PBTK model-based analysis of CYP3A4 induction and the toxicokinetics of the pyrrolizidine alkaloid retrorsine in man.

Cytochrome P450 (CYP)3A4 induction by drugs and pesticides plays a critical role in the enhancement of pyrrolizidine alkaloid (PA) toxicity as it leads to increased formation of hepatotoxic dehydro-PA metabolites. Addressing the need for a quantitative analysis of this interaction, we developed a physiologically-based toxicokinetic (PBTK) model. Specifically, the model describes the impact of the well-characterized CYP3A4 inducer rifampicin on the kinetics of retrorsine, which is a prototypic PA and contaminant in herbal teas. Based on consumption data, the kinetics after daily intake of retrorsine were simulated with concomitant rifampicin treatment. Strongest impact on retrorsine kinetics (plasma AUC 24 and C max reduced to 67% and 74% compared to the rifampicin-free reference) was predicted directly after withdrawal of rifampicin. At this time point, the competitive inhibitory effect of rifampicin stopped, while CYP3A4 induction was still near its maximum. Due to the impacted metabolism kinetics, the cumulative formation of intestinal retrorsine CYP3A4 metabolites increased to 254% (from 10 to 25 nmol), while the cumulative formation of hepatic CYP3A4 metabolites was not affected (57 nmol). Return to baseline PA toxicokinetics was predicted 14 days after stop of a 14-day rifampicin treatment. In conclusion, the PBTK model showed to be a promising tool to assess the dynamic interplay of enzyme induction and toxification pathways.

Meta-Analysis of Integrated Proteomic and Transcriptomic Data Discerns Structure-Activity Relationship of Carbon Materials with Different Morphologies.

The Fiber Pathogenicity Paradigm (FPP) establishes connections between fiber structure, durability, and disease-causing potential observed in materials like asbestos and synthetic fibers. While emerging nanofibers are anticipated to exhibit pathogenic traits according to the FPP, their nanoscale diameter limits rigidity, leading to tangling and loss of fiber characteristics. The absence of validated rigidity measurement methods complicates nanofiber toxicity assessment. By comprehensively analyzing 89 transcriptomics and 37 proteomics studies, this study aims to enhance carbon material toxicity understanding and proposes an alternative strategy to assess morphology-driven toxicity. Carbon materials are categorized as non-fibrous, high aspect ratio with shorter lengths, tangled, and rigid fibers. Mitsui-7 serves as a benchmark for pathogenic fibers. The meta-analysis reveals distinct cellular changes for each category, effectively distinguishing rigid fibers from other carbon materials. Subsequently, a robust random forest model is developed to predict morphology, unveiling the pathogenicity of previously deemed non-pathogenic NM-400 due to its secondary structures. This study fills a crucial gap in nanosafety by linking toxicological effects to material morphology, in particular regarding fibers. It demonstrates the significant impact of morphology on toxicological behavior and the necessity of integrating morphological considerations into regulatory frameworks.

PBTK modeling of the pyrrolizidine alkaloid retrorsine to predict liver toxicity in mouse and rat.

Retrorsine is a hepatotoxic pyrrolizidine alkaloid (PA) found in herbal supplements and medicines, food and livestock feed. Dose-response studies enabling the derivation of a point of departure including a benchmark dose for risk assessment of retrorsine in humans and animals are not available. Addressing this need, a physiologically based toxicokinetic (PBTK) model of retrorsine was developed for mouse and rat. Comprehensive characterization of retrorsine toxicokinetics revealed: both the fraction absorbed from the intestine (78%) and the fraction unbound in plasma (60%) are high, hepatic membrane permeation is dominated by active uptake and not by passive diffusion, liver metabolic clearance is 4-fold higher in rat compared to mouse and renal excretion contributes to 20% of the total clearance. The PBTK model was calibrated with kinetic data from available mouse and rat studies using maximum likelihood estimation. PBTK model evaluation showed convincing goodness-of-fit for hepatic retrorsine and retrorsine-derived DNA adducts. Furthermore, the developed model allowed to translate in vitro liver toxicity data of retrorsine to in vivo dose-response data. Resulting benchmark dose confidence intervals (mg/kg bodyweight) are 24.1-88.5 in mice and 79.9-104 in rats for acute liver toxicity after oral retrorsine intake. As the PBTK model was built to enable extrapolation to different species and other PA congeners, this integrative framework constitutes a flexible tool to address gaps in the risk assessment of PA.

Proportionality principle revisited - relationship between application rates and pesticide residue concentrations in food commodities.

BACKGROUND: The proportionality principle has been broadly used for over 10 years in regulatory assessments of pesticide residues. It allows extrapolation of supervised field trial data conducted at lower or higher application rates compared to the use pattern under evaluation by adjustment of measured concentrations, assuming direct proportionality between the rates applied and the resulting residues. This work revisits the principle idea by using supervised residue trials sets conducted under identical conditions but with deviating application rates. Four different statistical methods were used to investigate the relationship between application rates and residue concentrations and to draw conclusions on the statistical significance of the direct proportionality assumed. RESULTS: Based on over 5000 individual trial results, the assumption of direct proportionality was not confirmed to be statistically significant (P > 0.05) using three models: direct comparison of application rates and residue concentrations ratios and two linear log-log regression models correlating application rate and residue concentration or only residue concentrations per se. In addition, a fourth model analysed deviations between expected concentrations following direct proportional adjustment and measured residue values from corresponding field trials. In 56% of all cases, the deviation was larger than ±25%, which represents the tolerance usually accepted for the selection of supervised field trials in regulatory assessments. CONCLUSION: Overall, the assumption of direct proportionality between application rates and resulting residue concentrations of pesticides was not statistically significant. Although the proportionality approach is highly pragmatic in regulatory practice, its use should be considered carefully on a case-by-case basis. © 2023 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Phylogeny and spatiotemporal dynamics of hepatitis E virus infections in wild boar and deer from six areas of Germany during 2013-2017.

The hepatitis E virus (HEV) can cause acute and chronic hepatitis in humans. Infections with the zoonotic HEV genotype 3, which can be transmitted from infected wild boar and deer to humans, are increasingly detected in Europe. To investigate the spatiotemporal HEV infection dynamics in wild animal populations, a study involving 3572 samples of wild boar and three deer species from six different geographic areas in Germany over a 4-year period was conducted. The HEV-specific antibody detection rates increased between 2013-2014 and 2016-2017 in wild boar from 9.5% to 22.8%, and decreased in deer from 1.1% to 0.2%. At the same time, HEV-RNA detection rates increased in wild boar from 2.8% to 13.3% and in deer from 0.7% to 4.2%. Marked differences were recorded between the investigated areas, with constantly high detection rates in one area and new HEV introductions followed by increasing detection rates in others. Molecular typing identified HEV subtypes 3c, 3f, 3i and a putative new subtype related to Italian wild boar strains. In areas, where sufficient numbers of positive samples were available for further analysis, a specific subtype dominated over the whole observation period. Phylogenetic analysis confirmed the close relationship between strains from the same area and identified closely related human strains from Germany. The results suggest that the HEV infection dynamics in wild animals is dependent on the particular geographical area where area-specific dominant strains circulate over a long period. The virus can spread from wild boar, which represent the main wild animal reservoir, to deer, and generally from wild animals to humans.

Influence of motivational placebo-related factors on the effects of exercise treatment in depressive adolescents.

Recent meta-analyses reveal a moderate effect of physical activity (PA) in the treatment of adolescent depression. However, not only the underlying neurobiological mechanisms, also the influences of placebo-related motivational factors (beliefs and expectancies in sporting, enjoyment and prior sports experiences), are still unclear. Based on the data of our prior study "Mood Vibes", we hypothesized that placebo-inherent factors like positive prior sports experiences and motivational factors, (positive beliefs, expectancies, and enjoyment related to PA), would increase the effects of an add-on exercise-therapy in juvenile depression. From 64 included depressed adolescents, 41 underwent an intensive add-on PA-therapy. Motivational factors were assessed using sport-specific scales. The changes in depression scores under treatment were rated by self-rating scale (German "Childhood Depression Inventory", (DIKJ)). A mixed model for repeated measures (MMRM) was used to analyze the effects of the different motivational variates on DIKJ. While prior sports experiences had no impact, motivational factors showed a significant effect on PA-induced changes in DIKJ scores (p = 0.002). The demotivated participants improved less, whereas it was sufficient to be neutral towards sporting to benefit significantly more. Motivational placebo-related factors (beliefs, expectancies and enjoyment regarding PA) affected the outcomes of an exercise treatment in depressed adolescents. Yet, a neutral mindset was sufficient to profit more from PA. Prior sporting in the sense of positive conditioning and as a protective factor did not play a role. Knowledge about these influences could in a second step help to develop tailored therapies.

Analysis of German BSE Surveillance Data: Estimation of the Prevalence of Confirmed Cases versus the Number of Infected, but Non-Detected, Cattle to Assess Confidence in Freedom from Infection.

Quantitative risk assessments for Bovine spongiform encephalopathy (BSE) necessitate estimates for key parameters such as the prevalence of infection, the probability of absence of infection in defined birth cohorts, and the numbers of BSE-infected, but non-detected cattle entering the food chain. We estimated three key parameters with adjustment for misclassification using the German BSE surveillance data using a Gompertz model for latent (i.e., unobserved) age-dependent detection probabilities and a Poisson response model for the number of BSE cases for birth cohorts 1999 to 2015. The models were combined in a Bayesian framework. We estimated the median true BSE prevalence between 3.74 and 0.216 cases per 100,000 animals for the birth cohorts 1990 to 2001 and observed a peak for the 1996 birth cohort with a point estimate of 16.41 cases per 100,000 cattle. For birth cohorts ranging from 2002 to 2013, the estimated median prevalence was below one case per 100,000 heads. The calculated confidence in freedom from disease (design prevalence 1 in 100,000) was above 99.5% for the birth cohorts 2002 to 2006. In conclusion, BSE surveillance in the healthy slaughtered cattle chain was extremely sensitive at the time, when BSE repeatedly occurred in Germany (2000-2009), because the entry of BSE-infected cattle into the food chain could virtually be prevented by the extensive surveillance program during these years and until 2015 (estimated non-detected cases/100.000 [95% credible interval] in 2000, 2009, and 2015 are 0.64 [0.5,0.8], 0.05 [0.01,0.14], and 0.19 [0.05,0.61], respectively).

Community structure of domesticated pigs in livestock facilities.

The social structure of animal groups is considered to have an impact on their health and welfare. This could also be true for animals under commercial conditions, but research in this area has been limited. Pigs for example are known to be very social animals, but information about their grouping behavior is mostly derived from wild boars and a limited number of studies in seminatural and commercial conditions. Specifically under commercial conditions it is still unclear to what extent pig herds organize themselves in subgroups and how such group patterns emerge. To answer these questions, we tracked the positions of about 200 sows inside a barn during ongoing production over a period of five weeks and used these data to construct and analyze the animal contact networks. Our analysis showed a very high contact density and only little variation in the number of other animals that a specific animal is in contact with. Nevertheless, in each week we consistently detected three subgroups inside the barn, which also showed a clear spatial separation. Our results show that even in the high density environment of a commercial pig farm, the behavior of pigs to form differentiated groups is consistent with their behavior under seminatural conditions. Furthermore, our findings also imply that the barn layout could play an important role in the formation of the grouping pattern. These insights could be used to monitor and understand the spread of infectious diseases inside the barn better. In addition, our insights could potentially be used to improve the welfare of pigs.

Individual Physical Activity Behaviour and Group Composition as Determinants of the Effectiveness of a Childhood Obesity Intervention Program.

INTRODUCTION: Up to now, there is limited clarity on factors that determine the effectiveness of childhood obesity interventions. OBJECTIVE: This study intends to uncover individual- and program-level predictors of BMI-SDS and fitness to achieve significant, sustainable health improvements. METHODS: Data of 249 children with obesity or overweight who participated in an outpatient multidisciplinary program were analysed and compared to 54 waitlist controls. Linear regression models were used to examine associations between individual- and group-level variables and BMI-SDS and fitness. RESULTS: Among intervention children, BMI-SDS decreased by 0.19 units and physical fitness increased by 11.5%, versus a BMI-SDS decrease of 0.07 and a 1.8% decrease in fitness in the control group. Participants who reported being physically active before the program start achieved greater improvements in BMI-SDS (ß = -0.177, p < 0.05) and physical fitness (ß = 0.174, p < 0.05) than inactive peers. BMI-SDS decreased significantly more for members of gender-heterogeneous groups (ß = 0.194, p < 0.05) with a narrow age range (ß = 0.152, p < 0.05). CONCLUSIONS: The program under review is effective in counteracting juvenile obesity. The results give reason to believe that forming mixed-gender groups with a small age range and providing increased support for reportedly inactive children may improve program effectiveness.

[Evaluation of the Language-related Domain of the Pediatric Developmental Screening Instrument for Preschool Health Examinations (SOPESS): Results from the Prospective Child Health Survey ikidS]. / Evaluation der Sprachaufgaben des sozialpädiatrischen Entwicklungsscreenings für Schuleingangsuntersuchungen (SOPESS): Ergebnisse der prospektiven Kindergesundheitsstudie ikidS.

PURPOSE OF THE STUDY: Developmental delays at school enrollment can affect early educational achievement. Thus, diagnosis and treatment prior to school entry are important. In Germany, SOPESS - a pediatric developmental screening instrument for preschool health examinations (PHE) - was introduced in several federal states. We investigated the relationships between the results of the language-related domain of the SOPESS and later academic language competencies at the end of first grade. PROCEDURES: Data of the population-based cohort study ikidS (Rhineland Palatinate; Germany) and the PHE provided by public health authorities were linked at individual level. The relationship between the SOPESS-language risk score (range: 0 to 6, higher values indicate more developmental delay) and class teacher-based ratings of academic language competencies (range: -4 to+4, higher values indicate better competencies) was investigated with linear regression models and adjusted for several socio-economic and medical language predictors (e. g. age at school entry, gender, parental education, migration background, hearing disorder). The additional benefits of the SOPESS-language risk score was analyzed using analysis of variance. RESULTS: In total, 1357 children (48% girls, age at PHE 4.9-7.2 years) were included. A clear negative relationship between the SOPESS-language risk score and competencies in spoken and written language was found. Mean academic language competencies decreased with increasing SOPESS-language risk level from 0.8 (SD=1.7) at a risk score of 0 to-3.2 (SD=0.9) at a risk score of 6. The relationship persisted after adjusting for other language predictors. Analysis of variance showed significant benefits of the SOPESS-language risk score, even when further language predictors were considered. CONCLUSIONS: There was a clear relationship between results of the SOPESS-language screening and later academic language competencies. Hence, the language-related domain of the SOPESS may be useful for further recommendations of tailored special educational and medical support services, especially if additional socio-economic and medical factors are considered.

Maternal exercise conveys protection against NAFLD in the offspring via hepatic metabolic programming.

Maternal exercise (ME) during pregnancy has been shown to improve metabolic health in offspring and confers protection against the development of non-alcoholic fatty liver disease (NAFLD). However, its underlying mechanism are still poorly understood, and it remains unclear whether protective effects on hepatic metabolism are already seen in the offspring early life. This study aimed at determining the effects of ME during pregnancy on offspring body composition and development of NAFLD while focusing on proteomic-based analysis of the hepatic energy metabolism during developmental organ programming in early life. Under an obesogenic high-fat diet (HFD), male offspring of exercised C57BL/6J-mouse dams were protected from body weight gain and NAFLD in adulthood (postnatal day (P) 112). This was associated with a significant activation of hepatic AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor alpha (PPARα) and PPAR coactivator-1 alpha (PGC1α) signaling with reduced hepatic lipogenesis and increased hepatic ß-oxidation at organ programming peak in early life (P21). Concomitant proteomic analysis revealed a characteristic hepatic expression pattern in offspring as a result of ME with the most prominent impact on Cholesterol 7 alpha-hydroxylase (CYP7A1). Thus, ME may offer protection against offspring HFD-induced NAFLD by shaping hepatic proteomics signature and metabolism in early life. The results highlight the potential of exercise during pregnancy for preventing the early origins of NAFLD.

Saponin Micelles Lead to High Mucosal Permeation and In Vivo Efficacy of Solubilized Budesonide.

Due to fast nasal mucociliary clearance, only the dissolved drug content can effectively permeate the mucosa and be pharmaceutically active after intranasal application of suspensions. Therefore, the aim of this study was to increase the budesonide concentration in solution of a nasal spray formulation. Budesonide, a highly water-insoluble corticosteroid, was successfully solubilized using a micellar formulation comprising escin, propylene glycol and dexpanthenol in an aqueous buffered environment ("Budesolv"). A formulation based on this micellar system was well-tolerated in the nasal cavity as shown in a good laboratory practice (GLP) local tolerance study in rabbits. Ex vivo permeation studies into porcine nasal mucosa revealed a faster and more efficient absorption. Budesolv with 300 µg/mL solubilized budesonide resulted in a budesonide concentration of 42 µg/g tissue after only 15 min incubation. In comparison, incubation with the marketed product Rhinocort® aqua 64 (1.28 mg/mL budesonide as suspension) led to 15 µg/g tissue. The in vivo tumor-necrosis-factor (TNF)-α secretion in an acute lung inflammation mouse model was significantly reduced (p < 0.001) following a prophylactic treatment with Budesolv compared to Rhinocort® aqua 64. Successful treatment 15 min after the challenge was only possible with Budesolv (40% reduction of TNF-α, p = 0.0012) suggesting a faster onset of action. The data reveal that solubilization based on saponin micelles presents an opportunity for the development of products containing hardly soluble substances that result in a faster onset and a better topical treatment effect.

Can School-Based Physical Activity Projects Such as Skipping Hearts Have a Long-Term Impact on Health and Health Behavior?

Low physical activity, limited motor skills, and an increased number of overweight or obese children are major public health problems. Numerous school-based programs try to improve physical activity and health behavior in children but investigations on sustainable effects of these programs are rare. Therefore, we examined the long-term effects of the Skipping Hearts health promotion project. 486 children (57.7% female, 9.0 ± 0.6 years at baseline) participated in this non-randomized controlled longitudinal trial within a follow-up period of 3.5 years. Of these, 286 subjects received a one-time 90-min workshop in rope skipping (Basic-Workshop) and 140 additionally received 10 lessons in rope skipping (Champion-Program), 78 students served as controls. Anthropometrics, blood pressure, motor skills, screen-based media use, self-assessment of physical fitness, and physical activity were collected at both measurement points; endurance capacity and health-related quality of life only at follow-up. Standard deviation scores of body-mass-index (η2 = 0.005) and systolic blood pressure (η2 = 0.006) decreased, while diastolic blood pressure (η2 = 0.004), motor performance (η2 < 0.001), physical fitness, subjective physical activity (η2 = 0.008), and screen-based media use (η2 = 0.001) increased without significant difference in development between groups (all p > 0.05). At follow-up, groups did not differ in endurance capacity (η2 = 0.010) and health-related quality of life (η2 < 0.001). Skipping Hearts does not affect the long-term improvement of health status, motor performance, or health behavior. To improve the effects, the project should be implemented as a daily routine in schools to force the transfer of health behavior-related knowledge. Nevertheless, the project offers a physical activity that can be performed in children's everyday life without high costs.

Comparison of Bayesian and frequentist methods for prevalence estimation under misclassification.

BACKGROUND: Various methods exist for statistical inference about a prevalence that consider misclassifications due to an imperfect diagnostic test. However, traditional methods are known to suffer from truncation of the prevalence estimate and the confidence intervals constructed around the point estimate, as well as from under-performance of the confidence intervals' coverage. METHODS: In this study, we used simulated data sets to validate a Bayesian prevalence estimation method and compare its performance to frequentist methods, i.e. the Rogan-Gladen estimate for prevalence, RGE, in combination with several methods of confidence interval construction. Our performance measures are (i) error distribution of the point estimate against the simulated true prevalence and (ii) coverage and length of the confidence interval, or credible interval in the case of the Bayesian method. RESULTS: Across all data sets, the Bayesian point estimate and the RGE produced similar error distributions with slight advantages of the former over the latter. In addition, the Bayesian estimate did not suffer from the RGE's truncation problem at zero or unity. With respect to coverage performance of the confidence and credible intervals, all of the traditional frequentist methods exhibited strong under-coverage, whereas the Bayesian credible interval as well as a newly developed frequentist method by Lang and Reiczigel performed as desired, with the Bayesian method having a very slight advantage in terms of interval length. CONCLUSION: The Bayesian prevalence estimation method should be prefered over traditional frequentist methods. An acceptable alternative is to combine the Rogan-Gladen point estimate with the Lang-Reiczigel confidence interval.

Barriers and facilitating factors in the prevention of diabetes type 2 and gestational diabetes in vulnerable groups: A scoping review.

AIMS: Type 2 diabetes mellitus (T2DM) and gestational diabetes (GDM) are globally on the rise, accompanied by comorbidities and associated health costs. Increased physical activity, healthy nutrition, and weight loss have shown the potential to prevent T2DM/GDM. Despite this, reaching vulnerable groups remains a key challenge. The aim of this scoping review was to identify barriers and facilitating factors in the prevention of T2DM/GDM in vulnerable groups. METHODS: We conducted a systematic literature search in May 2018, updated in September 2019, in several databases (e.g. PubMed, Embase) to identify barriers and facilitating factors in the prevention of T2DM/GDM in vulnerable groups. Two reviewers independently screened the results. Extracted data was charted, categorized, and summarized. RESULTS: We included 125 articles. Ninety-eight studies were extracted, and eight categories of barriers and facilitating factors were formed. The most common categories of barriers were limited knowledge, family/friends, and economic factors, and the most common categories of facilitating factors were family/friends, social support, and knowledge. CONCLUSION: This scoping review identified various barriers and facilitating factors in vulnerable groups. Preventive interventions should consider these barriers and facilitating factors in developing preventive interventions or in adapting existing ones.

The feasibility and impact of instrument-assisted manual therapy (IAMT) for the lower back on the structural and functional properties of the lumbar area in female soccer players: a randomised, placebo-controlled pilot study design.

BACKGROUND: Myofascial (self-)treatments, such as foam rollers to therapeutic instruments in manual therapy, are utilized increasingly in prevention and therapy in healthy people, athletes, and patients suffering from chronic back pain. However, there is limited knowledge about the effectiveness of treatment and the underlying mechanisms of myofascial therapies, especially for instrument-assisted manual therapy (IAMT). Therefore, this pilot study will investigate the feasibility and impact of IAMT for the lumbar area compared with heat application and placebo treatment as a basis for calculating the sample size for further full studies. The primary outcomes will be a critical analysis of the feasibility of the measurement protocol in terms of time economy and expressiveness and of the short- and long-term effects on shear motion of the single tissue layers of the lower back obtained through ultrasound imaging. Secondary outcomes will include thickness and compressibility of the lumbar structures and flexibility of the dorsal structures, indentometry, and superficial skin temperature. METHODS: A minimum of 60 healthy, competitive 15-35-year-old female soccer players will be recruited and randomised into three groups. Short-term effects of IAMT on thoracolumbar structures will be compared with heat application and pressure-less placebo treatment. Long-term effects in the IAMT group will be tested after nine further interventions over a 5-week period (2×/week) and compared with the placebo group, which will not receive further treatments but will serve as a control. Intermediate and final testing of both groups will occur in weeks three and five. DISCUSSION: This pilot study will assess the feasibility and the impact of IAMT for the lower back particularly by examining the structural and functional properties of myofascial tissue using diagnostic ultrasound. These outcomes could evaluate the feasibility of the measurements used, shall build a basis for sample size calculation of further full studies, and might generate a greater understanding of myofascial therapies, especially IAMT, for the lower back and its benefits. If this approach proves to be practicable, next steps will be further full studies with soccer players, other sports, and patients with low back pain. TRIAL REGISTRATION: German Clinical Trials Register (DRKS00012252) 20.06.2018; retrospectively registered.

Metabolic Health-The Role of Adipo-Myokines.

Obesity is now a worldwide epidemic. In recent years, different phenotypes of obesity, ranging from metabolically healthy normal weight to metabolically unhealthy obese, were described. Although there is no standardized definition for these phenotypes or for metabolic health, the influence of lifestyle and early-life factors is undisputed. In this context, the ratio of muscle-to-fat tissue seems to play a crucial role. Both adipose tissue and skeletal muscle are highly heterogeneous endocrine organs secreting several hormones, with myokines and adipokines being involved in local autocrine/paracrine interactions and crosstalk with other tissues. Some of these endocrine factors are secreted by both tissues and are, therefore, termed adipo-myokines. High (cardiorespiratory) fitness as a surrogate parameter for an active lifestyle is epidemiologically linked to "better" metabolic health, even in the obese; this may be partly due to the role of adipo-myokines and the crosstalk between adipose and muscle tissue. Therefore, it is essential to consider (cardiovascular) fitness in the definition of metabolically healthy obese/metabolic health and to perform longitudinal studies in this regard. A better understanding of both the (early-life) lifestyle factors and the underlying mechanisms that mediate different phenotypes is necessary for the tailored prevention and personalized treatment of obesity.

High Maternal and Low Cord Blood Leptin Are Associated with BMI-SDS Gain in the First Year of Life.

BACKGROUND: Early infant weight development influences metabolic regulation later in life. For the prevention of obesity and metabolic diseases, it is important to understand the underlying mechanisms in detail. OBJECTIVES: This study aims to examine the effects of maternal anthropometric, sociodemographic, and lifestyle factors on maternal and cord blood leptin levels at birth and on the development of body mass index (BMI) standard deviation scores (SDS) in offspring up to 1 year of age. METHODS: Seventy-six mother-child pairs were enrolled in this follow-up analysis in a cross-sectional design. Standardized questionnaires were used to collect information regarding maternal anthropometrics, lifestyle habits, and sociodemographic conditions, and newborn weight, or, rather, BMI-SDS, development during the first year of life. RESULTS: Cord blood leptin (ß = -0.222, p = 0.074), maternal leptin (ß = 0.414, p = 0.001), and female sex of the offspring (ß = 0.385, p = 0.003) explained 29.0% of the variance in BMI-SDS changes in the first year of life. Cord blood leptin was influenced by newborn sex (male; ß = -0.220, p = 0.025) and maternal moderate-intensity physical activity in the third trimester (ß = 0.265, p = 0.007, corr. R2 = 9.2%); maternal leptin was influenced by maternal prepregnancy BMI (ß = 0.602, p < 0.001) and weight gain during pregnancy (ß = 0.247, p = 0.004, corr. R2 = 35.5%). CONCLUSIONS: Higher maternal and lower cord blood leptin levels are associated with a higher BMI-SDS increase during the first year of life. Maternal leptin is influenced by maternal BMI and weight gain during pregnancy, and cord blood leptin is influenced by maternal physical activity; therefore, it can be suggested that an active and healthy maternal lifestyle may play a pivotal and beneficial role in the offspring's weight development.

Impact of endurance exercise and probiotic supplementation on the intestinal microbiota: a cross-over pilot study.

BACKGROUND: The human microbiota has a broad range of functions contributing to metabolic processes and the activities of our immune system. Its influence on health, well-being and chronic diseases are discussed in various studies. The intestinal microbiota and the mucosal integrity are influenced by diet, environment and other lifestyle factors, including physical activity. There are correlations between cardiorespiratory fitness and important markers of intestinal health. However, data linking endurance exercise to microbiota composition are sparse. Many endurance athletes take probiotics to reduce gastrointestinal symptoms linked to exercise or immunosuppression, but the longitudinal data is insufficient.This randomised, controlled cross-over pilot study will examine the impact of specific endurance training and probiotic supplementation on the intestinal microbiota and mucosa in healthy, athletic students. OBJECTIVE: The aim of this pilot study is to elucidate the impact of physical activity on the intestinal microbiota and mucosa with regard to the effects of a probiotic supplementation. METHODS: In this pilot study, thirty non-specifically trained student athletes will participate in an intervention consisting of a two-week rest (baseline) period, a four-week exercise programme and a four-week probiotic intervention using SymbioLactComp®. The exercise programme consists of three 60-min running workouts per week at 70-85% of the peak heart rate (HRpeak). Primary endpoint of this pilot study is the feasibility and practicality of the intervention as well as a sample size estimation. Furthermore, anthropometric measurements and information on nutrition and lifestyle will be obtained. The peak oxygen uptake (VO2peak) and peak heart rate (HRpeak) (determined during a shuttle run test) as well as selected blood and saliva parameters (haemogram, cytokines) will be evaluated. Changes to the intestinal microbiota will be analysed by stool diagnostics (KyberKompaktPRO®, KyberPlus®). The potential changes may include microbiota composition, bacterial metabolites and mucosa- and immune markers. CONCLUSION: Results will be used for the design of a main randomised controlled trial with a larger collective based on feasibility, validity and sample size estimation as well as the potential effects of endurance exercise on intestinal microbiota and mucosa. Evidence-based information of an exercise-altered microbiota could be of importance for the prevention and therapy of intestinal or immune disorders. TRIAL REGISTRATION: German Clinical Trials Register: DRKS00011108. Retrospectively registered on 28 November 2016.

The disease burden associated with Campylobacter spp. in Germany, 2014.

Bacteria of the genus Campylobacter are an important cause of human illness worldwide. Campylobacter infections are expressed as gastroenteritis and can lead to severe sequelae like reactive arthritis, Guillain-Barré syndrome, irritable bowel syndrome and inflammatory bowel disease. In Germany, Campylobacter-associated gastroenteritis cases are notifiable but there is no reporting obligation for the sequelaes and the disease burden is clearly underestimated. The aim of our study was to quantify reliably the current disease burden of all Campylobacter spp.-associated diseases for Germany with the method of disability-adjusted life years (DALYs). DALYs combine mortality and morbidity in a single summary measure, whereby one DALY represents the loss of one year in full health. For acute gastroenteritis, we estimated 967 DALYs of which only 484 DALYs were detected within the reporting system. Overall, we estimated that 8811 DALYs were caused by the campylobacter-related diseases known so far. 98% of the DALYs were associated with morbidity and 2% with mortality. Mortality was caused by the health outcomes Gastroenteritis and Guillain-Barré syndrome exclusively.