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1.  Overview of healthcare system in the Czech Republic 
The EPMA Journal  2012;3(1):4.
The healthcare system in the Czech Republic underwent and still is undergoing dramatic changes since the Velvet revolution in 1989. History of the Czech healthcare system, main healthcare laws, and the current status of healthcare documented in the main healthcare indicators is described based on the several main sources as well as delivery of health services and the role of the main actors in healthcare system. The material is based mainly on Czech Health Statistics 2009, and HiT Summary, Health Care Systems in Translation, 2005, public information of Ministry of Health CR.
doi:10.1007/s13167-012-0139-9
PMCID: PMC3375100  PMID: 22738178
Czech Republic; Healthcare system; Politics; Financing; Predictive, Preventive and Personalised Medicine; Recommendations
2.  The Velvet Family of Fungal Regulators Contains a DNA-Binding Domain Structurally Similar to NF-κB 
PLoS Biology  2013;11(12):e1001750.
This study reveals an important family of fungal regulatory proteins to be transcription factors that contain a DNA-binding “velvet” domain structurally related to that of mammalian NFkB.
Morphological development of fungi and their combined production of secondary metabolites are both acting in defence and protection. These processes are mainly coordinated by velvet regulators, which contain a yet functionally and structurally uncharacterized velvet domain. Here we demonstrate that the velvet domain of VosA is a novel DNA-binding motif that specifically recognizes an 11-nucleotide consensus sequence consisting of two motifs in the promoters of key developmental regulatory genes. The crystal structure analysis of the VosA velvet domain revealed an unforeseen structural similarity with the Rel homology domain (RHD) of the mammalian transcription factor NF-κB. Based on this structural similarity several conserved amino acid residues present in all velvet domains have been identified and shown to be essential for the DNA binding ability of VosA. The velvet domain is also involved in dimer formation as seen in the solved crystal structures of the VosA homodimer and the VosA-VelB heterodimer. These findings suggest that defence mechanisms of both fungi and animals might be governed by structurally related DNA-binding transcription factors.
Author Summary
In many fungi, developmental processes and the synthesis of nonessential chemicals (secondary metabolites) are regulated by various external stimuli, such as light. Although fungi employ them for defensive purposes, secondary metabolites range from useful antibiotics to powerful toxins, so understanding the molecular processes that regulate their synthesis is of particular interest to us. In the mold Aspergillus nidulans the main regulators of these processes are the so-called “velvet” proteins VeA, VelB, and VosA, which share a 150-amino acid region known as the velvet domain. Velvet proteins interact with each other, alone (“homodimers”), in various combinations (“heterodimers”), and also with other proteins, but the molecular mechanism by which these proteins exert their regulatory function has been unclear. In this work we show that velvet proteins form a family of fungus-specific transcription factors that directly bind to target DNA, even though analysis of their amino acid sequence does not reveal any known DNA-binding domains or motifs. We determined the three-dimensional structure of the VosA-VosA homodimer and the VosA-VelB heterodimer and found that the structure of the velvet domain is strongly reminiscent of the N-terminal immunoglobulin-like domain found in the mammalian transcription factor NFκB-p50, despite the very low sequence similarity. We propose that, like NFκB, various homo- or heterodimers of velvet proteins modulate gene expression to drive development and defensive pathways in fungi.
doi:10.1371/journal.pbio.1001750
PMCID: PMC3876986  PMID: 24391470
3.  Tobacco Industry Manipulation of Tobacco Excise and Tobacco Advertising Policies in the Czech Republic: An Analysis of Tobacco Industry Documents 
PLoS Medicine  2012;9(6):e1001248.
Risako Shirane and colleagues examined the the Legacy Tobacco Documents Library and found evidence of transnational tobacco company influence over tobacco advertising and excise policy in the Czech Republic, a country with one of the poorest tobacco control records in Europe.
Background
The Czech Republic has one of the poorest tobacco control records in Europe. This paper examines transnational tobacco companies' (TTCs') efforts to influence policy there, paying particular attention to excise policies, as high taxes are one of the most effective means of reducing tobacco consumption, and tax structures are an important aspect of TTC competitiveness.
Methods and Findings
TTC documents dating from 1989 to 2004/5 were retrieved from the Legacy Tobacco Documents Library website, analysed using a socio-historical approach, and triangulated with key informant interviews and secondary data. The documents demonstrate significant industry influence over tobacco control policy. Philip Morris (PM) ignored, overturned, and weakened various attempts to restrict tobacco advertising, promoting voluntary approaches as an alternative to binding legislation. PM and British American Tobacco (BAT) lobbied separately on tobacco tax structures, each seeking to implement the structure that benefitted its own brand portfolio over that of its competitors, and enjoying success in turn. On excise levels, the different companies took a far more collaborative approach, seeking to keep tobacco taxes low and specifically to prevent any large tax increases. Collective lobbying, using a variety of arguments, was successful in delaying the tax increases required via European Union accession. Contrary to industry arguments, data show that cigarettes became more affordable post-accession and that TTCs have taken advantage of low excise duties by raising prices. Interview data suggest that TTCs enjoy high-level political support and continue to actively attempt to influence policy.
Conclusion
There is clear evidence of past and ongoing TTC influence over tobacco advertising and excise policy. We conclude that this helps explain the country's weak tobacco control record. The findings suggest there is significant scope for tobacco tax increases in the Czech Republic and that large (rather than small, incremental) increases are most effective in reducing smoking.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Every year, about 5 million people die from tobacco-related diseases and, if current trends continue, annual tobacco-related deaths will increase to 10 million by 2030. Faced with this global tobacco epidemic, national and international bodies have drawn up conventions and directives designed to control tobacco. For example, European Union (EU) Directives on tobacco control call for member states to ban tobacco advertising, promotion, and sponsorship and to adopt taxation policies (for example, high levels of tobacco excise tax) aimed at reducing tobacco consumption. Within the EU, implementation of tobacco control policies varies widely but the Czech Republic, which was formed in 1993 when Czechoslovakia split following the 1989 collapse of communism, has a particularly poor record. The Czech Republic, which joined the EU in 2004, is the only EU Member State not to have ratified the World Health Organization's Framework Convention on Tobacco Control, which entered into force in 2005, and its tobacco control policies were the fourth least effective in Europe in 2010.
Why Was This Study Done?
During the communist era, state-run tobacco monopolies controlled the supply of cigarettes and other tobacco products in Czechoslovakia. Privatization of these monopolies began in 1991 and several transnational tobacco companies (TTCs)—in particular, Philip Morris and British American Tobacco—entered the tobacco market in what was to become the Czech Republic. In this socio-historical study, which aims to improve understanding of both effective tobacco excise policy and the ways in which TTCs seek to influence policy in emerging markets, the researchers analyze publically available internal TTC documents and interview key informants to examine efforts made by TTCs to influence tobacco advertising and tobacco excise tax policies in the Czech Republic. A socio-historical study examines the interactions between individuals and groups in a historical context.
What Did the Researchers Do and Find?
The researchers analyzed 511 documents (dated 1989 onwards) in the Legacy Tobacco Documents Library website (a collection of internal tobacco industry documents released through US litigation cases) that mentioned tobacco control policies in the Czech Republic. They also analyzed information obtained from sources such as tobacco industry journals and data obtained in 2010 in interviews with key Czech informants (including a tobacco industry representative and a politician). The researchers' analysis of the industry documents indicates that Philip Morris ignored, overturned, and weakened attempts to restrict tobacco advertising and promoted voluntary approaches as an alternative to binding legislation. Importantly, while the internal documents show that Philip Morris lobbied for a specific excise tax (a fixed amount of tax per cigarette, a tax structure that favors the expensive brands that Philip Morris mainly markets), the European strategy employed at that time by British American Tobacco was to lobby for a mixed excise structure that combined an “ad valorem” tax (a tax levied as a proportion of price) and a specific tax, an approach that favors a mixed portfolio of tobacco brands. By contrast, the documents show that TTCs collaborated in trying to keep tobacco taxes low and in trying to prevent any large tax increases. This collective lobbying successfully delayed the tobacco tax increases required as a condition of the Czech Republic's accession to the EU. Finally, the interview data suggest that TTCs had high-level political support in the Czech Republic and continue actively to attempt to influence policy.
What Do These Findings Mean?
These findings provide clear evidence that Philip Morris and British American Tobacco (the two TTCs that have dominated the Czech market since privatization of the tobacco industry) have significantly influenced tobacco advertising and excise policy in the Czech Republic since 1989. The findings, which also suggest that this influence is ongoing, help to explain the Czech Republic's poor tobacco control record, which was reflected in a fall in the real price of cigarettes between 1990 and 2000. More generally, this study provides valuable insight into how TTCs might try to influence policy in other emerging markets. Improvements in global tobacco control, the researchers conclude, will be possible only if efforts are made to protect tobacco control policies from the vested interests of the tobacco industry, a principle enshrined in the WHO Framework Convention on Tobacco control, and if public and political attitudes to the industry shift.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001248.
The World Health Organization provides information about the dangers of tobacco (in several languages) and about its Framework Convention on Tobacco Control
For information about the tobacco industry's influence on policy, see the 2009 World Health Organization report Tobacco interference with tobacco control
The Framework Convention Alliance more information about the FCTC
Details of European Union legislation on excise duty applied to manufactured tobacco and on the manufacture, presentation and sale of tobacco products are available (in several languages)
The Legacy Tobacco Documents Library is a searchable public database of tobacco company internal documents detailing their advertising, manufacturing, marketing, sales, and scientific activities
The UK Centre for Tobacco Control Studies is a network of UK universities that undertakes original research, policy development, advocacy, and teaching and training in the field of tobacco control
SmokeFree, a website provided by the UK National Health Service, offers advice on quitting smoking and includes personal stories from people who have stopped smoking
Smokefree.gov, from the US National Cancer Institute, offers online tools and resources to help people quit smoking and not start again
doi:10.1371/journal.pmed.1001248
PMCID: PMC3383744  PMID: 22745606
4.  Theory and practice of informed consent in the Czech Republic 
Journal of Medical Ethics  2007;33(5):273-277.
The large‐scale change of Czech society since 1989 has involved the democratic transformation of the health system. To empower the patient was one important goal of the healthcare reform launched immediately after the Velvet Revolution. The process has been enhanced by the accession of the Czech Republic to the European Union and the adoption of important European conventions regulating the area. The concept of informed consent and a culture of negotiation are being inserted into a traditionally paternalistic culture. Our article describes the current situation on the issue of the communication of information on state of health and treatment, and on the question of the participation of the patient in decisions on treatment. We present empirical results of a public opinion survey on this issue. The results show a still prevailing submissive attitude towards the physicians, despite the fact that the concept of informed consent has become more and more publicly familiar (42% of respondents gave the completely correct answer regarding informed consent). The impact of age, education and sex on answers to the questionnaire was analysed. Men, younger and more educated respondents were more likely to show the autonomous attitude, whereas women, older and less educated people tended to show the traditional submissive attitude. Further, our article raises the question of the cultural and historical background within which the current ethically and legally binding norms (products of western democracies, in fact) are interpreted. The question is how far cultural modifications are tolerable in the practical implementation of universal ethical constructs (informed consent).
doi:10.1136/jme.2005.015164
PMCID: PMC2598120  PMID: 17470503
5.  Salaried general practice in Czechoslovakia: personal observations and impressions. 
In 1991, a visit was undertaken, to the former Czechoslovakia, during which discussions were held with general practitioners. Some personal observations and impressions from the visit are presented. For four decades, salaried general practice was a feature of the Czechoslovakian health care system. Primary health care comprised three strands: paediatric services, an occupational health service and community general practitioner care. The main point of service delivery was the polyclinic which, although being large and impersonal, provided easy access to other primary and secondary services. General practitioners, over half of whom were women, had regular leave entitlement and predictable hours of work, out of hours work being provided through separate contracts based on primary care emergency centres. However, doctors were poorly paid compared with industrial workers. Following the 'velvet revolution' in 1989, all aspects of the health service have been subject to major review, and salaried general practice is likely to give way to a more entrepreneurial system.
PMCID: PMC1372562  PMID: 8251221
6.  LaeA Control of Velvet Family Regulatory Proteins for Light-Dependent Development and Fungal Cell-Type Specificity 
PLoS Genetics  2010;6(12):e1001226.
VeA is the founding member of the velvet superfamily of fungal regulatory proteins. This protein is involved in light response and coordinates sexual reproduction and secondary metabolism in Aspergillus nidulans. In the dark, VeA bridges VelB and LaeA to form the VelB-VeA-LaeA (velvet) complex. The VeA-like protein VelB is another developmental regulator, and LaeA has been known as global regulator of secondary metabolism. In this study, we show that VelB forms a second light-regulated developmental complex together with VosA, another member of the velvet family, which represses asexual development. LaeA plays a key role, not only in secondary metabolism, but also in directing formation of the VelB-VosA and VelB-VeA-LaeA complexes. LaeA controls VeA modification and protein levels and possesses additional developmental functions. The laeA null mutant results in constitutive sexual differentiation, indicating that LaeA plays a pivotal role in inhibiting sexual development in response to light. Moreover, the absence of LaeA results in the formation of significantly smaller fruiting bodies. This is due to the lack of a specific globose cell type (Hülle cells), which nurse the young fruiting body during development. This suggests that LaeA controls Hülle cells. In summary, LaeA plays a dynamic role in fungal morphological and chemical development, and it controls expression, interactions, and modification of the velvet regulators.
Author Summary
Numerous fungi have the potential to infect immunocompromised patients or to contaminate and spoil our nutrients. They represent an increasing danger that threatens public health and agriculture. This requires improved understanding of fungal growth, development, dissemination of spores, and mycotoxin production. We have discovered two related fungal specific protein complexes that provide a molecular link among spore formation, fungal development, and secondary metabolite production. The subunit allocation of both complexes depends on each other, and they share a common subunit. These complexes comprise three related and in fungi conserved proteins of the velvet family that function in concert with a known regulator of secondary metabolism, LaeA. This protein controls the formation of both complexes but is only a part of the trimeric complex. We found that this regulator of secondary metabolism also possesses several developmental control functions in gene expression. These protein complexes discovered in the fungal model system Aspergillus nidulans are conserved in fungal pathogens where they might provide novel insights for understanding growth, development, and interaction with their respective hosts.
doi:10.1371/journal.pgen.1001226
PMCID: PMC2996326  PMID: 21152013
7.  Long-term changes in CO2 emissions in Austria and Czechoslovakia—Identifying the drivers of environmental pressures 
Energy Policy  2011;39(2):535-543.
This study presents fossil-fuel related CO2 emissions in Austria and Czechoslovakia (current Czech Republic and Slovakia) for 1830–2000. The drivers of CO2 emissions are discussed by investigating the variables of the standard Kaya identity for 1920–2000 and conducting a comparative Index Decomposition Analysis. Proxy data on industrial production and household consumption are analysed to understand the role of the economic structure. CO2 emissions increased in both countries in the long run. Czechoslovakia was a stronger emitter of CO2 throughout the time period, but per-capita emissions significantly differed only after World War I, when Czechoslovakia and Austria became independent. The difference in CO2 emissions increased until the mid-1980s (the period of communism in Czechoslovakia), explained by the energy intensity and the composition effects, and higher industrial production in Czechoslovakia. Counterbalancing factors were the income effect and household consumption. After the Velvet revolution in 1990, Czechoslovak CO2 emissions decreased, and the energy composition effect (and industrial production) lost importance. Despite their different political and economic development, Austria and Czechoslovakia reached similar levels of per-capita CO2 emissions in the late 20th century. Neither Austrian “eco-efficiency” nor Czechoslovak restructuring have been effective in reducing CO2 emissions to a sustainable level.
Research Highlights
►CO2 emissions in Austria and Czechoslovakia increased during industrialisation. ►The differences were strongest during periods of different political regimes. ►The main drivers for differences were energy composition and energy intensity.
doi:10.1016/j.enpol.2010.10.006
PMCID: PMC3056487  PMID: 21461052
Carbon dioxide emissions; Decomposition analysis; Energy transition
8.  MetaVelvet: an extension of Velvet assembler to de novo metagenome assembly from short sequence reads 
Nucleic Acids Research  2012;40(20):e155.
An important step in ‘metagenomics’ analysis is the assembly of multiple genomes from mixed sequence reads of multiple species in a microbial community. Most conventional pipelines use a single-genome assembler with carefully optimized parameters. A limitation of a single-genome assembler for de novo metagenome assembly is that sequences of highly abundant species are likely misidentified as repeats in a single genome, resulting in a number of small fragmented scaffolds. We extended a single-genome assembler for short reads, known as ‘Velvet’, to metagenome assembly, which we called ‘MetaVelvet’, for mixed short reads of multiple species. Our fundamental concept was to first decompose a de Bruijn graph constructed from mixed short reads into individual sub-graphs, and second, to build scaffolds based on each decomposed de Bruijn sub-graph as an isolate species genome. We made use of two features, the coverage (abundance) difference and graph connectivity, for the decomposition of the de Bruijn graph. For simulated datasets, MetaVelvet succeeded in generating significantly higher N50 scores than any single-genome assemblers. MetaVelvet also reconstructed relatively low-coverage genome sequences as scaffolds. On real datasets of human gut microbial read data, MetaVelvet produced longer scaffolds and increased the number of predicted genes.
doi:10.1093/nar/gks678
PMCID: PMC3488206  PMID: 22821567
9.  Secular trends: a ten-year comparison of the amount and type of physical activity and inactivity of random samples of adolescents in the Czech Republic 
BMC Public Health  2011;11:731.
Background
An optimal level of physical activity (PA) in adolescence influences the level of PA in adulthood. Although PA declines with age have been demonstrated repeatedly, few studies have been carried out on secular trends. The present study assessed levels, types and secular trends of PA and sedentary behaviour of a sample of adolescents in the Czech Republic.
Methods
The study comprised two cross-sectional cohorts of adolescents ten years apart. The analysis compared data collected through a week-long monitoring of adolescents' PA in 1998-2000 and 2008-2010. Adolescents wore either Yamax SW-701 or Omron HJ-105 pedometer continuously for 7 days (at least 10 hours per day) excluding sleeping, hygiene and bathing. They also recorded their number of steps per day, the type and duration of PA and sedentary behaviour (in minutes) on record sheets. In total, 902 adolescents (410 boys; 492 girls) aged 14-18 were eligible for analysis.
Results
Overweight and obesity in Czech adolescents participating in this study increased from 5.5% (older cohort, 1998-2000) to 10.4% (younger cohort, 2008-2010). There were no inter-cohort significant changes in the total amount of sedentary behaviour in boys. However in girls, on weekdays, there was a significant increase in the total duration of sedentary behaviour of the younger cohort (2008-2010) compared with the older one (1998-2000). Studying and screen time (television and computer) were among the main sedentary behaviours in Czech adolescents. The types of sedentary behaviour also changed: watching TV (1998-2000) was replaced by time spent on computers (2008-2010).
The Czech health-related criterion (achieving 11,000 steps per day) decreased only in boys from 68% (1998-2000) to 55% (2008-2010). Across both genders, 55%-75% of Czech adolescents met the health-related criterion of recommended steps per day, however less participants in the younger cohort (2008-2010) met this criterion than in the older cohort (1998-2000) ten years ago. Adolescents' PA levels for the monitored periods of 1998-2000 and 2008-2010 suggest a secular decrease in the weekly number of steps achieved by adolescent boys and girls.
Conclusion
In the younger cohort (2008-2010), every tenth adolescent was either overweight or obese; roughly twice the rate when compared to the older cohort (1998-2000). Sedentary behaviour seems relatively stable across the two cohorts as the increased time that the younger cohort (2008-2010) spent on computers is compensated with an equally decreased time spent watching TV or studying. Across both cohorts about half to three quarters of the adolescents met the health-related criterion for achieved number of steps. The findings show a secular decrease in PA amongst adolescents. The significant interaction effects (cohort × age; and cohort × gender) that this study found suggested that secular trends in PA differ by age and gender.
doi:10.1186/1471-2458-11-731
PMCID: PMC3192689  PMID: 21943194
10.  Neighbourhood socioeconomic status and cardiovascular risk factors: a multilevel analysis of nine cities in the Czech Republic and Germany 
BMC Public Health  2007;7:255.
Background
Previous studies have shown that deprived neighbourhoods have higher cardiovascular mortality and morbidity rates. Inequalities in the distribution of behaviour related risk factors are one possible explanation for this trend. In our study, we examined the association between cardiovascular risk factors and neighbourhood characteristics. To assess the consistency of associations the design is cross-national with data from nine industrial towns from the Czech Republic and Germany.
Methods
We combined datasets from two population based studies, one in Germany ('Heinz Nixdorf Recall (HNR) Study'), and one in the Czech Republic ('Health, Alcohol and Psychosocial Factors in Eastern Europe (HAPIEE) Study'). Participation rates were 56% in the HNR and 55% in the HAPIEE study. The subsample for this particular analysis consists of 11,554 men and women from nine German and Czech towns. Census based information on social characteristics of 326 neighbourhoods were collected from local administrative authorities. We used unemployment rate and overcrowding as area-level markers of socioeconomic status (SES). The cardiovascular risk factors obesity, hypertension, smoking and physical inactivity were used as response variables. Regression models were complemented by individual-level social status (education) and relevant covariates.
Results
Smoking, obesity and low physical activity were more common in deprived neighbourhoods in Germany, even when personal characteristics including individual education were controlled for. For hypertension associations were weak. In the Czech Republic associations were observed for smoking and physical inactivity, but not for obesity and hypertension when individual-level covariates were adjusted for. The strongest association was found for smoking in both countries: in the fully adjusted model the odds ratio for 'high unemployment rate' was 1.30 [95% CI 1.02–1.66] in the Czech Republic and 1.60 [95% CI 1.29–1.98] in Germany.
Conclusion
In this comparative study, the effects of neighbourhood deprivation varied by country and risk factor; the strongest and most consistent effects were found for smoking. Results indicate that area level SES is associated with health related lifestyles, which might be a possible pathway linking social status and cardiovascular disease. Individual-level education had a considerable influence on the association between neighbourhood characteristics and risk factors.
doi:10.1186/1471-2458-7-255
PMCID: PMC2099437  PMID: 17888149
11.  Political changes and trends in cardiovascular risk factors in the Czech Republic, 1985-92. 
BACKGROUND: Mortality from cardiovascular diseases is substantially higher in central and eastern Europe than in the west. After the fall of communism, these countries have undergone radical changes in their political, social, and economic environments but little is known about the impact of these changes on health behaviours or risk factors. Data from the Czech Republic, a country whose mortality rates from cardiovascular diseases are among the highest, were analysed in this report. OBJECTIVES: To examine the trends in cardiovascular risk factors in Czech population over the last decade during which a major and sudden change of the political and social system occurred in 1989, and whether the trends differed in relation to age and educational group. DESIGN AND SETTING: Data from three cross sectional surveys conducted in 1985, 1988, and 1992 as a part of the MONICA project were analysed. The surveys examined random samples of men and women aged 25-64 in six Czech districts and measured the following risk factors: smoking, blood pressure, body mass index (BMI), and total and high density lipoprotein (HDL) cholesterol. RESULTS: The numbers of subjects (response rate) examined were 2573 (84%) in 1985, 2769 (87%) in 1988, and 2353 (73%) in 1992. Total cholesterol and body mass index increased between 1985 and 1988 and decreased between 1988 and 1992. The prevalence of smoking was declining slightly in men between 1985 and 1992 but remained stable in women. There were only small changes in blood pressure. The decline in cholesterol and BMI in 1988-92 may be related to changes in foods consumption after the price deregulation in 1991. An improvement in risk profile was more pronounced in younger age groups, and the declines in cholesterol and obesity were substantially larger in men and women with higher education. By contrast, there was an increase in smoking in women educated only to primary level. CONCLUSION: Substantial changes in cholesterol, obesity, and women's smoking occurred in the Czech population after the political changes in 1989. Although a causal association cannot be claimed, national trends in foods consumption are consistent with changes in blood lipids and obesity. Further monitoring of trends is required to confirm these trends.
PMCID: PMC1060472  PMID: 9229056
12.  A Temperature-Responsive Network Links Cell Shape and Virulence Traits in a Primary Fungal Pathogen 
PLoS Biology  2013;11(7):e1001614.
Analysis of a transcriptional regulatory network in a fungal pathogen reveals that four interdependent transcription factors respond to human body temperature to trigger changes in cell shape and virulence gene expression.
Survival at host temperature is a critical trait for pathogenic microbes of humans. Thermally dimorphic fungal pathogens, including Histoplasma capsulatum, are soil fungi that undergo dramatic changes in cell shape and virulence gene expression in response to host temperature. How these organisms link changes in temperature to both morphologic development and expression of virulence traits is unknown. Here we elucidate a temperature-responsive transcriptional network in H. capsulatum, which switches from a filamentous form in the environment to a pathogenic yeast form at body temperature. The circuit is driven by three highly conserved factors, Ryp1, Ryp2, and Ryp3, that are required for yeast-phase growth at 37°C. Ryp factors belong to distinct families of proteins that control developmental transitions in fungi: Ryp1 is a member of the WOPR family of transcription factors, and Ryp2 and Ryp3 are both members of the Velvet family of proteins whose molecular function is unknown. Here we provide the first evidence that these WOPR and Velvet proteins interact, and that Velvet proteins associate with DNA to drive gene expression. Using genome-wide chromatin immunoprecipitation studies, we determine that Ryp1, Ryp2, and Ryp3 associate with a large common set of genomic loci that includes known virulence genes, indicating that the Ryp factors directly control genes required for pathogenicity in addition to their role in regulating cell morphology. We further dissect the Ryp regulatory circuit by determining that a fourth transcription factor, which we name Ryp4, is required for yeast-phase growth and gene expression, associates with DNA, and displays interdependent regulation with Ryp1, Ryp2, and Ryp3. Finally, we define cis-acting motifs that recruit the Ryp factors to their interwoven network of temperature-responsive target genes. Taken together, our results reveal a positive feedback circuit that directs a broad transcriptional switch between environmental and pathogenic states in response to temperature.
Author Summary
Microbial pathogens of humans display the ability to thrive at host temperature. So-called “thermally dimorphic” fungal pathogens, which include Histoplasma capsulatum, are a class of soil fungi that upon being inhaled into the human lung, undergo dramatic changes in cell shape and virulence gene expression in response to host temperature. The ability of these pathogens to cause disease is exquisitely coupled to temperature response. Here we elucidate the regulatory network that governs the ability of H. capsulatum to switch from a filamentous form in the soil environment to a pathogenic yeast form at body temperature. The circuit is driven by three transcription regulators (Ryp1, Ryp2, and Ryp3) that control yeast-phase growth. We show that these factors, which include two highly conserved proteins of the Velvet family of unknown function, bind to specific regulatory DNA elements and directly regulate expression of virulence genes. We identify and characterize Ryp4, a fourth regulator of this pathway, and define DNA motifs that recruit these transcription factors to their temperature-responsive target genes. Our results provide a molecular understanding of how changes in cell shape are linked to expression of virulence genes in thermally dimorphic fungi.
doi:10.1371/journal.pbio.1001614
PMCID: PMC3720256  PMID: 23935449
13.  Finding of widespread viral and bacterial revolution dsDNA translocation motors distinct from rotation motors by channel chirality and size 
Cell & Bioscience  2014;4:30.
Background
Double-stranded DNA translocation is ubiquitous in living systems. Cell mitosis, bacterial binary fission, DNA replication or repair, homologous recombination, Holliday junction resolution, viral genome packaging and cell entry all involve biomotor-driven dsDNA translocation. Previously, biomotors have been primarily classified into linear and rotational motors. We recently discovered a third class of dsDNA translocation motors in Phi29 utilizing revolution mechanism without rotation. Analogically, the Earth rotates around its own axis every 24 hours, but revolves around the Sun every 365 days.
Results
Single-channel DNA translocation conductance assay combined with structure inspections of motor channels on bacteriophages P22, SPP1, HK97, T7, T4, Phi29, and other dsDNA translocation motors such as bacterial FtsK and eukaryotic mimiviruses or vaccinia viruses showed that revolution motor is widespread. The force generation mechanism for revolution motors is elucidated. Revolution motors can be differentiated from rotation motors by their channel size and chirality. Crystal structure inspection revealed that revolution motors commonly exhibit channel diameters larger than 3 nm, while rotation motors that rotate around one of the two separated DNA strands feature a diameter smaller than 2 nm. Phi29 revolution motor translocated double- and tetra-stranded DNA that occupied 32% and 64% of the narrowest channel cross-section, respectively, evidencing that revolution motors exhibit channel diameters significantly wider than the dsDNA. Left-handed oriented channels found in revolution motors drive the right-handed dsDNA via anti-chiral interaction, while right-handed channels observed in rotation motors drive the right-handed dsDNA via parallel threads. Tethering both the motor and the dsDNA distal-end of the revolution motor does not block DNA packaging, indicating that no rotation is required for motors of dsDNA phages, while a small-angle left-handed twist of dsDNA that is aligned with the channel could occur due to the conformational change of the phage motor channels from a left-handed configuration for DNA entry to a right-handed configuration for DNA ejection for host cell infection.
Conclusions
The revolution motor is widespread among biological systems, and can be distinguished from rotation motors by channel size and chirality. The revolution mechanism renders dsDNA void of coiling and torque during translocation of the lengthy helical chromosome, thus resulting in more efficient motor energy conversion.
doi:10.1186/2045-3701-4-30
PMCID: PMC4060578  PMID: 24940480
DNA translocase; DsDNA viruses; Viral DNA packaging motor; Viral assembly; Bacteriophage; DNA helicase; Revolution force; Phi29; FtsK; RecA; Nanomotor
14.  An inquiry into good hospital governance: A New Zealand-Czech comparison 
Background
This paper contributes to research in health systems literature by examining the role of health boards in hospital governance. Health care ranks among the largest public sectors in OECD countries. Efficient governance of hospitals requires the responsible and effective use of funds, professional management and competent governing structures. In this study hospital governance practice in two health care systems – Czech Republic and New Zealand – is compared and contrasted. These countries were chosen as both, even though they are geographically distant, have a universal right to 'free' health care provided by the state and each has experienced periods of political change and ensuing economic restructuring. Ongoing change has provided the impetus for policy reform in their public hospital governance systems.
Methods
Two comparative case studies are presented. They define key similarities and differences between the two countries' health care systems. Each public hospital governance system is critically analysed and discussed in light of D W Taylor's nine principles of 'good governance'.
Results
While some similarities were found to exist, the key difference between the two countries is that while many forms of 'ad hoc' hospital governance exist in Czech hospitals, public hospitals in New Zealand are governed in a 'collegiate' way by elected District Health Boards. These findings are discussed in relation to each of the suggested nine principles utilized by Taylor.
Conclusion
This comparative case analysis demonstrates that although the New Zealand and Czech Republic health systems appear to show a large degree of convergence, their approaches to public hospital governance differ on several counts. Some of the principles of 'good governance' existed in the Czech hospitals and many were practiced in New Zealand. It would appear that the governance styles have evolved from particular historical circumstances to meet each country's specific requirements. Whether or not current practice could be improved by paying closer attention to theoretical models of 'good governance' is debatable.
doi:10.1186/1478-4505-4-2
PMCID: PMC1379643  PMID: 16460571
15.  A Blend of Chlorophytum Borivilianum and Velvet Bean Increases Serum Growth Hormone in Exercise-Trained Men 
Background:
Several isolated ingredients have been proposed to increase growth hormone (GH) release, including Chlorophytum borivilianum and Velvet bean. A combination of these two ingredients has been packaged within an investigational dietary supplement. It was the purpose of the present investigation to determine the impact of acute ingestion of this supplement on circulating GH in healthy, exercise-trained men.
Methods:
Fifteen men ingested the dietary supplement on two different days, separated by one week. Blood was collected from subjects before ingestion of the supplement and at 20, 40, 60, 80, 100, and 120 minutes post ingestion. GH was analyzed in serum samples using an ELISA method. Values for GH for each subject, at each collection time, were averaged over both test days and used in the main analysis.
Results:
Serum GH increased over time, with higher values at 60 minutes (1.56 ± 0.65 ng · mL−1; P = 0.04; +767%), 80 minutes (1.76 ± 0.69 ng · mL−1; P = 0.02; +878%), and 100 minutes (1.48 ± 0.62 ng · mL−1; P = 0.05; +722%) compared to pre ingestion (0.18 ± 0.04 ng · mL−1). A great deal of subject variability existed in the area under the curve (AUC) for GH, with pooled values ranging from 0.49 to 61.2 ng · mL−1 · 2 hr−1
Conclusion:
Acute ingestion of an investigational dietary supplement containing the active ingredients Chlorophytum borivilianum and Velvet bean results in an increase in circulating GH in exercise-trained men. Additional placebo controlled investigations are needed to extend these findings. Moreover, studies are needed to determine if chronic use of such supplementation leads to favorable changes in health-related parameters associated with increased circulating GH.
doi:10.4137/NMI.S8127
PMCID: PMC3738483  PMID: 23946662
supplements; growth hormone; Chlorophytum borivilianum; Velvet bean; Mucuna pruriens
16.  SCORE performance in Central and Eastern Europe and former Soviet Union: MONICA and HAPIEE results 
European Heart Journal  2013;35(9):571-577.
Aims
The Systematic COronary Risk Evaluation (SCORE) scale assesses 10 year risk of fatal atherosclerotic cardiovascular disease (CVD), based on conventional risk factors. The high-risk SCORE version is recommended for Central and Eastern Europe and former Soviet Union (CEE/FSU), but its performance has never been systematically assessed in the region. We evaluated SCORE performance in two sets of population-based CEE/FSU cohorts.
Methods and results
The cohorts based on the World Health Organization MONitoring of trends and determinants in CArdiovascular disease (MONICA) surveys in the Czech Republic, Poland (Warsaw and Tarnobrzeg), Lithuania (Kaunas), and Russia (Novosibirsk) were followed from the mid-1980s. The Health, Alcohol, and Psychosocial factors in Eastern Europe (HAPIEE) study follows Czech, Polish (Krakow), and Russian (Novosibirsk) cohorts from 2002–05. In Cox regression analyses, the high-risk SCORE ≥5% at baseline significantly predicted CVD mortality in both MONICA [n = 15 027; hazard ratios (HR), 1.7–6.3] and HAPIEE (n = 20 517; HR, 2.6–10.5) samples. While SCORE calibration was good in most MONICA samples (predicted and observed mortality were close), the risk was underestimated in Russia. In HAPIEE, the high-risk SCORE overpredicted the estimated 10 year mortality for Czech and Polish samples and adequately predicted it for Russia. SCORE discrimination was satisfactory in both MONICA and HAPIEE.
Conclusion
The high-risk SCORE underestimated the fatal CVD risk in Russian MONICA but performed well in most MONICA samples and Russian HAPIEE. This SCORE version might overestimate the risk in contemporary Czech and Polish populations.
doi:10.1093/eurheartj/eht189
PMCID: PMC3938861  PMID: 23786858
Cardiovascular mortality; Cardiovascular risk factors; SCORE risk function; Risk prediction; Central and Eastern Europe; Former Soviet Union
17.  Down syndrome, paternal age and education: comparison of California and the Czech Republic 
BMC Public Health  2005;5:69.
Background
The association between maternal age and risk of Down syndrome has been repeatedly shown in various populations. However, the effect of paternal age and education of parents has not been frequently studied. Comparative studies on Down syndrome are also rare. This study evaluates the epidemiological characteristics of Down syndrome in two culturally and socially contrasting population settings, in California and the Czech Republic.
Methods
The observed live birth prevalence of Down syndrome was studied among all newborns in the California counties monitored by California Birth Defects Monitoring Program from 1996 to 1997, and in the whole Czech Republic from 1994 to 1998. Logistic regression was used to analyze the data.
Results
A total of 516,745 (California) and 475,834 (the Czech Republic) infants were included in the analysis. Among them, 593 and 251, respectively, had Down syndrome. The mean maternal age of children with Down syndrome was 32.1 years in California and 26.9 years in the Czech Republic. Children born to older mothers were at greater risk of Down syndrome in both populations. The association with paternal age was mostly explained by adjusting for maternal age, but remained significant in the Czech Republic. The association between maternal education and Down syndrome was much stronger in California than in the Czech Republic but parental age influences higher occurrence of Down syndrome both in California and in the Czech Republic.
Conclusion
The educational gradient in California might reflect selective impact of prenatal diagnosis, elective termination, and acceptance of prenatal diagnostic measures in Californian population.
doi:10.1186/1471-2458-5-69
PMCID: PMC1166564  PMID: 15963229
18.  Efficient parallel and out of core algorithms for constructing large bi-directed de Bruijn graphs 
BMC Bioinformatics  2010;11:560.
Background
Assembling genomic sequences from a set of overlapping reads is one of the most fundamental problems in computational biology. Algorithms addressing the assembly problem fall into two broad categories - based on the data structures which they employ. The first class uses an overlap/string graph and the second type uses a de Bruijn graph. However with the recent advances in short read sequencing technology, de Bruijn graph based algorithms seem to play a vital role in practice. Efficient algorithms for building these massive de Bruijn graphs are very essential in large sequencing projects based on short reads. In an earlier work, an O(n/p) time parallel algorithm has been given for this problem. Here n is the size of the input and p is the number of processors. This algorithm enumerates all possible bi-directed edges which can overlap with a node and ends up generating Θ(nΣ) messages (Σ being the size of the alphabet).
Results
In this paper we present a Θ(n/p) time parallel algorithm with a communication complexity that is equal to that of parallel sorting and is not sensitive to Σ. The generality of our algorithm makes it very easy to extend it even to the out-of-core model and in this case it has an optimal I/O complexity of Θ(nlog(n/B)Blog(M/B)) (M being the main memory size and B being the size of the disk block). We demonstrate the scalability of our parallel algorithm on a SGI/Altix computer. A comparison of our algorithm with the previous approaches reveals that our algorithm is faster - both asymptotically and practically. We demonstrate the scalability of our sequential out-of-core algorithm by comparing it with the algorithm used by VELVET to build the bi-directed de Bruijn graph. Our experiments reveal that our algorithm can build the graph with a constant amount of memory, which clearly outperforms VELVET. We also provide efficient algorithms for the bi-directed chain compaction problem.
Conclusions
The bi-directed de Bruijn graph is a fundamental data structure for any sequence assembly program based on Eulerian approach. Our algorithms for constructing Bi-directed de Bruijn graphs are efficient in parallel and out of core settings. These algorithms can be used in building large scale bi-directed de Bruijn graphs. Furthermore, our algorithms do not employ any all-to-all communications in a parallel setting and perform better than the prior algorithms. Finally our out-of-core algorithm is extremely memory efficient and can replace the existing graph construction algorithm in VELVET.
doi:10.1186/1471-2105-11-560
PMCID: PMC2996408  PMID: 21078174
19.  e-Health, m-Health and healthier social media reform: the big scale view 
Introduction
In the upcoming decade, digital platforms will be the backbone of a strategic revolution in the way medical services are provided, affecting both healthcare providers and patients. Digital-based patient-centered healthcare services allow patients to actively participate in managing their own care, in times of health as well as illness, using personally tailored interactive tools. Such empowerment is expected to increase patients’ willingness to adopt actions and lifestyles that promote health as well as improve follow-up and compliance with treatment in cases of chronic illness. Clalit Health Services (CHS) is the largest HMO in Israel and second largest world-wide. Through its 14 hospitals, 1300 primary and specialized clinics, and 650 pharmacies, CHS provides comprehensive medical care to the majority of Israel’s population (above 4 million members). CHS e-Health wing focuses on deepening patient involvement in managing health, through personalized digital interactive tools. Currently, CHS e-Health wing provides e-health services for 1.56 million unique patients monthly with 2.4 million interactions every month (August 2011). Successful implementation of e-Health solutions is not a sum of technology, innovation and health; rather it’s the expertise of tailoring knowledge and leadership capabilities in multidisciplinary areas: clinical, ethical, psychological, legal, comprehension of patient and medical team engagement etc. The Google Health case excellently demonstrates this point. On the other hand, our success with CHS is a demonstration that e-Health can be enrolled effectively and fast with huge benefits for both patients and medical teams, and with a robust business model.
CHS e-Health core components
They include:
1. The personal health record layer (what the patient can see) presents patients with their own medical history as well as the medical history of their preadult children, including diagnoses, allergies, vaccinations, laboratory results with interpretations in layman’s terms, medications with clear, straightforward explanations regarding dosing instructions, important side effects, contraindications, such as lactation etc., and other important medical information. All personal e-Health services require identification and authorization.
2. The personal knowledge layer (what the patient should know) presents patients with personally tailored recommendations for preventative medicine and health promotion. For example, diabetic patients are push notified regarding their yearly eye exam. The various health recommendations include: occult blood testing, mammography, lipid profile etc. Each recommendation contains textual, visual and interactive content components in order to promote engagement and motivate the patient to actually change his health behaviour.
3. The personal health services layer (what the patient can do) enables patients to schedule clinic visits, order chronic prescriptions, e-consult their physician via secured e-mail, set SMS medication reminders, e-consult a pharmacist regarding personal medications. Consultants’ answers are sent securely to the patients’ personal mobile device.
On December 2009 CHS launched secured, web based, synchronous medical consultation via video conference. Currently 11,780 e-visits are performed monthly (May 2011). The medical encounter includes e-prescription and referral capabilities which are biometrically signed by the physician. On December 2010 CHS launched a unique mobile health platform, which is one of the most comprehensive personal m-Health applications world-wide. An essential advantage of mobile devices is their potential to bridge the digital divide. Currently, CHS m-Health platform is used by more than 45,000 unique users, with 75,000 laboratory results views/month, 1100 m-consultations/month and 9000 physician visit scheduling/month.
4. The Bio-Sensing layer (what physiological data the patient can populate) includes diagnostic means that allow remote physical examination, bio-sensors that broadcast various physiological measurements, and smart homecare devices, such as e-Pill boxes that gives seniors, patients and their caregivers the ability to stay at home and live life to its fullest. Monitored data is automatically transmitted to the patient’s Personal Health Record and to relevant medical personnel.
The monitoring layer is embedded in the chronic disease management platform, and in the interactive health promotion and wellness platform. It includes tailoring of consumer-oriented medical devices and service provided by various professional personnel—physicians, nurses, pharmacists, dieticians and more.
5. The Social layer (what the patient can share). Social media networks triggered an essential change at the humanity ‘genome’ level, yet to be further defined in the upcoming years. Social media has huge potential in promoting health as it combines fun, simple yet extraordinary user experience, and bio-social-feedback. There are two major challenges in leveraging health care through social networks:
a. Our personal health information is the cornerstone for personalizing healthier lifestyle, disease management and preventative medicine. We naturally see our personal health data as a super-private territory. So, how do we bring the power of our private health information, currently locked within our Personal Health Record, into social media networks without offending basic privacy issues?
b. Disease management and preventive medicine are currently neither considered ‘cool’ nor ‘fun’ or ‘potentially highly viral’ activities; yet, health is a major issue of everybody’s life. It seems like we are missing a crucial element with a huge potential in health behavioural change—the Fun Theory. Social media platforms comprehends user experience tools that potentially could break current misconception, and engage people in the daily task of taking better care of themselves.
CHS e-Health innovation team characterized several break-through applications in this unexplored territory within social media networks, fusing personal health and social media platforms without offending privacy. One of the most crucial issues regarding adoption of e-health and m-health platforms is change management. Being a ‘hot’ innovative ‘gadget’ is far from sufficient for changing health behaviours at the individual and population levels.
CHS health behaviour change management methodology includes 4 core elements:
1. Engaging two completely different populations: patients, and medical teams. e-Health applications must present true added value for both medical teams and patients, engaging them through understanding and assimilating “what’s really in it for me”. Medical teams are further subdivided into physicians, nurses, pharmacists and administrative personnel—each with their own driving incentive. Resistance to change is an obstacle in many fields but it is particularly true in the conservative health industry. To successfully manage a large scale persuasive process, we treat intra-organizational human resources as “Change Agents”. Harnessing the persuasive power of ~40,000 employees requires engaging them as the primary target group. Successful recruitment has the potential of converting each patient-medical team interaction into an exposure opportunity to the new era of participatory medicine via e-health and m-health channels.
2. Implementation waves: every group of digital health products that are released at the same time are seen as one project. Each implementation wave leverages the focus of the organization and target populations to a defined time span. There are three major and three minor implementation waves a year.
3. Change-Support Arrow: a structured infrastructure for every implementation wave. The sub-stages in this strategy include:
Cross organizational mapping and identification of early adopters and stakeholders relevant to the implementation wave
Mapping positive or negative perceptions and designing specific marketing approaches for the distinct target groups
Intra and extra organizational marketing
Conducting intensive training and presentation sessions for groups of implementers
Running conflict-prevention activities, such as advanced tackling of potential union resistance
Training change-agents with resistance-management behavioural techniques, focused intervention for specific incidents and for key opinion leaders
Extensive presence in the clinics during the launch period, etc.
The entire process is monitored and managed continuously by a review team.
4. Closing Phase: each wave is analyzed and a “lessons-learned” session concludes the changes required in the modus operandi of the e-health project team.
PMCID: PMC3571141
e-Health; mobile health; personal health record; online visit; patient empowerment; knowledge prescription
20.  The changing nutrition scenario 
The past seven decades have seen remarkable shifts in the nutritional scenario in India. Even up to the 1950s severe forms of malnutrition such as kwashiorkar and pellagra were endemic. As nutritionists were finding home-grown and common-sense solutions for these widespread problems, the population was burgeoning and food was scarce. The threat of widespread household food insecurity and chronic undernutrition was very real. Then came the Green Revolution. Shortages of food grains disappeared within less than a decade and India became self-sufficient in food grain production. But more insidious problems arising from this revolution were looming, and cropping patterns giving low priority to coarse grains and pulses, and monocropping led to depletion of soil nutrients and ‘Green Revolution fatigue’. With improved household food security and better access to health care, clinical manifestations of severe malnutrition virtually disappeared. But the decline in chronic undernutrition and “hidden hunger” from micronutrient deficiencies was slow. On the cusp of the new century, an added factor appeared on the nutritional scene in India. With steady urban migration, upward mobility out of poverty, and an increasingly sedentary lifestyle because of improvements in technology and transport, obesity rates began to increase, resulting in a dual burden. Measured in terms of its performance in meeting its Millennium Development Goals, India has fallen short. Despite its continuing high levels of poverty and illiteracy, India has a huge demographic potential in the form of a young population. This advantage must be leveraged by investing in nutrition education, household access to nutritious diets, sanitary environment and a health-promoting lifestyle. This requires co-operation from all the stakeholders, including governments, non government organizations, scientists and the people at large.
PMCID: PMC3818608  PMID: 24135189
Dual nutrition burden; green revolution; micronutrients; nutrition; supplementation
21.  Estimating the number of colorectal cancer patients treated with anti-tumour therapy in 2015: the analysis of the Czech National Cancer Registry 
BMC Public Health  2012;12:117.
Background
Colorectal cancer (CRC) represents a serious health care problem in the Czech Republic, introducing a need for a prospective modelling of the incidence and prevalence rates. The prevalence of patients requiring anti-tumour therapy is also of great importance, as it is directly associated with planning of health care resources.
Methods
This work proposes a population-based model for the estimation of stage-specific prevalence of CRC patients who will require active anti-tumour therapy in a given year. Its applicability is documented on records of the Czech National Cancer Registry (CNCR), which is used to estimate the number of patients potentially treated with anti-tumour therapy in the Czech Republic in 2015.
Results
Several scenarios are adopted to cover the plausible development of the incidence and survival rates, and the probability of an anti-tumour therapy initiation. Based on the scenarios, the model predicts an increase in CRC prevalence from 13% to 30% in comparison with the situation in 2008. Moreover, the model predicts that 10,074 to 11,440 CRC patients will be indicated for anti-tumour therapy in the Czech Republic in 2015. Considering all patients with terminal cancer recurrence and all patients primarily diagnosed in stage IV, it is predicted that 3,485 to 4,469 CRC patients will be treated for the metastatic disease in 2015, which accounts for more than one third (34-40%) of all CRC patients treated this year.
Conclusions
A new model for the estimation of the number of CRC patients requiring active anti-tumour therapy is proposed in this paper. The model respects the clinical stage as the primary stratification factor and utilizes solely the population-based cancer registry data. Thus, no specific hospital data records are needed in the proposed approach. Regarding the short-term prediction of the CRC burden in the Czech Republic, the model confirms a continuous increase in the burden that must be accounted for in the future planning of health care in the Czech Republic.
doi:10.1186/1471-2458-12-117
PMCID: PMC3315738  PMID: 22325812
22.  Early childhood caries trends and surveillance shortcomings in the Czech Republic 
BMC Public Health  2012;12:547.
Background
Despite the decline in childhood caries prevalence, seen particularly in 1980s, in recent years there have been reports that the declining trend has stopped or even reversed in some countries. The aim of the study was to analyse data from previous epidemiological studies on early childhood caries in the Czech Republic, conduct a secondary analysis of trend in dental caries prevalence, and discuss issues related to national oral health surveillance.
Methods
Since the 1990s, caries prevalence in preschool children was monitored by two independent bodies: Institute of Health Information and Statistics (IHIS) that conducted 5 cross-sectional surveys over the period 1994–2006, and Institute of Dental Research (IDR) that conducted 4 studies over the years 1998–2010. Both study series differed in methods of sample selection and approaches to examiner training. For the assessment of the caries prevalence trends, regression modelling was used for the following oral-health indicators: caries experience, mean number of teeth with untreated caries (dt) and percentage of caries-free children.
Results
In both study series, a significant overall trend of declining caries experience and level of untreated caries, and an increasing trend of percentage of caries-free children was observed (p < 0.05). In IHIS studies, caries experience reduced from 3.5 to 2.7; dt reduced from 2.2 to 1.5 and a proportion of caries-free children increased from 23.9 to 42.2%. In IDR studies, caries experience reduced from 3.7 to 2.98; dt reduced from 2.5 to 2.1 and a proportion of caries-free children increased from 26.7 to 44.9%.
Conclusions
Both study series identified a significant decline of caries prevalence particularly in the 1990s and early 2000s. By the end of the investigated period, flattening of the caries decline was observed. The positive trend was observed in the absence of any systematic preventive initiatives on a population level. With respect to the above the authors assume that in the Czech Republic there still is a potential for further caries reduction in preschool population. This, however, cannot be expected without any health policy interventions. Oral health surveillance in the Czech Republic should be promoted by competent regulatory authorities.
doi:10.1186/1471-2458-12-547
PMCID: PMC3434047  PMID: 22828200
Early childhood caries; Caries experience; Primary dentition; Oral health surveillance
23.  Age biases in a large HIV and sexual behaviour-related internet survey among MSM 
BMC Public Health  2013;13:826.
Background
Behavioural data from MSM are usually collected in non-representative convenience samples, increasingly on the internet. Epidemiological data from such samples might be useful for comparisons between countries, but are subject to unknown participation biases.
Methods
Self-reported HIV diagnoses from participants of the European MSM Internet Survey (EMIS) living in the Czech Republic, Germany, the Netherlands, Portugal, Sweden and the United Kingdom were compared with surveillance data, for both the overall diagnosed prevalence and for new diagnoses made in 2009. Country level prevalence and new diagnoses rates per 100 MSM were calculated based on an assumed MSM population size of 3% of the adult male population. Survey-surveillance discrepancies (SSD) for survey participation, diagnosed HIV prevalence and new HIV diagnoses were determined as ratios of proportions. Results are calculated and presented by 5-year age groups for MSM aged 15–64.
Results
Surveillance derived estimates of diagnosed HIV prevalence among MSM aged 15–64 ranged from 0.63% in the Czech Republic to 4.93% in the Netherlands. New HIV diagnoses rates ranged between 0.10 per 100 MSM in the Czech Republic and 0.48 per 100 in the Netherlands. Self-reported rates from EMIS were consistently higher, with prevalence ranging from 2.68% in the Czech Republic to 12.72% in the Netherlands, and new HIV diagnoses rates from 0.36 per 100 in Sweden to 1.44 per 100 in the Netherlands. Across age groups, the survey surveillance discrepancies (SSD) for new HIV diagnoses were between 1.93 in UK and 5.95 in the Czech Republic, and for diagnosed prevalence between 1.80 in Germany and 4.26 in the Czech Republic.
Internet samples of MSM were skewed towards younger age groups when compared to an age distribution of the general adult male population. Survey-surveillance discrepancies (SSD) for EMIS participation were inverse u-shaped across the age range. The two HIV-related SSD were u- or j-shaped with higher values for the very young and for older MSM. The highest discrepancies between survey and surveillance data regarding HIV-prevalence were observed in the oldest age group in Sweden and the youngest age group in Portugal.
Conclusion
Internet samples are biased towards a lower median age because younger men are over-represented on MSM dating websites and therefore may be more likely to be recruited into surveys. Men diagnosed with HIV were over-represented in the internet survey, and increasingly so in the older age groups. A similar effect was observed in the age groups younger than 25 years. Self-reported peak prevalence and peak HIV diagnoses rates are often shifted to higher age groups in internet samples compared to surveillance data. Adjustment for age-effects on online accessibility should be considered when linking data from internet surveys with surveillance data.
doi:10.1186/1471-2458-13-826
PMCID: PMC3847490  PMID: 24020518
MSM; Internet samples; HIV prevalence; Survey-surveillance discrepancies; Participation bias
24.  Changes in the Provision of Institutionalized Mental Health Care in Post-Communist Countries 
PLoS ONE  2012;7(6):e38490.
Background
General psychiatric and forensic psychiatric beds, supported housing and the prison population have been suggested as indicators of institutionalized mental health care. According to the Penrose hypothesis, decreasing psychiatric bed numbers may lead to increasing prison populations. The study aimed to assess indicators of institutionalized mental health care in post-communist countries during the two decades following the political change, and to explore whether the data are consistent with the Penrose hypothesis in that historical context.
Methodology/Principal Findings
General psychiatric and forensic psychiatric bed numbers, supported housing capacities and the prison population rates were collected in Azerbaijan, Belarus, Croatia, Czech Republic, East Germany, Hungary, Kazakhstan, Latvia, Poland, Romania, Russia and Slovenia. Percentage change of indicators over the decades 1989–1999, 1999–2009 and the whole period of 1989–2009 and correlations between changes of different indicators were calculated. Between 1989 and 2009, the number of general psychiatric beds was reduced in all countries. The decrease ranged from −11% in Croatia to −51% in East Germany. In 2009, the bed numbers per 100,000 population ranged from 44.7 in Azerbaijan to 134.4 in Latvia. Forensic psychiatric bed numbers and supported housing capacities increased in most countries. From 1989–2009, trends in the prison population ranged from a decrease of −58% in East Germany to an increase of 43% in Belarus and Poland. Trends in different indicators of institutionalised care did not show statistically significant associations.
Conclusions/Significance
After the political changes in 1989, post-communist countries experienced a substantial reduction in general psychiatric hospital beds, which in some countries may have partly been compensated by an increase in supported housing capacities and more forensic psychiatric beds. Changes in the prison population are inconsistent. The findings do not support the Penrose hypothesis in that historical context as a general rule for most of the countries.
doi:10.1371/journal.pone.0038490
PMCID: PMC3371010  PMID: 22715387
25.  Dietary habits in three Central and Eastern European countries: the HAPIEE study 
BMC Public Health  2009;9:439.
Background
The high cardiovascular mortality in Eastern Europe has often been attributed to poor diet, but individual-level data on nutrition in the region are generally not available. This paper describes the methods of dietary assessment and presents preliminary findings on food and nutrient intakes in large general population samples in Russia, Poland and the Czech Republic.
Methods
The HAPIEE (Health, Alcohol and Psychosocial factors In Eastern Europe) study examined random samples of men and women aged 45-69 years at baseline in Novosibirsk (Russia), Krakow (Poland) and six Czech urban centres in 2002-2005. Diet was assessed using a food frequency questionnaire (at least 136 items); complete dietary information was available for 26,870 persons.
Results
Total energy intakes among men ranged between 8.7 MJ in the Czech sample and 11.7 MJ in the Russian sample, while among women, energy intakes ranged between 8.2 MJ in the Czech sample and 9.8 MJ in the Russian sample. A Healthy Diet Indicator (HDI), ranging from a score of 0 (lowest) to 7 (highest), was developed using the World Health Organisation's (WHO) guidelines for the prevention of chronic diseases. The mean HDI scores were low, ranging from 1.0 (SD = 0.7) among the Polish subjects to 1.7 (SD = 0.8) among the Czech females. Very few subjects met the WHO recommended intakes for complex carbohydrates, pulses or nuts; intakes of saturated fatty acids, sugar and protein were too high. Only 16% of Polish subjects met the WHO recommendation for polyunsaturated fat intake. Consumption of fruits and vegetables was lower than recommended, especially among those Russian subjects who were assessed during the low intake season. Fewer than 65% of subjects consumed adequate amounts of calcium, magnesium and potassium, when compared with the United Kingdom's Reference Nutrient Intake.
Conclusion
This first large scale study of individual-based dietary intakes in the general population in Eastern Europe implies that intakes of saturated fat, sugar and complex carbohydrates are a cause for concern. The development of country-specific nutritional tools must be encouraged and nutritional campaigns must undergo continuing development.
doi:10.1186/1471-2458-9-439
PMCID: PMC2791768  PMID: 19951409

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