Rapid Manufacturing of Highly Cytotoxic Clinical-Grade SARS-CoV-2-specific T Cell Products Covering SARS-CoV-2 and Its Variants for Adoptive T Cell Therapy.

Objectives: Evaluation of the feasibility of SARS-CoV-2-specific T cell manufacturing for adoptive T cell transfer in COVID-19 patients at risk to develop severe disease. Methods: Antiviral SARS-CoV-2-specific T cells were detected in blood of convalescent COVID-19 patients following stimulation with PepTivator SARS-CoV-2 Select using Interferon-gamma Enzyme-Linked Immunospot (IFN-γ ELISpot), SARS-CoV-2 T Cell Analysis Kit (Whole Blood) and Cytokine Secretion Assay (CSA) and were characterized with respect to memory phenotype, activation state and cytotoxic potential by multicolor flow cytometry, quantitative real-time PCR and multiplex analyses. Clinical-grade SARS-CoV-2-specific T cell products were generated by stimulation with MACS GMP PepTivator SARS-CoV-2 Select using CliniMACS Prodigy and CliniMACS Cytokine Capture System (IFN-gamma) (CCS). Functionality of enriched T cells was investigated in cytotoxicity assays and by multiplex analysis of secreted cytotoxic molecules upon target recognition. Results: Donor screening via IFN-γ ELISpot allows for pre-selection of potential donors for generation of SARS-CoV-2-specific T cells. Antiviral T cells reactive against PepTivator SARS-CoV-2 Select could be magnetically enriched from peripheral blood of convalescent COVID-19 patients by small-scale CSA resembling the clinical-grade CCS manufacturing process and showed an activated and cytotoxic T cell phenotype. Four clinical-grade SARS-CoV-2-specific T cell products were successfully generated with sufficient cell numbers and purities comparable to those observed in donor pretesting via CSA. The T cells in the generated products were shown to be capable to replicate, specifically recognize and kill target cells in vitro and secrete cytotoxic molecules upon target recognition. Cell viability, total CD3+ cell number, proliferative capacity and cytotoxic potential remained stable throughout storage of up to 72 h after end of leukapheresis. Conclusion: Clinical-grade SARS-CoV-2-specific T cells are functional, have proliferative capacity and target-specific cytotoxic potential. Their function and phenotype remain stable for several days after enrichment. The adoptive transfer of partially matched, viable human SARS-CoV-2-specific T lymphocytes collected from convalescent individuals may provide the opportunity to support the immune system of COVID-19 patients at risk for severe disease.

[Presentation and evaluation of the haptic-visual ear surgery training system "HaptiVisT"]. / Vorstellung und Evaluation des haptisch-visuellen, ohrchirurgischen Trainingssystems "HaptiVisT".

BACKGROUND: Operations on the temporal bone are a special challenge for ENT surgeons. The aim of the BMBF-funded project was to develop a realistic training system for ear operations in the form of a "serious game". METHODS: The presented prototype of the HaptiVisT system functions as a training system for ear surgeries with visual feedback through a glasses-free 3D monitor and feedback by means of a haptic arm simulating the drill. A variety of training options is guaranteed by three available surgical procedures (antrotomy, mastoidectomy, posterior tympanotomy). A weighted point system enables the measurability of the training success. Following the technical development of the prototype, a prospective evaluation was carried out by eight ENT physicians and four students regarding "learning content" and "user experience". A standardized questionnaire was used (ordinal scale: 1=very good to 5=very bad). RESULTS: Regarding the learning content, the aspects "strengthening anatomy (mean=1.58)", "training hand-eye coordination (1.67)", "transferability into practice (1.83)", "usefulness for practice (1.33)" yielded good to very good scores. "User experience" also showed good results for the aspects "realism (2.29)", "interaction of haptics and optics (2.33)" and "immersion in the training system (1.89)". The "motivation factor" was very high for all test subjects (1.2). CONCLUSIONS: The training system for ear surgeries "HaptiVisT" offers the possibility of immersive training. Integration into the daily clinical routine and in particular into the medical training to become an ENT specialist therefore seems to make sense.

An After-School Football Session Transiently Improves Cognitive Function in Children.

The aim of the present study was to evaluate the effect of a real-world after-school football session on subsequent cognitive function in primary school children. Following ethical approval, 100 children (aged 8−9 year) from the same after-school football club were randomly assigned to either an intervention (60 min football activity) or control (continued to rest) group. Cognitive function (selective visual attention, short term memory and long-term memory) was assessed prior to, immediately following and 45 min following the football session (and at the respective timepoints in the control group). Data were analysed via two-way (group * time) mixed methods ANOVA. The pattern of change in all domains of cognition over time, was different between the football and control groups (group * time, all p < 0.001). Specifically, performance on all cognitive tasks was greater immediately following the football session in the intervention group compared to the control group (selective visual attention, p = 0.003; short-term memory, p = 0.004; long-term memory, p < 0.001). However, there was no difference between the group 45 min following the football session (p = 0.132−0.393). These findings suggest that an after-school football session enhances cognition immediately post-activity in primary school children.

Effects of 1 Year of Lifestyle Intervention on Institutionalized Older Adults.

The socio-economic and health consequences of our ageing population are well documented, with older adults living in long-term care facilities amongst the frailest possessing specific and significant healthcare and social care needs. These needs may be exacerbated through the sedentary behaviour which is prevalent within care home settings. Reducing sedentary time can reduce the risk of many diseases and improve functional health, implying that improvements in health may be gained by simply helping older adults substitute time spent sitting with time spent standing or in light-intensity ambulation. This study identified the impact of 1 year of lifestyle intervention in a group of older adults living in a long-term care setting in Italy. One hundred and eleven older adults (mean age, 82.37 years; SD = 10.55 years) participated in the study. Sixty-nine older adults were in the intervention group (35 without severe cognitive decline and 34 with dementia) and 42 older adults were in the control group. Data on physical functioning, basic activities of daily living (BADL) and mood were collected 4 times, before, during (every four months) and after the 1 year of intervention. The lifestyle intervention focused on improving the amount of time spent every week in active behaviour and physical activity (minimum 150 min of weekly activities). All participants completed the training program and no adverse events, related to the program, occurred. The intervention group showed steady and significant improvements in physical functioning and a stable situation in BADL and mood following the intervention in older adults with and without dementia, whilst the control group exhibited a significant decline over time. These results suggest that engagement in a physical activity intervention may benefit care home residents with and without dementia both physically and mentally, leading to improved social care and a reduced burden on healthcare services.

Force-feedback assisted and virtual fixtures based K-wire drilling simulation.

One common method to fix fractures of the human hand after an accident is an osteosynthesis with Kirschner wires (K-wires) to stabilize the bone fragments. The insertion of K-wires is a delicate minimally invasive surgery, because surgeons operate almost without a sight. Since realistic training methods are time consuming, costly and insufficient, a virtual-reality (VR) based training system for the placement of K-wires was developed. As part of this, the current work deals with the real-time bone drilling simulation using a haptic force-feedback device. To simulate the drilling, we introduce a virtual fixture based force-feedback drilling approach. By decomposition of the drilling task into individual phases, each phase can be handled individually to perfectly control the drilling procedure. We report about the related finite state machine (FSM), describe the haptic feedback of each state and explain, how to avoid jerking of the haptic force-feedback during state transition. The usage of the virtual fixture approach results in a good haptic performance and a stable drilling behavior. This was confirmed by 26 expert surgeons, who evaluated the virtual drilling on the simulator and rated it as very realistic. To make the system even more convincing, we determined real drilling feed rates through experimental pig bone drilling and transferred them to our system. Due to a constant simulation thread we can guarantee a precise drilling motion. Virtual fixtures based force-feedback calculation is able to simulate force-feedback assisted bone drilling with high quality and, thus, will have a great potential in developing medical applications.