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SNCAIP duplication may promote Group 4 medulloblastoma via induction of PRDM6, a poorly characterized member of the PRDF1 and RIZ1 homology domain-containing (PRDM) family of transcription factors. Here, we investigated the function of PRDM6 in human hindbrain neuroepithelial stem cells and tested PRDM6 as a driver of Group 4 medulloblastoma. We report that human PRDM6 localizes predominantly to the nucleus, where it causes widespread repression of chromatin accessibility and complex alterations of gene expression patterns. Genome-wide mapping of PRDM6 binding reveals that PRDM6 binds to chromatin regions marked by histone H3 lysine 27 trimethylation that are located within, or proximal to, genes. Moreover, we show that PRDM6 expression in neuroepithelial stem cells promotes medulloblastoma. Surprisingly, medulloblastomas derived from PRDM6-expressing neuroepithelial stem cells match human Group 3, but not Group 4, medulloblastoma. We conclude that PRDM6 expression has oncogenic potential but is insufficient to drive Group 4 medulloblastoma from neuroepithelial stem cells. We propose that both PRDM6 and additional factors, such as specific cell-of-origin features, are required for Group 4 medulloblastoma. Given the lack of PRDM6 expression in normal tissues and its oncogenic potential shown here, we suggest that PRDM6 inhibition may have therapeutic value in PRDM6-expressing medulloblastomas.

Abstract 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.

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. The Healthy Lifestyle Community Program (cohort 3) achieved a significant reduction in body weight (−1.8 kg) in a community‐based sample of mostly clinically healthy participants. This weight loss was sustained at the end of the study (16 months). Adherence to a healthy plant‐based diet correlated with improved risk markers.

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 ).

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.

BackgroundThe potential of adopting a healthy lifestyle to fight non-communicable diseases (NCDs) is not fully used. We hypothesised that the Healthy Lifestyle Community Programme (HLCP, cohort 1) reduces weight and other risk markers compared with baseline and control.Methods24-month, non-randomised, controlled intervention trial. Intervention: intensive 8-week phase with seminars, workshops and coaching focusing on a healthy lifestyle (eg, plant-based diet, physical activity, stress management) and group support followed by a 22-month alumni phase. Weight reduction as the primary outcome and other NCD risk parameters were assessed at six time points. Participants were recruited from the general population. Multiple linear regression analyses were conducted.Results143 participants (58±12 years, 71% female) were enrolled (91 in the intervention (IG) and 52 in the control group (CG)). Groups’ baseline characteristics were comparable, except participants of IG were younger, more often females, overweight and reported lower energy intake (kcal/day). Weight significantly decreased in IG at all follow-ups by −1.5 ± 1.9 kg after 8 weeks to −1.9 ± 4.0 kg after 24 months and more than in CG (except after 24 months). Being male, in the IG or overweight at baseline and having a university degree predicted more weight loss. After the intervention, there were more participants in the IG with a ‘high’ adherence (+12%) to plant-based food patterns. The change of other risk parameters was most distinct after 8 weeks and in people at elevated risk. Diabetes-related risk parameters did not improve.ConclusionThe HLCP was able to reduce weight and to improve aspects of the NCD risk profile. Weight loss in the IG was moderate but maintained for 24 months. Participants of lower educational status might benefit from even more practical units. Future interventions should aim to include more participants at higher risk.Trial registration numberDRKS00018821.

Rationale: The dietary components choline, betaine, and L-carnitine are converted by intestinal microbiota into the molecule trimethylamine (TMA). In the human liver, hepatic flavin-containing monooxygenase 3 oxidizes TMA to trimethylamine-N-oxide (TMAO). TMAO is considered a candidate marker for the risk of cardiovascular disease. Methodology: The Healthy Lifestyle Community Program cohort 3 (HLCP-3) intervention was conducted with participants recruited from the general population in Germany (intervention: n = 99; control: n = 48). The intervention included intensive educational workshops, seminars, and coaching activities. The assessment was conducted using a complete case analysis (CCA) of the participants. The intervention was carried out for a ten-week intensive phase and an alumni phase. The interventional program emphasizes adopting a healthy plant-based diet and reducing meat consumption, as adherence to such a diet may lead to lowering TMAO levels. Additionally, it provides general recommendations about physical activity, stress management, and community support. The control group did not receive any intervention. TMAO was evaluated using stable isotope dilution liquid chromatography, and tandem mass spectrometry was used to measure fasting plasma levels of TMAO. Objectives: The present study aimed to determine the impact of the Healthy Lifestyle Community Program (HLCP-3) on risk profiles for lifestyle-related diseases and TMAO plasma levels. Results: Significant decreases in most risk profile parameters were detected, and a non-significant decrease in plasma TMAO levels was observed in the intervention group (0.37 (−1.33; 0.59) µmol/L). Furthermore, for the intervention group, after a six-month follow-up period, there was a significant negative correlation between higher healthy plant diet index (hPDI) scores and a decrease in plasma TMAO (ß = −0.200, p = 0.027). Additionally, a significant negative correlation was observed between the TMAO level and the scores for adherence to the plant diet index (PDI) (r = −0.195; p = 0.023). Conclusions: HLCP-3 is effective at improving adherence to a plant-based diet and improving risk profile parameters. However, long-term interventions involving stricter dietary programs in the sense of a plant-based diet are recommended if significant decreases in TMAO levels are to be obtained.

Non-communicable diseases (NCD) are associated with high costs for healthcare systems. We evaluated changes in total costs, comprising direct and indirect costs, due to a 24-month non-randomized, controlled lifestyle intervention trial with six measurement time points aiming to improve the risk profile for NCDs. Overall, 187 individuals from the general population aged ≥18 years were assigned to either the intervention group (IG; n = 112), receiving a 10-week intensive lifestyle intervention focusing on a healthy, plant-based diet; physical activity; stress management; and community support, followed by a 22-month follow-up phase including monthly seminars, or a control group (CG; n = 75) without intervention. The complete data sets of 118 participants (IG: n = 79; CG: n = 39) were analyzed. At baseline, total costs per person amounted to 67.80 ± 69.17 EUR in the IG and 48.73 ± 54.41 EUR in the CG per week. The reduction in total costs was significantly greater in the IG compared to the CG after 10 weeks (p = 0.012) and 6 months (p = 0.004), whereas direct costs differed significantly after 10 weeks (p = 0.017), 6 months (p = 0.041) and 12 months (p = 0.012) between the groups. The HLCP-2 was able to reduce health-related economic costs, primarily due to the reduction in direct costs.

Rationale: The dietary components choline, betaine, and L-carnitine are converted by intestinal microbiota into the molecule trimethylamine (TMA). In the human liver, hepatic flavin-containing monooxygenase 3 oxidizes TMA to trimethylamine-N-oxide (TMAO). TMAO is considered a candidate marker for the risk of cardiovascular disease. Methodology: The Healthy Lifestyle Community Program cohort 3 (HLCP-3) intervention was conducted with participants recruited from the general population in Germany (intervention: n = 99; control: n = 48). The intervention included intensive educational workshops, seminars, and coaching activities. The assessment was conducted using a complete case analysis (CCA) of the participants. The intervention was carried out for a ten-week intensive phase and an alumni phase. The interventional program emphasizes adopting a healthy plant-based diet and reducing meat consumption, as adherence to such a diet may lead to lowering TMAO levels. Additionally, it provides general recommendations about physical activity, stress management, and community support. The control group did not receive any intervention. TMAO was evaluated using stable isotope dilution liquid chromatography, and tandem mass spectrometry was used to measure fasting plasma levels of TMAO. Objectives: The present study aimed to determine the impact of the Healthy Lifestyle Community Program (HLCP-3) on risk profiles for lifestyle-related diseases and TMAO plasma levels. Results: Significant decreases in most risk profile parameters were detected, and a non-significant decrease in plasma TMAO levels was observed in the intervention group (0.37 (−1.33; 0.59) µmol/L). Furthermore, for the intervention group, after a six-month follow-up period, there was a significant negative correlation between higher healthy plant diet index (hPDI) scores and a decrease in plasma TMAO (ß = −0.200, p = 0.027). Additionally, a significant negative correlation was observed between the TMAO level and the scores for adherence to the plant diet index (PDI) (r = −0.195; p = 0.023). Conclusions: HLCP-3 is effective at improving adherence to a plant-based diet and improving risk profile parameters. However, long-term interventions involving stricter dietary programs in the sense of a plant-based diet are recommended if significant decreases in TMAO levels are to be obtained.

Diets, but also overall food environments, comprise a variety of significant factors with direct and indirect impacts on human health. Eco-Regions are geographical areas with a territorial approach to rural development, utilizing organic food and farming practices, and principles and promoting sustainable communities and food systems. However, so far, little attention has been given to quantifying aspects of the health of citizens living in these sustainable transition territories. The project “Indicators for Assessment of Health Effects of Consumption of Sustainable, Organic School Meals in Eco-Regions” (INSUM) aims to identify and discuss research approaches and indicators that could be applied to effectively measure the somatic, mental, and social health dimensions of citizens in Eco-Regions, linked to the intake of organic foods in their diets. In this paper, we focus on the somatic (physical) health dimension. A two-day workshop was held to discuss suitable methodology with an interdisciplinary, international group of experts. The results showed the limitations of commonly used tools for measuring dietary intake (e.g., relying on the memory of participants), and nutritional biomarkers (e.g., variations in correlations with specific intakes) for research understanding dietary intake and the health effects of diets. To investigate the complexity of this issue, the most suitable approach seems to be the combination of traditional markers of physical and mental health alongside emerging indicators such as the microbiome, nutrigenomics, metabolomics, or inflammatory biomarkers. Using new, digital, non-invasive, and wearable technologies to monitor indicators could complement future research. We conclude that future studies should adopt systemic, multidisciplinary approaches by combining not only indicators of somatic and mental health and social wellbeing (MHSW) but also considering the potential benefits of organic diets for health as well as aspects of sustainability connected to food environments.