Impact of body mass index on worsening of diastolic function and impairment of left atrial strain in the general female urban population: a subanalysis of the Berlin female risk evaluation echocardiography follow-up study

Background: The association of body mass index (BMI) with diastolic dysfunction (DD) is well described in the literature. However, there is conflicting evidence and long-term follow-up data regarding effects of BMI on preclinical DD and left atrial (LA) function are scarce, highlighting the importance of early detection tools, such as myocardial strain. Purpose: The aim of our study was to prospectively analyze the impact of clinical and demographic parameters, especially of BMI, on worsening of diastolic function and left atrial strain (LAS) in an urban population of women with a low prevalence of cardiovascular risk factors. Methods and Results: An extensive clinical and echocardiographic assessment comprising the analysis of phasic LAS using two-dimensional speckle-tracking echocardiography (2D STE) was performed in 258 participants of the Berlin Female Risk Evaluation (BEFRI) trial between October 2019 and December 2020 after a mean follow-up period of 6.8 years. We compared clinical and echocardiographic parameters stratifying women by BMI < or ≥25 kg/m2, and we analyzed the impact of demographic characteristics on the worsening of DD and LA mechanics in the longer-term follow-up using univariate and multivariate regression analyses. 248 women were suitable for echocardiographic analysis of LAS using 2D STE. After a mean follow-up time of 6.8 years, LA reservoir strain (LASr) and LA conduit strain (LAScd) were significantly reduced in participants with a BMI ≥25 kg/m2 compared with women with a BMI <25 kg/m2 at baseline (30 ± 8% vs. 38 ± 9%, p < 0.0001; −14 ± 7% vs. −22 ± 8%, p < 0.0001). 28% of the overweighted women presented a deterioration of diastolic function at the time of follow-up in contrast with only 7% of the group with a BMI <25 kg/m2 (p < 0.0001). BMI remained significantly associated with LAS reductions after adjustment for other risk factors in multivariate regression analyses. Conclusion: Overweight and obesity are related to impaired LAS and to a worsening of diastolic function after a long-term follow-up in a cohort of randomly selected women

Impact of body mass index on worsening of diastolic function and impairment of left atrial strain in the general female urban population: a subanalysis of the Berlin female risk evaluation echocardiography follow-up study

BackgroundThe association of body mass index (BMI) with diastolic dysfunction (DD) is well described in the literature. However, there is conflicting evidence and long-term follow-up data regarding effects of BMI on preclinical DD and left atrial (LA) function are scarce, highlighting the importance of early detection tools, such as myocardial strain.PurposeThe aim of our study was to prospectively analyze the impact of clinical and demographic parameters, especially of BMI, on worsening of diastolic function and left atrial strain (LAS) in an urban population of women with a low prevalence of cardiovascular risk factors.Methods and ResultsAn extensive clinical and echocardiographic assessment comprising the analysis of phasic LAS using two-dimensional speckle-tracking echocardiography (2D STE) was performed in 258 participants of the Berlin Female Risk Evaluation (BEFRI) trial between October 2019 and December 2020 after a mean follow-up period of 6.8 years. We compared clinical and echocardiographic parameters stratifying women by BMI &lt; or ≥25 kg/m2, and we analyzed the impact of demographic characteristics on the worsening of DD and LA mechanics in the longer-term follow-up using univariate and multivariate regression analyses. 248 women were suitable for echocardiographic analysis of LAS using 2D STE. After a mean follow-up time of 6.8 years, LA reservoir strain (LASr) and LA conduit strain (LAScd) were significantly reduced in participants with a BMI ≥25 kg/m2 compared with women with a BMI &lt;25 kg/m2 at baseline (30 ± 8% vs. 38 ± 9%, p &lt; 0.0001; −14 ± 7% vs. −22 ± 8%, p &lt; 0.0001). 28% of the overweighted women presented a deterioration of diastolic function at the time of follow-up in contrast with only 7% of the group with a BMI &lt;25 kg/m2 (p &lt; 0.0001). BMI remained significantly associated with LAS reductions after adjustment for other risk factors in multivariate regression analyses.ConclusionOverweight and obesity are related to impaired LAS and to a worsening of diastolic function after a long-term follow-up in a cohort of randomly selected women

Assessing the combined effects of xenobiotics, climate change and predators on aquatic organisms in multiple stressor experiments - a case study with pyrimethanil

The environmental impact of climate change is meanwhile not only discussed in the scientific community but also in the general public. However, little is known about the interaction between climate change and pollutants like pesticides. A combination of multiple stressors (e.g. temperature, pollutants, predators) may lead to severe alterations for organisms such as changes in time of reproduction, reproductive success and growth performance, mortality and geographic distribution. The questions if aquatic organisms tend to react more sensitive towards incidents under climate change conditions remains. Therefore, within the present thesis the aquatic ecotoxicological profile of the fungicide pyrimethanil, as an exemplarily anthropogenic used contaminant, was examined. A large test battery of ecotoxicological standard tests and supplement bioassays with non-model species was conducted to investigate if species-specific or life stage-specific differences occur or if temperature alteration may change the impact of the fungicide. Two of the most sensitive species (Chironomus riparius and Daphnia magna) were used to investigate the acute and chronic thermal dependence of pyrimethanil effects. The results clearly depict that the ecotoxicity of pyrimethanil at optimal thermal conditions did not depend on the trophic level, but was species-specific. With regard to EC10 values the acute pyrimethanil toxicity on C. riparius increased with higher temperature (6.78 mg L-1 at 14°C and 3.06 mg L-1 at 26°C). The chronic response of D. magna to the NOEC (no observed effect concentration) of the fungicide (0.5 mg L-1) was examined in an experiment which lasted for several generations under three simulated near-natural temperature regimes (‘cold year, today’ (11 to 22.7°C), ‘warm year, today’ (14 to 25.2°C) and ‘warm year, 2080’ (16.5 to 28.1°C)). A pyrimethanil-induced mortality increase was buffered by the strongly related increase of the general reproductive capacity, while population growth was stronger influenced by temperature than by the fungicide. At a further pyrimethanil concentration (LOEC – lowest observed effect concentration: 1 mg L-1), a second generation could not be established by D. magna under all thermal regimes. Besides daphnids, the midge C. riparius was used for a second multigeneration study. In a bifactorial test design it was tested if climate change conditions alter or affect the impact of a low fungicide concentration on life history and genetic diversity. The NOAEC/2 (half of the no observed adverse effect concentration derived from a standard toxicity test) was used as a low pyrimethanil concentration to which laboratory populations of the midges were chronically exposed under the mentioned temperature scenarios. During the 140-day-multigeneration study, survival, emergence, reproduction, population growth, and genetic diversity of C. riparius were analyzed. The results reveal that high temperatures and pyrimethanil act synergistically on life history parameters of C. riparius. In simulated present-day scenarios, a NOAEC/2 of pyrimethanil provoked only slight to moderate beneficial or adverse effects. In contrast, an exposure to a NOAEC/2 concentration of pyrimethanil at a thermal situation likely for a summer under the future expactations uncovered adverse effects on mortality and population growth rate. In addition, genetic diversity was considerably reduced by pyrimethanil in the ‘warm year, 2080’ scenario, but only slightly under current climatic conditions. The multigeneration studies under near-natural thermal conditions indicate that not only the impact of climate change, but also low concentrations of pesticides may pose a reasonable risk for aquatic invertebrates in the future. This clearly shows that thermal and multigenerational effects should be considered when appraising the ecotoxicity of pesticides and assessing their future risk for the environment. In addition to temperature further multiple abiotic and biotic stressors alterate pollutant effects. Moreover, to better discriminate and understand the intrinsic and environmental correlates of changing aquatic ecosystems, it was experimentally unraveled how the effects of a low-dose of pyrimethanil on daphnids becomes modified by different temperatures (15°C, 20°C, 25°C) and in the presence/ absence of predator kairomones of Chaoborus flavicans larvae. The usage of a fractional multifactorial test design provided the possibility to investigate the individual growth, reproduction and population growth rate of Daphnia pulex via different exposure routes to the fungicide pyrimethanil at an environmentally relevant concentration (0.05 mg L-1) - either directly (via the water phase), indirectly (via algae food), dually (via water and food) or for multiple generations (fungicide treated source population). The number of neonates increased with increasing temperatures. At a temperature of 25°C no significant differences between the individual treatment groups were observed although the growth was overall inhibited due to pyrimethanil. Besides, at 15 and 20°C it is obvious that daphnids which were fed with contaminated algae had the lowest reproduction and growth rate. The obtained results clearly demonstrate that multiple stress factors can modify the response of daphnids to pollutants. The exposure routes of the contaminant are of minor importance, while temperature and the presence of a predator are the dominant factors impacting the reproduction of D. pulex. It can be concluded that low concentrations of pyrimethanil may disturb the zooplankton community at suboptimal temperature conditions, but the effects will become masked if chaoborid larvae are present. Therefore it seems necessary to observe prospectively if the combination of several stress factors like pesticide exposure and suboptimal temperature may influence the life history and sensitivity of several aquatic invertebrates differently. Besides standard test organisms it is inevitable to conduct test with aquatic invertebrate which are not yet considered regularly in ecotoxicological experiments. For example molluscs represent one of the largest phyla of macroinvertebrates with more than 100.000 species, being ecologically and economically important. Therefore, within the present study embryo, juvenile, half- and full-life cycle toxicity tests with the snail Physella acuta were performed to investigate the impact of pollutants on various life stages. Different concentrations of pyrimethanil (0.06-0.5 or 1.0 mg L-1) assessed at three temperatures (15°C, 20°C, 25°C) revealed that pyrimethanil caused concentration-dependent effects independent of temperature. Interestingly, the ecotoxicity of pyrimethanil was higher at lower temperature for the embryo hatching and F1 reproduction, but its ecotoxicity for the growth of juveniles and the F0 reproduction increased with increasing temperature. More specifically, it could have been observed that especially during the reproduction test high mortality rates occurred at the highest concentration of 1 mg L-1 at all temperatures. Due to high mortality rates no snails were available for the F1 at the highest concentrations (0.5 and 1.0 mg L-1). Compared to the F0, overall more egg masses were produced in the F1, being all fertile and no mortality occurred. For the F1-generation the strongest pyrimethanil effects were detected at 15°C. A comparison of effect concentrations between both generations showed that the F1 is more sensitive than the F0. These results indicate that an exposure over more than one generation may give a better overview of the impact of xenobiotics. With the establishment of an embryo and reproduction test under different temperatures and various concentrations of pyrimethanil with P. acuta we could successfully show that molluscs can respond more sensitive than model organisms and that both, chemical and thermal stressor strongly influence the behaviour of the pulmonates. It can be concluded that the high susceptibility for the fungicide observed in gastropods clearly demonstrates the complexity of pesticide-temperature interactions and the challenge to draw conclusions for the ecotoxicological risk assessment of pesticides under the impact of global climate change

Normative reference data, determinants, and clinical implications of right atrial reservoir function in women assessed by 2D speckle-tracking echocardiography

Brand A, Bathe M, Hübscher A, et al. Normative reference data, determinants, and clinical implications of right atrial reservoir function in women assessed by 2D speckle-tracking echocardiography. Echocardiography. 2018;35(10):1542-1549

Vilkår for samværsnektelse etter Den europeiske menneskerettskonvensjonen. Har Den europeiske menneskerettsdomstolen endret kravene som stilles for samværsværsnektelse ved svak tilknytning mellom foreldre og barn?

En undersøkelse av hvilke krav EMD stiller for å nekte samvær i saker ved svak tilknytning mellom foreldre og barn. Det har i juridisk teori blitt hevdet at EMD stiller lavere krav for å nekte samvær mellom foreldre og barn dersom forholdet dem imellom er svakt. En gjennomgang av EMDs praksis viser at et svakt forhold skal tas med i vurderingen av om samværsnektelsen er nødvendig. Kravet er imidlertid ikke endret: EMD krever fortsatt at det må foreligge ekstraordinære omstendigheter for å nekte samvær

Age-related atrial fibrosis

Many age-related diseases are associated with, and may be promoted by, cardiac fibrosis. Transforming growth factor (TGF)-β, hypoxia-induced factor (HIF), and the matrix metalloproteinase (MMP) system have been implicated in fibrogenesis. Thus, we investigated whether age is related to these systems and to atrial fibrosis. Right atrial appendages (RAA) obtained during heart surgery (n = 115) were grouped according to patients’ age (<50 years, 51–60 years, 61–70 years, or >70 years). Echocardiographic ejection fractions (EF) and fibrosis using Sirius-red-stained histological sections were determined. TGF-β was determined by quantitative RT-PCR and hypoxia-related factors [HIF1α, the vascular endothelial growth factor (VEGF)-receptor, CD34 (a surrogate marker for microvessel density), the factor inhibiting HIF (FIH), and prolyl hydroxylase 3 (PHD 3)] were detected by immunostaining. MMP-2 and -9 activity were determined zymographically, and mRNA levels of their common tissue inhibitor TIMP-1 were determined by RT-PCR. Younger patients (<50 years) had significantly less fibrosis (10.1% ± 4.4% vs 16.6% ± 8.3%) than older individuals (>70 years). While HIF1α, FIH, the VEGF-receptor, and CD34 were significantly elevated in the young, TGF-β and PHD3 were suppressed in these patients. MMP-2 and -9 activity was found to be higher while TIMP-1 levels were lower in older patients. Statistical analysis proved age to be the only factor influencing fibrogenesis. With increasing age, RAAs develop significantly more fibrosis. An increase of fibrotic and decrease of hypoxic signalling and microvessel density, coupled with differential expression of MMPs and TIMP-1 favouring fibrosis may have helped promote atrial fibrogenesis