Aim To explore the effect that the location of needle placement has on efficacy and tolerability of bone marrow aspirate concentrate injections during treatment of knee osteoarthritis. Methods Bone marrow aspirate concentrate injections were administered to 111 patients via superolateral, anteromedial or anterolateral portals. Pain was assessed by visual analog scale before and 3, 7, 14 and 21 days after intervention. Knee function was assessed by Western Ontario and McMaster Universities Osteoarthritis Index, Knee Injury and Osteoarthritis Outcome Score and International Knee Documentation Committee scores before and 1, 3, 6, 9 and 12 months after intervention. Results Significant differences in Western Ontario and McMaster Universities Osteoarthritis Index, Knee Injury and Osteoarthritis Outcome Score and International Knee Documentation Committee scores were observed 12 months post intervention compared with baseline (p less then 0.001 for all comparisons). No significant differences in outcome or pain scores were observed among groups. Conclusion All portals demonstrated similar clinical benefits up to 12 months after intervention. Trial registration number ClinicalTrials.gov (NCT03825133).The variegated squirrel bornavirus 1 (VSBV-1), a member of the family Bornaviridae, was discovered in 2015 in a series of lethal human infections. Screening approaches revealed kept exotic squirrels as the putative source of infection. Infectious virus was successfully isolated by co-cultivation of infected primary squirrel cells with permanent cell lines. For in vivo characterization, neonatal and adult Lewis rats were inoculated either intracranially, intranasally or subcutaneously. After 4.5 months, three out of fifteen neonatal intracranially inoculated rats were VSBV-1 genome positive in the central nervous system without showing clinical signs. Pathohistological examination revealed a non-purulent encephalitis. While infection of immune incompetent rats (neonatal) using the type species of mammalian bornaviruses, the Borna disease virus 1, proceed to an immune tolerant status, VSBV-1 infection could result in inflammation of neuronal tissue. Sequencing showed minor adaptations within the VSBV-1 genome comparing to the viral genomes from infected squirrels, cell cultures or rat tissues. In conclusion, we were able to generate the first VSBV-1 isolates and provide in vivo animal model data in Lewis rats revealing substantial differences between VSBV-1 and BoDV-1. Furthermore, the presented data are a precondition for insights into the transmission and pathogenesis of this novel zoonotic pathogen.Aim To study regulatory approaches for the implementation and utilization of the Hospital Exemption (HE) in nine EU countries. Materials & methods Using public regulatory documentation and interviews with authorities we characterized the national implementation process of the HE, including national implementation characteristics and two outcomes national licensing provisions and the amount of license holders. Results National licensing provisions vary substantially among selected countries as a result of different regulatory considerations that relate to unmet medical needs, benefit/risk balance, and innovation. The amount of license holders per country is moderate (0-11). Conclusion The HE facilitates HE utilization in clinical practice in some countries, yet safeguarding of public health and incentivizing commercial development is challenging.Obesity is a chronic, relapsing metabolic disease, linked to a number of health risks and serious complications. Although highly prevalent in adults in the United States, it is underdiagnosed and untreated. Primary care providers (PCPs) are uniquely poised to diagnose and treat patients with obesity, using a selection of treatment strategies including lifestyle modifications and pharmacotherapies. As a physiological regulator of appetite and energy intake, the glucagon-like peptide-1 receptor agonist (GLP-1 RA) liraglutide 3.0 mg is approved for chronic weight management in individuals with overweight (pre-obesity) or obesity. In this review, we provide an overview of the clinical data supporting the use of liraglutide 3.0 mg, as well as practical advice for PCPs on the initiation and maintenance of treatment over the long term. This also covers the management of side effects and how to manage patient expectations over time.The current migration assessment requirements regarding safety of plastic food contact materials in Europe (e.g. kitchen utensils, kitchen appliances, packaging, etc.) widely rely on migration testing. According to Annexe V of Regulation (EU) No 10/2011 migration testing requirements consider the specificities of repeated use applications only to a limited extent. Repeated use food contact materials should be tested for three consecutive times at the worst-case contact time and temperature. If diffusion controlled, the migration decreases with increasing number of repeated uses. Compared to single use applications, repeated use food contact materials typically exhibit much shorter contact times, much lower ratios of surface in contact with a given amount of food, and in some cases higher temperatures. Compared to real use, in many cases highly overestimated migration testing result are observed. #link# Overestimation by testing at the beginning of use may be coupled with underestimation at later times. National legislation of the Netherlands on food contact materials has established a classification for repeated use rubber materials based on the R-value indicating whether migration testing is required or not. selleck compound -value considers in more detail specificities of repeated use applications. This publication investigates to which extent it is possible to apply the approach to plastics food contact materials in Europe. It is practically impossible to perform migration tests for various materials by putting them many times in contact with food over a long period of time, typically several years, at several temperatures and areas to food amount ratios migration. Modelling has therefore been used to predict migration from various food contact materials under different repeated use scenarios. Realistic diffusion properties of materials and migrant partitioning behaviour have been assumed to minimise the risk of underestimation.