18 research outputs found

    A case of vertebral coalescence and lateral line deformity in Hypophthalamichthys nobilis (Richardson, 1844) obtained from aquaculture activity in Iran

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    Publisher's version. Journal homepage http://www.mrsntorino.it/cms/il-museo/attivita-editoriale.htmlVertebral coalescence and malformation in the lateral line are reported in a specimen of cultured cyprinid fish Hypophthalamichthys nobilis . Severe vertebral fusion was observed and described. Lateral line showed unusual undulation in the trunk region. Genetic and epigenetic causes may be implicated in these anomalies

    Linear Encodings of Bounded LTL Model Checking

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    We consider the problem of bounded model checking (BMC) for linear temporal logic (LTL). We present several efficient encodings that have size linear in the bound. Furthermore, we show how the encodings can be extended to LTL with past operators (PLTL). The generalised encoding is still of linear size, but cannot detect minimal length counterexamples. By using the virtual unrolling technique minimal length counterexamples can be captured, however, the size of the encoding is quadratic in the specification. We also extend virtual unrolling to Buchi automata, enabling them to accept minimal length counterexamples. Our BMC encodings can be made incremental in order to benefit from incremental SAT technology. With fairly small modifications the incremental encoding can be further enhanced with a termination check, allowing us to prove properties with BMC. Experiments clearly show that our new encodings improve performance of BMC considerably, particularly in the case of the incremental encoding, and that they are very competitive for finding bugs. An analysis of the liveness-to-safety transformation reveals many similarities to the BMC encodings in this paper. Using the liveness-to-safety translation with BDD-based invariant checking results in an efficient method to find shortest counterexamples that complements the BMC-based approach.Comment: Final version for Logical Methods in Computer Science CAV 2005 special issu

    Bacterial membrane-derived vesicles attenuate vancomycin activity against methicillin-resistant staphylococcus aureus

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    Methicillin-resistant Staphylococcus aureus (MRSA) has evolved numerous antimicrobial resistance mechanisms and is identified as a serious public health threat by the World Health Organization and U.S. Centers for Disease Control and Prevention. The glycopeptide vancomycin (VAN) remains a cornerstone of therapy for severe MRSA infections despite increasing reports of therapeutic failure in hospitalized patients with bacteremia or pneumonia. Recently, the role of released bacterial-derived membrane vesicles (MVs) in antibiotic resistance has garnered attention. Here we examined the effect of exogenous MRSA-derived MVs on VAN activity against MRSA in vitro, using minimum inhibitory concentration and checkerboard assays, and ex vivo, incorporating components of host innate immunity such as neutrophils and serum complement present in blood. Additionally, the proteome of MVs from VAN-exposed MRSA was characterized to determine if protein expression was altered. The presence of MVs increased the VAN MIC against MRSA to values where clinical failure is commonly observed. Furthermore, the presence of MVs increased survival of MRSA pre-treated with sub-MIC concentrations of VAN in whole blood and upon exposure to human neutrophils but not human serum. Unbiased proteomic analysis also showed an elevated expression of MV proteins associated with antibiotic resistance (e.g., marR) or proteins that are functionally linked to cell membrane/wall metabolism. Together, our findings indicate MRSA-derived MVs are capable of lowering susceptibility of the pathogen to VAN, whole-blood- and neutrophil-mediated killing, a new pharmacodynamic consideration for a drug increasingly linked to clinical treatment failures

    Pathophysiological effect of chronic and acute stress in Atlantic salmon, Salmo salar (Actinopterygii: Salmoniformes: Salmonidae)

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    The knowledge on the effect of different stress factors on Atlantic salmon, Salmo salar Linnaeus, 1758, is far from complete and therefore we decided to find out how the low water level stress could effect pathophysiological parameters such as: plasma cortisol level, haemoglobin, haematocrit, chloride (Cl−), sodium (Na+), osmolality, lactate, and glucose in this fish; and how this stressor affects the gut morphology. Two hundred and four juvenile Atlantic salmon were randomly distributed into six fibreglass tanks and divided into two groups: group 1 (control) and group 2 (low water level tress). The low water level stre did not affect growth performance and the pathophysiological parameters. Light- and transmission electron microscopy evaluations of the pyloric caeca and the distal intestine revealed that chronic stress had no effect on gut morphology. Low water level stress had no clear effects on pathophysiological parameters and gut morphology of Atlantic salmon

    A case of vertebral coalescence and lateral line deformity in Hypophthalamichthys nobilis (Richardson, 1844) obtained from aquaculture activity in Iran

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    Vertebral coalescence and malformation in the lateral line are reported in a specimen of cultured cyprinid fish Hypophthalamichthys nobilis . Severe vertebral fusion was observed and described. Lateral line showed unusual undulation in the trunk region. Genetic and epigenetic causes may be implicated in these anomalies

    Histological and bacteriological changes in intestine of beluga (Huso huso) following ex vivo exposure to bacterial strains

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    In the present study the intestinal sac method (ex vivo) was used to evaluate the interactions between lactic acid bacteria and staphylococci in the gastrointestinal (GI) tract of beluga (Huso huso). The distal intestine (DI) of beluga was exposed ex vivo to Staphylococcus aureus, Leuconostoc mesenteroides and Lactobacillus plantarum. Histological changes following bacterial exposure were assessed by light and electron microscopy. Control samples and samples exposed only to Leu. mesenteroides and a combination of Leu. mesenteroides and Staph. aureus, had a similar appearance to intact intestinal mucosal epithelium, with no signs of cellular damage. However, exposure of the DI to Staph. aureus and L. plantarum resulted in damaged epithelial cells and disorganized microvilli. Furthermore, 16S rDNA PCR denaturing gradient gel electrophoresis (PCR-DGGE) was used to investigate the adherent microbiota of distal beluga intestine. Several bacterial species were identified by DGGE in the present study that have not previously been identified in beluga

    Interaction of Antibiotics with Innate Host Defense Factors against Salmonella enterica Serotype Newport

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    ABSTRACT This study examines the pharmacodynamics of antimicrobials that are used to treat Salmonella with each other and with key components of the innate immune system. Antimicrobial synergy was assessed using time-kill and checkerboard assays. Antimicrobial interactions with innate immunity were studied by employing cathelicidin LL-37, whole-blood, and neutrophil killing assays. Ceftriaxone and ciprofloxacin were found to be synergistic in vitro against Salmonella enterica serotype Newport. Ceftriaxone, ciprofloxacin, and azithromycin each demonstrated synergy with the human cathelicidin defense peptide LL-37 in killing Salmonella. Exposure of Salmonella to sub-MICs of ceftriaxone resulted in enhanced susceptibility to LL-37, whole blood, and neutrophil killing. The activity of antibiotics in vivo against Salmonella may be underestimated in bacteriologic media lacking components of innate immunity. The pharmacodynamic interactions of antibiotics used to treat Salmonella with each other and with components of innate immunity warrant further study in light of recent findings showing in vivo selection of antimicrobial resistance by single agents in this pathogen. IMPORTANCE It is becoming increasingly understood that the current paradigms of in vitro antimicrobial susceptibility testing may have significant shortcomings in predicting activity in vivo. This study evaluated the activity of several antibiotics alone and in combination against clinical isolates of Salmonella enterica serotype Newport (meningitis case) utilizing both conventional and physiological media. In addition, the interactions of these antibiotics with components of the innate immune system were evaluated. Azithromycin, which has performed quite well clinically despite high MICs in conventional media, was shown to be more active in physiological media and to enhance innate immune system killing. Alternatively, chloramphenicol did not show enhanced immune system killing, paralleling its inferior clinical performance to other antibiotics that have been used to treat Salmonella meningitis. These findings are important additions to the building understanding of current in vitro antimicrobial assay limitations that hopefully will amount to future improvements in these assays to better predict clinical efficacy and activity in vivo

    Azithromycin Exerts Bactericidal Activity and Enhances Innate Immune Mediated Killing of MDR Achromobacter xylosoxidans

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    Azithromycin (AZM), the most commonly prescribed antibiotic in the United States, is thought to have no activity against multidrug-resistant Gram-negative pathogens such as Achromobacter xylosoxidans (AX) per standard minimum inhibitory concentration testing in cation-adjusted Mueller Hinton Broth. Here we provide the first report of AZM bactericidal activity against carbapenem-resistant isolates of AX, with a multifold decrease in minimum inhibitory concentration across 12 clinical isolates when examined under physiologic testing conditions that better recapitulate the in vivo human environment. This pharmaceutical activity, evident in eukaryotic tissue culture media, is associated with enhanced AZM intracellular penetration and synergistic killing with human whole blood, serum, and neutrophils. Additionally, AZM monotherapy inhibited preformed AX biofilm growth in a dose-dependent manner together with a reduction in viable bacteria. In an illustrative case, AZM in combination with piperacillin-tazobactam exerted clear therapeutic effects in a patient with carbapenem-resistant AX mediastinitis, sternal osteomyelitis, and aortic graft infection. Our study reinforces how current antimicrobial testing practices fail to recapitulate the host environment or host-pathogen interactions and may misleadingly declare complete resistance to useful agents, adversely affecting patient outcomes. We conclude that AZM merits further exploration in the treatment of drug-resistant AX infections. Novel approaches to antimicrobial susceptibility testing that better recapitulate the host environment should be considered, especially as infections caused by multidrug-resistant Gram-negative bacterial pathogens are expanding globally with high morbidity and mortality.publishedVersio
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