Effect of Mutation and Genetic Background on Drug Resistance in Mycobacterium tuberculosis

Bacterial factors may contribute to the global emergence and spread of drug-resistant tuberculosis (TB). Only a few studies have reported on the interactions between different bacterial factors. We studied drug-resistant Mycobacterium tuberculosis isolates from a nationwide study conducted from 2000 to 2008 in Switzerland. We determined quantitative drug resistance levels of first-line drugs by using Bactec MGIT-960 and drug resistance genotypes by sequencing the hot-spot regions of the relevant genes. We determined recent transmission by molecular methods and collected clinical data. Overall, we analyzed 158 isolates that were resistant to isoniazid, rifampin, or ethambutol, 48 (30.4%) of which were multidrug resistant. Among 154 isoniazid-resistant strains, katG mutations were associated with high-level and inhA promoter mutations with low-level drug resistance. Only katG(S315T) (65.6% of all isoniazid-resistant strains) and inhA promoter -15C/T (22.7%) were found in molecular clusters. M. tuberculosis lineage 2 (includes Beijing genotype) was associated with any drug resistance (adjusted odds ratio [OR], 3.0; 95% confidence interval [CI], 1.7 to 5.6; P < 0.0001). Lineage 1 was associated with inhA promoter -15C/T mutations (OR, 6.4; 95% CI, 2.0 to 20.7; P = 0.002). We found that the genetic strain background influences the level of isoniazid resistance conveyed by particular mutations (interaction tests of drug resistance mutations across all lineages; P < 0.0001). In conclusion, M. tuberculosis drug resistance mutations were associated with various levels of drug resistance and transmission, and M. tuberculosis lineages were associated with particular drug resistance-conferring mutations and phenotypic drug resistance. Our study also supports a role for epistatic interactions between different drug resistance mutations and strain genetic backgrounds in M. tuberculosis drug resistance.

A multi-proxy approach for revealing recent climatic changes in the Russian Altai

For the first time we present a multi-proxy data set for the Russian Altai, consisting of Siberian larch tree-ring width (TRW), latewood density (MXD), δ13C and δ18O in cellulose chronologies obtained for the period 1779–2007 and cell wall thickness (CWT) for 1900–2008. All of these parameters agree well between each other in the high-frequency variability, while the low-frequency climate information shows systematic differences. The correlation analysis with temperature and precipitation data from the closest weather station and gridded data revealed that annual TRW, MXD, CWT, and δ13C data contain a strong summer temperature signal, while δ18O in cellulose represents a mixed summer and winter temperature and precipitation signal. The temperature and precipitation reconstructions from the Belukha ice core and Teletskoe lake sediments were used to investigate the correspondence of different independent proxies. Low frequency patterns in TRW and δ13C chronologies are consistent with temperature reconstructions from nearby Belukha ice core and Teletskoe lake sediments showing a pronounced warming trend in the last century. Their combination could be used for the regional temperature reconstruction. The long-term δ18O trend agrees with the precipitation reconstruction from the Teletskoe lake sediment indicating more humid conditions during the twentieth century. Therefore, these two proxies could be combined for the precipitation reconstruction.

Spatial and temporal variation in population genetic structure of wild Nile tilapia (Oreochromis niloticus) across Africa

Background: Reconstructing the evolutionary history of a species is challenging. It often depends not only on the past biogeographic and climatic events but also the contemporary and ecological factors, such as current connectivity and habitat heterogeneity. In fact, these factors might interact with each other and shape the current species distribution. However, to what extent the current population genetic structure reflects the past and the contemporary factors is largely unknown. Here we investigated spatio-temporal genetic structures of Nile tilapia (Oreochromis niloticus) populations, across their natural distribution in Africa. While its large biogeographic distribution can cause genetic differentiation at the paleo-biogeographic scales, its restricted dispersal capacity might induce a strong genetic structure at micro-geographic scales. Results: Using nine microsatellite loci and 350 samples from ten natural populations, we found the highest genetic differentiation among the three ichthyofaunal provinces and regions (Ethiopian, Nilotic and Sudano-Sahelian) (R(ST) = 0.38 - 0.69). This result suggests the predominant effect of paleo-geographic events at macro-geographic scale. In addition, intermediate divergences were found between rivers and lakes within the regions, presumably reflecting relatively recent interruptions of gene flow between hydrographic basins (R(ST) = 0.24 - 0.32). The lowest differentiations were observed among connected populations within a basin (R(ST) = 0.015 in the Volta basin). Comparison of temporal sample series revealed subtle changes in the gene pools in a few generations (F = 0 - 0.053). The estimated effective population sizes were 23 - 143 and the estimated migration rate was moderate (m similar to 0.094 - 0.097) in the Volta populations. Conclusions: This study revealed clear hierarchical patterns of the population genetic structuring of O. niloticus in Africa. The effects of paleo-geographic and climatic events were predominant at macro-geographic scale, and the significant effect of geographic connectivity was detected at micro-geographic scale. The estimated effective population size, the moderate level of dispersal and the rapid temporal change in genetic composition might reflect a potential effect of life history strategy on population dynamics. This hypothesis deserves further investigation. The dynamic pattern revealed at micro-geographic and temporal scales appears important from a genetic resource management as well as from a biodiversity conservation point of view.

Private Publishing in Moscow and St. Petersburg: Historical Background, Present Situation and Trends"

This research was a complex study of the economic and socio-cultural aspects of the development of Russian private publishing in the second half of the19th and early 20th centuries, during the periods of 'war communism' and the New Economic Policy of 1917 to 1930, and during the reform of book publishing in 1986-1999. Conclusions about private book publishing in Moscow and St. Petersburg were extrapolated to Russia-wide problems of the development of this field. Svichenskaya sees her main achievement as having identified the economic and legal concepts behind the development of private book publishing over the period in question in the context of state and corporate regulation of publishing. Here the state was the main influence on its development and there was a paradox in the relations between the state authorities and private publishers, in that the latter constantly suffered from repression by the former but at the same time were dependent on state support. The research identified the administrative process of the liquidation of private publishing at the end of the 1920s and showed that its present flourishing is closely linked with the establishment of a preferential mode for the development of this sector. Private publishing now represents around 80% of domestic publishing, in terms both of the number of publishing houses and of the number of volumes published, and so plays the major role in satisfying the demand for books in Russia. Svichenskaya predicts that in the coming years private publishing will see a further concentration of growth and a tendency to monopolies and also the increasing specialisation of the publishing repertoire. She outlines a suggested concept of state management in publishing and ways to optimise this. In the transitional period of adaptation to the market regulation of publishing, these include a continuing degree of state protectionism, the creation of a favourable investment climate, privatisation of the printing companies with the aim of modernising these, and the development of coordinated corporate policies.

A qualitative study on the role of cultural background in patients perspectives on rehabilitation

Background Low back pain (LBP) is one of the major concerns in health care. In Switzerland, musculoskeletal problems represent the third largest illness group with 9.4 million consultations per year. The return to work rate is increased by an active treatment program and saves societal costs. However, results after rehabilitation are generally poorer in patients with a Southeast European cultural background than in other patients. This qualitative research about the rehabilitation of patients with LBP and a Southeast European cultural background, therefore, explores possible barriers to successful rehabilitation. Methods We used a triangulation of methods combining three qualitative methods of data collection: 13 semi-structured in-depth interviews with patients who have a Southeast European cultural background and live in Switzerland, five semi-structured in-depth interviews and two focus groups with health professionals, and a literature review. Between June and December 2008, we recruited participants at a Rehabilitation Centre in the German-speaking part of Switzerland. Results To cope with pain, patients prefer passive strategies, which are not in line with recommended coping strategies. Moreover, the families of patients tend to support passive behaviour and reduce the autonomy of patients. Health professionals and researchers propagate active strategies including activity in the presence of pain, yet patients do not consider psychological factors contributing to LBP. The views of physicians and health professionals are in line with research evidence demonstrating the importance of psychosocial factors for LBP. Treatment goals focusing on increasing daily activities and return to work are not well understood by patients partly due to communication problems, which is something that patients and health professionals are aware of. Additional barriers to returning to work are caused by poor job satisfaction and other work-related factors. Conclusions LBP rehabilitation can be improved by addressing the following points. Early management of LBP should be activity-centred instead of pain-centred. It is mandatory to implement return to work management early, including return to adapted work, to improve rehabilitation for patients. Rehabilitation has to start when patients have been off work for three months. Using interpreters more frequently would improve communication between health professionals and patients, and reduce misunderstandings about treatment procedures. Special emphasis must be put on the process of goal-formulation by spending more time with patients in order to identify barriers to goal attainment. Information on the return to work process should also include the financial aspects of unemployment and disability.