Recombinant rabies viral vectors have proven useful for applications including retrograde targeting of projection neurons and monosynaptic tracing, but their cytotoxicity has limited their use to short-term experiments. Here we introduce a new class of double-deletion-mutant rabies viral vectors that left transduced cells alive and healthy indefinitely. Deletion of the viral polymerase gene abolished cytotoxicity and reduced transgene expression to trace levels but left vectors still able to retrogradely infect projection neurons and express recombinases, allowing downstream expression of other transgene products such as fluorophores and calcium indicators. The morphology of retrogradely targeted cells appeared unperturbed at 1 year postinjection. Whole-cell patch-clamp recordings showed no physiological abnormalities at 8 weeks. Longitudinal two-photon structural and functional imaging in vivo, tracking thousands of individual neurons for up to 4 months, showed that transduced neurons did not die but retained stable visual response properties even at the longest time points imaged.

Background: Non-thermal plasma provides an interesting therapeutic opportunity to control redox-based processes, e.g. wound healing. Results: The transcription factor NRF2 and downstream signaling molecules were found to act as key controllers orchestrating the cellular response. Conclusions: Plasma triggers hormesis-like processes in keratinocytes. Significance: These findings facilitate the understanding of plasma-tissue interaction and its deduced clinical application.

The use of phase-adapted wound dressings represents best practice (BP) in chronic wound treatment. However, efficacy is often limited and associated care requirements are high. Cold atmospheric plasmajet (CAP-jet) is a promising new therapeutic tool for these wounds. In the present multicenter, randomized, open-label, prospective, clinical trial, non-inferiority of the CAP-jet versus BP was assessed in 78 patients with infected or non-infected chronic wounds of different etiology. Primary outcome measure was the sum of granulation tissue, furthermore wound area reduction, healing rate, time to complete healing, changes in wound pH value, infection score, exudate level and local tolerability were assessed. In CAP-jet treated wounds compared to control, the sum of granulation tissue was significantly higher (p < 0.0001) and wound area reduced significantly faster (p < 0.001). Furthermore, wound pH value decreased significantly faster (p = 0.0123) and local infection was overcome more rapidly by CAP-jet therapy. In 58.97% CAP-jet- vs. 5.13% BP-treated patients, complete healing of chronic ulcers was documented after 6 weeks. Treatment with CAP-jet appeared not only non-inferior, but even superior to BP in all wound entities analyzed with a favorable tolerability profile. Thus, treatment with the CAP-jet provides beneficial effects in chronic wound treatment regarding promotion of the wound healing process.

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