relationship between blood alcohol content (BAC) and the lethality of suicide methods. Autopsy data on 315 South Korean suicide completers with a positive BAC were collected from a nationwide pool between May 2015 and November 2015, and the methods were dichotomised as suicide methods of low lethality (SMLL; drug/chemical overdose and sharp objects, n=67) and suicide methods of high lethality (SMHL; everything else, n=243). BAC at the time of autopsy and various suicide-related factors of these two groups were compared with logistic regression analyses. Compared to suicide completers with a BAC in the lowest range of 0.011-0.049%, suicide completers with a BAC in the range of 0.150-0.199% were more likely to use SMHL (odds ratio [OR]: 3.644, 95% confidence interval [CI]: 1.221-10.874). Additionally, the adoption of SMHL was significantly associated with the absence of a psychiatric illness (OR: 0.433, 95% CI: 0.222-0.843) and a younger age; the OR for high BAC among subjects in their 40s was 0.266 (95% CI: 0.083-0.856); in their 50s, 0.183 (95% CI: 0.055-0.615); and in their 60s, 0.057 (95% CI: 0.015-0.216). The relationship between BAC and suicide method lethality was represented by a bell-shaped pattern in which suicide methods of high lethality were more likely to be used by suicide completers with mid-range BAC levels. The increased impulsivity and impairments in particular executive functions, including planning and organization, associated with acute alcohol use may influence the selection of a particular suicide method based on its lethality. Copyright © 2017 Elsevier Inc. All rights reserved.

Evaluation of limiting factors affecting photovoltaic performance of low-temperature-processed TiO₂ films in dye-sensitized solar cells.

PubMed

Lee, Taek-Yong; Kim, Hui-Seon; Park, Nam-Gyu

2014-04-14

Limiting factors affecting photovoltaic performance of dye-sensitized solar cell employing low-temperature-processed TiO2 films were investigated. TiO2 films were prepared at a low temperature of 200 °C using the normal alcohol-containing binder-free TiO2 paste (LT200). Their photovoltaic performance was compared to a high-temperature (550 °C) annealed TiO2 film prepared using a polymer binder containing TiO2 paste (HT550). Compared to the proportional increase in conversion efficiency with TiO2 film thickness upto 14 μm for HT550, the increase in efficiency was terminated at relatively smaller thickness of about 8 μm for LT200 mainly due to unaugmented photocurrent. From the transient photocurrent-voltage studies, the electron transport rate was found to be almost identical, while charge recombination was one order of magnitude faster for LT200. Consequently, the electron diffusion length was more than 2-3 times shorter for LT200 than for HT550. Electron diffusion length and electron life time obtained from electrochemical impedance analysis were well consistent with those observed from transient measurement. Density of states (DOS) was evaluated to be shallow and narrow in LT200, which was responsible for limiting photovoltaic performance in the low-temperature processed TiO2 film. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Toxicity and motor changes in Africanized honey bees (Apis mellifera L.) exposed to fipronil and imidacloprid.

PubMed

Bovi, Thaís S; Zaluski, Rodrigo; Orsi, Ricardo O

2018-01-01

This study evaluated the in vitro toxicity and motor activity changes in African-derived adult honey bees (Apis mellifera L.) exposed to lethal or sublethal doses of the insecticides fipronil and imidacloprid. Mortality of bees was assessed to determine the ingestion and contact lethal dose for 24 h using probit analysis. Motor activities in bees exposed to lethal (LD50) and sublethal doses (1/500th of the lethal dose) of both insecticides were evaluated in a behavioral observation box at 1 and 4 h. Ingestion and contact lethal doses of fipronil were 0.2316 ? 0.0626 and 0.0080 ? 0.0021 μg/bee, respectively. Ingestion and contact lethal doses of imidacloprid were 0.1079 ? 0.0375 and 0.0308 ? 0.0218 μg/bee, respectively. Motor function of bees exposed to lethal doses of fipronil and imidacloprid was impaired; exposure to sublethal doses of fipronil but not imidacloprid impaired motor function. The insecticides evaluated in this study were highly toxic to African-derived A. mellifera and caused impaired motor function in these pollinators.

Acute toxicity of 353-nonylphenol and its metabolites for zebrafish embryos.

PubMed

Kammann, Ulrike; Vobach, Michael; Wosniok, Werner; Schäffer, Andreas; Telscher, Andreas

2009-03-01

Nonylphenol (NP) can be detected in the aquatic environment all over the world. It is applied as a technical mixture of isomers of which 353-NP is the most relevant both in terms of abundance (about 20% of total mass) and endocrine potential. 353-NP is metabolised in sewage sludge. The aims of the present study were to determine and to compare the acute toxicity of t-NP, 353-NP and its metabolites as well as to discuss if the toxicity of 353-NP changes during degradation. 353-NP and two of its metabolites were synthesised. The zebrafish embryo test was performed according to standard protocols. Several lethal and non-lethal endpoints during embryonal development were reported. NOEL, LOEL and EC50 were calculated. All tested compounds caused lethal as well as non-lethal malformations during embryo development. 353-NP showed a higher toxicity (EC50 for lethal endpoints 6.7 mg/L) compared to its metabolites 4-(3.5-dimethyl-3-heptyl)-2-nitrophenol (EC50 13.3 mg/L) and 4-(3,5-dimethyl-3-heptyl)-2-bromophenol (EC50 27.1 mg/L). In surface water, concentrations of NP are far below the NOEC identified by the zebrafish embryo test. However, in soils and sewage sludge, concentrations may reach or even exceed these concentrations. Therefore, sludge-treated sites close to surface waters should be analysed for NP and its metabolites in order to detect an unduly high contamination due to runoff events. The results of the present study point out that the toxicity of 353-NP probably declines during metabolisation in water, sediment and soil, but does not vanish since the major metabolites exhibit a clear toxic potential for zebrafish embryos. Metabolites of environmental pollutants should be included in the ecotoxicological test strategy for a proper risk assessment.

Feedbacks Between Deformation and Fluid Flow in Mantle Shear Zones from Zabargad, Red Sea

NASA Astrophysics Data System (ADS)

Tommasi, A.; Boudier, F. I.; Vauchez, A. R.; Zaderatzky, M.

2016-12-01

Peridotites in the Zabargad island, Red Sea, record different stages of lithospheric thinning and asthenospheric upwelling during rifting. Field mapping highlights a pervasive high-temperature NW-SE, subvertical foliation with lineations pluning 50°NW. This foliation is overprinted by a series of lower-temperature mylonitic zones with slightly oblique foliations and subhorizontal lineations, which record progressive strain localization under retrogressive conditions during the final exhumation of the peridotites (Nicolas and Boudier, JGR 1987). We performed a petrostructural study of ca. 50 samples collected by A. Nicolas and F. Boudier in the 80s from the different deformation facies. This study highlights: (1) a rather pervasive, but highly heterogeneous distribution of the LT deformation and (2) a feedback between deformation and fluid flow. The HT deformation is recorded in medium grained plagioclase- and spinel-peridotites by a homogeneous foliation and lineation marked by a shape-preferred orientation of plagioclase and olivine and a consistent CPO of all major-rock forming phases. The LT temperature deformation results in dynamic recrystallization of olivine leading to a marked grain size reduction by dynamic recrystallization of olivine, remobilization of orthopyroxene by dissolution-precipitation, and crystallization of amphibole. Increasing finite strain is recorded by the increase in the volume of the fine-grained material and of the amphibole proportion. The latter may attain in totally recrystallized cm-wide ultramylonite bands up to 30%. This together with the strong amphibole SPO and CPO corroborate fluid focusing and enhanced reaction rates into active shear zones. In the LT shear zones we also document: (1) changes in the olivine CPO, indicating changes in the dominant slip system and (2) unusual orthopyroxene CPO, which we interpret as due to oriented crystallization. Static replacement of pyroxenes by amphibole with no associated LT deformation is also observed indicating that the presence of fluids does not suffice to trigger strain localization.

Population biology of an endangered species: the common guitarfish Rhinobatos rhinobatos in Lebanese marine waters of the eastern Mediterranean Sea.

PubMed

Lteif, M; Mouawad, R; Khalaf, G; Lenfant, P; Verdoit-Jarraya, M

2016-04-01

This study focuses on the population biology of the common guitarfish Rhinobatos rhinobatos, a cartilaginous fish listed as Endangered in the International Union for the Conservation of Nature (IUCN) Red List. Between December 2012 and January 2014, 67 individuals were collected by bottom longlining in coastal Lebanese marine waters at different ports at depths ranging from 10 to 110 m. The total length (L(T)) of the specimens ranged from 50 to 143 cm, and the mean ± s.d. was 76.2 ± 19.7 cm. The most common L(T) classes were between 60 and 70 cm. The total mass of the specimens ranged from 410 to 10,000 g, and the mean ± s.d. was 1841 ± 1987 g. A total of 34 males and 33 females were collected, and the sex ratio was not significantly different from 1:1. The mass and L(T) relationship showed positive allometric growth (b = 3.096 and r(2)  = 0.99), and the mean ± s.d. L(T) at which 50% of the individuals were sexually mature was 84.73 ± 5.81 cm for females and 78.57 ± 4.88 cm for males. The gonado-somatic and hepato-somatic indices were determined along with a condition factor, and parturition appeared to occur in winter. The primary prey items found in the fish stomachs during the autumn and winter seasons were Penaeidae. The results of this study will help to parameterize models of the population dynamics for this exploited fish stock to ensure the long-term sustainability of its fishery. © 2016 The Fisheries Society of the British Isles.

Analysis of the temporal-spatial distribution of ionosphere scale height based on COSMIC occultation data

NASA Astrophysics Data System (ADS)

Ma, Xin-Xin; Lin, Zhan; Jin, Hong-Lin; Chen, Hua-Ran; Jiao, Li-Guo

2017-11-01

In this study, the distribution characteristics of scale height at various solar activity levels were statistically analyzed using the Constellation Observing System for Meteorology, Ionosphere, and Climate (COSMIC) radio occultation data for 2007-2013. The results show that: (1) in the mid-high latitude region, the daytime (06-17LT) scale height exhibits annual variations in the form of a single peak structure with the crest appearing in summer. At the high latitude region, an annual variation is also observed for nighttime (18-05LT) scale height; (2) changes in the spatial distribution of the scale height occur. The crests are deflected towards the north during daytime (12-14LT) at a geomagnetic longitude of 60°W-180°W, and they are distributed roughly along the geomagnetic equator at 60°W-180°E. In the approximate region of 120°W-150°E and 50°S-80°S, the scale height values are significantly higher than those in other mid-latitude areas. This region enlarges with increased solar activity, and shows an approximately symmetric distribution about 0° geomagnetic longitude. Nighttime (00-02LT) scale height values in the high-latitude region are larger than those in the low-mid latitude region. These results could serve as reference for the study of ionosphere distribution and construction of the corresponding profile model.

Measurement of the interference structure function R{sub LT} for the {sup 12}C(e,e{sup {prime}}p) reaction in the quasielastic region

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

Holtrop, M.; Jordan, D.; McIlvain, T.

1998-12-01

The coincidence cross section and the interference structure function, R{sub LT}, were measured for the {sup 12}C(e,e{sup {prime}}p)thinsp{sup 11}B reaction at quasielastic kinematics and central momentum transfer of {vert_bar}{rvec q}{vert_bar}=400thinspMeV/c. The measurement was at an opening angle of {theta}{sub pq}=11{degree}, covering a range in missing energy of E{sub m}=0 to 65 MeV. The R{sub LT} structure function is found to be consistent with zero for E{sub m}{gt}50thinspMeV, confirming an earlier study which indicated that R{sub L} vanishes in this region. The integrated strengths of the p- and s-shell are compared with a distorted wave impulse approximation (DWIA) calculation. The s-shellmore » strength and shape are also compared with a Hartree Fock{endash}random phase approximation (HF-RPA) calculation. The DWIA calculation does not succeed in giving a consistent description of both the cross section data and the extracted R{sub LT} response for either shell. The HF-RPA calculation describes the data more consistently, which may be due to the inclusion of 2-body currents in this calculation. {copyright} {ital 1998} {ital The American Physical Society}« less

Sewage sludge amendment and inoculation with plant-parasitic nematodes do not facilitate the internalization of Salmonella Typhimurium LT2 in lettuce plants.

PubMed

Fornefeld, Eva; Baklawa, Mohamed; Hallmann, Johannes; Schikora, Adam; Smalla, Kornelia

2018-05-01

Contamination of fruits and vegetables with Salmonella is a serious threat to human health. In order to prevent possible contaminations of fresh produce it is necessary to identify the contributing ecological factors. In this study we investigated whether the addition of sewage sludge or the presence of plant-parasitic nematodes foster the internalization of Salmonella enterica serovar Typhimurium LT2 into lettuce plants, posing a potential threat for human health. Greenhouse experiments were conducted to investigate whether the amendment of sewage sludge to soil or the presence of plant-parasitic nematodes Meloidogyne hapla or Pratylenchus crenatus promote the internalization of S. Typhimurium LT2 from soil into the edible part of lettuce plants. Unexpectedly, numbers of cultivable S. Typhimurium LT2 decreased faster in soil with sewage sludge than in control soil but not in root samples. Denaturing gradient gel electrophoresis analysis revealed shifts of the soil bacterial communities in response to sewage sludge amendment and time. Infection and proliferation of nematodes inside plant roots were observed but did not influence the number of cultivable S. Typhimurium LT2 in the root samples or in soil. S. Typhimurium LT2 was not detected in the leaf samples 21 and 49 days after inoculation. The results indicate that addition of sewage sludge, M. hapla or P. crenatus to soil inoculated with S. Typhimurium LT2 did not result in an improved survival in soil or internalization of lettuce plants. Copyright © 2017. Published by Elsevier Ltd.

Characteristics and Outcomes of Neutropenia after Orthotopic Liver Transplantation

PubMed Central

Alraddadi, B; Nierenberg, NE; Price, LL; Chow, JKL; Poutsiaka, DD; Rohrer, RJ; Cooper, JT; Freeman, RB; Snydman, DR

2015-01-01

Neutropenia after orthotopic liver transplantation (LT) is relatively common but the factors associated with its development remain elusive. We assessed possible predictors of neutropenia (absolute neutrophil count [ANC] less than or equal to 1000/mm3) within the first year of LT in a cohort of 304 patients at a tertiary medical center between 1999 and 2009 using time-dependent survival analysis to identify risk factors for neutropenia. In addition, we analyzed neutropenia as a predictor of the clinical outcomes of death, blood stream infection (BSI), invasive fungal infection (IFI), Cytomegalovirus (CMV) disease and graft rejection within the first year of LT. Of the 304 LT recipients, 73 (24%) developed neutropenia, 5 (7%) of whom had grade 4 neutropenia (ANC less than 500/mm3). The following were independent predictors for neutropenia: Child-Turcotte-Pugh score (HR 1.15; 95% CI 1.02, 1.28; p=0.02), BSI (HR 2.89; 95% CI 1.64, 5.11; p=<0.001), CMV disease (HR 4.28; 95% CI 1.55, 11.8; p=0.005), baseline tacrolimus trough level (HR 1.02; 95% CI 1.01, 1.03; p=0.007) and later era LT (2004–2009 versus 1999–2003) (HR 2.28; 95% CI 1.43, 3.65; p=<0.001). Moreover, neutropenia was found to be an independent predictor for mortality within the first year of LT (HR 3.76; 95% CI 1.84, 7.68; p= <0.001). Conclusion Our data suggest that neutropenia within a year after LT is not unusual and is an important predictor of mortality. PMID:26336061

The ability of filgrastim to mitigate mortality following LD50/60 total-body irradiation is administration time-dependent.

PubMed

Farese, Ann M; Brown, Cassandra R; Smith, Cassandra P; Gibbs, Allison M; Katz, Barry P; Johnson, Cynthia S; Prado, Karl L; MacVittie, Thomas J

2014-01-01

The identification of the optimal administration schedule for an effective medical countermeasure is critical for the effective treatment of individuals exposed to potentially lethal doses of radiation. The efficacy of filgrastim (Neupogen®), a potential medical countermeasure, to improve survival when initiated at 48 h following total body irradiation in a non-human primate model of the hematopoietic syndrome of the acute radiation syndrome was investigated. Animals were exposed to total body irradiation, antero-posterior exposure, total midline tissue dose of 7.5 Gy, (target lethal dose 50/60) delivered at 0.80 Gy min, using linear accelerator-derived 6 MV photons. All animals were administered medical management. Following irradiation on day 0, filgrastim (10 μg kg d) or the control (5% dextrose in water) was administered subcutaneously daily through effect (absolute neutrophil count ≥ 1,000 cells μL for three consecutive days). The study (n = 80) was powered to demonstrate a 25% improvement in survival following the administration of filgrastim or control beginning at 48 ± 4 h post-irradiation. Survival analysis was conducted on the intention-to-treat population using a two-tailed null hypothesis at a 5% significance level. Filgrastim, initiated 48 h after irradiation, did not improve survival (2.5% increase, p = 0.8230). These data demonstrate that efficacy of a countermeasure to mitigate lethality in the hematopoietic syndrome of the acute radiation syndrome can be dependent on the interval between irradiation and administration of the medical countermeasure.

An Enhancing Effect of Gold Nanoparticles on the Lethal Action of 2450 MHz Electromagnetic Radiation in Microwave Oven

PubMed Central

Mollazadeh-Moghaddam, Kamyar; Moradi, Bardia Varasteh; Dolatabadi-Bazaz, Reza; Shakibae, Mojtaba; Shahverdi, Ahmad Reza

2011-01-01

Today, there is an increasing interest in the use of metal nanoparticles in health sciences. Amongst all nanoparticles, the gold nanoparticles have been known to kill the cancer cells under hyperthermic condition by near-infrared frequency electromagnetic waves. On the other hand, although there are different physiochemical methods for disinfection of microbial pollution, however applications of irradiated gold nanoparticles against microorganisms have not yet been investigated. In this study, gold nanoparticles were prepared using D-glucose and characterized (particle size <26 nm). In the next step, the enhancing effect of the non toxic level of gold nanoparticles (50 µg/mL) on the antimicrobial activity of 2450 MHz electromagnetic radiation generated at a microwave oven operated at low power (100 W), was investigated by time-kill course assay against Staphylococcus aureus (S.aureus) ATCC 29737. The results showed that application of gold nanoparticles can enhance the lethal effect of low power microwave in a very short exposure time (5 s). PMID:23407707

The Flavonoid 7,4'-Dihydroxyflavone Prevents Dexamethasone Paradoxical Adverse Effect on Eotaxin Production by Human Fibroblasts.

PubMed

Liu, Changda; Yang, Nan; Chen, Xiaoke; Tversky, Jody; Zhan, Jixun; Chehade, Mirna; Miller, Rachel L; Li, Xiu-Min

2017-03-01

Eotaxin/CCL-11 is a major chemoattractant that contributes to eosinophilic inflammation in asthma. Glucocorticoids inhibit inflammation, but long-time exposure may cause paradoxical adverse effects by augmenting eotaxin/CCL-11production. The aim of this study was to determine if 7,4'-dihydroxyflavone (7,4'-DHF), the eotaxin/CCL11 inhibitor isolated from Glycyrrhiza uralensis, reduces in vitro eotaxin production induced by long-time dexamethasone (Dex) exposure, and if so, to elucidate the mechanisms of this inhibition. Human lung fibroblast-1 cells were used to identify the potency of 7,4'-DHF compared with other compounds from G. uralensis, to compare 7,4'-DHF with Dex on eotaxin production following 24-h short-time culture and 72-h longer-time (LT) culture, and to determine the effects of the 7,4'-DHF on Dex LT culture augmented eotaxin production and molecule mechanisms. 7,4'-DHF was the most potent eotaxin/CCL-11 inhibitor among the ten compounds and provided continued suppression. In contrast to short-time culture, Dex LT culture increased constitutively, and IL-4/TNF-α stimulated eotaxin/CCL11 production by human lung fibroblast-1 cells. This adverse effect was abrogated by 7,4'-DHF co-culture. 7,4'-DHF significantly inhibited Dex LT culture augmentation of p-STAT6 and impaired HDAC2 expression. This study demonstrated that 7,4'-DHF has the ability to consistently suppress eotaxin production and prevent Dex-paradoxical adverse effects on eotaxin production. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Ribavirin protects Syrian hamsters against lethal hantavirus pulmonary syndrome--after intranasal exposure to Andes virus.

PubMed

Ogg, Monica; Jonsson, Colleen B; Camp, Jeremy V; Hooper, Jay W

2013-11-08

Andes virus, ANDV, harbored by wild rodents, causes the highly lethal hantavirus pulmonary syndrome (HPS) upon transmission to humans resulting in death in 30% to 50% of the cases. As there is no treatment for this disease, we systematically tested the efficacy of ribavirin in vitro and in an animal model. In vitro assays confirmed antiviral activity and determined that the most effective doses were 40 µg/mL and above. We tested three different concentrations of ribavirin for their capability to prevent HPS in the ANDV hamster model following an intranasal challenge. While the highest level of ribavirin (200 mg/kg) was toxic to the hamster, both the middle (100 mg/kg) and the lowest concentration (50 mg/kg) prevented HPS in hamsters without toxicity. Specifically, 8 of 8 hamsters survived intranasal challenge for both of those groups whereas 7 of 8 PBS control-treated animals developed lethal HPS. Further, we report that administration of ribavirin at 50 mg/kg/day starting on days 6, 8, 10, or 12 post-infection resulted in significant protection against HPS in all groups. Administration of ribavirin at 14 days post-infection also provided a significant level of protection against lethal HPS. These data provide in vivo evidence supporting the potential use of ribavirin as a post-exposure treatment to prevent HPS after exposure by the respiratory route.

Terrorist Attacks Escalate in Frequency and Fatalities Preceding Highly Lethal Attacks

PubMed Central

Martens, Andy; Sainudiin, Raazesh; Sibley, Chris G.; Schimel, Jeff; Webber, David

2014-01-01

Highly lethal terrorist attacks, which we define as those killing 21 or more people, account for 50% of the total number of people killed in all terrorist attacks combined, yet comprise only 3.5% of terrorist attacks. Given the disproportionate influence of these incidents, uncovering systematic patterns in attacks that precede and anticipate these highly lethal attacks may be of value for understanding attacks that exact a heavy toll on life. Here we examined whether the activity of terrorist groups escalates–both in the number of people killed per attack and in the frequency of attacks–leading up to highly lethal attacks. Analyses of terrorist attacks drawn from a state-of-the-art international terrorism database (The Global Terrorism Database) showed evidence for both types of escalation leading up to highly lethal attacks, though complexities to the patterns emerged as well. These patterns of escalation do not emerge among terrorist groups that never commit a highly lethal attack. PMID:24755753

Metabolic syndrome after pediatric liver transplantation.

PubMed

Kosola, Silja; Lampela, Hanna; Makisalo, Heikki; Lohi, Jouko; Arola, Johanna; Jalanko, Hannu; Pakarinen, Mikko

2014-10-01

Half of adult liver transplantation (LT) recipients develop metabolic syndrome, but the prevalence after childhood LT remains unknown. We conducted a national cross-sectional study of all living patients who had undergone LT between 1987 and 2007 at an age less than 18 years. We gathered information on blood pressure, body composition, serum lipids, glucose metabolism, and histological liver fat content. The diagnostic criteria for metabolic syndrome of the American Heart Association and the International Diabetes Federation were used. After a median post-LT follow-up time of 12 years, half of all patients had no components of metabolic syndrome. The prevalence of overweight/obesity was 20%, and the prevalence of hypertension was 24%. Serum triglycerides were high in 9%, and high-density lipoprotein levels were low in 23%. Fasting glucose levels were impaired in 14%, but none had diabetes. Altogether, 9 patients (14%) had metabolic syndrome. Moderate liver steatosis found in protocol liver biopsy samples was associated with the accumulation of metabolic syndrome features (P = 0.01). No significant associations were found between immunosuppressive medications and metabolic syndrome. In conclusion, the prevalence of metabolic syndrome after childhood LT is similar to the prevalence in the general population of the same age. Guidelines for the general population, therefore, seem valid for the prevention and treatment of metabolic syndrome after pediatric LT as well. © 2014 American Association for the Study of Liver Diseases.

A score model for predicting post-liver transplantation survival in HBV cirrhosis-related hepatocellular carcinoma recipients: a single center 5-year experience.

PubMed

Wang, Li-Ying; Zheng, Shu-Sen; Xu, Xiao; Wang, Wei-Lin; Wu, Jian; Zhang, Min; Shen, Yan; Yan, Sheng; Xie, Hai-Yang; Chen, Xin-Hua; Jiang, Tian-An; Chen, Fen

2015-02-01

The prognostic prediction of liver transplantation (LT) guides the donor organ allocation. However, there is currently no satisfactory model to predict the recipients' outcome, especially for the patients with HBV cirrhosis-related hepatocellular carcinoma (HCC). The present study was to develop a quantitative assessment model for predicting the post-LT survival in HBV-related HCC patients. Two hundred and thirty-eight LT recipients at the Liver Transplant Center, First Affiliated Hospital, Zhejiang University School of Medicine between 2008 and 2013 were included in this study. Their post-LT prognosis was recorded and multiple risk factors were analyzed using univariate and multivariate analyses in Cox regression. The score model was as follows: 0.114X(Child-Pugh score)-0.002X(positive HBV DNA detection time)+0.647X(number of tumor nodules)+0.055X(max diameter of tumor nodules)+0.231XlnAFP+0.437X(tumor differentiation grade). The receiver operating characteristic curve analysis showed that the area under the curve of the scoring model for predicting the post-LT survival was 0.887. The cut-off value was 1.27, which was associated with a sensitivity of 72.5% and a specificity of 90.7%, respectively. The quantitative score model for predicting post-LT survival proved to be sensitive and specific.

The preparation of neem oil microemulsion (Azadirachta indica) and the comparison of acaricidal time between neem oil microemulsion and other formulations in vitro.

PubMed

Xu, Jiao; Fan, Qiao-Jia; Yin, Zhong-Qiong; Li, Xu-Ting; Du, Yong-Hua; Jia, Ren-Yong; Wang, Kai-Yu; Lv, Cheng; Ye, Gang; Geng, Yi; Su, Gang; Zhao, Ling; Hu, Ting-Xiu; Shi, Fei; Zhang, Li; Wu, Chang-Long; Tao, Cui; Zhang, Ya-Xue; Shi, Dong-Xia

2010-05-11

The preparation of neem oil microemulsion and its acaricidal activity in vitro was developed in this study. In these systems, the mixture of Tween-80 and the sodium dodecyl benzene sulfonate (SDBS) (4:1, by weight) was used as compound surfactant; the mixture of compound surfactant and hexyl alcohol (4:1, by weight) was used as emulsifier system; the mixture of neem oil, emulsifier system and water (1:3.5:5.5, by weight) was used as neem oil microemulsion. All the mixtures were stired in 800 rpm for 15 min at 40 degrees C. The acaricidal activity was measured by the speed of kill. The whole lethal time value of 10% neem oil microemulsion was 192.50 min against Sarcoptes scabiei var. cuniculi larvae in vitro. The median lethal time value was 81.7463 min with the toxicity regression equations of Y=-6.0269+3.1514X. These results demonstrated that neem oil microemulsion was effective against Sarcoptes scabie var. cuniculi larvae in vitro. (c) 2010. Published by Elsevier B.V. All rights reserved.

Supplemental intermittent-day heat training and the lactate threshold.

PubMed

Gollan, Stuart; Chalmers, Samuel; Alderton, Stephen; Norton, Kevin

2017-04-01

Heat acclimation over consecutive days has been shown to improve aerobic-based performance. Recently, it has been suggested that heat training can improve performance in a temperate environment. However, due to the multifactorial training demands of athletes, consecutive-day heat training may not be suitable. The current study aimed to investigate the effect of brief (8×30min) intermittent (every 3-4 days) supplemental heat training on the second lactate threshold point (LT 2 ) in temperate and hot conditions. 21 participants undertook eight intermittent-day mixed-intensity treadmill exercise training sessions in hot (30°C; 50% relative humidity [RH]) or temperate (18°C; 30% RH) conditions. A pre- and post-incremental exercise test occurred in temperate (18°C; 30% RH) and hot conditions (30°C; 50% RH) to determine the change in LT 2 . The heat training protocol did not improve LT 2 in temperate (Effect Size [ES]±90 confidence interval=0.10±0.16) or hot (ES=0.26±0.26) conditions. The primary finding was that although the intervention group had a change greater than the SWC, no statistically significant improvements were observed following an intermittent eight day supplemental heat training protocol comparable to a control group training only in temperate conditions. This is likely due to the brief length of each heat training session and/or the long duration between each heat exposure. Copyright © 2017 Elsevier Ltd. All rights reserved.

Embryo developmental events and the egg case of the Aleutian skate Bathyraja aleutica (Gilbert) and the Alaska skate Bathyraja parmifera (Bean).

PubMed

Hoff, G R

2009-02-01

Embryo development events were correlated with egg-case changes for the Aleutian skate Bathyraja aleutica and the Alaska skate Bathyraja parmifera. Yolk absorption underwent two phases: that of steady absorption during early development and that of rapid yolk absorption during the final development stages. Total length (L(T)) for 50% of the pre-hatching embryos egg-case jelly disappearance was 92.04 mm (range 81-102 mm) and 99.36 mm (range 81-100 mm) for B. aleutica and B. parmifera, respectively, allowing the inner chamber to open to seawater flow. The tail filament underwent three phases of growth: rapid elongation during early development (<100 mm embryo L(T)), stasis of tail filament length during the remainder of embryo development and rapid absorption soon after hatching. Complete tail filament development coincided with the disappearance of egg-case jelly. Clasper buds first developed at embryos >70 mm L(T) for both species and the sex ratio was 1:1 well before hatching. Egg cases that were devoid of an ova or developing embryo were c. 5.0 and 6.5% of the egg cases examined for B. aleutica and B. parmifera, respectively. Measurements showed that egg cases containing only egg jelly were smaller in both width and length than those possessing an ova. Embryo stages were punctuated with distinct events that correlated with egg case changes controlling the internal environment of the developing embryo.

Time trade-off and attitudes toward euthanasia: implications of using 'death' as an anchor in health state valuation.

PubMed

Augestad, Liv A; Rand-Hendriksen, Kim; Stavem, Knut; Kristiansen, Ivar Sønbø

2013-05-01

Health state values are by convention anchored to 'perfect health' and 'death.' Attitudes toward death may consequently influence the valuations. We used attitudes toward euthanasia (ATE) as a sub-construct for attitudes toward death. We compared the influence on values elicited with time trade-off (TTO), lead-time TTO (LT-TTO) and visual analogue scale (VAS).Since the 'death' anchor is most explicit in TTO, we hypothesized that TTO values would be most influenced by ATE. Respondents valued eight EQ-5D health states with VAS, then TTO (n = 328) or LT-TTO (n = 484). We measured ATE on a scale from -2 (fully disagree) to 2 (fully agree) and used multiple linear regressions to predict VAS, TTO, and LT-TTO values by ATE, sex, age, and education. A one-point increase on the ATE scale predicted a mean TTO value change of -.113 and LT-TTO change of -.072. Demographic variables, but not ATE, predicted VAS values. TTO appears to measure ATE in addition to preferences for health states. Different ways of incorporating death in the valuation may impact substantially on the resulting values. 'Death' is a metaphysically unknown concept, and implications of attitudes toward death should be investigated further to evaluate the appropriateness of using 'death' as an anchor.

Clustered lot quality assurance sampling to assess immunisation coverage: increasing rapidity and maintaining precision.

PubMed

Pezzoli, Lorenzo; Andrews, Nick; Ronveaux, Olivier

2010-05-01

Vaccination programmes targeting disease elimination aim to achieve very high coverage levels (e.g. 95%). We calculated the precision of different clustered lot quality assurance sampling (LQAS) designs in computer-simulated surveys to provide local health officers in the field with preset LQAS plans to simply and rapidly assess programmes with high coverage targets. We calculated sample size (N), decision value (d) and misclassification errors (alpha and beta) of several LQAS plans by running 10 000 simulations. We kept the upper coverage threshold (UT) at 90% or 95% and decreased the lower threshold (LT) progressively by 5%. We measured the proportion of simulations with < or =d individuals unvaccinated or lower if the coverage was set at the UT (pUT) to calculate beta (1-pUT) and the proportion of simulations with >d unvaccinated individuals if the coverage was LT% (pLT) to calculate alpha (1-pLT). We divided N in clusters (between 5 and 10) and recalculated the errors hypothesising that the coverage would vary in the clusters according to a binomial distribution with preset standard deviations of 0.05 and 0.1 from the mean lot coverage. We selected the plans fulfilling these criteria: alpha < or = 5% beta < or = 20% in the unclustered design; alpha < or = 10% beta < or = 25% when the lots were divided in five clusters. When the interval between UT and LT was larger than 10% (e.g. 15%), we were able to select precise LQAS plans dividing the lot in five clusters with N = 50 (5 x 10) and d = 4 to evaluate programmes with 95% coverage target and d = 7 to evaluate programmes with 90% target. These plans will considerably increase the feasibility and the rapidity of conducting the LQAS in the field.

Management of immunosuppressive therapy in liver transplant recipients who develop bloodstream infection.

PubMed

Bartoletti, Michele; Vandi, Giacomo; Furii, Francesca; Bertuzzo, Valentina; Ambretti, Simone; Tedeschi, Sara; Pascale, Renato; Cristini, Francesco; Campoli, Caterina; Morelli, Maria Cristina; Cescon, Matteo; Pinna, Antonio Daniele; Viale, Pierluigi; Giannella, Maddalena

2018-05-29

Data about the optimal management of immunosuppressive therapy in liver transplant (LT) recipients with bloodstream infection (BSI) are missing. We aimed to describe the management of immunosuppressive therapy at diagnosis of BSI in LT recipients and to assess its impact on 28-day mortality. We performed a single-centre retrospective study of all LT recipients diagnosed with BSI, over 10-year period. Multivariate Cox regression analysis of risk factors for all-cause 28-day mortality was adjusted for the propensity score of being managed with "any reduction" in immunosuppressive therapy at the diagnosis of BSI. We identified 209 episodes of BSI in 157 LT recipients: 107 (68%) male, median age 54 (IQR 48-63) years. "Any reduction" was made in 90 (43%) cases including: dosage reduction of ≥1 immunosuppressive drug in 31 (15%), discontinuation of ≥1 immunosuppressive drug in 28 (13%), both dosage reduction and discontinuation in 13 (6%), complete withdrawal of immunosuppressive therapy in 18 (9%) cases. All-cause 28-day mortality rate was 13.4%, varying from 22% to 7% (p=0.002) in cases with and without "any reduction". Cox regression showed septic shock (aHR 3.15, p=0.007) and "any reduction" (aHR 2.50, p=0.02) as independent risk factors for all-cause 28-day mortality, while Escherichia coli (aHR 0.38, p=0.03) and source control (aHR 0.43, p=0.04) were protective factors. The final model did not change after the introduction of the propensity score for "any reduction". Any reduction in the immunosuppressive therapy was common and was associated with worse outcome in LT recipients developing BSI. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

New results on equatorial thermospheric winds and temperatures from Ethiopia, Africa

NASA Astrophysics Data System (ADS)

Tesema, Fasil; Mesquita, Rafael; Meriwether, John; Damtie, Baylie; Nigussie, Melessew; Makela, Jonathan; Fisher, Daniel; Harding, Brian; Yizengaw, Endawoke; Sanders, Samuel

2017-03-01

Measurements of equatorial thermospheric winds, temperatures, and 630 nm relative intensities were obtained using an imaging Fabry-Perot interferometer (FPI), which was recently deployed at Bahir Dar University in Ethiopia (11.6° N, 37.4° E, 3.7° N magnetic). The results obtained in this study cover 6 months (53 nights of useable data) between November 2015 and April 2016. The monthly-averaged values, which include local winter and equinox seasons, show the magnitude of the maximum monthly-averaged zonal wind is typically within the range of 70 to 90 ms-1 and is eastward between 19:00 and 21:00 LT. Compared to prior studies of the equatorial thermospheric wind for this local time period, the magnitude is considerably weaker as compared to the maximum zonal wind speed observed in the Peruvian sector but comparable to Brazilian FPI results. During the early evening, the meridional wind speeds are 30 to 50 ms-1 poleward during the winter months and 10 to 25 ms-1 equatorward in the equinox months. The direction of the poleward wind during the winter months is believed to be mainly caused by the existence of the interhemispheric wind flow from the summer to winter hemispheres. An equatorial wind surge is observed later in the evening and is shifted to later local times during the winter months and to earlier local times during the equinox months. Significant night-to-night variations are also observed in the maximum speed of both zonal and meridional winds. The temperature observations show the midnight temperature maximum (MTM) to be generally present between 00:30 and 02:00 LT. The amplitude of the MTM was ˜ 110 K in January 2016 with values smaller than this in the other months. The local time difference between the appearance of the MTM and a pre-midnight equatorial wind was generally 60 to 180 min. A meridional wind reversal was also observed after the appearance of the MTM (after 02:00 LT). Climatological models, HWM14 and MSIS-00, were compared to the observations and the HWM14 model generally predicted the zonal wind observations well with the exception of higher model values by 25 ms-1 in the winter months. The HWM14 model meridional wind showed generally good agreement with the observations. Finally, the MSIS-00 model overestimated the temperature by 50 to 75 K during the early evening hours of local winter months. Otherwise, the agreement was generally good, although, in line with prior studies, the model failed to reproduce the MTM peak for any of the 6 months compared with the FPI data.

Improvements in bladder, bowel and sexual outcomes following task-specific locomotor training in human spinal cord injury.

PubMed

Hubscher, Charles H; Herrity, April N; Williams, Carolyn S; Montgomery, Lynnette R; Willhite, Andrea M; Angeli, Claudia A; Harkema, Susan J

2018-01-01

Locomotor training (LT) as a therapeutic intervention following spinal cord injury (SCI) is an effective rehabilitation strategy for improving motor outcomes, but its impact on non-locomotor functions is unknown. Given recent results of our labs' pre-clinical animal SCI LT studies and existing overlap of lumbosacral spinal circuitries controlling pelvic-visceral and locomotor functions, we addressed whether LT can improve bladder, bowel and sexual function in humans at chronic SCI time-points (> two years post-injury). Prospective cohort study; pilot trial with small sample size. Eight SCI research participants who were undergoing 80 daily one-hour sessions of LT on a treadmill using body-weight support, or one-hour of LT and stand training on alternate days, as part of another research study conducted at the Kentucky Spinal Cord Injury Research Center, University of Louisville, were enrolled in this pilot trial. Urodynamic assessments were performed and International Data Set questionnaire forms completed for bladder, bowel and sexual functions at pre-and post-training time points. Four usual care (non-trained; regular at-home routine) research participants were also enrolled in this study and had the same assessments collected twice, at least 3 months apart. Filling cystometry documented significant increases in bladder capacity, voiding efficiency and detrusor contraction time as well as significant decreases in voiding pressure post-training relative to baseline. Questionnaires revealed a decrease in the frequency of nocturia and urinary incontinence for several research participants as well as a significant decrease in time required for defecation and a significant increase in sexual desire post-training. No significant differences were found for usual care research participants. These results suggest that an appropriate level of sensory information provided to the spinal cord, generated through task-specific stepping and/or loading, can positively benefit the neural circuitries controlling urogenital and bowel functions. ClinicalTrials.gov NCT03036527.

Improvements in bladder, bowel and sexual outcomes following task-specific locomotor training in human spinal cord injury

PubMed Central

Williams, Carolyn S.; Montgomery, Lynnette R.; Willhite, Andrea M.; Angeli, Claudia A.; Harkema, Susan J.

2018-01-01

Objective Locomotor training (LT) as a therapeutic intervention following spinal cord injury (SCI) is an effective rehabilitation strategy for improving motor outcomes, but its impact on non-locomotor functions is unknown. Given recent results of our labs’ pre-clinical animal SCI LT studies and existing overlap of lumbosacral spinal circuitries controlling pelvic-visceral and locomotor functions, we addressed whether LT can improve bladder, bowel and sexual function in humans at chronic SCI time-points (> two years post-injury). Study design Prospective cohort study; pilot trial with small sample size. Methods Eight SCI research participants who were undergoing 80 daily one-hour sessions of LT on a treadmill using body-weight support, or one-hour of LT and stand training on alternate days, as part of another research study conducted at the Kentucky Spinal Cord Injury Research Center, University of Louisville, were enrolled in this pilot trial. Urodynamic assessments were performed and International Data Set questionnaire forms completed for bladder, bowel and sexual functions at pre-and post-training time points. Four usual care (non-trained; regular at-home routine) research participants were also enrolled in this study and had the same assessments collected twice, at least 3 months apart. Results Filling cystometry documented significant increases in bladder capacity, voiding efficiency and detrusor contraction time as well as significant decreases in voiding pressure post-training relative to baseline. Questionnaires revealed a decrease in the frequency of nocturia and urinary incontinence for several research participants as well as a significant decrease in time required for defecation and a significant increase in sexual desire post-training. No significant differences were found for usual care research participants. Conclusions These results suggest that an appropriate level of sensory information provided to the spinal cord, generated through task-specific stepping and/or loading, can positively benefit the neural circuitries controlling urogenital and bowel functions. Trial registration ClinicalTrials.gov NCT03036527 PMID:29385166

Timed Light Therapy for Sleep and Daytime Sleepiness Associated With Parkinson Disease: A Randomized Clinical Trial.

PubMed

Videnovic, Aleksandar; Klerman, Elizabeth B; Wang, Wei; Marconi, Angelica; Kuhta, Teresa; Zee, Phyllis C

2017-04-01

Impaired sleep and alertness are some of the most common nonmotor manifestations of Parkinson disease (PD) and currently have only limited treatment options. Light therapy (LT), a widely available treatment modality in sleep medicine, has not been systematically studied in the PD population. To determine the safety and efficacy of LT on excessive daytime sleepiness (EDS) associated with PD. This randomized, placebo-controlled, clinical intervention study was set in PD centers at Northwestern University and Rush University. Participants were 31 patients with PD receiving stable dopaminergic therapy with coexistent EDS, as assessed by an Epworth Sleepiness Scale score of 12 or greater, and without cognitive impairment or primary sleep disorder. Participants were randomized 1:1 to receive bright LT or dim-red LT (controlled condition) twice daily in 1-hour intervals for 14 days. This trial was conducted between March 1, 2007, and October 31, 2012. Data analysis of the intention-to-treat population was conducted from November 1, 2012, through April 30, 2016. The primary outcome measure was the change in the Epworth Sleepiness Scale score comparing the bright LT with the dim-red LT. Secondary outcome measures included the Pittsburgh Sleep Quality Index score, the Parkinson's Disease Sleep Scale score, the visual analog scale score for daytime sleepiness, and sleep log-derived and actigraphy-derived metrics. Among the 31 patients (13 males and 18 females; mean [SD] disease duration, 5.9 [3.6] years), bright LT resulted in significant improvements in EDS, as assessed by the Epworth Sleepiness Scale score (mean [SD], 15.81 [3.10] at baseline vs 11.19 [3.31] after the intervention). Both bright LT and dim-red LT were associated with improvements in sleep quality as captured by mean (SD) scores on the Pittsburg Sleep Quality Index (7.88 [4.11] at baseline vs 6.25 [4.27] after bright LT, and 8.87 [2.83] at baseline vs 7.33 [3.52] after dim-red LT) and the Parkinson's Disease Sleep Scale (97.24 [22.49] at baseline vs 106.98 [19.37] after bright LT, and 95.11 [19.86] at baseline vs 99.28 [16.94] after dim-red LT). Bright LT improved several self-reported mean (SD) sleep metrics, including sleep fragmentation (number of overnight awakenings, 1.51 [1.03] at baseline vs 0.92 [0.97] after the intervention), sleep quality (sleep diary score, 3.03 [1.01] at baseline vs 3.53 [0.91] after the intervention), and ease of falling asleep (sleep diary score, 2.32 [0.89] at baseline vs 1.83 [0.88] after the intervention). Light therapy was associated with increased daily physical activity as assessed by actigraphy (average activity [SD] counts, 165.01 [66.87] at baseline vs 194.59 [87.81] after the intervention). Light therapy was well tolerated and may be a feasible intervention for improving the sleep-wake cycles in patients with PD. Further studies are required to determine optimal parameters of LT for PD. clinicaltrials.gov Identifier: NCT01338649.

Effects of dietary potato by-product and rumen-protected histidine on growth, carcass characteristics and quality attributes of beef.

PubMed

Thornton, K J; Richard, R P; Colle, M J; Doumit, M E; de Veth, M J; Hunt, C W; Murdoch, G K

2015-09-01

We hypothesized that variable composition in finishing rations, more specifically; the proportion of potato-by-product (PBP) and rumen protected histidine (His) supplementation may influence growth and meat quality attributes. Two different diets were fed (1) finishing ration with corn and barley as grains (CB, n = 20) and (2) substitution of 10% corn, DM basis, with PBP (PBP, n = 20). Additionally, half of each dietary treatment received 50 g/hd/d rumen protected His (HS, n= 20) while the other half received no supplement (NS, n = 20). Inclusion of 10% PBP or HS did not affect growth or carcass traits. Color stability was analyzed using Hunter color values as well as AMSA visual appraisal in both longissimus thoracis (LT) and gluteus medius (GM) muscles. The LT, but not the GM, of CB steers was more color stable over a 9 d simulated retail display compared to those fed a PB diet. Steers receiving HS produced significantly (P < 0.05) more color stable LT and GM steaks. Copyright © 2015 Elsevier Ltd. All rights reserved.

50 Years Air Force Issues Book 1997

DTIC Science & Technology

1997-01-01

12 Space Launches and Operations ............................................................................ 13 Non ...In the near-term, we are developing lethal and 1997. non -lethal AEFs for deployment to areas We are also undertaking a variety of measures outside the...providing missile early warning data to NATO and Japan, and we have extended this service to other nations as well. Non -combatant Evacuation Operations (NEO

Physiological and training characteristics of recreational marathon runners

PubMed Central

Gordon, Dan; Wightman, Sarah; Basevitch, Itay; Johnstone, James; Espejo-Sanchez, Carolina; Beckford, Chelsea; Boal, Mariette; Scruton, Adrian; Ferrandino, Mike; Merzbach, Viviane

2017-01-01

Purpose The aim of this study was to examine the physical and training characteristics of recreational marathon runners within finish time bandings (2.5–3 h, 3–3.5 h, 3.5–4 h, 4–4.5 h and >4.5 h). Materials and methods A total of 97 recreational marathon runners (age 42.4 ± 9.9 years; mass 69.2 ± 11.3 kg; stature 172.8 ± 9.1 cm), with a marathon finish time of 229.1 ± 48.7 min, of whom n = 34 were female and n = 63 were male, completed an incremental treadmill test for the determination of lactate threshold (LT1), lactate turn point (LT2) and running economy (RE). Following a 7-min recovery, they completed a test to volitional exhaustion starting at LT2 for the assessment of V˙O2max. In addition, all participants completed a questionnaire gathering information on their current training regimes exploring weekly distances, training frequencies, types of sessions, longest run in a week, with estimations of training speed, and load and volume derived from these data. Results Training frequency was shown to be significantly greater for the 2.5–3 h group compared to the 3.5–4 h runners (P < 0.001) and >4.5 h group (P = 0.004), while distance per session (km·session−1) was significantly greater for the 2.5–3 h group (16.1 ± 4.2) compared to the 3.5–4 h group (15.5 ± 5.2; P = 0.01) and >4.5 h group (10.3 ± 2.6; P = 0.001). Race speed correlated with LT1 (r = 0.791), LT2 (r = 0.721) and distance per session (r = 0.563). Conclusion The data highlight profound differences for key components of marathon running (V˙O2max, LT1, LT2, RE and % V˙O2max) within a group of recreational runners with the discriminating training variables being training frequency and the absolute training speed. PMID:29200895

Pressure-induced structural change in liquid GeI₄.

PubMed

Fuchizaki, Kazuhiro; Nishimura, Hironori; Hase, Takaki; Saitoh, Hiroyuki

2017-12-13

The similarity in the shape of the melting curve of GeI₄ to that of SnI₄ suggests that a liquid-liquid transition as observed in liquid SnI₄ is also expected to occur in liquid GeI₄. Because the slope of the melting curve of GeI₄ abruptly changes at around 3 GPa, in situ synchrotron diffraction measurements were conducted to examine closely the structural changes upon compression at around 3 GPa. The reduced radial distribution functions of the high- and low-pressure liquid states of GeI₄ share the same feature inherent in the high-pressure (high-density) and low-pressure (low-density) radial distribution functions of liquid SnI₄. This feature allows us to introduce local order parameters that we may use to observe the transition. Unlike the transition in liquid SnI₄, the transition from the low-pressure to the high-pressure structure seems sluggish. We speculate that the liquid-liquid critical point of GeI₄ is no longer a thermodynamically stable state and is slightly located below the melting curve. As a result, the structural change is said to be a crossover rather than a transition. The behavior of the local-order parameters implies a metastable extension of the liquid-liquid phase boundary with a negative slope. . © 2017 IOP Publishing Ltd.

Radiation lethality in the opossum

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

Prasad, N.; Bushong, S.C.; North, L.B.

1976-12-01

Groups of male opossum (Didelphis virginiana) at 6 months of age were exposed to 350, 500, 550, 600, 650, 700, and 750 rad of whole-body /sup 60/Co radiation at a midline dose rate of 125 rad/min. The 30-day LD/sub 50/ was 511 rad with 95% confidence limits of 454 to 576 rad. The overall mean survival time was 17.9 days and the highest incidence of death occurred on the 16th day.

Biodefense-driven murine model of pneumonic melioidosis.

PubMed

Jeddeloh, J A; Fritz, D L; Waag, D M; Hartings, J M; Andrews, G P

2003-01-01

A whole-body mouse model of pneumonic melioidosis was established for future evaluation of biodefense vaccine candidates. The aerosol 50% lethal doses of Burkholderia pseudomallei strain 1026b for BALB/c and C57BL/6 mice and the times to death, dissemination in organs, and tissue loads after exposure of the mice to low- and high-dose aerosols are reported. In addition, rpsL mutant backgrounds were attenuated in this acute model of disease.

Magnetotransport study of topological superconductor Cu_0.10Bi₂Se₃ single crystal.

PubMed

Li, Mingtao; Fang, Yifei; Zhang, Jincang; Yi, Hemian; Zhou, Xingjiang; Lin, Chengtian

2018-02-02

We report a magnetotransport study of vortex-pinning in Cu_0.10Bi₂Se₃ single crystal. The sample is demonstrated to be in clean limit and absent of Pauli spin-limiting effect. Interestingly, the resistivity versus magnetic field shows an anomalously pronounced increase when approaching the superconducting-normal state boundary for both B∥ab and B∥c configurations. We have investigated the flux-flowing behavior under various magnetic field and temperatures, enabling us to establish its anisotropic vortex phase diagram. Our results suggest the Cu_0.10Bi₂Se₃ can be served as one unique material for exploring exotic surface vortex states in topological superconductors. © 2018 IOP Publishing Ltd.

Evaluation of the Lethal Potency of Scorpion and Snake Venoms and Comparison between Intraperitoneal and Intravenous Injection Routes

PubMed Central

Oukkache, Naoual; Jaoudi, Rachid El; Ghalim, Noreddine; Chgoury, Fatima; Bouhaouala, Balkiss; Mdaghri, Naima El; Sabatier, Jean-Marc

2014-01-01

Scorpion stings and snake bites are major health hazards that lead to suffering of victims and high mortality. Thousands of injuries associated with such stings and bites of venomous animals occur every year worldwide. In North Africa, more than 100,000 scorpion stings and snake bites are reported annually. An appropriate determination of the 50% lethal doses (LD50) of scorpion and snake venoms appears to be an important step to assess (and compare) venom toxic activity. Such LD50 values are also commonly used to evaluate the neutralizing capacity of specific anti-venom batches. In the present work, we determined experimentally the LD50 values of reference scorpion and snake venoms in Swiss mice, and evaluated the influence of two main venom injection routes (i.e., intraperitoneal (IP) versus intravenous (IV)). The analysis of experimental LD50 values obtained with three collected scorpion venoms indicates that Androctonus mauretanicus (Am) is intrinsically more toxic than Androctonus australis hector (Aah) species, whereas the latter is more toxic than Buthus occitanus (Bo). Similar analysis of three representative snake venoms of the Viperidae family shows that Cerastes cerastes (Cc) is more toxic than either Bitis arietans (Ba) or Macrovipera lebetina (Ml) species. Interestingly, the venom of Elapidae cobra snake Naja haje (Nh) is far more toxic than viper venoms Cc, Ml and Ba, in agreement with the known severity of cobra-related envenomation. Also, our data showed that viper venoms are about three-times less toxic when injected IP as compared to IV, distinct from cobra venom Nh which exhibited a similar toxicity when injected IP or IV. Overall, this study clearly highlights the usefulness of procedure standardization, especially regarding the administration route, for evaluating the relative toxicity of individual animal venoms. It also evidenced a marked difference in lethal activity between venoms of cobra and vipers, which, apart from the nature of toxins, might be attributed to the rich composition of high molecular weight enzymes in the case of viper venoms. PMID:24926799

Using accelerated life testing procedures to compare the relative sensitivity of rainbow trout and the federally listed threatened bull trout to three commonly used rangeland herbicides (picloram, 2,4-D, and clopyralid).

PubMed

Fairchild, James F; Allert, Ann; Sappington, Linda S; Nelson, Karen J; Valle, Janet

2008-03-01

We conducted 96-h static acute toxicity studies to evaluate the relative sensitivity of juveniles of the threatened bull trout (Salvelinus confluentus) and the standard cold-water surrogate rainbow trout (Onchorhyncus mykiss) to three rangeland herbicides commonly used for controlling invasive weeds in the northwestern United States. Relative species sensitivity was compared using three procedures: standard acute toxicity testing, fractional estimates of lethal concentrations, and accelerated life testing chronic estimation procedures. The acutely lethal concentrations (ALC) resulting in 50% mortality at 96 h (96-h ALC50s) were determined using linear regression and indicated that the three herbicides were toxic in the order of picloram acid > 2,4-D acid > clopyralid acid. The 96-h ALC50 values for rainbow trout were as follows: picloram, 41 mg/L; 2.4-D, 707 mg/L; and clopyralid, 700 mg/L. The 96-h ALC50 values for bull trout were as follows: picloram, 24 mg/L; 2.4-D, 398 mg/L; and clopyralid, 802 mg/L. Fractional estimates of safe concentrations, based on 5% of the 96-h ALC50, were conservative (overestimated toxicity) of regression-derived 96-h ALC5 values by an order of magnitude. Accelerated life testing procedures were used to estimate chronic lethal concentrations (CLC) resulting in 1% mortality at 30 d (30-d CLC1) for the three herbicides: picloram (1 mg/L rainbow trout, 5 mg/L bull trout), 2,4-D (56 mg/L rainbow trout, 84 mg/L bull trout), and clopyralid (477 mg/L rainbow trout; 552 mg/L bull trout). Collectively, the results indicated that the standard surrogate rainbow trout is similar in sensitivity to bull trout. Accelerated life testing procedures provided cost-effective, statistically defensible methods for estimating safe chronic concentrations (30-d CLC1s) of herbicides from acute toxicity data because they use statistical models based on the entire mortality:concentration:time data matrix.

Using accelerated life testing procedures to compare the relative sensitivity of rainbow trout and the federally listed threatened bull trout to three commonly used rangeland herbicides (picloram, 2,4-D, and clopyralid)

USGS Publications Warehouse

Fairchild, J.F.; Allert, A.; Sappington, L.S.; Nelson, K.J.; Valle, J.

2008-01-01

We conducted 96-h static acute toxicity studies to evaluate the relative sensitivity of juveniles of the threatened bull trout (Salvelinus confluentus) and the standard cold-water surrogate rainbow trout (Onchorhyncus mykiss) to three rangeland herbicides commonly used for controlling invasive weeds in the northwestern United States. Relative species sensitivity was compared using three procedures: standard acute toxicity testing, fractional estimates of lethal concentrations, and accelerated life testing chronic estimation procedures. The acutely lethal concentrations (ALC) resulting in 50% mortality at 96 h (96-h ALC50s) were determined using linear regression and indicated that the three herbicides were toxic in the order of picloram acid > 2,4-D acid > clopyralid acid. The 96-h ALC50 values for rainbow trout were as follows: picloram, 41 mg/L; 2.4-D, 707 mg/L; and clopyralid, 700 mg/L. The 96-h ALC50 values for bull trout were as follows: picloram, 24 mg/L; 2.4-D, 398 mg/L; and clopyralid, 802 mg/L. Fractional estimates of safe concentrations, based on 5% of the 96-h ALC50, were conservative (overestimated toxicity) of regression-derived 96-h ALC5 values by an order of magnitude. Accelerated life testing procedures were used to estimate chronic lethal concentrations (CLC) resulting in 1% mortality at 30 d (30-d CLC1) for the three herbicides: picloram (1 mg/L rainbow trout, 5 mg/L bull trout), 2,4-D (56 mg/L rainbow trout, 84 mg/L bull trout), and clopyralid (477 mg/L rainbow trout; 552 mg/L bull trout). Collectively, the results indicated that the standard surrogate rainbow trout is similar in sensitivity to bull trout. Accelerated life testing procedures provided cost-effective, statistically defensible methods for estimating safe chronic concentrations (30-d CLC1s) of herbicides from acute toxicity data because they use statistical models based on the entire mortality:concentration: time data matrix. ?? 2008 SETAC.

Extracts of Renealmia alpinia (Rottb.) MAAS Protect against Lethality and Systemic Hemorrhage Induced by Bothrops asper Venom: Insights from a Model with Extract Administration before Venom Injection

PubMed Central

Patiño, Arley Camilo; Quintana, Juan Carlos; Gutiérrez, José María; Rucavado, Alexandra; Benjumea, Dora María; Pereañez, Jaime Andrés

2015-01-01

Renealmia alpinia (Rottb.) MAAS, obtained by micropropagation (in vitro) and wild forms have previously been shown to inhibit some toxic activities of Bothrops asper snake venom if preincubated before injection. In this study, assays were performed in a murine model in which extracts were administered for three days before venom injection. R. alpinia extracts inhibited lethal activity of B. asper venom injected by intraperitoneal route. Median Effective Dose (ED50) values were 36.6 ± 3.2 mg/kg and 31.7 ± 5.4 mg/kg (p > 0.05) for R. alpinia wild and in vitro extracts, respectively. At a dose of 75 mg/kg, both extracts totally inhibited the lethal activity of the venom. Moreover, this dose prolonged survival time of mice receiving a lethal dose of venom by the intravenous route. At 75 mg/kg, both extracts of R. alpinia reduced the extent of venom-induced pulmonary hemorrhage by 48.0% (in vitro extract) and 34.7% (wild extract), in agreement with histological observations of lung tissue. R. alpinia extracts also inhibited hemorrhage in heart and kidneys, as evidenced by a decrease in mg of hemoglobin/g of organ. These results suggest the possibility of using R. alpinia as a prophylactic agent in snakebite, a hypothesis that needs to be further explored. PMID:25941768

Extracts of Renealmia alpinia (Rottb.) MAAS Protect against Lethality and Systemic Hemorrhage Induced by Bothrops asper Venom: Insights from a Model with Extract Administration before Venom Injection.

PubMed

Patiño, Arley Camilo; Quintana, Juan Carlos; Gutiérrez, José María; Rucavado, Alexandra; Benjumea, Dora María; Pereañez, Jaime Andrés

2015-04-30

Renealmia alpinia (Rottb.) MAAS, obtained by micropropagation (in vitro) and wild forms have previously been shown to inhibit some toxic activities of Bothrops asper snake venom if preincubated before injection. In this study, assays were performed in a murine model in which extracts were administered for three days before venom injection. R. alpinia extracts inhibited lethal activity of B. asper venom injected by intraperitoneal route. Median Effective Dose (ED50) values were 36.6 ± 3.2 mg/kg and 31.7 ± 5.4 mg/kg (p > 0.05) for R. alpinia wild and in vitro extracts, respectively. At a dose of 75 mg/kg, both extracts totally inhibited the lethal activity of the venom. Moreover, this dose prolonged survival time of mice receiving a lethal dose of venom by the intravenous route. At 75 mg/kg, both extracts of R. alpinia reduced the extent of venom-induced pulmonary hemorrhage by 48.0% (in vitro extract) and 34.7% (wild extract), in agreement with histological observations of lung tissue. R. alpinia extracts also inhibited hemorrhage in heart and kidneys, as evidenced by a decrease in mg of hemoglobin/g of organ. These results suggest the possibility of using R. alpinia as a prophylactic agent in snakebite, a hypothesis that needs to be further explored.

Effects of UVB radiation on grazing of two cladocerans from high-altitude Andean lakes

PubMed Central

Rejas, Danny

2017-01-01

Climate change and water extraction may result in increased exposition of the biota to ultraviolet-B radiation (UVB) in high-altitude Andean lakes. Although exposition to lethal doses in these lakes is unlikely, sub-lethal UVB doses may have strong impacts in key compartments such as zooplankton. Here, we aimed at determining the effect of sub-lethal UVB doses on filtration rates of two cladoceran species (Daphnia pulicaria and Ceriodaphnia dubia). We firstly estimated the Incipient Limiting Concentration (ILC) and the Gut Passage Time (GPT) for both species. Thereafter we exposed clones of each species to four increasing UVB doses (treatments): i) DUV-0 (Control), ii) DUV-1 (0.02 MJ m2), iii) DUV-2 (0.03 MJ m2) and iv) DUV-3 (0.15 MJ m2); and estimated their filtration rates using fluorescent micro-spheres. Our results suggest that increasing sub-lethal doses of UVB radiation may strongly disturb the structure and functioning of high-altitude Andean lakes. Filtration rates of D. pulicaria were not affected by the lowest dose applied (DUV-1), but decreased by 50% in treatments DUV-2 and DUV-3. Filtration rates for C. dubia were reduced by more than 80% in treatments DUV-1 and DUV-2 and 100% of mortality occurred at the highest UVB dose applied (DUV-3). PMID:28379975

Cornhusker Army Ammunition Plant Remedial Investigation/Feasibility Study; UST and AST Site Investigation.

DTIC Science & Technology

1997-10-01

50000 1000 500000 Chromium CR JS16/SS18 4.05 5000 6.96 50000 Cobalt CO JS16/SS18 1.42 1000 25 50000 Copper CU JS16/SS18 0.965 2500 5 25000 Cyanide...5000 2 10000 Cadmium CD JS13/SS14 0.515 2000 5 5000 Calcium CA JS13/SS14 72 5000 50 5000 Chromium CR JS13/SS14 0.669 5000 22.4 7500 Cobalt CO JS13...ED SS14 21 ! Barium 130 UGL WELL G0053 24-Mar-92 ED SS14 21 Chromium LT 22.4 UGL WELL G0053 ! 24-Mar-92 ED SS14 21 : Cobalt LT ; 10.8 UGL WELL

Freeze Tolerance of Nine Zoysiagrass Cultivars Using Natural Cold Acclimation and Freeze Chambers

USDA-ARS?s Scientific Manuscript database

Winter hardiness of zoysiagrass (Zoysia spp.) cultivars is an important attribute throughout the biogeographical transition zone, thus the inability to withstand freezing temperatures may limit the use of these cultivars. The objective of this research was to determine the freeze tolerance (LT50) of...

[Bile duct atresia: outline for a solution].

PubMed

Broto, J; Asensio, M; Gil Vernet, J M; Marhuenda, C; Boix Ochoa, J

2000-07-01

Biliary atresia continues to be a serious and relatively rare disease (1/50,000 newborns) and whose long-term prognosis has changed drastically since the appearance of liver transplant (LT) as a therapeutic weapon. The combination of two factors, early diagnosis and correct application of Kasai's surgical technique, is essential to obtain acceptable results and sufficient biliary drainage allowing the children to overcome the critical 7 kg barrier and place them in the lesser morbi-mortality range in relation to a possible LT. But we must keep in mind that despite its critics, Kasai's technique can guarantee, both in our own experience and in the literature, ten years survival percentages over 50% with correct hepatic function, as well as clinical normality and a quality of life clearly superior to first years post-LT. We present the evolution of a group of 20 patients affected with biliary atresia, diagnosed in our center since 1985, the year when pediatric LT began to be used as a therapeutic procedure in this country. We valued the age of intervention, technique, immediate and long-term results and the evolution and necessity of LT. All 20 patients were analyzed individually, and they currently have an age range from 2-14 years and were all operated by Kasai's technique. We classified the patients as having good, regular or poor results with regards to biliary flow, normalization of billirubin levels and clinical evolution. Sixteen patients presented biliary flow of such an extent that 14 of them, classified as good, completely normalized the billirubin levels. Two others, presently aged 14 and 8 years respectively, present average levels of 2.5-5.5 mg/100 ml and are classified as regular in a situation of advisable transplant, although with an acceptable hepatic function. Only one case, the first in the poor group, did not initially present biliary elimination and died at age six months while on the waiting list. Three other cases in the same group presented insufficient biliary elimination and were transplanted with 7, 11 and 12.5 kg, respectively. The second died in the first year post-transplant. In our opinion, action in biliary atresia must be early and based on the correct application of Kasai's technique, seeking to achieve a biliar flow that eliminates or distances the patient as far as possible from the necessity of a future LT. Three lines come together to obtain this target: an early diagnosis, a correct application of Kasai's technique, and an implication in the follow-up and treatment of these children by the hepatic transplant groups. All this advises us, as is done in other countries, to create reference centers for the study of neonatal cholestasis where an accumulated experience of a relatively rare pathology can be taken advantage of.

Air Force Follow-On Review. Protecting The Force: Lessons From Fort Hood

DTIC Science & Technology

2010-01-01

Executive Summary body markings, assessing the potential for violence, clarifying firearms policies, and pro- moting consistent application of policies...Mr. Byron Cotton Lt Col Christopher Alonzo Lt Col Cheryl Scaglione Lt Col Sonya Collins Lt Col Kristine Blackwell Lt Col Christopher Oleksa Lt Col

Impaired pharmacokinetics of levothyroxine in severely obese volunteers.

PubMed

Michalaki, Marina A; Gkotsina, Margarita I; Mamali, Irene; Markantes, Georgios K; Faltaka, Amalia; Kalfarentzos, Fotios; Vagenakis, Apostolos G; Markou, Kostas B

2011-05-01

Suppressive or replacement doses of levothyroxine (LT4) are affected by the rate and extent of the active ingredient absorbed, as well as by the lean body mass. Obesity has reached epidemic proportions worldwide and is related with many comorbidities. The aim of this study was to determine the pharmacokinetic parameters of LT4 in severely obese individuals and compared them with similar data in lean control subjects. We studied 62 euthyroid subjects who had negative tests for anti-thyroid peroxidise antibodies (Ab-TPO). Thirty eight of these subjects were severely obese but otherwise healthy (severe obese subjects [SOS] group). Twenty-four were healthy control subjects (control group), with a body mass index of 23.3 ± 1.7 kg/m(2). Subjects received 600 μg oral sodium LT4 after an overnight fast. Serum triiodothyronine (T3), T4, and thyroid-stimulating hormone were measured at baseline. Serum T4 and T3 was measured 0.5, 1, 1.5, 2, 2.5, 3, and 4 hours after LT4 administration. Baseline serum T4 and thyroid-stimulating hormone concentrations were higher in the SOS group than in the control group; serum T3 was similar in the two groups. The corrected area under the curve and the maximum T4 concentration after LT4 administration were lower, whereas the time to maximum concentration from the baseline was higher in SOS than in the control group. The estimated plasma volume was higher in the SOS than in the control group. Mean serum T3 levels increased gradually during the four hours after LT4 administration in the control group. In contrast, they decreased gradually in the SOS group. Severely obese individuals may need higher LT4 suppressive or replacement doses than normal-weight individuals due, among other factors, to impaired LT4 pharmacokinetic parameters. The latter could be attributed to their higher plasma volume and/or to delayed gastrointestinal LT4 absorption. T4 conversion to T3 might be defective in severe obesity.

SCHISTOSOMIASIS: AGE OF SNAILS AND SUSCEPTIBILITY TO X-IRRADIATION

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

Szumlewicz, A.P.

1964-04-17

Studies on sensitivity of Australorbis glabratus to x rays have defined the chronological and physiological age at which the snail is most sensitive to radiation damage. Results showed that the dose producing 50-percent mortality at 30 days after irradiation increased with age but that at 90 days it was practically constant from 2 to 210 days of age. In view of the avaiIable data on recovery from radiation damage caused by doses from 6000 to 9000 roentgens it is suggested that doses above those causing 50% lethality at 60 days but below those causing 50% lethality for 30 days shouldmore » be considered in setting up radiation barriers to cortrol snails in water-distribution systems. (auth)« less

Donor hypernatremia before procurement and early outcomes following pediatric liver transplantation.

PubMed

Kaseje, Neema; McLin, Valerie; Toso, Christian; Poncet, Antoine; Wildhaber, Barbara E

2015-08-01

The demand for transplantable organs far outweighs the supply. Recently, efforts have been made to increase the donor pool by adopting extended criteria for livers, including those from hypernatremic donors. Currently, there is no clear evidence that the use of organs from hypernatremic donors has detrimental effects on pediatric liver transplantation (LT) recipients. Our aim was to use the Scientific Registry of Transplant Recipients database to evaluate the effects of donor hypernatremia on 30-day outcomes in pediatric LT recipients. We performed an analysis of 2325 children who underwent whole or partial LT between 2005 and 2010. First, we sought to determine a donor sodium threshold for increased mortality following pediatric LT. Second, we examined rates of mortality and graft failure at 30 days after LT in patients receiving grafts from hypernatremic donors compared to patients receiving grafts from normonatremic donors. Hypernatremia was defined as a donor sodium level of ≥160 µmol/L. The primary outcome measure was mortality at 30 days after transplant. The secondary outcome measure was graft failure at 30 days after transplant. There was no threshold sodium level for increased 30-day mortality following pediatric LT. Mean recipient ages/weights, Pediatric End-Stage Liver Disease/Model for End-Stage Liver Disease scores, and mean cold and warm ischemia times were similar between the 2 study groups. There were no significant differences in mortality rates (3.9% versus 4.5%; P = 0.87) and graft failure rates (2.2% versus 1.9%; P = 1.00) in patients receiving grafts from hypernatremic donors compared to patients receiving grafts from normonatremic donors at 30 days after LT. In conclusion, donor hypernatremia just before procurement does not appear to have negative effects on mortality and graft failure rates at 30 days following pediatric LT. © 2015 American Association for the Study of Liver Diseases.

Analysis of Wearable and Smartphone-Based Technologies for the Measurement of Barbell Velocity in Different Resistance Training Exercises

PubMed Central

Balsalobre-Fernández, Carlos; Marchante, David; Baz-Valle, Eneko; Alonso-Molero, Iván; Jiménez, Sergio L.; Muñóz-López, Mario

2017-01-01

The purpose of this study was to analyze the validity, reliability, and accuracy of new wearable and smartphone-based technology for the measurement of barbell velocity in resistance training exercises. To do this, 10 highly trained powerlifters (age = 26.1 ± 3.9 years) performed 11 repetitions with loads ranging 50–100% of the 1-Repetition maximum in the bench-press, full-squat, and hip-thrust exercises while barbell velocity was simultaneously measured using a linear transducer (LT), two Beast wearable devices (one placed on the subjects' wrist –BW–, and the other one directly attached to the barbell –BB–) and the iOS PowerLift app. Results showed a high correlation between the LT and BW (r = 0.94–0.98, SEE = 0.04–0.07 m•s−1), BB (r = 0.97–0.98, SEE = 0.04–0.05 m•s−1), and the PowerLift app (r = 0.97–0.98, SEE = 0.03–0.05 m•s−1) for the measurement of barbell velocity in the three exercises. Paired samples T-test revealed systematic biases between the LT and BW, BB and the app in the hip-thrust, between the LT and BW in the full-squat and between the LT and BB in the bench-press exercise (p < 0.001). Moreover, the analysis of the linear regression on the Bland-Altman plots showed that the differences between the LT and BW (R2 = 0.004–0.03), BB (R2 = 0.007–0.01), and the app (R2 = 0.001–0.03) were similar across the whole range of velocities analyzed. Finally, the reliability of the BW (ICC = 0.910–0.988), BB (ICC = 0.922–0.990), and the app (ICC = 0.928–0.989) for the measurement of the two repetitions performed with each load were almost the same than that observed with the LT (ICC = 0.937–0.990). Both the Beast wearable device and the PowerLift app were highly valid, reliable, and accurate for the measurement of barbell velocity in the bench-press, full-squat, and hip-thrust exercises. These results could have potential practical applications for strength and conditioning coaches who wish to measure barbell velocity during resistance training. PMID:28894425

Analysis of Wearable and Smartphone-Based Technologies for the Measurement of Barbell Velocity in Different Resistance Training Exercises.

PubMed

Balsalobre-Fernández, Carlos; Marchante, David; Baz-Valle, Eneko; Alonso-Molero, Iván; Jiménez, Sergio L; Muñóz-López, Mario

2017-01-01

The purpose of this study was to analyze the validity, reliability, and accuracy of new wearable and smartphone-based technology for the measurement of barbell velocity in resistance training exercises. To do this, 10 highly trained powerlifters (age = 26.1 ± 3.9 years) performed 11 repetitions with loads ranging 50-100% of the 1-Repetition maximum in the bench-press, full-squat, and hip-thrust exercises while barbell velocity was simultaneously measured using a linear transducer (LT), two Beast wearable devices (one placed on the subjects' wrist -BW-, and the other one directly attached to the barbell -BB-) and the iOS PowerLift app. Results showed a high correlation between the LT and BW ( r = 0.94-0.98, SEE = 0.04-0.07 m•s -1 ), BB ( r = 0.97-0.98, SEE = 0.04-0.05 m•s -1 ), and the PowerLift app ( r = 0.97-0.98, SEE = 0.03-0.05 m•s -1 ) for the measurement of barbell velocity in the three exercises. Paired samples T -test revealed systematic biases between the LT and BW, BB and the app in the hip-thrust, between the LT and BW in the full-squat and between the LT and BB in the bench-press exercise ( p < 0.001). Moreover, the analysis of the linear regression on the Bland-Altman plots showed that the differences between the LT and BW ( R 2 = 0.004-0.03), BB ( R 2 = 0.007-0.01), and the app ( R 2 = 0.001-0.03) were similar across the whole range of velocities analyzed. Finally, the reliability of the BW (ICC = 0.910-0.988), BB (ICC = 0.922-0.990), and the app (ICC = 0.928-0.989) for the measurement of the two repetitions performed with each load were almost the same than that observed with the LT (ICC = 0.937-0.990). Both the Beast wearable device and the PowerLift app were highly valid, reliable, and accurate for the measurement of barbell velocity in the bench-press, full-squat, and hip-thrust exercises. These results could have potential practical applications for strength and conditioning coaches who wish to measure barbell velocity during resistance training.

A SEARCH FOR L/T TRANSITION DWARFS WITH PAN-STARRS1 AND WISE. II. L/T TRANSITION ATMOSPHERES AND YOUNG DISCOVERIES

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

Best, William M. J.; Liu, Michael C.; Magnier, Eugene A.

The evolution of brown dwarfs from L to T spectral types is one of the least understood aspects of the ultracool population, partly for lack of a large, well-defined, and well-characterized sample in the L/T transition. To improve the existing census, we have searched ≈28,000 deg{sup 2} using the Pan-STARRS1 and Wide-field Infrared Survey Explorer surveys for L/T transition dwarfs within 25 pc. We present 130 ultracool dwarf discoveries with estimated distances ≈9–130 pc, including 21 that were independently discovered by other authors and 3 that were previously identified as photometric candidates. Seventy-nine of our objects have near-IR spectral types ofmore » L6–T4.5, the most L/T transition dwarfs from any search to date, and we have increased the census of L9–T1.5 objects within 25 pc by over 50%. The color distribution of our discoveries provides further evidence for the “L/T gap,” a deficit of objects with (J − K){sub MKO} ≈ 0.0–0.5 mag in the L/T transition, and thus reinforces the idea that the transition from cloudy to clear photospheres occurs rapidly. Among our discoveries are 31 candidate binaries based on their low-resolution spectral features. Two of these candidates are common proper motion companions to nearby main sequence stars; if confirmed as binaries, these would be rare benchmark systems with the potential to stringently test ultracool evolutionary models. Our search also serendipitously identified 23 late-M and L dwarfs with spectroscopic signs of low gravity implying youth, including 10 with vl-g or int-g gravity classifications and another 13 with indications of low gravity whose spectral types or modest spectral signal-to-noise ratio do not allow us to assign formal classifications. Finally, we identify 10 candidate members of nearby young moving groups (YMG) with spectral types L7–T4.5, including three showing spectroscopic signs of low gravity. If confirmed, any of these would be among the coolest known YMG members and would help to determine the effective temperature at which young brown dwarfs cross the L/T transition.« less

Patterns of depressive symptom remission during the treatment of seasonal affective disorder with cognitive-behavioral therapy or light therapy.

PubMed

Meyerhoff, Jonah; Young, Michael A; Rohan, Kelly J

2018-05-01

To elucidate mechanisms related to remission in winter seasonal affective disorder (SAD), we explored the course of individual depressive symptom offset across two distinct treatment modalities that show comparable outcomes at treatment endpoint: cognitive-behavioral therapy for SAD (CBT-SAD) and light therapy (LT). One hundred seventy-seven adults with SAD in a depressive episode were randomized to 6-weeks of CBT-SAD (n = 88) or LT (n = 89). Symptoms were assessed via the 29-item Structured Interview Guide for the Hamilton Rating Scale for Depression-SAD Version (SIGH-SAD) at pretreatment and weekly during treatment. Survival analyses were conducted for the 17 SIGH-SAD items endorsed by more than 40 participants at pretreatment. Within each of the included symptoms, data from participants who endorsed the symptom at pretreatment and who had 3 or fewer weeks missing were included. For most (13/17; 76%) symptoms, CBT-SAD and LT did not differ in time to remission. However, for four symptoms (early insomnia, psychic anxiety, hypersomnia, and social withdrawal), LT led to symptom remission more quickly than CBT-SAD. Symptom remission progressed comparably across CBT-SAD and LT for most symptoms. Despite the fact that the two treatments led to similar remission rates and improvements at treatment endpoint, for early insomnia, psychic anxiety, hypersomnia, and social withdrawal, LT led to symptom remission faster than CBT-SAD. These results suggest different mechanisms and pathways to the same therapeutic end. Speedier remission of early insomnia and hypersomnia is consistent with the theory that SAD is related to a pathological circadian phase-shift that can be corrected with LT. © 2018 Wiley Periodicals, Inc.

The duration of light treatment and therapy outcome in seasonal affective disorder.

PubMed

Knapen, S E; van de Werken, M; Gordijn, M C M; Meesters, Y

2014-09-01

Seasonal affective disorder (SAD) is characterized by recurrent episodes of major depression with a seasonal pattern, treated with light therapy (LT). Duration of light therapy differs. This study investigates retrospectively whether a single week of LT is as effective as two weeks, whether males and females respond differently, and whether there is an effect of expectations as assessed before treatment. 83 women, and 25 men received either one-week (n=42) or two weeks (n=66) of LT were included in three studies. Before LT, patients׳ expectations on therapy response were assessed. Depression severity was similar in both groups before treatment (F(1,106)=0.19ns) and decreased significantly during treatment (main effect "time" F(2,105)=176.7, p<0.001). The speed of therapy response differs significantly in treatment duration, in favor of 1 week (F(2,105)=3.2, p=0.046). A significant positive correlation between expectations and therapy response was found in women (ρ=0.243, p=0.027) and not in men (ρ=-0.154,ns). When expectation was added as a covariate in the repeated-measures analysis it shows a positive effect of the level of expectation on the speed of therapy response (F(2,104)=4.1, p=0.018). A limitation is the retrospective design. There is no difference between 1 and 2 weeks of LT in overall therapy outcome, but the speed of therapy response differed between 1 week LT and 2 weeks LT. Together with the significant correlation between expectations and therapy response in women, we hypothesize that expectations play a role in the speed of therapy response. Copyright © 2014 Elsevier B.V. All rights reserved.

Students insert the laryngeal tube quicker and more often successful than the esophageal-tracheal combitube in a manikin.

PubMed

Hüter, Lars; Schwarzkopf, Konrad; Rödiger, Jörg; Preussler, Niels P; Schreiber, Torsten

2009-08-01

Endotracheal intubation remains the standard of airway management. Because intubation skills are difficult to acquire, for medical students teaching of easier to learn techniques should be considered. We retrospectively analyzed data that were collected in a University teaching facility. 264 medical students were taught how to use laryngeal tube (LT) and Esophageal Tracheal Combitube((R)) (ETC) in a manikin. The students underwent one of two different types of extraglottic airway management training consisting of either long lecture (30min) and intensive training (2h) (group IT, n=48), or brief (10min) lecture and 20min of training (group BT, n=216). Both groups underwent a test 6 weeks after training, group IT had an additional test 24h after training. After 24h students in group IT were faster using the LT than the ETC (31.7s+/-2.1 vs. 51.9s+/-5.8, p<0.001). Up to 6 weeks after training students were able to place the LT significantly faster than the ETC in both groups (26.5s+/-2.1 vs. 53.9s+/-5.8 group IT and 43.4s+/-1.6 vs. 103.8s+/-4.4 group BT, p<0.001). At 24h and 6 weeks following intensive training, there was no statistical difference in the time required for insertion of either device. Following different training scenarios in a manikin, students were able to place the LT much faster than the ETC. Even brief training was sufficient to generate short insertion times for the LT.

The Spanish Lung Transplant Registry: first report of results (2006-2010).

PubMed

Coll, Elisabeth; Santos, Francisco; Ussetti, Pietat; Canela, Mercedes; Borro, José María; De La Torre, Mercedes; Varela, Andrés; Zurbano, Felipe; Mons, Roberto; Morales, Pilar; Pastor, Juan; Salvatierra, Angel; de Pablo, Alicia; Gámez, Pablo; Moreno, Antonio; Solé, Juan; Román, Antonio

2013-02-01

The Spanish Lung Transplant Registry (SLTR) began its activities in 2006 with the participation of all the lung transplantation (LT) groups with active programs in Spain. This report presents for the first time an overall description and results of the patients who received lung transplants in Spain from 2006 to 2010. LT activity has grown progressively, and in this time period 951 adults and 31 children underwent lung transplantation. The mean age of the recipients was 48.2, while the mean age among the lung donors was 41.7. In adult LT, the most frequent cause for lung transplantation was emphysema/COPD, followed by idiopathic pulmonary fibrosis, both representing more than 60% the total number of indications. The probability for survival after adult LT to one and three years was 72% and 60%, respectively, although in patients who survived until the third month post-transplantation, these survival rates reached 89.7% and 75.2%. The factors that most clearly influenced patient survival were the age of the recipient and the diagnosis that indicated the transplantation. Among the pediatric transplantations, cystic fibrosis was the main cause for transplantation (68%), with a one-year survival of 80% and a three-year survival of 70%. In adult as well as pediatric transplantations, the most frequent cause of death was infection. These data confirm the consolidated situation of LT in Spain as a therapeutic option for advanced chronic respiratory disease, both in children as well as in adults. Copyright © 2012 SEPAR. Published by Elsevier Espana. All rights reserved.

Integration of the physiological factors determining endurance performance ability.

PubMed

Coyle, E F

1995-01-01

This model is used to understand the interrelationships of the physiological factors determining endurance performance ability during prolonged exercise. Early studies found that marathon runners maintain a velocity in competition that corresponds to the intensity at which lactate begins to accumulate in blood and muscle [7, 8, 19]. From this observation, the concept developed that this blood lactate threshold (LT Vo2) reflects the degree of muscular stress, glycogenolysis and fatigue. However, it was not clear whether the lactate accumulation was a result of cardiovascular limitations linked to oxygen delivery, as reflected by Vo2max [54], as opposed to metabolic factors in the exercising muscle related to the extent to which mitochondrial respiration is disturbed to maintain a given rate of O2 consumption [29, 30]. Two studies were performed to determine whether LT Vo2 was tightly coupled to Vo2max. In one study, endurance-trained ischemic heart disease patients were observed to possess a Vo2max that was 18% below that of normal master athletes who followed the patient's training program and who displayed the same performance ability as the patients. Both the patients and the normal men displayed an identical LT Vo2 (i.e., 37 ml/kg/min) (Fig. 2.5). Therefore, performance was determined primarily by LT Vo2 instead of Vo2max in this situation, albeit with abnormal subjects. In a second study we assembled two groups of competitive cyclists who were identical in Vo2max but differed by having a high or low LT Vo2 (82% vs. 66% Vo2max) [13]. When cycling at 80-88% Vo2max, the low LT group displayed more than a 2-fold higher rate of muscle glycogen use and blood lactate concentration, and as a result were able to exercise only one-half as long as the high LT group. Performance time for a given Vo2 was clearly related to LT Vo2 instead of Vo2max (Fig. 2.6). This is not to say that Vo2max plays no role in determining LT Vo2, because as in heart disease patients, it clearly sets the upper limit. Indeed, we have seen that much of the variance (i.e., 31-72%) in LT Vo2 is related to Vo2max. (Fig. 2.11.) However, improvements in performance after the first 2-3 yr of intense training are associated with improvements in LT Vo2, whereas Vo2max generally increases very little thereafter (Table 2.3). The next question concerns the factors responsible for further increases in LT Vo2 and Performance. Another major factor determining LT Vo2 is the muscle's Aerobic Enzyme Activity or mitochondrial respiratory capacity, as discussed in previous reviews [29, 30].(ABSTRACT TRUNCATED AT 400 WORDS)

Comparison of Airway Management Methods in Entrapped Patients: A Manikin Study.

PubMed

Martin, Andrew B; Lingg, Jim; Lubin, Jeffrey S

2016-01-01

Endotracheal intubation remains one of the most challenging skills in prehospital care. There is a minimal amount of data on the optimal technique to use when managing the airway of an entrapped patient. We hypothesized that use of a blindly placed device would result in both the shortest time to airway management and highest success rate. A difficult airway manikin was placed in a cervical collar and secured upside down in an overturned vehicle. Experienced paramedics and prehospital registered nurses used four different methods to secure the airway: direct laryngoscopy, digital intubation, King LT-D, and CMAC video laryngoscopy. Each participant was given three opportunities to secure the airway using each technique in random order. A study investigator timed each attempt and confirmed successful placement, which was determined upon inflation of the manikin's lungs. Intubation success rates were analyzed using a general estimating equations model to account for repeated measures and a linear mixed effects model for average time. Twenty-two prehospital providers participated in the study. The one-pass success rate for the King LT-D was significantly higher than direct laryngoscopy (OR 0.048, CI 0.006-0.351, p < 0.01) and digital intubation (OR 0.040, CI 0.005-0.297, p < 0.01). However, there was no statistical difference between the one-pass success rate of the King LT-D and CMAC video laryngoscopy (OR 0.302, 95% CI 0.026-3.44, p = 0.33). The one-pass median placement time of the King LT-D (22 seconds, IQR 17-26) was significantly lower (p < 0.001) than direct laryngoscopy (60 seconds, IQR 42-75), digital intubation (38 seconds, IQR 26-74), and the CMAC (51 seconds, IQR 43-76). In this study, while the King LT-D offered the quickest airway placement, success rates were not significantly greater than intubation using the CMAC video laryngoscope. Intubation using direct laryngoscopy and digital intubation were less successful and took more time. Use of a blindly placed device or a video laryngoscope may provide the best avenues for airway management of entrapped patients.

Room temperature synthesis of ReS₂ through aqueous perrhenate sulfidation.

PubMed

Borowiec, Joanna; Gillin, William P; Willis, Maureen; Boi, Filippo; He, Yi; Wen, Jiqiu; Wang, Shanling; Schulz, Leander

2017-12-29

In this study, a direct sulfidation reaction of ammonium perrhenate (NH₄ReO₄) leading to a synthesis of rhenium disulfide (ReS₂) is demonstrated. These finding reveal the first example of a simplistic bottom-up approach to the chemical synthesis of crystalline ReS₂. The reaction presented here takes place at room temperature, in an ambient and solvent-free environment and without the necessity of a catalyst. The atomic composition and structure of the as-synthesized product were characterized using several analysis techniques including energy dispersive X-ray (EDX) spectroscopy, X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), transmission electron microscopy (TEM), Raman spectroscopy, thermogravimetric analysis (TGA) and differential scannig calorimetry (DSC). The results indicated the formation of a lower symmetry (1T_d) ReS₂ with a low degree of layer stacking. © 2017 IOP Publishing Ltd.

Immunization with a novel Clostridium perfringens epsilon toxin mutant rETX(Y196E)-C confers strong protection in mice.

PubMed

Yao, Wenwu; Kang, Jingjing; Kang, Lin; Gao, Shan; Yang, Hao; Ji, Bin; Li, Ping; Liu, Jing; Xin, Wenwen; Wang, Jinglin

2016-04-06

Epsilon toxin (ETX) is produced by toxinotypes B and D of Clostridium perfringens. It can induce lethal enterotoxemia in domestic animals, mainly in sheep, goats and cattle, causing serious economic losses to global animal husbandry. In this study, a novel and stable epsilon toxin mutant rETX(Y196E)-C, obtained by substituting the 196th tyrosine (Y196) with glutamic acid (E) and introducing of 23 amino acids long C-terminal peptide, was determined as a promising recombinant vaccine candidate against enterotoxemia. After the third vaccination, the antibody titers against recombinant wild type (rETX) could reach 1:10(5) in each immunized group, and the mice were completely protected from 100 × LD50 (50% lethal dose) of rETX challenge. The mice in 15 μg subcutaneously immunized group fully survived at the dose of 500 × LD50 of rETX challenge and 80% of mice survived at 180 μg (1000 × LD50) of rETX administration. In vitro, immune sera from 15 μg subcutaneously immunized group could completely protect MDCK cells from 16 × CT50 (50% lethal dose of cells) of rETX challenge and protect against 10 × LD50 dose (1.8 μg) of rETX challenge in mice. These data suggest that recombinant protein rETX(Y196E)-C is a potential vaccine candidate for future applied researches.

Modulated elliptic wave and asymptotic solitons in a shock problem to the modified Korteweg-de Vries equation

NASA Astrophysics Data System (ADS)

Kotlyarov, Vladimir; Minakov, Alexander

2015-07-01

We study the long-time asymptotic behavior of the Cauchy problem for the modified Korteweg—de Vries equation with an initial function of the step type. This function rapidly tends to zero as x\\to +∞ and to some positive constant c as x\\to -∞ . In 1989 Khruslov and Kotlyarov have found (Khruslov and Kotlyarov 1989 Inverse Problems 5 1075-88) that for a large time the solution breaks up into a train of asymptotic solitons located in the domain 4{c}2t-{C}N{ln}t\\lt x≤slant 4{c}2t ({C}N is a constant). The number N of these solitons grows unboundedly as t\\to ∞ . In 2010 Kotlyarov and Minakov have studied temporary asymptotics of the solution of the Cauchy problem on the whole line (Kotlyarov and Minakov 2010 J. Math. Phys. 51 093506) and have found that in the domain -6{c}2t\\lt x\\lt 4{c}2t this solution is described by a modulated elliptic wave. We consider here the modulated elliptic wave in the domain 4{c}2t-{C}N{ln}t\\lt x\\lt 4{c}2t. Our main result shows that the modulated elliptic wave also breaks up into solitons, which are similar to the asymptotic solitons in Khruslov and Kotlyarov (1989 Inverse Problems 5 1075-88), but differ from them in phase. It means that the modulated elliptic wave does not represent the asymptotics of the solution in the domain 4{c}2t-{C}N{ln}t\\lt x\\lt 4{c}2t. The correct asymptotic behavior of the solution is given by the train of asymptotic solitons given in Khruslov and Kotlyarov (1989 Inverse Problems 5 1075-88). However, in the asymptotic regime as t\\to ∞ in the region 4{c}2t-\\displaystyle \\frac{N+1/4}{c}{ln}t\\lt x\\lt 4{c}2t-\\displaystyle \\frac{N-3/4}{c}{ln}t we can watch precisely a pair of solitons with numbers N. One of them is the asymptotic soliton while the other soliton is generated from the elliptic wave. Their phases become closer to each other for a large N, i.e. these solitons are also close to each other. This result gives the answer on a very important question about matching of the asymptotic formulas in the mentioned region where the both formulas are well-defined. Thus we have here a new and previously unknown mechanism (5.35) of matching of the asymptotics of the solution in the adjacent regions.

Adaptation of the length-active tension relationship in rabbit detrusor

PubMed Central

Almasri, Atheer M.; Bhatia, Hersch; Klausner, Adam P.; Ratz, Paul H.

2009-01-01

Studies have shown that the length-tension (L-T) relationships in airway and vascular smooth muscles are dynamic and can adapt to length changes over a period of time. Our prior studies have shown that the passive L-T relationship in rabbit detrusor smooth muscle (DSM) is also dynamic and that DSM exhibits adjustable passive stiffness (APS) characterized by a passive L-T curve that can shift along the length axis as a function of strain history and activation history. The present study demonstrates that the active L-T curve for DSM is also dynamic and that the peak active tension produced at a particular muscle length is a function of both strain and activation history. More specifically, this study reveals that the active L-T relationship, or curve, does not have a unique peak tension value with a single ascending and descending limb, but instead reveals that multiple ascending and descending limbs can be exhibited in the same DSM strip. This study also demonstrates that for DSM strips not stretched far enough to reveal a descending limb, the peak active tension produced by a maximal KCl-induced contraction at a short, passively slack muscle length of 3 mm was reduced by 58.6 ± 4.1% (n = 15) following stretches to and contractions at threefold the original muscle length, 9 mm. Moreover, five subsequent contractions at the short muscle length displayed increasingly greater tension; active tension produced by the sixth contraction was 91.5 ± 9.1% of that produced by the prestretch contraction at that length. Together, these findings indicate for the first time that DSM exhibits length adaptation, similar to vascular and airway smooth muscles. In addition, our findings demonstrate that preconditioning, APS and adaptation of the active L-T curve can each impact the maximum total tension observed at a particular DSM length. PMID:19675182

Lethal and sub-lethal effects from short-term exposure of Rhyzopertha dominica on wheat treated with Storicide II®

USDA-ARS?s Scientific Manuscript database

Hard red winter wheat was treated at 0 (untreated control), 25, 50, 75, and 100% of the label rate of the insecticide Storicide II®, which is chlorpyrifos-methyl and deltamethrin applied at label rates of 3 and 0.5 ppm, respectively. Paired male and female Rhyzopertha dominica F., the lesser grain b...

Protective effects of S+ ketamine and atropine against lethality and brain damage during soman-induced status epilepticus in guinea-pigs.

PubMed

Dorandeu, Frederic; Baille, Valerie; Mikler, John; Testylier, Guy; Lallement, Guy; Sawyer, Thomas; Carpentier, Pierre

2007-05-20

Soman poisoning is known to induce full-blown tonic-clonic seizures, status epilepticus (SE), seizure-related brain damage (SRBD) and lethality. Previous studies in guinea-pigs have shown that racemic ketamine (KET), with atropine sulfate (AS), is very effective in preventing death, stopping seizures and protecting sensitive brain areas when given up to 1h after a supra-lethal challenge of soman. The active ketamine isomer, S(+) ketamine (S-KET), is more potent than the racemic mixture and it also induces less side-effects. To confirm the efficacy of KET and to evaluate the potential of S-KET for delayed medical treatment of soman-induced SE, we studied different S-KET dose regimens using the same paradigm used with KET. Guinea-pigs received pyridostigmine (26 microg/kg, IM) 30min before soman (62 microg/kg, 2 LD(50), IM), followed by therapy consisting of atropine methyl nitrate (AMN) (4 mg/kg, IM) 1min following soman exposure. S-KET, with AS (10mg/kg), was then administered IM at different times after the onset of seizures, starting at 1h post-soman exposure. The protective efficacy of S-KET proved to be comparable to KET against lethality and SRBD, but at doses two to three times lower. As with KET, delaying treatment by 2h post-poisoning greatly reduced efficacy. Conditions that may have led to an increased S-KET brain concentration (increased doses or number of injections, adjunct treatment with the oxime HI-6) did not prove to be beneficial. In summary, these observations confirm that ketamine, either racemic or S-KET, in association with AS and possibly other drugs, could be highly effective in the delayed treatment of severe soman intoxication.

Access to means of suicide, occupation and the risk of suicide: a national study over 12 years of coronial data.

PubMed

Milner, A; Witt, K; Maheen, H; LaMontagne, A D

2017-04-04

Availability of lethal means is a significant risk factor for suicide. This study investigated whether occupations with greater access to lethal means had higher suicide rates than those without access, and further, whether this relationship differed for females versus males. A retrospective mortality study was conducted across the Australian population over the period 2001 to 2012. Data from the Australian Bureau of Statistics, which collects Census information on occupation for the Australian population, and the National Coroners Information System, which records information on suicide deaths, were combined. Employed suicide records were coded by occupation and work-related access to lethal means. Descriptive analysis and negative binomial regression were used to assess the relationship between access to means and suicide. Persons in occupations with access to firearms, medicines or drugs, and carbon monoxide more frequently used these methods to end their lives than those without access to means. Females employed in occupations with access to means had suicide rates that were 3.02 times greater (95% CI 2.60 to 3.50, p < 0.001) than those employed in occupations without access. Males in occupations with access had suicide rates that were 1.24 times greater than those without access (95% CI 1.16 to 1.33, p < 0.001). Work-related access to means is a risk factor for suicide in the employed population, but is associated with a greater risk for females than males. The findings of this study suggest the importance of controlling access to lethal methods in occupations where these are readily available.

The lymphotoxin promoter is stimulated by HTLV-I tax activation of NF-kappa B in human T-cell lines.

PubMed

Paul, N L; Millet, I; Ruddle, N H

1993-07-01

The HTLV-I transcriptional activator tax was used to gain insight into the mechanism of lymphotoxin (LT; TNF-beta) gene induction. Tax-expressing cell lines produce LT biologic activity. An LT promoter (LT-293) CAT construct that contained an NF-kappa B site was active in the LT-producing C81-66-45 cell line, which contains defective HTLV-I but expresses tax. The observation that a mutated LT-kappa B construct (M1-CAT) was inactive in C81-66-45, confirmed the importance of NF-kappa B in LT gene expression. Tax was transfected into HTLV-I-negative human T-cell lines. Jurkat T cells stably expressing tax contained elevated levels of NF-kappa B that directly bound to the LT-kappa B site. Tax co-transfected with reporter constructs into Jurkat cells maximally activated HTLV-I-LTR-CAT and kappa B-fos-CAT and also activated LT-293 to a lesser extent. In JM T cells, tax induced LT-293 activity by two- to four-fold, though there was no induction of M1-CAT. The increase in LT-293 CAT activity mirrored the increase in LT biologic activity seen under these conditions. These studies, the first to demonstrate induction of LT promoter activity over basal levels, indicate that HTLV-I tax causes low-level activation of both endogenous LT and the LT promoter, at least in part through activation of NF-kappa B.

Cognitive fatigue in patients with myasthenia gravis.

PubMed

Jordan, Berit; Schweden, Tabea L K; Mehl, Theresa; Menge, Uwe; Zierz, Stephan

2017-09-01

Cognitive fatigue has frequently been reported in myasthenia gravis (MG). However, objective assessment of cognitive fatigability has never been evaluated. Thirty-three MG patients with stable generalized disease and 17 healthy controls underwent a test battery including repeated testing of attention and concentration (d2-R) and Paced Auditory Serial Addition Test. Fatigability was based on calculation of linear trend (LT) reflecting dynamic performance within subsequent constant time intervals. Additionally, fatigue questionnaires were used. MG patients showed a negative LT in second d2-R testing, indicating cognitive fatigability. This finding significantly differed from stable cognitive performance in controls (P < 0.05). Results of Paced Auditory Serial Addition Test testing did not differ between groups. Self-assessed fatigue was significantly higher in MG patients compared with controls (P < 0.001), but did not correlate with LT. LT quantifies cognitive fatigability as an objective measurement of performance decline in MG patients. Self-assessed cognitive fatigue is not correlated with objective findings. Muscle Nerve 56: 449-457, 2017. © 2016 Wiley Periodicals, Inc.

Contrasting pollen histories of MIS 5e and the Holocene from Lake Titicaca (Bolivia/Peru)

NASA Astrophysics Data System (ADS)

Hanselman, Jennifer A.; Gosling, William D.; Paduano, Gina M.; Bush, Mark B.

2005-10-01

Two long sediment records (cores LTO1-2B and LT01-3B) from Lake Titicaca, Bolivia/Peru, are compared with a previously analysed Holocene record from this lake (core NE98-1PC). The Holocene records of LT01-2B and NE98-1PC are similar. There are striking differences, however, between the MIS 5e sections of the long cores and the Holocene records. In these records, temperature is probably the dominant parameter that determines the total fossil pollen concentration and is used to time the onset and termination of deglaciation. In contrast, the relative and absolute abundance of specific taxa (e.g. Polylepis/Acaena, Chenopodiaceae) are indicators of relative moisture availability. Although the Holocene contains a period of aridity between ca. 8000 cal. yr BP and 4300 cal. yr BP, it is a minor event compared with the more extreme aridity of MIS 5e. Core LT01-3B showed similar trends during MIS 5e when compared to LT01-2B, as did NE98-1PC when comparing Holocene records. MIS 5e and the Holocene are markedly different interglacials, depicted by shifts in pollen concentration and taxa representation over time.

Studies on toxicity of OTEC plant components on marine animals from the Gulf of Mexico. Annual report for period October 1979-September 1980

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

Venkataramiah, A.; Lakshmi, G.J.; Best, C.

1981-06-01

This project was undertaken as a part of the OTEC environmental studies plan on the toxicity of OTEC working fluids to marine organisms. Ammonia and chlorine were chosen as they pose the greatest potential environmental threat. Acute and chronic bioassays determined the LT/sub 50/, LC/sub 50/ and the behavior of mullet (Mugil cephalus), sargassum shrimp (Latreutes fucorum) and filefish (Monocanthus hispidus).

Diurnal evolution of the F region electron density local time gradient at low and middle latitudes resolved by the Swarm constellation

NASA Astrophysics Data System (ADS)

Xiong, Chao; Zhou, Yun-Liang; Lühr, Hermann; Ma, Shu-Ying

2016-09-01

In this study we have provided new insights into the local time gradient of F region electron density (ΔNe) derived from the lower pair of Swarm satellites flying side by side. Our result shows that the electron density (Ne) increase starts just at sunrise, around 06:00 LT, simultaneously at low and middle latitudes due to the increased photoionization. At equatorial latitudes the increase in electron density gets even steeper after 07:00 LT, and the steepest increase of electron density (about 3 · 1010 m-3 within 6 min) occurs around 09:00 LT. We suggest that the upward vertical plasma drift in connection with the buildup of the equatorial fountain effect plays a major role. We also found that the local time variations of the equatorial ionization anomaly (EIA) crest electron density during daytime are similar to the respective evolutions at the equator, but about 1-2 h delayed. We relate this delay to the response time between the equatorial electric field and the buildup of the plasma fountain. At equinox months a fast decrease of the F region electron density is seen at the EIA trough region during the prereversal enhancement, while an increase is found meanwhile at crest regions. Afterward, a fast decrease of the EIA crest electron density occurs between 19:00 and 23:00 LT, with seasonal dependence. The local time gradient between Swarm A and C shows also prominent longitudinal wave-4 pattern around August months, and the phase of DE3 in ΔNe is found to be delayed by 6 h compared to that in Ne.