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Background: Intravenous drug use (IVDU) represents the major factor of HCV transmission, but the treatment uptake among people who inject drugs (PWID) remains low owing to a false presumption of low efficacy. The aim of our study was to assess treatment efficacy in PWID and factors determining adherence to therapy., Methods: A total of 278 consecutive patients starting DAA (direct-acting antivirals) therapy were included, divided into two groups: individuals with a history of IVDU, PWID group (N = 101) and the control group (N = 177) without a history of IVDU., Results: Sustained virological response 12 weeks after the end of therapy (SVR12) was achieved by 99/101 (98%) and 172/177 (98%) patients in the PWID and control group, respectively; in PWID group, two patients were lost to follow-up, and in the control group, four patients relapsed and one was lost to follow-up. PWID patients postponed appointments significantly more often, 29 (28.7%) in PWID versus 7 (4%) in the control group, p = 0.001. Thirteen of 101 (12.9%) and six of 177 (3.4%) patients in the PWID and in the control group, respectively, missed at least one visit (p < 0.01). However, postponing visits led to a lack of medication in only one PWID. In the PWID group, older age (p < 0.05; OR 1.07, 95% CI 1.00-1.20) and stable housing (p < 0.01; OR 9.70, 95% CI 2.10-56.20) were factors positively contributing to adherence. Contrarily, a stable job was a factor negatively influencing adherence (p < 0.05; OR 0.24, 95% CI 0.06-0.81). In the control group, none of the analyzed social and demographic factors had an impact on adherence to therapy., Conclusions: In PWID, treatment efficacy was excellent and was comparable with SVR of the control group. Stable housing and older age contributed to a better adherence to therapy.

Adenosine receptors are a family of G protein-coupled receptors with increased attention as drug targets on different indications. We investigate the thermodynamics of ligand binding to the A 3 adenosine receptor subtype, focusing on a recently reported series of diarylacetamidopyridine inhibitors via molecular dynamics simulations. With a combined approach of thermodynamic integration and one-step perturbation, we characterize the impact of the charge distribution in a central heteroaromatic ring on the binding affinity prediction. Standard charge distributions according to the GROMOS force field yield values in good agreement with the experimental data and previous free energy calculations. Subsequently, we examine the thermodynamics of inhibitor binding in terms of the energetic and entropic contributions. The highest entropy penalties are found for inhibitors with methoxy substituents in meta position of the aryl groups. This bulky group restricts rotation of aromatic rings attached to the pyrimidine core which leads to two distinct poses of the ligand. Our predictions support the previously proposed binding pose for the o-methoxy ligand, yielding in this case a very good correlation with the experimentally measured affinities with deviations below 4 kJ/mol.

[This corrects the article DOI: 10.1371/journal.pone.0167927.].

Background: This study presents antigenic and genetic characteristics of Neisseria meningitidis strains recovered from invasive meningococcal disease (IMD) in the Czech Republic in 1971-2015., Material and Methods: A total of 1970 isolates from IMD, referred to the National Reference Laboratory for Meningococcal Infections in 1971-2015, were studied. All isolates were identified and characterized by conventional biochemical and serological tests. Most isolates (82.5%) were characterized by multilocus sequence typing method., Results: In the study period 1971-2015, the leading serogroup was B (52.4%), most often assigned to clonal complexes cc32, cc41/44, cc18, and cc269. A significant percentage of strains were of serogroup C (41.4%), with high clonal homogeneity due to hyperinvasive complex cc11, which played an important role in IMD in the Czech Republic in the mid-1990s. Serogroup Y isolates, mostly assigned to cc23, and isolates of clonally homogeneous serogroup W have also been recovered more often over the last years., Conclusion: The incidence of IMD and distribution of serogroups and clonal complexes of N. meningitidis in the Czech Republic varied over time, as can be seen from the long-term monitoring, including molecular surveillance data. Data from the conventional and molecular IMD surveillance are helpful in refining the antimeningococcal vaccination strategy in the Czech Republic., Competing Interests: The authors have declared that no competing interests exist.

Although stinging nettle (Urtica dioica) has been shown to reduce HM (heavy metal) content in soil, its wider phytoremediation potential has been neglected. Urtica dioica was cultivated in soils contaminated with HMs or polychlorinated biphenyls (PCBs). After four months, up to 33% of the less chlorinated biphenyls and 8% of HMs (Zn, Pb, Cd) had been removed. Bacteria were isolated from the plant tissue, with the endophytic bacteria Bacillus shackletonii and Streptomyces badius shown to have the most significant effect. These bacteria demonstrated not only benefits for plant growth, but also extreme tolerance to As, Zn and Pb. Despite these results, the native phytoremediation potential of nettles could be improved by biotechnologies. Transient expression was used to investigate the functionality of the most common constitutive promoter, CaMV 35S in Urtica dioica. This showed the expression of the CUP and bphC transgenes. Collectively, our findings suggest that remediation by stinging nettle could have a much wider range of applications than previously thought., Competing Interests: The authors have declared that no competing interests exist.