Prevalence of and risk factors for quinolone-resistant Neisseria gonorrhoeae infection in Ontario

Background

Quinolone-resistant Neisseria gonorrhoeae has swiftly emerged in Canada. We sought to determine its prevalence in the province of Ontario and to investigate risk factors for quinolone-resistant N. gonorrhoeae infection in a Canadian setting.

Methods

We used records from the Public Health Laboratory of the Ontario Agency for Health Protection and Promotion in Toronto, Ontario, and the National Microbiology Laboratory in Winnipeg, Manitoba, to generate epidemic curves for N. gonorrhoeae infection. We extracted limited demographic data from 2006 quinolone-resistant N. gonorrhoeae isolates and from a random sample of quinolone-susceptible isolates. We also extracted minimum inhibitory concentrations for commonly tested antibiotics.

Results

Between 2002 and 2006, the number of N. gonorrhoeae infections detected by culture decreased by 26% and the number of cases detected by nucleic acid amplification testing increased 6-fold. The proportion of N. gonorrhoeae isolates with resistance to quinolones increased from 4% to 28% over the same period. Analysis of 695 quinolone-resistant N. gonorrhoeae isolates and 688 quinolone-susceptible control isolates from 2006 showed a higher proportion of men (odds ratio [OR] 3.1, 95% confidence interval [CI] 2.3–4.1) and patients over 30 years of age (OR 3.1, 95% CI 2.4–3.8) in the quinolone-resistant group. The proportion of men who have sex with men appeared to be relatively similar in both groups (OR 1.4, 95% CI 1.1–1.8). Quinolone-resistant strains were more resistant to penicillin (p < 0.001), tetracycline (p < 0.001) and erythromycin (p < 0.001). All isolates were susceptible to cefixime, ceftriaxone, azithromycin and spectinomycin.

Interpretation

During 2006 in Ontario, 28% of N. gonorrhoeae isolates were resistant to quinolones. Infections in heterosexual men appear to have contributed significantly to the quinolone resistance rate. Medical practitioners should be aware of the widespread prevalence of quinolone-resistant N. gonorrhoeae and avoid quinolone use for empiric therapy.After declining for a number of years, Neisseria gonorrhoeae infections are once more on the rise in Canada. Between 1997 and 2007, reported incidence of the disease more than doubled, from 15 to 35 cases per 100 000.¹ To address the emergence of quinolone-resistant N. gonorrhoeae strains, the empiric treatment regimens for N. gonorrhoeae infection were recently revised in the 2006 Canadian Guidelines on Sexually Transmitted Infections.^2,3 Quinolones are no longer recommended for empiric therapy for N. gonorrhoeae infection.³In Canada, quinolone resistance in N. gonorrhoeae isolates increased from an estimated 2% in 2001 to 16% in 2005.⁴ Demographic risk factors for quinolone-resistant N. gonorrhoeae infection have not been studied. American studies have associated quinolone-resistant N. gonorrhoeae infection with men who have sex with men,^5,6 antibiotic use,^5,7 age above 35 years,⁵ HIV infection⁵ and travel to Asia.⁶ Public health data from the provinces of Quebec⁸ and Alberta² have also suggested an association between quinolone-resistant infection and men who have sex with men. In this study we generated epidemic curves for N. gonorrhoeae and quinolone-resistant N. gonorrhoeae infection in the province of Ontario. We also investigated demographic risk factors for quinolone-resistant N. gonorrhoeae infection.     

Assessing genetic diversity for conservation management: a case study of a threatened reptile

The consequences of inbreeding in small isolated populations are well documented, yet populations are often managed in isolation to avoid irreversibly mixing genetic lineages and to maintain the historic integrity of each population. Three remaining populations of Whitaker's skink ( Cyclodina whitakeri ) in New Zealand, remnants of a once wider distribution, illustrate the conflict between this genetic goal (separate management of populations) with the more tangible and immediate threats of small population size and inbreeding. Middle and Castle Islands harbour populations of C. whitakeri and have been separated from each other and from the mainland for ∼10 000 years. The single mainland population at Pukerua Bay is extremely small, declining and deemed a high priority for management. We sequenced a 550 bp region of mitochondrial DNA (mtDNA,ND2) and genotyped animals from all three populations at 13 microsatellite loci. The population of C. whitakeri at Pukerua Bay showed marked differences from the island populations at both mtDNA (unique, fixed haplotype) and microsatellite loci ( F _ST∼0.20), and private alleles were detected at a high frequency (24% of all alleles). However, we attribute this pattern to an historic genetic gradient coupled with rapid genetic drift. Further, animals in captivity show genetic signatures of both Pukerua Bay and island populations, despite the goal to maintain a pure Pukerua Bay stock. The mixed genetic stock in captivity provides an opportunity for the addition of skinks from Middle Island to evaluate the risks of further population hybridization, including the disruption of potential local adaptation, while mitigating the risks of inbreeding.     

Effect of organotin compounds and hexachlorophene on brain adenosine cyclic 3',5'-monophosphate metabolism.

The effect of triethyltin (TET), triphenyltin (TPT), hexachlorophene (HCP) and cuprizone on adenosine cyclic 3',5'-monophosphate (cyclic AMP) production in rat brain was examined both in vitro and in vivo. TET and TPT inhibited basal adenylate cyclase activity of brain homogenate at a concentration as low as 1 microM in vitro but these compounds had no effect on norepinephrine (NE) and dopamine(DA)-stimluated enzyme activity. HCP and cuprizone failed to inhibit adenylate cyclase activity. In vivo TET given intravenously at a dose rate of 10 mg/kg decreased the cyclic AMP content of cerebrum, but not of medulla. TPT and HCP give intravenously and intraperitoneally respectively failed to decrease the cyclic AMP content of the cerebrum. In the case of TET the reduction in cyclic AMP content of the cerebrum was prevented by maintaining the rats normothermic after treatment. On the basis of these results the inhibition of adenylate cyclase produced by TET in brain homogenates in vitro would not appear to be involved in the development of nervous changes associated with acute TET toxicity, or in the production of progressive brain oedema caused by TET, HCP and cuprizone.     

Associations of Forest Type,Parasitism and Body Condition of Two European Passerines,Fringilla coelebs and Sylvia atricapilla

Human-induced forest modification can alter parasite-host interactions and might change the persistence of host populations. We captured individuals of two widespread European passerines (Fringilla coelebs and Sylvia atricapilla) in southwestern Germany to disentangle the associations of forest types and parasitism by haemosporidian parasites on the body condition of birds. We compared parasite prevalence and parasite intensity, fluctuating asymmetries, leukocyte numbers, and the heterophil to lymphocyte ratio (H/L-ratio) among individuals from beech, mixed-deciduous and spruce forest stands. Based on the biology of bird species, we expected to find fewer infected individuals in beech or mixed-deciduous than in spruce forest stands. We found the highest parasite prevalence and intensity in beech forests for F. coelebs. Although, we found the highest prevalence in spruce forests for S. atricapilla, the highest intensity was detected in beech forests, partially supporting our hypothesis. Other body condition or health status metrics, such as the heterophil to lymphocyte ratio (H/L-ratio), revealed only slight differences between bird populations inhabiting the three different forest types, with the highest values in spruce for F. coelebs and in mixed-deciduous forests for S. atricapilla. A comparison of parasitized versus non-parasitized individuals suggests that parasite infection increased the immune response of a bird, which was detectable as high H/L-ratio. Higher infections with blood parasites for S. atricapilla in spruce forest indicate that this forest type might be a less suitable habitat than beech and mixed-deciduous forests, whereas beech forests seem to be a suboptimal habitat regarding parasitism for F. coelebs.     

Stochastic analysis of the GAL genetic switch in Saccharomyces cerevisiae: Modeling and experiments reveal hierarchy in glucose repression

Background

Most mathematical models of biochemical pathways consider either signalling events that take place within a single cell in isolation, or an 'average' cell which is considered to be representative of a cell population. Likewise, experimental measurements are often averaged over populations consisting of hundreds of thousands of cells. This approach ignores the fact that even within a genetically-homogeneous population, local conditions may influence cell signalling and result in phenotypic heterogeneity. We have developed a multi-scale computational model that accounts for emergent heterogeneity arising from the influences of intercellular signalling on individual cells within a population. Our approach was to develop an ODE model of juxtacrine EGFR-ligand activation of the MAPK intracellular pathway and to couple this to an agent-based representation of individual cells in an expanding epithelial cell culture population. This multi-scale, multi-paradigm approach has enabled us to simulate Extracellular signal-regulated kinase (Erk) activation in a population of cells and to examine the consequences of interpretation at a single cell or population-based level using virtual assays.

Results

A model consisting of a single pair of interacting agents predicted very different Erk activation (phosphorylation) profiles, depending on the formation rate and stability of intercellular contacts, with the slow formation of stable contacts resulting in low but sustained activation of Erk, and transient contacts resulting in a transient Erk signal. Extension of this model to a population consisting of hundreds to thousands of interacting virtual cells revealed that the activated Erk profile measured across the entire cell population was very different and may appear to contradict individual cell findings, reflecting heterogeneity in population density across the culture. This prediction was supported by immunolabelling of an epithelial cell population grown in vitro, which confirmed heterogeneity of Erk activation.

Conclusion

These results illustrate that mean experimental data obtained from analysing entire cell populations is an oversimplification, and should not be extrapolated to deduce the signal:response paradigm of individual cells. This multi-scale, multi-paradigm approach to biological simulation provides an important conceptual tool in addressing how information may be integrated over multiple scales to predict the behaviour of a biological system.     

Conservation and restoration of New Zealand Island ecosystems

An ecological collapse has precipitated pioneering conservation initiatives in New Zealand. Many terrestrial communities in t he New Zealand archipelago have been devastated by over-exploitation, introduced mammals and habitat destruction. More recently, marine ecosystems have been depleted by over-harvesting. To mitigate against these losses, conservation in terrestrial environments has focused on protection of species and habitats. A similar approach is now under way in marine environments with the establishment of ‘no-take’ marine reserves. On land, conservation is now reaching beyond protection t o the eradication of pests from islands and restoration of their terrestrial ecosystems. Restoration on islands not only reduces threats to rare species; it also raises opportunities to investigate how species interact. In the sea, marine reserves not only enhance the diversity of depleted marine communities; they may also augment stocks of commercially harvested species. These initiatives provide many lessons that could be applied to degraded habitats elsewhere.     

Sera from patients with type 2 diabetes and neuropathy induce autophagy and colocalization with mitochondria in SY5Y cells

The etiology of diabetic neuropathy is multifactorial and not fully elucidated, although oxidative stress and mitochondrial dysfunction are major factors. We reported previously that complement-inactivated sera from type 2 diabetic patients with neuropathy induce apoptosis in cultured neuronal cells, possibly through an autoimmune immunoglobulin-mediated pathway. Recent evidence supports an emerging role for autophagy in a variety of diseases. Here we report that exposure of human neuroblastoma SH-SY5Y cells to sera from type 2 diabetic patients with neuropathy is associated with increased levels of autophagosomes that is likely mediated by increased titers of IgM or IgG autoimmune immunoglobulins. The increased presence of macroautophagic vesicles was monitored using a specific immunohistochemical marker for autophagosomes, anti-LC3-II immunoreactivity, as well as the immunohistochemical signal for beclin-1, and was associated with increased co-localization with mitochondria in the cells exposed to diabetic neuropathic sera. We also report that dorsal root ganglia removed from streptozotocin-induced diabetic rats exhibit increased levels of autophagosomes and co-localization with mitochondria in neuronal soma, concurrent with enhanced binding of IgG and IgM autoimmune immunoglobulins. To our knowledge, this is the first evidence that the presence of autophagosomes is increased by a serum factor, likely autoantibody(ies) in a pathological condition. Stimulation of autophagy by an autoantibody-mediated pathway can provide a critical link between the immune system and the loss of function and eventual demise of neuronal tissue in type 2 diabetes.     

Effect of isoproterenol (ISO) on rat heart,liver, kidney,and muscle tissue levels of zinc,copper, and magnesium

X-ray fluorescence and atomic absorption spectrometry were used to measure the concentrations of zinc, copper, and magnesium in the heart, liver, skeletal muscle, and kidney following isoproterenol-induced myocardial necrosis in male albino rats. Serum activities of lactic dehydrogenase (LDH), creatine phosphokinase (CPK), and glutamic oxaloacetic transaminase (SGOT) were also measured. There was depletion of myocardial zinc, copper, and magnesium on d 1, followed by an uptake of all these elements on d 2. The liver showed a significant uptake of magnesium, along with depletion of copper. There was no change in the kidney and skeletal muscle concentrations of these elements. Possible explanations for the observed changes and their therapeutic significance are presented.