Susceptibility patterns in Neisseria gonorrhoeae in Nuuk, Greenland, 2015-2018: a short communication.

Antimicrobial resistance in Neisseria gonorrhoeae (GC) has made gonorrhoea control and treatment more complex globally. In Greenland, the incidence of gonorrhoea is high and there is a need for continued surveillance of antimicrobial susceptibility.This study investigated gonococcal isolates obtained in Greenland's capital Nuuk between January 2015 and June 2018. Subsequent to collection, isolates were tested for ciprofloxacin and ceftriaxone susceptibility in order to monitor the resistance pattern among GC strains. 150 GC strains were isolated in Nuuk during the observation period (139 males, 93%; 11 females, 7%). All strains were fully susceptible to ceftriaxone. 49% of the GC strains were susceptible to ciprofloxacin. The median minimal inhibitory concentration (MIC) for ceftriaxone among GC strains resistant to ciprofloxacin was higher than among GC strains susceptible to ciprofloxacin. No differences in ciprofloxacin susceptibility and median MICs for ceftriaxone were observed by collection year. In conclusion no ceftriaxone resistance has been found in Nuuk to date. Continued easy access to diagnostics and treatment combined with increased and more systematic surveillance of antimicrobial susceptibility in Nuuk is recommended. Further, it is advisable to investigate the possibilities for intermittent sampling in Greenland outside of Nuuk, if obstacles in relation to sending sampling material to Nuuk can be bypassed.

Total costs of treating venous thromboembolism: implication of different cost perspectives in a Danish setting.

Aim: Optimal use of scarce resources is a focus in the healthcare sector, as resources devoted to health care are limited. Costs and health economic analyses can help guide decision-making concerning treatments. One important factor is the choice of cost perspective that can range from a focus on narrow drug budget costs to broader economic perspectives. In the case of treatment with oral anticoagulants in patients with venous thromboembolism (VTE), encompassing deep vein thrombosis and pulmonary embolism, the aim of this cost analysis was to illustrate the differences in costs when applying different cost perspectives.Methods: In a cost analysis, pairwise comparisons of average costs of 6 months standard treatment with either a low molecular weight heparin parenteral anticoagulant (LMWH) and a Vitamin K Antagonist (VKA) versus one of the non-vitamin K oral anticoagulants [NOACs; dabigatran etexilate, rivaroxaban, apixaban, and edoxaban) used in daily clinical practice in Denmark for VTE patients were carried out. Each analysis included the results from five different cost analyses with increasingly broader cost perspectives going from the narrowest "drug cost only" perspective to the broadest "societal" perspective.Results: Focusing on "drug costs only", LMWH/VKA was associated with the lowest costs compared to all NOACs. However, including the economic impact of preventing recurrent VTE and limit bleedings, apixaban and rivaroxaban resulted in slightly lower health care costs than LMWH/VKA. When applying the "societal perspective", the total costs saved with apixaban and rivaroxaban compared to LMWH/VKA further increased, with apixaban having the lowest total costs.Conclusions: The present study's case of oral anticoagulants in VTE treatment illustrated the importance of the cost perspective in the choice of therapy. If decision-making were based on drug costs only, instead of applying a health care sector or societal cost perspective, suboptimal decisions may be likely.

Rapid change in the ciprofloxacin resistance pattern among Neisseria gonorrhoeae strains in Nuuk, Greenland: time to reconsider preventive and treatment strategies.

OBJECTIVES: Sexually transmitted infections (STIs), including infections with Neisseria gonorrhoeae (GC), are highly incident in Greenland. Since January 2011, GC testing has been performed on urine with nucleic acid amplification tests (NAATs) by strand displacement amplification (Becton Dickinson ProbeTec). Monitoring of GC antibiotic susceptibility by culture was introduced in Nuuk in 2012. Until 2014, no cases of ciprofloxacin-resistant GC strains were reported. In this paper, we report the finding of ciprofloxacin-resistant GC and describe the most recent incidence of GC infections in Greenland. METHODS: The number of urine NAATs and culture-positive swabs from January to October 2014 were obtained from the Central Laboratory at Queens Ingrid's Hospital in Nuuk and stratified on gender, place and period of testing. Incidence rates were estimated as number of urine NAAT * (12/10) per 100,000 inhabitants. Men in Nuuk with a positive NAAT for GC were encouraged to provide a urethral swab for culture and susceptibility testing. RESULTS: From January to October 2014, a total of 5,436 urine GC NAATs were performed on patients from Nuuk and 9,031 from the rest of Greenland. Of these, 422 (8%) and 820 (9%) were positive, respectively. From January to August, 6 (15%) cultures from Nuuk were ciprofloxacin resistant while in September and October, 26 (59%) were ciprofloxacin resistant (p<0.01). In total, 35 (40%) of 88 culture-positive isolates showed ciprofloxacin resistance. GC incidence in Nuuk was 3,017 per 100,000 inhabitants per year, compared to 2,491 per 100,000 inhabitants per year in the rest of Greenland. CONCLUSION: Within a short period, a rapid and dramatic change in ciprofloxacin susceptibility among GC strains isolated in Nuuk was documented and recommendation for first line treatments has changed. Continued monitoring and rethinking of primary and secondary preventive initiatives is highly recommended in this high GC incidence setting.

High yield purification of full-length functional hERG K+ channels produced in Saccharomyces cerevisiae.

The hERG potassium channel is essential for repolarization of the cardiac action potential. Due to this vital function, absence of unintended and potentially life-threatening interactions with hERG is required for approval of new drugs. The structure of hERG is therefore one of the most sought-after. To provide purified hERG for structural studies and new hERG biomimetic platforms for detection of undesirable interactions, we have developed a hERG expression platform generating unprecedented amounts of purified and functional hERG channels. Full-length hERG, with or without a C-terminally fused green fluorescent protein (GFP) His 8-tag was produced from a codon-optimized hERG cDNA in Saccharomyces cerevisiae. Both constructs complemented the high potassium requirement of a knock-out Saccharomyces cerevisiae strain, indicating correct tetramer assembly in vivo. Functionality was further demonstrated by Astemizole binding to membrane embedded hERG-GFP-His 8 with a stoichiometry corresponding to tetramer assembly. The 156 kDa hERG-GFP protein accumulated to a membrane density of 1.6%. Fluorescence size exclusion chromatography of hERG-GFP-His 8 solubilized in Fos-Choline-12 supplemented with cholesteryl-hemisuccinate and Astemizole resulted in a monodisperse elution profile demonstrating a high quality of the hERG channels. hERG-GFP-His 8 purified by Ni-affinity chromatography maintained the ability to bind Astemizole with the correct stoichiometry indicating that the native, tetrameric structure was preserved. To our knowledge this is the first reported high-yield production and purification of full length, tetrameric and functional hERG. This significant breakthrough will be paramount in obtaining hERG crystal structures, and in establishment of new high-throughput hERG drug safety screening assays.

Low prevalence of ciprofloxacin-resistant Neisseria gonorrhoeae in Nuuk, Greenland.

During a 35-day period, 32 isolates of Neisseria gonorrhoeae strains were collected by culture from patients with positive nucleic acid amplification test results in Nuuk, Greenland, where ciprofloxacin is the preferred treatment. All isolates were quinolone susceptible, suggesting that resistance is rare. Sampling patients for culture before treatment may prove useful in reestablishing surveillance.

Cognitive-affective neural plasticity following active-controlled mindfulness intervention.

Mindfulness meditation is a set of attention-based, regulatory, and self-inquiry training regimes. Although the impact of mindfulness training (MT) on self-regulation is well established, the neural mechanisms supporting such plasticity are poorly understood. MT is thought to act through interoceptive salience and attentional control mechanisms, but until now conflicting evidence from behavioral and neural measures renders difficult distinguishing their respective roles. To resolve this question we conducted a fully randomized 6 week longitudinal trial of MT, explicitly controlling for cognitive and treatment effects with an active-control group. We measured behavioral metacognition and whole-brain blood oxygenation level-dependent (BOLD) signals using functional MRI during an affective Stroop task before and after intervention in healthy human subjects. Although both groups improved significantly on a response-inhibition task, only the MT group showed reduced affective Stroop conflict. Moreover, the MT group displayed greater dorsolateral prefrontal cortex responses during executive processing, consistent with increased recruitment of top-down mechanisms to resolve conflict. In contrast, we did not observe overall group-by-time interactions on negative affect-related reaction times or BOLD responses. However, only participants with the greatest amount of MT practice showed improvements in response inhibition and increased recruitment of dorsal anterior cingulate cortex, medial prefrontal cortex, and right anterior insula during negative valence processing. Our findings highlight the importance of active control in MT research, indicate unique neural mechanisms for progressive stages of mindfulness training, and suggest that optimal application of MT may differ depending on context, contrary to a one-size-fits-all approach.

Long-term meditation is associated with increased gray matter density in the brain stem.

Extensive practice involving sustained attention can lead to changes in brain structure. Here, we report evidence of structural differences in the lower brainstem of participants engaged in the long-term practice of meditation. Using magnetic resonance imaging, we observed higher gray matter density in lower brain stem regions of experienced meditators compared with age-matched nonmeditators. Our findings show that long-term practitioners of meditation have structural differences in brainstem regions concerned with cardiorespiratory control. This could account for some of the cardiorespiratory parasympathetic effects and traits, as well as the cognitive, emotional, and immunoreactive impact reported in several studies of different meditation practices.

Structure function relationships of transgenic starches with engineered phosphate substitution and starch branching.

Potato tuber starch was genetically engineered in the plant by the simultaneous antisense suppression of the starch branching enzyme (SBE) I and II isoforms. Starch prepared from 12 independent lines and three control lines were characterised with respect to structural and physical properties. The lengths of the amylopectin unit chains, the concentrations of amylose and monoesterified phosphate were significantly increased in the transgenically engineered starches. Size exclusion chromatography with refractive index detection (SEC-RI) indicated a minor decrease in apparent molecular size of the amylose and the less branched amylopectin fractions. Differential scanning calorimetry (DSC) revealed significantly higher peak temperatures for gelatinisation and retrogradation of the genetically engineered starches whereas the enthalpies of gelatinisation were lower. Aqueous gels prepared from the transgenic starches showed increased gel elasticity and viscosity. Principle component analysis (PCA) of the data set discriminated the control lines from the transgenic lines and revealed a high correlation between phosphate concentration and amylopectin unit chain length. The PCA also indicated that the rheological characteristics were primarily influenced by the amylose concentration. The phosphate and the amylopectin unit chain lengths had influenced primarily the pasting and rheological properties of the starch gels.