Preclinical cardiac disease in women and men with primary aldosteronism

Purpose We tested the sex-specific associations between primary aldosteronism (PA), left ventricular (LV) hypertrophy and LV systolic myocardial function. Material and methods Conventional and speckle tracking echocardiography was performed in 109 patients with PA and 89 controls with essential hypertension (EH). LV hypertrophy was identified if LV mass index exceeded 47.0 g/m2.7 in women and 50.0 g/m2.7 in men. LV systolic myocardial function was assessed by global longitudinal strain (GLS) and midwall shortening. Results PA patients had higher prevalence of LV hypertrophy (52 vs. 21%, p < 0.001) than EH patients in both sexes, while GLS did not differ by sex or hypertension aetiology. In multivariable analyses, presence of LV hypertrophy was associated with PA and obesity in both sexes, while lower systolic myocardial function, whether measured by GLS or midwall shortening, was not associated with PA, but primarily with higher body mass index and LV mass index, respectively, in both sexes (all p < 0.05). Conclusion Having PA was associated with higher prevalence of LV hypertrophy both in women and men, compared to EH. PA was not associated with LV systolic myocardial function in either sex.publishedVersio

Strain Construction and Process Development for Efficient Recombinant Production of Mannuronan C-5 Epimerases in Hansenula polymorpha

Alginates are linear polysaccharides produced by brown algae and some bacteria and are composed of β-D-mannuronic acid (M) and α-L-guluronic acid (G). Alginate has numerous present and potential future applications within industrial, medical and pharmaceutical areas and G rich alginates are traditionally most valuable and frequently used due to their gelling and viscosifying properties. Mannuronan C-5 epimerases are enzymes converting M to G at the polymer level during the biosynthesis of alginate. The Azotobacter vinelandii epimerases AlgE1-AlgE7 share a common structure, containing one or two catalytic A-modules (A), and one to seven regulatory R-modules (R). Despite the structural similarity of the epimerases, they create different M-G patterns in the alginate; AlgE4 (AR) creates strictly alternating MG structures whereas AlgE1 (ARRRAR) and AlgE6 (ARRR) create predominantly G-blocks. These enzymes are therefore promising tools for producing in vitro tailor-made alginates. Efficient in vitro epimerization of alginates requires availability of recombinantly produced alginate epimerases, and for this purpose the methylotrophic yeast Hansenula polymorpha is an attractive host organism. The present study investigates whether H. polymorpha is a suitable expression system for future large-scale production of AlgE1, AlgE4, and AlgE6. H. polymorpha expression strains were constructed using synthetic genes with reduced repetitive sequences as well as optimized codon usage. High cell density cultivations revealed that the largest epimerases AlgE1 (147 kDa) and AlgE6 (90 kDa) are subject to proteolytic degradation by proteases secreted by the yeast cells. However, degradation could be controlled to a large extent either by co-expression of chaperones or by adjusting cultivation conditions. The smaller AlgE4 (58 kDa) was stable under all tested conditions. The results obtained thus point toward a future potential for using H. polymorpha in industrial production of mannuronan C-5 epimerases for in vitro tailoring of alginates.publishedVersio

Socioeconomic inequalities in stillbirth rates in Europe: measuring the gap using routine data from the Euro-Peristat Project

Background Previous studies have shown that socioeconomic position is inversely associated with stillbirth risk, but the impact on national rates in Europe is not known. We aimed to assess the magnitude of social inequalities in stillbirth rates in European countries using indicators generated from routine monitoring systems. Methods Aggregated data on the number of stillbirths and live births for the year 2010 were collected for three socioeconomic indicators (mothers’ educational level, mothers’ and fathers’ occupational group) from 29 European countries participating in the Euro-Peristat project. Educational categories were coded using the International Standard Classification of Education (ISCED) and analysed as: primary/lower secondary, upper secondary and postsecondary. Parents’ occupations were grouped using International Standard Classification of Occupations (ISCO-08) major groups and then coded into 4 categories: No occupation or student, Skilled/ unskilled workers, Technicians/clerical/service occupations and Managers/professionals. We calculated risk ratios (RR) for stillbirth by each occupational group as well as the percentage population attributable risks using the most advantaged category as the reference (post-secondary education and professional/managerial occupations). Results Data on stillbirth rates by mothers’ education were available in 19 countries and by mothers’ and fathers’ occupations in 13 countries. In countries with these data, the median RR of stillbirth for women with primary and lower secondary education compared to women with postsecondary education was 1.9 (interquartile range (IQR): 1.5 to 2.4) and 1.4 (IQR: 1.2 to 1.6), respectively. For mothers’ occupations, the median RR comparing outcomes among manual workers with managers and professionals was 1.6 (IQR: 1.0–2.1) whereas for fathers’ occupations, the median RR was 1.4 (IQR: 1.2–1.8). When applied to the entire set of countries with data about mothers’ education, 1606 out of 6337 stillbirths (25 %) would not have occurred if stillbirth rates for all women were the same as for women with post-secondary education in their country. Conclusions Data on stillbirths and socioeconomic status from routine systems showed widespread and consistent socioeconomic inequalities in stillbirth rates in Europe. Further research is needed to better understand differences between countries in the magnitude of the socioeconomic gradient

Attitudes toward gambling among adolescents

It is well documented that attitudes toward gambling are a good predictor of problem gambling during adolescence. However, so far, little is known about what factors are associated with adolescents' gambling attitudes. This study used cross-sectional data (N = 2055, response rate 70.4%) from a representative sample of 17-year-olds in Norway to investigate the relationship between demographic, personality, motivational and social variables and gambling attitudes. Overall, adolescents' attitudes toward gambling were slightly negative. A multivariate analysis revealed that more favourable attitudes toward gambling were most strongly associated with family/peer approval of gambling. In addition, significant associations were found for gender (males more favourable); Sensation Seeking (positive association); Agreeableness (negative association); and family/peer gambling history (positive association for lifetime gambling, negative association for problematic gambling). Although a variety of individual-level and social factors are associated with more favourable attitudes toward gambling, it appears that family and peer approval of gambling are most important

Preclinical cardiac disease in women and men with primary aldosteronism

Purpose We tested the sex-specific associations between primary aldosteronism (PA), left ventricular (LV) hypertrophy and LV systolic myocardial function. Material and methods Conventional and speckle tracking echocardiography was performed in 109 patients with PA and 89 controls with essential hypertension (EH). LV hypertrophy was identified if LV mass index exceeded 47.0 g/m2.7 in women and 50.0 g/m2.7 in men. LV systolic myocardial function was assessed by global longitudinal strain (GLS) and midwall shortening. Results PA patients had higher prevalence of LV hypertrophy (52 vs. 21%, p < 0.001) than EH patients in both sexes, while GLS did not differ by sex or hypertension aetiology. In multivariable analyses, presence of LV hypertrophy was associated with PA and obesity in both sexes, while lower systolic myocardial function, whether measured by GLS or midwall shortening, was not associated with PA, but primarily with higher body mass index and LV mass index, respectively, in both sexes (all p < 0.05). Conclusion Having PA was associated with higher prevalence of LV hypertrophy both in women and men, compared to EH. PA was not associated with LV systolic myocardial function in either sex

Strain Construction and Process Development for Efficient Recombinant Production of Mannuronan C-5 Epimerases in Hansenula polymorpha

Alginates are linear polysaccharides produced by brown algae and some bacteria and are composed of β-D-mannuronic acid (M) and α-L-guluronic acid (G). Alginate has numerous present and potential future applications within industrial, medical and pharmaceutical areas and G rich alginates are traditionally most valuable and frequently used due to their gelling and viscosifying properties. Mannuronan C-5 epimerases are enzymes converting M to G at the polymer level during the biosynthesis of alginate. The Azotobacter vinelandii epimerases AlgE1-AlgE7 share a common structure, containing one or two catalytic A-modules (A), and one to seven regulatory R-modules (R). Despite the structural similarity of the epimerases, they create different M-G patterns in the alginate; AlgE4 (AR) creates strictly alternating MG structures whereas AlgE1 (ARRRAR) and AlgE6 (ARRR) create predominantly G-blocks. These enzymes are therefore promising tools for producing in vitro tailor-made alginates. Efficient in vitro epimerization of alginates requires availability of recombinantly produced alginate epimerases, and for this purpose the methylotrophic yeast Hansenula polymorpha is an attractive host organism. The present study investigates whether H. polymorpha is a suitable expression system for future large-scale production of AlgE1, AlgE4, and AlgE6. H. polymorpha expression strains were constructed using synthetic genes with reduced repetitive sequences as well as optimized codon usage. High cell density cultivations revealed that the largest epimerases AlgE1 (147 kDa) and AlgE6 (90 kDa) are subject to proteolytic degradation by proteases secreted by the yeast cells. However, degradation could be controlled to a large extent either by co-expression of chaperones or by adjusting cultivation conditions. The smaller AlgE4 (58 kDa) was stable under all tested conditions. The results obtained thus point toward a future potential for using H. polymorpha in industrial production of mannuronan C-5 epimerases for in vitro tailoring of alginates

Persistent cardiac organ damage in surgically and medically treated primary aldosteronism

Objective: We compared persistent cardiac organ damage in patients treated surgically or medically for primary aldosteronism. Methods: Eighty-four patients (age 57 ± 11 years, 27% women) with primary aldosteronism underwent echocardiography at time of diagnosis and after one year of treatment (49% adrenalectomy, 51% medical treatment). Persistent cardiac organ damage was defined as presence of left ventricle (LV) hypertrophy, low LV midwall shortening, global longitudinal strain and/or enlarged left atrium both at baseline and at follow-up. Results: At one year, a significant regression of LV hypertrophy was observed in surgically (44 vs. 22%, P= 0.039), but not in medically treated patients (60 vs. 51%, P = 0.206). The prevalence of enlarged left atrium was reduced in both groups (both P < 0.001), whereas systolic myocardial function remained unchanged. In multivariable logistic regression analysis, medical treatment [odds ratio (OR) 4.88 (95% confidence interval (CI) 1.26–18.88)] was a strong predictor of persistent LV hypertrophy independent of higher BMI [OR 1.20 (95% CI 1.04–1.38)] and presence of diabetes [OR 6.48 (95% CI 1.20–34.83), all P < 0.05]. Persistently low midwall shortening was associated with suppressed plasma renin after one year [OR 6.11 (95% CI 1.39–26.7)] and lower renal function [OR 0.96 (95% CI 0.94–0.99), both P < 0.05]. The strongest predictor of persistently low global longitudinal strain was higher HbA1c [OR 2.37 (95% CI 1.12–5.02), P = 0.024]. Conclusion: Persistent cardiac organ damage was more common in the medical treatment group and associated with incomplete aldosterone blockade, impaired renal function and presence of metabolic comorbidities.publishedVersio