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Background: Bulgarian poetic folklore reflects an agrarian culture deeply connected with land and nature. However, traditional ecological knowledge (TEK) transmitted through Bulgarian folklore is scarcely assessed. Questions: What are the dimensions of the TEK related to plant diversity (native and introduced) that appear in Bulgarian folk songs and what is their potential as transmitters of ТЕК? Data description: The lyrics of 10,113 Bulgarian folk songs were excerpted from major academic collections and a set of unpublished songs. Study site and dates: Current study covers songs that have been documented since mid-19th century onwards in the present and former Bulgarian territories and in areas that have been inhabited by ethnic Bulgarians abroad. Methods: Common plant names and descriptions of plants and landscapes were used to detect botanical affiliations of the denoted plants. We focused on frequencies of plant representations and their functions associated with cultural, agricultural and food-processing practices. Results: A total of 146 plant taxa from 109 genera were mentioned in 47.3 % of the studied songs. Over 60 % of the most frequently mentioned taxa were archaeophytes while neophytes were represented by seven taxa, denoting everyday and spiritual importance of nature. Conclusions: Bulgarian folk songs presented wide range of nature-related information typically reported for ethnic groups outside Europe. Quantification of TEK preserved in documented poetic folklore and further assessment of performance of nature-rich folklore would allow development additional tools for evaluation of cultural significance of species, landscapes and ecosystems as well as for development of educational and inspirational materials.

The Mediterranean diet (MD) has been sponsored worldwide as a healthy and sustainable diet. Our aim was to update and compare MD adherence and food choices across several Southern European countries: Spain (SP), Portugal (PT), Italy (IT), Greece (GR), and Cyprus (CY) (MED, Mediterranean), and Bulgaria (BG) and the Republic of North Macedonia (NMK) (non-MED, non-Mediterranean). Participants (N = 3145, ≥18 y) completed a survey (MeDiWeB) with sociodemographic, anthropometric, and food questions (14-item Mediterranean Diet Adherence Screener, 14-MEDAS). The MED and non-MED populations showed moderate (7.08 ± 1.96) and weak (5.58 ± 1.82) MD adherence, respectively, with significant yet small differences across countries (SP &gt, PT &gt, GR &gt, IT &gt, CY &gt, BG &gt, NMK, p-value &lt, 0.001). The MED participants scored higher than the non-MED ones for most of the Mediterranean-typical foods, with the greatest differences found for olive oil (OO) and white meat preference. In most countries, ≥70% of the participants reported quantities of red meat, butter, sweet drinks, and desserts below the recommended cutoff points, whereas &lt, 50% achieved the targets for plant-based foods, OO, fish, and wine. Being a woman and increasing age were associated with superior adherence (p-value &lt, 0.001), but differences were rather small. Our results suggest that the campaigns carried out to support and reinforce the MD and to promote plant-based foods have limited success across Southern Europe, and that more hard-hitting strategies are needed.

Background: Forty years after Alma Ata, there is renewed commitment to strengthen primary health care as a foundation for achieving universal health coverage, but there is limited consensus on how to build strong primary health care systems to achieve these goals. Methods: We convened a diverse group of global stakeholders for a high-level dialogue on how to create an enabling ecosystem for disruptive primary care innovation. We focused our discussion on four themes: workforce innovation and strengthening; impactful use of data and technology; private sector engagement; and innovative financing mechanisms. Findings: Here, we present a summary of our convening’s proceedings, with specific recommendations for strengthening primary health care systems within each of these four domains. Conclusions: In the wake of the Astana Declaration, there is global consensus that high-quality primary health care must be the foundation for universal health coverage. Significant disruptive innovation will be required to realize this goal. We offer our recommendations to the global community to catalyze further discourse and inform policy-making and program development on the path to Health for All by 2030.

We evaluated cardiovascular disease (CVD) risk associated with darunavir treatment and examined the demographic/clinical characteristics of darunavir users based on data from Janssen-sponsored clinical trials, post-marketing pharmacovigilance databases, and administrative claims databases. First, selected CVD events [myocardial infarction, stroke, sudden death, invasive cardiovascular procedures (coronary artery angioplasty or bypass, or carotid endarterectomy)] were analyzed in 19 Janssen-sponsored phase 2–4 studies (incidence rates estimated from pooled data; 95% confidence intervals derived from Poisson distribution). Second, analyses were conducted to identify spontaneously reported CVD events in post-marketing pharmacovigilance databases and evaluate disproportional reporting of CVD events for darunavir (using Empirical Bayesian Geometric Mean scores). Third, baseline demographic/clinical characteristics of human immunodeficiency virus-1 (HIV-1)–infected patients in general and new users of darunavir and atazanavir were explored using three US administrative claims databases. Among 19 Janssen-sponsored clinical trials (treatment durations ≤ 6 years), the CVD event rate (95% CI) per 1000 person-years (pooled population; n = 5713) was 6.15 (2.91–11.89), and was lower for patients who used once-daily darunavir/ritonavir 800/100 mg [0.71 (0.16–3.05); n = 1326] versus twice-daily darunavir/ritonavir 600/100 mg [9.21 (4.94–16.04); n = 3058]. Trend analysis of post-marketing pharmacovigilance data showed that cumulative CVD event reporting rates for darunavir users (any dose) generally declined over time. Spontaneously reported CVD events were not disproportionately reported with darunavir versus other protease inhibitors. Compared with the general HIV-1–infected population and atazanavir users, higher proportions of darunavir users were male, older, and had comorbidities associated with CVD risk based on results from US administrative claims databases. This comprehensive review of Janssen-sponsored clinical trial, post-marketing, and epidemiological data does not suggest that CVD should be considered an important risk for users of darunavir.

Allium siculum Ucria is a perennial bulbous plant that occurs in Bulgaria as A. siculum subsp. dioscoridis (Sm.) K. Richt. The plant is locally known as “samardala”. Its herbage is used traditionally by local communities in Bulgaria as edible green and for preparation of salty spice mixtures. The study was focused on the documentation of traditional knowledge about samardala, covering local collection and cultivation practices, processing methods and consumption preferences. The respondents (aged 30–86 years, 50% over 65) were local producers and small-scale salesmen of the herbage and samardala-containing spices. To assess the health features of samardala spices the total phenol and flavonoid content was measured in home-consumed or marketed flavoured salts. Overall appreciation of the plant and related food products was found to be very high; presenting a considerable engagement of the locals in plant cultivation and gathering, laborious processing and consumption. Traditional ecological knowledge about the biology, phenology and ecology of the samardala plant and methods for its processing is still preserved by elderly people who rely mostly on their own cultivated plants. Although the introduction of modern appliances has altered the method of production, its main stages and the recipes are preserved. Modernization of the processing method has not affected the quality of the products and faster processing could be a contributing factor for the higher content of biologically active substances. Phenolic content was about twice as low as the flavonoid content, following the same pattern for all tested flavoured salts. Measures for better management of natural populations and promotion of cultivation practices of A. siculum subsp. dioscoridis would ensure the sustainable quality of traditional products as well as conservation of the natural plant resources.

The home garden is a unique human-nature interspace that accommodates a diverse spectrum of plant species and provides multiple services to households. One of the most important roles of home gardens is to shelter the agricultural plant diversity that provides for diverse and healthy nutrition, especially in rural communities. While tropical home gardens have received wide recognition due to their provisional function for the local communities, temperate and especially European home gardens have been discussed less frequently as a source of subsistence. The main objectives of the current study were to document plant species grown in Bulgarian rural home gardens and to explore related local knowledge and cultural practices that influence food plant diversity, its selection and preservation. Field work was focused on settlements situated in eight provinces in South and North-West Bulgaria. Participants representing 65 home gardens were approached through semi-structured interviews. Home gardens were found to harbor 145 cultivated and semi-cultivated plant taxa, used as food, medicinal and aromatic plants and as animal fodder. Members of the Rosaceae family were most numerous. The largest part of the garden area was occupied by vegetable crops of Solanaceae and Cucurbitaceae. In 63.1% of the studied households, the food growing area comprised more than 2/3 of the total size of the garden. Most preferred crops reflected the social and cultural importance of food self-provisioning, especially in the rural areas. The provisional role of the home gardens in regard to preparation of traditional foods and the driving forces for seed saving are discussed.

This study provides comprehensive validation of the 14-item Mediterranean Diet Adherence Screener (14-MEDAS) in an adult population from Greece (GR), Portugal (PT), Italy (IT), Spain (SP), Cyprus (CY), Republic of North Macedonia (NMK), and Bulgaria (BG). A moderate association between the 14-MEDAS and the reference food diary was estimated for the entire population (Pearson r = 0.573, p-value &lt, 0.001, Intraclass Correlation Coefficient (ICC) = 0.692, p-value &lt, 0.001) with the strongest correlation found in GR, followed by PT, IT, SP, and CY. These results were supported by kappa statistics in GR, PT, IT, and SP with &ge, 50% of food items exhibiting a fair or better agreement. Bland&ndash, Altman analyses showed an overestimation of the 14-MEDAS score in the whole population (0.79 &plusmn, 1.81, 95%Confidence Interval (CI) 0.61, 0.96), but this value was variable across countries, with GR, NMK, and BG exhibiting the lowest bias. Taking all analyses together, the validation achieved slightly better results in the Mediterranean countries but a definitive validation ranking order was not evident. Considering growing evidence of the shift from Mediterranean Diet (MD) adherence and of the importance of culture in making food choices it is crucial that we further improve validation protocols with specific applications to compare MD adherence across countries.

Treatment for chronic hepatitis C virus (HCV) infection is evolving from interferon (IFN)-based therapy to direct-acting antiviral (DAA) agents, yet some safety concerns have arisen involving cardiac toxicity. In this study, we sought to better understand the potential off-target toxicities of new DAAs. We retrospectively evaluated the clinical and pathological findings of the sentinel case in a phase II study that led to clinical development discontinuation for BMS-986094, an HCV nucleotide polymerase (nonstructural 5B) inhibitor. We also report on outcomes from other patients in the same study, including electrocardiogram changes, cardiovascular biomarkers, and transthoracic echocardiograms. Thirty-four patients received IFN-free BMS-986094 regimens. Six patients had left ventricular ejection fractions (LVEFs)

Ruscus aculeatus L. is a perennial semi-shrub with distinctive leaf-like branches (cladodes). Rhizomes and roots contain steroidal saponins (ruscogenins) that are used in medicine and cosmetics for their anti-inflammatory, venotonic and antihaemorroidal activity. Problematic cultivation of the species causes in many countries unsustainable over-collection from the wild. Tissue culture propagation of R. aculeatus was carried out for conservation and propagation purposes. The impact of the clonal origin (genotype) on the ruscogenin biosynthesis, genome-size stability and propagation traits and morpho-physiological response to long-term cultivation in vitro was studied. Production of ruscogenins in fully developed regenerants was quantified by high-performance liquid chromatography (HPLC). Genome-size stability of the clones was assessed by flow cytometry. Slow growth and prolonged lag-phase were characteristic for the whole propagation cycle. Produced plantlets with well-defined organs were suitable for direct ex vitro planting. Genome DNA content of all clones was stable and comparable to native plants. Ruscogenin biosynthesis was clone-specific, presenting distinctive profiles of the cultures. Our results imply that clone origin and culture type might influence saponin biosynthesis in Ruscus. These traits should be considered in the ex situ conservation of the genetic diversity of this species and by production of planting material as well.

PURPOSE: Strategy and major results of the Environmentally Sustainable Socio-Economic Development of Rural Areas (ESSEDRA) project are presented. The project relies on collaborative network involving 8 Balkan countries (including Turkey) with leading partnership of Slow Food International and European Forum on Nature Conservation and Pastoralism (UK). The overall purpose is to involve local communities in protecting the environment, especially in safeguarding agrobiodiversity and related traditional knowledge, to mitigate the impact of climate change and to secure the sustainable development of rural areas. METHODS: The activities aim at advocating the role of small-scale farmers in biodiversity protection, promoting targeted models and actions to preserve biodiversity, and exchanging best practices and knowledge at a multiregional level. RESULTS: Outcomes from the first stage of the project are presented and in the overall Balkan agriculture tendencies is discussed focusing on the current problems in Bulgarian small-scale agriculture. CONCLUSIONS: Steps for common approach for community-based regional development, biodiversity conservation, policy influencing, advocacy and capacity building in the field, collaboration between stakeholders are proposed.

Introduction We evaluated cardiovascular disease (CVD) risk associated with darunavir treatment and examined the demographic/clinical characteristics of darunavir users based on data from Janssen-sponsored clinical trials, post-marketing pharmacovigilance databases, and administrative claims databases. Methods First, selected CVD events [myocardial infarction, stroke, sudden death, invasive cardiovascular procedures (coronary artery angioplasty or bypass, or carotid endarterectomy)] were analyzed in 19 Janssen-sponsored phase 2–4 studies (incidence rates estimated from pooled data; 95% confidence intervals derived from Poisson distribution). Second, analyses were conducted to identify spontaneously reported CVD events in post-marketing pharmacovigilance databases and evaluate disproportional reporting of CVD events for darunavir (using Empirical Bayesian Geometric Mean scores). Third, baseline demographic/clinical characteristics of human immunodeficiency virus-1 (HIV-1)–infected patients in general and new users of darunavir and atazanavir were explored using three US administrative claims databases. Results Among 19 Janssen-sponsored clinical trials (treatment durations ≤ 6 years), the CVD event rate (95% CI) per 1000 person-years (pooled population; n = 5713) was 6.15 (2.91–11.89), and was lower for patients who used once-daily darunavir/ritonavir 800/100 mg [0.71 (0.16–3.05); n = 1326] versus twice-daily darunavir/ritonavir 600/100 mg [9.21 (4.94–16.04); n = 3058]. Trend analysis of post-marketing pharmacovigilance data showed that cumulative CVD event reporting rates for darunavir users (any dose) generally declined over time. Spontaneously reported CVD events were not disproportionately reported with darunavir versus other protease inhibitors. Compared with the general HIV-1–infected population and atazanavir users, higher proportions of darunavir users were male, older, and had comorbidities associated with CVD risk based on results from US administrative claims databases. Conclusions This comprehensive review of Janssen-sponsored clinical trial, post-marketing, and epidemiological data does not suggest that CVD should be considered an important risk for users of darunavir. Electronic supplementary material The online version of this article (10.1007/s40268-018-0238-8) contains supplementary material, which is available to authorized users.

Peginterferon alfa (alfa) increases the risk of autoimmune disease. Peginterferon lambda-1a (Lambda) acts through a receptor with a more liver-specific distribution compared to the alfa receptor. In a phase-2b study, 525 treatment-naive patients with chronic hepatitis C virus (HCV) infection received ribavirin and Lambda interferon (120, 180, or 240 μg) or alfa interferon (180 μg) for 24 (genotypes 2 and 3) or 48 (genotypes 1 and 4) weeks. Retrospective analysis found that adverse events of MedDRA-coded thyroid dysfunction and abnormal levels of thyroid-stimulating hormone (TSH) were significantly more frequent with alfa versus Lambda (12% versus 2.6% and 15.2% versus 3.4%, respectively, both P0.0001). Most Lambda recipients with abnormal TSH had levels below the lower limit of normal; the frequency of low and high TSH was similar in alfa recipients with abnormal TSH. Blinded review by an endocrinologist found that new-onset primary hypothyroidism or painless thyroiditis was less frequent with Lambda versus alfa (0.5% and 1.8% versus 5.3% and 7.5%, respectively, P0.0001). Most TSH elevations reflected new-onset hypothyroidism requiring treatment, while most markedly suppressed TSH values reflected probable painless thyroiditis and resolved without sequelae. In conclusion, HCV-infected patients treated with Lambda/ribavirin experienced fewer adverse events of thyroid dysfunction compared with patients treated with alfa/ribavirin.

A recurrent hepatitis C virus (HCV) infection after liver transplantation (LT) can lead to accelerated allograft injury and fibrosis. The aim of this article is to report the first ever use of daclatasvir (DCV; also known as BMS-790052), a potent orally administered nonstructural 5A replication complex inhibitor, in combination with peginterferon α (PEG-IFNα) and ribavirin in an LT recipient. A 49-year-old female developed a severe recurrent HCV genotype 1b infection 4 months after transplantation with severe cholestasis on biopsy, an HCV RNA level of 10,000,000 IU/mL, an alkaline phosphatase level of 1525 IU/mL, and a total bilirubin level of 8.4 mg/dL. Despite partial virological suppression with PEG-IFNα and ribavirin, progressive allograft failure ensued and culminated in retransplantation at 9 months. Three months after the second transplant, DCV (20 mg/day), PEG-IFNα2a (180 μg/week), and ribavirin (800 mg/day) were prescribed for early recurrent cholestatic HCV. Serum HCV RNA became undetectable at week 3 of treatment and remained undetectable during 24 weeks of triple therapy and during the posttreatment follow-up. DCV was well tolerated, and the trough drug levels were within the targeted range throughout the treatment. The cyclosporine trough levels were also stable during and after therapy. In conclusion, the lack of anticipated drug-drug interactions between DCV and calcineurin inhibitors and the potent antiviral efficacy of DCV make this agent (in combination with PEG-IFN and ribavirin) an attractive antiviral regimen worthy of further study in LT recipients with recurrent HCV. Liver Transpl, 2012. © 2012 AASLD.

Patients with chronic hepatitis C virus (HCV) infection who have not had a response to therapy with peginterferon and ribavirin may benefit from the addition of multiple direct-acting antiviral agents to their treatment regimen.This open-label, phase 2a study included an exploratory cohort of 21 patients with chronic HCV genotype 1 infection who had not had a response to previous therapy (i.e., had not had ≥2 log(10) decline in HCV RNA after ≥12 weeks of treatment with peginterferon and ribavirin). We randomly assigned patients to receive the NS5A replication complex inhibitor daclatasvir (60 mg once daily) and the NS3 protease inhibitor asunaprevir (600 mg twice daily) alone (group A, 11 patients) or in combination with peginterferon alfa-2a and ribavirin (group B, 10 patients) for 24 weeks. The primary end point was the percentage of patients with a sustained virologic response 12 weeks after the end of the treatment period.A total of 4 patients in group A (36%; 2 of 9 with HCV genotype 1a and 2 of 2 with genotype 1b) had a sustained virologic response at 12 weeks after treatment and also at 24 weeks after treatment.. Six patients (all with HCV genotype 1a) had viral breakthrough while receiving therapy, and resistance mutations to both antiviral agents were found in all cases; 1 patient had a viral response at the end of treatment but had a relapse after the treatment period. All 10 patients in group B had a sustained virologic response at 12 weeks after treatment, and 9 had a sustained virologic response at 24 weeks after treatment. Diarrhea was the most common adverse event in both groups. Six patients had transient elevations of alanine aminotransferase levels to more than 3 times the upper limit of the normal range.This preliminary study involving patients with HCV genotype 1 infection who had not had a response to prior therapy showed that a sustained virologic response can be achieved with two direct-acting antiviral agents only. In addition, a high rate of sustained virologic response was achieved when the two direct-acting antiviral agents were combined with peginterferon alfa-2a and ribavirin. (Funded by Bristol-Myers Squibb; ClinicalTrials.gov number, NCT01012895.).

Giemsa C-banded idiograms were established from eight Crepis species of Bulgarian origin (Crepis viscidula, C. paludosa, C. conyzaefolia, C. bithynica var. bithynica and var. fodorii, C. pulchra, C. sancta, C. setosa, and C. zacintha) that had been previously studied for genome size and karyotype shape using classical methods. All taxa are diploids with descending chromosome numbers, x = 6, 5, 4, and 3. Satellites were always heterochromatic. Small but distinct centromeric bands were of general occurrence (except perhaps in C. paludosa) and terminal bands were present at least in some chromosomes of the karyotypes. Higher amounts of heterochromatin in the form of terminal and intercalary bands were found in C. bithynica and C. zacintha, but banding patterns were not so specifically similar as to indicate common origin. There are a number of particular karyotypic characters which may turn out to be phylogenetically significant when corresponding information on many related taxa becomes available. Correlations of karyotypic parameters were calculated. In heterochromatin only percent heterochromatin, but not absolute heterochromatin amount, and genome size were significantly correlated. This is the result of a strong euchromatin variation but independent heterochromatin variation.

Ten Crepis species from Bulgaria—five perennials (C. viscidula, C. paludosa, C. conyzaefolia, C. bithynica, C. schachtii), four annuals (C. pulchra, C. sancta, C. setosa, C. zacintha) and one biennial (C. biennis)—were analysed karyologically using haematoxylin staining, Feulgen cytophotometry (scanning densitometry and video-based image analysis), and DNA flow cytometry with propidium iodide. All taxa but the biennial are diploids with descending basic chromosome numbers, x=6, 5, 4, 3. Significant positive correlations were found between nuclear DNA content and karyotype length and nuclear DNA content and karyotypic asymmetry. Together with the results of previous authors our data suggest that evolutionary advancement could be correlated with more symmetrical karyotypes. Negative significant correlations were established between presumably advanced growth habit (from rhizomatous and tap-rooted perennials towards highly specialized annuals) and chromosome number and karyotype length. Nuclear DNA 1C-values on average were higher in perennials than in annuals, but the ranges were overlapping and the differences not significant. Crepis biennis (2 n=c. 40, presumably 10x) had the highest DNA quantity, but calculated at its x-level ranked relatively low in the species sample.

Ten populations ofCrepis foetida from Bulgaria belonging to the three subspeciesfoetida, rhoeadifolia, andcommutata were analyzed karyologically using haematoxylin staining, Giemsa C-banding, fluorochrome banding, Ag-NOR staining, Feulgen cytophotometry (scanning densitometry and video-based image analysis), and propidium iodide flow cytometry. The quantitatively-evaluated karyotype structure was similar among all populations, with minor variation in a few intercalary sites only and in the amount of NOR-associated heterochromatin (satellites). In contrast to the karyotypic constancy the genome size ofC. foetida subsp.commutata was about 10% lower than those of the other two subspecies, which had similar genome sizes. The genome size measurements using three different methods resulted in highly correlated data. The genome size difference adds some weight to previous taxonomic opinions treatingC. foetida subsp.commutata at species level, asC. commutata.

Recurrent HCV infection following liver transplantation can lead to accelerated allograft injury that is difficult to treat with interferon. The aim of this study is to describe the first ever use of an interferon-free, all oral regimen in a liver transplant recipient with severe recurrent HCV. A 54-year-old male with HCV genotype 1b developed severe cholestatic HCV at 6 months posttransplant with ascites, AST 503 IU/mL, alkaline phosphatase of 298 IU/mL, HCV RNA of 12 000 000 IU/mL, and histological cholestasis with pericellular fibrosis. Sofosbuvir, an HCV polymerase inhibitor (400 mg/day), and daclatasvir, an HCV NS5A replication complex inhibitor (60 mg/day), were co-administered for 24 weeks. Within 4 weeks of initiating treatment, serum HCV RNA levels became undetectable and liver biochemistries normalized with concomitant resolution of ascites. The patient achieved a sustained virological response with undetectable HCV RNA at 9 months posttreatment. During and following treatment, the daily dose and blood level of tacrolimus remained stable and unchanged. The rapid and sustained suppression of HCV replication in this liver transplant recipient provides great promise for the use of combination oral antiviral regimens in other immunosuppressed and interferon refractory HCV patients.

Iron nanoparticles occur naturally in the environment, but their exposure increases dramatically due to the field of nanotechnology and –medicine. It is poorly understood how the intracellular cooperative mechanisms of submicron particles and microorganisms function on mammalian immune system. In this study, superparamagnetic iron oxide (SPIO) submicron particles will be used to benefit the research within environmental diseases, addressing the biocompatibility of these particles. The size-dependent effects in the immune system of two carboxyl coated SPIO particles with stated sizes 100 nm and 1 µm will be studied in vitro. It would be interesting to determine whether these particles were able to activate the inflammasome, but still, the precise molecular mechanisms for the activation remain unknown. In order to reveal the biocompatibility of these particles, tests were performed as a function of particle concentration ranging from 0.01 to 100 µg/mL using both whole blood and peripheral blood mononuclear cells (PBMC) isolated from healthy donors. The monocytes were first primed with Lipopolysaccharide from Escherichia coli 0111:B4 strain, followed by stimulation with increasing concentrations of the submicron particles. Flow cytometry on whole blood samples identified up-regulation of CD11b monocytes and granulocytes by the particles. In addition, Terminal Complement Complex analyses proved activation of the complement system. It is possible that the particles have been coated with C3b by the complement and phagocytized by the monocytes through CD11b/CD18 receptor. Cytokine secretion from monocytes and whole blood was measured with sandwich ELISA and Bio-plex. The smaller particles seemed to induce higher inflammatory responses than the larger ones. It was, however, interesting to find that the particles themselves caused secretion of active IL-1β without being primed in advance. The mechanisms of the NLRP3 inflammasome activation might be explained by ROS production due to iron imbalance in the cytoplasm. Toxicity of the particles was seen at 10 µg/mL, suggesting their potentially low biocompatibility above this concentration. However, it is suggested better biocompatibility of the silica coated 1 µm particles than the polysaccharide coated 100 nm particles.

BACKGROUND The oxazolidinone PNU-100480 is superior to linezolid against experimental murine tuberculosis. Two metabolites contribute to but do not fully account for its superiority. This study examined the safety, tolerability, pharmacokinetics, and mycobactericidal activity of single ascending doses of PNU-100480. METHODS Nineteen healthy volunteers received 2 escalating single oral doses (35-1500 mg) of PNU-100480 or placebo. Eight subjects received 4 daily doses of 300 mg of linezolid. Drug concentrations and bactericidal activity against Mycobacterium tuberculosis in whole-blood bactericidal culture were measured. RESULTS All doses were safe and well tolerated. PNU-100480 doses to 1000 mg were well absorbed and showed approximately proportional increases in exposures of parent and metabolites. The geometric mean maximal concentrations of PNU-100480, PNU-101603, and PNU-101244 (sulfoxide and sulfone metabolites) at 1000 mg were 839, 3558, and 54 ng/mL, respectively. The maximal whole-blood bactericidal activity (-0.37 +/- .06 log/day) occurred at combined PNU levels > or =2 times the minimum inhibitory concentration. The observed geometric mean maximal concentration for linezolid was 6425 ng/mL. Its maximal whole-blood bactericidal activity also occurred at > or =2 times the minimum inhibitory concentration, but it was only -0.16 +/- .05 log/day (P< .001) Neither drug showed enhanced activity at higher concentrations. CONCLUSIONS Single doses of PNU-100480 to 1000 mg were well tolerated and exhibited antimycobacterial activity superior to 300 mg of linezolid at steady state. Additional studies are warranted to define its role in drug-resistant tuberculosis.

Ethnolinguistic studies are important for understanding an ethnic group's ideas on the world, expressed in its language. Comparing corresponding aspects of such knowledge might help clarify problems of origin for certain concepts and words, e.g. whether they form common heritage, have an independent origin, are borrowings, or calques. The current study was conducted on the material in Slavonic, Baltic, Germanic, Romance, Finno-Ugrian, Turkic and Albanian languages. The bear was chosen as being a large, dangerous animal, important in traditional culture, whose name is widely reflected in folk plant names. The phytonyms for comparison were mostly obtained from dictionaries and other publications, and supplemented with data from databases, the co-authors' field data, and archival sources (dialect and folklore materials). More than 1200 phytonym use records (combinations of a local name and a meaning) for 364 plant and fungal taxa were recorded to help find out the reasoning behind bear-nomination in various languages, as well as differences and similarities between the patterns among them. Among the most common taxa with bear-related phytonyms were Arctostaphylos uva-ursi (L.) Spreng., Heracieum sphondylium L., Acanthus mollis L., and Allium ursinum L., with Latin loan translation contributing a high proportion of the phytonyms. Some plants have many and various bear-related phytonyms, while others have only one or two bear names. Features like form and/or surface generated the richest pool of names, while such features as colour seemed to provoke rather few associations with bears. The unevenness of bear phytonyms in the chosen languages was not related to the size of the language nor the present occurence of the Brown Bear in the region. However, this may, at least to certain extent, be related to the amount of the historical ethnolinguistic research done on the selected languages.