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Background: The European post-authorisation study (EU PAS) register is a repository launched in 2010 by the European Medicines Agency (EMA). All EMA-requested PAS, commonly observational studies, must be recorded in this register. Multi-database studies (MDS) leveraging secondary data have become an important strategy to conduct PAS in recent years, as reflected by the type of studies registered in the EU PAS register. Objectives: To analyse and describe PAS in the EU PAS register, with focus on MDS. Methods: Studies in the EU PAS register from inception to 31st December 2018 were described concerning transparency, regulatory obligations, scope, study type (e.g., observational study, clinical trial, survey, systematic review/meta-analysis), study design, type of data collection and target population. MDS were defined as studies conducted through secondary use of >1 data source not linked at patient-level. Data extraction was carried out independently by 14 centres with expertise in pharmacoepidemiology, using publicly available information in the EU PAS register including study protocol, whenever available, using a standardised data collection form. For validation purposes, a second revision of key fields for a 15% random sample of studies was carried out by a different centre. The inter-rater reliability (IRR) was then calculated. Finally, to identify predictors of primary data collection-based studies/versus those based on secondary use of healthcare databases) or MDS (vs. non-MDS), odds ratios (OR) and 95% confidence intervals (CI) were calculated fitting univariate logistic regression models. Results: Overall, 1426 studies were identified. Clinical trials (N = 30; 2%), systematic reviews/meta-analyses (N = 16; 1%) and miscellaneous study designs (N = 46; 3%) were much less common than observational studies (N = 1227; 86%). The protocol was available for 63% (N = 360) of 572 observational studies requested by a competent authority. Overall, 36% (N = 446) of ob

Citrus limon (L.) Burm. F. is an important evergreen fruit crop whose rhizosphere and phyllosphere microbiota have been characterized, while seed microbiota is still unknown. Bacterial and fungal endophytes were isolated from C. limon surface-sterilized seeds. The isolated fungi—belonging to Aspergillus, Quambalaria and Bjerkandera genera—and bacteria—belonging to Staphylococcus genus—were characterized for indoleacetic acid production and phosphate solubilization. Next Generation Sequencing based approaches were then used to characterize the endophytic bacterial and fungal microbiota structures of surface-sterilized C. limon seeds and of shoots obtained under aseptic conditions from in vitro growing seedlings regenerated from surface-sterilized seeds. This analysis highlighted that Cutibacterium and Acinetobacter were the most abundant bacterial genera in both seeds and shoots, while Cladosporium and Debaryomyces were the most abundant fungal genera in seeds and shoots, respectively. The localization of bacterial endophytes in seed and shoot tissues was revealed by Fluorescence In Situ Hybridization coupled with Confocal Laser Scanning Microscopy revealing vascular bundle colonization. Thus, these results highlighted for the first time the structures of endophytic microbiota of C. limon seeds and the transmission to shoots, corroborating the idea of a vertical transmission of plant microbiota and suggesting its crucial role in seed germination and plant development.

Background/Objectives: As only 1% of clinically eligible subjects choose to undergo surgical treatment for obesity, other options should be investigated. This study aimed to assess the effects of intensive lifestyle modification (ILM) with or without 3-mg liraglutide daily vs. sleeve gastrectomy (SG) on BMI after 1 year. Subjects/methods: In this study performed at an Italian university hospital, non-diabetic patients eligible for bariatric surgery were recruited from a weight-loss clinic and had the option to choose from three possible weight-loss programmes up to an allocation of 25 subjects in each arm matched by BMI and age. ILM consisted in 813. kcal of a very low-calorie diet (VLCD) for 1 month, followed by a diet of 12. kcal/kg body weight of high protein and high fat for 11 months plus 30. min of brisk walking daily and at least 3. h of aerobic exercise weekly. SG patients followed a VLCD for 1 month and a free diet thereafter. Patients were evaluated at baseline and at 1, 3, 6, 9 and 12 months. Results: A total of 75 patients were enrolled; retention was 100% in the SG and 85% in the two medical arms. SG reduced BMI by 32% (P <. 0.001 vs. medical arm), while ILM + liraglutide and ILM led to BMI reductions of 24% and 14%, respectively (P <. 0.001). More women allocated themselves to the ILM + liraglutide group. Weight loss was 43. kg with SG, 26. kg with ILM + liraglutide and 15. kg with ILM alone. Lean body mass reductions were -11.6. kg with SG, -6.3. kg with ILM and -8.3. kg with ILM + liraglutide. Prevalence of prediabetes was significantly lower with ILM + liraglutide, and insulin resistance was reduced by about 70% by both ILM + liraglutide and SG vs. 39% by ILM alone. Cardiometabolic risk factors were greatly reduced in all three groups. Discussion: At least in the short-term, liraglutide 3.0. mg once daily associated with drastic calorie-intake restriction and intensive physical activity promoted a 24% weight loss, which was almost two times gr