Azithromycin Treatment Failure Among Primary and Secondary Syphilis Patients in Shanghai

Azithromycin has been used to treat primary and secondary syphilis and as prophylaxis for sexual partners. We evaluated syphilis treatment failure in patients who received azithromycin therapy

Extended non-stationary chimera-like region in a network of non-identical coupled Van der Pol’s oscillators

Chimera states are peculiar spatiotemporal patterns of coupled oscillators composed of coherent and incoherent groups. In this paper, we study a network of non-identical coupled Van der Pol’s oscillators and investigate the robustness of the chimera states against the oscillators frequency mismatches. The dynamical behaviors of the network are obtained for various coupling strengths and ranges, in different inhomogeneity levels, and the phase diagrams are presented. It is observed that the parameter inhomogeneity leads to the occurrence of synchronization in higher coupling strengths and expansion of the chimera region. In contrast to the identical network, in the non-identical network, a great deal of the chimera region belongs to the non-stationary chimera

Regulatory T cells in peripheral blood and cerebrospinal fluid of syphilis patients with and without neurological involvement.

BACKGROUND: Syphilis, a sexually transmitted disease caused by spirochetal bacterium Treponema pallidum, can progress to affect the central nervous system, causing neurosyphilis. Accumulating evidence suggest that regulatory T cells (Tregs) may play an important role in the pathogenesis of syphilis. However, little is known about Treg response in neurosyphilis. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed Treg frequencies and Transforming Growth Factor-β (TGF-β) levels in the blood and CSF of 431 syphilis patients without neurological involvement, 100 neurosyphilis patients and 100 healthy donors. Suppressive function of Tregs in peripheral blood was also assessed. Among syphilis patients without neurological involvement, we found that secondary and serofast patients had increased Treg percentages, suppressive function and TGF-β levels in peripheral blood compared to healthy donors. Serum Rapid Plasma Reagin (RPR) titers were positively correlated with Treg numbers in these patients. Compared to these syphilis patients without neurological involvement, neurosyphilis patients had higher Treg frequency in peripheral blood. In the central nervous system, neurosyphilis patients had higher numbers of leukocytes in CSF compared to syphilis patients without neurological involvement. CD4(+) T cells were the predominant cell type in the inflammatory infiltrates in CSF of neurosyphilis patients. Interestingly, among these neurosyphilis patients, a significant decrease in CSF CD4(+) CD25(high) Treg percentage and number was observed in symptomatic neurosyphilis patients compared to those of asymptomatic neurosyphilis patients, which may be associated with low CSF TGF-β levels. CONCLUSIONS: Our findings suggest that Tregs might play an important role in both bacterial persistence and neurologic compromise in the pathogenesis of syphilis

Chaotický oscilátor s fracmemristorem a vlastnostmi vícestability a antimonotonicity

Memristor is a non-linear circuit element in which voltage-current relationship is determined by the previous values of the voltage and current, generally the history of the circuit. The nonlinearity in this component can be considered as a fractional-order form, which yields a fractional memristor (fracmemristor). In this paper, a fractional-order memristor in a chaotic oscillator is applied, while the other electronic elements are of integer order. The fractional-order range is determined in a way that the circuit has chaotic solutions. Also, the statistical and dynamical features of this circuit are analyzed. Tools like Lyapunov exponents and bifurcation diagram show the existence of multistability and antimonotonicity, two less common properties in chaotic circuits.Memristor je nelineární obvodový prvek, u kterého je relace napětí-proud dána předchozími hodnotami napětí a proudu, tedy historií obvodu. Nelinearita v této součástce může být uvažována necelistvého řádu, čímž dostáváme fraktální memristor (fracmemristor). V tomto článku je memristor fraktálního řádz zapojen v chaotickém oscilátoru, zatímco ostatní obvodové prvky jsou celistvého řádu. Rozsah fraktálního řádu je určen tím, aby obvod vykazoval chaotické řešení. Analyzovány jsou statistické a dynamické vlastnosti obvodu. Nástroje jako Ljapunovské exponenty a bifurkační diagram ukazuje existenci vícestability a antimonotonicity, tedy dvě méně běžné vlastnosti chaoticých systémů

Absolute number of leukocytes, percentage and numbers of CD4⁺ T cells, Tregs, and TGF-β levels in CSF from different types of syphilis patients.

a<p>CSF samples from 20 syphilis patients without neurological involvement, 23 asymptomatic, 7 meningeal and 14 parenchymal neurosyphilis patients were analyzed by flow cytometry.</p>b<p>vs. syphilis patients without neurological involvement;</p>c<p>vs. asymptomatic neurosyphilis patients;</p>d<p>vs. meningeal neurosyphilis patients;</p>e<p>percentage (%) among CD45⁺ leukocytes;</p>f<p>percentage (%) among CD4⁺ T cells.</p>g<p>TGF-β levels were examined in 41 syphilis patients without neurological involvement and 63 neurosyphilis patients.</p><p><b>Abbreviations</b>: NS, Not Significant.</p

Treg frequencies in peripheral blood of neurosyphilis patients.

<p>The percentage of CD25^high (<b>A</b>) and Foxp3⁺ (<b>B</b>) among CD4⁺ T cells in peripheral blood of healthy controls, and syphilis patients without (including primary, secondary, latent and serofast syphilis) and with (including both asymptomatic and symptomatic neurosyphilis) neurological involvement are shown. The percentage of CD25^high (<b>C</b>) and Foxp3⁺ (<b>D</b>) among CD4⁺ T cells in peripheral blood of different types of neurosyphilis patients. Individual frequencies for every patient analyzed are shown. <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0002528#s3" target="_blank">Results</a> represent the mean ± SEM. A and B, Kruskal-Wallis test; C and D, One-way ANOVA. *, P<0.05, ***, P<0.001.</p

Association of circulating Treg numbers with serum RPR titers in primary, secondary, latent and serofast syphilis patients.

<p>Serum RPR titers are plotted against circulating CD4⁺ CD25^high Treg frequencies in primary (<b>A</b>, n = 64), secondary (<b>B</b>, n = 96), latent (<b>C</b>, n = 86) and serofast (<b>D</b>, n = 43) syphilis patients. Each dot represents an individual patient. The straight line in each graph is the result of linear regression analysis. Pearson's correlation coefficients (r) and P values are shown.</p

Treg activity in the peripheral blood of early and serofast syphilis patients.

<p>(<b>A</b>) Peripheral blood mononuclear cells (PBMC) were stained for flow cytometric analysis and lymphocytes were gated according to forward and side scatter characteristics. Representative plots show the gates of CD4⁺ CD25^high and CD4⁺ Foxp3⁺ T cells in the lymphocyte gate. CD25 and Foxp3 expression among CD4⁺ T cells are also shown. (<b>B</b>) The percentage of CD25^high and Foxp3⁺ among CD4⁺ T cells in peripheral blood of healthy controls, and in patients with primary, secondary, latent and serofast syphilis. Individual frequencies for every patient analyzed are shown. (<b>C</b>) CD4⁺ CD25⁺ T cells and CD4⁺ CD25⁻ T cells were purified from peripheral blood of healthy donors, and patients with primary, secondary, latent and serofast syphilis. The mean percent inhibition of the proliferative response by CD4⁺ CD25⁺ T cells derived from three to five individuals per group is shown. <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0002528#s3" target="_blank">Results</a> are representative of three independent experiments. (<b>D</b>) Serum concentrations of TGF-β were measured in healthy controls, and in patients with primary, secondary syphilis, latent, and serofast syphilis. <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0002528#s3" target="_blank">Results</a> represent the mean or the mean ± SEM. (<b>E</b>) Correlation of serum TGF-β concentration with circulating CD4⁺ CD25^high Treg frequencies in syphilis patients (n = 176). Each dot represents an individual patient. B, Kruskal-Wallis test; C and D, One-way ANOVA; E, Pearson's correlation. *, P<0.05; **, P<0.01; ***, P<0.001.</p

Schematic diagram summarizing the role of Treg in syphilis.

<p>APC, antigen presenting cells; Th1, T helper cell type 1; Treg, regulatory T cells; CSF, cerebrospinal fluid; CNS, central nervous system; DC, dendritic cells.</p

Factors that influence normalization of each laboratory measure in the final Cox regression models.

<p>HR, hazard ratio; NS, in the stepwise model and therefore not included in the final model;</p>a<p>Early (secondary and early latent) stage versus late latent stage and unknown duration;</p>b<p>aqueous crystalline pencillin G,4MU intravenous every 4 h for 14 days versus ceftriaxone, 2 g intravenous daily for 10 days;</p>c<p>Greater than the median value versus less than or equal to the median value in subjects with each abnormality. Median values were as follows: CSF WBC count, 8.8 cells/ml; CSF protein concentration, 68 mg/dl; CSF-VDRL titer, 1∶4; serum RPR test titer, 1∶64.</p>d<p>CSF IL-17 positive (≥0.5 pg/ml) versus CSF IL-17 negative (<0.5 pg/ml).</p