Cortical Structure Alterations and Social Behavior Impairment in p50-Deficient Mice

Alterations in genes that regulate neurodevelopment can lead to cortical malformations, resulting in malfunction during postnatal life. The NF-κB pathway has a key role during neurodevelopment by regulating the maintenance of the neural progenitor cell pool and inhibiting neuronal differentiation. In this study, we evaluated whether mice lacking the NF-κB p50 subunit (KO) present alterations in cortical structure and associated behavioral impairment. We found that, compared with wild type (WT), KO mice at postnatal day 2 present an increase in radial glial cells, an increase in Reelin protein expression levels, in addition to an increase of specific layer thickness. Moreover, adult KO mice display abnormal columnar organization in the somatosensory cortex, a specific decrease in somatostatin- and parvalbumin-expressing interneurons, altered neurite orientation, and a decrease in Synapsin I protein levels. Concerning behavior, KO mice, in addition to an increase in locomotor and exploratory activity, display impairment in social behaviors, with a reduction in social interaction. Finally, we found that risperidone treatment decreased hyperactivity of KO mice, but had no effect on defective social interaction. Altogether, these data add complexity to a growing body of data, suggesting a link between dysregulation of the NF-κB pathway and neurodevelopmental disorders pathogenesis

The carbon footprint of Italian schools meals: An optimal choice of dishes in vegan, vegetarian, and omnivorous menus

This study aims to assess the carbon footprint associated with vegan, vegetarian, and omnivorous menus for primary school lunches in Italy. For this purpose, healthy and acceptable menus with minimal greenhouse gas emissions have been designed by a binary linear programming model. The results show that the adoption of a specific diet may help in reducing the carbon footprint of menus, but it is the optimal selection of dishes that ultimately makes the difference. Interestingly enough, the optimal choice of dishes and the restriction of meat consumption in omnivorous menus can lead up to a 40% emission reduction compared to the current school lunch menu of the municipality of Rome. Moreover, the optimal choice of dishes in vegan menus provides the menu with the lowest carbon footprint among all kinds of diets

Analysis of bundles and drivers of change of multiple ecosystem services in an Alpine region

Approaches based on the concept of ecosystem services need analyses of the sets of spatially correlated services (i.e. bundles) and of the external factors that modify the ecosystem service supply (i.e. drivers of change). At present, appropriate methods to analyse bundles and drivers of change are still under development. This study proposes a method based on a combination of spatial and statistical analyses to define bundles and to explain the drivers of change of 24 ecosystem services in Trentino, an Alpine region of Italy. Results show that multiple services can be grouped in a few number of bundles with a complex shape. When mapping multiple services across the territory, the spatial units of representation are a combination of the intrinsic units of representation of single ecosystem services and land use classes. Land use management was found as the external factor that causes the greatest variability of the ecosystem services distribution across the region

Influence of sex, age, pubertal maturation and body mass index on circulating white blood cell counts in healthy European adolescents—the HELENA study

Percentiles 10th, 25th, 50th, 75th and 90th are presented for circulating white blood cells (WBC), neutrophils, lymphocytes, monocytes, eosinophils and basophils in healthy European adolescents (12.5–17.5 years, n = 405, 48.9 % boys), considering age, sex, puberty and body mass index (BMI). CD3+ (mature T cells), CD4+ (T helper), CD8+ (T cytotoxic), CD16+56+ (natural killer), CD19+ (B cells), CD3+CD45RA+, CD4+CD45RA+, CD8+CD45RA+ (naïve), CD3+CD45RO+, CD4+CD45RO+ and CD8+CD45RO+ (memory) lymphocytes were also analysed by immunophenotyping. Girls presented higher WBC, neutrophil, CD3+CD45RO+ and CD4+CD45RO+ cell counts and CD3+/CD19+ ratio, and lower CD3+CD45RA+ and CD4+CD45RA+ counts than boys. Age was associated with higher neutrophil counts and CD3+/CD19+, and lower CD19+ counts; in boys, with lower CD3+CD45RA+, CD4+CD45RA+ and CD8+CD45RA+ counts as well; in girls, with higher WBC, CD3+CD45RO+ and CD4+CD45RO+ counts. Pubertal maturation in boys was associated with lower WBC and lymphocyte counts; in girls, with higher basophil, CD3+CD45RO+ and CD4+CD45RO+ values. BMI was associated with higher WBC counts; in boys, also with higher lymphocyte counts; in girls, with higher neutrophil, CD4+, CD3+CD45RO+ and CD4+CD45RO+ counts. Conclusion: Our study provides normative values for circulating immune cells in adolescents, highlighting the importance of considering sex, age, pubertal maturation and BMI when establishing reference ranges for WBC in paediatric populations

Simulation of Daily Iron Intake by Actual Diet Considering Future Trends in Wheat and Rice Biofortification, Environmental, and Dietary Factors: An Italian Case Study

Background and aim: Cereals’ iron content is a major contributor to dietary iron intake in Europe and a potential for biofortification. A simulation of daily iron intake from wheat and rice over the next 20 years will be quantified. Methods: Food items, and energy and iron intake by age classes are estimated using the Italian dietary survey (IV SCAI). Iron intake and adequacy estimation trends were categorized in four scenarios compared to a baseline (basic scenario; only climate change effects): over wheat and rice biofortification effects (scenario 1); over the shift in whole wheat consumption of up to 50% of the total amount of wheat-based foods (scenario 2); over the shift in brown rice consumption up to 100% of the total amount of rice (scenario 3); over the cumulative effects of biofortifications and whole wheat and brown rice consumption (scenario 4). Results: Increasing the iron intake from wheat and rice biofortification and the shift in whole wheat consumption is similar and sufficient to recover the baseline iron depletion effect due to climate change. The shift in brown rice consumption produces a negligible increment in iron intake. The cumulative effects of the corrective actions considered in the scenarios can significantly reduce the iron intake inadequacy, despite not reaching the recommended levels. Conclusions: Corrective actions including biofortification and whole grain consumption are still far from ensuring the full recovery in children and females of fertile age as at-risk groups of iron deficiency. Further actions are needed considering other biofortified food sources, fortified foods, and/or dietary food diversification

Lifestyle patterns and endocrine, metabolic, and immunological biomarkers in European adolescents: The HELENA study

Objective: To evaluate the association of lifestyle patterns related to physical activity (PA), sedentariness, and sleep with endocrine, metabolic, and immunological health biomarkers in European adolescents. Methods: The present cross-sectional study comprised 3528 adolescents (1845 girls) (12.5-17.5 years) enrolled in the Healthy Lifestyle in Europe by Nutrition in Adolescence Study. Cluster analysis was performed by including body composition, PA by accelerometry, self-reported sedentary behaviors, and sleep duration. We also measured endocrine, metabolic, and immunological biomarkers. Results: Three-cluster solutions were identified: (a) light-PA time, moderate-vigorous-PA time and sedentary time, (b) light-PA time, moderate-vigorous-PA time, sedentary time and sleep time, (c) light-PA time, moderate-vigorous-PA time, sedentary time and body composition. In addition, each cluster solution was defined as: “healthy,” “medium healthy,” and “unhealthy” according to the presented rating. Analysis of variance showed that overall the healthiest groups from the three clusters analyzed presented a better metabolic profile. A decision tree analysis showed that leptin had a strong association with cluster 3 in both boys and girls, high-density lipoprotein cholesterol had the strongest association with clusters 1 and 3 in boys. Cortisol had the strongest association with cluster 1. HOMA index (homeostatic model assessment) and C3 showed a strong association with cluster 3 in girls. Conclusions: Our results support the existence of different interactions between metabolic health and lifestyle patterns related to PA, sedentariness, and sleep, with some gender-specific findings. These results highlight the importance to consider multiple lifestyle-related health factors in the assessment of adolescents' health to plan favorable strategies.The HELENA Study was carried out with the financial support of the European Community Sixth RTD Framework Programme (Contract FOODCT-2005-007034). The study was partially supported by the Redes temáticas de Investigación Cooperativa RETIC (Red SAMID RD16/0022), and by the University of Granada, Plan Propio de Investigación 2016, Excellence actions: Units of Excellence; Unit of Excellence on Exercise and Health (UCEES)

Changes in physical activity patterns from adolescence to young adulthood: the BELINDA study

Physical activity (PA) is recognized as a marker of health. The aim was to investigate PA differences from adolescence to young adulthood. European adolescents included in the HELENA study were invited to participate in a follow-up study, 10 years later. The present study included 141 adults (25.0 ± 1.4 years) for whom valid accelerometer data were available in adolescence and adulthood. Changes in PA by sex, weight and maternal education level were explored with interactions. Time spent in sedentary activity, light PA (LPA) and moderate PA (MPA) increased by 39.1, 59.6 and 6.6 min/day, respectively, whereas the time spent in vigorous PA (VPA) decreased by 11.3 min/day compared with adolescent VPA (p < 0.05). Increases in MPA were greater on weekends compared with weekdays, but we found a greater decrease in VPA on weekdays compared with weekends. Moderate-to-vigorous PA (MVPA) decreased significantly on weekdays (–9.6 min/day; 95%CI, –15.9 to –3.4), while it increased on weekends (8.4 min/day; 95%CI, 1.9 to 14.8). Significant heterogeneity was found across sexes for VPA and MVPA, with a stronger decrease in VPA in males compared with females and a significant decrease in MVPA (–12.5 min/day; 95%CI, –20.4 to –4.5) in males but not in females (1.9 min/day; 95%CI, –5.5 to 9.2). No significant heterogeneity was found to be linked to maternal education level or weight, irrespective of PA level. Conclusion: Our data suggest that the transition from adolescence to young adulthood is a critical period for lifestyle PA habits. A decline in VPA and an increasingly sedentary time were observed. The observed changes are worrying and may increase the risk of developing adverse health consequences later in life

Identifying the best treatment choice for relapsing/refractory glioblastoma: a systematic review with multiple Bayesian network meta-analyses

Background: Glioblastoma is a highly aggressive primary central nervous system tumor characterized by poor outcomes. In case of relapse or progression to adjuvant chemotherapy, there is no univocal preferred regimen for relapsing glioblastoma. Methods: We conducted a systematic review and Bayesian trial-level network meta-analyses (NMA) to identify the regimens associated with the best outcomes. The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS) and overall response rates (ORR). We estimated separate treatment rankings based on the surface under the cumulative ranking curve values. Only phase II/III prospective comparative trials were included. Results: Twenty-four studies (3733 patients and 27 different therapies) were ultimately included. Twenty-three different regimens were compared for OS, 21 for PFS, and 26 for ORR. When taking lomustine as a common comparator, only regorafenib was likely to be significantly superior in terms of OS (hazard ratio: 0.50, 95% credible interval: 0.33-0.75). Regorafenib was significantly superior to other 16 (69.6%) regimens, including NovoTTF-100A, bevacizumab monotherapy, and several bevacizumab-based combinations. Regarding PFS and ORR, no treatment was clearly superior to the others. Conclusions: This NMA supports regorafenib as one of the best available options for relapsing/refractory glioblastoma. Lomustine, NovoTTF-100A, and bevacizumab emerge as other viable alternative regimens. However, evidence on regorafenib is controversial at best. Moreover, most studies were underpowered, with varying inclusion criteria and primary endpoints, and no longer adapted to the most recent glioblastoma classification. A paradigmatic change in clinical trials’ design for relapsing/refractory glioblastoma and more effective treatments are urgently required

WNT Oncogenic Transcription Requires MYC Suppression of Lysosomal Activity and EPCAM Stabilization in Gastric Tumors

Background &amp; Aims: WNT signaling is central to spatial tissue arrangement and regulating stem cell activity, and it represents the hallmark of gastrointestinal cancers. Although its role in driving intestinal tumors is well characterized, WNT's role in gastric tumorigenesis remains elusive. Methods: We have developed mouse models to control the specific expression of an oncogenic form of β-catenin (CTNNB1) in combination with MYC activation in Lgr5+ cells of the gastric antrum. We used multiomics approaches applied in vivo and in organoid models to characterize their cooperation in driving gastric tumorigenesis. Results: We report that constitutive β-catenin stabilization in the stomach has negligible oncogenic effects and requires MYC activation to induce gastric tumor formation. Although physiologically low MYC levels in gastric glands limit β-catenin transcriptional activity, increased MYC expression unleashes the WNT oncogenic transcriptional program, promoting β-catenin enhancer invasion without a direct transcriptional cooperation. MYC activation induces a metabolic rewiring that suppresses lysosomal biogenesis through mTOR and ERK activation and MiT/TFE inhibition. This prevents EPCAM degradation by macropinocytosis, promoting β-catenin chromatin accumulation and activation of WNT oncogenic transcription. Conclusion: Our results uncovered a new signaling framework with important implications for the control of gastric epithelial architecture and WNT-dependent oncogenic transformation