610 Medizin und Gesundheit
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Background:
From birth to young adulthood, health and development of young people are strongly linked to their living situation, including their family's socioeconomic position (SEP) and living environment. The impact of regional characteristics on development in early childhood beyond family SEP has been rarely investigated. This study aimed to identify regional predictors of global developmental delay at school entry taking family SEP into consideration.
Method:
We used representative, population-based data from mandatory school entry examinations of the German federal state of Brandenburg in 2018/2019 with n=22,801 preschool children. By applying binary multilevel models, we hierarchically analyzed the effect of regional deprivation defined by the German Index of Socioeconomic Deprivation (GISD) and rurality operationalized as inverted population density of the children's school district on global developmental delay (GDD) while adjusting for family SEP (low, medium and high)
Results:
Family SEP was significantly and strongly linked to GDD. Children with the highest family SEP showed a lower odds for GDD compared to a medium SEP (female: OR=4.26, male: OR=3.46) and low SEP (female: OR=16.58, male: OR=12.79). Furthermore, we discovered a smaller, but additional and independent effect of regional socioeconomic deprivation on GDD, with a higher odds for children from a more deprived school district (female: OR=1.35, male: OR=1.20). However, rurality did not show a significant link to GDD in preschool children beyond family SEP and regional deprivation.
Conclusion:
Family SEP and regional deprivation are risk factors for child development and of particular interest to promote health of children in early childhood and over the life course.
We recently demonstrated that the sympathetic nervous system can be voluntarily activated following a training program consisting of cold exposure, breathing exercises, and meditation. This resulted in profound attenuation of the systemic inflammatory response elicited by lipopolysaccharide (LPS) administration. Herein, we assessed whether this training program affects the plasma metabolome and if these changes are linked to the immunomodulatory effects observed. A total of 224 metabolites were identified in plasma obtained from 24 healthy male volunteers at six timepoints, of which 98 were significantly altered following LPS administration. Effects of the training program were most prominent shortly after initiation of the acquired breathing exercises but prior to LPS administration, and point towards increased activation of the Cori cycle. Elevated concentrations of lactate and pyruvate in trained individuals correlated with enhanced levels of anti-inflammatory interleukin (IL)-10. In vitro validation experiments revealed that co-incubation with lactate and pyruvate enhances IL-10 production and attenuates the release of pro-inflammatory IL-1 beta and IL-6 by LPS-stimulated leukocytes. Our results demonstrate that practicing the breathing exercises acquired during the training program results in increased activity of the Cori cycle. Furthermore, this work uncovers an important role of lactate and pyruvate in the anti-inflammatory phenotype observed in trained subjects.
We recently demonstrated that the sympathetic nervous system can be voluntarily activated following a training program consisting of cold exposure, breathing exercises, and meditation. This resulted in profound attenuation of the systemic inflammatory response elicited by lipopolysaccharide (LPS) administration. Herein, we assessed whether this training program affects the plasma metabolome and if these changes are linked to the immunomodulatory effects observed. A total of 224 metabolites were identified in plasma obtained from 24 healthy male volunteers at six timepoints, of which 98 were significantly altered following LPS administration. Effects of the training program were most prominent shortly after initiation of the acquired breathing exercises but prior to LPS administration, and point towards increased activation of the Cori cycle. Elevated concentrations of lactate and pyruvate in trained individuals correlated with enhanced levels of anti-inflammatory interleukin (IL)-10. In vitro validation experiments revealed that co-incubation with lactate and pyruvate enhances IL-10 production and attenuates the release of pro-inflammatory IL-1 beta and IL-6 by LPS-stimulated leukocytes. Our results demonstrate that practicing the breathing exercises acquired during the training program results in increased activity of the Cori cycle. Furthermore, this work uncovers an important role of lactate and pyruvate in the anti-inflammatory phenotype observed in trained subjects.
Food Neophilie
(2023)
Trotz der eindeutigen Vorteile einer ausgewogenen Ernährung halten sich viele Menschen weltweit nicht an entsprechende Ernährungsrichtlinien. Um angemessene Strategien zur Unterstützung einer gesundheitsfördernden Ernährung zu entwickeln, ist ein Verständnis der zugrunde liegenden Faktoren unerlässlich. Insbesondere die Gruppe der älteren Erwachsenen stellt dabei eine wichtige Zielgruppe für ernährungsbezogene Präventions- und Interventionsansätze dar. Einer der vielen Faktoren, die als Determinanten einer gesundheitsfördernden Ernährung diskutiert werden, ist die Food Neophilie, also die Bereitschaft, neue und unbekannte Lebensmittel auszuprobieren. Aktuelle Forschungsergebnisse legen nahe, dass die Food Neophilie positiv mit einer gesundheitsfördernden Ernährung in Verbindung steht, allerdings ist die bisherige Forschung in diesem Bereich äußerst begrenzt. Das Ziel der Dissertation war es, das Konstrukt der Food Neophilie sowie seine Beziehung zu gesundheitsförderndem Ernährungsverhalten im höheren Erwachsenenalter grundlegend zu erforschen, um das Potenzial der Food Neophilie für die Gesundheitsförderung älterer Erwachsener besser zu verstehen. Dabei wurde im Rahmen der ersten Publikation zunächst untersucht, wie sich das Konstrukt der Food Neophilie reliabel und valide erfassen lässt, um weiterführende Untersuchungen der Food Neophilie zu ermöglichen. Die psychometrische Validierung der deutschen Version der Variety Seeking Tendency Scale (VARSEEK) basierte auf zwei unabhängigen Stichproben mit insgesamt N = 1000 Teilnehmenden und bestätigte, dass es sich bei der Skala um ein reliables und valides Messinstrument zur Erfassung der Food Neophilie handelt. Darauf aufbauend wurde im Rahmen der zweiten Publikation die Beziehung der Food Neophilie und der Ernährungsqualität über die Zeit hinweg analysiert. Die prospektive Untersuchung von N = 960 Teilnehmenden des höheren Erwachsenenalters (M = 63.4 Jahre) anhand einer Cross-Lagged-Panel-Analyse ergab hohe zeitliche Stabilitäten der Food Neophilie und der Ernährungsqualität über einen Zeitraum von drei Jahren. Es zeigte sich zudem ein positiver querschnittlicher Zusammenhang zwischen der Food Neophilie und der Ernährungsqualität, jedoch wurde die Food Neophilie nicht als signifikante Determinante der Ernährungsqualität über die Zeit hinweg identifiziert. In der dritten Publikation wurden schließlich nicht nur die individuellen Auswirkungen der Food Neophilie auf die Ernährungsqualität betrachtet, sondern auch potenzielle dynamische Wechselwirkungen innerhalb von Partnerschaften einbezogen. Hierzu erfolgte mittels eines Actor-Partner-Interdependence-Modells eine Differenzierung potenzieller intra- und interpersoneller Einflüsse der Food Neophilie auf die Ernährungsqualität. Im Rahmen der dyadischen Analyse zeigte sich bei N = 390 heterosexuellen Paaren im höheren Erwachsenenalter (M = 64.0 Jahre) ein Dominanzmuster: Während die Food Neophilie der Frauen positiv mit ihrer eigenen Ernährungsqualität und der ihrer Partner zusammenhing, war die Food Neophilie der Männer nicht mit der Ernährungsqualität des Paares assoziiert. Insgesamt leistet die vorliegende Dissertation einen wertvollen Beitrag zum umfassenden Verständnis der Food Neophilie sowie ihrer Rolle im Kontext der Ernährungsgesundheit älterer Erwachsener. Trotz fehlender Vorhersagekraft über die Zeit hinweg deutet der positive Zusammenhang zwischen Food Neophilie und Ernährungsqualität darauf hin, dass die Fokussierung auf eine positive und neugierige Einstellung gegenüber Lebensmitteln eine innovative Perspektive für Präventions- und Interventionsansätze zur Unterstützung einer gesundheitsfördernden Ernährung älterer Erwachsener bieten könnte.
Temperature-related excess mortality in German cities at 2 °C and higher degrees of global warming
(2020)
Background: Investigating future changes in temperature-related mortality as a function of global mean temperature (GMT) rise allows for the evaluation of policy-relevant climate change targets. So far, only few studies have taken this approach, and, in particular, no such assessments exist for Germany, the most populated country of Europe.
Methods: We assess temperature-related mortality in 12 major German cities based on daily time-series of all-cause mortality and daily mean temperatures in the period 1993-2015, using distributed-lag non-linear models in a two-stage design. Resulting risk functions are applied to estimate excess mortality in terms of GMT rise relative to pre-industrial levels, assuming no change in demographics or population vulnerability.
Results: In the observational period, cold contributes stronger to temperature-related mortality than heat, with overall attributable fractions of 5.49% (95%CI: 3.82-7.19) and 0.81% (95%CI: 0.72-0.89), respectively. Future projections indicate that this pattern could be reversed under progressing global warming, with heat-related mortality starting to exceed cold-related mortality at 3 degrees C or higher GMT rise. Across cities, projected net increases in total temperature-related mortality were 0.45% (95%CI: -0.02-1.06) at 3 degrees C, 1.53% (95%CI: 0.96-2.06) at 4 degrees C, and 2.88% (95%CI: 1.60-4.10) at 5 degrees C, compared to today's warming level of 1 degrees C. By contrast, no significant difference was found between projected total temperature-related mortality at 2 degrees C versus 1 degrees C of GMT rise.
Conclusions: Our results can inform current adaptation policies aimed at buffering the health risks from increased heat exposure under climate change. They also allow for the evaluation of global mitigation efforts in terms of local health benefits in some of Germany's most populated cities.
Temperature-related excess mortality in German cities at 2 °C and higher degrees of global warming
(2020)
Background: Investigating future changes in temperature-related mortality as a function of global mean temperature (GMT) rise allows for the evaluation of policy-relevant climate change targets. So far, only few studies have taken this approach, and, in particular, no such assessments exist for Germany, the most populated country of Europe.
Methods: We assess temperature-related mortality in 12 major German cities based on daily time-series of all-cause mortality and daily mean temperatures in the period 1993-2015, using distributed-lag non-linear models in a two-stage design. Resulting risk functions are applied to estimate excess mortality in terms of GMT rise relative to pre-industrial levels, assuming no change in demographics or population vulnerability.
Results: In the observational period, cold contributes stronger to temperature-related mortality than heat, with overall attributable fractions of 5.49% (95%CI: 3.82-7.19) and 0.81% (95%CI: 0.72-0.89), respectively. Future projections indicate that this pattern could be reversed under progressing global warming, with heat-related mortality starting to exceed cold-related mortality at 3 degrees C or higher GMT rise. Across cities, projected net increases in total temperature-related mortality were 0.45% (95%CI: -0.02-1.06) at 3 degrees C, 1.53% (95%CI: 0.96-2.06) at 4 degrees C, and 2.88% (95%CI: 1.60-4.10) at 5 degrees C, compared to today's warming level of 1 degrees C. By contrast, no significant difference was found between projected total temperature-related mortality at 2 degrees C versus 1 degrees C of GMT rise.
Conclusions: Our results can inform current adaptation policies aimed at buffering the health risks from increased heat exposure under climate change. They also allow for the evaluation of global mitigation efforts in terms of local health benefits in some of Germany's most populated cities.
Background
Secondary endosymbionts of aphids provide benefits to their hosts, but also impose costs such as reduced lifespan and reproductive output. The aphid Aphis fabae is host to different strains of the secondary endosymbiont Hamiltonella defensa, which encode different putative toxins. These strains have very different phenotypes: They reach different densities in the host, and the costs and benefits (protection against parasitoid wasps) they confer to the host vary strongly.
Results
We used RNA-Seq to generate hypotheses on why four of these strains inflict such different costs to A. fabae. We found different H. defensa strains to cause strain-specific changes in aphid gene expression, but little effect of H. defensa on gene expression of the primary endosymbiont, Buchnera aphidicola. The highly costly and over-replicating H. defensa strain H85 was associated with strongly reduced aphid expression of hemocytin, a marker of hemocytes in Drosophila. The closely related strain H15 was associated with downregulation of ubiquitin-related modifier 1, which is related to nutrient-sensing and oxidative stress in other organisms. Strain H402 was associated with strong differential regulation of a set of hypothetical proteins, the majority of which were only differentially regulated in presence of H402.
Conclusions
Overall, our results suggest that costs of different strains of H. defensa are likely caused by different mechanisms, and that these costs are imposed by interacting with the host rather than the host's obligatory endosymbiont B. aphidicola.
A sufficient quantitative understanding of aluminium (Al) toxicokinetics (TK) in man is still lacking, although highly desirable for risk assessment of Al exposure. Baseline exposure and the risk of contamination severely limit the feasibility of TK studies administering the naturally occurring isotope Al-27, both in animals and man. These limitations are absent in studies with Al-26 as a tracer, but tissue data are limited to animal studies. A TK model capable of inter-species translation to make valid predictions of Al levels in humans-especially in toxicological relevant tissues like bone and brain-is urgently needed. Here, we present: (i) a curated dataset which comprises all eligible studies with single doses of Al-26 tracer administered as citrate or chloride salts orally and/or intravenously to rats and humans, including ultra-long-term kinetic profiles for plasma, blood, liver, spleen, muscle, bone, brain, kidney, and urine up to 150 weeks; and (ii) the development of a physiology-based (PB) model for Al TK after intravenous and oral administration of aqueous Al citrate and Al chloride solutions in rats and humans. Based on the comprehensive curated Al-26 dataset, we estimated substance-dependent parameters within a non-linear mixed-effect modelling context. The model fitted the heterogeneous Al-26 data very well and was successfully validated against datasets in rats and humans. The presented PBTK model for Al, based on the most extensive and diverse dataset of Al exposure to date, constitutes a major advancement in the field, thereby paving the way towards a more quantitative risk assessment in humans.
External temperature change has been shown to modify epigenetic patterns, such as DNA methylation, which regulates gene expression. DNA methylation is heritable, and as such provides a mechanism to convey environmental information to subsequent generations. Studies on epigenetic response to temperature increase are still scarce in wild mammals, even more so studies that compare tissue-specific epigenetic responses. Here, we aim to address differential epigenetic responses on a gene and gene pathway level in two organs, liver and testis. We chose these organs, because the liver is the main metabolic and thermoregulation organ, and epigenetic modifications in testis are potentially transmitted to the F2 generation. We focused on the transmission of DNA methylation changes to naive male offspring after paternal exposure to an ambient temperature increase of 10 degrees C, and investigated differential methylated regions of sons sired before and after the paternal exposure using Reduced Representation Bisulfite Sequencing. We detected both a highly tissue-specific epigenetic response, reflected in genes involved in organ-specific metabolic pathways, and a more general regulation of single genes epigenetically modified in both organs. We conclude that genomes are context-specifically differentially epigenetically regulated in response to temperature increase. These findings emphasize the epigenetic relevance in cell differentiation, which is essential for the specific function(s) of complex organs, and is represented in a diverse molecular regulation of genes and gene pathways. The results also emphasize the paternal contribution to adaptive processes.