Influenza A virus-derived defective interfering particles for antiviral treatment

Here, we report on genetically engineered, propagation-incompetent influenza A virus (IAV) particles, so-called defective interfering particles (DIPs) that have been suggested as a promising novel antiviral agent. Typically, IAV DIPs harbor a large internal deletion in one of their eight genomic viral RNA (vRNA) segments. Further, DIPs are capable of hijacking cellular and viral resources upon co-infection with fully infectious standard virus (STV), resulting in an antiviral effect. Besides this replication interference, DIP infection also stimulates innate immunity, adding to the antiviral efficacy. So far, DIPs were produced in embryonated chicken eggs. To improve scalability and flexibility of processes as well as to increase product quality, we established a cell culture-based DIP production system [1,2]. This includes the development of a genetically engineered virus-cell propagation system that allows production of DIPs without the need to add infectious STV to complement missing gene functions of DIPs. Specifically, the MDCK suspension cell line generated expresses the PB2 protein [2], encoded by segment 1 (S1) of IAV, which is not expressed by “DI244” - a prototypic, well-characterized DIP harboring a deletion in S1. Using this cell culture-based production process in batch [2,3] and perfusion mode [4] at laboratory scale, we show that we can achieve very high DI244 titers of up to 2.6E+11 DIPs/mL. Infections of mice demonstrated that intranasal administration of the produced DI244 material resulted in no apparent toxic effects and in a full rescue of mice co-treated with an otherwise lethal dose of IAV [2]. Please click Download on the upper right corner to see the full abstract

Global Perspectives on Task Shifting and Task Sharing in Neurosurgery.

BACKGROUND: Neurosurgical task shifting and task sharing (TS/S), delegating clinical care to non-neurosurgeons, is ongoing in many hospital systems in which neurosurgeons are scarce. Although TS/S can increase access to treatment, it remains highly controversial. This survey investigated perceptions of neurosurgical TS/S to elucidate whether it is a permissible temporary solution to the global workforce deficit. METHODS: The survey was distributed to a convenience sample of individuals providing neurosurgical care. A digital survey link was distributed through electronic mailing lists of continental neurosurgical societies and various collectives, conference announcements, and social media platforms (July 2018-January 2019). Data were analyzed by descriptive statistics and univariate regression of Likert Scale scores. RESULTS: Survey respondents represented 105 of 194 World Health Organization member countries (54.1%; 391 respondents, 162 from high-income countries and 229 from low- and middle-income countries [LMICs]). The most agreed on statement was that task sharing is preferred to task shifting. There was broad consensus that both task shifting and task sharing should require competency-based evaluation, standardized training endorsed by governing organizations, and maintenance of certification. When perspectives were stratified by income class, LMICs were significantly more likely to agree that task shifting is professionally disruptive to traditional training, task sharing should be a priority where human resources are scarce, and to call for additional TS/S regulation, such as certification and formal consultation with a neurosurgeon (in person or electronic/telemedicine). CONCLUSIONS: Both LMIC and high-income countries agreed that task sharing should be prioritized over task shifting and that additional recommendations and regulations could enhance care. These data invite future discussions on policy and training programs

Status and Trends of Physical Activity Surveillance, Policy, and Research in 164 Countries: Findings From the Global Observatory for Physical Activity—GoPA! 2015 and 2020 Surveys

Background: Physical activity (PA) surveillance, policy, and research efforts need to be periodically appraised to gain insight into national and global capacities for PA promotion. The aim of this paper was to assess the status and trends in PA surveillance, policy, and research in 164 countries. Methods: We used data from the Global Observatory for Physical Activity (GoPA!) 2015 and 2020 surveys. Comprehensive searches were performed for each country to determine the level of development of their PA surveillance, policy, and research, and the findings were verified by the GoPA! Country Contacts. Trends were analyzed based on the data available for both survey years. Results: The global 5-year progress in all 3 indicators was modest, with most countries either improving or staying at the same level. PA surveillance, policy, and research improved or remained at a high level in 48.1%, 40.6%, and 42.1% of the countries, respectively. PA surveillance, policy, and research scores decreased or remained at a low level in 8.3%, 15.8%, and 28.6% of the countries, respectively. The highest capacity for PA promotion was found in Europe, the lowest in Africa and low- and lower-middle-income countries. Although a large percentage of the world’s population benefit from at least some PA policy, surveillance, and research efforts in their countries, 49.6 million people are without PA surveillance, 629.4 million people are without PA policy, and 108.7 million live in countries without any PA research output. A total of 6.3 billion people or 88.2% of the world’s population live in countries where PA promotion capacity should be significantly improved. Conclusion: Despite PA is essential for health, there are large inequalities between countries and world regions in their capacity to promote PA. Coordinated efforts are needed to reduce the inequalities and improve the global capacity for PA promotion