The healthful plant-based diet index as a tool for obesity prevention—The healthy lifestyle community program cohort 3 study

Background: World-wide the prevalence of obesity is high, and promoting a shift toward more healthful and more plant-based dietary patterns appears to be one promising strategy to address this issue. A dietary score to assess adherence to a healthy plant-based diet is the healthful plant-based diet index. While there is evidence from cohort studies that an increased healthful plant-based diet index is associated with improved risk markers, evidence from intervention studies is still lacking. Methods: A lifestyle intervention was conducted with mostly middle-aged and elderly participants from the general population (n = 115). The intervention consisted of a 16-month lifestyle program focusing on a healthy plant-based diet, physical activity, stress management, and community support. Results: After 10 weeks, significant improvements were seen in dietary quality, body weight, body mass index, waist circumference, total cholesterol, measured and calculated low-density lipoprotein (LDL) cholesterol, oxidized LDL particles, non-high-density lipoprotein cholesterol, remnant cholesterol, glucose, insulin, blood pressure, and pulse pressure. After 16 months, significant decreases were seen in body weight (−1.8 kg), body mass index (−0.6 kg/m2), and measured LDL cholesterol (−12 mg/dl). Increases in the healthful plant-based diet index were associated with risk marker improvements. Conclusions: The recommendation of moving toward a plant-based diet appears acceptable and actionable and may improve body weight. The healthful plant-based diet index can be a useful parameter for intervention studies

Healthy lifestyle changes favourably affect common carotid intima-media thickness: the Healthy Lifestyle Community Programme (cohort 2)

Common carotid intima-media thickness (ccIMT) progression is a risk marker for cardiovascular disease (CVD), whereas healthy lifestyle habits are associated with lower ccIMT. The objective of the present study was to test whether a healthy lifestyle intervention can beneficially affect ccIMT progression. A community-based non-randomised, controlled lifestyle intervention was conducted, focusing on a predominantly plant-based diet (strongest emphasis), physical activity, stress management and social health. Assessments of ccIMT were made at baseline, 6 months and 1 year. Participants had an average age of 57 years and were recruited from the general population in rural northwest Germany (intervention: n 114; control: n 87). From baseline to 1 year, mean ccIMT significantly increased in both the intervention (0.026 [95 % CI 0.012, 0.039] mm) and control group (0.045 [95 % CI 0.033, 0.056] mm). The 1-year trajectory of mean ccIMT was lower in the intervention group (P = 0.022; adjusted for baseline). In a subgroup analysis with participants with high baseline mean ccIMT (≥0.800 mm), mean ccIMT non-significantly decreased in the intervention group (-0.016 [95 % CI -0.050, 0.017] mm; n 18) and significantly increased in the control group (0.065 [95 % CI 0.033, 0.096] mm; n 12). In the subgroup, the 1-year trajectory of mean ccIMT was significantly lower in the intervention group (between-group difference: -0.051 [95 % CI -0.075, -0.027] mm; P < 0.001; adjusted for baseline). The results indicate that healthy lifestyle changes may beneficially affect ccIMT within 1 year, particularly if baseline ccIMT is high

Effect of a 1-Year Controlled Lifestyle Intervention on Body Weight and Other Risk Markers (the Healthy Lifestyle Community Programme, Cohort 2)

Introduction: The prevalence of obesity is high and increasing worldwide. Obesity is generally associated with an increased risk of chronic disease and mortality. The objective of the study was to test the effect of a lifestyle intervention on body weight and other chronic disease risk markers. Methods: A non-randomized controlled trial was conducted, including mostly middle-aged and elderly participants recruited from the general population in rural northwest Germany (intervention: n = 114; control: n = 87). The intervention consisted of a 1-year lifestyle programme, focussing on four key areas: a largely plant-based diet (strongest emphasis), physical activity, stress management, and community support. Parameters were assessed at baseline, 10 weeks, 6 months, and 1 year. The control group received no intervention. Results: Compared to the control, in the intervention group, significantly lower 1-year trajectories were observed for body weight, body mass index (BMI), waist circumference (WC), total cholesterol, calculated LDL cholesterol, non-HDL cholesterol, remnant cholesterol (REM-C), glucose, HbA1c, and resting heart rate (RHR). However, between-group differences at 1 year were small for glucose, HbA1c, and cholesterol (apart from REM-C). No significant between-group differences were found for 1-year trajectories of measured LDL cholesterol, HDL cholesterol, triglycerides, insulin, blood pressure, and pulse pressure. Conclusion: The intervention successfully reduced body weight, BMI, WC, REM-C, and RHR. However, at 1 year, effectiveness of the intervention regarding other risk markers was either very modest or could not be shown

Exploratory analysis of the effect of a controlled lifestyle intervention on inflammatory markers – the Healthy Lifestyle Community Programme (cohort 2)

Background: Chronic low-grade inflammation is associated with an increased risk of chronic disease and mortality. The objective of the study was to test the effect of a healthy lifestyle intervention on biomarkers of inflammation (among other risk markers). Methods: We conducted a non-randomized controlled trial with mostly middle-aged and elderly participants from the general population in rural northwest Germany (intervention: n = 114; control: n = 87). The intervention consisted of a 1-year lifestyle programme focusing on diet (largely plant-based; strongest emphasis), physical activity, stress management, and social support. High-sensitivity C-reactive protein (hs-CRP) was assessed at baseline, 10 weeks, 6 months, and 1 year. Homocysteine (Hcy) was assessed at baseline, 10 weeks, and 1 year. Adiponectin (Apn) was assessed at baseline and 10 weeks. An exploratory analysis of these inflammatory markers assessing the between-group differences with ANCOVA was conducted. Results: The 1-year trajectory of hs-CRP was significantly lower in the intervention group compared to control (between-group difference: -0.8 (95% CI -1.2, -0.3) mg/l; p = 0.001; adjusted for baseline). The 1-year trajectory of Hcy was non-significantly higher in the intervention compared to control (between-group difference: 0.2 (95% CI -0.3, 0.7) µmol/l; p = 0.439; adjusted for baseline). From baseline to 10 weeks, Apn decreased significantly more in the intervention group compared to control (between-group difference: -1.6 (95% CI -2.7, -0.5) µg/ml; p = 0.004; adjusted for baseline). Conclusions: Our study shows that healthy lifestyle changes can lower hs-CRP and Apn levels and are unlikely to significantly affect Hcy levels within 1 year. Trial registration: German Clinical Trials Register (DRKS; reference: DRKS00018775, registered 12 Sept 2019; retrospectively registered; www.drks.de)

Literatur der Archäologie: Materialität und Rhetorik im 18. und 19. Jahrhundert

Seit der Einführung des Konzepts einer »Archäologie des Wissens« ist wiederholt versucht worden, den Begriff der Archäologie für eine allgemeine Kulturtheorie zu funktionalisieren. Umfangreich erschienen in der Folge die Archäologien, als deren Gegenstände nicht einmal mehr die Gegenwart oder die Zukunft undenkbar sind. Daneben musste sich, wie alle Kulturwissenschaften, das institutionelle Fach Archäologie mit dem prägenden Einfluss sprachlicher Bedingungen auf die Gewinnung von Erkenntnissen auseinandersetzen. Dies verweist auf eine zentrale Problematik, die eng an der Kombination von Archäologie und Germanistik in der konzeptionellen Gestaltung des Forschungskollegs Morphomata orientiert ist, nämlich das wechselseitige Verhältnis visuell wahrgenommener und literarisch vermittelter Form sowie ihre Bezüge zu einer ihnen zugrunde liegenden Vorstellung. Der vorliegende Sammelband will über Fallbeispiele aus den Blickwinkeln der Fachdisziplinen der Archäologie und der Literaturwissenschaften Veränderungen und Persistenzen in der Erschließung von Antike deutlich machen. Im Zentrum der Beiträge stehen erstens die Verwendung des Begriffs »Archäologie« außerhalb des aus heutiger Sicht dafür charakteristischen Feldes der Ausgrabung und deutenden Erfassung überlieferter materialer Fundstücke, zweitens die dichterische Darstellung archäologischer Tätigkeit im modernen Sinne der sich ausbildenden Fachdisziplin und drittens Literatur als Medium der Formulierung und Systematisierung generierter Wissensbestände bzw. intersubjektiver Diskursivität der Archäologie

Causal integration of multi-omics data with prior knowledge to generate mechanistic hypotheses.

Multi-omics datasets can provide molecular insights beyond the sum of individual omics. Various tools have been recently developed to integrate such datasets, but there are limited strategies to systematically extract mechanistic hypotheses from them. Here, we present COSMOS (Causal Oriented Search of Multi-Omics Space), a method that integrates phosphoproteomics, transcriptomics, and metabolomics datasets. COSMOS combines extensive prior knowledge of signaling, metabolic, and gene regulatory networks with computational methods to estimate activities of transcription factors and kinases as well as network-level causal reasoning. COSMOS provides mechanistic hypotheses for experimental observations across multi-omics datasets. We applied COSMOS to a dataset comprising transcriptomics, phosphoproteomics, and metabolomics data from healthy and cancerous tissue from eleven clear cell renal cell carcinoma (ccRCC) patients. COSMOS was able to capture relevant crosstalks within and between multiple omics layers, such as known ccRCC drug targets. We expect that our freely available method will be broadly useful to extract mechanistic insights from multi-omics studies

Adenosine/A2B receptor signaling ameliorates the effects of ageing and counteracts obesity

The combination of aging populations with the obesity pandemic results in an alarming rise in non-communicable diseases. Here, we show that the enigmatic adenosine A2B receptor (A2B) is abundantly expressed in skeletal muscle (SKM) as well as brown adipose tissue (BAT) and might be targeted to counteract age-related muscle atrophy (sarcopenia) as well as obesity. Mice with SKM-specific deletion of A2B exhibited sarcopenia, diminished muscle strength, and reduced energy expenditure (EE), whereas pharmacological A2B activation counteracted these processes. Adipose tissue-specific ablation of A2B exacerbated age-related processes and reduced BAT EE, whereas A2B stimulation ameliorated obesity. In humans, A2B expression correlated with EE in SKM, BAT activity, and abundance of thermogenic adipocytes in white fat. Moreover, A2B agonist treatment increased EE from human adipocytes, myocytes, and muscle explants. Mechanistically, A2B forms heterodimers required for adenosine signaling. Overall, adenosine/A2B signaling links muscle and BAT and has both anti-aging and anti-obesity potential

Dissecting CD8+ T cell pathology of severe SARS-CoV-2 infection by single-cell immunoprofiling

Introduction: SARS-CoV-2 infection results in varying disease severity, ranging from asymptomatic infection to severe illness. A detailed understanding of the immune response to SARS-CoV-2 is critical to unravel the causative factors underlying differences in disease severity and to develop optimal vaccines against new SARS-CoV-2 variants. Methods: We combined single-cell RNA and T cell receptor sequencing with CITE-seq antibodies to characterize the CD8+ T cell response to SARS-CoV-2 infection at high resolution and compared responses between mild and severe COVID-19. Results: We observed increased CD8+ T cell exhaustion in severe SARS-CoV-2 infection and identified a population of NK-like, terminally differentiated CD8+ effector T cells characterized by expression of FCGR3A (encoding CD16). Further characterization of NK-like CD8+ T cells revealed heterogeneity among CD16+ NK-like CD8+ T cells and profound differences in cytotoxicity, exhaustion, and NK-like differentiation between mild and severe disease conditions. Discussion: We propose a model in which differences in the surrounding inflammatory milieu lead to crucial differences in NK-like differentiation of CD8+ effector T cells, ultimately resulting in the appearance of NK-like CD8+ T cell populations of different functionality and pathogenicity. Our in-depth characterization of the CD8+ T cell-mediated response to SARS-CoV-2 infection provides a basis for further investigation of the importance of NK-like CD8+ T cells in COVID-19 severity.</p

Ventromedial Prefrontal Cortex Activation Is Associated with Memory Formation for Predictable Rewards

During reinforcement learning, dopamine release shifts from the moment of reward consumption to the time point when the reward can be predicted. Previous studies provide consistent evidence that reward-predicting cues enhance long-term memory (LTM) formation of these items via dopaminergic projections to the ventral striatum. However, it is less clear whether memory for items that do not precede a reward but are directly associated with reward consumption is also facilitated. Here, we investigated this question in an fMRI paradigm in which LTM for reward-predicting and neutral cues was compared to LTM for items presented during consumption of reliably predictable as compared to less predictable rewards. We observed activation of the ventral striatum and enhanced memory formation during reward anticipation. During processing of less predictable as compared to reliably predictable rewards, the ventral striatum was activated as well, but items associated with less predictable outcomes were remembered worse than items associated with reliably predictable outcomes. Processing of reliably predictable rewards activated the ventromedial prefrontal cortex (vmPFC), and vmPFC BOLD responses were associated with successful memory formation of these items. Taken together, these findings show that consumption of reliably predictable rewards facilitates LTM formation and is associated with activation of the vmPFC