Health inequalities in Germany: do regional-level variables explain differentials in cardiovascular risk?

Breckenkamp J, Mielck A, Razum O. Health inequalities in Germany: do regional-level variables explain differentials in cardiovascular risk? BMC Public Health. 2007;7(1): 132.Background: Socioeconomic status is a predictor not only of mortality, but also of cardiovascular risk and morbidity. An ongoing debate in the field of social inequalities and health focuses on two questions: 1) Is individual health status associated with individual income as well as with income inequality at the aggregate (e. g. regional) level? 2) If there is such an association, does it operate via a psychosocial pathway (e.g. stress) or via a ´´neo-materialistic´´ pathway (e.g. systematic under-investment in societal infrastructures)? For the first time in Germany, we here investigate the association between cardiovascular health status and income inequality at the area level, controlling for individual socio-economic status. Methods: Individual-level explanatory variables (age, socio-economic status) and outcome data (body mass index, blood pressure, cholesterol level) as well as the regional-level variable (proportion of relative poverty) were taken from the baseline survey of the German Cardiovascular Prevention Study, a cross-sectional, community-based, multi-center intervention study, comprising six socio-economically diverse intervention regions, each with about 1800 participants aged 25–69 years. Multilevel modeling was used to examine the effects of individual and regional level variables. Results: Regional effects are small compared to individual effects for all risk factors analyzed. Most of the total variance is explained at the individual level. Only for diastolic blood pressure in men and for cholesterol in both men and women is a statistically significant effect visible at the regional level. Conclusion: Our analysis does not support the assumption that in Germany cardiovascular risk factors were to a large extent associated with income inequality at regional level

Household item ownership and self-rated health: material and psychosocial explanations

BACKGROUND: There has been an ongoing debate whether the effects of socioeconomic factors on health are due to absolute poverty and material factors or to relative deprivation and psychosocial factors. In the present analyses, we examined the importance for health of material factors, which may have a direct effect on health, and of those that may affect health indirectly, through psychosocial mechanisms. METHODS: Random national samples of men and women in Hungary (n = 973) and Poland (n = 1141) were interviewed (response rates 58% and 59%, respectively). The subjects reported their self-rated health, socioeconomic circumstances, including ownership of different household items, and perceived control over life. Household items were categorised as "basic needs", "socially oriented", and "luxury". We examined the association between the ownership of different groups of items and self-rated health. Since the lists of household items were different in Hungary and Poland, we conducted parallel identical analyses of the Hungarian and Polish data. RESULTS: The overall prevalence of poor or very poor health was 13% in Poland and 25% in Hungary. Education, material deprivation and the number of household items were all associated with poor health in bivariate analyses. All three groups of household items were positively related to self-rated health in age-adjusted analyses. The relation of basic needs items to poor health disappeared after controlling for other socioeconomic variables (mainly material deprivation). The relation of socially oriented and luxury items to poor health, however, persisted in multivariate models. The results were similar in both datasets. CONCLUSIONS: These data suggest that health is influenced by both material and psychosocial aspects of socioeconomic factors

Modeling inflammation and oxidative stress in gastrointestinal disease development using novel organotypic culture systems

Gastroesophageal reflux disease (GERD), Barrett's esophagus (BE), graft-versus-host disease (GVHD), and inflammatory bowel diseases such as ulcerative colitis and Crohn's disease are common human gastrointestinal diseases that share inflammation as a key driver for their development. A general outcome resulting from these chronic inflammatory conditions is increased oxidative stress. Oxidative stress is caused by the generation of reactive oxygen and nitrogen species that are part of the normal inflammatory response, but are also capable of damaging cellular DNA, protein, and organelles. Damage to DNA can include DNA strand breaks, point mutations due to DNA adducts, as well as alterations in methylation patterns leading to activation of oncogenes or inactivation of tumor suppressors. There are a number of significant long-term consequences associated with chronic oxidative stress, most notably cancer. Infiltrating immune cells and stromal components of tissue including fibroblasts contribute to dynamic changes occurring in tissue related to disease development. Immune cells can potentiate oxidative stress, and fibroblasts have the capacity to contribute to advanced growth and proliferation of the epithelium and any resultant cancers. Disease models for GERD, BE, GVHD, and ulcerative colitis based on three-dimensional human cell and tissue culture systems that recapitulate in vivo growth and differentiation in inflammatory-associated microphysiological environments would enhance our understanding of disease progression and improve our ability to test for disease-prevention strategies. The development of physiologically relevant, human cell-based culture systems is therefore a major focus of our research. These novel models will be of enormous value, allowing us to test hypotheses and advance our understanding of these disorders, and will have a translational impact allowing us to more rapidly develop therapeutic and chemopreventive agents. In summary, this work to develop advanced human cell-based models of inflammatory conditions will greatly improve our ability to study, prevent, and treat GERD, BE, GVHD, and inflammatory bowel disease. The work will also foster the development of novel therapeutic and preventive strategies that will improve patient care for these important clinical conditions. © 2013 BioMed Central Ltd

Impact of Space Weather on Climate and Habitability of Terrestrial Type Exoplanets

The current progress in the detection of terrestrial type exoplanets has opened a new avenue in the characterization of exoplanetary atmospheres and in the search for biosignatures of life with the upcoming ground-based and space missions. To specify the conditions favorable for the origin, development and sustainment of life as we know it in other worlds, we need to understand the nature of astrospheric, atmospheric and surface environments of exoplanets in habitable zones around G-K-M dwarfs including our young Sun. Global environment is formed by propagated disturbances from the planet-hosting stars in the form of stellar flares, coronal mass ejections, energetic particles, and winds collectively known as astrospheric space weather. Its characterization will help in understanding how an exoplanetary ecosystem interacts with its host star, as well as in the specification of the physical, chemical and biochemical conditions that can create favorable and/or detrimental conditions for planetary climate and habitability along with evolution of planetary internal dynamics over geological timescales. A key linkage of (astro) physical, chemical, and geological processes can only be understood in the framework of interdisciplinary studies with the incorporation of progress in heliophysics, astrophysics, planetary and Earth sciences. The assessment of the impacts of host stars on the climate and habitability of terrestrial (exo)planets will significantly expand the current definition of the habitable zone to the biogenic zone and provide new observational strategies for searching for signatures of life. The major goal of this paper is to describe and discuss the current status and recent progress in this interdisciplinary field and to provide a new roadmap for the future development of the emerging field of exoplanetary science and astrobiology.Comment: 206 pages, 24 figures, 1 table; Review paper. International Journal of Astrobiology (2019

The Random Nature of Genome Architecture: Predicting Open Reading Frame Distributions

Background: A better understanding of the size and abundance of open reading frames (ORFS) in whole genomes may shed light on the factors that control genome complexity. Here we examine the statistical distributions of open reading frames (i.e. distribution of start and stop codons) in the fully sequenced genomes of 297 prokaryotes, and 14 eukaryotes. Methodology/Principal Findings: By fitting mixture models to data from whole genome sequences we show that the size-frequency distributions for ORFS are strikingly similar across prokaryotic and eukaryotic genomes. Moreover, we show that i) a large fraction (60–80%) of ORF size-frequency distributions can be predicted a priori with a stochastic assembly model based on GC content, and that (ii) size-frequency distributions of the remaining “non-random” ORFs are well-fitted by log-normal or gamma distributions, and similar to the size distributions of annotated proteins. Conclusions/Significance: Our findings suggest stochastic processes have played a primary role in the evolution of genome complexity, and that common processes govern the conservation and loss of functional genomics units in both prokaryotes and eukaryotes.8 page(s

A two step Bayesian approach for genomic prediction of breeding values

<p>Abstract</p> <p>Background</p> <p>In genomic models that assign an individual variance to each marker, the contribution of one marker to the posterior distribution of the marker variance is only one degree of freedom (df), which introduces many variance parameters with only little information per variance parameter. A better alternative could be to form clusters of markers with similar effects where markers in a cluster have a common variance. Therefore, the influence of each marker group of size <it>p </it>on the posterior distribution of the marker variances will be <it>p </it>df.</p> <p>Methods</p> <p>The simulated data from the 15^thQTL-MAS workshop were analyzed such that SNP markers were ranked based on their effects and markers with similar estimated effects were grouped together. In step 1, all markers with minor allele frequency more than 0.01 were included in a SNP-BLUP prediction model. In step 2, markers were ranked based on their estimated variance on the trait in step 1 and each 150 markers were assigned to one group with a common variance. In further analyses, subsets of 1500 and 450 markers with largest effects in step 2 were kept in the prediction model.</p> <p>Results</p> <p>Grouping markers outperformed SNP-BLUP model in terms of accuracy of predicted breeding values. However, the accuracies of predicted breeding values were lower than Bayesian methods with marker specific variances.</p> <p>Conclusions</p> <p>Grouping markers is less flexible than allowing each marker to have a specific marker variance but, by grouping, the power to estimate marker variances increases. A prior knowledge of the genetic architecture of the trait is necessary for clustering markers and appropriate prior parameterization.</p

Genetic and phenotypic characterisation of inherited myopathies in a tertiary neuromuscular centre

Diagnosis of inherited myopathies can be a challenging and lengthy process due to broad genetic and phenotypic heterogeneity. In this study we applied focused exome sequencing to investigate a cohort of 100 complex adult myopathy cases who remained undiagnosed despite extensive investigation. We evaluated the frequency of genetic diagnoses, clinical and pathological factors most likely to be associated with a positive diagnosis, clinical pitfalls and new phenotypic insights that could help to guide future clinical practice. We identified pathogenic/likely pathogenic variants in 32/100 cases. TTN-related myopathy was the most common diagnosis (4/32 cases) but the majority of positive diagnoses related to a single gene each. Childhood onset of symptoms was more likely to be associated with a positive diagnosis. Atypical and new clinico-pathological phenotypes with diagnostic pitfalls were identified. These include the new emerging group of neuromyopathy genes (HSPB1, BICD2) and atypical biopsy findings: COL6A-related myopathy with mitochondrial features, DOK7 presenting as myopathy with minicores and DES-related myopathy without myofibrillar pathology. Our data demonstrates the diagnostic efficacy of broad NGS screening when combined with detailed clinico-pathological phenotyping in a complex neuromuscular cohort. Atypical clinico-pathological features may delay the diagnostic process if smaller targeted gene panels are used

Group B Streptococcal Disease Worldwide for Pregnant Women, Stillbirths, and Children: Why, What, and How to Undertake Estimates?

Improving maternal, newborn, and child health is central to Sustainable Development Goal targets for 2030, requiring acceleration especially to prevent 5.6 million deaths around the time of birth. Infections contribute to this burden, but etiological data are limited. Group B Streptococcus (GBS) is an important perinatal pathogen, although previously focus has been primarily on liveborn children, especially early-onset disease. In this first of an 11-article supplement, we discuss the following: (1) Why estimate the worldwide burden of GBS disease? (2) What outcomes of GBS in pregnancy should be included? (3) What data and epidemiological parameters are required? (4) What methods and models can be used to transparently estimate this burden of GBS? (5) What are the challenges with available data? and (6) How can estimates address data gaps to better inform GBS interventions including maternal immunization? We review all available GBS data worldwide, including maternal GBS colonization, risk of neonatal disease (with/without intrapartum antibiotic prophylaxis), maternal GBS disease, neonatal/infant GBS disease, and subsequent impairment, plus GBS-associated stillbirth, preterm birth, and neonatal encephalopathy. We summarize our methods for searches, meta-analyses, and modeling including a compartmental model. Our approach is consistent with the World Health Organization (WHO) Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER), published in The Lancet and the Public Library of Science (PLoS). We aim to address priority epidemiological gaps highlighted by WHO to inform potential maternal vaccination