Diminished Virulence Of A Sar-lagr- Mutant Of Staphylococcus Aureus In The Rabbit Model Of Endocarditis

Microbial pathogenicity in Staphylococcus aureus is a complex process involving a number of virulence genes that are regulated by global regulatory systems including sar and agr. To evaluate the roles of these two loci in virulence, we constructed sar-lagr- mutants of strains RN6390 and RN450 and compared their phenotypic profiles to the corresponding single sar- and agr- mutants and parents. The secretion of all hemolysins was absent in the sar-lagr- mutants while residual β-hemolysin activity remained in single agr- mutants. The fibronectin binding capacity was significantly diminished in both single sar- mutants and double mutants when compared with parents while the reduction in fibrinogen binding capacity in the double mutants was modest. In the rabbit endocarditis model, there was a significant decrease in both infectivity rates and intravegetation bacterial densities with the double mutant as compared to the parent (RN6390) at 103-106 CFU inocula despite comparable levels of early bacteremia among various challenge groups. Notably, fewer bacteria in the double mutant group adhered to valvular vegetations at 30 min after challenge (106 CFU) than the parent group. These studies suggest that both the sar and agr loci are involved in initial valvular adherence, intravegetation persistence and multiplication of S. aureus in endocarditis.94518151822Waldvogel, F.A., Staphylococcus aureus (1985) Principles and Practice of Infectious Diseases, pp. 1097-1116. , G. L. Mandell, R. G. Douglas, Jr., and J. E. Bennett, editors. John Wiley & Sons, New YorkNeu, H.C., The crisis in antibiotic resistance (1992) Science (Wash. 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Immun., 61, pp. 919-925Cheung, A.L., Koomey, J.M., Butler, C.A., Projan, S.J., Fischetti, V.A., Regulation of exoprotein expression in Staphylococcus aureus by a locus (sar) distinct from agr (1992) Proc. Natl. Acad. Sci. USA, 89, pp. 6462-6466Cheung, A.L., Yeaman, M., Bayer, A.S., The role of the sar locus of Staphylococcus aureus in the induction of endocarditis in rabbits (1994) Infect. Immun., 62, pp. 1719-1725Vandenesch, F., Kornblum, J., Novick, R.P., A temporal signal, independent of agr, is required for hla but not spa transcription in Staphylococcus aureus (1991) J. Bacteriol., 173, pp. 6313-6320Cheung, A.L., Ying, P., Regulation of α and β hemolysins by the sar locus of Staphylococcus aureus (1994) J. Bacteriol., 176, pp. 580-585Rescei, P., Kreiswirth, B., O'Reilly, M., Schlievert, P., Gruss, A., Novick, R.P., Regulation of exoprotein gene expression in Staphylococcus aureus by agr (1986) Mol. & Gen. 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Synthesis of chitosan oligomers/propolis/silver-nanoparticles composite systems and study of their activity against Diplodia seriata

The synthesis and characterization of composites of oligomeric chitosan with propolis extract which allow the incorporation of a third component (silver nanoparticles) are reported, together with their application in aqueous or hydroalcoholic solutions with a view to the formation of adhesive substances or nanofilms for the protection of vineyards against harmful xylophagous fungi. The antimicrobial properties of the association of the two biological products or those resulting from the incorporation of silver nanoparticles (NPs) are studied and discussed. The efficacy of the chitosan oligomers/propolis/silver NPs ternary system is assessed in vitro for Diplodia fungi. A preliminary study on the convenience of replacing propolis with gentisic acid is also presented

Two-soliton collisions in a near-integrable lattice system

We examine collisions between identical solitons in a weakly perturbed Ablowitz-Ladik (AL) model, augmented by either onsite cubic nonlinearity (which corresponds to the Salerno model, and may be realized as an array of strongly overlapping nonlinear optical waveguides), or a quintic perturbation, or both. Complex dependences of the outcomes of the collisions on the initial phase difference between the solitons and location of the collision point are observed. Large changes of amplitudes and velocities of the colliding solitons are generated by weak perturbations, showing that the elasticity of soliton collisions in the AL model is fragile (for instance, the Salerno's perturbation with the relative strength of 0.08 can give rise to a change of the solitons' amplitudes by a factor exceeding 2). Exact and approximate conservation laws in the perturbed system are examined, with a conclusion that the small perturbations very weakly affect the norm and energy conservation, but completely destroy the conservation of the lattice momentum, which is explained by the absence of the translational symmetry in generic nonintegrable lattice models. Data collected for a very large number of collisions correlate with this conclusion. Asymmetry of the collisions (which is explained by the dependence on the location of the central point of the collision relative to the lattice, and on the phase difference between the solitons) is investigated too, showing that the nonintegrability-induced effects grow almost linearly with the perturbation strength. Different perturbations (cubic and quintic ones) produce virtually identical collision-induced effects, which makes it possible to compensate them, thus finding a special perturbed system with almost elastic soliton collisions.Comment: Phys. Rev. E, in pres

Colonic transit in children and adolescents with chronic constipation

AbstractObjectiveThe aim of this study was to assess clinical features and colonic transit patterns in Brazilian children with refractory constipation.MethodsFrom 2010 to 2013, 79 constipated patients received follow-up care in a tertiary hospital. Of these patients, 28 (aged 8–14 years) were refractory to conventional therapy and underwent a simplified visual method of nuclear colonic transit study, by ingestion of a liquid meal containing 9.25MBq/kg of 99mTc-phytate. Abdominal static images were taken immediately and at two, six, 24, 30, and 48h after ingestion for qualitative analysis of the radio marker progression through the colon.ResultsTwo patterns of colonic transit were found: slow colonic transit (SCT, n=14), when images at 48h showed a larger part of the tracer remained in proximal and transverse colon, and distal retention (DR, n=14), when after 30h, the radio isotope passed the transverse colon and was retained in the rectosigmoid up to 48h. The SCT and DR group included, respectively, nine and ten males; median ages in the nuclear study of 11 and 10 years, p=0.207; median duration of constipation of seven and six years, p=0.599. Constipation appearing during first year age (p=0.04) and report of soft stools (p=0.02) were more common in SCT patients. Palpable abdominal fecal impaction was found only in DR group. Appendicostomy for antegrade continence enema was successful in 4/12 (30%) of SCT patients (median follow-up: 2.4 years).ConclusionNuclear transit study distinguished two colonic dysmotility patterns and was useful for guiding refractory patients to specific therapies

Improving the performance of a preference-based multi-objective algorithm to optimize food treatment processes

This work focuses on the optimization of some high-pressure and temperature food treatments. When dealing with real--life multi-objective optimization problems, the computational cost of evaluating the considered objective functions is usually quite high. Therefore, only a reduced number of iterations is affordable for the optimization algorithm. However, using fewer iterations can lead to inaccurate solutions far from the real Pareto optimal front. In this work, we analyze and compare different mechanisms to improve the convergence of a preference-based multi-objective optimization algorithm called Weighting Achievement Scalarizing Function Genetic Algorithm. The combination of these techniques has been applied for optimizing a particular food treatment process. In particular, the proposed method based on the introduction of an advanced population achieves important improvements in the considered quality indicator measures

Higher Order Evaluation of the Critical Temperature for Interacting Homogeneous Dilute Bose Gases

We use the nonperturbative linear \delta expansion method to evaluate analytically the coefficients c_1 and c_2^{\prime \prime} which appear in the expansion for the transition temperature for a dilute, homogeneous, three dimensional Bose gas given by T_c= T_0 \{1 + c_1 a n^{1/3} + [ c_2^{\prime} \ln(a n^{1/3}) +c_2^{\prime \prime} ] a^2 n^{2/3} + {\cal O} (a^3 n)\}, where T_0 is the result for an ideal gas, a is the s-wave scattering length and n is the number density. In a previous work the same method has been used to evaluate c_1 to order-\delta^2 with the result c_1= 3.06. Here, we push the calculation to the next two orders obtaining c_1=2.45 at order-\delta^3 and c_1=1.48 at order-\delta^4. Analysing the topology of the graphs involved we discuss how our results relate to other nonperturbative analytical methods such as the self-consistent resummation and the 1/N approximations. At the same orders we obtain c_2^{\prime\prime}=101.4, c_2^{\prime \prime}=98.2 and c_2^{\prime \prime}=82.9. Our analytical results seem to support the recent Monte Carlo estimates c_1=1.32 \pm 0.02 and c_2^{\prime \prime}= 75.7 \pm 0.4.Comment: 29 pages, 3 eps figures. Minor changes, one reference added. Version in press Physical Review A (2002

Asymptotically Improved Convergence of Optimized Perturbation Theory in the Bose-Einstein Condensation Problem

We investigate the convergence properties of optimized perturbation theory, or linear $\delta$ expansion (LDE), within the context of finite temperature phase transitions. Our results prove the reliability of these methods, recently employed in the determination of the critical temperature T_c for a system of weakly interacting homogeneous dilute Bose gas. We carry out the explicit LDE optimized calculations and also the infrared analysis of the relevant quantities involved in the determination of $T_c$ in the large-N limit, when the relevant effective static action describing the system is extended to O(N) symmetry. Then, using an efficient resummation method, we show how the LDE can exactly reproduce the known large-N result for $T_c$ already at the first non-trivial order. Next, we consider the finite N=2 case where, using similar resummation techniques, we improve the analytical results for the nonperturbative terms involved in the expression for the critical temperature allowing comparison with recent Monte Carlo estimates of them. To illustrate the method we have considered a simple geometric series showing how the procedure as a whole works consistently in a general case.Comment: 38 pages, 3 eps figures, Revtex4. Final version in press Phys. Rev.

Mechanical stress and inflammation have opposite effects on Wnt signaling in human chondrocytes

Dysregulation of Wingless and Int-1 (Wnt) signaling has been strongly associated with development and progression of osteoarthritis (OA). Here, we set out to investigate the independent effects of either mechanical stress (MS) or inflammation on Wnt signaling in human neocartilage pellets, and to relate this Wnt signaling to OA pathophysiology. OA synovium-conditioned media (OAS-CM) was collected after incubating synovium from human end-stage OA joints for 24 h in medium. Cytokine levels in the OAS-CM were determined with a multiplex immunoassay (Luminex). Human neocartilage pellets were exposed to 20% MS, 2% OAS-CM or 1 ng/mL Interleukin-1 & beta; (IL-1 & beta;). Effects on expression levels of Wnt signaling members were determined by reverse transcription-quantitative polymerase chain reaction. Additionally, the expression of these members in articular cartilage from human OA joints was analyzed in association with joint space narrowing (JSN) and osteophyte scores. Protein levels of IL-1 & beta;, IL-6, IL-8, IL-10, tumor necrosis factor & alpha;, and granulocyte-macrophage colony-stimulating factor positively correlated with each other. MS increased noncanonical WNT5A and FOS expression. In contrast, these genes were downregulated upon stimulation with OAS-CM or IL-1 & beta;. Furthermore, Wnt inhibitors DKK1 and FRZB decreased in response to OAS-CM or IL-1 & beta; exposure. Finally, expression of WNT5A in OA articular cartilage was associated with increased JSN scores, but not osteophyte scores. Our results demonstrate that MS and inflammatory stimuli have opposite effects on canonical and noncanonical Wnt signaling in human neocartilage. Considering the extent to which MS and inflammation contribute to OA in individual patients, we hypothesize that targeting specific Wnt pathways offers a more effective, individualized approach.Orthopaedics, Trauma Surgery and Rehabilitatio

An altered microbiota pattern precedes Type 2 diabetes mellitus development: From the CORDIOPREV study

Introduction. A distinctive gut microbiome have been linked to type 2 diabetes mellitus (T2DM). We aimed to evaluate whether gut microbiota composition, in addition to clinical biomarkers, could improve the prediction of new incident cases of diabetes in patients with coronary heart disease. Methods All the patients from the CORDIOPREV (Clinical Trials.gov.Identifier: NCT00924937) study without T2DM at baseline were included (n = 462). Overall, 107 patients developed it after a median of 60 months. The gut microbiota composition was determined by 16S rRNA gene sequencing and predictive models were created using hold-out method. Results. A gut microbiota profile associated with T2DM development was determined through a microbiome-based predictive model. The addition of microbiome data to clinical parameters (variables included in FINDRISC risk score and the diabetes risk score of the American Diabetes Association, HDL, triglycerides and HbA1c) improved the prediction increasing the area under the curve from 0.632 to 0.946. Furthermore, a microbiome-based risk score including the ten most discriminant genera, was associated with the probability of develop T2DM. Conclusión. These results suggest that a microbiota profile is associated to the T2DM development. An integrate predictive model of microbiome and clinical data that can improve the prediction of T2DM is also proposed, if is validated in independent populations to prevent this disease